Note: This page contains sample records for the topic leukemia nuclear bodies from Science.gov.
While these samples are representative of the content of Science.gov,
they are not comprehensive nor are they the most current set.
We encourage you to perform a real-time search of Science.gov
to obtain the most current and comprehensive results.
Last update: August 15, 2014.
1

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

2

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

PubMed Central

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

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

2008-01-01

3

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

4

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

5

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

PubMed Central

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.

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

2013-01-01

6

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

Microsoft Academic Search

Progressive multifocal leukoencephalopathy is a fatal viral-induced demyelinating disease that was once rare but has become\\u000a more prevalent today. Over the past decades, much has been learned about the disease from molecular study of the etiological\\u000a agent of the disease, JC virus. Recently, promyelocytic leukemia nuclear bodies (PML-NBs), punctuate structures for important\\u000a nuclear functions in eukaryotic cells, were identified as

Yukiko Shishido-Hara

2010-01-01

7

A new spectrin, beta IV, has a major truncated isoform that associates with promyelocytic leukemia protein nuclear bodies and the nuclear matrix.  

PubMed

We isolated cDNAs that encode a 77-kDa peptide similar to repeats 10-16 of beta-spectrins. Its gene localizes to human chromosome 19q13.13-q13.2 and mouse chromosome 7, at 7.5 centimorgans. A 289-kDa isoform, similar to full-length beta-spectrins, was partially assembled from sequences in the human genomic DNA data base and completely cloned and sequenced. RNA transcripts are seen predominantly in the brain, and Western analysis shows a major peptide that migrates as a 72-kDa band. This new gene, spectrin betaIV, thus encodes a full-length minor isoform (SpbetaIVSigma1) and a truncated major isoform (SpbetaIVSigma5). Immunostaining of cells shows a micropunctate pattern in the cytoplasm and nucleus. In mesenchymal stem cells, the staining concentrates at nuclear dots that stain positively for the promyelocytic leukemia protein (PML). Expression of SpbetaIVSigma5 fused to green fluorescence protein in cells produces nuclear dots that include all PML bodies, which double in number in transfected cells. Deletion analysis shows that partial repeats 10 and 16 of SpbetaIVSigma5 are necessary for nuclear dot formation. Immunostaining of whole-mount nuclear matrices reveals diffuse positivity with accentuation at PML bodies. Spectrin betaIV is the first beta-spectrin associated with a subnuclear structure and may be part of a nuclear scaffold to which gene regulatory machinery binds. PMID:11294830

Tse, W T; Tang, J; Jin, O; Korsgren, C; John, K M; Kung, A L; Gwynn, B; Peters, L L; Lux, S E

2001-06-29

8

Promyelocytic leukemia isoform IV confers resistance to encephalomyocarditis virus via the sequestration of 3D polymerase in nuclear bodies.  

PubMed

Promyelocytic leukemia (PML) protein is the organizer of nuclear matrix-associated nuclear bodies (NBs), and its conjugation to the small ubiquitin-like modifier (SUMO) is required for the formation of these structures. Several alternatively spliced PML transcripts from a single PML gene lead to the production of seven PML isoforms (PML isoform I [PMLI] to VII [PMLVII]), which all share a N-terminal region that includes the RBCC (RING, B boxes, and a ?-helical coiled-coil) motif but differ in the C-terminal region. This diversity of PML isoforms determines the specific functions of each isoform. There is increasing evidence implicating PML in host antiviral defense and suggesting various strategies involving PML to counteract viral production. We reported that mouse embryonic fibroblasts derived from PML knockout mice are more sensitive than wild-type cells to infection with encephalomyocarditis virus (EMCV). Here, we show that stable expression of PMLIV or PMLIVa inhibited viral replication and protein synthesis, leading to a substantial reduction of EMCV multiplication. This protective effect required PMLIV SUMOylation and was not observed with other nuclear PML isoforms (I, II, III, V, and VI) or with the cytoplasmic PMLVII. We demonstrated that only PMLIV interacted with EMCV 3D polymerase (3Dpol) and sequestered it within PML NBs. The C-terminal region specific to PMLIV was required for both interaction with 3Dpol and the antiviral properties. Also, depletion of PMLIV by RNA interference significantly boosted EMCV production in interferon-treated cells. These findings indicate the mechanism by which PML confers resistance to EMCV. They also reveal a new pathway mediating the antiviral activity of interferon against EMCV. PMID:21994459

Maroui, Mohamed Ali; Pampin, Mathieu; Chelbi-Alix, Mounira K

2011-12-01

9

Calpain 5 is highly expressed in the central nervous system (CNS), carries dual nuclear localization signals, and is associated with nuclear promyelocytic leukemia protein bodies.  

PubMed

Calpain 5 (CAPN5) is a non-classical member of the calpain family. It lacks the EF hand motif characteristic of classical calpains but retains catalytic and Ca(2+) binding domains, and it contains a unique C-terminal domain. TRA-3, an ortholog of CAPN5, has been shown to be involved in necrotic cell death in Caenorhabditis elegans. CAPN5 is expressed throughout the CNS, but its expression relative to other calpains and subcellular distribution has not been investigated previously. Based on relative mRNA levels, Capn5 is the second most highly expressed calpain in the rat CNS, with Capn2 mRNA being the most abundant. Unlike classical calpains, CAPN5 is a non-cytosolic protein localized to the nucleus and extra-nuclear locations. CAPN5 possesses two nuclear localization signals (NLS): an N-terminal monopartite NLS and a unique bipartite NLS closer to the C terminus. The C-terminal NLS contains a SUMO-interacting motif that contributes to nuclear localization, and mutation or deletion of both NLS renders CAPN5 exclusively cytosolic. Dual NLS motifs are common among transcription factors. Interestingly, CAPN5 is found in punctate domains associated with promyelocytic leukemia (PML) protein within the nucleus. PML nuclear bodies are implicated in transcriptional regulation, cell differentiation, cellular response to stress, viral defense, apoptosis, and cell senescence as well as protein sequestration, modification, and degradation. The roles of nuclear CAPN5 remain to be determined. PMID:24838245

Singh, Ranjana; Brewer, M Kathryn; Mashburn, Charles B; Lou, Dingyuan; Bondada, Vimala; Graham, Brantley; Geddes, James W

2014-07-11

10

Childhood leukemia around nuclear facilities.  

National Technical Information Service (NTIS)

This Information Bulletin highlights the conclusion made from an Atomic Energy Control Board of Canada (AECB) study on the incidence of childhood leukemia near nuclear facilities. All of the locations with the nuclear facilities are located in Ontario, th...

1991-01-01

11

JC Virus Inclusions in Progressive Multifocal Leukoencephalopathy: Scaffolding Promyelocytic Leukemia Nuclear Bodies Grow With Cell Cycle Transition Through an S-to-G2-Like State in Enlarging Oligodendrocyte Nuclei  

PubMed Central

Abstract In progressive multifocal leukoencephalopathy, JC virus–infected oligodendroglia display 2 distinct patterns of intranuclear viral inclusions: full inclusions in which progeny virions are present throughout enlarged nuclei and dot-shaped inclusions in which virions are clustered in subnuclear domains termed “promyelocytic leukemia nuclear bodies” (PML-NBs). Promyelocytic leukemia nuclear bodies may serve a scaffolding role in viral progeny production. We analyzed the formation process of intranuclear viral inclusions by morphometry and assessed PML-NB alterations in the brains of 2 patients with progressive multifocal leukoencephalopathy. By immunohistochemistry, proliferating cell nuclear antigen was most frequently detected in smaller nuclei; cyclin A was detected in larger nuclei. This suggests an S-to-G2 cell cycle transition in infected cells associated with nuclear enlargement. Sizes of PML-NBs were variable, but they were usually either small speckles 200 to 400 nm in diameter or distinct spherical shells with a diameter of 1 ?m or more. By confocal microscopy, JC virus capsid proteins were associated with both small and large PML-NBs, but disruption of large PML-NBs was observed by ground-state depletion fluorescence nanoscopy. Clusters of progeny virions were also detected by electron microscopy. Our data suggest that, in progressive multifocal leukoencephalopathy, JC virus produces progeny virions in enlarging oligodendrocyte nuclei in association with growing PML-NBs and with cell cycle transition through an S-to-G2-like state.

Yazawa, Takuya; Nagane, Motoo; Higuchi, Kayoko; Abe-Suzuki, Shiho; Kurata, Morito; Kitagawa, Masanobu; Kamma, Hiroshi; Uchihara, Toshiki

2014-01-01

12

JC virus inclusions in progressive multifocal leukoencephalopathy: scaffolding promyelocytic leukemia nuclear bodies grow with cell cycle transition through an S-to-G2-like state in enlarging oligodendrocyte nuclei.  

PubMed

In progressive multifocal leukoencephalopathy, JC virus-infected oligodendroglia display 2 distinct patterns of intranuclear viral inclusions: full inclusions in which progeny virions are present throughout enlarged nuclei and dot-shaped inclusions in which virions are clustered in subnuclear domains termed "promyelocytic leukemia nuclear bodies" (PML-NBs). Promyelocytic leukemia nuclear bodies may serve a scaffolding role in viral progeny production. We analyzed the formation process of intranuclear viral inclusions by morphometry and assessed PML-NB alterations in the brains of 2 patients with progressive multifocal leukoencephalopathy. By immunohistochemistry, proliferating cell nuclear antigen was most frequently detected in smaller nuclei; cyclin A was detected in larger nuclei. This suggests an S-to-G2 cell cycle transition in infected cells associated with nuclear enlargement. Sizes of PML-NBs were variable, but they were usually either small speckles 200 to 400 nm in diameter or distinct spherical shells with a diameter of 1 ?m or more. By confocal microscopy, JC virus capsid proteins were associated with both small and large PML-NBs, but disruption of large PML-NBs was observed by ground-state depletion fluorescence nanoscopy. Clusters of progeny virions were also detected by electron microscopy. Our data suggest that, in progressive multifocal leukoencephalopathy, JC virus produces progeny virions in enlarging oligodendrocyte nuclei in association with growing PML-NBs and with cell cycle transition through an S-to-G2-like state. PMID:24709678

Shishido-Hara, Yukiko; Yazawa, Takuya; Nagane, Motoo; Higuchi, Kayoko; Abe-Suzuki, Shiho; Kurata, Morito; Kitagawa, Masanobu; Kamma, Hiroshi; Uchihara, Toshiki

2014-05-01

13

Recruitment of cyclin G2 to promyelocytic leukemia nuclear bodies promotes dephosphorylation of ?H2AX following treatment with ionizing radiation  

PubMed Central

Cyclin G2 (CycG2) and Cyclin G1 (CycG1), two members of the Cyclin G subfamily, share high amino acid homology in their Cyclin G boxes. Functionally, they play a common role as association partners of the B?? subunit of protein phosphatase 2A (PP2A) and regulate PP2A function, and their expression is increased following DNA damage. However, whether or not CycG1 and CycG2 have distinct roles during the cellular DNA damage response has remained unclear. Here, we report that CycG2, but not CycG1, co-localized with promyelocytic leukemia (PML) and ?H2AX, forming foci following ionizing radiation (IR), suggesting that CycG2 is recruited to sites of DNA repair and that CycG1 and CycG2 have distinct functions. PML failed to localize to nuclear foci when CycG2 was depleted, and vice versa. This suggests that PML and CycG2 mutually influence each other’s functions following IR. Furthermore, we generated CycG2-knockout (Ccng2?/?) mice to investigate the functions of CycG2. These mice were born healthy and developed normally. However, CycG2-deficient mouse embryonic fibroblasts displayed an abnormal response to IR. Dephosphorylation of ?H2AX and checkpoint kinase 2 following IR was delayed in Ccng2?/? cells, suggesting that DNA damage repair may be perturbed in the absence of CycG2. Although knockdown of B?? in wild-type cells also delayed dephosphorylation of ?H2AX, knockdown of B?? in Ccng2?/? cells prolonged this delay, suggesting that CycG2 cooperates with B?? to dephosphorylate ?H2AX. Taken together, we conclude that CycG2 is localized at DNA repair foci following DNA damage, and that CycG2 regulates the dephosphorylation of several factors necessary for DNA repair.

Naito, Yoko; Naito, Yoko; Yabuta, Norikazu; Yabuta, Norikazu; Sato, Jun; Sato, Jun; Ohno, Shouichi; Ohno, Shouichi; Sakata, Muneki; Sakata, Muneki; Kasama, Takashi; Kasama, Takashi; Ikawa, Masahito; Ikawa, Masahito; Nojima, Hiroshi; Nojima, Hiroshi

2013-01-01

14

Biophysical and functional analyses suggest that adenovirus E4-ORF3 protein requires higher-order multimerization to function against promyelocytic leukemia protein nuclear bodies.  

PubMed

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. PMID:22573317

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

2012-06-29

15

Whole-genome screening identifies proteins localized to distinct nuclear bodies  

PubMed Central

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.

Fong, Ka-wing; Li, Yujing; Wang, Wenqi; Ma, Wenbin; Li, Kunpeng; Qi, Robert Z.; Liu, Dan; Songyang, Zhou

2013-01-01

16

Proteins associated with the promyelocytic leukemia gene product (PML)-containing nuclear body move to the nucleolus upon inhibition of proteasome-dependent protein degradation  

PubMed Central

Several recent findings have indicated that the promyelocytic leukemia gene product (PML) oncogenic domains (PODs) are involved in proteasome-mediated degradation of ubiquitinated proteins. We wanted to examine the intracellular distribution of PML protein in the presence of a proteasome inhibitor. We used high-resolution microscopy to study the distribution of PML protein and other POD-associated proteins along with the proteasomes themselves under normal conditions and in cells treated with the proteasome inhibitor, MG132. Inhibition of the proteasomes in MCF-7, HeLa, and IB-4 cell lines resulted in a radical redistribution of the POD-associated proteins PML, Sp100, and SUMO-1. After 6–10 h of MG132 treatment, PML, Sp100, and SUMO-1 were no longer detectable in the PODs and accumulated mainly in the nucleolus. Moreover, MG132 treatment changed the cellular distribution of the proteasomes. Interestingly, this included the accumulation in euchromatin areas of the nucleus and within the nucleoli. Several non-POD-associated proteins did not change their cellular distribution under the same conditions. The accumulation of POD-associated proteins and proteasomes in the nucleoli of MG132-treated cells indicates that these proteins may target the nucleoli under normal conditions and that the nucleolus may have a function in the regulation of proteasomal protein degradation.

Mattsson, Karin; Pokrovskaja, Katja; Kiss, Csaba; Klein, George; Szekely, Laszlo

2001-01-01

17

Promyelocytic leukemia bodies tether to early endosomes during mitosis.  

PubMed

During mitosis the nuclear envelope breaks down, leading to potential interactions between cytoplasmic and nuclear components. PML bodies are nuclear structures with tumor suppressor and antiviral functions. Early endosomes, on the other hand, are cytoplasmic vesicles involved in transport and growth factor signaling. Here we demonstrate that PML bodies form stable interactions with early endosomes immediately following entry into mitosis. The 2 compartments remain stably associated throughout mitosis and dissociate in the cytoplasm of newly divided daughter cells. We also show that a minor subset of PML bodies becomes anchored to the mitotic spindle poles during cell division. The study demonstrates a stable mitosis-specific interaction between a cytoplasmic and a nuclear compartment. PMID:24675887

Palibrk, Vuk; Lång, Emma; Lång, Anna; Schink, Kay Oliver; Rowe, Alexander D; Bøe, Stig Ove

2014-06-01

18

Proliferating cell nuclear antigen expression in childhood acute leukemia.  

PubMed

Proliferating cell nuclear antigen (PCNA) is a 36-Kd nuclear protein, identified as the auxiliary protein of DNA polymerase delta, that is upregulated in activated proliferating cells from a variety of tissues and species, including human lymphocytes. We have examined by two-dimensional polyacrylamide gel electrophoresis the expression of PCNA in various subtypes of childhood acute leukemia and have found differences in its expression according to subtype. These differences were not related to the initial peripheral white blood count, age, or sex, and appeared to reflect differences in proliferative activity between subtypes of acute leukemia. PMID:1975505

Keim, D; Hailat, N; Hodge, D; Hanash, S M

1990-09-01

19

NCI Scientists Discover How T-Cell Leukemia Viruses Evade Body's Defense Mechanisms  

Cancer.gov

NCI scientists have discovered how human T-cell leukemia virus type 1 (HTLV-1), which infects about 20 million people worldwide, evades being held in check by one of the body's natural defense mechanisms. An active infection with HTLV-1 leads to T-cell leukemia in up to five percent of all cases worldwide.

20

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

21

Leukemia  

MedlinePLUS

... leukemias. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: Elsevier Saunders; 2011: ... leukemias. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: Elsevier Saunders; 2011: ...

22

21 CFR 892.1330 - Nuclear whole body scanner.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 false Nuclear whole body scanner. 892.1330 Section 892.1330 Food...Devices § 892.1330 Nuclear whole body scanner. (a) Identification. A nuclear whole body scanner is a device intended to...

2010-04-01

23

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

NASA Astrophysics Data System (ADS)

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

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

2010-04-01

24

Acute Lymphoblastic Leukemia (ALL)  

MedlinePLUS

... this page Print this page Acute lymphoblastic leukemia (ALL) Acute lymphoblastic leukemia (ALL) is a fast-growing cancer of a type ... that your body needs. Tweet Acute lymphoblastic leukemia (ALL), also called acute lymphocytic leukemia or acute lymphoid ...

25

In acute promyelocytic leukemia NB4 cells, the synthetic retinoid CD437 induces contemporaneously apoptosis, a caspase-3-mediated degradation of PML/RARalpha protein and the PML retargeting on PML-nuclear bodies.  

PubMed

CD437-induced apoptosis has been investigated in NB4, a human t(15;17) acute promyelocytic leukemia (APL) cell line, and in the retinoic acid (RA)-resistant NB4-R1 derivative subclone. Both NB4 and NB4-R1 cells underwent rapid apoptosis in response to low doses of CD437 (10(-7)M). This apoptosis did not require the activation of classical retinoid receptors and like arsenic (As)-induced apoptosis was preceded by the rapid activation of a caspase-3-like enzymatic activity as indicated by the increase of DEVD-pNA hydrolytic activity, by the processing of procaspase-3 protein and by the cleavage of poly(ADP-ribose) polymerase (PARP). Furthermore, it was demonstrated that the caspase-3-like proteolytic activity is responsible for the degradation of both the PML/RARalpha oncogenic protein and the normal RARalpha proteins. In CD437-treated cells, PML proteins were not degraded and PML relocalization on PMLNBs occurred in all the cells before death. CD437-induced apoptosis and receptor degradation were proteasome independent and not influenced either by inhibitors of protein tyrosine kinases (PTK), protein tyrosine phosphatases (PTPases) and serine proteases or by glutathione levels. Moreover, our data suggested that as for As2O3-induced apoptosis Bc12 modulation is not significant for CD437-induced apoptosis of NB4 cells. Since CD437 induces in vitro the rapid apoptosis of both RA-sensitive and -resistant APL cells, it could represent the first retinoid potentially able to eradicate in vivo malignant leukemia blasts. PMID:10374879

Giannì, M; de Thé, H

1999-05-01

26

Pharmacogenetic risk factors for altered bone mineral density and body composition in pediatric acute lymphoblastic leukemia  

PubMed Central

Background This study investigates pharmacogenetic risk factors for bone mineral (apparent) density (BM(A)D) and body composition in pediatric acute lymphoblastic leukemia Design and Methods We determined the influence of SNPs in 4 genes (vitamin-D receptor (VDR: BsmI/ApaI/TaqI and Cdx-2/GATA), collagen type I alpha 1 (SpI), estrogen receptor 1 (ESR1: PvuII/XbaI), glucocorticoid receptor (BclI)) on body composition, BM(A)D and fracture risk during dexamethasone-based pediatric acute lymphoblastic leukemia treatment. Body composition and BMD were measured repeatedly during and after treatment using dual energy X-ray absorptiometry. Results Non-carriers of VDR 5?-end (Cdx-2/GATA) haplotype 3 revealed a significant larger fat gain than carriers (?%fat: non-carriers: +1.76SDS, carriers: +0.77SDS, P<0.001). At diagnosis and during therapy, lumbar spine BMD was significantly higher in non-carriers of VDR 5?-end (Cdx-2/GATA) haplotype 3 than in carriers. The other SNPs did not influence BMD or fracture risk during/after treatment. The year after treatment completion, lean body mass increased in non-carriers of ESR1 (PvuII/XbaI) haplotype 3 and decreased in carriers (? lean body mass: non-car-riers:+0.28SDS, carriers: ?0.55SDS, P<0.01). Conclusions Only VDR 5?-end (Cdx-2/GATA) haplotype 3 was identified as protective factor against excessive fat gain and as a risk factor for lower lumbar spine BMD during treatment. Carrying ESR1 (PvuII/XbaI) haplotype 3 negatively influenced recovery of lean body mass after pediatric acute lymphoblastic leukemia treatment.

te Winkel, Mariel L.; van Beek, Robert D.; de Muinck Keizer-Schrama, Sabine M.P.F.; Uitterlinden, Andre G.; Hop, Wim C.J.; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

2010-01-01

27

Cystine Starvation Induces Reversible Large-Body Formation from Nuclear Bodies in T24 Cells  

Microsoft Academic Search

Nuclear bodies (PML nuclear bodies; also referred to as PODs or ND10) are small intranuclear structures which contain PML as an essential constituent and from several to 20 or more of them are present per nucleus. When starved of amino acids, nuclear bodies reversibly form one or more doughnut-shaped large bodies in T24 cells. Here, I present evidence that cystine

Hiroya Kamei

1997-01-01

28

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

29

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

30

Total-body irradiation before bone marrow transplantation for acute leukemia in first or second complete remission  

Microsoft Academic Search

Aim  In order to assess the influence of total-body irradiation (TBI) on the outcome and incidence of complication after bone marrow\\u000a transplantation (BMT), we retrospectively analyzed our patients treated for acute leukemia and conditioned with TBI prior\\u000a to BMT.\\u000a \\u000a \\u000a \\u000a Patients and Methods  Between 1980 and 1993, 326 patients referred to our department with acute non-lymphoblastic leukemia (ANLL, n=182) and acute\\u000a lymphoblastic leukemia

Y. Belkacémi; F. Pène; E. Touboul; B. Rio; V. Leblond; N. C. Gorin; A. Laugier; C. Gemici; M. Housset; M. Ozsahin

1998-01-01

31

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

ClinicalTrials.gov

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

2013-10-29

32

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

33

Creatinine as a measure of lean body mass during treatment of acute lymphoblastic leukemia in childhood.  

PubMed

Protein energy malnutrition is well-recognized in children with acute leukemia and may result in loss of lean body mass (LBM) with attendant morbidities. Much of the LBM consists of skeletal muscle, the mass of which is reflected in urinary creatinine excretion. As accurate 24 hours urine collections are challenging in children, we investigated the prospect that serum creatinine concentration provides a measure of LBM. Eleven children with acute lymphoblastic leukemia were assessed at 7 time points (6-mo intervals) from diagnosis to 1 year after the completion of therapy. LBM was measured as fat-free mass by dual energy x-ray absorptiometry (DXA scans) and correlated with serum creatinine concentration and 24 hours urine creatinine excretion. As expected, there was a strong correlation between 24 hours urinary creatinine excretion and LBM from DXA scans (r=0.79, P<0.001). Serum creatinine concentration also correlated with LBM (r=0.52, P<0.001). Serum creatinine concentration provides a surrogate measure of LBM in children with acute lymphoblastic leukemia. This will be especially useful in countries with limited resources in which more sophisticated measures, such as DXA scans, are seldom available. PMID:21178703

Morrison, Judy; Nayiager, Trishana; Webber, Colin E; Sala, Alessandra; Barr, Ronald

2011-01-01

34

Acute Lymphoblastic Leukemia (ALL)  

MedlinePLUS

... this page Print this page Acute lymphoblastic leukemia (ALL) Acute lymphoblastic leukemia (ALL) is a fast-growing cancer of a type ... that your body needs. Tweet Acute Lymphoblastic Leukemia (ALL) Symptoms of ALL How transplant can treat ALL ...

35

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

36

21 CFR 892.1330 - Nuclear whole body scanner.  

Code of Federal Regulations, 2013 CFR

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 detector whose position moves in one direction with respect to the...

2013-04-01

37

21 CFR 892.1130 - Nuclear whole body counter.  

Code of Federal Regulations, 2013 CFR

A nuclear whole body counter is a device intended to measure the amount of radionuclides in the entire body. This generic type of device may include signal analysis and display equipment, patient and equipment supports, component parts, and accessories. (b)...

2013-04-01

38

21 CFR 892.1330 - Nuclear whole body scanner.  

Code of Federal Regulations, 2012 CFR

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1330 Nuclear whole body scanner. (a) Identification. A nuclear...

2012-04-01

39

21 CFR 892.1130 - Nuclear whole body counter.  

Code of Federal Regulations, 2012 CFR

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1130 Nuclear whole body counter. (a) Identification. A nuclear...

2012-04-01

40

21 CFR 892.1130 - Nuclear whole body counter.  

Code of Federal Regulations, 2011 CFR

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1130 Nuclear whole body counter. (a) Identification. A nuclear...

2011-04-01

41

21 CFR 892.1330 - Nuclear whole body scanner.  

Code of Federal Regulations, 2011 CFR

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1330 Nuclear whole body scanner. (a) Identification. A nuclear...

2011-04-01

42

21 CFR 892.1130 - Nuclear whole body counter.  

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1130 Nuclear whole body counter. (a) Identification. A nuclear...

2014-04-01

43

21 CFR 892.1330 - Nuclear whole body scanner.  

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1330 Nuclear whole body scanner. (a) Identification. A nuclear...

2014-04-01

44

21 CFR 892.1130 - Nuclear whole body counter.  

Code of Federal Regulations, 2010 CFR

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1130 Nuclear whole body counter. (a) Identification. A nuclear...

2010-04-01

45

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

PubMed

The objective of this paper was to study cancer incidence, especially leukemia in children (<15 years), in the vicinity of Finnish nuclear power plants (NPPs). We used three different approaches: ecological analysis at municipality level, residential cohorts defined from census data, and case-control analysis with individual residential histories. The standardized incidence ratio of childhood leukemia for the seven municipalities in the vicinity of NPPs was 1.0 (95% CI 0.6, 1.6) compared to the rest of Finland. The two cohorts defined by censuses of 1980 and 1990 gave rate ratios of 1.0 (95% CI 0.3, 2.6) and 0.9 (95% CI 0.2, 2.7), respectively, for childhood leukemia in the population residing within 15 km from the NPPs compared to the 15-50 km zone. The case-control analysis with 16 cases of childhood leukemia and 64 matched population-based controls gave an odds ratio for average distance between residence and NPP in the closest 5-9.9 km zone of 0.7 (95% CI 0.1, 10.4) compared to > or =30 km zone. Our results do not indicate an increase in childhood leukemia and other cancers in the vicinity of Finnish NPPs though the small sample size limits the strength of conclusions. The conclusion was the same for adults. PMID:20037792

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

2010-04-01

46

Nuclear export signal within CALM is necessary for CALM-AF10-induced leukemia.  

PubMed

The CALM-AF10 fusion gene, which results from a t(10;11) translocation, is found in a variety of hematopoietic malignancies. Certain HOXA cluster genes and MEIS1 genes are upregulated in patients and mouse models that express CALM-AF10. Wild-type clathrin assembly lymphoid myeloid leukemia protein (CALM) primarily localizes in a diffuse pattern within the cytoplasm, whereas AF10 localizes in the nucleus; however, it is not clear where CALM-AF10 acts to induce leukemia. To investigate the influence of localization on leukemogenesis involving CALM-AF10, we determined the nuclear export signal (NES) within CALM that is necessary and sufficient for cytoplasmic localization of CALM-AF10. Mutations in the NES eliminated the capacity of CALM-AF10 to immortalize murine bone-marrow cells in vitro and to promote development of acute myeloid leukemia in mouse models. Furthermore, a fusion of AF10 with the minimal NES can immortalize bone-marrow cells and induce leukemia in mice. These results suggest that during leukemogenesis, CALM-AF10 plays its critical roles in the cytoplasm. PMID:24397609

Suzuki, Mai; Yamagata, Kazutsune; Shino, Mika; Aikawa, Yukiko; Akashi, Koichi; Watanabe, Toshio; Kitabayashi, Issay

2014-03-01

47

Regulation of Neuronal Differentiation by Proteins Associated with Nuclear Bodies  

PubMed Central

Nuclear bodies are large sub-nuclear structures composed of RNA and protein molecules. The Survival of Motor Neuron (SMN) protein localizes to Cajal bodies (CBs) and nuclear gems. Diminished cellular concentration of SMN is associated with the neurodegenerative disease Spinal Muscular Atrophy (SMA). How nuclear body architecture and its structural components influence neuronal differentiation remains elusive. In this study, we analyzed the effects of SMN and two of its interaction partners in cellular models of neuronal differentiation. The nuclear 23 kDa isoform of Fibroblast Growth Factor – 2 (FGF-223) is one of these interacting proteins – and was previously observed to influence nuclear bodies by destabilizing nuclear gems and mobilizing SMN from Cajal bodies (CBs). Here we demonstrate that FGF-223 blocks SMN-promoted neurite outgrowth, and also show that SMN disrupts FGF-223-dependent transcription. Our results indicate that FGF-223 and SMN form an inactive complex that interferes with neuronal differentiation by mutually antagonizing nuclear functions. Coilin is another nuclear SMN binding partner and a marker protein for Cajal bodies (CBs). In addition, coilin is essential for CB function in maturation of small nuclear ribonucleoprotein particles (snRNPs). The role of coilin outside of Cajal bodies and its putative impacts in tissue differentiation are poorly defined. The present study shows that protein levels of nucleoplasmic coilin outside of CBs decrease during neuronal differentiation. Overexpression of coilin has an inhibitory effect on neurite outgrowth. Furthermore, we find that nucleoplasmic coilin inhibits neurite outgrowth independent of SMN binding revealing a new function for coilin in neuronal differentiation.

Forthmann, Benjamin; van Bergeijk, Jeroen; Lee, Yu-Wei; Lubben, Verena; Schill, Yvonne; Brinkmann, Hella; Ratzka, Andreas; Stachowiak, Michal K.; Hebert, Michael; Grothe, Claudia; Claus, Peter

2013-01-01

48

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

49

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

ClinicalTrials.gov

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

2014-07-22

50

Fludarabine Phosphate, Low-Dose Total-Body Irradiation, and Peripheral Blood Stem Cell Transplant Followed By Donor Lymphocyte Infusion in Treating Older Patients With Chronic Myeloid Leukemia  

ClinicalTrials.gov

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

2013-12-02

51

Aberrant Recruitment of the Nuclear Receptor Corepressor Histone Deacetylase Complex by the Acute Myeloid Leukemia Fusion Partner ETO  

Microsoft Academic Search

Nuclear receptor corepressor (CoR)-histone deacetylase (HDAC) complex recruitment is indispensable for the biological activities of the retinoic acid receptor fusion proteins of acute promyelocytic leukemias. We report here that ETO (eight-twenty-one or MTG8), which is fused to the acute myelogenous leukemia 1 (AML1) transcription factor in t(8;21) AML, interacts via its zinc finger region with a conserved domain of the

VANIA GELMETTI; JINSONG ZHANG; MIRCO FANELLI; SAVERIO MINUCCI; PIER GIUSEPPE PELICCI; MITCHELL A. LAZAR

1998-01-01

52

Assembly of the Nuclear Transcription and Processing Machinery: Cajal Bodies (Coiled Bodies) and Transcriptosomes  

Microsoft Academic Search

We have examined the distribution of RNA transcription and processing factors in the amphibian oocyte nucleus or germinal vesicle. RNA polymerase I (pol I), pol II, and pol III occur in the Cajal bodies (coiled bodies) along with various components required for transcription and processing of the three classes of nuclear transcripts: mRNA, rRNA, and pol III transcripts. Among these

Joseph G. Gall; Michel Bellini; Christine Murphy

1999-01-01

53

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

PubMed Central

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

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

2007-01-01

54

Childhood leukemias associated with fallout from nuclear testing  

Microsoft Academic Search

Continuing concern over the possible carcinogenic effects of low-level radiation prompted us to study the population of Utah because of its exposure to fallout from 26 nuclear tests between 1951 and 1958. Certain rural counties (high-level counties) received most of the fallout during that period. We reviewed all deaths from childhood (under 15 years of age) cancers occurring in the

Joseph L. Lyon; Melville R. Klauber; John W. Gardner; King S. Udall

1979-01-01

55

The relativistic nuclear many-body problem  

Microsoft Academic Search

This volume presents sections which explore important aspects of relativistic baryons, nuclear models, relativistic Hartree descriptions of nuclei, quantum hadrodynamics, the dynamical quantum vacuum, charged mesons, relativistic pion dynamics, two-nucleon correlations, electroweak interactions with nuclei, and quantum chromodynamics. Appendixes cover notation and conventions, dimensional regularization, path-integral derivation of Feynman rules, and the Feynman rules in local gauge theories.

