Expression of caspase-3 gene in apoptotic HL-60 cell and different human tumor cell lines

International Nuclear Information System (INIS)

Li Xiaoming; Song Tianbao

1999-01-01

Objective: To research the expression of caspase-3 gene in the apoptotic and the control HL-60 cells and in the different human tumor cell lines. Methods: Caspase-3 mRNA in the control and γ-radiation-induced apoptotic HL-60 cells, and in the 6 types of human tumor cell lines, was analysed by Northern blot. Results: The caspase-3 gene transcript was more highly expressed in leukemia cells HL-60, CEM, K562 and neuroblastoma SH-SY5Y than in cervical adenocarcinoma HeLa and breast carcinoma MCF7, and more highly in the radiation-induced apoptotic HL-60 than in the control HL-60 cells. Conclusion: The high level of expression of caspase-3 may aid the efforts to understand the tumor cell sensitivity to radiation, apoptosis and its inherent ability to survive

Synthesis of minoxidil conjugates and their evaluation as HL-60 differentiation agents.

Science.gov (United States)

Stoica, Sonia; Magoulas, George E; Antoniou, Antonia I; Suleiman, Sherif; Cassar, Analisse; Gatt, Lucienne; Papaioannou, Dionissios; Athanassopoulos, Constantinos M; Schembri-Wismayer, Pierre

2016-02-15

Activation of minoxidil (MNX) with N,N'-carbonyldiimidazole and coupling with natural polyamines (PAs) and commercially available aliphatic or aromatic amines provided a series of new conjugates which were evaluated for their ability to induce differentiation to HL-60 acute myeloid leukemia cancer cells, using a modified NBTZ reduction test. Although neither MNX nor 4,4'-methylenedianiline (MDA) or 2,7-diaminofluorene (DAF), alone or in combination, had any effect, the MNX-spermine (SPM) conjugate (11) and the conjugates 7 and 8 of MNX with MDA and DAF exhibited a differentiation-inducing effect at a concentration of 10 μM without being toxic on proliferating human peripheral blood mononuclear cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

Zebrafish as a Model for the Study of Human Myeloid Malignancies

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Jeng-Wei Lu

2015-01-01

Full Text Available Myeloid malignancies are heterogeneous disorders characterized by uncontrolled proliferation or/and blockage of differentiation of myeloid progenitor cells. Although a substantial number of gene alterations have been identified, the mechanism by which these abnormalities interact has yet to be elucidated. Over the past decades, zebrafish have become an important model organism, especially in biomedical research. Several zebrafish models have been developed to recapitulate the characteristics of specific myeloid malignancies that provide novel insight into the pathogenesis of these diseases and allow the evaluation of novel small molecule drugs. This report will focus on illustrative examples of applications of zebrafish models, including transgenesis, zebrafish xenograft models, and cell transplantation approaches, to the study of human myeloid malignancies.

C/EBPγ deregulation results in differentiation arrest in acute myeloid leukemia

Czech Academy of Sciences Publication Activity Database

Alberich-Jorda, M.; Wouters, B.; Balaštík, Martin; Shapiro-Koss, C.; Zhang, H.; DiRuscio, A.; Radomska, H.S.; Ebralidze, A.K.; Amabile, G.; Ye, M.; Zhang, J.Y.; Lowers, I.; Avellino, R.; Melcnick, A.; Figueroa, M.E.; Valk, P.J.M.; Delwel, R.; Tenen, D.G.

2012-01-01

Roč. 122, č. 12 (2012), s. 4490-4504 ISSN 0021-9738 Grant - others:NIH(US) CA118316; NIH(US) HL56745 Institutional support: RVO:68378050 Keywords : C/EBP transcription factor * acute myeloid leukemia * differentiation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 12.812, year: 2012

Ultraviolet B irradiation of human leukaemia HL-60 cells in vitro induces apoptosis

International Nuclear Information System (INIS)

Martin, S.J.; Cotter, T.G.

1991-01-01

UV radiation is known to be a potent agent for the induction of programmed cell death (apoptosis) in human skin. However, the mechanistic aspects of UV-induced apoptosis remain ill-defined. In this study the effects of varying periods of UV-irradiation on the human leukaemia HL-60 cell line and on five other human cell lines were investigated.HL-60 cells were found to rapidly undergo apoptosis en masse after short periods of UV-irradiation whereas prolonged exposure of these cells to this form of radiation induced a more rapid form of cell death which was suggestive of necrosis, the pathological mode of cell death. UV-induced apoptosis in cell lines was characterized by morphological changes as well as DNA fragmentation into unit multiples of ∼ 200 bp, which was indicative of endogenous endonuclease activation. This DNA fragmentation pattern was not detected in cells immediately after UV-irradiation, and was therefore not the result of direct UV-induced DNA damage. UV-induced apoptosis of the HL-60 cell line was found to require extracellular calcium and to be inhibited in a dose-dependent way by zinc added to the culture medium. (author)

Luteoloside Inhibits Proliferation of Human Chronic Myeloid ...

African Journals Online (AJOL)

Purpose: To investigate the effects of luteoloside on the proliferation of human chronic myeloid leukemia K562 cells and whether luteoloside induces cell cycle arrest and apoptosis in K562 cells. Methods: Luteoloside's cytotoxicity was assessed using a cell counting kit. Cell cycle distribution was analysed by flow cytometry ...