J. W. Negele; B. D. Serot; E. Vogt; J. D. Walecka

1986-01-01

56

Nuclear bodies in the Drosophila germinal vesicle  

Microsoft Academic Search

The germinal vesicle of the Drosophila oocyte is transcriptionally quiescent during the latter part of the first meiotic prophase. Concomitant with silencing of\\u000a the genome, the nucleolus disappears at an early stage and the chromatin condenses into a compact mass called the karyosome.\\u000a A prominent Cajal body (endobody) is present during most of prophase, attached to the karyosome. Components of

Ji-Long Liu; Michael Buszczak; Joseph G. Gall

2006-01-01

57

Murine Leukemia Virus Uses NXF1 for Nuclear Export of Spliced and Unspliced Viral Transcripts  

PubMed Central

ABSTRACT Intron-containing mRNAs are subject to restricted nuclear export in higher eukaryotes. Retroviral replication requires the nucleocytoplasmic transport of both spliced and unspliced RNA transcripts, and RNA export mechanisms of gammaretroviruses are poorly characterized. Here, we report the involvement of the nuclear export receptor NXF1/TAP in the nuclear export of gammaretroviral RNA transcripts. We identified a conserved cis-acting element in the pol gene of gammaretroviruses, including murine leukemia virus (MLV) and xenotropic murine leukemia virus (XMRV), named the CAE (cytoplasmic accumulation element). The CAE enhanced the cytoplasmic accumulation of viral RNA transcripts and the expression of viral proteins without significantly affecting the stability, splicing, or translation efficiency of the transcripts. Insertion of the CAE sequence also facilitated Rev-independent HIV Gag expression. We found that the CAE sequence interacted with NXF1, whereas disruption of NXF1 ablated CAE function. Thus, the CAE sequence mediates the cytoplasmic accumulation of gammaretroviral transcripts in an NXF1-dependent manner. Disruption of NXF1 expression impaired cytoplasmic accumulations of both spliced and unspliced RNA transcripts of XMRV and MLV, resulting in their nuclear retention or degradation. Thus, our results demonstrate that gammaretroviruses use NXF1 for the cytoplasmic accumulation of both spliced and nonspliced viral RNA transcripts. IMPORTANCE Murine leukemia virus (MLV) has been studied as one of the classic models of retrovirology. Although unspliced host messenger RNAs are rarely exported from the nucleus, MLV actively exports unspliced viral RNAs to the cytoplasm. Despite extensive studies, how MLV achieves this difficult task has remained a mystery. Here, we have studied the RNA export mechanism of MLV and found that (i) the genome contains a sequence which supports the efficient nuclear export of viral RNAs, (ii) the cellular factor NXF1 is involved in the nuclear export of both spliced and unspliced viral RNAs, and, finally, (iii) depletion of NXF1 results in nuclear retention or degradation of viral RNAs. Our study provides a novel insight into MLV nuclear export.

Sakuma, Toshie; Davila, Jaime I.; Malcolm, Jessica A.; Kocher, Jean-Pierre A.; Tonne, Jason M.

2014-01-01

58

Few-Body Nuclear Wave Functions  

NASA Astrophysics Data System (ADS)

This is where the abstract should be placed. It should consist of one paragraph and give a concise summary of the material in the article below. Replace the title, authors, and addresses within the curly brackets with your own title, authors, and addresses. You may have as many authors and addresses as you wish. It's preferable not to use footnotes in the abstract or the title; the acknowledgments for funding bodies etc. are placed in a separate section at the end of the text.

Chaudhary, Irfan; Hagelstein, Peter L.

2005-12-01

59

NUP98 fusion in human leukemia: dysregulation of the nuclear pore and homeodomain proteins.  

PubMed

NUP98 is fused to a variety of partner genes, including abdominal B-like HOX, in human myeloid and T-cell malignancies via chromosomal translocation involving 11p15. NUP98 encodes a 98-kd nucleoporin that is a component of the nuclear pore complex and functions in nucleocytoplasmic transport, with its N-terminal GLFG repeats used as a docking site for karyopherins. Disruption of NUP98 may affect the nuclear pore function, and the abnormal expression and altered function of fusion partners may also be critical for leukemia development. Recent studies using mouse models expressing NUP98-HOX have confirmed its leukemogenic potential, and cooperative genes for NUP98-HOXA9 in leukemogenesis have been identified in these studies.Thus, the NUP98 chimera is a unique molecule that provides valuable information regarding nuclear pore function and the role of the homeobox protein in leukemogenesis/carcinogenesis. PMID:16105755

Nakamura, Takuro

2005-07-01

60

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

61

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

62

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

PubMed

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. PMID:1954939

Gardner, M J

1991-08-01

63

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

64

Nuclear matter equation of state and three-body forces  

SciTech Connect

The energy per particle, symmetry energy, pressure, and free energy are calculated for symmetric nuclear matter using BHF approach with modern nucleon-nucleon CD-Bonn, Nijm1, Argonne v{sub 18}, and Reid 93 potentials. To obtain saturation in nuclear matter we add three-body interaction terms which are equivalent to a density-dependent two-nucleon interaction a la Skyrme force. Good agreement is obtained in comparison with previous theoretical estimates and experimental data.

Mansour, H. M. M.; Algamoudi, A. M. A. [Cairo University, Physics Department, Faculty of Science (Egypt)

2012-04-15

65

Reversible Large-Body Formation from Nuclear Bodies upon Amino Acid(s) Starvation in T24 Cells  

Microsoft Academic Search

AP435 dot, a nuclear dot-like structure that is recognized by a monoclonal antibody AP435 MAb and that seems to correlate with perinuclear intermediate filaments, was identified as a nuclear body by double immunofluorescent staining with AP435 MAb and the nuclear-body-specific antibody ?Sp100 or mAb 5E10. In T24 cells, nuclear bodies usually appear as small entities with an apparent diameter ranging

Hiroya Kamei

1996-01-01

66

Nuclear pockets and clefts in the lymphoid cell population of bone marrow and blood of children with acute lymphoblastic leukemia.  

PubMed Central

Ultrastructural investigation of the nuclei of the lymphoid cell population of bone marrow and blood of children with acute lymphoblastic leukemia regularly shows the presence of two types of nuclear pockets and nuclear clefts. The incidences of these nuclear features decrease significantly during cytostatic therapy. The pockets consist of either a cytoplasmic segment enclosed by a nuclear heterochromatin bridge or a nuclear segment enclosed by an intranuclear cleft. One type of nuclear cleft is, for its greater part of whole length, situated just under the nuclear surface. The other type of cleft is oriented more or less perpendicular to the nuclear surface. It is proposed that these four types be designated as nuclear pockets and nuclear clefts "Type 1" and "Type 2." Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14

Schuurmans Stekhoven, J. H.; Holland, R.

1986-01-01

67

Murine Leukemia Virus Uses TREX Components for Efficient Nuclear Export of Unspliced Viral Transcripts  

PubMed Central

Previously we reported that nuclear export of both unspliced and spliced murine leukemia virus (MLV) transcripts depends on the nuclear export factor (NXF1) pathway. Although the mRNA export complex TREX, which contains Aly/REF, UAP56, and the THO complex, is involved in the NXF1-mediated nuclear export of cellular mRNAs, its contribution to the export of MLV mRNA transcripts remains poorly understood. Here, we studied the involvement of TREX components in the export of MLV transcripts. Depletion of UAP56, but not Aly/REF, reduced the level of both unspliced and spliced viral transcripts in the cytoplasm. Interestingly, depletion of THO components, including THOC5 and THOC7, affected only unspliced viral transcripts in the cytoplasm. Moreover, the RNA immunoprecipitation assay showed that only the unspliced viral transcript interacted with THOC5. These results imply that MLV requires UAP56, THOC5 and THOC7, in addition to NXF1, for nuclear export of viral transcripts. Given that naturally intronless mRNAs, but not bulk mRNAs, require THOC5 for nuclear export, it is plausible that THOC5 plays a key role in the export of unspliced MLV transcripts.

Sakuma, Toshie; Tonne, Jason M.; Ikeda, Yasuhiro

2014-01-01

68

Adult leukemia and proximity-based surrogates for exposure to Pilgrim plant`s nuclear emissions  

SciTech Connect

Possible associations between adult leukemia incidence and proximity-based surrogate measures of potential for exposure to radioactive emission from the Pilgrim nuclear power plant in Plymouth, Massachusetts, were investigated. Include din this study were 105 nonchronic lymphocytic leukemia cases, diagnosed between 1978 and 1986 at age 13 y or older, that occured in 22 towns near Pilgrim; population controls numbered 208. Residence within 4 mi (6.4 km) of Pilgrim during {open_quotes}high-emissions{close_quotes} years was related to case-control status (adjusted odds ratio [OR] = 3.88, 95% confidence interval [95% Cl] = 0.81-10.64). A high {open_quotes}exposure{close_quotes} score (i.e., a value that accounted for downwind time) was also related to case-control status (OR = 3.46, 95% Cl = 1.50-7.96). Some statistically significant dose-response trends were found. Cautious interpretation of associations is warranted in light of the low levels of reported emission. 42 refs., 1 fig., 4 tabs.

Morris, M.S.; Knorr, R.S. [Massachusetts Dept. of Public Health, Boston, MA (United States)

1996-07-01

69

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

70

Inhibition of Sp1 Functions by Its Sequestration into PML Nuclear Bodies  

PubMed Central

Promyelocytic leukemia nuclear bodies (PML NBs) are comprised of PML and a striking variety of its associated proteins. Various cellular functions have been attributed to PML NBs, including the regulation of gene expression. We report here that induced expression of PML recruits Sp1 into PML NBs, leading to the reduction of Sp1 transactivation function. Specifically, Chromatin immunoprecipitation (ChIP) assay demonstrated that induced expression of PML significantly diminishes the amount of Sp1 binding to its target gene promoter, immunofluorescence staining showed dramatic increase in the co-localization between PML and Sp1 upon induction of PML expression, moreover, PML and Sp1 co-fractionated in the core nuclear matrix. Our study further showed that PML promotes SUMOylation of Sp1 in a RING-motif-dependent manner, SUMOylation of Sp1 facilitates physical interaction between Sp1 and PML and recruitment of Sp1 into the PML NBs, the SUMO binding motif of PML was also important for its interaction with Sp1. The results of this study demonstrate a novel mechanism by which PML regulates gene expression through sequestration of the transcription factor into PML NBs.

Li, June; Zou, Wen-Xin; Chang, Kun-Sang

2014-01-01

71

Geographical and temporal trends of childhood leukemia in relation to the nuclear plant in the Negev, Israel, 1960-1985.  

PubMed

Gardner et al. (Br Med J 1990; 300: 423-429) reported a high relative risk for childhood leukemia among children, aged 0-24 years at time of diagnosis, born to fathers employed at the Sellafield nuclear plant in the U.K. As a result we looked for spatial and temporal trends of childhood and young adult leukemia in the Negev, where a nuclear plant has been in operation since 1960. We divided the Negev into an Eastern part where plant employees are likely to live, and a Western part where this is quite unlikely. Reported leukemia cases were provided by the Israel Cancer Registry for the age group 0-24, and for the period 1960-1985. We checked this file against data obtained from the hospitals in the area. We added 6 more cases in the Eastern Negev, none in the Western Negev, and none of the reported cases was discarded. There was a total of 192 cases, of which 52% were acute lymphatic leukemia. Jewish and Bedouin children were studied separately. Among Jewish children the average annual incidence rate for the Eastern Negev was 2.76/100,000, the Western Negev 3.51. Over time the leukemia rates were consistently higher in the Western Negev among children aged 0-9 years, which holds especially for acute lymphatic leukemia. There was a sudden increase among girls born during the period 1970-1979 in the northern part of the Western Negev, which was not noticed among boys. No excess cases were found in the small towns around the plant. PMID:1844266

Sofer, T; Goldsmith, J R; Nusselder, I; Katz, L

72

Nuclear protein IK undergoes dynamic subcellular translocation and forms unique nuclear bodies during the cell cycle.  

PubMed

IK is a nuclear protein containing a unique domain named RED due to the presence of a repetitive arginine (R), aspartic (E), and glutamic acid (D) sequence. To date, the function of this protein remains largely unknown despite of a couple of previous studies in the literature. Here we report that depletion of IK via RNA interference results in mitotic arrest. We also demonstrate that IK undergoes dynamic translocation during interphase and mitosis. In particular, IK is primarily present in some interphase cells as nuclear foci/bodies which do not co-localize with nucleoli, PMA bodies and Cajal bodies. Pull-down analysis coupled with mass spectrometry reveals that IK is associated with DHX15, a putative ATP-dependent RNA helicase. Our results strongly suggest that IK may participate in pre-mRNA splicing and that it may be a useful biomarker for a new nuclear structure in the cell. PMID:24252166

Hu, Liyan; Yang, Feikun; Liu, Xianan; Xu, Dazhong; Dai, Wei

2013-01-01

73

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

Code of Federal Regulations, 2013 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...

2013-07-01

74

Human T-Cell Leukemia Virus Type 1 Tax Protein Binds to Assembled Nuclear Proteasomes and Enhances Their Proteolytic Activity  

Microsoft Academic Search

The human T-cell leukemia virus type 1 (HTLV-1) Tax protein activates the HTLV-1 long terminal repeat and key regulatory proteins involved in inflammation, activation, and proliferation and may induce cell transformation. Tax is also the immunodominant target antigen for cytotoxic T cells in HTLV-1 infection. We found that Tax bound to assembled nuclear proteasomes, but Tax could not be detected

JORIS HEMELAAR; FRANCOISE BEX; BRUCE BOOTH; VINCENZO CERUNDOLO; ANDREW MCMICHAEL; SUSAN DAENKE

2001-01-01

75

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

76

PML-nuclear bodies decrease with age and their stress response is impaired in aged individuals  

PubMed Central

Background Promyelocytic leukemia nuclear bodies (PML-NBs) have been depicted as structures which are involved in processing cell damages and DNA double-strand break repairs. The study was designed to evaluate differences in patients’ PML-NBs response to stress factors like a cancerous disease and ionizing radiation exposure dependent on age. Methods In order to clarify the role of PML-NBs in the aging process, we examined peripheral blood monocytes of 134 cancer patients and 41 healthy individuals between 22 and 92 years of age, both before and after in vitro irradiation. Additionally, we analyzed the samples of the cancer patients after in vivo irradiation. Cells were immunostained and about 1600 cells per individual were analyzed for the presence of PML- and ?H2AX foci. Results The number of existing PML-NBs per nucleus declined with age, while the number of ?H2AX foci increased with age. There was a non-significant trend that in vivo irradiation increased the number of PML-NBs in cells of young study participants, while in older individuals PML-NBs tended to decrease. It can be assumed that PML-NBs decrease in number during the process of aging. Conclusion The findings suggest that there is a dysfunctional PML-NBs stress response in aged cells.

2014-01-01

77

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

PubMed

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

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

2014-03-17

78

Assembly of the Nuclear Transcription and Processing Machinery: Cajal Bodies (Coiled Bodies) and Transcriptosomes  

PubMed Central

We have examined the distribution of RNA transcription and processing factors in the amphibian oocyte nucleus or germinal vesicle. RNA polymerase I (pol I), pol II, and pol III occur in the Cajal bodies (coiled bodies) along with various components required for transcription and processing of the three classes of nuclear transcripts: mRNA, rRNA, and pol III transcripts. Among these components are transcription factor IIF (TFIIF), TFIIS, splicing factors, the U7 small nuclear ribonucleoprotein particle, the stem–loop binding protein, SR proteins, cleavage and polyadenylation factors, small nucleolar RNAs, nucleolar proteins that are probably involved in pre-rRNA processing, and TFIIIA. Earlier studies and data presented here show that several of these components are first targeted to Cajal bodies when injected into the oocyte and only subsequently appear in the chromosomes or nucleoli, where transcription itself occurs. We suggest that pol I, pol II, and pol III transcription and processing components are preassembled in Cajal bodies before transport to the chromosomes and nucleoli. Most components of the pol II transcription and processing pathway that occur in Cajal bodies are also found in the many hundreds of B-snurposomes in the germinal vesicle. Electron microscopic images show that B-snurposomes consist primarily, if not exclusively, of 20- to 30-nm particles, which closely resemble the interchromatin granules described from sections of somatic nuclei. We suggest the name pol II transcriptosome for these particles to emphasize their content of factors involved in synthesis and processing of mRNA transcripts. We present a model in which pol I, pol II, and pol III transcriptosomes are assembled in the Cajal bodies before export to the nucleolus (pol I), to the B-snurposomes and eventually to the chromosomes (pol II), and directly to the chromosomes (pol III). The key feature of this model is the preassembly of the transcription and processing machinery into unitary particles. An analogy can be made between ribosomes and transcriptosomes, ribosomes being unitary particles involved in translation and transcriptosomes being unitary particles for transcription and processing of RNA.

Gall, Joseph G.; Bellini, Michel; Wu, Zheng'an; Murphy, Christine

1999-01-01

79

Tax Protein of Human T-Cell Leukemia Virus Type I Binds to the Ankyrin Motifs of Inhibitory Factor kappaB and Induces Nuclear Translocation of Transcription Factor NF-kappaB Proteins for Transcriptional Activation  

Microsoft Academic Search

Human T-cell leukemia virus type I causes adult T-cell leukemia and tropical spastic paraparesis, and its regulator protein Tax has been implicated in the pathogenic activity of human T-cell leukemia virus type I. Tax activates transcription of viral and cellular genes through specific enhancers: the 21-bp enhancer of human T-cell leukemia virus type I, the nuclear factor kappa B (NF-kappa

Hiroshi Hirai; Takeshi Suzuki; Jun-Ichi Fujisawa; Jun-Ichiro Inoue; Mitsuaki Yoshida

1994-01-01

80

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

81

Association between baseline body mass index and overall survival among patients over age 60 with acute myeloid leukemia.  

PubMed

Acute myeloid leukemia (AML) is more common and more lethal among patients over the age of 60. Increased body mass index (BMI) has been associated with a higher incidence of various malignancies, including AML. We sought to determine whether patient BMI at the time of AML diagnosis is related to overall survival (OS) among elderly patients. We identified 97 patients with AML diagnosed after the age of 60 and treated with cytarabine-based induction chemotherapy. The median age was 68 years (range 60-87); 52% of patients were male, and our study population was predominantly white (89% of patients). The median OS for all patients was 316 days (95% CI 246-459). The hazard ratio for mortality was increased among patients with a BMI < 25 compared to BMI ? 30 (HR 2.14, P = 0.009, 95% CI 1.21-3.77), as well as with older age (HR 1.76, P = 0.015, 95% CI 1.12-2.79) and with secondary versus de novo disease (HR 1.95, P = 0.006, 95% CI 1.21-3.14). After multivariable analysis, we did not find a significant association between OS and other potential confounders such as coronary artery disease or diabetes among these patients. We conclude that increased BMI was independently associated with improved OS among older AML patients at our institution. PMID:23619915

Brunner, Andrew M; Sadrzadeh, Hossein; Feng, Yang; Drapkin, Benjamin J; Ballen, Karen K; Attar, Eyal C; Amrein, Philip C; McAfee, Steven L; Chen, Yi-Bin; Neuberg, Donna S; Fathi, Amir T

2013-08-01

82

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

ClinicalTrials.gov

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

2014-04-28

83

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

ClinicalTrials.gov

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

2014-07-10

84

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

85

Whole-body Sleeping Beauty mutagenesis can cause penetrant leukemia/lymphoma and rare high-grade glioma without associated embryonic lethality  

PubMed Central

The Sleeping Beauty (SB) transposon system has been used as a somatic mutagen to identify candidate cancer genes. In previous studies, efficient leukemia/lymphoma formation on an otherwise wild-type genetic background occurred in mice undergoing whole-body mobilization of transposons, but was accompanied by high levels of embryonic lethality. To explore the utility of SB for large-scale cancer gene discovery projects, we have generated mice that carry combinations of different transposon and transposase transgenes. We have identified a transposon/transposase combination that promotes highly penetrant leukemia/lymphoma formation on an otherwise wild-type genetic background, yet does not cause embryonic lethality. Infiltrating gliomas also occurred at lower penetrance in these mice. SB-induced or accelerated tumors do not harbor large numbers of chromosomal amplifications or deletions, indicating that transposon mobilization likely promotes tumor formation by insertional mutagenesis of cancer genes, and not by promoting wide-scale genomic instability. Cloning of transposon insertions from lymphomas/leukemias identified common insertion sites at known and candidate novel cancer genes. These data indicate that a high mutagenesis rate can be achieved using SB without high levels of embryonic lethality or genomic instability. Furthermore, the SB system can be used to identify new genes involved in lymphomagenesis/leukemiogenesis.

Collier, Lara S.; Adams, David J.; Hackett, Christopher S.; Bendzick, Laura E.; Akagi, Keiko; Davies, Michael N.; Diers, Miechaleen D.; Rodriguez, Fausto J.; Bender, Aaron M.; Tieu, Christina; Matise, Ilze; Dupuy, Adam J.; Copeland, Neal G.; Jenkins, Nancy A.; Hodgson, J. Graeme; Weiss, William A.; Jenkins, Robert B.; Largaespada, David A.

2009-01-01

86

Ionizing Radiation and Risk of Chronic Lymphocytic Leukemia in the 15-Country Study of Nuclear Industry Workers  

PubMed Central

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.

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, Helene; Telle-Lamberton, Maylis

2014-01-01

87

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

88

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

89

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

SciTech Connect

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

Komura, Naoyuki [Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-0061 (Japan); Asakawa, Mayako [Department of Microbiology and Immunology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Umezawa, Kazuo [Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-0061 (Japan)]. E-mail: umezawa@applc.keio.ac.jp; Segawa, Kaoru [Department of Microbiology and Immunology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan)

2007-08-01

90

Paraspeckles are subpopulation-specific nuclear bodies that are not essential in mice  

PubMed Central

Nuclei of higher organisms are well structured and have multiple, distinct nuclear compartments or nuclear bodies. Paraspeckles are recently identified mammal-specific nuclear bodies ubiquitously found in most cells cultured in vitro. To investigate the physiological role of paraspeckles, we examined the in vivo expression patterns of two long noncoding RNAs, NEAT1_1 and NEAT1_2, which are essential for the architectural integrity of nuclear bodies. Unexpectedly, these genes were only strongly expressed in a particular subpopulation of cells in adult mouse tissues, and prominent paraspeckle formation was observed only in the cells highly expressing NEAT1_2. To further investigate the cellular functions of paraspeckles, we created an animal model lacking NEAT1 by gene targeting. These knockout mice were viable and fertile under laboratory growth conditions, showing no apparent phenotypes except for the disappearance of paraspeckles. We propose that paraspeckles are nonessential, subpopulation-specific nuclear bodies formed secondary to particular environmental triggers.

Naganuma, Takao; Shioi, Go; Hirose, Tetsuro

2011-01-01

91

Periodic expression of Sm proteins parallels formation of nuclear Cajal bodies and cytoplasmic snRNP-rich bodies.  

PubMed

Small nuclear ribonucleoproteins (snRNPs) play a fundamental role in pre-mRNA processing in the nucleus. The biogenesis of snRNPs involves a sequence of events that occurs in both the nucleus and cytoplasm. Despite the wealth of biochemical information about the cytoplasmic assembly of snRNPs, little is known about the spatial organization of snRNPs in the cytoplasm. In the cytoplasm of larch microsporocytes, a cyclic appearance of bodies containing small nuclear RNA (snRNA) and Sm proteins was observed during anther meiosis. We observed a correlation between the occurrence of cytoplasmic snRNP bodies, the levels of Sm proteins, and the dynamic formation of Cajal bodies. Larch microsporocytes were used for these studies. This model is characterized by natural fluctuations in the level of RNA metabolism, in which periods of high transcriptional activity are separated from periods of low transcriptional activity. In designing experiments, the authors considered the differences between the nuclear and cytoplasmic phases of snRNP maturation and generated a hypothesis about the direct participation of Sm proteins in a molecular switch triggering the formation of Cajal bodies. PMID:21904826

Smoli?ski, Dariusz J; Wróbel, Bogdan; Noble, Anna; Zienkiewicz, Agnieszka; Górska-Brylass, Alicja

2011-11-01

92

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

93

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

94

Selective inhibitors of nuclear export show that CRM1/XPO1 is a target in chronic lymphocytic leukemia  

PubMed Central

The nuclear export protein XPO1 is overexpressed in cancer, leading to the cytoplasmic mislocalization of multiple tumor suppressor proteins. Existing XPO1-targeting agents lack selectivity and have been associated with significant toxicity. Small molecule selective inhibitors of nuclear export (SINEs) were designed that specifically inhibit XPO1. Genetic experiments and X-ray structures demonstrate that SINE covalently bind to a cysteine residue in the cargo-binding groove of XPO1, thereby inhibiting nuclear export of cargo proteins. The clinical relevance of SINEs was explored in chronic lymphocytic leukemia (CLL), a disease associated with recurrent XPO1 mutations. Evidence is presented that SINEs can restore normal regulation to the majority of the dysregulated pathways in CLL both in vitro and in vivo and induce apoptosis of CLL cells with a favorable therapeutic index, with enhanced killing of genomically high-risk CLL cells that are typically unresponsive to traditional therapies. More importantly, SINE slows disease progression, and improves overall survival in the E?-TCL1-SCID mouse model of CLL with minimal weight loss or other toxicities. Together, these findings demonstrate that XPO1 is a valid target in CLL with minimal effects on normal cells and provide a basis for the development of SINEs in CLL and related hematologic malignancies.

Lapalombella, Rosa; Sun, Qingxiang; Williams, Katie; Tangeman, Larissa; Jha, Shruti; Zhong, Yiming; Goettl, Virginia; Mahoney, Emilia; Berglund, Caroline; Gupta, Sneha; Farmer, Alicia; Mani, Rajeswaran; Johnson, Amy J.; Lucas, David; Mo, Xiaokui; Daelemans, Dirk; Sandanayaka, Vincent; Shechter, Sharon; McCauley, Dilara; Shacham, Sharon; Kauffman, Michael

2012-01-01

95

FINAL HEIGHT AND BODY MASS INDEX AFTER TREATMENT FOR CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA KON?NA VIŠINA IN INDEKS TELESNE MASE PRI BOLNIKIH, ZDRAVLJENIH ZARADI AKUTNE LIMFOBLASTNE LEVKEMIJE V OTROŠTVU  

Microsoft Academic Search

Background Newer and more agressive forms of chemotherapy and newer protocols in the treatment have increased the survival rate of children with malignancies. Improved survival rates in children treated for acute lymphoblastic leukemia have focused attention on late effects including disorders of growth and puberty, and development of overweight or obesity. Methods The height and weight expressed as body mass

Mojca Žerjav-Tanšek; Janez Jazbec; Lorna Zaletel-Zadravec; Tadej Battelino

96

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

97

ELECTRON MICROSCOPY OF BACILLUS MEGATERIUM UNDERGOING ISOLATION OF ITS NUCLEAR BODIES  

PubMed Central

Fitz-James, Philip (University of Western Ontario, London, Canada). Electron microscopy of Bacillus megaterium undergoing isolation of its nucelar bodies. J. Bacteriol. 87:1202–1210. 1964.—The various steps of treatment leading to the isolation of nuclear bodies were followed by thin-section electron microscopy. Nuclear rearrangement (condensation then dispersion) accompanied the treatment of washed rejuvenated cells with sucrose stabilizing buffer. Liberation of protoplasts with lysozyme did not greatly alter nuclear form. Strongly cationic buffers used for subsequent lipase digestion again caused a marked aggregation of the nucleoids. The isolated nuclear bodies were found as masses of uranyl- and lead-stainable fibers in various degrees of aggregation, possibly damaged by the isolation procedures. Images

Fitz-James, Philip

1964-01-01

98

Double minute chromatin bodies and other chromosome alterations in human myeloid HL-60 leukemia cells susceptible or resistant to induction of differentiation by phorbol-12-myristate-13-acetate  

SciTech Connect

An analysis of the chromosomal karyotype of the human promyelocytic HL-60 leukemia cell line and of a number of its sublines that exhibit varying degrees of resistance to induction of differentiation by phorbol-12-myristate-13-acetate was conducted. The HL-60 cell line and the derived sublines contained two consistent marker chromosomes (9p- and t(10;13)), which suggested that they have a common and possibly clonal origin. HL-60 cells that are susceptible to phorbol-12-myristate-13-acetate-induced cell differentiation contained double minute chromatine bodies. The sublines with different degrees of resistance showed a corresponding sequential reduction of double minute chromatin bodies in metaphase cells. This loss of double minute chromatin bodies was not associated with an appearance of homogeneously staining chromosomal regions. Resistant and susceptible HL-60 cell differed also in a number of other chromosomal alteration, including gains or losses involving chromosomes 5, 8, 11, 13, 16, and 17. Thus, it is suggested that acquisition of resistance to phorbol-12-myristate-13-acetate-induced cell differentiation in the HL-60 cells may involve one or more of the above chromosomal changes.

Au, W.W.; Callaham, M.F.; Workman, M.L.; Huberman, E.

1983-12-01

99

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

SciTech Connect

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

Ryan, Colm M.; Kindle, Karin B.; Collins, Hilary M. [Gene Regulation Group, Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD (United Kingdom)] [Gene Regulation Group, Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD (United Kingdom); Heery, David M., E-mail: david.heery@nottingham.ac.uk [Gene Regulation Group, Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD (United Kingdom)

2010-01-01

100

Increased Induction of Osteopetrosis, but Unaltered Lymphomagenicity, by Murine Leukemia Virus SL3-3 after Mutation of a Nuclear Factor 1 Site in the Enhancer  

Microsoft Academic Search

SL3-3 is a murine leukemia virus which is only weakly bone pathogenic but highly T-cell lymphomagenic. A major pathogenic determinant is the transcriptional enhancer comprising several transcription factor binding sites, among which are three identical sites for nuclear factor 1 (NF1). We have investigated the pathogenic properties of NF1 site enhancer mutants of SL3-3. Two different mutants carrying a 3-bp

STEEN ETHELBERG; BARBARA D. TZSCHASCHEL; ARNE LUZ; SALVADOR J. DIAZ-CANO; FINN SKOU PEDERSEN; JORG SCHMIDT

101

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

102

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

103

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

PubMed

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

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

2014-04-01

104

Genetic Analysis of Nuclear Bodies: From Nondeterministic Chaos to Deterministic Order  

PubMed Central

The eukaryotic nucleus is a congested place, and macromolecular crowding is thought to play an important role in increasing the relative concentrations of nuclear proteins, thereby accelerating the rates of biochemical reactions. Crowding is also thought to provide the environment needed for formation of nuclear bodies/subcompartments, such as the Cajal Body (CB) and the Histone Locus Body (HLB), via self-organization. In this chapter, we contrast the theories of stochastic self-organization and hierarchical self-organization in their application to nuclear body assembly, using CBs and HLBs as paradigms. Genetic ablation studies in Drosophila on components of CBs and HLBs, have revealed an order to the assembly of these structures that is suggestive of a hierarchical model of self-organization. These studies also show that function(s) attributed to the nuclear bodies are largely unaffected in their absence, reinforcing an emerging theme in the field that the purpose of these subdomains may be to enhance the efficiency and specificity of reactions.

Rajendra, T.K.; Praveen, Kavita; Matera, A. Gregory

2014-01-01

105

Splitting of the one-body potential in spin-polarized isospin-symmetric nuclear matter  

SciTech Connect

Spin-polarized symmetric nuclear matter is studied within the Dirac-Brueckner-Hartree-Fock approach. We pay particular attention to the difference between the one-body potentials of upward and downward polarized nucleons. This is formally analogous to the Lane potential for isospin-asymmetric nuclear matter. We point out the necessity for additional information on this fundamentally important quantity and suggest ways to constrain it.

Sammarruca, Francesca [Department of Physics, University of Idaho, Moscow, Idaho 83844-0903 (United States)

2010-08-15

106

Identification of Nuclear Dicing Bodies Containing Proteins for MicroRNA Biogenesis in Living Arabidopsis Plants  

PubMed Central

MicroRNAs (miRNAs) are important for regulating gene expression in muticellular organisms. MiRNA processing is a two step process, in animal cells the first step is nuclear and the second step cytoplasmic, whereas in plant cells both steps occur in the nucleus via the enzyme Dicer-like1 (DCL1) [1, 2] and other proteins including the zinc finger domain protein Serrate (SE) [3, 4] and a double-stranded RNA (DsRNA) binding domain protein Hyponastic Leaves1 (HYL1) [5–7]. Furthermore, plant miRNAs are methylated by Hua Enhancer (HEN1) at their 3’ ends [8] and loaded onto Argonuate1 (AGO1) [9]. However, little is known about the cellular basis of miRNA biogenesis. Using live-cell imaging, we show here that DCL1 and HYL1 colocalize in discrete nuclear bodies in addition to being present in a low level diffuse nucleoplasmic distribution. These bodies, which we refer to as nuclear dicing bodies (D-bodies), differ from Cajal bodies [10, 11]. A mutated DCL1 with impaired function in miRNA processing fails to target to D-bodies, and an introduced pri-miRNA transcrpt is recruited to D-bodies. Furthermore, bi-molecular fluorescence complementation (BiFC) shows that DCL1, HYL1 and SE interact in D-bodies. Based upon these data we propose that D-bodies are crucial for orchestrating pri-miRNA processing and/or storage/assembly of miRNA processing complexes in the nuclei of plant cells.

Fang, Yuda; Spector, David L.

2007-01-01

107

Sequential combination of decitabine and idarubicin synergistically enhances anti-leukemia effect followed by demethylating Wnt pathway inhibitor promoters and downregulating Wnt pathway nuclear target  

PubMed Central

Background The methylation inhibitor 5-Aza-2?-deoxycytidine (decitabine, DAC) has a great therapeutic value for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). But decitabine monotherapy was associated with a relatively low rate of complete remission in AML and MDS. We aimed to investigate the effect of several anti-leukemia drugs in combination with decitabine on the proliferation of myeloid leukemia cells, to select the most efficient combination group and explore the associated mechanisms of these combination therapies. Methods Cell proliferation was tested by MTT assay and CFU-GM assay. Cell apoptosis was evaluated by Annexin V and PI staining in cell culture, TUNEL assay and transmission electron microscopy in animal study. MicroPET was used to imaging the tumor in mouse model. Molecular studies were conducted using microarray expression analysis, which was used to explore associated pathways, and real-time quantitative reverse transcription-PCR, western blot and immunohistochemistry, used to assess regulation of Wnt/?-catenin pathway. Statistical significance among groups was determined by one-way ANOVA analysis followed by post hoc Bonferroni’s multiple comparison test. Results Among five anti-leukemia agents in combining with decitabine, the sequential combination of decitabine and idarubicin induced synergistic cell death in U937 cells, and this effect was verified in HEL, SKM-1 cells and AML cells isolated from AML patients. Importantly, tumor growth inhibition in this sequential combination was found to be higher than in single agent or controls in vivo. Moreover, sequential combination of the two agents induced apoptosis and depression of the Wnt/?-catenin pathway in both AML cell culture and animal studies. Conclusions The findings demonstrated that sequentially combination of decitabine and idarubicin had synergistic anti-leukemia effects. These effects were mainly attributed to demethylation of Wnt/?-catenin pathway inhibitors and downregulation of Wnt/?-catenin pathway nuclear targets.

2014-01-01

108

Nuclear Receptor Unfulfilled Regulates Axonal Guidance and Cell Identity of Drosophila Mushroom Body Neurons  

Microsoft Academic Search

Nuclear receptors (NRs) comprise a family of ligand-regulated transcription factors that control diverse critical biological processes including various aspects of brain development. Eighteen NR genes exist in the Drosophila genome. To explore their roles in brain development, we knocked down individual NRs through the development of the mushroom bodies (MBs) by targeted RNAi. Besides recapitulating the known MB phenotypes for

Suewei Lin; Yaling Huang; Tzumin Lee; Brian D. McCabe

2009-01-01

109

Prohibitin 2 represents a novel nuclear AKT substrate during all-trans retinoic acid-induced differentiation of acute promyelocytic leukemia cells.  

PubMed

The AKT/PKB kinase is essential for cell survival, proliferation, and differentiation; however, aberrant AKT activation leads to the aggressiveness and drug resistance of many human neoplasias. In the human acute promyelocytic leukemia cell line NB4, nuclear AKT activity increases during all-trans retinoic acid (ATRA)-mediated differentiation. As nuclear AKT activity is associated with differentiation, we sought to identify the nuclear substrates of AKT that were phosphorylated after ATRA treatment. A proteomics-based search for nuclear substrates of AKT in ATRA-treated NB4 cells was undertaken by using 2D-electrophoresis/mass spectrometry (MS) in combination with an anti-AKT phospho-substrate antibody. Western blot analysis, an in vitro kinase assay, and/or site-directed mutagenesis were performed to further characterize the MS findings. MS analysis revealed prohibitin (PHB)-2, a multifunctional protein involved in cell cycle progression and the suppression of oxidative stress, to be a putative nuclear substrate of AKT. Follow-up studies confirmed that AKT phosphorylates PHB2 on Ser-91 and that forced expression of the PHB2(S91A) mutant results in a rapid loss of viability and apoptotic cell death. Activation of nuclear AKT during ATRA-mediated differentiation results in the phosphorylation of several proteins, including PHB2, which may serve to coordinate nuclear-mitochondrial events during differentiation.-Bavelloni, A., Piazzi, M., Faenza, I., Raffini, M., D'Angelo, A., Cattini, L., Cocco, L., Blalock, W. L. Prohibitin 2 represents a novel nuclear AKT substrate during all-trans-retinoic acid-induced differentiation of acute promyelocytic leukemia cells. PMID:24522204

Bavelloni, Alberto; Piazzi, Manuela; Faenza, Irene; Raffini, Mirco; D'Angelo, Antonietta; Cattini, Luca; Cocco, Lucio; Blalock, William L

2014-05-01

110

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

111

Low-dose fractionated total body irradiation (TBI) adversely affects prognosis of patients with leukemia receiving an HLA-matched allogeneic bone marrow transplant from an unrelated donor (UD-BMT)  

Microsoft Academic Search

The optimal total body irradiation (TBI) regimen for unrelated donor bone marrow transplant (UD-BMT) is unknown. In the present study we analyze the outcomes of two different TBI regimens used in our center for patients with leukemia undergoing an UD-BMT. Between January 1994 and August 2001, 99 consecutive UD-BMT patients entered this comparative study. The conditioning regimen consisted of cyclophosphamide,

R Corvò; T Lamparelli; B Bruno; S Barra; MT Van Lint; V Vitale; A Bacigalupo

2002-01-01

112

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

SciTech Connect

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

Elmehdawi, Fatima; Wheway, Gabrielle; Szymanska, Katarzyna [Division of Clinical Sciences, Leeds Institute of Molecular Medicine, Level 8, Wellcome Trust Brenner Building, University of Leeds, Leeds, LS9 7TF West Yorkshire (United Kingdom)] [Division of Clinical Sciences, Leeds Institute of Molecular Medicine, Level 8, Wellcome Trust Brenner Building, University of Leeds, Leeds, LS9 7TF West Yorkshire (United Kingdom); Adams, Matthew [BioScreening Technology Group, Biomedical Health Research Center, Wellcome Trust Brenner Building, University of Leeds, Leeds, LS9 7TF West Yorkshire (United Kingdom)] [BioScreening Technology Group, Biomedical Health Research Center, Wellcome Trust Brenner Building, University of Leeds, Leeds, LS9 7TF West Yorkshire (United Kingdom); High, Alec S. [Department of Histopathology, Bexley Wing, St. James's University Hospital, Beckett Street, Leeds, LS9 7TF West Yorkshire (United Kingdom)] [Department of Histopathology, Bexley Wing, St. James's University Hospital, Beckett Street, Leeds, LS9 7TF West Yorkshire (United Kingdom); Johnson, Colin A., E-mail: c.johnson@leeds.ac.uk [Division of Clinical Sciences, Leeds Institute of Molecular Medicine, Level 8, Wellcome Trust Brenner Building, University of Leeds, Leeds, LS9 7TF West Yorkshire (United Kingdom); Robinson, Philip A. [Division of Clinical Sciences, Leeds Institute of Molecular Medicine, Level 8, Wellcome Trust Brenner Building, University of Leeds, Leeds, LS9 7TF West Yorkshire (United Kingdom)] [Division of Clinical Sciences, Leeds Institute of Molecular Medicine, Level 8, Wellcome Trust Brenner Building, University of Leeds, Leeds, LS9 7TF West Yorkshire (United Kingdom)

2013-02-01

113

Weak response of cold symmetric nuclear matter at three-body cluster level  

NASA Astrophysics Data System (ADS)

We have studied the Fermi and Gamow-Teller responses of cold symmetric nuclear matter within a unified dynamical model, suitable to account for both short- and long-range correlation effects. The formalism of correlated basis functions has been used to construct two-body effective interactions and one-body effective weak operators. The inclusion of the three-body cluster term allowed for the incorporation in our scheme of a realistic model of three-nucleon interactions, referred to as Urbana IX (UIX). Moreover, our results show that the sizable dependence of the effective weak operator on the details of the correlation functions is in fact unphysical, and disappears once the three-body cluster term is taken into account.

Lovato, Alessandro; Losa, Cristina; Benhar, Omar

2013-03-01

114

Dynamic force-induced direct dissociation of protein complexes in a nuclear body in living cells.  

PubMed

Despite past progress in understanding mechanisms of cellular mechanotransduction, it is unclear whether a local surface force can directly alter nuclear functions without intermediate biochemical cascades. Here we show that a local dynamic force via integrins results in direct displacements of coilin and SMN proteins in Cajal bodies and direct dissociation of coilin-SMN associated complexes. Spontaneous movements of coilin increase more than those of SMN in the same Cajal body after dynamic force application. Fluorescence resonance energy transfer changes of coilin-SMN depend on force magnitude, an intact F-actin, cytoskeletal tension, Lamin A/C, or substrate rigidity. Other protein pairs in Cajal bodies exhibit different magnitudes of fluorescence resonance energy transfer. Dynamic cyclic force induces tiny phase lags between various protein pairs in Cajal bodies, suggesting viscoelastic interactions between them. These findings demonstrate that dynamic force-induced direct structural changes of protein complexes in Cajal bodies may represent a unique mechanism of mechanotransduction that impacts on nuclear functions involved in gene expression. PMID:22643893

Poh, Yeh-Chuin; Shevtsov, Sergey P; Chowdhury, Farhan; Wu, Douglas C; Na, Sungsoo; Dundr, Miroslav; Wang, Ning

2012-01-01

115

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

PubMed

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. PMID:20111623

Zienkiewicz, K; Bednarska, E

2009-01-01

116

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

117

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

118

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

119

Plasma Cell Leukemia (PCL): A Report on 15 Patients  

Microsoft Academic Search

Fifteen patients presenting with plasma tients developed meningeal plasma cell cell leukemia (PCL) are reported in detail. leukemia and is reported in detail. Cyto- The clinicopathologic features of PCL differ morphologic assessment of PCL cells from typical myeloma and resemble those showed nuclear immaturity and obvious of acute leukemia: patients with PCL have nuclear\\/cytoplasmic asynchrony. Despite less bone disease but

R. K. Woodruff; J. S. Malpas; A. M. Paxton; T. A. Lister

1978-01-01

120

Leukemia Ecology: Ecological Prophylaxis of Leukemia.  

National Technical Information Service (NTIS)

Contents: Etiopathogenesis of leukemia; Ecological leukemogenic factors; Epidemiology of leukemias; Geochemical environment in relationship to health and disease; Leukemia risk factor bank; Perspectives of leukemia prophylaxis by ecological and dietary me...

J. Aleksandrowica A. B. Skotnicki

1982-01-01

121

The murine nuclear orphan receptor GCNF is expressed in the XY body of primary spermatocytes.  

PubMed

We have studied the expression of the nuclear orphan receptor GCNF (germ cell nuclear factor) on the mRNA and protein level in pubertal and adult mouse testes. We show by Northern and Western blot analyses and by in situ hybridization that GCNF is expressed in spermatocytes and round spermatids of adult mouse testis suggesting that GCNF may be a transcriptional regulator of spermatogenesis. Since the GCNF protein is accumulated in the XY body of late pachytene spermatocytes, it may be involved in transcriptional inactivation of sex chromosomes. PMID:9845324

Bauer, U M; Schneider-Hirsch, S; Reinhardt, S; Benavente, R; Maelicke, A

1998-11-20

122

Human herpesvirus-8-encoded LNA1 accumulates in heterochromatin-associated nuclear bodies  

Microsoft Academic Search

Subnuclear distribution of the human herpesvirus-8 (HHV-8)-encoded nuclear protein LNA-1 was analysed at high resolution in body cavity (BC) lymphoma-derived cell lines, in cell hybrids between BC cells and various human and mouse cells and in freshly infected K562 and ECV cell lines. Three- dimensional reconstruction of nuclei from optical sections and quantitative analysis of the distribution of LNA-1 fluorescence

Laszlo Szekely; Csaba Kiss; Karin Mattsson; Elena Kashuba; Katja Pokrovskaja; Attila Juhasz; Pia Holmvall; George Klein

1999-01-01

123

Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha  

Microsoft Academic Search

Oleylethanolamide (OEA) is a naturally occurring lipid that regulates satiety and body weight. Although structurally related to the endogenous cannabinoid anandamide, OEA does not bind to cannabinoid receptors and its molecular targets have not been defined. Here we show that OEA binds with high affinity to the peroxisome-proliferator-activated receptor-alpha (PPAR-alpha), a nuclear receptor that regulates several aspects of lipid metabolism.

Jin Fu; Silvana Gaetani; Fariba Oveisi; Jesse Lo Verme; Antonia Serrano; Fernando Rodríguez de Fonseca; Anja Rosengarth; Hartmut Luecke; Barbara Di Giacomo; Giorgio Tarzia; Daniele Piomelli

2003-01-01

124

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

NASA Astrophysics Data System (ADS)

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

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

2014-04-01

125

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

126

Gamma ray nuclear resonance absorption: an alternative method for in vivo body composition studies.  

PubMed

We have evaluated gamma ray nuclear resonance absorption (gamma-NRA) on nitrogen, a mature technology proposed and developed by Soreq NRC for detecting explosives, as an alternative to neutron activation for in vivo assaying of body nitrogen. The principles of the gamma-NRA method are outlined, and a test facility constructed at McMaster University's Accelerator Laboratory is described. The results of a feasibility study recently performed there on phantoms and animal tissue are presented and discussed. gamma-NRA is a full imaging technique that essentially constitutes element-specific absorptiometry--i.e., it can generate projections of the mass distribution for a specific element, along with a conventional radiograph of the patient. From the transmission profile of an individual scanned by 9.17 MeV gamma rays, local or whole body nitrogen content can be determined via the resonant attenuation undergone when the beam encounters regions of nitrogen concentration. The advantages of gamma-NRA over neutron activation are (a) radiation doses delivered to the body are at least one order of magnitude lower, thus allowing repeated measurements on individual patients and also rendering the method ethically acceptable for application to children; (b) gamma-NRA is inherently free from uncertainties related to nonuniform distributions of the element in question within the body; (c) it is applicable to patients of varying size and shape; and (d) it yields both nitrogen images and conventional radiographic images of the body. PMID:10865748

Vartsky, D; Goldberg, M B; Bar, D; Goldschmidt, A; Feldman, G; Sayag, E; Katz, D; Stronach, I M; Stark, J W; Prestwich, W V; McNeill, F E; Chettle, D R

2000-05-01

127

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

PubMed

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. PMID:21785410

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

2011-08-17

128

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

129

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

130

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

131

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

Microsoft Academic Search

Surface and body wave magnitudes are determined for 15 USSR underground nuclear weapons tests conducted at Novaya Zemlya between 1964 and 1976 and are used to estimate yields. These events include the largest underground explosions detonated by the Soviet Union. A histogram of body wave magnitude (m\\/sub b\\/) values indicates a clustering of explosions at a few specific yields. The

L. R. Sykes; G. C. Wiggins

1986-01-01

132

Yields of Soviet Underground Nuclear Explosions at Novaya Zemlya, 1964-1976, from Seismic Body and Surface Waves  

Microsoft Academic Search

Surface and body wave magnitudes are determined for 15 U.S.S.R. underground nuclear weapons tests conducted at Novaya Zemlya between 1964 and 1976 and are used to estimate yields. These events include the largest underground explosions detonated by the Soviet Union. A histogram of body wave magnitude (mb) values indicates a clustering of explosions at a few specific yields. The most

Lynn R. Sykes; Graham C. Wiggins

1986-01-01

133

Increased health care utilization by survivors of childhood lymphoblastic leukemia is confined to those treated with cranial or total body irradiation: a case cohort study  

PubMed Central

Background Previous studies have indicated that survivors of childhood acute lymphoblastic leukemia (ALL) have an increased morbidity measured in terms of health care utilization. However, earlier studies have several potentially important limitations. To overcome some of these, we investigated hospital contact rates, and predictors thereof, among 5-year survivors of ALL in a population-based setting, and compared them to a control cohort regarding outcome measures from a comprehensive nation-wide health register. Methods All individuals diagnosed with ALL before the age of 18 in Southern Sweden during 1970–1999 and alive January 2007 (n?=?213; male?=?107) were identified through the Swedish Cancer Register. Each subject was matched to fifty controls, identified in the Swedish Population Register. All study subjects were linked to the National Hospital Register and detailed information was obtained on all hospital contacts (hospital admissions and outpatients visits) starting five years after cancer diagnosis, and the corresponding date for the controls, until 2009. Results The median follow-up among the 5-year survivors of ALL was 16 years (range 5–33), accruing a total of 3,527 person-years. Of the 213 5-year survivors, 105 (49.3%) had at least one hospital contact compared to 3,634 (34.1%) of the controls (p?body irradiation (45% and 7%, respectively) had an increased risk of at least one hospital contact (OR 2.3, 95%CI; 1.5–3.6 and OR 11.0, 95%CI; 3.2–50.7, respectively), while there was no significant difference between the non-irradiated survivors and controls. Conclusions We show that irradiated survivors of childhood ALL have an increased morbidity measured in terms of hospital contacts, in comparison to non-irradiated survivors and controls, while non-irradiated survivors have not. These findings are encouraging regarding the future morbidity of children currently treated for ALL, as radiotherapy is necessary only for a minority of these.

2014-01-01

134

Acute myeloid leukemia  

MedlinePLUS

... For information on other types of leukemia, see: Chronic lymphocytic leukemia (CLL) Chronic myelogenous leukemia (CML) Leukemia ... number of platelets. A white blood cell count ( WBC ) is usually high but can be low or ...

135

Blast cells with nuclear extrusions in the form of micronuclei are associated with MYC amplification in acute myeloid leukemia  

Microsoft Academic Search

We report three cases of acute myeloid leukemia without maturation [AML-M1 subtype according to the French-American-British classification (FAB)] with the presence of MYC oncogene amplification in form of double minutes (dmin) or homogeneously staining region (hsr). Blasts cells showed a particular morphology with extrusion of chromatin material. We observed by FISH the phenomenon of MYC aggregation in interphase cells and

Olaya Villa; Marta Salido; María Encarnación Pérez-Vila; Ana Ferrer; Leonor Arenillas; Carmen Pedro; Blanca Espinet; Cristina Corzo; Sergi Serrano; Soledad Woessner; Lourdes Florensa; Francesc Solé

2008-01-01

136

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

NASA Astrophysics Data System (ADS)

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

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

2014-01-01

137

Leukemia -- Eosinophilic  

MedlinePLUS

... Signs Diagnosis Stages Treatment Options About Clinical Trials Latest Research Coping with Side Effects After Treatment Questions to ... leukemia that provides basic information and areas of research. Or, choose “Next” ... boxes located on the right side of your screen.

138

Incomplete Chromatin Condensation in Enlarged Rat Myelocytic Leukemia Cells  

PubMed Central

The distinguishable morphologic features of nuclei of acute myelogenous leukemia cells with enlarged size and finely distributed nuclear chromatin indicate incomplete chromosome condensation that can be related to elevated gene expression. To confirm this, interphase chromosome structures were studied in exponentially growing rat myelomonocytic leukemia 1 cells isolated at the University of Debrecen (My1/De cells). This cell line was established from primary rat leukemia chemically induced by 7,12-dimethylbenz[a]anthracene treatment. The enlarged nuclei of My1/De cells allowed improved fluorescent visualization of chromosomal structures. Increased resolution revealed major interphase intermediates consisting of (1) veil-like chromatin, (2) chromatin ribbon, (3) chromatin funnel, (4) chromatin bodies, (5) elongated prechromosomes, (6) seal-ring, spiral shaped, and circular chromosomal subunits, (7) elongated, bent, u- and v-shaped prechromosomes, and (8) metaphase chromosomes. Results confirmed the existence of the chromatin funnel, the first visible interphase chromosome generated by the supercoiling of the chromatin ribbon. Other intermediates not seen previously included the spiral subunits that are involved in the chromonemic folding of metaphase chromosomes. The existence of spiral subunits favors the helical coil model of chromosome condensation. Incomplete chromatin condensation in leukemia cells throughout the cell cycle is an indication of euchromatization contributing to enhanced gene expression and is regarded as a leukemic factor.

Trencsenyi, Gyorgy; Nagy, Gabor; Bako, Fruzsina; Kertai, Pal

2012-01-01

139

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

PubMed

Tripartite motif-containing 22 (TRIM22) exhibits antiviral and growth inhibitory properties, but there has been no study on the localization and dynamics of the endogenous TRIM22 protein. We report here that TRIM22 is dramatically induced by progesterone in MDA-MB-231-derived ABC28 cells and T47D cells. This induction was associated with an increase in TRIM22 nuclear bodies (NB), and an even more prominent increase in nucleolar TRIM22 bodies. Distinct endogenous TRIM22 NB were also demonstrated in several other cell lines including MCF7 and HeLa cells. These TRIM22 NB resemble Cajal bodies, co-localized with these structures and co-immunoprecipitated with p80-coilin. However, IFNgamma-induced TRIM22 in HeLa and MCF7 cells did not form NB, implying the forms and distribution of TRIM22 are regulated by specific cellular signals. This notion is also supported by the observation that TRIM22 NB undergoes dynamic cell-cycle dependent changes in distribution such that TRIM22 NB started to form in early G0/G1 but became dispersed in the S-phase. In light of its potential antiviral and antitumor properties, the findings here provide an interesting gateway to study the relationship between the different forms and functions of TRIM22. PMID:19331816

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

2009-05-01

140

The role of three-nucleon forces and many-body processes in nuclear pairing  

NASA Astrophysics Data System (ADS)

We present microscopic valence-shell calculations of pairing gaps in the calcium isotopes, focusing on the role of three-nucleon (3N) forces and many-body processes. In most cases, we find a reduction in pairing strength when the leading chiral 3N forces are included, compared to results with low-momentum 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 many-body 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, J. D.; Menéndez, J.; Schwenk, A.

2013-07-01

141

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

NASA Astrophysics Data System (ADS)

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

Kim, Yeong E.; Zubarev, Alexander L.

1996-05-01

142

The U3 Region of Moloney Murine Leukemia Virus Contains Position-independent Cis-acting Sequences Involved in the Nuclear Export of Full-length Viral Transcripts.  

PubMed

The distinguishing feature of self-inactivating (SIN) retroviral vectors is the deletion of the enhancer/promoter sequences in the U3 region of the 3' long terminal repeat. This design is used to overcome transcriptional interference and prevent downstream transcription from the 3' long terminal repeat. SIN vectors were derived from a number of different retroviruses. Studies of SIN vectors show that extensive U3 deletions in HIV-based vectors do not alter viral titers or the in vitro and in vivo properties of the vectors. However, deletion of the U3 sequences in ?- and ?-retroviruses correlates with defects in 3' RNA processing and reduces viral titers by >10-fold. Here, we studied the steps in the retroviral life cycle that are affected by the deletion of sequences in the 3' U3 region of Moloney murine leukemia virus-derived retroviral vectors. The results show that the amounts of both full-length and internal RNA transcripts of U3-minus vectors are reduced in the nuclei of transfected cells, an effect that is probably due to a general defect in 3' RNA processing. Furthermore, full-length RNA transcripts were also defective in terms of nuclear export. This defect was complemented by transferring the U3 region to another position within the retroviral vector, indicating that the U3 region contains position-independent cis-acting sequences that are required for the transport of full-length viral transcripts. The results also suggest that the leader region of Moloney murine leukemia virus contains inhibitory/regulatory sequences, which prevent export and mediate nuclear retention of full-length viral RNA. PMID:24878957

Volkova, Natalia A; Fomina, Elena G; Smolnikova, Viktoryia V; Zinovieva, Natalia A; Fomin, Igor K

2014-07-18

143

Interaction of nuclear factors with upstream sequences of a lipid body membrane protein gene from carrot.  

PubMed Central

To study the regulation of gene expression during embryo development, we isolated a gene, DC 59, expressed in embryos but not in mature carrot plants. Sequence and S1 analysis showed that the gene was composed of one exon encoding a polypeptide of 19 kilodaltons and was highly homologous to the lipid body membrane protein gene L3 from maize. The plant hormone abscisic acid regulated the accumulation of DC 59 mRNA. To understand the mechanism of embryo-specific and hormonal regulation of DC 59, 5' DNA fragments were incubated with nuclear proteins. Two adjacent regions (from -706 to -235) interacted with nuclear extracts from embryos, resulting in the formation of four complexes (C1, C2, C3, and C4). Factors involved in the formation of the C3 and C4 complexes could be competed with sequences upstream of DC 8, a gene that is coordinately expressed with DC 59 during embryo development. DNase I footprinting analysis revealed that nuclear extracts from embryos bound to four AT-rich sequences, and the protected motifs within fragment V were located in the highly homologous upstream regions of DC 59 and DC 8 genes.

Hatzopoulos, P; Franz, G; Choy, L; Sung, R Z

1990-01-01

144

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

ClinicalTrials.gov

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

2014-06-16

145

Nuclear Fragile X Mental Retardation Protein Is localized to Cajal Bodies  

PubMed Central

Fragile X syndrome is caused by loss of function of a single gene encoding the Fragile X Mental Retardation Protein (FMRP). This RNA-binding protein, widely expressed in mammalian tissues, is particularly abundant in neurons and is a component of messenger ribonucleoprotein (mRNP) complexes present within the translational apparatus. The absence of FMRP in neurons is believed to cause translation dysregulation and defects in mRNA transport essential for local protein synthesis and for synaptic development and maturation. A prevalent model posits that FMRP is a nucleocytoplasmic shuttling protein that transports its mRNA targets from the nucleus to the translation machinery. However, it is not known which of the multiple FMRP isoforms, resulting from the numerous alternatively spliced FMR1 transcripts variants, would be involved in such a process. Using a new generation of anti-FMRP antibodies and recombinant expression, we show here that the most commonly expressed human FMRP isoforms (ISO1 and 7) do not localize to the nucleus. Instead, specific FMRP isoforms 6 and 12 (ISO6 and 12), containing a novel C-terminal domain, were the only isoforms that localized to the nuclei in cultured human cells. These isoforms localized to specific p80-coilin and SMN positive structures that were identified as Cajal bodies. The Cajal body localization signal was confined to a 17 amino acid stretch in the C-terminus of human ISO6 and is lacking in a mouse Iso6 variant. As FMRP is an RNA-binding protein, its presence in Cajal bodies suggests additional functions in nuclear post-transcriptional RNA metabolism. Supporting this hypothesis, a missense mutation (I304N), known to alter the KH2-mediated RNA binding properties of FMRP, abolishes the localization of human FMRP ISO6 to Cajal bodies. These findings open unexplored avenues in search for new insights into the pathophysiology of Fragile X Syndrome.

Tremblay, Sandra; Rose, Timothy M.; Cote, Jocelyn; De Koninck, Paul; Khandjian, Edouard W.

2013-01-01

146

Treatment Options for Hairy Cell Leukemia  

MedlinePLUS

... marrow makes too many lymphocytes (a type of white blood cell). Hairy cell leukemia is a cancer ... other substances to all tissues of the body. White blood cells that fight infection and disease. Platelets ...

147

Double minute chromatin bodies and other chromosome alterations in human myeloid HL60 leukemia cells susceptible or resistant to induction of differentiation by phorbol-12-myristate-13-acetate  

Microsoft Academic Search

An analysis of the chromosomal karyotype of the human promyelocytic HL-60 leukemia cell line and of a number of its sublines that exhibit varying degrees of resistance to induction of differentiation by phorbol-12-myristate-13-acetate was conducted. The HL-60 cell line and the derived sublines contained two consistent marker chromosomes (9p- and t(10;13)), which suggested that they have a common and possibly

W. W. Au; M. F. Callaham; M. L. Workman; E. Huberman

1983-01-01

148

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

NASA Astrophysics Data System (ADS)

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

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

149

Characterization of nuclear protein binding to a site in the long terminal repeat of a murine leukemia virus: comparison with the NFAT complex.  

PubMed Central

We previously identified a protein-binding site (MLPal) that is located downstream of the enhancer element in the long terminal repeat (LTR) of a mink cell focusing-forming (MCF) murine leukemia virus (F. K. Yoshimura, K. Diem, H. Chen, and J. Tupper, J. Virol. 67:2298-2304, 1993). We determined that the MLPal site regulates transcription specifically in T cells and affects the lymphomagenicity of the MCF isolate 13 murine leukemia virus with a single enhancer repeat in its LTR. In this report, we present evidence that two different proteins, a T-cell-specific protein and a ubiquitous protein, bind the MLPal site in a sequence-specific manner. By mutational analysis, we determined that the T-cell-specific and the ubiquitous proteins require different nucleotides in the MLPal sequence for DNA binding. By competitive electrophoretic mobility shift assays, we demonstrated that the T-cell-specific protein that binds MLPal is identical or similar to a protein from nonactivable T cells that interacts with the binding site of the nuclear factor of activated T cells (NFAT). Unlike the NFAT-binding site, however, the MLPal site does not bind proteins that are inducible by T-cell activation. We observed that the MLPal sequence is conserved in the LTRs of other mammalian retroviruses that cause T-cell diseases. Furthermore, the MLPal sequence is present in the transcriptional regulatory regions of cellular genes that either are expressed specifically in T cells or are commonly rearranged by provirus integration in thymic lymphomas. Thus, the MLPal-binding proteins may play a role in the transcriptional regulation not only of the MCF virus LTR but also of cellular genes involved in T-cell development.

Yoshimura, F K; Diem, K

1995-01-01

150

Understanding Leukemia  

MedlinePLUS

... I 800.955.4572 I www.LLS.org Tracking Your Leukemia Tests These tips may help you ... Tyrosine kinase inhibitor (TKI). A drug that blocks cell growth. Gleevec®, Sprycel® and Tasigna® are TKIs that ... team consists of master’s level oncology professionals who are available by phone Monday through Friday, 9 am to 6 pm ( ...

151

Leukemia Vaccines  

Microsoft Academic Search

Evidence that immunological effector mechanisms contribute to the elimination of leukemic blasts in allogeneic bone marrow transplantation supports the concept that the immune system plays a prominent role in the control of leukemic disease. For patients with high-risk acute leukemia, relapse prevention in the setting of minimal residual disease is paramount. This review discusses vaccine strategies aimed to stimulate a

Ludmila Glouchkova; Birgit Ackermann; Dagmar Dilloo

2003-01-01

152

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

Code of Federal Regulations, 2010 CFR

40 Ç Protection of Environment Ç 23 Ç 2010-07-01 Ç 2010-07-01 Ç false Ç Inclusion bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera; exemption from the requirement of a tolerance. Ç 180.1149 Ç Section 180.1149 Ç Protection of Environment Ç ENVIRONMENTAL PROTECTION...

2010-07-01

153

Busulfan\\/Melphalan\\/Antithymocyte Globulin Followed by Unrelated Donor Cord Blood Transplantation for Treatment of Infant Leukemia and Leukemia in Young Children: The Cord Blood Transplantation Study (COBLT) Experience  

Microsoft Academic Search

A non-total body irradiation-containing preparative regimen was studied in young children (<4 years old) undergoing unrelated donor cord blood transplantation as part of the Cord Blood Transplantation trial for the treatment of acute lymphoblastic leukemia (n = 14), acute myeloid leukemia (n = 13), undifferentiated leukemia (n = 1), juvenile myelomonocytic leukemia (n = 2), and myelodysplastic syndromes (n =

Donna A. Wall; Shelly L. Carter; Nancy A. Kernan; Neena Kapoor; Naynesh R. Kamani; Joel A. Brochstein; Haydar Frangoul; Rakesh K. Goyal; John T. Horan; Daniel Pietryga; John E. Wagner; Joanne Kurtzberg

2005-01-01

154

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

NASA Astrophysics Data System (ADS)

The International EFES-IN2P3 conference on "Many body correlations from dilute to dense nuclear systems" was held at the Institut Henri Poincaré (IHP), Paris, France, from 15-18 February 2011, on the occasion of the retirement of our colleague Peter Schuck. Correlations play a decisive role in various many-body systems such as nuclear systems, condensed matter and quantum gases. Important examples include: pairing correlations (Cooper pairs) which give rise to nuclear superfluidity (analogous to superconductivity in condensed matter); particle-hole (RPA) correlations in the description of the ground state beyond mean-field theory; clusters; and ?-particle correlations in certain nuclei. Also, the nucleons themselves can be viewed as clusters of three quarks. During the past few years, researchers have started to study how the character of these correlations changes with the variation of the density. For instance, the Cooper pairs in dense matter can transform into a Bose-Einstein condensate (BEC) of true bound states at low density (this is the BCS-BEC crossover studied in ultracold Fermi gases). Similar effects play a role in neutron matter at low density, e.g., in the "neutron skin" of exotic nuclei. The ?-cluster correlation becomes particularly important at lower density, such as in the excited states of some nuclei (e.g., the ?-condensate-like structure in the Hoyle state of 12C) or in the formation of compact stars. In addition to nuclear physics, topics from astrophysics (neutron stars), condensed matter, and quantum gases were discussed in 48 talks and 19 posters, allowing the almost 90 participants from different communities to exchange their ideas, experiences and methods. The conference dinner took place at the Musée d'Orsay, and all the participants enjoyed the very pleasant atmosphere. One session of the conference was dedicated to the celebration of Peter's retirement. We would like to take this opportunity to wish Peter all the best and we hope that he will continue his scientific work full of creative and original ideas. We would like to thank all those who helped to make the conference a success: Nguyen van Giai, S Fujii, J Margueron, K Hagino, and Y Kanada-En'yo for their help with the organization; the advisory committee for suggesting invited speakers; V Frois for her administrative help; L Petizon for the website; and the director of IPN Orsay, F Azaiez, for his support. We are indebted to IHP for providing the lecture hall free of charge, and we acknowledge the financial support from JSPS through its EFES core-to-core program, from CNRS (IN2P3 and INP), and from LIA France-Japon. Last but not least, we are grateful to all of the participants for making the conference exciting and successful. Takaharu Otsuka, Michael Urban, Taiichi YamadaEditors of the proceedings

Otsuka, Takaharu; Urban, Michael; Yamada, Taiichi

2011-09-01

155

Abnormal distribution of heterogeneous nuclear ribonucleoproteins in sporadic inclusion body myositis.  