Resistance of human and mouse myeloid leukemia cells to UV radiation

International Nuclear Information System (INIS)

Poljak-Blazi, M.; Osmak, M.; Hadzija, M.

1989-01-01

Sensitivity of mouse bone marrow and myeloid leukemia cells and sensitivity of human myeloid leukemia cells to UV light was tested. Criteria were the in vivo colony-forming ability of UV exposed cells and the inhibition of DNA synthesis during post-irradiation incubation for 24 h in vitro. Mouse bone marrow cells irradiated with a small dose of UV light (5 J/m 2 ) and injected into x-irradiated animals did not form hemopoietic colonies on recipient's spleens, and recipients died. However, mouse leukemia cells, after irradiation with higher doses of UV light, retained the ability to form colonies on the spleens, and all recipient mice died with typical symptoms of leukemia. In vitro, mouse bone marrow cells exhibited high sensitivity to UV light compared to mouse myeloid leukemia cells. Human leukemia cells were also resistant to UV light, but more sensitive than mouse leukemia cells. (author)

Anti-Leukemic Activity of Shikonin: Role of ERP57 in Shikonin Induced Apoptosis in Acute Myeloid Leukemia

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Rachana Trivedi

2016-07-01

Full Text Available Background/Aims: ER-Stress and activation of unfolded protein response belong to the major factors involved in chemoresistance in cancer cells. In this study we investigated the effect of shikonin on the survival of acute myeloid leukemia cells and the role of ER-stress protein ERP57, a protein disulfide isomerase, in improvement of chemotherapy. Methods: Using MTT assay we studied cytotoxic effects of shikonin on HL-60 cells. The flow cytometry was adopted to examine the shikonin induced mode of cell death in HL-60 cells. The overall protein expression alteration resulting from shikonin treatment was investigated using proteomics methods. Western blotting was performed to quantify the alteration in protein expression in HL-60 after shikonin treatment. Silencing and overexpression studies were carried out to highlight the therapeutic role of ERP57 in shikonin effect on AML cells. Results: Shikonin induces apoptosis in HL-60 cells without significant effect on Primary cells from healthy volunteers. The apoptotic effect was dose and time dependent and was accompanied by strong alteration in cell proteome. Among the proteins targeted by shikonin, ERP57 was significantly downregulated in HL-60 after treatment. Compared to healthy control ERP57 was found to be highly expressed in AML cell line HL60 and was downregulated after shikonin treatment. Overexpression of ERP57 protected HL-60 from shikonin induced apoptosis, whereas knockdown of ERP57 expression resulted in increase in shikonin induced apoptosis. Conclusions: Our results demonstrate that ERP57 plays a crucial role in resistance towards shikonin induced apoptosis in AML cells. Targeting of ERP57 might offer a new therapeutic option for the treatment of acute myeloid leukemia.

Apoptotic effect of a novel kefir product, PFT, on multidrug-resistant myeloid leukemia cells via a hole-piercing mechanism

Science.gov (United States)

GHONEUM, MAMDOOH; GIMZEWSKI, JAMES

2014-01-01

We examined the apoptotic effect of a novel Probiotics Fermentation Technology (PFT) kefir grain product; PFT is a natural mixture composed primarily of Lactobacillus kefiri P-IF, a specific strain of L. kefiri with unique growth characteristics. The aim of this study was to examine the apoptotic effect of PFT on human multidrug-resistant (MDR) myeloid leukemia (HL60/AR) cells in vitro and explore the mechanistic approach underlying its effect. HL60/AR cells were cultured with PFT (0.6–5.0 mg/ml) for 3 days. The apoptotic effect of PFT was assessed through examination of percent apoptosis, caspase 3 activation, Bcl-2 expression levels and changes in mitochondrial membrane potential (MMP). PFT induced apoptosis in HL60/AR cells in a dose-dependent manner which was maximal at 67.5% for 5 mg/ml. Induction of apoptosis was associated with activation of caspase 3, decreased expression of Bcl-2 and decreased polarization of MMP. In addition, PFT showed a unique characteristic of piercing holes in HL60/AR cells, as indicated by AFM studies. This hole induction may be responsible for the apoptotic effect on cancer cells. These results suggest that PFT may act as a potential therapy for the treatment of MDR leukemia. PMID:24430613

BCL-x{sub L}/MCL-1 inhibition and RARγ antagonism work cooperatively in human HL60 leukemia cells

Energy Technology Data Exchange (ETDEWEB)

Perri, Mariarita; Yap, Jeremy L.; Yu, Jianshi [Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N Pine Street, Baltimore, MD 21201 (United States); Cione, Erika [Department of Pharmacy, Health and Nutritional Sciences, Ed. Polifunzionale, University of Calabria, 87036 Rende, CS (Italy); Fletcher, Steven [Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N Pine Street, Baltimore, MD 21201 (United States); Kane, Maureen A., E-mail: mkane@rx.umaryland.edu [Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N Pine Street, Baltimore, MD 21201 (United States)