PubMed

Previous histopathologic studies of sporadic inclusion body myositis (sIBM) identified sarcoplasmic aggregation and myonuclear depletion of the predominantly nuclear heterogeneous nuclear ribonucleoprotein (hnRNP) TDP-43 in sIBM myofibers. Here, we examined sIBM muscle for abnormalities in two other hnRNPs hnRNPA1 and hnRNPA2B1, mutations in which cause multisystem proteinopathy associated with rimmed-vacuolar myopathies. Muscle biopsy specimens from 13 patients with sIBM and 13 patients without sIBM (dermatomyositis N=3, polymyositis N=3, muscular dystrophy N=3, motor neuron disease N=2, non-neuromuscular disease N=2) underwent immunohistochemistry for hnRNPA1, hnRNPA2B1, and TDP-43. Muscle transcriptional microarray data from 27 patients with sIBM and 12 patients without neuromuscular disease was analyzed. Depletion of hnRNPA1 and hnRNPA2B1 was present in 15% and 7% of sIBM myonuclei, respectively, compared with 1% and 0% of myonuclei in non-sIBM muscle. Sarcoplasmic aggregates of hnRNPA1 and hnRNPA2B1 distinct from TDP-43 aggregates were also found in sIBM. hnRNPA1 and hnRNPA2B1, as well as other hnRNPs, gene expression was unaltered in sIBM compared to normal muscle. Along with TDP-43, other hnRNPs, including hnRNPA1 and hnRNPA2B1, are depleted from sIBM myonuclei at the protein but not transcript level. The depletion of multiple hnRNPs from sIBM myonuclei together with their sarcoplasmic aggregation suggests that one aspect of sIBM pathophysiology may involve abnormal RNA metabolism that includes hyperassembly of ribonucleoprotein granules mediated by prion-like domains in hnRNPs, evolving into pathological aggregates. PMID:24857366

Pinkus, Jack L; Amato, Anthony A; Taylor, J Paul; Greenberg, Steven A

2014-07-01

156

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

157

Polypyrimidine tract-binding protein and heterogeneous nuclear ribonucleoprotein A1 bind to human T-cell leukemia virus type 2 RNA regulatory elements.  

PubMed Central

Efficient expression of human T-cell leukemia virus (HTLV) and human immunodeficiency virus structural proteins requires Rx and Rev proteins, respectively. Decreased expression of Gag and Env appears to be due, in part, to intragenic RNA sequences, termed cis-acting repressive sequences (CRS), and may be mediated by binding of specific cellular factors. We demonstrated previously that two cellular proteins, p60CRS and p40CRS, interact with HTLV type 2.5' long terminal repeat CRS RNA and that the interaction of both proteins with CRS RNA correlates with function (A. C. Black, C. T. Ruland, J. Luo, A. Bakker, J. K. Fraser, and J. D. Rosenblatt, Virology 200:29-41, 1994). By radioimmunoprecipitation of HeLa nuclear proteins UV cross-linked to CRS RNAs with murine monoclonal antibodies, we now show that p40CRS is heterogeneous nuclear ribonucleoprotein (hnRNP) A1 and p60CRS is polypyrimidine tract-binding protein or hnRNP I. These immunoprecipitation results were confirmed by an immunobinding assay with hnRNP I and hnRNP AI antibodies and by cross-competition electrophoretic mobility shift experiments. In addition, we mapped a putative hnRNP A1 binding site in U5 RNA and demonstrated that p40CRS (hnRNP A1) binding to that site correlates with CRS function. Since both hnRNP I and hnRNP A1 have been shown to influence splicing and potentially other steps in RNA processing, the binding of both hnRNP I and hnRNP A1 to HTLV RNA regulatory elements may alter retrovirus RNA processing and may be involved in regulation by Rex.

Black, A C; Luo, J; Watanabe, C; Chun, S; Bakker, A; Fraser, J K; Morgan, J P; Rosenblatt, J D

1995-01-01

158

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

159

Occupation, hobbies, and acute leukemia in adults.  

PubMed

Occupational and industrial exposures have been implicated in the etiology of leukemia, yet uncertainty remains regarding potential high risk occupations. We examined the associations between self-reported occupations and hobbies and acute leukemia risk using data from 811 cases and 637 controls participating in a case-control study in the U.S. and Canada. We found that several occupations may increase the risk of acute leukemia, particularly occupations related to petroleum products, rubber, nuclear energy, munitions, plastics, and electronics manufacturing. Differences were noted according to histological type. Other occupations and hobbies were not clearly associated with risk. PMID:16111530

Terry, Paul D; Shore, David L; Rauscher, Garth H; Sandler, Dale P

2005-10-01

160

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

161

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

162

Allogeneic bone marrow transplantation for children with acute leukemia: long-term follow-up of patients prepared with high-dose cytosine arabinoside and fractionated total body irradiation  

Microsoft Academic Search

High-dose therapy and allogeneic matched sibling bone marrow transplantation (BMT) is considered to be the treatment of choice for children with relapsed acute lymphoblastic leukemia (ALL), or for children with acute myeloid leukemia (AML) in first remission. However, the rate of bone marrow relapse after transplant for either of these diseases remains high. In this study, we assessed the efficacy

BG Gordon; PI Warkentin; SE Strandjord; M Abromowitch; E Bayever; JL Harper; PF Coccia

1997-01-01

163

Leukemia Trial Results  

MedlinePLUS

... Compared with Ofatumumab in Patients with Previously Treated Chronic Lymphocytic Leukemia (Posted: 06/27/2014) - In an international randomized ... III clinical trial, patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who were ...

164

Leukemia & Lymphoma Society  

MedlinePLUS

The Leukemia & Lymphoma Society (LLS) is the world's largest voluntary health agency dedicated to blood cancer. The LLS mission: Cure leukemia, lymphoma, Hodgkin's disease and myeloma, and improve the quality ...

165

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

166

The t(15;17) translocation alters a nuclear body in a retinoic acid-reversible fashion.  

PubMed

Nuclear bodies (NBs) are ultrastructurally defined granules predominantly found in dividing cells. Here we show that PML, a protein involved in the t(15;17) translocation of acute promyelocytic leukaemia (APL), is specifically bound to a NB. PML and several NB-associated proteins, found as auto-antigens in primary biliary cirrhosis (PBC), are co-localized and co-regulated. The APL-derived PML-RAR alpha fusion protein is shown to be predominantly localized in the cytoplasm, whereas a fraction is nuclear and delocalizes the NB antigens to multiple smaller nuclear clusters devoid of ultrastructural organization. RA administration (which in APL patients induces blast differentiation and consequently complete remissions) causes the re-aggregation of PML and PBC auto-antigens onto the NB, while PML-RAR alpha remains mainly cytoplasmic. Thus, PML-RAR alpha expression leads to a RA-reversible alteration of a nuclear domain. These results shed a new light on the pathogenesis of APL and provide a molecular link between NBs and oncogenesis. PMID:8131741

Koken, M H; Puvion-Dutilleul, F; Guillemin, M C; Viron, A; Linares-Cruz, G; Stuurman, N; de Jong, L; Szostecki, C; Calvo, F; Chomienne, C

1994-03-01

167

Three-body description of direct nuclear reactions: Comparison with the continuum discretized coupled channels method  

SciTech Connect

The continuum discretized coupled channels (CDCC) method is compared with the exact solution of the three-body Faddeev equations in momentum space. We present results for (i) elastic and breakup observables of d+{sup 12}C at E{sub d}=56 MeV (ii) elastic scattering of d+{sup 58}Ni at E{sub d}=80 MeV, and (iii) elastic, breakup, and transfer observables for {sup 11}Be+p at E{sub {sup 11}Be}/A=38.4 MeV. Our comparative studies show that in the first two cases, the CDCC method is a good approximation of the full three-body Faddeev solution, but for the {sup 11}Be exotic nucleus, depending on the observable or the kinematic regime, it may miss some of the dynamic three-body effects that appear through the explicit coupling to the transfer channel.

Deltuva, A.; Cravo, E.; Fonseca, A. C. [Centro de Fisica Nuclear da Universidade de Lisboa, P-1649-003 Lisboa (Portugal); Moro, A. M. [Departamento de FAMN, Univ. de Sevilla (Spain); Nunes, F. M. [NSCL and Dept. of Physics and Astronomy, Michigan State University, East Lansing Michigan 48824 (United States)

2007-12-15

168

Apoptosis in acute leukemia.  

PubMed

In leukemias and malignant tumors the balance between apoptosis and cell proliferation is dysregulated. This review deals with the apoptosis in acute leukemia. There are several publications about the molecular basis of decreased apoptosis in acute lymphoid leukemia (ALL) and AML. However, there have been contradictory results. Different results are published about the correlation of the spontaneous and induced apoptosis in leukemia with prognosis. The potential causes of these contradictions are discussed. PMID:15158085

Schuler, Dezso; Szende, Béla

2004-07-01

169

Chronic neutrophilic leukemia  

Microsoft Academic Search

Summary Chronic neutrophilic leukemia (CNL) is a very rare entity, which has to be included among the chronic myeloid leukemias. Once an underlying cause of neutrophilia is excluded, the diagnosis of CNL is based on exclusion of chronic granulocytic and other types of chronic myeloid leukemias. The classification proposed by Sheperd et al. has proven to be helpful, but it

R. Zittoun; D. Réa; L. Hoang Ngoc; S. Ramond

1994-01-01

170

Studies of a laser/nuclear thermal-hardened body armor. Final report, 31 Jan 91-30 Sep 91  

SciTech Connect

The problem of laser/nuclear hardening of body armors and other applications, such as rigid wall, etc, has been investigated in this study. Earlier results from studies of hardening against space systems, which were supported by the Air Force Office of Scientific Research (AFOSR) and carried out by the Principal Investigator during 1984 to 1989 are summarized. The concepts of particle layer and photon multiple scattering inside the layers were utilized in developing a laser shield to protect against laser weapons in the 0.22 to 2.4 micrometer region of the spectrum. Protection against the threats from C02 laser weapons are addressed, and the development of a protective shield is detailed. It is now possible to apply a coating that will protect against laser/nuclear threats and reduction of solar loads for 0.22 to 16 micrometers of the spectrum. Applications are expected for rigid walls (Army containers), human body armor, thermal jackets for military hardware, etc. Finally, a mathematical model was created to help predict how the laser hardening material will behave under specific constraints that have not yet been tested in the laboratory. Also, this model can be used to extrapolate the performance of similar materials/coatings in the mid- to far-infrared wavelengths and also predict the broadband performance.

Misconi, N.Y.; Caldarella, G.J.; Roach, J.F.

1992-08-01

171

Decades Later, Chernobyl Accident Yields Clues to Leukemia Risk  

MedlinePLUS

... of cleanup workers from the Chernobyl nuclear power plant have revealed a link between ionizing radiation and chronic lymphocytic leukemia. (Photo courtesy of Dr. Victor Kryuchkov, Burnazyan Federal Medical Biophysics Center) Exposure to low doses of ionizing ...

172

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

Microsoft Academic Search

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.

H. H. Hyman; J. J. Katz

1961-01-01

173

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

174

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

175

Long-term remission of Philadelphia chromosome-positive acute lymphoblastic leukemia after allogeneic hematopoietic cell transplantation from matched sibling donors: a 20-year experience with the fractionated total body irradiation-etoposide regimen.  

PubMed

Allogeneic hematopoietic cell transplantation (HCT) is the only known curative modality for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL). Sixty-seven patients with HLA-matched sibling donors received fractionated total body irradiation (FTBI) and high-dose VP16, whereas 11 patients received FTBI/VP16/cyclophosphamide, and 1 patient received FTBI/VP16/busulfan. The median age was 36 years. At the time of HCT, 49 patients (62%) were in first complete remission (CR1) and 30 patients (38%) were beyond CR1 (> CR1). The median follow-up was 75 months (range, 14-245 months). The 10-year overall survival for the CR1 and beyond CR1 patients was 54% and 29% (P = .01), respectively, and event-free survival was 48% and 26% (P = .02), respectively. There was no significant difference in relapse incidence (28% vs 41%, P = .28), but nonrelapse mortality was significantly higher in the beyond CR1 patients, (31% vs 54%, P = .03, respectively). By univariate analysis, factors affecting event-free and overall survival were white blood cell count at diagnosis (< 30 x 10(9)/L vs > 30 x 10(9)/L) and disease status (CR1 vs > CR1). The median time to relapse for CR1 and for beyond CR1 patients was 12 months and 9 months, respectively. Our results indicate that FTBI/VP16 with or without cyclophosphamide confers long-term survival in Ph(+) ALL patients and that disease status at the time of HCT is an important predictor of outcome. PMID:18519812

Laport, Ginna G; Alvarnas, Joseph C; Palmer, Joycelynne M; Snyder, David S; Slovak, Marilyn L; Cherry, Athena M; Wong, Ruby M; Negrin, Robert S; Blume, Karl G; Forman, Stephen J

2008-08-01

176

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

PubMed

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

Wu, Guo-Zheng; Xu, Zong-Xue

2012-07-01

177

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

PubMed Central

We report a novel connection between nuclear 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., M.A. Hoyt, C. Chan, L. Goetsch, D. Botstein, and B. Byers. 1993. J. Cell Biol. 122:743–751). Here, we show that Ndc1p is a membrane protein of the NE that localizes to both NPCs and SPBs. Indirect immunofluorescence microscopy shows that Ndc1p displays punctate, nuclear peripheral localization that colocalizes with a known NPC component, Nup49p. Additionally, distinct spots of Ndc1p localization colocalize with a known SPB component, Spc42p. Immunoelectron microscopy shows that Ndc1p localizes to the regions of NPCs and SPBs that interact with the NE. The NPCs in ndc1-1 mutant cells appear to function normally at the nonpermissive temperature. Finally, we have found that a deletion of POM152, which encodes an abundant but nonessential nucleoporin, suppresses the SPB duplication defect associated with a mutation in the NDC1 gene. We show that Ndc1p is a shared component of NPCs and SPBs and propose a shared function in the assembly of these organelles into the NE.

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

1998-01-01

178

Heterochromatin Instability in Cancer: From the Barr Body to Satellites and the Nuclear Periphery  

PubMed Central

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.

Carone, Dawn M.; Lawrence, Jeanne B.

2012-01-01

179

Optical atomic magnetometer at body temperature for magnetic particle imaging and nuclear magnetic resonance.  

PubMed

Optical atomic magnetometers are often bulky and operate at elevated temperatures that impose restrictions on studying biological samples. Here we report a miniaturized Cs-based magnetometer, in contrast to conventionally used K- and Rb-based ones, with high sensitivity. The magnetic shield employed is more compact, and the optimal operation temperature of 37 degrees C is lower than previous magnetometers and is suitable for biological research. Applications include scanning magnetic imaging of functionalized magnetic particles and nuclear magnetic resonance of water. We reveal that the stability and sensitivity of the apparatus are not significantly affected by the absence of a laser stabilization device. PMID:20195311

Garcia, Nissa C; Yu, Dindi; Yao, Li; Xu, Shoujun

2010-03-01

180

[State of cerebral neuronal nuclear chromatin during multimodal stimuli to the body].  

PubMed

The state of nuclear DNA, revealed by the microfluorometric method, changed unequally in conditions of dissimilar afferentation in different classes of the neurones in the neocortex and the hippocampal dentate fascia. It may be assumed that the examined classes of cells (large pyramids and stellate neurones of the sensorimotor zone of the cerebral cortex and the granular cells of the dentate fascia of the hippocampus) possess a different structural functional organization of genome. This probably accounts for the peculiarities of their functioning. PMID:716596

Krylov, O A; Sokolova, Z A; Fedorova, K N

1978-01-01

181

Ultrastructure of cytoplasmic nucleolus-like bodies and nuclear RNP particles in late prophase of tipulid spermatocytes.  

PubMed

Late prophase stages of Pales ferruginea (Tipulidae) spermatocytes were examined by means of conventional electron microscopic section technique, combined with cytochemical methods. The cytoplasm of cells in diakinesis contains nucleolus-like bodies (NLB) 1 mum in diameter which are formed in diplotene at the pores of the nuclear membrane. They are compound structures consisting of fibro-granular RNP material which is associated wth one or two electron-dense gobules. The RNP material has a hollow core which contains polyribosomes. The NLBs possibly indicate rRNA gene amplification. At diakinesis the nucleus contains numerous electron-dense RNP particles scattered throughout the chromatin-free karyoplasm, and associated with the condensed chromosomes. The diameter of the chromation associated particles is markedly higher (mean 630 A) than that of the free particles (mean 540 A). The RNP particles seem to be aggregates of 200 A subunits. They are regarded as transcription products of chromosomal genes. PMID:985745

Fuge, H

1976-07-30

182

Stages of Chronic Lymphocytic Leukemia  

MedlinePLUS

... stages are used for chronic lymphocytic leukemia: Stage 0 In stage 0 chronic lymphocytic leukemia , there are ... or check-ups. Treatment Options by Stage Stage 0 Chronic Lymphocytic Leukemia Treatment of stage 0 chronic ...

183

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

ClinicalTrials.gov

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

2013-10-07

184

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

PubMed

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

Sykes, L R; Wiggins, G C

1986-01-01

185

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

PubMed Central

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

Sykes, Lynn R.; Wiggins, Graham C.

1986-01-01

186

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

SciTech Connect

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

Sykes, L.R.; Wiggins, G.C.

1986-01-01

187

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

NASA Astrophysics Data System (ADS)

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

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

2012-12-01

188

TCP1 complex proteins interact with phosphorothioate oligonucleotides and can co-localize in oligonucleotide-induced nuclear bodies in mammalian cells  

PubMed Central

Phosphorothioate (PS) antisense oligonucleotides (ASOs) have been successfully developed as drugs to reduce the expression of disease-causing genes. PS-ASOs can be designed to induce degradation of complementary RNAs via the RNase H pathway and much is understood about that process. However, interactions of PS-ASOs with other cellular proteins are not well characterized. Here we report that in cells transfected with PS-ASOs, the chaperonin T-complex 1 (TCP1) proteins interact with PS-ASOs and enhance antisense activity. The TCP1-? subunit co-localizes with PS-ASOs in distinct nuclear structures, termed phosphorothioate bodies or PS-bodies. Upon Ras-related nuclear protein (RAN) depletion, cytoplasmic PS-body-like structures were observed and nuclear concentrations of PS-ASOs were reduced, suggesting that TCP1-? can interact with PS-ASOs in the cytoplasm and that the nuclear import of PS-ASOs is at least partially through the RAN-mediated pathway. Upon free uptake, PS-ASOs co-localize with TCP1 proteins in cytoplasmic foci related to endosomes/lysosomes. Together, our results indicate that the TCP1 complex binds oligonucleotides with TCP1-? subunit being a nuclear PS-body component and suggest that the TCP1 complex may facilitate PS-ASO uptake and/or release from the endocytosis pathway.

Liang, Xue-hai; Shen, Wen; Sun, Hong; Prakash, Thazha P.; Crooke, Stanley T.

2014-01-01

189

TCP1 complex proteins interact with phosphorothioate oligonucleotides and can co-localize in oligonucleotide-induced nuclear bodies in mammalian cells.  

PubMed

Phosphorothioate (PS) antisense oligonucleotides (ASOs) have been successfully developed as drugs to reduce the expression of disease-causing genes. PS-ASOs can be designed to induce degradation of complementary RNAs via the RNase H pathway and much is understood about that process. However, interactions of PS-ASOs with other cellular proteins are not well characterized. Here we report that in cells transfected with PS-ASOs, the chaperonin T-complex 1 (TCP1) proteins interact with PS-ASOs and enhance antisense activity. The TCP1-? subunit co-localizes with PS-ASOs in distinct nuclear structures, termed phosphorothioate bodies or PS-bodies. Upon Ras-related nuclear protein (RAN) depletion, cytoplasmic PS-body-like structures were observed and nuclear concentrations of PS-ASOs were reduced, suggesting that TCP1-? can interact with PS-ASOs in the cytoplasm and that the nuclear import of PS-ASOs is at least partially through the RAN-mediated pathway. Upon free uptake, PS-ASOs co-localize with TCP1 proteins in cytoplasmic foci related to endosomes/lysosomes. Together, our results indicate that the TCP1 complex binds oligonucleotides with TCP1-? subunit being a nuclear PS-body component and suggest that the TCP1 complex may facilitate PS-ASO uptake and/or release from the endocytosis pathway. PMID:24861627

Liang, Xue-Hai; Shen, Wen; Sun, Hong; Prakash, Thazha P; Crooke, Stanley T

2014-08-01

190

Disruption of PML-Associated Nuclear Bodies by IE1 Correlates with Efficient Early Stages of Viral Gene Expression and DNA Replication in Human Cytomegalovirus Infection  

Microsoft Academic Search

In human cytomegalovirus (HCMV) infection, both of the major immediate-early proteins IE1(IE68, UL123) and IE2(IE86, UL122) target to PML protein-associated nuclear bodies known as PODs or ND10 at very early times after infection. IE1 causes a redistribution of both PML and IE1 from the PODs into a nuclear diffuse form, whereas IE2 initially localizes adjacent to PODs but later associates

Jin-Hyun Ahn; Gary S. Hayward

2000-01-01

191

Nuclear domain 10 of the viral aspect  

PubMed Central

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

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

2013-01-01

192

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

193

Unitary-model-operator approach to nuclear many-body theory  

NASA Astrophysics Data System (ADS)

The structure of the unitary-model-operator approach (UMOA) is discussed in the framework of general effective interaction theory. The properties of the two-body effective interaction ?12, introduced as a basic element in UMOA, are clarified. The effective interaction ?12 has some desirable features to be E-independent, Hermitian and decoupled between two spaces of two-particle states consisting of occupied and unoccupied orbits. It is noted that these properties of ?12 are advantageous over the usual Brueckner approach. The theory is applied to the calculation of the ground-state properties in 16O with various nucleon-nucleon potentials including the Bonn potential. The result is reasonable in comparison with those obtained in the usual Brueckner-Hartree-Fock calculation. The use of the Bonn potential with rather weaker tensor component leads to a better result. It is shown that the results for the saturation property, the binding energy versus charge radius, lie beyond the Coester band and get near to the experimental value.

Suzuki, K.; Okamoto, R.; Kumagai, H.

1994-07-01

194

Acute Myeloid Leukemia  

MedlinePLUS

... Treatments include chemotherapy, other drugs, radiation therapy, stem cell transplants, and targeted therapy. Targeted therapy uses substances that attack cancer cells without harming normal cells. Once the leukemia ...

195

Total Body Irradiation and Cyclophosphamide Plus Antithymocyte Globulin Regimen Is Well Tolerated and Promotes Stable Engraftment as a Preparative Regimen before T Cell-Replete Haploidentical Transplantation for Acute Leukemia.  

PubMed

We compared total body irradiation (TBI, 700 cGy)/cyclophosphamide (Cy, 3.6 g/m(2))/simustine (250 mg/m(2)) plus antithymocyte globulin (ATG) (TBI/Cy plus ATG) with cytarabine (8 g/m(2))/i.v. busulfan (Bu, 9.6 mg/kg)/Cy (3.6 g/m(2))/simustine (250 mg/m(2)) plus ATG (modified Bu/Cy plus ATG) as preparative therapy in T cell-replete haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for acute leukemia. From August 2009 to August 2013, 38 consecutive patients using TBI/Cy plus ATG regimen for T cell-replete haplo-HSCT (TBI group) at our center were eligible, which contained 28 high-risk and 10 standard-risk patients. A nested case-control study was designed. Seventy-seven patients using modified Bu/Cy plus ATG regimen (Bu group) were randomly selected in a 1 to 3:1 ratio matching for age, disease and status, year of HSCT (±2 years), and length of follow-up. Only 1 graft failure occurred in the TBI group. The incidence and time of neutrophil and platelet engraftment were comparable between the 2 groups. Severe grades III/IV graft-versus-host disease was observed in 13.4% of Bu group and only 2.6% of TBI group (P = .083). More toxicity of the liver (37.7% versus 10.5%; P = .002) and more hemorrhagic cystitis occurred in the Bu group (49.3% versus 23.7%, P = .008). Diarrhea was more common in the TBI group (44.7% versus 22.1%; P = .031). No significant differences were found in the 2-year incidences of relapse (26.5% for TBI group versus 32.3% for Bu group, P = .742), 1-year transplant-related mortality (12.6% versus 16.2%, P = .862), 2-year overall survival (60.2% versus 57.0%, P = .937), and 2-year incidence of disease-free survival (57.9% versus 56.6%, P = .845) between the 2 groups. We conclude that the TBI/Cy plus ATG regimen seems to be feasible in T cell-replete haplo-HSCT, which promotes stable engraftment and a lower incidence of liver toxicity and hemorrhagic cystitis. However, longer follow-up is necessary to determine the late relapse rate and late toxicity. PMID:24747336

Fu, Haixia; Xu, Lanping; Liu, Daihong; Liu, Kaiyan; Zhang, Xiaohui; Chen, Huan; Chen, Yuhong; Han, Wei; Wang, Yu; Wang, Jingzhi; Wang, Fengrong; Huang, Xiaojun

2014-08-01

196

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

197

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

198

Adipocytes impair leukemia treatment in mice  

PubMed Central

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

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

2009-01-01

199

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

SciTech Connect

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

Harker, W.G.; Slade, D.L.; Parr, R.L. (Univ. of Utah, Salt Lake City (United States)); Drake, F.H. (SmithKline Beecham Pharmaceuticals, King of Prussia, PA (United States))

1991-10-15

200

Ohio State study shows how chronic inflammation can cause leukemia  

Cancer.gov

A hormone-like substance produced by the body to promote inflammation can cause an aggressive form of leukemia when present at high levels, according to a new study by researchers at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. The study shows that high levels of interleukin-15 (IL-15) alone can cause large granular lymphocytic (LGL) leukemia, a rare and usually fatal form of cancer, in an animal model. The researchers also developed a treatment for the leukemia that showed no discernible side effects in the animal model.

201

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

ClinicalTrials.gov

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

2014-04-25

202

Interference with polyhedral inclusion body (PIB) production in Trichoplusia ni cells infected with a high passage strain of Autographa californica nuclear polyhedrosis virus (NPV)  

Microsoft Academic Search

Summary Trichoplusia ni cells infected with a low passage (LP) strain ofAutographa californica nuclear polyhedrosis virus (NPV) produce large numbers of polyhedral inclusion bodies (PIBs). Interference with PIB production occurs whenT. ni cells are first inoculated with a high passage (HP) strain and then challenged with the LP strain. PIB production is reduced 100 fold to the level seen with

A. H. McIntosh; R. Shamy; C. Ilsley

1979-01-01

203

Population cytogenetics of leukemia  

Microsoft Academic Search

Chronic myelogenous and acute leukemia are reviewed with regard to data obtained prior to banding of chromosomes, data obtained with banding of chromosomes, and pH-negative patients. Abnormal chromosome patterns of patients are described. Relationships of chromosome abnormalities in acute and chronic myelogenous leukemia are discussed and chromosomal abnormalities in other neoplastic conditions are reviewed. (HLW)

1975-01-01

204

Cytogenetics in acute leukemia  

Microsoft Academic Search

Cytogenetic analyses in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) have revealed a great number of non-random chromosome abnormalities. In many instances, molecular studies of these abnormalities identified specific genes implicated in the process of leukemogenesis. The more common chromosome aberrations have been associated with specific laboratory and clinical characteristics, and are now being used as diagnostic and

Krzysztof Mrózek; Nyla A Heerema; Clara D Bloomfield

2004-01-01

205

Hairy cell leukemia  

Microsoft Academic Search

In 24 patients with hairy cell leukemia, histological and fine structural findings from biopsies of the bone marrow are reported and their validity is compared with other diagnostic procedures available. Diagnosis by light microscopy of anterior iliac crest biopsies obtained by the method of myelotomy is possible with a high degree of accuracy. The differentiation of hairy cell leukemia from

K. F. Vykoupil; J. Thiele; A. Georgii

1976-01-01

206

The Family Leukemia Association  

ERIC Educational Resources Information Center

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

Pollitt, Eleanor

1976-01-01

207

Leukemia Steering Committee Roster  

Cancer.gov

Leukemia Steering Committee Roster Co-chairs Jerry Radich, M.D.Fred Hutchinson Cancer CenterSeattle, WA Wendy Stock, M.D.University of ChicagoChicago, IL Members Fred Appelbaum, M.D.Fred Hutchinson Cancer CenterSeattle, WA Deborah Banker, Ph.D.Leukemia

208

Immunotherapy for Pediatric Leukemia  

PubMed Central

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

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

2013-01-01

209

Acute leukemia in women.  

PubMed

The treatment and survival outcome of acute leukemia in women is generally similar to that of men. However, acute leukemia in women poses additional challenges in clinical practice. In addition to important precautions during therapy, such as prevention of abnormal uterine bleeding in premenopausal women and therapy during pregnancy, women who are survivors of acute leukemia face unique and potentially long-term health-related problems. In this review, we address the aforementioned issues, as well as the various health and psychosocial challenges faced by women who survive childhood leukemia during their path to adulthood. Finally, we address the issue of therapy-related acute leukemia in the category of women who are survivors of breast and ovarian cancer. PMID:20187729

Lo-Coco, Francesco; Fouad, Tamer M; Ramadan, Safaa M

2010-03-01

210

Immunotoxins for leukemia.  

PubMed

Unconjugated monoclonal antibodies that target hematopoietic differentiation antigens have been developed to treat hematologic malignancies. Although some of these have activity against chronic lymphocytic leukemia and hairy cell leukemia, in general, monoclonal antibodies have limited efficacy as single agents in the treatment of leukemia. To increase their potency, the binding domains of monoclonal antibodies can be attached to protein toxins. Such compounds, termed immunotoxins, are delivered to the interior of leukemia cells based on antibody specificity for cell surface target antigens. Recombinant immunotoxins have been shown to be highly cytotoxic to leukemic blasts in vitro, in xenograft model systems, and in early-phase clinical trials in humans. These agents will likely play an increasing role in the treatment of leukemia. PMID:24578503

Wayne, Alan S; Fitzgerald, David J; Kreitman, Robert J; Pastan, Ira

2014-04-17

211

Molecular characterization of NDP52, a novel protein of the nuclear domain 10, which is redistributed upon virus infection and interferon treatment  

Microsoft Academic Search

The nuclear domain (ND)10 also described as POD or Kr bodies is involved in the development of acute promyelocytic leukemia and virus-host interac- tions. Immunofluorescence analysis using a variety of human autoimmune sera and monoclonal antibodies showed a typical dot like nuclear staining for ND10, suggesting that this structure consists of several pro- teins. Two of the ND10 proteins, Spl00

Frank Korioth; Christian Gieffers; Gerd G. Maul; Jfirgen Frey

1995-01-01

212

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

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; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

2013-04-09

213

The effect of body weight on altered expression of nuclear receptors and cyclooxygenase-2 in human colorectal cancers  

PubMed Central

Background Epidemiological studies on risk factors for colorectal cancer (CRC) have mainly focused on diet, and being overweight is now recognized to contribute significantly to CRC risk. Overweight and obesity are defined as an excess of adipose tissue mass and are associated with disorders in lipid metabolism. Peroxisome proliferator-activated receptors (PPARs) and retinoid-activated receptors (RARs and RXRs) are important modulators of lipid metabolism and cellular homeostasis. Alterations in expression and activity of these ligand-activated transcription factors might be involved in obesity-associated diseases, which include CRC. Cyclooxygenase-2 (COX-2) also plays a critical role in lipid metabolism and alterations in COX-2 expression have already been associated with unfavourable clinical outcomes in epithelial tumors. The objective of this study is to examine the hypothesis questioning the relationship between alterations in the expression of nuclear receptors and COX-2 and the weight status among male subjects with CRC. Method The mRNA expression of the different nuclear receptor subtypes and of COX-2 was measured in 20 resected samples of CRC and paired non-tumor tissues. The association between expression patterns and weight status defined as a body mass index (BMI) was statistically analyzed. Results No changes were observed in PPAR? mRNA expression while the expression of PPAR?, retinoid-activated receptors and COX-2 were significantly increased in cancer tissues compared to normal colon mucosa (P ? 0.001). The weight status appeared to be an independent factor, although we detected an increased level of COX-2 expression in the normal mucosa from overweight patients (BMI ? 25) compared to subjects with healthy BMI (P = 0.002). Conclusion Our findings show that alterations in the pattern of nuclear receptor expression observed in CRC do not appear to be correlated with patient weight status. However, the analysis of COX-2 expression in normal colon mucosa from subjects with a high BMI suggests that COX-2 deregulation might be driven by excess weight during the colon carcinogenesis process.

Delage, Barbara; Rullier, Anne; Capdepont, Maylis; Rullier, Eric; Cassand, Pierrette

2007-01-01

214

Body-wave magnitudes of underground nuclear explosions at major test sites derived by the maximum-likelihood method  

NASA Astrophysics Data System (ADS)

Body-wave magnitudes (mb) of ~600 underground nuclear tests have been derived from station amplitudes collected by the International Seismological Centre (ISC), by a joint inversion for mb and station-specific magnitude corrections (Lilwall 1986). The maximum-likelihood method was used, to reduce the upward bias of network mean magnitudes caused by data censoring for low-magnitude disturbances where stations do not report arrivals that are hidden by the ambient noise at the time. Threshold noise levels at each station were derived from the ISC amplitudes using the method of Kelly and Lacoss (1969). The joint inversion is valid only for sites where enough explosions occurred, and stations with enough arrivals (a minimum of three for both), for a statistical treatment to be valid. It is used on the sites: Kazakhstan and Novaya Zemlya, former Soviet Union; Singer, China; Mururoa and Fangataufa, French Polynesia; and Nevada, USA. At sites where four or more arrivals could be used to derive magnitudes and station terms for twenty-five or more explosions (Nevada, Kazakhstan and Mururoa), the resulting magnitudes and station terms were fixed and a second inversion carried out to derive magnitudes for additional explosions with as few as three arrivals. A further ~90 magnitudes were derived thus, mostly of Nevada explosions.

Peacock, Sheila; Douglas, Alan; Bowers, David; Selby, Neil

2013-04-01

215

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

216

Saccharomyces cerevisiae MPS2 encodes a membrane protein localized at the spindle pole body and the nuclear envelope.  

PubMed

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 (). 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. PMID:10397772

Muñoz-Centeno, M C; McBratney, S; Monterrosa, A; Byers, B; Mann, C; Winey, M

1999-07-01

217

Enhancement of U4/U6 Small Nuclear Ribonucleoprotein Particle Association in Cajal Bodies Predicted by Mathematical Modeling  

PubMed Central

Spliceosomal small nuclear ribonucleoprotein particles (snRNPs) undergo specific assembly steps in Cajal bodies (CBs), nonmembrane-bound compartments within cell nuclei. An example is the U4/U6 di-snRNP, assembled from U4 and U6 monomers. These snRNPs can also assemble in the nucleoplasm when cells lack CBs. Here, we address the hypothesis that snRNP concentration in CBs facilitates assembly, by comparing the predicted rates of U4 and U6 snRNP association in nuclei with and without CBs. This was accomplished by a random walk-and-capture simulation applied to a three-dimensional model of the HeLa cell nucleus, derived from measurements of living cells. Results of the simulations indicated that snRNP capture is optimal when nuclei contain three to four CBs. Interestingly, this is the observed number of CBs in most cells. Microinjection experiments showed that U4 snRNA targeting to CBs was U6 snRNP independent and that snRNA concentration in CBs is ?20-fold higher than in nucleoplasm. Finally, combination of the simulation with calculated association rates predicted that the presence of CBs enhances U4 and U6 snRNP association by up to 11-fold, largely owing to this concentration difference. This provides a chemical foundation for the proposal that these and other cellular compartments promote molecular interactions, by increasing the local concentration of individual components.

Klingauf, Mirko; Stanek, David

2006-01-01

218

Mie light scattering calculations for an Indian age-related nuclear cataract with a high density of multilamellar bodies  

PubMed Central

Purpose Multilamellar bodies (MLBs) are lipid-coated spheres (1–4 µm in diameter) found with greater frequency in the nuclear region of human age-related cataracts compared with human transparent lenses. Mie light scattering calculations have demonstrated that MLBs are potential sources of forward light scattering in human age-related nuclear cataracts due to their shape, size, frequency, and cytoplasmic contents, which often differ in refractive index from their surroundings. Previous studies have used data from several non-serial tissue sections viewed by light microscopy to extrapolate a volume and have assumed that MLBs are random in distribution. Currently, confocal microscopy is being used to examine actual tissue volumes from age-related nuclear cataracts and transparent lenses collected in India to confirm MLB shape, size, frequency, and randomness. These data allow Mie scattering calculations to be done with directly observed MLBs in intact tissue. Methods Whole Indian donor lenses and Indian lens nuclei after extracapsular cataract extraction were immersion-fixed in 10% formalin for 24 h and in 4% paraformaldehyde for 24 h before sectioning with a Vibratome. The 160 µm thick sections were stained for 24 h in the lipid dye DiI (1,1’-dilinoleyl-3,3,3?,3? tetramethylindocarbocyanine, 4-chlorobenzenesulfonate), washed, stabilized in Permount under coverslips and examined with a Zeiss LSM 510 confocal microscope. Individual volumes of tissue (each typically 500,000 µm3) were examined using a plan-apochromat 63X oil (NA=1.4) lens. Other lenses were prepared for electron microscopy and histological examination using previously described procedures. Results Analysis of tissue volumes within Indian age-related nuclear cataracts and transparent lenses has confirmed that most MLBs are 1–4 µm in diameter and typically spherical with some occurring as doublets or in clusters. Most Indian cataracts and transparent lenses are similar to samples obtained in the United States. One cataract contained as many as 400,000 MLBs per mm3 –100 times more than in cataracts collected in the United States. Pairwise distribution analysis has revealed that MLBs even in this exceptional case are found with a distribution that appears to be random. Mie calculations indicate that more than 90% of the incident light could be scattered by the high density of MLBs. Conclusions An important finding was that one advanced Indian cataract contained many more MLBs than cataracts examined from India and previously from the United States. This indicates that specific conditions or susceptibilities may exist that promote the formation of excessive MLBs. Based on the extremely high frequency, as well as their spherical shape, large size, and apparent random distribution, the MLBs are predicted according to Mie light scattering calculations to cause high amounts of forward scattering sufficient to produce nuclear opacity.

Johnsen, Sonke; Metlapally, Sangeetha; Costello, M. Joseph; Ramamurthy, Balasubramanya; Krishna, Pravin V.; Balasubramanian, Dorairajan

2008-01-01

219

Sorafenib 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 Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia

2013-01-08

220

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

PubMed Central

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.

Gibeaux, Romain; Politi, Antonio Z.; Nedelec, Francois; Antony, Claude; Knop, Michael

2013-01-01

221

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

222

B30.2/SPRY domain in tripartite motif-containing 22 is essential for the formation of distinct nuclear bodies.  

PubMed

Tripartite motif-containing 22 (TRIM22) is an important antiviral protein that forms distinct nuclear bodies (NB) in many cell types. This study aims to identify functional domains/residues for TRIM22's nuclear localization and NB formation. Deletion of the really-interesting-new-gene (RING) domain, which is essential for its antiviral property, abolished TRIM22 NB formation. However, mutation of two critical residues Cys15 and Cys18 to alanine in the RING domain, did not affect NB formation notably. Although the deletion of the putative bipartite nuclear localization signal (NLS) abolished TRIM22 localization and NB formation, the B30.2/SplA and ryanodine receptor (SPRY) domain, and residues 491-494 specifically are also essential for nuclear localization and NB formation. PMID:19481078

Sivaramakrishnan, Gayathri; Sun, Yang; Rajmohan, Rajamuthiah; Lin, Valerie C L

2009-06-18

223

Juvenile myelomonocytic leukemia and chronic myelomonocytic leukemia  

Microsoft Academic Search

In 1982, chronic myelomonocytic leukemia (CMML) was first classified in the category of myelodysplastic syndromes (MDSs), but it always seemed somewhat out of place compared with the rest of the MDS categories. In the 1990s, many argued that there were two different forms of CMML, a proliferative type and a myelodysplastic type. Then in 2001 the World Health Organization created

P D Emanuel

2008-01-01

224

Flavopiridol in Treating Patients With Chronic Lymphocytic Leukemia  

ClinicalTrials.gov

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

2013-01-16

225

An ARID Domain-Containing Protein within Nuclear Bodies Is Required for Sperm Cell Formation in Arabidopsis thaliana  

PubMed Central

In plants, each male meiotic product undergoes mitosis, and then one of the resulting cells divides again, yielding a three-celled pollen grain comprised of a vegetative cell and two sperm cells. Several genes have been found to act in this process, and DUO1 (DUO POLLEN 1), a transcription factor, plays a key role in sperm cell formation by activating expression of several germline genes. But how DUO1 itself is activated and how sperm cell formation is initiated remain unknown. To expand our understanding of sperm cell formation, we characterized an ARID (AT-Rich Interacting Domain)-containing protein, ARID1, that is specifically required for sperm cell formation in Arabidopsis. ARID1 localizes within nuclear bodies that are transiently present in the generative cell from which sperm cells arise, coincident with the timing of DUO1 activation. An arid1 mutant and antisense arid1 plants had an increased incidence of pollen with only a single sperm-like cell and exhibited reduced fertility as well as reduced expression of DUO1. In vitro and in vivo evidence showed that ARID1 binds to the DUO1 promoter. Lastly, we found that ARID1 physically associates with histone deacetylase 8 and that histone acetylation, which in wild type is evident only in sperm, expanded to the vegetative cell nucleus in the arid1 mutant. This study identifies a novel component required for sperm cell formation in plants and uncovers a direct positive regulatory role of ARID1 on DUO1 through association with histone acetylation.

Zheng, Binglian; He, Hui; Zheng, Yanhua; Wu, Wenye; McCormick, Sheila

2014-01-01

226

What Is Childhood Leukemia?  

MedlinePLUS

... bones. New blood cells (red blood cells, white blood cells, and platelets) are made there. In infants, active bone marrow ... form white blood cells (other than lymphocytes), red blood cells, or platelets. Hybrid or mixed lineage leukemias: In these rare ...

227

Acute Lymphoblastic Leukemia  

MedlinePLUS

... has spread, your physician may order a chest x-ray, lumbar puncture (which collects fluid from the spinal ... The treatment of ALL is done in multiple phases. The first phase kills the leukemia cells in ...

228

Hairy cell leukemia  

MedlinePLUS

... B cells, a type of white blood cell (lymphocyte). ... Kantarjian H, O’Brien S. The chronic leukemias. In Goldman L, Schafer AI, eds. Cecil Medicine . 24th ed. Philadelphia, PA: Saunders Elsevier; 2011:chap 190. National Comprehensive Cancer Network. ...

229

Drugs Approved for Leukemia  

Cancer.gov

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

230

Population Cytogenetics of Leukemia.  

National Technical Information Service (NTIS)

Chronic myelogenous and acute leukemia are reviewed with regard to data obtained prior to banding of chromosomes, data obtained with banding of chromosomes, and pH-negative patients. Abnormal chromosome patterns of patients are described. Relationships of...

J. Rowley

1975-01-01

231

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

2013-08-01

232

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

ClinicalTrials.gov

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

2013-01-22

233

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

234

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

235

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

ClinicalTrials.gov

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

2013-04-01

236

The Latency-Associated Nuclear Antigen Tethers the Kaposi's Sarcoma-Associated Herpesvirus Genome to Host Chromosomes in Body Cavity-Based Lymphoma Cells  

Microsoft Academic Search

Viruses that establish latent infection must maintain their DNA in the host nucleus through many cellular generations. Here we identify a novel mechanism by which the gammaherpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) may achieve this persistence in latently infected body cavity-based lymphoma (BCBL) cells. We find that KSHV genomic DNA is associated with host chromosomes and colocalizes with the latency-associated nuclear

Murray A. Cotter; Erle S. Robertson

1999-01-01

237

ZNF198, a zinc finger protein rearranged in myeloproliferative disease, localizes to the PML nuclear bodies and interacts with SUMO-1 and PML  

SciTech Connect

The ZNF198/FGFR1 fusion gene in atypical myeloproliferative disease produces a constitutively active cytoplasmic tyrosine kinase, unlike ZNF198 which is normally a nuclear protein. We have now shown that the ZNF198/FGFR1 fusion kinase interacts with the endogenous ZNF198 protein suggesting that the function of ZNF198 may be compromised in cells expressing it. Little is currently known about the endogenous function of ZNF198 and to investigate this further we performed a yeast two-hybrid analysis and identified SUMO-1 as a binding partner of ZNF198. These observations were confirmed using co-immunoprecipitation which demonstrated that ZNF198 is covalently modified by SUMO-1. Since many of the SUMO-1-modified proteins are targeted to the PML nuclear bodies we used confocal microscopy to show that SUMO-1, PML and ZNF198 colocalize to punctate structures, shown by immunocytochemistry to be PML bodies. Using co-immunoprecipitation we now show that PML and sumoylated ZNF198 can be found in a protein complex in the cell. Mutation of the SUMO-1 binding site in wild-type ZNF198 resulted in loss of distinct PML bodies, reduced PML levels and a more dispersed nuclear localization of the PML protein. In cells expressing ZNF198/FGFR1, which also lack the SUMO-1 binding site, SUMO-1 is preferentially localized in the cytoplasm, which is associated with loss of distinct PML bodies. Recently, arsenic trioxide (ATO) was proposed as an alternative therapy for APL that was resistant to traditional therapy. Treatment of cells expressing ZNF198/FGFR1 with ATO demonstrated reduced autophosphorylation of the ZNF198/FGFR1 protein and induced apoptosis, which is not seen in cells expressing wild-type ZNF198. Overall our results suggest that the sumoylation of ZNF198 is important for PML body formation and that the abrogation of sumoylation of ZNF198 in ZNF198/FGFR1 expressing cells may be an important mechanism in cellular transformation.

Kunapuli, Padmaja [Department of Cancer Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263 (United States); Kasyapa, Chitta S. [Department of Cancer Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263 (United States); Chin, Suet-Feung [Cancer Genomics Program, Hutchison/MRC Research Centre, Cambridge CB2 2XZ (United Kingdom); Caldas, Carlos [Cancer Genomics Program, Hutchison/MRC Research Centre, Cambridge CB2 2XZ (United Kingdom); Cowell, John K. [Department of Cancer Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263 (United States)]. E-mail: John.Cowell@RoswellPark.org

2006-11-15

238

The Drosophila homolog of human AF10/AF17 leukemia fusion genes (Dalf) encodes a zinc finger/leucine zipper nuclear protein required in the nervous system for maintaining EVE expression and normal growth.  

PubMed

Sibling neurons in the embryonic central nervous system (CNS) of Drosophila can adopt distinct states as judged by gene expression and axon projection. In the NB4-2 lineage, two even-skipped (eve)-expressing sibling neuronal cells, RP2 and RP2sib, are formed in each hemineuromere. Throughout embryogenesis, only RP2, but not RP2sib, maintains eve expression. In this report, we describe a P-element induced mutation that alters the expression pattern of EVE in RP2 motoneurons in the Drosophila embryonic CNS. The mutation was mapped to a Drosophila homolog of human AF10/AF17 leukemia fusion genes (alf), and therefore named Dalf. Like its human counterparts, Dalf encodes a zinc finger/leucine zipper nuclear protein that is widely expressed in embryonic and larval tissues including neurons and glia. In Dalf mutant embryos, the RP2 motoneuron no longer maintains EVE expression. The effect of the Dalf mutation on EVE expression is RP2-specific and does not affect other characteristics of the RP2 motoneuron. In addition to the embryonic phenotype, Dalf mutant larvae are retarded in their growth and this defect can be rescued by the ectopic expression of a Dalf transgene under the control of a neuronal GAL4 driver. This indicates a requirement for Dalf function in the nervous system for maintaining gene expression and the facilitation of normal growth. PMID:11165485

Bahri, S M; Chia, W; Yang, X

2001-02-01

239

The role of the cytoskeleton in cell body enlargement, increased nuclear eccentricity and chromatolysis in axotomized spinal motor neurons  

Microsoft Academic Search

BACKGROUND: When spinal motor axons are injured, the nucleolus, nucleus and cell body of the injured cell transiently increase in size, the nucleus becomes more eccentrically placed, and the organization of polyribosomes into Nissl bodies is temporarily disrupted. The mechanisms for these classical morphological responses to axotomy have not been satisfactorily explained. RESULTS: In this study we address the role

David L McIlwain; Victoria B Hoke

2005-01-01

240

Obatoclax, Fludarabine, and Rituximab in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia  

ClinicalTrials.gov

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

2013-09-27

241

[Classification of myeloid leukemias].  

PubMed

Myeloid leukemia in this series corresponds to the myeloid neoplasms of the 4th WHO classification of pathology and genetics of tumor of haematopoietic and lymphoid tissue. The myeloid neoplasms are composed of six categories, which are 1) myeloproliferative neoplasms (MPN), a new category of 2) myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1, 3) myelodysplastic syndrome (MDS)/MPN, 4) MDS, 5) acute myeloid leukemia (AML) and related precursor neoplasms, and 6) acute leukemias of ambiguous lineage. In MPNs without chronic myelogenous leukemia, the genetic marker of JAK2 V617F is added to the diagnostic criteria for polycythemia vera, essential thrombocythemia and primary myelofibrosis. MDS has the new subtype of refractory cytopenia with unilineage dysplasia composed of refractory anemia, refractory neutropenia and refractory thrombocytopenia. AML with t(9; 11) (p22;q23); MLLT3-MLL, AML with t(6;9) (p23; q34); DEK-NUP214, AML with inv(3) (q21q26.2) or t(3; 3) (q21 ; q26.2); RPN1-EVI1 and AML (megakaryoblastic) with t(1; 22) (p13; q13); RBM15-MKL1 are added to the subtype of AML with recurrent genetic abnormalities, and AML with gene mutations of NPM1 and CEBPA are also added as provisional entities of it. The myeloid neoplasms of the 4th WHO classification are comprehensive and seem to be dynamic by incorporating the results of leukemia researches. PMID:19860179

Kuriyama, Kazutaka

2009-10-01

242

Gastrointestinal manifestations of leukemia.  

PubMed

Gastrointestinal (GI) manifestations of leukemia occur in up to 25% of patients at autopsy, generally during relapse. Its presence varies with the type of leukemia and has been decreasing over time due to improved chemotherapy. Gross leukemic lesions are most common in the stomach, ileum, and proximal colon. Leukemia in the esophagus and stomach includes hemorrhagic lesions from petechiae to ulcers, leukemic infiltrates, pseudomembranous esophagitis, and fungal esophagitis. Lesions in the small and large bowel are usually hemorrhagic or infiltrative. Infiltration of lymphoreticular organs, mainly spleen, liver, and lymph nodes, is more prominent in chronic than acute leukemia. Neutropenic enterocolitis, a necrotizing process involving the cecum, ascending colon, and terminal ileum, is increasing in incidence due to greater intensity of chemotherapy. Distension of bowel leads to mucosal breaches, permitting entry of organisms that grow profusely in the absence of neutrophils. Ischemic necrosis follows, leading to perforation and/or peritonitis. Patients present with fever, abdominal pain, diarrhea, nausea, vomiting, abdominal distension and tenderness. Ultrasound and computed tomography scans show thickening of the bowel wall. Treatment is supportive with surgery for necrosis and perforation. The main GI causes of death in leukemia are hemorrhage, infection, and necrotizing enterocolitis. PMID:21913980

Ebert, Ellen C; Hagspiel, Klaus D

2012-03-01

243

Tanespimycin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, Chronic Myelomonocytic Leukemia, or Myelodysplastic Syndromes  

ClinicalTrials.gov

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(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; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

2013-09-27

244

[Leukemia stem cell].  

PubMed

Cancer is the main cause of death in advanced countries. It has become progressively clear that cancer cells are distributed in a developmental hierarchy, in which whole cancer tissues originate from cancer stem cells(CSCs). CSCs were first discovered in a case of acute myeloid leukemia. Leukemia stem cells(LSCs)are resistant to conventional chemotherapies because of their dormancy and are therefore the cause of minimal residual disease and relapse. Many investigators are working to develop novel therapeutic strategies for eliminating LSCs. LSC biology is discussed in the first part of this review, and the therapeutic approach to LSC targeting is described in the latter part. PMID:24743272

Iwasaki, Hiromi

2014-03-01

245

Predictions of Leukemia Risks to Astronauts from Solar Particle Events  

NASA Technical Reports Server (NTRS)

Leukemias consisting of acute and chronic myeloid leukemia and acute lymphatic lymphomas represent the earliest cancers that appear after radiation exposure, have a high lethality fraction, and make up a significant fraction of the overall fatal cancer risk from radiation for adults. Several considerations impact the recommendation of a preferred model for the estimation of leukemia risks from solar particle events (SPE's): The BEIR VII report recommends several changes to the method of calculation of leukemia risk compared to the methods recommended by the NCRP Report No. 132 including the preference of a mixture model with additive and multiplicative components in BEIR VII compared to the additive transfer model recommended by NCRP Report No. 132. Proton fluences and doses vary considerably across marrow regions because of the characteristic spectra of primary solar protons making the use of an average dose suspect. Previous estimates of bone marrow doses from SPE's have used an average body-shielding distribution for marrow based on the computerized anatomical man model (CAM). We have developed an 82-point body-shielding distribution that faithfully reproduces the mean and variance of SPE doses in the active marrow regions (head and neck, chest, abdomen, pelvis and thighs) allowing for more accurate estimation of linear- and quadratic-dose components of the marrow response. SPE's have differential dose-rates and a pseudo-quadratic dose response term is possible in the peak-flux period of an event. Also, the mechanistic basis for leukemia risk continues to improve allowing for improved strategies in choosing dose-rate modulation factors and radiation quality descriptors. We make comparisons of the various choices of the components in leukemia risk estimates in formulating our preferred model. A major finding is that leukemia could be the dominant risk to astronauts for a major solar particle event.

Cucinotta, F. A.; Atwell, W.; Kim, M. Y.; George, K. A.; Ponomarev, A.; Nikjoo, H.; Wilson, J. W.

2006-01-01

246

Role of Integrin Alpha4 in Drug Resistance of Leukemia  

PubMed Central

Chemotherapeutic drug resistance in acute lymphoblastic leukemia (ALL) is a significant problem, resulting in poor responsiveness to first-line treatment or relapse after transient remission. Classical anti-leukemic drugs are non-specific cell cycle poisons; some more modern drugs target oncogenic pathways in leukemia cells, although in ALL these do not play a very significant role. By contrast, the molecular interactions between microenvironment and leukemia cells are often neglected in the design of novel therapies against drug resistant leukemia. It was shown however, that chemotherapy resistance is promoted in part through cell–cell contact of leukemia cells with bone marrow (BM) stromal cells, also called cell adhesion-mediated drug resistance (CAM-DR). Incomplete response to chemotherapy results in persistence of resistant clones with or without detectable minimal residual disease (MRD). Approaches for how to address CAM-DR and MRD remain elusive. Specifically, studies using anti-functional antibodies and genetic models have identified integrin alpha4 as a critical molecule regulating BM homing and active retention of normal and leukemic cells. Pre-clinical evidence has been provided that interference with alpha4-mediated adhesion of ALL cells can sensitize them to chemotherapy and thus facilitate eradication of ALL cells in an MRD setting. To this end, Andreeff and colleagues recently provided evidence of stroma-induced and alpha4-mediated nuclear factor-?B signaling in leukemia cells, disruption of which depletes leukemia cells of strong survival signals. We here review the available evidence supporting the targeting of alpha4 as a novel strategy for treatment of drug resistant leukemia.

Shishido, Stephanie; Bonig, Halvard; Kim, Yong-Mi

2014-01-01

247

A novel triple-modality reporter gene for whole-body fluorescent, bioluminescent, and nuclear noninvasive imaging  

Microsoft Academic Search

Two genetic reporter systems were developed for multimodality reporter gene imaging of different molecular-genetic processes using fluorescence, bioluminescence (BLI), and nuclear imaging techniques. The eGFP cDNA was fused at the N-terminus with HSV1-tk cDNA bearing a nuclear export signal from MAPKK (NES-HSV1-tk) or with truncation at the N-terminus of the first 45 amino acids (?45HSV1-tk) and with firefly luciferase at

Vladimir Ponomarev; Michael Doubrovin; Inna Serganova; Jelena Vider; Aleksander Shavrin; Tatiana Beresten; Anna Ivanova; Ludmila Ageyeva; Vilia Tourkova; Julius Balatoni; William Bornmann; Ronald Blasberg; Juri Gelovani Tjuvajev

2004-01-01

248

Leukemia in benzene workers  

Microsoft Academic Search

To evaluate the possible association between occupational exposure to benzene and subsequent death from leukemia, the National Institute for Occupational Safety and Health (NIOSH) conducted a retrospective cohort mortality study of workers who had been exposed to benzene in the manufacture of rubber hydrochloride at two locations in Ohio. Ascertainment of vital status was accomplished for 98% of the cohort.

Robert A. Rinsky; Ronald J. Young; Alexander B. Smith

1981-01-01

249

Plasma cell leukemia  

Microsoft Academic Search

Plasma cell leukemia (PCL) is a rare, yet aggressive plasma cell (PC) neoplasm, variant of multiple myeloma (MM), characterized by high levels of PCs circulating in the peripheral blood. PCL can either originate de novo (primary PCL) or as a secondary leukemic transformation of MM (secondary PCL). Presenting signs and symptoms are similar to those seen in MM such as

Flavio Albarracin; Rafael Fonseca

2011-01-01

250

Familial Chronic Lymphocytic Leukemia.  

National Technical Information Service (NTIS)

Chronic lymphocytic leukemia (CLL) was previously documented in a father and 4 of his offspring. Follow-up studies revealed spontaneous regression of the disease in 1 patient and shifts in the clinical patterns in other patients; the unaffected sibling de...

C. Y. Neuland W. A. Blattner D. L. Mann M. C. Fraser S. Tsai

1983-01-01

251

Leukemia Steering Committee  

Cancer.gov

The LKSC follows an efficient, cost-effective, science-driven, and transparent process to identify and promote the "Best Science" in clinical research on leukemia and related diseases by addressing the design and prioritization of phase III trials and large phase II studies.

252

Selective activation of NFAT by promyelocytic leukemia protein  

Microsoft Academic Search

Promyelocytic leukemia (PML) protein is a tumor suppressor with complicated action mechanisms not yet fully understood. In this study, we found that the nuclear factor of activated T cell (NFAT) is an unexpected partner of PML: PML specifically enhanced the transcription activation of NFAT. In PML-null mouse embryonic fibroblasts, no transcription activity of NFAT could be detected. There was a

Y-H Lo; C-C Wu; H-M Shih; M-Z Lai

2008-01-01

253

Quantitative studies on graft-versus-leukemia after allogeneic bone marrow transplantation in rat models for acute myelocytic and lymphocytic leukemia.  

PubMed

The major shortcoming of present day treatment of leukemia by bone marrow transplantation (BMT) remains leukemia relapse. It has become clear that a graft-versus-host reaction (GVHR) is accompanied by a graft-versus-leukemia reaction (GVLR) which may prevent leukemia relapse. In two non-immunogenic rat leukemia models, the Brown Norway acute myelocytic leukemia (BNML) and the WAG/Rij acute lymphocytic leukemia L4415, total body irradiation (TBI) was given to induce 'minimal residual disease' (MRD). Subsequently, it was attempted to evoke a GVLR by using syngeneic or allogeneic BMT, with or without addition of graded numbers of lymphocytes. In both leukemia models the addition of high numbers of syngeneic lymphocytes to the syngeneic graft had no antileukemic effect. Allogeneic marrow grafts, which contain at the most 8% lymphocytes, only resulted in a GVLR when splenocytes were added. The therapeutic window was found to be narrow, i.e. in fully mismatched BMT the number of allogeneic splenocytes resulting in a significant GVLR (2-3 log leukemic cell kill) without inducing (lethal) acute GVHD was critical. Increasing the number of allogeneic spleen cells added to the allogeneic BM graft induced lethal acute GVHD. To date, our data indicate that the GVLR is an allogeneic effect, inseparable from GVHD. PMID:7951103

Kloosterman, T C; Tielemans, M J; Martens, A C; van Bekkum, D W; Hagenbeek, A

1994-07-01

254

Proton nuclear magnetic resonance spectroscopy reveals cellular lipids involved in resistance to adriamycin and taxol by the K562 leukemia cell line.  

PubMed

Proton nuclear magnetic resonance spectroscopy was performed on whole cells to study lipids and metabolites in Adriamycin- and Taxol-resistant K562 cells expressing multidrug resistance (MDR) and their sensitive counterparts. With one-dimensional spectra, both resistant cell lines showed lower fatty acid methylene:methyl ratios and higher choline:methyl ratios than sensitive cells. Using two-dimensional COSY spectra, a decrease in the glutamine content was evidenced in resistant cells. When these cells were maintained in culture medium without the drug, the fatty acid signals were partially recovered. Adriamycin-resistant K562 cells were also treated for 4 days with a high dose of verapamil, a MDR-reversing agent. The nuclear magnetic resonance spectra of verapamil-treated cells also showed partial recovery of fatty acid signals. These results could be paralleled with the reversion of the resistant phenotype, as evidenced by measuring the inhibiting concentration of Adriamycin and vinblastine in K562adr cells cultured without the drug or after short-term exposure to verapamil. Conversely, P-glycoprotein and mRNA expression and DNA amplification of the mdr gene were not modified when compared to resistant cells, suggesting that the MDR phenotype could be partially reversed independently of the mdr gene amplification and expression. These results demonstrate the role of lipids in the resistance phenomenon. PMID:8758912

Le Moyec, L; Tatoud, R; Degeorges, A; Calabresse, C; Bauza, G; Eugène, M; Calvo, F

1996-08-01

255

Leukemia and Benzene  

PubMed Central

Excessive exposure to benzene has been known for more than a century to damage the bone marrow resulting in decreases in the numbers of circulating blood cells, and ultimately, aplastic anemia. Of more recent vintage has been the appreciation that an alternative outcome of benzene exposure has been the development of one or more types of leukemia. While many investigators agree that the array of toxic metabolites, generated in the liver or in the bone marrow, can lead to traumatic bone marrow injury, the more subtle mechanisms leading to leukemia have yet to be critically dissected. This problem appears to have more general interest because of the recognition that so-called “second cancer” that results from prior treatment with alkylating agents to yield tumor remissions, often results in a type of leukemia reminiscent of benzene-induced leukemia. Furthermore, there is a growing literature attempting to characterize the fine structure of the marrow and the identification of so called “niches” that house a variety of stem cells and other types of cells. Some of these “niches” may harbor cells capable of initiating leukemias. The control of stem cell differentiation and proliferation via both inter- and intra-cellular signaling will ultimately determine the fate of these transformed stem cells. The ability of these cells to avoid checkpoints that would prevent them from contributing to the leukemogenic response is an additional area for study. Much of the study of benzene-induced bone marrow damage has concentrated on determining which of the benzene metabolites lead to leukemogenesis. The emphasis now should be directed to understanding how benzene metabolites alter bone marrow cell biology.

Snyder, Robert

2012-01-01

256

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

257

Treatment of Children with Acute Myeloid Leukemia  

MedlinePLUS

... Next Topic Treatment of children with acute promyelocytic leukemia Treatment of children with acute myeloid leukemia Treatment for most children ... 2014 Back to top » Guide Topics What Is Leukemia in Children? Causes, Risk Factors, and Prevention Early Detection, Diagnosis, ...

258

How Is Chronic Lymphocytic Leukemia Staged?  

MedlinePLUS

... How is chronic lymphocytic leukemia treated? How is chronic lymphocytic leukemia staged? For most cancers, staging is the process ... and the results of imaging tests. Staging for chronic lymphocytic leukemia A staging system is a standardized way for ...

259

Gemtuzumab Ozogamicin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Acute Promyelocytic 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); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia

2014-07-21

260

MS-275 and Azacitidine in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia  

ClinicalTrials.gov

Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

2014-04-09

261

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

262

Measurement of Total Body Radioactivity in Man. An Evaluation of Detector Geometries with Applications in Radiation Protection and Nuclear Medicine.  

National Technical Information Service (NTIS)

Techniques for the determination of whole-body radioactivity in man using uncollimated NaI(Tl) detectors have been studied. Geometrical effects and photon attenuation effects due to the different shapes of humans as well as due to varying in-vivo radioact...