2014-10-01

The acute promyelocytic leukemia (APL) subtype of acute myeloid leukemia (AML) is characterized by chromosomal translocations that result in fusion proteins, including the promyelocytic leukemia–retinoic acid receptor, alpha fusion protein (PML–RARα). All-trans retinoic acid (atRA) treatment is the standard drug treatment for APL yielding cure rates >80% by activating transcription and proteasomal degradation of retinoic acid receptor, alpha (RARα). Whereas combination therapy with As{sub 2}O{sub 3} has increased survival further, patients that experience relapse and are refractory to atRA and/or As{sub 2}O{sub 3} is a clinically significant problem. BCL-2 family proteins regulate apoptosis and over-expression of anti-apoptotic B-cell leukemia/lymphoma 2 (BCL-2) family proteins has been associated with chemotherapeutic resistance in APL including impairment of the ability of atRA to induce growth arrest and differentiation. Here we investigated the novel BH3 domain mimetic, JY-1-106, which antagonizes the anti-apoptotic BCL-2 family members B-cell lymphoma-extra large (BCL-x{sub L}) and myeloid cell leukemia-1 (MCL-1) alone and in combination with retinoids including atRA, AM580 (RARα agonist), and SR11253 (RARγ antagonist). JY-1-106 reduced cell viability in HL-60 cells alone and in combination with retinoids. The combination of JY-1-106 and SR11253 had the greatest impact on cell viability by stimulating apoptosis. These studies indicate that dual BCL-x{sub L}/MCL-1 inhibitors and retinoids could work cooperatively in leukemia treatment. - Highlights: • Novel Bcl-x{sub L}/Mcl-1 inhibitor JY-1-106 reduces HL60 cell viability. • JY-1-106 is investigated in combination with retinoic acid, AM580, and SR11253. • AM580 is an RARα agonist; SR11253 is an RARγ antagonist. • Combined use of JY-1-106/SR11253 exhibited the greatest cell viability reduction. • JY-1-106 alone or in combination with retinoids induces apoptosis.

Dose- and Time-Dependent Response of Human Leukemia (HL-60 Cells to Arsenic Trioxide Treatment

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Paul B. Tchounwou

2006-06-01

Full Text Available The treatment of acute promyelocytic leukemia (APL has been based on the administration of all-trans retinoic acid plus anthracycline chemotherapy, which is very effective as first line therapy; however 25 to 30% of patients will relapse with their disease becoming refractory to conventional therapy. Recently, studies have shown arsenic trioxide to be effective in the treatment of acute promyelocytic leukemia. In this study, we used the human leukemia (HL-60 cell line as a model to evaluate the cytoxicity of arsenic trioxide based on the MTT assay. Data obtained from this assay indicated that arsenic trioxide significantly reduced the viability of HL-60 cells, showing LD50 values of 14.26 + 0.5μg/mL, 12.54 + 0.3μg/mL, and 6.4 + 0.6μg/mL upon 6, 12, and 24 hours of exposure, respectively; indicating a dose- and time-dependent response relationship. Findings from the present study indicate that arsenic trioxide is highly cytotoxic to human leukemia (HL-60 cells, supporting its use as an effective therapeutic agent in the management of acute promyelocytic leukemia.

Gene expression profiling for nitric oxide prodrug JS-K to kill HL-60 myeloid leukemia cells.

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Liu, Jie; Malavya, Swati; Wang, Xueqian; Saavedra, Joseph E; Keefer, Larry K; Tokar, Erik; Qu, Wei; Waalkes, Michael P; Shami, Paul J

2009-07-01

The nitric oxide (NO) prodrug JS-K is shown to have anticancer activity. To profile the molecular events associated with the anticancer effects of JS-K, HL-60 leukemia cells were treated with JS-K and subjected to microarray and real-time RT-PCR analysis. JS-K induced concentration- and time-dependent gene expression changes in HL-60 cells corresponding to the cytolethality effects. The apoptotic genes (caspases, Bax, and TNF-alpha) were induced, and differentiation-related genes (CD14, ITGAM, and VIM) were increased. For acute phase protein genes, some were increased (TP53, JUN) while others were suppressed (c-myc, cyclin E). The expression of anti-angiogenesis genes THBS1 and CD36 and genes involved in tumor cell migration such as tissue inhibitors of metalloproteinases, were also increased by JS-K. Confocal analysis confirmed key gene changes at the protein levels. Thus, multiple molecular events are associated with JS-K effects in killing HL-60, which could be molecular targets for this novel anticancer NO prodrug.

Probiotic assessment of Enterococcus durans 6HL and Lactococcus lactis 2HL isolated from vaginal microflora.

Science.gov (United States)

Nami, Yousef; Abdullah, Norhafizah; Haghshenas, Babak; Radiah, Dayang; Rosli, Rozita; Khosroushahi, Ahmad Yari

2014-08-01

Forty-five lactic acid bacteria (LAB) were isolated from the vaginal specimens of healthy fertile women, and the identities of the bacteria were confirmed by sequencing of their 16S rDNA genes. Among these bacteria, only four isolates were able to resist and survive in low pH, bile salts and simulated in vitro digestion conditions. Lactococcus lactis 2HL, Enterococcus durans 6HL, Lactobacillus acidophilus 36YL and Lactobacillus plantarum 5BL showed the best resistance to these conditions. These strains were evaluated further to assess their ability to adhere to human intestinal Caco-2 cells. Lactococcus lactis 2HL and E. durans 6HL were the most adherent strains. In vitro tests under neutralized pH proved the antimicrobial activity of both strains. Results revealed that the growth of Escherichia coli O26, Staphylococcus aureus and Shigella flexneri was suppressed by both LAB strains. The antibiotic susceptibility tests showed that these strains were sensitive to all nine antibiotics: vancomycin, tetracycline, ampicillin, penicillin, gentamicin, erythromycin, clindamycin, sulfamethoxazole and chloramphenicol. These data suggest that E. durans 6HL and Lactococcus lactis 2HL could be examined further for their useful properties and could be developed as new probiotics. © 2014 The Authors.