Y. Naversten

1982-01-01

263

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

264

Treatment of Acute Myeloid Leukemia  

Microsoft Academic Search

\\u000a The acute myeloid leukemias (AML) represent a heterogeneous group of malignancies derived from the pluripotent hematopoietic\\u000a stem cell. These leukemias are generally characterized by genetic lesions that result in a combination of defects causing\\u000a unregulated proliferation of cells and defects in cellular maturation (Gilliland and Griffin 2002). AML accounts for approximately\\u000a 15–20% of acute leukemia in children. In contrast to

Brenda Gibson; John Perentesis; Todd A. Alonzo; Gertjan J. L. Kaspers

265

Plasma cell leukemia with myelofibrosis  

Microsoft Academic Search

Summary We describe a case of plasma cell leukemia associated with myelofibrosis. A 60-year-old woman was admitted due to lumbago and monoclonal hypergammaglobulinemia. Peripheral blood showed about 40% of plasma-cell-like cells. A bone marrow aspiration was dry tap. The patient was diagnosed as having plasma cell leukemia with myelofibrosis by bone marrow biopsy. Plasma cell leukemia as well as myelofibrosis

T. Murayama; T. Matsui; Y. Hayashi; T. Taniguchi; M. Ito; T. Natazuka; S. Imoto; N. Iwata; T. Isobe; H. Ito; K. Chihara

1994-01-01

266

Phase 1 Study of Terameprocol (EM-1421) in Patients With Leukemia  

ClinicalTrials.gov

Leukemias; Acute Myeloid Leukemia (AML); Acute Lymphocytic Leukemia (ALL); Adult T Cell Leukemia (ATL); Chronic Myeloid Leukemia (CML-BP); Chronic Lymphocytic Leukemia (CLL); Myelodysplastic Syndrome (MDS); Chronic Myelomonocytic Leukemia (CMML)

2009-01-29

267

Childhood Cancer: Leukemia (For Parents)  

MedlinePLUS

... are diagnosed with leukemia are referred to a pediatric oncologist, a specialist in childhood ... other health care professionals. Certain patient features (such as age and initial white blood ...

268

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

ClinicalTrials.gov

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

2013-01-10

269

Hairy cell leukemia  

Microsoft Academic Search

Opinion statement  The standard therapy for hairy cell leukemia (HCL) is with the nucleoside analogs, 2’-deoxycoformycin (dCF) or 2-chlorodeoxyadenosine\\u000a (CdA), which produce morphologic complete remissions (CRs) in the majority of patients, although residual hairy cells can\\u000a frequently be detected by molecular or immunologic techniques. Relapses continue to occur over time, but most patients respond\\u000a well to retreatment withthe same agent. The

Lynn Savoie; James B. Johnston

2001-01-01

270

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

271

Primary plasma cell leukemia  

Microsoft Academic Search

Four cases of primary plasma cell leukemia (PPCL) admitted to Zhongshan Hospital from 1959 to 1987 are reported with a review\\u000a on additional 40 cases reported in China. Comparing with the 57 cases of multiple myeloma (MM) treated in our hospital, the\\u000a following features were observed in PPCL: (1) The age was younger, with a mean of 45.2 years, 34.1%

Cai Zeji; Zhang Guozhen

1991-01-01

272

Plasma cell leukemia  

Microsoft Academic Search

Opinion statement  Plasma cell leukemia (PCL) is a rare aggressive variant of multiple myeloma (MM) characterized by a fulminant course and poor\\u000a prognosis. The median survival is measured in months. Therapy and prognosis partially depend on whether the disease presents\\u000a de novo or as a secondary process involving the leukemic transformation of a previously diagnosed MM. Secondary PCL represents\\u000a a terminal

Suzanne R. Hayman; Rafael Fonseca

2001-01-01

273

Hairy Cell Leukemia Variant  

Microsoft Academic Search

A 59-year-old man presented with lymphocytosis with huge splenomegaly. The abnormal lymphocytes had a high nucleoplasmxytoplasm ratio, a prominent nucleolus and hairy cytoplasmic projections. Immunophenotyping revealed B-cell leukemia with negative reactions to CD5 and CD25. Cytogenetic study showed 46, XY, der(5)t(5;6)(q35;p21), del(7)(p13)\\/ 46, idem, add(22)(q13). The patient did not respond to chlorambucil and a combination of cyclophosphamide, vincristine and prednisolone.

Po Dunn; Lee-Yung Shih; Yat-Sen Ho; Hwai-Fang Tien

1995-01-01

274

Chronic myelogenous leukemia  

Microsoft Academic Search

Chronic myelogenous leukemia (CML) consists of a clonal malignancy that arises from a pluripotent hematopoietic stem call.\\u000a In most cases, neoplastic cells are characterized by the formation of a shortened chromosome 22 called the Philadelphia chromosome.\\u000a It results from a reciprocal translocation between long arms of chromosomes 9 and 22. A rearranged gene (bcr-abl) is the consequence of this translocation,

Vito Michele Lauta

2003-01-01

275

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

276

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 ...

277

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

278

Thyroiditis mimicking relapse of acute lymphoblastic leukemia: Gallium-67 scan suggested the diagnosis  

PubMed Central

Acute lymphoblastic leukemia (ALL) is the most common form of leukemia in childhood and accounts for 85% of cases. ALL frequently presents as an infectious process with an abrupt onset of high fever. Thyroid disease has been reported to have a strong association with acute leukemia. Gallium (Ga-67) citrate has been used in the investigation of patients labeled as having pyrexia of unknown origin. We report a case of a 13-year-old female patient who presented with fever and suspected disease relapse after a period of disease remission; however, gallium-67 citrate whole body scan suggested the diagnosis of thyroiditis.

Othman, Saleh

2010-01-01

279

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

280

Local Energy-Density Functional Approach to Many-Body Nuclear Systems with S-Wave Pairing  

NASA Astrophysics Data System (ADS)

The ground-state properties of superfluid nuclear systems with 1S0 pairing are studied within a local energy-density functional (LEDF) approach. A new form of the LEDF is proposed with a volume part which fits the Friedman-Pandharipande and Wiringa-Fiks-Fabrocini equation of state at low and moderate densities and allows an extrapolation to higher densities which preserves causality. For inhomogeneous systems, a surface term is added, with two free parameters, which has a fractional form like a Padé approximant containing the square of the density gradient in both the numerator and denominator. In addition to the direct and exchange Coulomb interaction energy, an effective density-dependent Coulomb-nuclear correlation term is included with one more free parameter. A three-parameter fit to the masses and radii of about 100 spherical nuclei has shown that the latter term gives a contribution of the same order of magnitude as the Nolen-Schiffer anomaly in the Coulomb displacement energy. The root-mean-square deviations from experimental masses and radii with the proposed LEDF come out about a factor of two smaller than those obtained with the conventional functionals based on the Skyrme or finite-range Gogny force, or on relativistic mean-field theory. The generalized variational principle is formulated leading to the self-consistent Gor'kov equations which are sovled exactly, with physical boundary conditions both for the bound and scattering states. The method is used to calculate the differential observables such as odd-even mass differences and staggering in charge radii. With a zero-range density-dependent cutoff pairing interaction incorporating a density-gradient term, the evolution of these observables is reproduced reasonably well, including the kinks at magic neutron numbers and the sizes of the associated staggering. An extrapolation from the pairing properties of finite nuclei to pairing in infinite nuclear matter is discussed. A "reference" value of the pairing gap ?F? 3.3 MeV is found for subsaturated nuclear matter at about 0.65 of the equilibrium density. With the formulated LEDF approach, we study also the dilute limit in both the weak and strong coupling regimes. Within the sum rules approach it is shown that the density-dependent pairing may also induce sizeable staggering and kinks in the evolution of the mean energies of multipole excitations.

Fayans, S. A.; Zawischa, D.

281

[Chronic myelomonocytic leukemia in adults].  

PubMed

Chronic myelomonocytic leukemia (CMML) is characterized by the association of myelodysplastic features and proliferation of both granulocytic and monocytic series. This disease frequently indolent, may however demonstrate progressive course and/or transform to acute leukemia. Nosologic and diagnostic problems raised by this malignant hematological pathology, its clinical and biological presentations, and current treatments are reported in this review. PMID:9404487

Baudard, M; Delmer, A; Zittoun, R

1997-09-01

282

Developmental Outcome of Childhood Leukemia.  

ERIC Educational Resources Information Center

Literature on developmental and psychosocial outcomes of childhood leukemia is reviewed, focusing on preschool-age children. Studies are categorized in terms of outcome measures: intelligence/achievement, neuropsychological, memory/attention, and psychosocial tests. Evidence suggests that preschool children with leukemia are at high risk for…

Coniglio, Susan J.; Blackman, James A.

1995-01-01

283

The effect of chronic hypoxia on the number and nuclear diameter of type I cells in the carotid bodies of rats.  

PubMed Central

We measured the number and nuclear diameter of type I cells in the carotid bodies of 10 normal rats and in 10 rats living in a hypobaric chamber at a pressure of 460 mm Hg for 25 to 96 days. In normal rats, the number of type I rats, the number ranged from 15.92 to 30.77 times 10-3 with a mean of 40.79 times 10-3 which differed significantly from that in the control group. In 5 hypoxic rats the number of type I cells was less than the highest figure in the control group. The mean diameter of the nuclei of type I cells of hypoxic rats (5.5 mu) was greater than that of the controls (5.0 mu). The largest type I nuclei were seen in those rats which had been subjected to hypoxia for the shortest time. Images Fig 1 Fig 2

Laidler, P.; Kay, J. M.

1975-01-01

284

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

285

SJG-136 in Treating Patients With Relapsed or Refractory Acute Leukemia, Myelodysplastic Syndromes, Blastic Phase Chronic Myelogenous Leukemia, or Chronic Lymphocytic 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(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Chronic Lymphocytic Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

2013-09-27

286

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

287

What Happens After Treatment for Childhood Leukemia?  

MedlinePLUS

... LIST » What happens after treatment for childhood leukemia? Social and emotional issues during and after treatment of childhood leukemia Late ... your child’s doctor about childhood leukemia? Next Topic Social and emotional issues during and after treatment of childhood leukemia What ...

288

Bendamustine Plus Alemtuzumab for Refractory Chronic Lymphocytic Leukemia (CLL)  

ClinicalTrials.gov

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

2013-08-20

289

[Molecular targeted therapy in lymphoid leukemias].  

PubMed

Recent advances in the treatment of lymphoid leukemias have incorporated molecular targeted drugs (CD20-targeting rituximab and BCR-ABL tyrosine kinase inhibitors) into the traditional chemotherapeutic agents. This article reviews novel molecular targeted therapies for patients with lymphoid leukemias including acute lymphoblastic leukemia, chronic lymphocytic leukemia, hairly cell leukemia and HTLV-I-related adult T-cell leukemia. Investigational agents that will be discussed in this review include inotuzumab, blinatumomab, alemtuzumab, ofatumumab, ibrutinib, idelalisib, bafetinib, lenalidomide, ABT-199 and mogamulizumab. Novel approaches warrant continued research to improve outcomes for patients with lymphoid leukemias. PMID:25016810

Kojima, Kensuke; Ando, Toshihiko; Kimura, Shinya

2014-06-01

290

Clinicopathologic analysis of acute myeloid leukemia arising from chronic myelomonocytic leukemia.  

PubMed

Acute myeloid leukemia arising from chronic myelomonocytic leukemia is currently classified as acute myeloid leukemia with myelodysplasia-related changes, a high-risk subtype. However, the specific features of these cases have not been well described. We studied 38 patients with chronic myelomonocytic leukemia who progressed to acute myeloid leukemia. We compared the clinicopathologic and genetic features of these cases with 180 patients with de novo acute myeloid leukemia and 34 patients with acute myeloid leukemia following myelodysplastic syndromes. We also examined features associated with progression from chronic myelomonocytic leukemia to acute myeloid leukemia by comparing the progressed chronic myelomonocytic leukemia cases with a cohort of chronic myelomonocytic leukemia cases that did not transform to acute myeloid leukemia. Higher white blood cell count, marrow cellularity, karyotype risk score, and Revised International Prognostic Scoring System score were associated with more rapid progression from chronic myelomonocytic leukemia to acute myeloid leukemia. Patients with acute myeloid leukemia ex chronic myelomonocytic leukemia were older (P<0.01) and less likely to receive aggressive treatment (P=0.02) than de novo acute myeloid leukemia patients. Most cases showed monocytic differentiation and fell into the intermediate acute myeloid leukemia karyotype risk group; 55% had normal karyotype and 17% had NPM1 mutation. Median overall survival was 6 months, which was inferior to de novo acute myeloid leukemia (17 months, P=0.002) but similar to post myelodysplastic syndrome acute myeloid leukemia. On multivariate analysis of all acute myeloid leukemia patients, only age and karyotype were independent prognostic variables for overall survival. Our findings indicate that acute myeloid leukemia following chronic myelomonocytic leukemia displays aggressive behavior and support placement of these cases within the category of acute myeloid leukemia with myelodysplasia-related changes. The poor prognosis of these patients may be related to an older population and lack of favorable-prognosis karyotypes that characterize many de novo acute myeloid leukemia cases. PMID:23307061

Courville, Elizabeth L; Wu, Yue; Kourda, Jihen; Roth, Christine G; Brockmann, Jillian; Muzikansky, Alona; Fathi, Amir T; de Leval, Laurence; Orazi, Attilio; Hasserjian, Robert P

2013-06-01

291

Fast and accurate quantitative metabolic profiling of body fluids by nonlinear sampling of 1H–13C two-dimensional nuclear magnetic resonance spectroscopy.  

PubMed

Two-dimensional (2D) nuclear magnetic resonance (NMR) methods have shown to be an excellent analytical tool for the identification and characterization of statistically relevant changes in low-abundance metabolites in body fluid. The advantage of 2D NMR in terms of minimized ambiguities in peak assignment, aided in metabolite identifications and comprehensive metabolic profiling comes with the cost of increased NMR data collection time; making it inconvenient choice for routine metabolic profiling. We present here a method for the reduction in NMR data collection time of 2D (1)H-(13)C NMR spectroscopy for the purpose of quantitative metabolic profiling. Our method combines three techniques; which are nonlinear sampling (NLS), forward maximum (FM) entropy reconstruction, and J-compensated quantitative heteronuclear single quantum (HSQC) (1)H-(13)C NMR spectra. We report here that approximately 22-fold reduction in 2D NMR data collection time for the body fluid samples can be achieved by this method, without any compromise in quantitative information recovery of various low abundance metabolites. The method has been demonstrated in standard mixture solution, native, and lyophilized human urine samples. Our proposed method has potential to make quantitative metabolic profiling by 2D NMR as a routine method for various metabonomic studies. PMID:23061661

Rai, Ratan Kumar; Sinha, Neeraj

2012-11-20

292

Substrate profiling of human vaccinia-related kinases identifies coilin, a Cajal body nuclear protein, as a phosphorylation target with neurological implications.  

PubMed

Protein phosphorylation by kinases plays a central role in the regulation and coordination of multiple biological processes. In general, knowledge on kinase specificity is restricted to substrates identified in the context of specific cellular responses, but kinases are likely to have multiple additional substrates and be integrated in signaling networks that might be spatially and temporally different, and in which protein complexes and subcellular localization can play an important role. In this report the substrate specificity of atypical human vaccinia-related kinases (VRK1 and VRK2) using a human peptide-array containing 1080 sequences phosphorylated in known signaling pathways has been studied. The two kinases identify a subset of potential peptide targets, all of them result in a consensus sequence composed of at least four basic residues in peptide targets. Linear peptide arrays are therefore a useful approach in the characterization of kinases and substrate identification, which can contribute to delineate the signaling network in which VRK proteins participate. One of these target proteins is coilin; a basic protein located in nuclear Cajal bodies. Coilin is phosphorylated in Ser184 by both VRK1 and VRK2. Coilin colocalizes and interacts with VRK1 in Cajal bodies, but not with the mutant VRK1 (R358X). VRK1 (R358X) is less active than VRK1. Altered regulation of coilin might be implicated in several neurological diseases such as ataxias and spinal muscular atrophies. PMID:21920476

Sanz-García, Marta; Vázquez-Cedeira, Marta; Kellerman, Efrat; Renbaum, Paul; Levy-Lahad, Ephrat; Lazo, Pedro A

2011-12-21

293

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

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

2014-04-23

295

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

296

Acute Myeloid Leukemia (AML) Treatment in Adults (Beyond the Basics)  

MedlinePLUS

... Initial treatment of acute promyelocytic leukemia in adults Molecular biology of acute promyelocytic leukemia Molecular genetics of acute ... Initial treatment of acute promyelocytic leukemia in adults Molecular biology of acute promyelocytic leukemia Molecular genetics of acute ...

297

Chronic Myelomonocytic Leukemia (CMML) and Juvenile Myelomonocytic Leukemia (JMML)  

MedlinePLUS

... attack the disease (graft-versus-leukemia effect). The theory being tested with a reduced-intensity transplant is ... shown to play a role in helping the growth of JMML cells. This drug has been approved ...

298

Nuclear Aggresomes Form by Fusion of PML-associated AggregatesV?  

PubMed Central

Nuclear aggregates formed by proteins containing expanded poly-glutamine (poly-Q) tracts have been linked to the pathogenesis of poly-Q neurodegenerative diseases. Here, we show that a protein (GFP170*) lacking poly-Q tracts forms nuclear aggregates that share characteristics of poly-Q aggregates. GFP170* aggregates recruit cellular chaperones and proteasomes, and alter the organization of nuclear domains containing the promyelocytic leukemia (PML) protein. These results suggest that the formation of nuclear aggregates and their effects on nuclear architecture are not specific to poly-Q proteins. Using GFP170* as a model substrate, we explored the mechanistic details of nuclear aggregate formation. Fluorescence recovery after photobleaching and fluorescence loss in photobleaching analyses show that GFP170* molecules exchange rapidly between aggregates and a soluble pool of GFP170*, indicating that the aggregates are dynamic accumulations of GFP170*. The formation of cytoplasmic and nuclear GFP170* aggregates is microtubule-dependent. We show that within the nucleus, GFP170* initially deposits in small aggregates at or adjacent to PML bodies. Time-lapse imaging of live cells shows that small aggregates move toward each other and fuse to form larger aggregates. The coalescence of the aggregates is accompanied by spatial rearrangements of the PML bodies. Significantly, we find that the larger nuclear aggregates have complex internal substructures that reposition extensively during fusion of the aggregates. These studies suggest that nuclear aggregates may be viewed as dynamic multidomain inclusions that continuously remodel their components.

Fu, Lianwu; Gao, Ya-sheng; Tousson, Albert; Shah, Anish; Chen, Tung-Ling L.; Vertel, Barbara M.; Sztul, Elizabeth

2005-01-01

299

Cilengitide in Treating 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 Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b)

2013-01-23

300

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

301

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

302

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

303

Decitabine and Bortezomib in Treating 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(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

2014-03-19

304

Decitabine in Treating Patients With Previously Untreated 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); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

2013-02-25

305

Vaccine Therapy Plus Immune Adjuvant in Treating Patients With Chronic Myeloid Leukemia, Acute Myeloid Leukemia, or Myelodysplastic Syndrome  

ClinicalTrials.gov

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia in Remission; Chronic Phase Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndromes; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

2013-01-04

306

Stages of Chronic Myelogenous Leukemia  

MedlinePLUS

... or other substances to identify and attack specific cancer cells without harming normal cells. Tyrosine kinase inhibitors are targeted therapy drugs used to treat chronic myelogenous leukemia. Imatinib mesylate , ...

307

Management of chronic lymphocytic leukemia  

PubMed Central

In the last decade, the management of chronic lymphocytic leukemia has undergone profound changes that have been driven by an improved understanding of the biology of the disease and the approval of several new drugs. Moreover, many novel drugs are currently under evaluation for rapid approval or have been approved by regulatory agencies, further broadening the available therapeutic armamentarium for patients with chronic lymphocytic leukemia. The use of novel biological and genetic parameters combined with a careful clinical evaluation allows us to dissect some of the heterogeneity of the disease and to distinguish patients with a very mild onset and course, who often will not need any treatment, from those with an intermediate prognosis and a third group with a very aggressive course (high-risk leukemia). On this background, it becomes increasingly challenging to select the right treatment strategy. In this paper, we describe our own approach to the management of different patients with chronic lymphocytic leukemia.

Ghia, Paolo; Hallek, Michael

2014-01-01

308

What Is Chronic Myelomonocytic Leukemia?  

MedlinePLUS

... In this way CMML is more like a myeloproliferative disease ( myelo -- bone marrow, proliferative -- excessive growth). Chronic myeloid leukemia is an example of a myeloproliferative disease where there is an overproduction of white ...

309

How Is Childhood Leukemia Classified?  

MedlinePLUS

... mature into megakaryocytes (the cells that make platelets). World Health Organization (WHO) classification of AML The FAB ... phases, but a common system (proposed by the World Health Organization) is described below. If the leukemia ...

310

Chromatin redistribution of the DEK oncoprotein represses hTERT transcription in leukemias.  

PubMed

Although numerous factors have been found to modulate hTERT transcription, the mechanism of its repression in certain leukemias remains unknown. We show here that DEK represses hTERT transcription through its enrichment on the hTERT promoter in cells from chronic and acute myeloid leukemias, chronic lymphocytic leukemia, but not acute lymphocytic leukemias where hTERT is overexpressed. We isolated DEK from the hTERT promoter incubated with nuclear extracts derived from fresh acute myelogenous leukemia (AML) cells and from cells expressing Tax, an hTERT repressor encoded by the human T cell leukemia virus type 1. In addition to the recruitment of DEK, the displacement of two potent known hTERT transactivators from the hTERT promoter characterized both AML cells and Tax-expressing cells. Reporter and chromatin immunoprecipitation assays permitted to map the region that supports the repressive effect of DEK on hTERT transcription, which was proportionate to the level of DEK-promoter association but not with the level of DEK expression. Besides hTERT repression, this context of chromatin redistribution of DEK was found to govern about 40% of overall transcriptional modifications, including those of cancer-prone genes. In conclusion, DEK emerges as an hTERT repressor shared by various leukemia subtypes and seems involved in the deregulation of numerous genes associated with leukemogenesis. PMID:24563617

Karam, Maroun; Thenoz, Morgan; Capraro, Valérie; Robin, Jean-Philippe; Pinatel, Christiane; Lancon, Agnès; Galia, Perrine; Sibon, David; Thomas, Xavier; Ducastelle-Lepretre, Sophie; Nicolini, Franck; El-Hamri, Mohamed; Chelghoun, Youcef; Wattel, Eric; Mortreux, Franck

2014-01-01

311

Updates of the nuclear equation of state for core-collapse supernovae and neutron stars: effects of 3-body forces, QCD, and magnetic fields  

NASA Astrophysics Data System (ADS)

We summarize several new developments in the nuclear equation of state for supernova simulations and neutron stars. We discuss an updated and improved Notre-Dame-Livermore Equation of State (NDL EoS) for use in supernovae simulations. This Eos contains many updates. Among them are the effects of 3- body nuclear forces at high densities and the possible transition to a QCD chiral and/or super-conducting color phase at densities. We also consider the neutron star equation of state and neutrino transport in the presence of strong magnetic fields. We study a new quantum hadrodynamic (QHD) equation of state for neutron stars (with and without hyperons) in the presence of strong magnetic fields. The parameters are constrained by deduced masses and radii. The calculated adiabatic index for these magnetized neutron stars exhibit rapid changes with density. This may provide a mechanism for star-quakes and flares in magnetars. We also investigate the strong magnetic field effects on the moments of inertia and spin down of neutron stars. The change of the moment of inertia associated with emitted magnetic flares is shown to match well with observed glitches in some magnetars. We also discuss a perturbative calculation of neutrino scattering and absorption in hot and dense hyperonic neutron-star matter in the presence of a strong magnetic field. The absorption cross-sections show a remarkable angular dependence in that the neutrino absorption strength is reduced in a direction parallel to the magnetic field and enhanced in the opposite direction. The pulsar kick velocities associated with this asymmetry comparable to observed pulsar velocities and may affect the early spin down rate of proto-neutron star magnetars with a toroidal field configuration.

Mathews, G. J.; Meixner, M.; Olson, J. P.; Suh, I.-S.; Kajino, T.; Maruyama, T.; Hidaka, J.; Ryu, C.-Y.; Cheoun, M.-K.; Lan, N. Q.

2013-07-01

312

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

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 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

314

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

315

Immunotherapy in acute myeloid leukemia.  

PubMed

Treatment of acute myeloid leukemia (AML) with current chemotherapy regimens is still disappointing, with overall survival rates of ? 40% at 5 years. It is now well established that AML cells can evade the immune system through multiple mechanisms, including the expression of the enzyme indoleamine 2,3 dioxygenase. Immunotherapeutic strategies, including both active, such as vaccination with leukemia-associated antigens, and passive, such as adoptive transfer of allogeneic natural killer cells, may overcome leukemia escape and lead to improved cure. Allogeneic hemopoeitic stem cell transplantation, the most effective treatment of AML, is the best known model of immunotherapy. Following transplant, recipient AML cells are eradicated by donor immune cells through the graft-versus-leukemia (GVL) effect. However, GVL is clinically associated with graft-versus-host disease, the major cause of mortality after transplant. GVL is mediated by donor T cells recognizing either leukemia-associated antigens or minor as well as major histocompatibility antigens. Several innovative strategies have been devised to generate leukemia reactive T cells so as to increase GVL responses with no or little graft-versus-host disease. PMID:24341888

Arpinati, Mario; Curti, Antonio

2014-01-01

316

Antibody therapy for pediatric leukemia.  

PubMed

Despite increasing cure rates for pediatric leukemia, relapsed disease still carries a poor prognosis with significant morbidity and mortality. Novel targeted therapies are currently being investigated in an attempt to reduce adverse events and improve survival outcomes. Antibody therapies represent a form of targeted therapy that offers a new treatment paradigm. Monoclonal antibodies are active in pediatric acute lymphoblastic leukemia (ALL) and are currently in Phase III trials. Antibody-drug conjugates (ADCs) are the next generation of antibodies where a highly potent cytotoxic agent is bound to an antibody by a linker, resulting in selective targeting of leukemia cells. ADCs are currently being tested in clinical trials for pediatric acute myeloid leukemia and ALL. Bispecific T cell engager (BiTE) antibodies are a construct whereby each antibody contains two binding sites, with one designed to engage the patient's own immune system and the other to target malignant cells. BiTE antibodies show great promise as a novel and effective therapy for childhood leukemia. This review will outline recent developments in targeted agents for pediatric leukemia including monoclonal antibodies, ADCs, and BiTE antibodies. PMID:24795859

Vedi, Aditi; Ziegler, David S

2014-01-01

317

Antibody Therapy for Pediatric Leukemia  

PubMed Central

Despite increasing cure rates for pediatric leukemia, relapsed disease still carries a poor prognosis with significant morbidity and mortality. Novel targeted therapies are currently being investigated in an attempt to reduce adverse events and improve survival outcomes. Antibody therapies represent a form of targeted therapy that offers a new treatment paradigm. Monoclonal antibodies are active in pediatric acute lymphoblastic leukemia (ALL) and are currently in Phase III trials. Antibody-drug conjugates (ADCs) are the next generation of antibodies where a highly potent cytotoxic agent is bound to an antibody by a linker, resulting in selective targeting of leukemia cells. ADCs are currently being tested in clinical trials for pediatric acute myeloid leukemia and ALL. Bispecific T cell engager (BiTE) antibodies are a construct whereby each antibody contains two binding sites, with one designed to engage the patient’s own immune system and the other to target malignant cells. BiTE antibodies show great promise as a novel and effective therapy for childhood leukemia. This review will outline recent developments in targeted agents for pediatric leukemia including monoclonal antibodies, ADCs, and BiTE antibodies.

Vedi, Aditi; Ziegler, David S.

2014-01-01

318

[Juvenile myelomonocytic leukemias].  

PubMed

Juvenile myelomonocytic leukemias (JMML) are rare but severe myelodysplastic and myeloproliferative neoplasms of infancy. They represent about 10 new cases per year in France and preferentially affect males. JMML are all stem cell diseases the common denominator of which is RAS pathway dysregulation, due to mutations in RAS (NRAS, KRAS) or RAS regulatory components (PTPN11, NF1 or CBL). This leads to an hypersensivity of myeloid progenitors to GM-CSF (granulo-macrophagic colony stimulating factor) which induces in turn excessive monocytic and macrophagic proliferation in blood and bone marrow. All organs can be infiltrated by this monocytic proliferation leading to multisystemic failure. Blast crisis with transformation into acute myeloid leukemia occurs in one third of patients. A salient feature of JMML is their frequent association with predisposition syndromes such as Noonan syndrome, neurofibromatosis and CBL syndrome, which are developmental diseases associated with a constitutional RAS pathway deregulation, now grouped under the name RASopathies. Clinical heterogeneity makes JMML diagnosis difficult. Splenomagaly is the most constant sign. Palor, adenopathy, respiratory or cutaneous symptoms can also be present. Blood smear shows monocytosis (>1×10(9)/L) presence of myeloid progenitors and abnormal basophils. The demonstration of an endogeneous in vitro growth of myeloid progenitors although not very specific can help JMML diagnosis. Nowadays, genetic typing has to be included in the workup of JMML diagnosis and allows to evidence a mutation in more than 90% of cases. JMML have a poor prognosis. The only curative treatment is bone marrow transplantation but approximately 35% of patients relapse. JMML clinical course is highly heterogeneous and unpredictable. Some rare patients have an indolent evolution or even spontaneous remission. Age over two years, thrombopenia below 33×10(9)/L and high foetal hemoglobin (HbF) level for age are poor prognosis criteria but hardly predict individual outcome. Several research directions are currently being explored to improve prognosis prediction and provide more effective targeted treatments. PMID:24691193

Lachenaud, Julie; Strullu, Marion; Baruchel, André; Cavé, Hélène

2014-03-01

319

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

2014-07-28

320

Body Piercing  

MedlinePLUS

MENU Return to Web version Body Piercing Body Piercing What is body piercing? Body piercing is when a hole is made in your skin or through a part of ... pierce? The earlobe is the most common body piercing. Other common places to pierce include the eyebrow, ...

321

Immunophenotypic evidence of leukemia after induction therapy predicts relapse: results from a prospective Children's Cancer Group study of 252 patients with acute myeloid leukemia  

Microsoft Academic Search

Approximately 40% of children with acute myeloid leukemia (AML) who respond to initial therapy subsequently relapse. Mul- tidimensional flow cytometry employing a standardized panel of monoclonal anti- bodies enables the detection of small numbers of occult leukemic cells that persist during therapy using technology adaptable by most clinical laboratories. We performed a prospective, blinded evaluation of bone marrow specimens obtained

Eric L. Sievers; Beverly J. Lange; Todd A. Alonzo; Robert B. Gerbing; Irwin D. Bernstein; Franklin O. Smith; Robert J. Arceci; William G. Woods; Michael R. Loken

2003-01-01

322

Differentiation therapy of leukemia: 3 decades of development  

PubMed Central

A characteristic feature of leukemia cells is a blockade of differentiation at a distinct stage in cellular maturation. In the 1970s and 1980s, studies demonstrating the capabilities of certain chemicals to induce differentiation of hematopoietic cell lines fostered the concept of treating leukemia by forcing malignant cells to undergo terminal differentiation instead of killing them through cytotoxicity. The first promising reports on this notion prompted a review article on this subject by us 25 years ago. In this review, we revisit this interesting field of study and report the progress achieved in the course of nearly 3 decades. The best proof of principle for differentiation therapy has been the treatment of acute promyelocytic leukemia with all-trans retinoic acid. Attempts to emulate this success with other nuclear hormone ligands such as vitamin D compounds and PPAR? agonists or different classes of substances such as hematopoietic cytokines or compounds affecting the epigenetic landscape have not been successful on a broad scale. However, a multitude of studies demonstrating partial progress and improvements and, finally, the new powerful possibilities of forward and reverse engineering of differentiation pathways by manipulation of transcription factors support the continued enthusiasm for differentiation therapy of leukemia in the future.

Stewart, Daphne; Koeffler, H. Phillip

2009-01-01

323

Role of the SUMO-interacting motif in HIPK2 targeting to the PML nuclear bodies and regulation of p53  

SciTech Connect

Homeodomain-interacting protein kinase 2 (HIPK2) is a key regulator of various transcription factors including p53 and CtBP in the DNA damage signaling pathway. PML-nuclear body (NB) is required for HIPK2-mediated p53 phosphorylation at Ser46 and induction of apoptosis. Although PML-NB targeting of HIPK2 has been shown, much is not clear about the molecular mechanism of HIPK2 recruitment to PML-NBs. Here we show that HIPK2 colocalizes specifically with PML-I and PML-IV. Mutational analysis showed that HIPK2 recruitment to PML-IV-NBs is mediated by the SUMO-interaction motifs (SIMs) of both PML-IV and HIPK2. Wild-type HIPK2 associated with SUMO-conjugated PML-IV at a higher affinity than with un-conjugated PML-IV, while the association of a HIPK2 SIM mutant with SUMO-modified PML-IV was impaired. In colony formation assays, HIPK2 strongly suppressed cell proliferation, but HIPK2 SIM mutants did not. In addition, activation and phosphorylation of p53 at the Ser46 residue were impaired by HIPK2 SIM mutants. These results suggest that SIM-mediated HIPK2 targeting to PML-NBs is crucial for HIPK2-mediated p53 activation and induction of apoptosis.

Sung, Ki Sa; Lee, Yun-Ah [Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of)] [Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Kim, Eui Tae [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of)] [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Lee, Seung-Rock [Department of Biochemistry, Research Center for Aging and Geriatrics, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190 (Korea, Republic of)] [Department of Biochemistry, Research Center for Aging and Geriatrics, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190 (Korea, Republic of); Ahn, Jin-Hyun [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of)] [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Choi, Cheol Yong, E-mail: choicy@skku.ac.kr [Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of)

2011-04-15

324

RAC GTPases in Tobacco and Arabidopsis Mediate Auxin-Induced Formation of Proteolytically Active Nuclear Protein Bodies That Contain AUX/IAA ProteinsW?  

PubMed Central

Auxin signaling relies on ubiquitin ligase SCFTIR1-mediated 26S proteasome-dependent proteolysis of a large family of short-lived transcription regulators, auxin/indole acetic acid (Aux/IAA), resulting in the derepression of auxin-responsive genes. We have shown previously that a subset of Rac GTPases is activated by auxin, and they in turn stimulate auxin-responsive gene expression. We show here that increasing Rac signaling activity promotes Aux/IAA degradation, whereas downregulating that activity results in the reduction of auxin-accelerated Aux/IAA proteolysis. Observations reported here reveal a novel function for these Rac GTPases as regulators for ubiquitin/26S proteasome-mediated proteolysis and further consolidate their role in auxin signaling. Moreover, our study reveals a cellular process whereby auxin induces and Rac GTPases mediate the recruitment of nucleoplasmic Aux/IAAs into proteolytically active nuclear protein bodies, into which components of the SCFTIR1, COP9 signalosome, and 26S proteasome are also recruited.

Tao, Li-zhen; Cheung, Alice Y.; Nibau, Candida; Wu, Hen-ming

2005-01-01

325

Leukemia in Utah and radioactive fallout from the Nevada test site. A case-control study  

SciTech Connect

Previous studies reported an association between leukemia rates and amounts of fallout in southwestern Utah from nuclear tests (1952 to 1958), but individual radiation exposures were unavailable. Therefore, a case-control study with 1177 individuals who died of leukemia and 5330 other deaths (controls) was conducted using estimates of dose to bone marrow computed from fallout deposition rates and subjects' residence locations. A weak association between bone marrow dose and all types of leukemia, all ages, and all time periods after exposure was found. This overall trend was not statistically significant, but significant trends in excess risk were found in subgroups defined by cell type, age, and time after exposure. The greatest excess risk was found in those individuals in the high-dose group with acute leukemia who were younger than 20 years at exposure and who died before 1964. These results are consistent with previous studies and with risk estimates for other populations exposed to radiation.

Stevens, W.; Thomas, D.C.; Lyon, J.L.; Till, J.E.; Kerber, R.A.; Simon, S.L.; Lloyd, R.D.; Elghany, N.A.; Preston-Martin, S. (Univ. of Utah School of Medicine, Salt Lake City (USA))

1990-08-01

326

Risk-Adapted Chemotherapy in Younger Patients With Newly Diagnosed Standard-Risk Acute Lymphoblastic Leukemia  

ClinicalTrials.gov

B-cell Childhood Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

2014-02-17

327

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

2014-06-27

328

Phase I/II Study of Nilotinib/Ruxolitinb Therapy for TKI Resistant Ph-Leukemia  

ClinicalTrials.gov

Chronic Phase Chronic Myeloid Leukemia; Accelerated Phase Chronic Myeloid Leukemia; Blastic Phase Chronic Myeloid Leukemia; Philadelphia Positive Acute Lymphoblastic Leukemia; Resistant to Tyrosine Kinase Inhibitor Therapy

2013-08-01

329

Graft-versus-leukemia in rat MHC-mismatched bone marrow transplantation is merely an allogeneic effect.  

PubMed

One of the major problems in the treatment of leukemia with bone marrow transplantation (BMT) remains leukemia relapse. It has been clearly shown that graft-versus-host disease (GVHD) is accompanied by a graft-versus-leukemia reaction (GVLR) which reduces the incidence of leukemia relapse. To date, discussion is still going on as to whether GVHD and GVLR are either two different reactions or are exerting their effects through the same mechanism(s). In two rat leukemia models, namely the Brown Norway acute myelocytic leukemia (BNML) and the WAG/Rij acute lymphocytic leukemia L4415, total body irradiation (TBI) was given to induce a state of so-called minimal residual disease (MRD). Subsequently, it was attempted to evoke a GVLR distinct from GVHD by using semi-allogeneic hybrid-to-parent or parent-to-hybrid BMT, with or without the addition of graded numbers of lymphocytes. In both leukemia models applying hybrid-to-parent BMT, the addition of high numbers of semi-allogeneic lymphocytes to the semi-allogeneic graft had no antileukemic effect. In parent-to-hybrid BMT, the grafts sharing their alloantigens with the leukemia cells did not induce an anti-leukemic effect, irrespective of the number of lymphocytes present in the graft or the induction of evident GVHD. When the parental graft was histoincompatible with the leukemia cells, transplantation of bone marrow alone induced a significant increase in life span correlating with 2.8 log leukemia cell kill (LCK).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7655385

Kloosterman, T C; Martens, A C; van Bekkum, D W; Hagenbeek, A

1995-04-01

330

Spc98p Directs the Yeast ?-Tubulin Complex into the Nucleus and Is Subject to Cell Cycle-dependent Phosphorylation on the Nuclear Side of the Spindle Pole Body  

PubMed Central

In the yeast Saccharomyces cerevisiae, microtubules are organized by the spindle pole body (SPB), which is embedded in the nuclear envelope. Microtubule organization requires the ?-tubulin complex containing the ?-tubulin Tub4p, Spc98p, and Spc97p. The Tub4p complex is associated with cytoplasmic and nuclear substructures of the SPB, which organize the cytoplasmic and nuclear microtubules. Here we present evidence that the Tub4p complex assembles in the cytoplasm and then either binds to the cytoplasmic side of the SPB or is imported into the nucleus followed by binding to the nuclear side of the SPB. Nuclear import of the Tub4p complex is mediated by the essential nuclear localization sequence of Spc98p. Our studies also indicate that Spc98p in the Tub4p complex is phosphorylated at the nuclear, but not at the cytoplasmic, side of the SPB. This phosphorylation is cell cycle dependent and occurs after SPB duplication and nucleation of microtubules by the new SPB and therefore may have a role in mitotic spindle function. In addition, activation of the mitotic checkpoint stimulates Spc98p phosphorylation. The kinase Mps1p, which functions in SPB duplication and mitotic checkpoint control, seems to be involved in Spc98p phosphorylation. Our results also suggest that the nuclear and cytoplasmic Tub4p complexes are regulated differently.

Pereira, Gislene; Knop, Michael; Schiebel, Elmar

1998-01-01

331

Autopsy Study of Leukemia in Hiroshima.  

National Technical Information Service (NTIS)

The present study concerns 157 cases of leukemia autopsied at ABCC Hiroshima during 1949-1962. The epidemiologic characteristics of the survivor and immigrant populations are discussed with special reference to leukemia and to the comparability of the var...

R. E. Anderson T. Yamamoto A. Yamada D. W. Will

1964-01-01

332

Treatment Option Overview (Adult Acute Lymphoblastic Leukemia)  

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 ...

333

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 ...

334

Stages of Adult Acute Lymphoblastic Leukemia  

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 ...

335

Acute Lymphoblastic Leukemia (ALL) (For Parents)  

MedlinePLUS

... Parents > Diseases & Conditions > Cancer & Tumors > Acute Lymphoblastic Leukemia (ALL) Print A A A Text Size What's in ... child will develop acute lymphoblastic, or lymphoid, leukemia (ALL). This is the most common type of childhood ...

336

General Information about Childhood Acute Lymphoblastic Leukemia  

MedlinePLUS

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

337

Treatment Options for Adult Acute Lymphoblastic Leukemia  

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 ...

338

Treatment Option Overview (Childhood Acute Lymphoblastic Leukemia)  

MedlinePLUS

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

339

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

340

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

341

The Childhood Leukemia International Consortium  

PubMed Central

Background Acute leukemia is the most common cancer in children under 15 years of age; 80% are acute lymphoblastic leukemia (ALL) and 17% are acute myeloid leukemia (AML). Childhood leukemia shows further diversity based on cytogenetic and molecular characteristics, which may relate to distinct etiologies. Case–control studies conducted worldwide, particularly of ALL, have collected a wealth of data on potential risk factors and in some studies, biospecimens. There is growing evidence for the role of infectious/immunologic factors, fetal growth, and several environmental factors in the etiology of childhood ALL. The risk of childhood leukemia, like other complex diseases, is likely to be influenced both by independent and interactive effects of genes and environmental exposures. While some studies have analyzed the role of genetic variants, few have been sufficiently powered to investigate gene–environment interactions. Objectives The Childhood Leukemia International Consortium (CLIC) was established in 2007 to promote investigations of rarer exposures, gene–environment interactions and subtype-specific associations through the pooling of data from independent studies. Methods By September 2012, CLIC included 22 studies (recruitment period: 1962–present) from 12 countries, totaling approximately 31 000 cases and 50 000 controls. Of these, 19 case–control studies have collected detailed epidemiologic data, and DNA samples have been collected from children and child–parent trios in 15 and 13 of these studies, respectively. Two registry-based studies and one study comprising hospital records routinely obtained at birth and/or diagnosis have limited interview data or biospecimens. Conclusions CLIC provides a unique opportunity to fill gaps in knowledge about the role of environmental and genetic risk factors, critical windows of exposure, the effects of gene–environment interactions and associations among specific leukemia subtypes in different ethnic groups.

Metayer, Catherine; Milne, Elizabeth; Clavel, Jacqueline; Infante-Rivard, Claire; Petridou, Eleni; Taylor, Malcolm; Schuz, Joachim; Spector, Logan G.; Dockerty, John D.; Magnani, Corrado; Pombo-de-Oliveira, Maria S.; Sinnett, Daniel; Murphy, Michael; Roman, Eve; Monge, Patricia; Ezzat, Sameera; Mueller, Beth A.; Scheurer, Michael E.; Armstrong, Bruce K.; Birch, Jill; Kaatsch, Peter; Koifman, Sergio; Lightfoot, Tracy; Bhatti, Parveen; Bondy, Melissa L.; Rudant, Jeremie; O'Neill, Kate; Miligi, Lucia; Dessypris, Nick; Kang, Alice Y.; Buffler, Patricia A.

2013-01-01

342

Relapse risk after umbilical cord blood transplantation: enhanced graft-versus-leukemia effect in recipients of 2 units.  

PubMed

Umbilical cord blood (UCB) transplantation is potentially curative for acute leukemia. This analysis was performed to identify risk factors associated with leukemia relapse following myeloablative UCB transplantation. Acute leukemia patients (n = 177; 88 with acute lymphoblastic leukemia and 89 with acute myeloid leukemia) were treated at a single center. Patients received a UCB graft composed of either 1 (47%) or 2 (53%) partially human leukocyte antigen (HLA)-matched unit(s). Conditioning was with cyclophosphamide and total body irradiation with or without fludarabine. The incidence of relapse was 26% (95% confidence interval [CI], 19%-33%). In multivariate analysis, relapse was higher in advanced disease patients (> or = third complete remission [CR3]; relative risk [RR], 3.6; P < .01), with a trend toward less relapse in recipients of 2 UCB units (RR = 0.6; P = .07). However, relapse was lower for CR1-2 patients who received 2 UCB units (RR 0.5; P < .03). Leukemia-free survival was 40% (95% CI, 30%-51%) and 51% (95% CI, 41%-62%) for single- and double-unit recipients, respectively (P = .35). Although it is known that transplantation in CR1 and CR2 is associated with less relapse risk, this analysis reveals an enhanced graft-versus-leukemia effect in acute leukemia patients after transplantation with 2 partially HLA-matched UCB units. This trial was registered at http://clinicaltrials.gov as NCT00309842. PMID:19706886

Verneris, Michael R; Brunstein, Claudio G; Barker, Juliet; MacMillan, Margaret L; DeFor, Todd; McKenna, David H; Burke, Michael J; Blazar, Bruce R; Miller, Jeffrey S; McGlave, Philip B; Weisdorf, Daniel J; Wagner, John E

2009-11-01

343

Relapse risk after umbilical cord blood transplantation: enhanced graft-versus-leukemia effect in recipients of 2 units  

PubMed Central

Umbilical cord blood (UCB) transplantation is potentially curative for acute leukemia. This analysis was performed to identify risk factors associated with leukemia relapse following myeloablative UCB transplantation. Acute leukemia patients (n = 177; 88 with acute lymphoblastic leukemia and 89 with acute myeloid leukemia) were treated at a single center. Patients received a UCB graft composed of either 1 (47%) or 2 (53%) partially human leukocyte antigen (HLA)–matched unit(s). Conditioning was with cyclophosphamide and total body irradiation with or without fludarabine. The incidence of relapse was 26% (95% confidence interval [CI], 19%-33%). In multivariate analysis, relapse was higher in advanced disease patients (? third complete remission [CR3]; relative risk [RR], 3.6; P < .01), with a trend toward less relapse in recipients of 2 UCB units (RR = 0.6; P = .07). However, relapse was lower for CR1-2 patients who received 2 UCB units (RR 0.5; P < .03). Leukemia-free survival was 40% (95% CI, 30%-51%) and 51% (95% CI, 41%-62%) for single- and double-unit recipients, respectively (P = .35). Although it is known that transplantation in CR1 and CR2 is associated with less relapse risk, this analysis reveals an enhanced graft-versus-leukemia effect in acute leukemia patients after transplantation with 2 partially HLA-matched UCB units. This trial was registered at http://clinicaltrials.gov as NCT00309842.

Brunstein, Claudio G.; Barker, Juliet; MacMillan, Margaret L.; DeFor, Todd; McKenna, David H.; Burke, Michael J.; Blazar, Bruce R.; Miller, Jeffrey S.; McGlave, Philip B.; Weisdorf, Daniel J.; Wagner, John E.

2009-01-01

344

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

ClinicalTrials.gov

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

2013-01-22

345

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

346

Nuclear Medicine Imaging  

MedlinePLUS

Nuclear Medicine Imaging What you need to know about… A nuclear medicine procedure is sometimes described as an “inside-out” ... that is directed through the patient’s body. Nuclear medicine procedures use small amounts of radioactive materials, called ...

347

Role of SUMO in RNF4-mediated Promyelocytic Leukemia Protein (PML) Degradation  

PubMed Central

Promyelocytic leukemia protein (PML) is a tumor suppressor acting as the organizer of subnuclear structures called PML nuclear bodies (NBs). Both covalent modification of PML by the small ubiquitin-like modifier (SUMO) and non-covalent binding of SUMO to the PML SUMO binding domain (SBD) are necessary for PML NB formation and maturation. PML sumoylation and proteasome-dependent degradation induced by the E3 ubiquitin ligase, RNF4, are enhanced by the acute promyelocytic leukemia therapeutic agent, arsenic trioxide (As2O3). Here, we established a novel bioluminescence resonance energy transfer (BRET) assay to dissect and monitor PML/SUMO interactions dynamically in living cells upon addition of therapeutic agents. Using this sensitive and quantitative SUMO BRET assay that distinguishes PML sumoylation from SBD-mediated PML/SUMO non-covalent interactions, we probed the respective roles of covalent and non-covalent PML/SUMO interactions in PML degradation and interaction with RNF4. We found that, although dispensable for As2O3-enhanced PML sumoylation and RNF4 interaction, PML SBD core sequence was required for As2O3- and RNF4-induced PML degradation. As confirmed with a phosphomimetic mutant, phosphorylation of a stretch of serine residues, contained within PML SBD was needed for PML interaction with SUMO-modified protein partners and thus for NB maturation. However, mutation of these serine residues did not impair As2O3- and RNF4-induced PML degradation, contrasting with the known role of these phosphoserine residues for casein kinase 2-promoted PML degradation. Altogether, these data suggest a model whereby sumoylation- and SBD-dependent PML oligomerization within NBs is sufficient for RNF4-mediated PML degradation and does not require the phosphorylation-dependent association of PML with other sumoylated partners.

Percherancier, Yann; Germain-Desprez, Delphine; Galisson, Frederic; Mascle, Xavier H.; Dianoux, Laurent; Estephan, Patricia; Chelbi-Alix, Mounira K.; Aubry, Muriel

2009-01-01

348

[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 symptoms 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

2013-10-01

349

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

ClinicalTrials.gov

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

2014-04-07

350

The European LeukemiaNet: achievements and perspectives.  

PubMed

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 in 2002, the European LeukemiaNet has steadily expanded and has unified leukemia research across Europe. The European LeukemiaNet grew from two major roots: 1) the German Competence Network on Acute and Chronic Leukemias; and 2) the collaboration of European Investigators on Chronic Myeloid Leukemia. The European LeukemiaNet has improved leukemia research and management across Europe. Its concept has led to funding by the European Commission as a network of excellence. Other sources (European Science Foundation; European LeukemiaNet-Foundation) will take over when the support of the European Commission ends. PMID:21048032

Hehlmann, Rüdiger; Grimwade, David; Simonsson, Bengt; Apperley, Jane; Baccarani, Michele; Barbui, Tiziano; Barosi, Giovanni; Bassan, Renato; Béné, Marie C; Berger, Ute; Büchner, Thomas; Burnett, Alan; Cross, Nicolas C P; de Witte, Theo J M; Döhner, Hartmut; Dombret, Hervé; Einsele, Hermann; Engelich, Georg; Foà, Robin; Fonatsch, Christa; Gökbuget, Nicola; Gluckman, Elaine; Gratwohl, Alois; Guilhot, Francois; Haferlach, Claudia; Haferlach, Thorsten; Hallek, Michael; Hasford, Jörg; Hochhaus, Andreas; Hoelzer, Dieter; Kiladjian, Jean-Jaques; Labar, Boris; Ljungman, Per; Mansmann, Ulrich; Niederwieser, Dietger; Ossenkoppele, Gert; Ribera, José M; Rieder, Harald; Serve, Hubert; Schrotz-King, Petra; Sanz, Miguel A; Saussele, Susanne

2011-01-01

351

The European LeukemiaNet: achievements and perspectives  

PubMed Central

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 in 2002, the European LeukemiaNet has steadily expanded and has unified leukemia research across Europe. The European LeukemiaNet grew from two major roots: 1) the German Competence Network on Acute and Chronic Leukemias; and 2) the collaboration of European Investigators on Chronic Myeloid Leukemia. The European LeukemiaNet has improved leukemia research and management across Europe. Its concept has led to funding by the European Commission as a network of excellence. Other sources (European Science Foundation; European LeukemiaNet-Foundation) will take over when the support of the European Commission ends.

Hehlmann, Rudiger; Grimwade, David; Simonsson, Bengt; Apperley, Jane; Baccarani, Michele; Barbui, Tiziano; Barosi, Giovanni; Bassan, Renato; Bene, Marie C.; Berger, Ute; Buchner, Thomas; Burnett, Alan; Cross, Nicolas C.P.; de Witte, Theo J.M.; Dohner, Hartmut; Dombret, Herve; Einsele, Hermann; Engelich, Georg; Foa, Robin; Fonatsch, Christa; Gokbuget, Nicola; Gluckman, Elaine; Gratwohl, Alois; Guilhot, Francois; Haferlach, Claudia; Haferlach, Thorsten; Hallek, Michael; Hasford, Jorg; Hochhaus, Andreas; Hoelzer, Dieter; Kiladjian, Jean-Jaques; Labar, Boris; Ljungman, Per; Mansmann, Ulrich; Niederwieser, Dietger; Ossenkoppele, Gert; Ribera, Jose M.; Rieder, Harald; Serve, Hubert; Schrotz-King, Petra; Sanz, Miguel A.; Saussele, Susanne

2011-01-01

352

Molecular diagnostics in acute leukemias.  

PubMed

Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) both represent highly heterogeneous entities on the basis of diverse cyto- and molecular genetic alterations with considerable influence on prognosis and therapeutic decisions. In recent years, insights into the complex network of molecular markers underlying this diversity have shown marked progress due to the detection of novel mutations, such as nucleophosmin gene (NPM1) in AML, and due to the description of cooperation pathways in leukemogenesis. Also, targeted therapeutic strategies are continuously expanding as illustrated by the tyrosine kinase inhibitor (TKI) imatinib for BCR-ABL positive ALL. Thus, molecular analysis based on various techniques, such as polymerase chain reaction (PCR) has become an essential part of the diagnostic panel for acute leukemia. In addition, cytomorphology, cytogenetics, fluorescence in situ hybridization (FISH), and immunophenotyping with multiparameter flow cytometry (MFC) need to be applied for diagnosis. During the course of disease, the residual leukemic cell load can be monitored by highly sensitive quantitative PCR techniques ("real-time PCR"). At present, new techniques, such as high throughput sequencing (next generation sequencing, NGS) or gene expression profiling with microarrays are being explored for use in hematological malignancies, and are being evaluated in preclinical studies. This demonstrates that molecular diagnostics for acute leukemias are in continuous development. This review summarizes the most important recurrent molecular markers seen in acute leukemias, their role in prognosis and therapy and provides an overview on the relevant PCR techniques. PMID:19817644

Bacher, Ulrike; Schnittger, Susanne; Haferlach, Claudia; Haferlach, Torsten

2009-01-01

353

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

354

PLASMA CELL LEUKEMIA  

PubMed Central

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

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

2014-01-01

355

Acute lymphoblastic leukemia: background.  

PubMed

Acute lymphoblastic leukemia is a fascinating disease for the cytogeneticist, as so many cases have a clone detectable by cytogenetics or FISH, and because identifying the abnormalities provides such useful information to the clinician. However, it is also a frustrating disease, as it has technical challenges such as a marked tendency for the sample to clot during harvesting, frequently poor chromosome morphology, and, especially in the high count cases, failure to provide any divisions at all for analysis. For these reasons, this book includes two chapters on the practical aspects of undertaking cytogenetic studies in ALL to illustrate contrasting approaches. The first is from a laboratory that is a world leader in its success rates, which has an enviably low sample/cytogeneticist ratio, and which is usually able to expect a good-sized sample commensurate with the importance given to a diagnostic cytogenetic study. The second is from a laboratory that also has a good success rate, despite having to cope with a higher workload and often much smaller samples. This is not to imply that each technique is limited to such circumstances; both are worthy of study and emulation. PMID:12744206

Swansbury, John

2003-01-01

356

Biomarkers in Bone Marrow Samples From Pediatric Patients With High-Risk Acute Myeloid Leukemia  

ClinicalTrials.gov

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 Childhood Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

2014-02-13

357

Tn polyagglutination preceding acute leukemia.  

PubMed

Tn polyagglutination (persistent mixed-field polyagglutination) was detected in the blood of a 66-yr-old male laborer at the time of a splenectomy for life-threatening thrombocytopenia. Confirmation that the polyagglutination was caused by Tn activation was established by the use of lectins, by failure of the patient's red cells to react with sera from other patients with Tn polyagglutination, by weak aggregation with polybrene, by low red cell sialic acid levels, and by the persistence of polyagglutination over several years of testing. Two years after the discovery of the Tn polyagglutination, the patient developed acute myelomonocytic leukemia. Vigorous chemotherapy regimens resulted in clinical remission of the leukemia and the Tn polyagglutination. This report describes the first known case of Tn polyagglutination preceding the development of acute myelogenous leukemia. PMID:286607

Ness, P M; Garratty, G; Morel, P A; Perkins, H A

1979-07-01

358

Genomic heterogeneity in acute leukemia.  

PubMed

Acquired genetic aberrations are the underlying cause of leukemogenesis in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). The karyotypes of AML and ALL cases are generally quite simple as seen by chromosome banding analysis, with few genetic changes and a limited number of subclones. However, investigations using fluorescence in situ hybridization, loss of heterozygosity analysis, single-nucleotide polymorphism arrays, and, most recently, massively parallel sequencing have challenged this view. In particular, comparison of diagnostic and relapse samples, modeling in transgenic mice, and whole-exome and whole-genome sequencing have indicated that widespread genomic heterogeneity, which is masked by a dominant clone, may be present in AML and ALL. In the present review, our current knowledge of genomic heterogeneity in acute leukemia is summarized. PMID:23363651

Paulsson, K

2013-01-01

359

Polycomb repressive complex 2 is required for MLL-AF9 leukemia  

PubMed Central

A growing body of data suggests the importance of epigenetic mechanisms in cancer. Polycomb repressive complex 2 (PRC2) has been implicated in self-renewal and cancer progression, and its components are overexpressed in many cancers. However, its role in cancer development and progression remains unclear. We used conditional alleles for the PRC2 components enhancer of zeste 2 (Ezh2) and embryonic ectoderm development (Eed) to characterize the role of PRC2 function in leukemia development and progression. Compared with wild-type leukemia, Ezh2-null MLL-AF9–mediated acute myeloid leukemia (AML) failed to accelerate upon secondary transplantation. However, Ezh2-null leukemias maintained self-renewal up to the third round of transplantation, indicating that Ezh2 is not strictly required for MLL-AF9 AML, but plays a role in leukemia progression. Genome-wide analyses of PRC2-mediated trimethylation of histone 3 demonstrated locus-specific persistence of H3K27me3 despite inactivation of Ezh2, suggesting partial compensation by Ezh1. In contrast, inactivation of the essential PRC2 gene, Eed, led to complete ablation of PRC2 function, which was incompatible with leukemia growth. Gene expression array analyses indicated more profound gene expression changes in Eed-null compared with Ezh2-null leukemic cells, including down-regulation of Myc target genes and up-regulation of PRC2 targets. Manipulating PRC2 function may be of therapeutic benefit in AML.

Neff, Tobias; Sinha, Amit U.; Kluk, Michael J.; Zhu, Nan; Khattab, Mohamed H.; Stein, Lauren; Xie, Huafeng; Orkin, Stuart H.; Armstrong, Scott A.

2012-01-01

360

Refolding of soluble leukemia inhibitory factor receptor fusion protein (gp 190 sol DAF) from urea  

Microsoft Academic Search

The insoluble inclusion bodies of soluble leukemia inhibitory factor receptor fusion protein (gp 190 sol DAF ) was solubilized in 8 M urea on the unfolding transitions, and several factors on the aggregate formation were indirectly analyzed for the refolding of gp 190 sol DAF. Results indicate that the refolding yield can be considerably increased at lowering concentration of the

Houqi Liu; Jean-François Moreau; Norbert Gualde; Jiliang Fu

1997-01-01

361

Murine Leukemia Virus Spreading in Mice Impaired in the Biogenesis of Secretory Lysosomes and Ca2  

Microsoft Academic Search

Background: Retroviruses have been observed to bud intracellularly into multivesicular bodies (MVB), in addition to the plasma membrane. Release from MVB is thought to occur by Ca2+-regulated fusion with the plasma membrane. Principal Findings: To address the role of the MVB pathway in replication of the murine leukemia virus (MLV) we took advantage of mouse models for the Hermansky-Pudlak syndrome

Regulated Exocytosis; Wai-Tsing Chan; Nathan M. Sherer; Pradeep D. Uchil; Edward K. Novak; Richard T. Swank

2008-01-01

362

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

2014-05-13

363

Immunological Characterization of Normal and Leukemia-associated Antigens of Acute Myelomonocytic Leukemia and Chronic Myelogenous Leukemia in Blast Crisis1  

Microsoft Academic Search

Nonhuman primate antisera defining leukemia-associ ated and normal T- and B-lymphocyte-associated anti gens were used to characterize serologically the cells from acute myelomonocytic leukemia (AMML) and chronic myelogenous leukemia patients in blast crisis (CML-BC). Earlier studies demonstrated that nonhuman primate an tisera to chronic lymphocytic leukemia, acute myelogen ous leukemia, and chronic myelogenous leukemia cells were able to distinguish between

T. Mohanakumar; D. S. Miller; J. Anderson; R. S. Metzgar

364

Sorafenib in Treating Patients With Refractory or Relapsed Acute Leukemia, Myelodysplastic Syndromes, or Blastic Phase 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 Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

2013-09-27

365

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

366

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

367

GTI-2040 in Treating Patients With Relapsed, Refractory, or High-Risk Acute Leukemia, High-Grade Myelodysplastic Syndromes, or Refractory or Blastic Phase Chronic Myelogenous Leukemia  

ClinicalTrials.gov

Acute Undifferentiated 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); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

2013-04-09

368

Hairy Cell Leukemia (‘Leukemic Reticuloendotheliosis’), Reticulosarcoma, and Monocytic Leukemia  

Microsoft Academic Search

Cytochemical and electron-microscopic studies have been carried out on leukemic monocytes and ‘hairy cells’ (HC), ‘reticulosarcoma’ (RS) cells and cells of cases of ‘reticulosis’ and ‘reticulosarcoma cell leukemia’. Additional investigations included quantitative determinations of the urinary lysozyme excretion, skin window studies, testing of the phagocytosis of ferritin by HC, and labelling of the Fc receptors on HC at the ultrastructural

F. Schmalzl; D. Huhn; H. Asamer; H. Braunsteiner

1975-01-01

369

Extramedullary Relapse of Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation: Different Characteristics between Acute Myelogenous Leukemia and Acute Lymphoblastic Leukemia.  

PubMed

Extramedullary relapse (EMR) of acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a contributor to post-transplantation mortality and remains poorly understood, especially the different characteristics of EMR in patients with acute myelogenous leukemia (AML) and those with acute lymphoblastic leukemia (ALL). To investigate the incidence, risk factors, and clinical outcomes of EMR for AML and ALL, we performed a retrospective analysis of 362 patients with AL who underwent allo-HSCT at the First affiliated Hospital of Soochow University between January 2001 and March 2012. Compared with patients with AML, those with ALL had a higher incidence of EMR (12.9% versus 4.6%; P = .009). The most common site of EMR was the central nervous system, especially in the ALL group. Multivariate analyses identified the leading risk factors for EMR in the patients with AML as advanced disease status at HSCT, hyperleukocytosis at diagnosis, history of extramedullary leukemia before HSCT, and a total body irradiation-based conditioning regimen, and the top risk factors for EMR in the patients with ALL as hyperleukocytosis at diagnosis, adverse cytogenetics, and transfusion of peripheral blood stem cells. The prognosis for EMR of AL is poor, and treatment options are very limited; however, the estimated 3-year overall survival (OS) was significantly lower in patients with AML compared with those with ALL (0 versus 18.5%; P = .000). The characteristics of post-allo-HSCT EMR differed between the patients with AML and those with ALL, possibly suggesting different pathogenetic mechanisms for EMR of AML and EMR of ALL after allo-HSCT; further investigation is needed. PMID:24704575

Ge, Ling; Ye, Fan; Mao, Xinliang; Chen, Jia; Sun, Aining; Zhu, Xiaming; Qiu, Huiying; Jin, Zhengming; Miao, Miao; Fu, Chengcheng; Ma, Xiao; Chen, Feng; Xue, Shengli; Ruan, Changgeng; Wu, Depei; Tang, Xiaowen

2014-07-01

370

Plasma cell leukemia.  

PubMed

Plasma cell leukemia (PCL) is a rare, yet aggressive plasma cell (PC) neoplasm, variant of multiple myeloma (MM), characterized by high levels of PCs circulating in the peripheral blood. PCL can either originate de novo (primary PCL) or as a secondary leukemic transformation of MM (secondary PCL). Presenting signs and symptoms are similar to those seen in MM such as renal insufficiency, hypercalcemia, lytic bone lesions, anemia, and thrombocytopenia, but can also include hepatomegaly and splenomegaly. The diagnostic evaluation of a patient with suspected PCL should include a review of the peripheral blood smear, bone marrow aspiration and biopsy, serum protein electrophoresis (SPEP) with immunofixation, and protein electrophoresis of an aliquot from a 24h urine collection (UPEP). The diagnosis is made when a monoclonal population of PCs is present in the peripheral blood with an absolute PC count exceeding 2000/?L and PC comprising 20% or more of the peripheral blood white cells. The prognosis of PCL is poor with a median survival of 7 to 11 months. Survival is even shorter (2 to 7 months) when PCL occurs in the context of refractory or relapsing MM. There have been no prospective randomized trials investigating the treatment of PCL. Recommendations are primarily based upon data from small retrospective series, case reports, and extrapolation of data from patients with MM. In general, patients are treated with induction therapy followed by hematopoietic cell transplantation (HCT) in those who are appropriate candidates for this approach. The best induction regimen for PCL is not known and there is great variability in clinical practice. Newer agents that are being incorporated into frontline and salvage therapy for MM have also demonstrated activity in PCL such as Immunomodulatory agents and the use of bortezomib with different combinations. PMID:21295388

Albarracin, Flavio; Fonseca, Rafael

2011-05-01

371

Acute myeloid leukemia.  