Activity of the hypoxia-activated prodrug, TH-302, in preclinical human acute myeloid leukemia models.

Science.gov (United States)

Portwood, Scott; Lal, Deepika; Hsu, Yung-Chun; Vargas, Rodrigo; Johnson, Megan K; Wetzler, Meir; Hart, Charles P; Wang, Eunice S

2013-12-01

Acute myeloid leukemia (AML) is an aggressive hematologic neoplasm. Recent evidence has shown the bone marrow microenvironment in patients with AML to be intrinsically hypoxic. Adaptive cellular responses by leukemia cells to survive under low oxygenation also confer chemoresistance. We therefore asked whether therapeutic exploitation of marrow hypoxia via the hypoxia-activated nitrogen mustard prodrug, TH-302, could effectively inhibit AML growth. We assessed the effects of hypoxia and TH-302 on human AML cells, primary samples, and systemic xenograft models. We observed that human AML cells and primary AML colonies cultured under chronic hypoxia (1% O2, 72 hours) exhibited reduced sensitivity to cytarabine-induced apoptosis as compared with normoxic controls. TH-302 treatment resulted in dose- and hypoxia-dependent apoptosis and cell death in diverse AML cells. TH-302 preferentially decreased proliferation, reduced HIF-1α expression, induced cell-cycle arrest, and enhanced double-stranded DNA breaks in hypoxic AML cells. Hypoxia-induced reactive oxygen species by AML cells were also diminished. In systemic human AML xenografts (HEL, HL60), TH-302 [50 mg/kg intraperitoneally (i.p.) 5 times per week] inhibited disease progression and prolonged overall survival. TH-302 treatment reduced the number of hypoxic cells within leukemic bone marrows and was not associated with hematologic toxicities in nonleukemic or leukemic mice. Later initiation of TH-302 treatment in advanced AML disease was as effective as earlier TH-302 treatment in xenograft models. Our results establish the preclinical activity of TH-302 in AML and provide the rationale for further clinical studies of this and other hypoxia-activated agents for leukemia therapy. ©2013 AACR.

TRIM32 promotes retinoic acid receptor α-mediated differentiation in human promyelogenous leukemic cell line HL60

International Nuclear Information System (INIS)

Sato, Tomonobu; Okumura, Fumihiko; Iguchi, Akihiro; Ariga, Tadashi; Hatakeyama, Shigetsugu

2012-01-01

Highlights: ► TRIM32 enhanced RARα-mediated transcriptional activity even in the absence of RA. ► TRIM32 stabilized RARα in the human promyelogenous leukemic cell line HL60. ► Overexpression of TRIM32 in HL60 cells induced granulocytic differentiation. ► TRIM32 may function as a coactivator for RARα-mediated transcription in APL cells. -- Abstract: Ubiquitination, one of the posttranslational modifications, appears to be involved in the transcriptional activity of nuclear receptors including retinoic acid receptor α (RARα). We previously reported that an E3 ubiquitin ligase, TRIM32, interacts with several important proteins including RARα and enhances transcriptional activity of RARα in mouse neuroblastoma cells and embryonal carcinoma cells. Retinoic acid (RA), which acts as a ligand to nuclear receptors including RARα, plays crucial roles in development, differentiation, cell cycles and apoptosis. In this study, we found that TRIM32 enhances RARα-mediated transcriptional activity even in the absence of RA and stabilizes RARα in the human promyelogenous leukemic cell line HL60. Moreover, we found that overexpression of TRIM32 in HL60 cells suppresses cellular proliferation and induces granulocytic differentiation even in the absence of RA. These findings suggest that TRIM32 functions as one of the coactivators for RARα-mediated transcription in acute promyelogenous leukemia (APL) cells, and thus TRIM32 may become a potentially therapeutic target for APL.

Radotinib Induces Apoptosis of CD11b+ Cells Differentiated from Acute Myeloid Leukemia Cells.

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Sook-Kyoung Heo

Full Text Available Radotinib, developed as a BCR/ABL tyrosine kinase inhibitor (TKI, is approved for the second-line treatment of chronic myeloid leukemia (CML in South Korea. However, therapeutic effects of radotinib in acute myeloid leukemia (AML are unknown. In the present study, we demonstrate that radotinib significantly decreases the viability of AML cells in a dose-dependent manner. Kasumi-1 cells were more sensitive to radotinib than NB4, HL60, or THP-1 cell lines. Furthermore, radotinib induced CD11b expression in NB4, THP-1, and Kasumi-1 cells either in presence or absence of all trans-retinoic acid (ATRA. We found that radotinib promoted differentiation and induced CD11b expression in AML cells by downregulating LYN. However, CD11b expression induced by ATRA in HL60 cells was decreased by radotinib through upregulation of LYN. Furthermore, radotinib mainly induced apoptosis of CD11b+ cells in the total population of AML cells. Radotinib also increased apoptosis of CD11b+ HL60 cells when they were differentiated by ATRA/dasatinib treatment. We show that radotinib induced apoptosis via caspase-3 activation and the loss of mitochondrial membrane potential (ΔΨm in CD11b+ cells differentiated from AML cells. Our results suggest that radotinib may be used as a candidate drug in AML or a chemosensitizer for treatment of AML by other therapeutics.

Effect of coumarins on HL-60 cell differentiation.