PubMed

Through the hard work of a large number of investigators, the biology of acute myeloid leukemia (AML) is becoming increasingly well understood, and as a consequence, new therapeutic targets have been identified and new model systems have been developed for testing novel therapies. How these new therapies can be most effectively studied in the clinic and whether they will ultimately improve cure rates are questions of enormous importance. In this article, Dr. Jacob Rowe presents a summary of the current state-of-the-art therapy for adult AML. His contribution emphasizes the fact that AML is not a single disease, but a number of related diseases each distinguished by unique cytogenetic markers which in turn help determine the most appropriate treatment. Dr. Jerald Radich continues on this theme, emphasizing how these cytogenetic abnormalities, as well as other mutations, give rise to abnormal signal transduction and how these abnormal pathways may represent ideal targets for the development of new therapeutics. A third contribution by Dr. Frederick Appelbaum describes how AML might be made the target of immunologic attack. Specifically, strategies using antibody-based or cell-based immunotherapies are described including the use of unmodified antibodies, drug conjugates, radioimmunoconjugates, non-ablative allogeneic transplantation, T cell adoptive immunotherapy and AML vaccines. Finally, Dr. John Dick provides a review of the development of the NOD/SCID mouse model of human AML emphasizing both what it has taught us about the biology of the disease as well as how it can be used to test new therapies. Taken together, these reviews are meant to help us understand more about where we are in the treatment of AML, where we can go and how we might get there. PMID:11722979

Appelbaum, F R; Rowe, J M; Radich, J; Dick, J E

2001-01-01

372

Leukemia - Chronic Myeloid - CML  

MedlinePLUS

... 9;22) causes two genes called BCR and ABL to become one fusion gene called BCR-ABL . It is found only in the blood-forming ... in other organs of the body. The BCR-ABL gene causes myeloid cells to make an abnormal ...

373

Combination Chemotherapy With or Without Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia  

ClinicalTrials.gov

Adult Acute Lymphoblastic Leukemia in Remission; B-cell Adult Acute Lymphoblastic Leukemia; L1 Adult Acute Lymphoblastic Leukemia; L2 Adult Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

2014-06-02

374

A fraction of neurofibromin interacts with PML bodies in the nucleus of the CCF astrocytoma cell line  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer We validate the use of specific anti-Nf1 antibodies for immunofluorescence studies. Black-Right-Pointing-Pointer We detect Nf1 in the cytoplasm and nucleus of CCF cells. Black-Right-Pointing-Pointer We demonstrate that Nf1 partially colocalizes with PML nuclear bodies. Black-Right-Pointing-Pointer We demonstrate that there is a direct interaction between a fraction of Nf1 and the PML bodies. -- Abstract: Neurofibromatosis type 1 is a common genetic disease that causes nervous system tumors, and cognitive deficits. It is due to mutations within the NF1 gene, which encodes the Nf1 protein. Nf1 has been shown to be involved in the regulation of Ras, cAMP and actin cytoskeleton dynamics. In this study, using immunofluorescence experiments, we have shown a partial nuclear localization of Nf1 in the astrocytoma cell line: CCF and we have demonstrated that Nf1 partially colocalizes with PML (promyelocytic leukemia) nuclear bodies. A direct interaction between Nf1 and the multiprotein complex has further been demonstrated using 'in situ' proximity ligation assay (PLA).

Godin, Fabienne; Villette, Sandrine; Vallee, Beatrice; Doudeau, Michel; Morisset-Lopez, Severine [Centre de Biophysique Moleculaire, Centre National de la Recherche Scientifique (CNRS), UPR 4301, Universite d'Orleans et INSERM, rue Charles Sadron, 45071 Orleans Cedex 2 (France)] [Centre de Biophysique Moleculaire, Centre National de la Recherche Scientifique (CNRS), UPR 4301, Universite d'Orleans et INSERM, rue Charles Sadron, 45071 Orleans Cedex 2 (France); Ardourel, Maryvonne; Hevor, Tobias [Laboratoire de Neurobiologie, Universite d'Orleans, BP 6759, 45067 Orleans Cedex 2 (France)] [Laboratoire de Neurobiologie, Universite d'Orleans, BP 6759, 45067 Orleans Cedex 2 (France); Pichon, Chantal [Centre de Biophysique Moleculaire, Centre National de la Recherche Scientifique (CNRS), UPR 4301, Universite d'Orleans et INSERM, rue Charles Sadron, 45071 Orleans Cedex 2 (France)] [Centre de Biophysique Moleculaire, Centre National de la Recherche Scientifique (CNRS), UPR 4301, Universite d'Orleans et INSERM, rue Charles Sadron, 45071 Orleans Cedex 2 (France); Benedetti, Helene, E-mail: helene.benedetti@cnrs-orleans.fr [Centre de Biophysique Moleculaire, Centre National de la Recherche Scientifique (CNRS), UPR 4301, Universite d'Orleans et INSERM, rue Charles Sadron, 45071 Orleans Cedex 2 (France)] [Centre de Biophysique Moleculaire, Centre National de la Recherche Scientifique (CNRS), UPR 4301, Universite d'Orleans et INSERM, rue Charles Sadron, 45071 Orleans Cedex 2 (France)

2012-02-24

375

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

376

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

377

Targeting Progressive Chronic Lymphocytic Leukemia  

Cancer.gov

In this study, researchers are testing the effectiveness of an immunotoxin called LMB-2 in selectively killing chronic lymphocytic leukemia (CLL) cells. LMB-2 binds to a protein called CD25 and delivers a bacterial toxin that may kill the cells.

378

Vasculitides in hairy cell leukemia  

Microsoft Academic Search

Forty-two cases of vasculitis coincident with hairy cell leukemia (HCL) havebeen reported, of which 17 had panarteritis nodosa (PAN), 21 had cutaneous leukocytoclastic vasculitis (LCV), and 4 had vessel wall infiltration by hairy cells. PAN generally occurred after the diagnosis of HCL, splenectomy, and infection. HBs antigen was detected in 3 of 12 patients tested, whereas immune complexes were positive

Paul Hasler; Hansjörg Kistler; Heini Gerber

1995-01-01

379

Immunoregulatory properties of childhood leukemias  

SciTech Connect

Investigation of in vitro humoral immune responses and immunoregulatory properties of leukemic cell was carried out in 17 children with acute leukemia prior to therapy. Leukemias were of the non-T, non-B-cell type in 13 patients and of T-cell origin in four. Bone marrow and peripheral blood cells consisted of 24-96% lymphoblasts and were generally deficient in surface Ig-positive cells. Induction of Ig secreting cells in response to pokeweed mitogen was markedly decreased in marrow and peripheral mononuclear cell cultures of leukemic patients. Co-culture of leukemic cells with normal lymphocytes led to marked deviations from the expected Ig secreting-cell response of the cell mixtures. The predominant effect was enhancement, as was the case with eight non-T, non-B-cell and one T-cell leukemia samples. Suppression of the Ig secreting-cell response was observed in only three instances, two with non-T, non-B-cell and one with T-cell leukemia samples. These findings implicate non-T, non-B as well as more differentiated leukemic cells in having the potential for modifying Ig production by B cells.

Banker, D.S.; Pahwa, R.N.; Miller, D.R.; Hilgartner, M.W.; Good, R.A.; Pahwa, S.G.

1982-07-01

380

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

2014-03-20

381

Drosophila Cajal bodies: accessories not included  

PubMed Central

Cajal bodies are nuclear sites of small ribonucleoprotein (RNP) remodeling and maturation. A recent study describes the discovery of the Drosophila Cajal body, revealing some interesting insights into the subnuclear organization of RNA processing machineries among different species.

Matera, A. Gregory

2006-01-01

382

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

ClinicalTrials.gov

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; 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

2014-06-02

383

Blinatumomab in Treating Younger Patients With Relapsed B-Cell Acute Lymphoblastic Leukemia  

ClinicalTrials.gov

B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia

2014-05-19

384

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

385

General Approach to Treatment of Chronic Myelomonocytic Leukemia  

MedlinePLUS

... More treatment information about chronic myelomonocytic leukemia General approach to treatment of chronic myelomonocytic leukemia Stem cell transplant (SCT) is the only way to cure patients with chronic myelomonocytic (MY-eh-loh-MAH-noh-SIH-tik) leukemia (CMML). ...

386

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 ...

387

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 ...

388

What's New in Childhood Leukemia Research and Treatment?  

MedlinePLUS

... Next Topic Additional resources for 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 ...

389

Monoclonal Antibody Therapy in Treating Patients With Chronic Lymphocytic Leukemia, Lymphocytic Lymphoma, Acute Lymphoblastic Leukemia, or Acute Myeloid Leukemia  

ClinicalTrials.gov

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

2013-06-03

390

An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein  

SciTech Connect

The promyelocytic leukemia protein (PML) forms nuclear bodies (NB) that can be redistributed by virus infection. In particular, lymphocytic choriomeningitis virus (LCMV) influences disruption of PML NB through the interaction of PML with the arenaviral Z protein. In a previous report, we have shown that the disulfide compound NSC20625 has antiviral and virucidal properties against arenaviruses, inducing unfolding and oligomerization of Z without affecting cellular RING-containing proteins such as the PML. Here, we further studied the effect of the zinc-finger-reactive disulfide NSC20625 on PML-Z interaction. In HepG2 cells infected with LCMV or transiently transfected with Z protein constructs, treatment with NSC20625 restored PML distribution from a diffuse-cytoplasmic pattern to punctate, discrete NB which appeared identical to NB found in control, uninfected cells. Similar results were obtained in cells transfected with a construct expressing a Z mutant in zinc-binding site 2 of the RING domain, confirming that this Z-PML interaction requires the integrity of only one zinc-binding site. Altogether, these results show that the compound NSC20625 suppressed Z-mediated PML NB disruption and may be used as a tool for designing novel antiviral strategies against arenavirus infection.

Garcia, C.C. [Laboratory of Virology, Department of Biological Chemistry, School of Sciences, University of Buenos Aires, 1428 Buenos Aires (Argentina)] [Laboratory of Virology, Department of Biological Chemistry, School of Sciences, University of Buenos Aires, 1428 Buenos Aires (Argentina); Topisirovic, I. [Institute de Recherche en Immunologie et en Cancerologie, Universite de Montreal, Montreal, QC, Canada H3T 1J4 (Canada)] [Institute de Recherche en Immunologie et en Cancerologie, Universite de Montreal, Montreal, QC, Canada H3T 1J4 (Canada); Djavani, M. [Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, MD 21201 (United States)] [Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, MD 21201 (United States); Borden, K.L.B. [Institute de Recherche en Immunologie et en Cancerologie, Universite de Montreal, Montreal, QC, Canada H3T 1J4 (Canada)] [Institute de Recherche en Immunologie et en Cancerologie, Universite de Montreal, Montreal, QC, Canada H3T 1J4 (Canada); Damonte, E.B. [Laboratory of Virology, Department of Biological Chemistry, School of Sciences, University of Buenos Aires, 1428 Buenos Aires (Argentina)] [Laboratory of Virology, Department of Biological Chemistry, School of Sciences, University of Buenos Aires, 1428 Buenos Aires (Argentina); Salvato, M.S., E-mail: msalvato@ihv.umaryland.edu [Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, MD 21201 (United States)

2010-03-19

391

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

Microsoft Academic Search

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,

CATHERINE DENICOURT; ELSY EDOUARD; ERIC RASSART

1999-01-01

392

Chronic Lymphocytic Leukemia (PDQ): Treatment  

MedlinePLUS

... cells grow into (and restore) the body’s blood cells. Biologic therapy Biologic therapy is a treatment that uses the patient's immune system to fight cancer. Substances made by the body or made in ...

393

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

394

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

395

Diffuse Calcinosis cutis in a Patient with Congenital Leukemia and Leukemia cutis  

Microsoft Academic Search

We report an unusual case of congenital leukemia with leukemia cutis (LC) and diffuse calcinosis cutis. A newborn girl presented with widespread dusky red and yellowish cutaneous nodules and papules. Bone marrow morphology was consistent with the diagnosis of acute monocytic leukemia of the FAB M5 type. Skin biopsy specimens confirmed the presence of a leukemic infiltrate and revealed calcium

Giles G. Lestringant; Isabelle Masouyé; Mohammed El-Hayek; Christophe Girardet; Tom Révész; Philippe M. Frossard

2000-01-01

396

Have we been wrong about ionizing radiation and chronic lymphocytic leukemia?  

PubMed

It is almost axiomatic that chronic lymphocytic leukemia (CLL) is not caused by ionizing radiation. This assumption has been challenged recently by a critical re-appraisal of existing data. A recent paper implicated radon exposure in Czech uranium miners as a possible cause of CLL and in this issue of Leukemia Research the first paper examining the incidence of CLL among those exposed to radiation from the accident at the nuclear power plant in Chernobyl is published. It suggests that CLL occurring among the clean-up workers was of a more aggressive form than is normally seen in the community. PMID:17915317

Hamblin, Terry J

2008-04-01

397

Therapy of childhood acute myelogenous leukemias  

Microsoft Academic Search

Acute myelogenous leukemia (AML) accounts for approximately 20% of acute leukemias in children. Although AML is more resistant\\u000a to chemotherapy than acute lymphoblastic leukemia (ALL), significant progress in improving outcome for AML patients has been\\u000a achieved over the past 15 years. This can be attributed to intensification of chemotherapy, increased use of bone marrow transplantation,\\u000a and improved supportive care. Thus

J. Vormoor; J. Boos; K. Stahnke; H. Jürgens; J. Ritter; U. Creutzig

1996-01-01

398

Effect of a body-tie structure fabricated by partial trench isolation on the suppression of floating body effect induced soft errors in SOI SRAM investigated using nuclear probes  

NASA Astrophysics Data System (ADS)

Soft errors induced by proton, helium and oxygen ion irradiations were measured as a function of distance between a body electrode under partial trench isolation and a metal pad connected to a tungsten via for the first metal layer of a silicon-on-insulator (SOI) static random access memory. Abnormal drain charges induced by ion irradiations with various distances in the SOI metal oxide semiconductor field effect transistor were simulated to be compared with the experimental results. The soft errors were found to depend on the distance between the body electrode and the metal pad in the case of the abnormal drain charge, which is induced by incident ions, lower than the critical charge of the SRAM cells. The soft errors did not depend on the distance for the abnormal drain charges higher than the critical charge.

Abo, Satoshi; Masuda, Naoyuki; Wakaya, Fujio; Onoda, Shinobu; Makino, Takahiro; Hirao, Toshio; Ohshima, Takeshi; Iwamatsu, Toshiaki; Oda, Hidekazu; Takai, Mikio

2011-10-01

399

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

400

Body Parts  

NSDL National Science Digital Library

In this online game, learners test their knowledge of human anatomy. Learners are presented a mystery image of a body part and use their mouse to select the proper body part from a full size anatomical model (known as "Jerome"). Learners try to match all 10 body parts correctly. Use this activity to review human anatomy and/or introduce learners to the use of anatomical models.

National Museum Of American History, Smithsonian I.

2012-06-26

401

17-N-Allylamino-17-Demethoxygeldanamycin in Treating Young Patients With Relapsed or Refractory Solid Tumors or Leukemia  

ClinicalTrials.gov

Acute Undifferentiated Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

2013-06-03

402

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

403

Ikaros gene expression and leukemia.  

PubMed

The Ikaros (Ik) protein, or LyF1, was initially described as a protein binding to regulatory sequences of a number of genes expressed in murine lymphoid cells. Ikaros is a critical regulator of normal hematopoietic stem cell differentiation, as evidenced by dramatic defects in the lymphoid compartments, in homozygous animals with gene inactivation. Because differential splicing produces multiple isoforms with potentially different functions, Ikaros provides a unique model to study how post-transcriptional mechanisms may be involved in neoplastic processes. Indeed, several groups including ours have underlined evidences that expression of different Ikaros isoforms vary among different types of leukemias. The predominance of short isoforms in certain subsets is intriguing. Here, additional observations reinforced the hypothesis that Ikaros expression may be deregulated in human leukemias. Whether this is a cause or a consequence of the leukemic process remains speculative. Other human diseases however, provide examples of abnormal post-transcriptional regulations that have been further characterized. PMID:11908734

Tonnelle, Cécile; Calmels, Boris; Maroc, Christine; Gabert, Jean; Chabannon, Christian

2002-01-01

404

Rhabdomyosarcoma masquerading as acute leukemia.  

PubMed

Rhabdomyosarcoma (RMS) masquerading as acute leukemia (AL) is very rare. We describe three cases with RMS without any symptoms of solid tumors. Bone marrow (BM) showed approximately 95% of blast-like abnormal cells, lacking almost all of the surface antigens of myeloid- and lymphoid-lineage. The immunohistochemistry revealed positive of the cells for actin, desmin and myoglobin. It is important to examine BM samples by immunohistochemistry, when a flow cytometric analysis reveals an unusual presentation. PMID:18837429

Shinkoda, Yuichi; Nagatoshi, Yoshihisa; Fukano, Reiji; Nishiyama, Kenichi; Okamura, Jun

2009-02-01

405

Biclonal primary plasma cell leukemia  

Microsoft Academic Search

Authors present a multiparameter pathological study in a case of rapid biclonal primary plasma cell leukemia. The immunohistochemical\\u000a data revealed aberrant phenotypes (monocyte, epithelial and T-cell) probably in connection with microenvironmental influences.\\u000a Biclonality can be attributed to class switching during malignant transformation. Static image cytometry showed aneuploidy.\\u000a The blasts of this process are active immunoregulatory cells.

Zoltán TÓth; József Sipos

1998-01-01

406

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

407

Hyperlipidemia in acute lymphoblastic leukemia.  

PubMed

Studies were conducted on lipemic serum obtained from a 26 month old male to determine possible mechanisms for the association of a Type V hyperlipidemic phenotype with advanced lymphoblastic leukemia (ALL). Antibodies to apolipoproteins and endogenous heparin were not detected as previously reported. Fatty acid analysis of the triglyceride esters revealed a high proportion of stearic-acid (18:0) which was associated with a slower in vitro degradation of very low density lipoproteins (VLDL) by human milk lipoprotein lipase (LPL). This suggests that a cause of the hyperlipidemia could be abnormal composition of triglycerides which render the VLDL a poor substrate for lipoprotein lipase. Hyperlipidemia in leukemia may be more prevalent than previously realized since nine other cases of newly diagnosed ALL have been studied who had moderate hypertriglyceridemia associated with elevated ApoB and low ApoA-I levels, but normal triglyceride composition. These findings suggest that the abnormal triglyceride composition is a late feature of the hyperlipidemia in leukemia, as observed in the case studied. PMID:6585175

Blackett, P R; Koren, E; Blackstock, R; Downs, D; Wang, C S

1984-01-01

408

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

409

p53 expression in myeloid cells of myelodysplastic syndromes. Association with evolution of overt leukemia.  

PubMed Central

To assess p53 expression in the hematopoietic cells of the bone marrow in premalignant as well as malignant conditions, we examined immunohistochemically bone marrow biopsies from patients with myelodysplastic syndromes (MDS, n = 51), acute myeloid leukemia (n = 42) and as a nonneoplastic condition, aplastic anemia (n = 20) and samples from individuals who had no hematological disorder (control, n = 12). Nuclear accumulation of p53 protein was found in seven of 51 patients with MDS (14%) and two of 42 acute myeloid leukemia patients (5%), whereas patients with aplastic anemia and control subjects were uniformly negative for p53 protein. In the bone marrow of patient with MDS, p53-positive cells constituted about 5 to 30% of the total bone marrow cells. Two-color immunohistochemical analysis revealed that the p53-positive cells were also positive for the myeloid cell marker. Half of the MDS cases that evolved to overt leukemia (seven of 14) exhibited positive p53 reaction in the bone marrow at the time of initial diagnosis. This frequency (50%) was significantly higher than that in de novo acute myeloid leukemia cases. All of the seven MDS cases that exhibited p53 expression at the time of initial diagnosis developed overt leukemia later, and p53 expression was maintained throughout the progression of MDS. The results suggest that p53 mutations that occur in the myeloid cells in MDS may confer a growth advantage to these cells resulting in the progression to overt leukemia. Thus, immunohistochemical examination for p53 is very useful for predicting the evolution to overt leukemia from MDS. Images Figure 1 Figure 2

Kitagawa, M.; Yoshida, S.; Kuwata, T.; Tanizawa, T.; Kamiyama, R.

1994-01-01

410

Commentary: childhood cancer near nuclear power stations  

PubMed Central

In 2008, the KiKK study in Germany reported a 1.6-fold increase in solid cancers and a 2.2-fold increase in leukemias among children living within 5 km of all German nuclear power stations. The study has triggered debates as to the cause(s) of these increased cancers. This article reports on the findings of the KiKK study; discusses past and more recent epidemiological studies of leukemias near nuclear installations around the world, and outlines a possible biological mechanism to explain the increased cancers. This suggests that the observed high rates of infant leukemias may be a teratogenic effect from incorporated radionuclides. Doses from environmental emissions from nuclear reactors to embryos and fetuses in pregnant women near nuclear power stations may be larger than suspected. Hematopoietic tissues appear to be considerably more radiosensitive in embryos/fetuses than in newborn babies. Recommendations for advice to local residents and for further research are made.

2009-01-01

411

Eltrombopag Olamine in Improving Platelet Recovery in Older Patients With Acute Myeloid Leukemia Undergoing Chemotherapy  

ClinicalTrials.gov

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; 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); Secondary Acute Myeloid Leukemia

2014-04-29

412

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

413

RBC nuclear scan  

MedlinePLUS

An RBC nuclear scan uses small amounts of radioactive material to mark (tag) red blood cells (RBCs). Your body is then ... radiation -- it does not give off radiation. Most nuclear scans (including an RBC scan) are not recommended ...

414

New Window into the Human Body  

NASA Technical Reports Server (NTRS)

Michael Vannier, MD, a former NASA engineer, recognized the similarity between NASA's computerized image processing technology and nuclear magnetic resonance. With technical assistance from Kennedy Space Center, he developed a computer program for Mallinckrodt Institute of Radiology enabling Nuclear Magnetic Resonance (NMR) to scan body tissue for earlier diagnoses. Dr. Vannier feels that "satellite imaging" has opened a new window into the human body.

1985-01-01

415

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

2014-06-06

416

Bortezomib, Sorafenib Tosylate, and Decitabine 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; Untreated Adult Acute Myeloid Leukemia

2014-07-28

417

A dose escalation study of total body irradiation followed by high-dose etoposide and allogeneic blood stem cell transplantation for the treatment of advanced hematologic malignancies  

Microsoft Academic Search

Since approximately 30% of leukemia patients relapse after allogeneic BMT using total body irradiation (TBI)-based preparative regimens, treatment intensity may be suboptimal. The killing of leukemia cells is proportional to the radiation absorbed dose. We studied the feasibility and toxicity of escalating the doses of fractionated TBI above our previous prescription of 13.5 Gy. Sixteen evaluable patients with advanced hematologic

RM Sobecks; CK Daugherty; DE Hallahan; GF Laport; ND Wagner; RA Larson

2000-01-01

418

Targeting Leukemia: From Bench to Bedside  

NSDL National Science Digital Library

FASEB Breakthroughs in Bioscience article. As researchers discovered effective treatments for leukemia, there remained a stumbling block: the drugs that killed leukemia cells were unable to penetrate into the brain and spinal cord. Fortunately, using animal models, scientists were able to develop a direct injection and irradiation protocol that eliminated this problem.

Margie Patlak (Federation of American Societies for Experimental Biology Office of Public Affairs)

2002-03-01

419

Targeting cathepsin G in myeloid leukemia  

PubMed Central

Cathepsin G (CG) is a serine protease normally found within the azurophil granules of neutrophils. CG is expressed during the early stages of normal myeloid differentiation and—aberrantly—by myeloid leukemia cells. We have recently identified CG-derived HLA-A*0201-binding peptides that constitute promising targets for the immunotherapy of myeloid leukemia.

Alatrash, Gheath

2013-01-01

420

Acute leukemia following treatment of malignant glioma  

Microsoft Academic Search

We report two patients with acute myeloid leukemia (AML) following therapy for malignant glioma; one was a young women treated heavily with alkylating agents for glioblastoma and the other a young man treated with high doses of procarbazine, lomustine, and vincristine (PCV) for anaplastic astrocytoma. We found 26 other examples of therapy related leukemia in adult and pediatric brain tumor

James R. Perry; Mark T. Brown; Jon P. Gockerman

1998-01-01

421

Hairy cell leukemia masquerading as infective endocarditis.  

PubMed

Hairy cell leukemia is a chronic lymphoproliferative disorder affecting middle-aged adults, with the median age of 50-55 years. We report a case of hairy cell leukemia who presented with fever, splinter haemorrhages and moderate splenomegaly, simulating infective endocarditis. There was bicytopenia at presentation and hairy cells were seen in the peripheral blood. PMID:24426343

Ramasamy, Chandramohan; Dubashi, Biswajit; Rekha, J Sree; Basu, Debdatta; Jain, Ankit; Dutta, Tarun Kumar

2013-06-01

422

Stages of Adult Acute Myeloid Leukemia  

MedlinePLUS

... or pain, and the following are true: The complete blood count is abnormal . At least 20% of the cells in the bone marrow are blasts ( leukemia cells). ... been treated and the following are true: The complete blood count is normal. Less than 5% of the cells in the bone marrow are blasts ( leukemia cells). ...

423

Acute lymphocytic leukemia masquerading as acute osteomyelitis  

Microsoft Academic Search

Two children each developed a focal destructive bone lesion accompanied by intermittent fever, swelling, tenderness and elevated ESR. Blood counts were normal; bone marrow aspiration showed acute leukemia. The bone lesions healed in both patients after anti-leukemic therapy. We suggest that the similar roentgenographic appearance of osteomyelitis, bone infarction and focal destructive lesions in leukemia probably reflects a common, basically

Anneliese L. Sitarz; W. E. Berdon; J. A. Wolff; D. H. Baker

1980-01-01

424

Trisomy 13: A New Recurring Chromosome Abnormality in Acute Leukemia  

Microsoft Academic Search

A new recurring chromosome abnormality was identified in 8 of 621 consecutive successfully karyotyped adults with de novo acute leukemia. These eight patients had trisomy 13 as the sole cytogenetic abnormality. On central morpho- logic review, five cases were classified as subtypes of acute myeloid leukemia, one as acute mixed lymphoid and my- eloid leukemia, one as acute lymphoid leukemia,

Hartmut Dohner; Diane C. Arthur; Edward D. Ball; Robert E. Sobol; Frederick R. Davey; David Lawrence; Lawrence Gordon; Shivanand R. Patil; Rawatmal B. Surana; Joseph R. Testa; Ram S. Verma; Charles A. Schiffer; Doris H. Wurster-Hill; Clara D. Bloomfield

1990-01-01

425

Chronic myeloid leukemia: mechanisms of blastic transformation  

PubMed Central

The BCR-ABL1 oncoprotein transforms pluripotent HSCs and initiates chronic myeloid leukemia (CML). Patients with early phase (also known as chronic phase [CP]) disease usually respond to treatment with ABL tyrosine kinase inhibitors (TKIs), although some patients who respond initially later become resistant. In most patients, TKIs reduce the leukemia cell load substantially, but the cells from which the leukemia cells are derived during CP (so-called leukemia stem cells [LSCs]) are intrinsically insensitive to TKIs and survive long term. LSCs or their progeny can acquire additional genetic and/or epigenetic changes that cause the leukemia to transform from CP to a more advanced phase, which has been subclassified as either accelerated phase or blastic phase disease. The latter responds poorly to treatment and is usually fatal. Here, we discuss what is known about the molecular mechanisms leading to blastic transformation of CML and propose some novel therapeutic approaches.

Perrotti, Danilo; Jamieson, Catriona; Goldman, John; Skorski, Tomasz

2010-01-01

426

Mechanisms of mixed-lineage leukemia  

PubMed Central

Summary Advances in our understanding of the genetic determinants of leukemia have translated to better treatment options and improved survival of patients with acute myeloid and acute lymphoid leukemia. However, some leukemias, such as those bearing 11q23 (MLL) translocations, result in aggressive diseases with a relatively poor prognosis, despite improved treatments such as allogeneic hematopoietic stem cell transplantation. This article will briefly review the functions and regulation of wild-type MLL during normal hematopoiesis, while focusing on recent advances in our understanding of the molecular mechanisms governing MLL leukemias. The transcriptional targets, cooperating signaling pathways and molecular machinery involved in MLL-associated leukemias will be discussed, as well as how these may be harnessed for more personalized treatment of this disease.

Muntean, Andrew G

2013-01-01

427

Mitochondrial and nuclear DNA phylogeography of Thymallus spp. (grayling) provides evidence of ice-age mediated environmental perturbations in the world's oldest body of fresh water, Lake Baikal  

Microsoft Academic Search

Theories on the hydrological history of Lake Baikal, the world's oldest and deepest body of freshwater, and its surrounding great rivers, are currently based solely on geological evidence and are conflicting. Baikal is inhabited by numerous zoogeographical enigmas but their high level of endemism has hindered phylogeographic inferences. We provide a biological perspective of the region's palaeo-hydrological development based on

Mikko T. Koskinen; Igor Knizhin; Craig R. Primmer; Christian Schlotterer; Steven Weiss

2002-01-01

428

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

429

Vorinostat and Idarubicin in Treating Patients With Relapsed or Refractory Leukemia or Myelodysplastic Syndromes  

ClinicalTrials.gov

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; 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); Blastic Phase Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

2013-09-27

430

Midostaurin and Azacitidine in Treating Elderly Patients With Acute Myelogenous Leukemia  

ClinicalTrials.gov

Hematopoietic/Lymphoid Cancer; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

2013-10-11

431

Body lice  

MedlinePLUS

... be checked for head and public lice if you have body lice. ... live in clothing. To get rid of lice, destroy infected clothing ... also prescribe a cream that you put on your skin or a wash that ...

432

Body Swatter  

NSDL National Science Digital Library

Students work in cooperative groups to research and write questions for an active game designed to review the major organs of the systems of the human body (digestive, respiratory, circulatory, and excretory system).

2013-02-15

433

Body Image  

MedlinePLUS

... surgery Breast surgery Botox Liposuction Varicose or spider veins Body dysmorphic disorder (BDD) Eating disorders Anorexia nervosa ... policy | Disclaimers | FOIA | Link to us | USA.gov | Viewers and players A federal government website managed by ...

434

Perspectives on the Causes of Childhood Leukemia  

PubMed Central

Acute leukemia is the most common cancer in children but the causes of the disease in the majority of cases are not known. About 80% are precursor-B cell in origin (CD19+, CD10+), and this immunophenotype has increased in incidence over the past several decades in the Western world. Part of this increase may be due to the introduction of new chemical exposures into the child's environment including parental smoking, pesticides, traffic fumes, paint and household chemicals. However, much of the increase in leukemia rates is likely linked to altered patterns of infection during early childhood development, mirroring causal pathways responsible for a similarly increased incidence of other childhood-diagnosed immune-related illnesses including allergy, asthma, and type 1 diabetes. Factors linked to childhood leukemia that are likely surrogates for immune stimulation include exposure to childcare settings, parity status and birth order, vaccination history, and population mixing. In case-control studies, acute lymphoblastic leukemia (ALL) is consistently inversely associated with greater exposure to infections, via daycare and later birth order. New evidence suggests also that children who contract leukemia may harbor a congenital defect in immune responder status, as indicated by lower levels of the immunosuppressive cytokine IL-10 at birth in children who grow up to contract leukemia, as well as higher need for clinical care for infections within the first year of life despite having lower levels of exposure to infections. One manifestation of this phenomenon may be leukemia clusters which tend to appear as a leukemia “outbreak” among populations with low herd immunity to a new infection. Critical answers to the etiology of childhood leukemia will require incorporating new tools into traditional epidemiologic approaches – including the classification of leukemia at a molecular scale, better exposure assessments at all points in a child's life, a comprehensive understanding of genetic risk factors, and an appraisal of the interplay between infectious exposures and the status of immune response in individuals.

Wiemels, Joseph

2013-01-01

435

Body Systems  

NSDL National Science Digital Library

What are the parts and functions of the different systems in the body? Circulatory System Watch the Circulatory System and the Heart video. Complete one of the Circulatory System quizzes. Excretory System Label the parts of the excretory system. Respiratory System Quiz Complete respiratory system quiz to review parts. Skeletal System Label each part of the skeletal system. Vocabulary Review Change the settings to only include body system terms and play Hangman to review new vocabulary. ...

2011-11-02

436

ETO, a Target of t(8;21) in Acute Leukemia, Interacts with the N-CoR and mSin3 Corepressors  

Microsoft Academic Search

t(8;21) is one of the most frequent translocations associated with acute myeloid leukemia. It produc