Science.gov (United States)

Kawaii, S; Tomono, Y; Katase, E; Ogawa, K; Yano, M

2000-01-01

Twenty-eight coumarins, including 7 furocoumarins, were examined for their activity of induction of terminal differentiation of human promyelocytic leukemia cells (HL-60) by nitro blue tetrazolium (NBT) reducing, nonspecific esterase, specific esterase and phagocytic activities. Esculetin, nordalbergin, 6,7-dihydroxy-4-methylcoumarin and imperatorin had strong activity among the coumarins examined. HL-60 cells treated with these coumarins differentiated into mature monocyte/macrophage. The structure-activity relationship established from the results revealed that 6,7-dihydroxy moiety had an important role in the induction of differentiation of HL-60.

Antiproliferative activity of pristimerin isolated from Maytenus ilicifolia (Celastraceae) in human HL-60 cells.

Science.gov (United States)

Costa, Patricia Marçal da; Ferreira, Paulo Michel Pinheiro; Bolzani, Vanderlan da Silva; Furlan, Maysa; de Freitas Formenton Macedo Dos Santos, Vânia Aparecida; Corsino, Joaquim; de Moraes, Manoel Odorico; Costa-Lotufo, Letícia Veras; Montenegro, Raquel Carvalho; Pessoa, Cláudia

2008-06-01

Pristimerin has been shown to be cytotoxic to several cancer cell lines. In the present work, the cytotoxicity of pristimerin was evaluated in human tumor cell lines and in human peripheral blood mononuclear cells (PBMC). This work also examined the effects of pristimerin (0.4; 0.8 and 1.7 microM) in HL-60 cells, after 6, 12 and 24h of exposure. Pristimerin reduced the number of viable cells and increased number of non-viable cells in a concentration-dependent manner by tripan blue test showing morphological changes consistent with apoptosis. Nevertheless, pristimerin was not selective to cancer cells, since it inhibited PBMC proliferation with an IC50 of 0.88 microM. DNA synthesis inhibition assessed by 5-bromo-2'-deoxyuridine (BrdU) incorporation in HL-60 cells was 70% and 83% for the concentrations of 0.4 and 0.8 microM, respectively. Pristimerin (10 and 20 microM) was not able to inhibit topoisomerase I. In AO/EB (acridine orange/ethidium bromide) staining, all tested concentrations reduced the number of HL-60 viable cells, with the occurrence of necrosis and apoptosis in a concentration-dependent manner, results in agreement with trypan blue exclusion findings. The analysis of membrane integrity and internucleosomal DNA fragmentation by flow cytometry in the presence of pristimerin indicated that treated cells underwent apoptosis. The present data point to the importance of pristimerin as representative of an emerging class of potential anticancer chemicals, exhibiting an antiproliferative effect by inhibiting DNA synthesis and triggering apoptosis.

Rhein triggers apoptosis via induction of endoplasmic reticulum stress, caspase-4 and intracellular calcium in primary human hepatic HL-7702 cells

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KoraMagazi, Arouna [Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu (China); Wang, Dandan [Department of Pharmacology, China Pharmaceutical University, Nanjing, Jiangsu (China); Yousef, Bashir; Guerram, Mounia [Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu (China); Yu, Feng, E-mail: yufengcpu14@yahoo.com [Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu (China); Department of Pharmacology, China Pharmaceutical University, Nanjing, Jiangsu (China); Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Nanjing, Jiangsu (China)

2016-04-22

Rhein is an active component of rhubarb; a traditional Chinese medicine reported to induce apoptosis and cause liver toxicity. However, rhein's apoptotic-inducing effects, as well as its molecular mechanisms of action on hepatic cells need to be further explored. In the present study, rhein was found to trigger apoptosis in primary human hepatic HL-7702 cells as showed by annexin V/PI double staining assay and nuclear morphological changes demonstrated by Hoechst 33258 staining. Moreover, it was observed that the mechanism implicated in rhein-induced apoptosis was caspase-dependent, presumably via ER-stress associated pathways, as illustrated by up-regulation of glucose-regulated protein 78 (GRP 78), PKR-like ER kinase (PERK), C-Jun N-terminal kinase (JNK) and CCAAT/enhancer-binding protein homologous protein (CHOP). Meanwhile, caspase-4 as a hallmark of ER-stress, was also showed to be activated following by caspase-3 activation. Furthermore, rhein also promoted intracellular elevation of calcium that contributed in apoptosis induction. Interestingly, pre-treatment with calpain inhibitor I reduced the effects of rhein on apoptosis induction and JNK activation. These data suggested that rhein-induced apoptosis through ER-stress and elevated intracellular calcium level in HL-7702 cells. - Highlights: • Rhein triggers apoptotic cell death on primary human hepatic HL-7702 cells. • Rhein leads to caspase-4 activation in HL-7702 cells. • Rhein induces endoplasmic reticulum stress pathways in HL-7702 cells. • Rhein causes elevation of intracellular calcium concentrations in HL-7702 cells.

FUSION OF SENDAI VIRUS WITH HUMAN HL-60 AND CEM CELLS - DIFFERENT KINETICS OF FUSION FOR 2 ISOLATES

NARCIS (Netherlands)

DELIMA, MCP; NIR, S; FLASHER, D; KLAPPE, K; HOEKSTRA, D; DUZGUNES, N

1991-01-01

The kinetics of fusion of Sendai virus (Z strain) with the human promyelocytic leukemia cell line HL-60, and the human T lymphocytic leukemia cell line CEM was investigated. Fusion was monitored by fluorescence dequenching of octadecylrhodamine (R-18) incorporated in the viral membrane. For one

Retinoic acid-induced granulocytic differentiation of HL60 human promyelocytic leukemia cells is preceded by downregulation of autonomous generation of inositol lipid-derived second messengers

International Nuclear Information System (INIS)

Porfiri, E.; Hoffbrand, A.V.; Wickremasinghe, R.G.

1991-01-01

Inositol phosphates (InsPs) and diacyglycerol (DAG) are second messengers derived via the breakdown of inositol phospholipids, and which play important signalling roles in the regulation of proliferation of some cell types. The authors have studied the operation of this pathway during the early stages of retionic acid (RA)-induced granulocytic differentiation of HL60 myeloid leukemia cells. The autonomous breakdown of inositol lipids that occurred in HL60 cells labeled with [3H] inositol was completely abolished following 48 hours of RA treatment. The rate of influx of 45Ca2+ was also significantly decreased at 48 hours, consistent with the role of inositol lipid-derived second messengers in regulating Ca2+ entry into cells. The downregulation of inositol lipid metabolism clearly preceded the onset of reduced proliferation induced by RA treatment, and was therefore not a consequence of decreased cell growth. The generation of InsPs in RA-treated cells was reactivated by the fluoroaluminate ion, a direct activator of guanine nucleotide-binding protein(s) (G proteins) that regulate the inositol lipid signalling pathway. Subtle alterations to a regulatory mechanism may therefore mediate the RA-induced downregulation of this pathway. The data are consistent with the hypothesis that the autonomous generation of inositol lipid-derived second messengers may contribute to the continuous proliferation of HL60 cells, and that the RA-induced downregulation of this pathway may, in turn, play a role in signalling the cessation of proliferation that preceedes granulocytic differentiation

Multiplex CRISPR/Cas9-Based Genome Editing in Human Hematopoietic Stem Cells Models Clonal Hematopoiesis and Myeloid Neoplasia.

Science.gov (United States)

Tothova, Zuzana; Krill-Burger, John M; Popova, Katerina D; Landers, Catherine C; Sievers, Quinlan L; Yudovich, David; Belizaire, Roger; Aster, Jon C; Morgan, Elizabeth A; Tsherniak, Aviad; Ebert, Benjamin L

2017-10-05

Hematologic malignancies are driven by combinations of genetic lesions that have been difficult to model in human cells. We used CRISPR/Cas9 genome engineering of primary adult and umbilical cord blood CD34 + human hematopoietic stem and progenitor cells (HSPCs), the cells of origin for myeloid pre-malignant and malignant diseases, followed by transplantation into immunodeficient mice to generate genetic models of clonal hematopoiesis and neoplasia. Human hematopoietic cells bearing mutations in combinations of genes, including cohesin complex genes, observed in myeloid malignancies generated immunophenotypically defined neoplastic clones capable of long-term, multi-lineage reconstitution and serial transplantation. Employing these models to investigate therapeutic efficacy, we found that TET2 and cohesin-mutated hematopoietic cells were sensitive to azacitidine treatment. These findings demonstrate the potential for generating genetically defined models of human myeloid diseases, and they are suitable for examining the biological consequences of somatic mutations and the testing of therapeutic agents. Copyright © 2017 Elsevier Inc. All rights reserved.

Genes encoded within 8q24 on the amplicon of a large extrachromosomal element are selectively repressed during the terminal differentiation of HL-60 cells.

Science.gov (United States)

Hirano, Tetsuo; Ike, Fumio; Murata, Takehide; Obata, Yuichi; Utiyama, Hiroyasu; Yokoyama, Kazunari K

2008-04-02

Human acute myeloblastic leukemia HL-60 cells become resistant to differentiation during long-term cultivation. After 150 passages, double minute chromosomes (dmins) found in early-passaged cells are replaced by large extrachromosomal elements (LEEs). In a DNA library derived from a purified fraction of LEEs, 12.6% (23/183) of clones were assigned to 8q24 and 9.2% (17/183) were assigned to 14q11 in the human genome. Fluorescence in situ hybridization (FISH) revealed a small aberrant chromosome, which had not been found in early-passaged cells, in addition to the purified LEEs. We determined that each LEE consisted of six discontinuous segments in a region that extended for 4.4Mb over the 8q24 locus. Five genes, namely, Myc (a proto-oncogene), NSMCE2 (for a SUMO ligase), CCDC26 (for a retinoic acid-dependent modulator of myeloid differentiation), TRIB1 (for a regulator of MAPK kinase) and LOC389637 (for a protein of unknown function), were encoded by the amplicon. Breaks in the chromosomal DNA within the amplicon were found in the NSMCE2 and CCDC26 genes. The discontinuous structure of the amplicon unit of the LEEs was identical with that of dmins in HL-60 early-passaged cells. The difference between them seemed, predominantly, to be the number (10-15 copies per LEE versus 2 or 3 copies per dmin) of constituent units. Expression of the Myc, NSMCE2, CCDC26 and LOC389637 and TRIB1 genes was constitutive in all lines of HL-60 cells and that of the first four genes was repressed during the terminal differentiation of early-passaged HL-60 cells. We also detected abnormal transcripts of CCDC26. Our results suggest that these genes were selected during the development of amplicons. They might be amplified and, sometimes, truncated to contribute to the maintenance of HL-60 cells in an undifferentiated state.

Hypermethylation of the GATA binding protein 4 (GATA4) promoter in Chinese pediatric acute myeloid leukemia

International Nuclear Information System (INIS)

Tao, Yan-Fang; Fang, Fang; Hu, Shao-Yan; Lu, Jun; Cao, Lan; Zhao, Wen-Li; Xiao, Pei-Fang; Li, Zhi-Heng; Wang, Na-Na; Xu, Li-Xiao; Du, Xiao-Juan; Sun, Li-Chao; Li, Yan-Hong; Li, Yi-Ping; Xu, Yun-Yun; Ni, Jian; Wang, Jian; Feng, Xing; Pan, Jian

2015-01-01

Acute myeloid leukemia (AML) is the second-most common form of leukemia in children. Aberrant DNA methylation patterns are a characteristic feature of AML. GATA4 has been suggested to be a tumor suppressor gene regulated by promoter hypermethylation in various types of human cancers although the expression and promoter methylation of GATA4 in pediatric AML is still unclear. Transcriptional expression levels of GATA4 were evaluated by semi-quantitative and real-time PCR. Methylation status was investigated by methylation-specific PCR (MSP) and bisulfate genomic sequencing (BGS). The prognostic significance of GATA4 expression and promoter methylation was assessed in 105 cases of Chinese pediatric acute myeloid leukemia patients with clinical follow-up records. MSP and BGS analysis showed that the GATA4 gene promoter is hypermethylated in AML cells, such as the HL-60 and MV4-11 human myeloid leukemia cell lines. 5-Aza treatment significantly upregulated GATA4 expression in HL-60 and MV4-11 cells. Aberrant methylation of GATA4 was observed in 15.0 % (3/20) of the normal bone marrow control samples compared to 56.2 % (59/105) of the pediatric AML samples. GATA4 transcript levels were significantly decreased in AML patients (33.06 ± 70.94; P = 0.011) compared to normal bone marrow/idiopathic thrombocytopenic purpura controls (116.76 ± 105.39). GATA4 promoter methylation was correlated with patient leukocyte counts (WBC, white blood cells) (P = 0.035) and minimal residual disease MRD (P = 0.031). Kaplan-Meier survival analysis revealed significantly shorter overall survival time in patients with GATA4 promoter methylation (P = 0.014). Epigenetic inactivation of GATA4 by promoter hypermethylation was observed in both AML cell lines and pediatric AML samples; our study implicates GATA4 as a putative tumor suppressor gene in pediatric AML. In addition, our findings imply that GATA4 promoter methylation is correlated with WBC and MRD. Kaplan-Meier survival analysis

Acridones as inducers of HL-60 cell differentiation.

Science.gov (United States)

Kawaii, S; Tomono, Y; Katase, E; Ogawa, K; Yano, M; Takemura, Y; Ju-ichi, M; Ito, C; Furukawa, H

1999-03-01

Fifteen acridone alkaloids were examined for their activity of induction of human promyelocytic leukemia cell (HL-60) differentiation. HL-60 cells were differentiated into mature monocyte/macrophage by atalaphyllidine (9), atalaphyllinine (12), and des-N-methylnoracronycine (13). The activities of NBT reduction, nonspecific esterase, and phagocytosis, were induced by 2.5 microM of 9, 12, and 13. After a 4-day treatment, 9, 12, and 13 at 10 microM inhibited clonal proliferation of HL-60 cells by 28, 96, and 63%, respectively. The structure-activity relationship established from the results revealed that hydroxyl group at C-1 and prenyl group at C-2 had an important role.

Rho GTPase expression in human myeloid cells.

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Suzanne F G van Helden

Full Text Available Myeloid cells are critical for innate immunity and the initiation of adaptive immunity. Strict regulation of the adhesive and migratory behavior is essential for proper functioning of these cells. Rho GTPases are important regulators of adhesion and migration; however, it is unknown which Rho GTPases are expressed in different myeloid cells. Here, we use a qPCR-based approach to investigate Rho GTPase expression in myeloid cells.We found that the mRNAs encoding Cdc42, RhoQ, Rac1, Rac2, RhoA and RhoC are the most abundant. In addition, RhoG, RhoB, RhoF and RhoV are expressed at low levels or only in specific cell types. More differentiated cells along the monocyte-lineage display lower levels of Cdc42 and RhoV, while RhoC mRNA is more abundant. In addition, the Rho GTPase expression profile changes during dendritic cell maturation with Rac1 being upregulated and Rac2 downregulated. Finally, GM-CSF stimulation, during macrophage and osteoclast differentiation, leads to high expression of Rac2, while M-CSF induces high levels of RhoA, showing that these cytokines induce a distinct pattern. Our data uncover cell type specific modulation of the Rho GTPase expression profile in hematopoietic stem cells and in more differentiated cells of the myeloid lineage.

Induced apoptosis by mild hyperthermia occurs via telomerase inhibition on the three human myeloid leukemia cell lines: TF-1, K562, and HL-60.

Science.gov (United States)

Deezagi, Abdolkhaleg; Manteghi, Sanaz; Khosravani, Pardis; Vaseli-Hagh, Neda; Soheili, Zahra-Soheila

2009-09-01

The purpose of this research was to understand the effect of hyperthermia on the telomerase activity in human leukemic cell lines (HL-60, K562, and TF-1). The cells were treated by hyperthermia at the range of 41-44 degrees C for 120 min and incubated for 96 h. Then telomerase activity, cell proliferation, and apoptosis were assessed. The results indicated that hyperthermia significantly induced apoptosis on the cells. The cells exhibited pre-apoptotic pattern at 41 and 42 degrees C at 60-120 min and apoptotic pattern at 43 and 44 degrees C over 30 min after hyperthermia. Telomerase activity (that was assayed immediately after hyperthermia) was stable at 41-42 degrees C for 60 min but decreased to 35-40% at 120 min. However, at severe hyperthermia (43-44 degrees C) telomerase activity was decreased in a time- and dose-dependent manner. Following hyperthermia (41-44 degrees C up to 120 min), the cells were incubated for 96 h. In these conditions, the telomerase activity was decreased by about 60-80% in comparison with that untreated control cells.

Development of A Chimeric Antigen Receptor Targeting C-Type Lectin-Like Molecule-1 for Human Acute Myeloid Leukemia

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Eduardo Laborda

2017-10-01

Full Text Available The treatment of patients with acute myeloid leukemia (AML with targeted immunotherapy is challenged by the heterogeneity of the disease and a lack of tumor-exclusive antigens. Conventional immunotherapy targets for AML such as CD33 and CD123 have been proposed as targets for chimeric antigen receptor (CAR-engineered T-cells (CAR-T-cells, a therapy that has been highly successful in the treatment of B-cell leukemia and lymphoma. However, CD33 and CD123 are present on hematopoietic stem cells, and targeting with CAR-T-cells has the potential to elicit long-term myelosuppression. C-type lectin-like molecule-1 (CLL1 or CLEC12A is a myeloid lineage antigen that is expressed by malignant cells in more than 90% of AML patients. CLL1 is not expressed by healthy Hematopoietic Stem Cells (HSCs, and is therefore a promising target for CAR-T-cell therapy. Here, we describe the development and optimization of an anti-CLL1 CAR-T-cell with potent activity on both AML cell lines and primary patient-derived AML blasts in vitro while sparing healthy HSCs. Furthermore, in a disseminated mouse xenograft model using the CLL1-positive HL60 cell line, these CAR-T-cells completely eradicated tumor, thus supporting CLL1 as a promising target for CAR-T-cells to treat AML while limiting myelosuppressive toxicity.

Gingival enlargement as an early diagnostic indicator in therapy-related acute myeloid leukemia: A rare case report and review of literature

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Triveni M Gowda

2013-01-01

Full Text Available Treatment for Hodgkin′s lymphoma (HL has resulted in excellent survival rates but is associated with increased risks of secondary therapy-related acute myeloid leukemia (t-AML. Gingival enlargement associated with bleeding and ulceration is the most common rapidly appearing oral manifestations of leukemic involvement. An 8 months pregnant patient reported with generalized gingival enlargement, with localized cyanotic and necrotic papillary areas. Co-relating the hematological report with the oral lesions and her past medical history of HL, a diagnosis of t-AML secondary to treatment for HL was made by the oncologist. As oral lesions are one of the initial manifestations of acute leukemia, they may serve as a significant diagnostic indicator for the dental surgeons and their important role in diagnosing and treating such cases. Furthermore, this case report highlights the serious complication of t-AML subsequent to HL treatment and the important role that a general and oral health care professional may play in diagnosing and treating such cases.

Targeting Human C-Type Lectin-Like Molecule-1 (CLL1) with a Bispecific Antibody for Acute Myeloid Leukemia Immunotherapy**

OpenAIRE

Lu, Hua; Zhou, Quan; Deshmukh, Vishal; Phull, Hardeep; Ma, Jennifer; Tardif, Virginie; Naik, Rahul R.; Bouvard, Claire; Zhang, Yong; Choi, Seihyun; Lawson, Brian R.; Zhu, Shoutian; Kim, Chan Hyuk; Schultz, Peter G.

2014-01-01

Acute myeloid leukemia (AML), the most common acute adult leukemia and the second most common pediatric leukemia, still has a poor prognosis. Human C-type lectin-like molecule-1 (CLL1) is a recently identified myeloid lineage restricted cell surface marker, which is overexpressed in over 90% of AML patient myeloid blasts and in leukemic stem cells. Here, we describe the synthesis of a novel bispecific antibody, αCLL1-αCD3, using the genetically encoded unnatural amino acid, p-acetylphenylalan...

BETULINIC ACID WAS MORE CYTOTOXIC TOWARDS THE HUMAN BREAST CANCER CELL LINE MDA-MB-231 THAN THE HUMAN PROMYELOCYTIC LEUKAEMIA CELL LINE HL-60

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LATIFAH SAIFUL YAZAN

2009-01-01

Full Text Available Betulinic acid (BA is a pentacyclic triterpene found in several botanical sources that has been shown to cause apoptosis in a number of cell lines. This study was undertaken to determine the in vitro cytotoxic properties of BA towards the human mammary carcinoma cell line MDA-MB-231 and the human promyelocytic leukaemia cell line HL-60 and the mode of the induced cell death. The cytotoxicity and mode of cell death of BA were determined using the MTT assay and DNAfragmentation analysis, respectively. In our study, the compound was found to be cytotoxic to MDA-MB-231 and HL-60 cells with IC50 values of 58 μg/mL and 134 μg/mL, respectively. Cells treated with high concentrations of BA exhibited features characteristic of apoptosis such as blebbing, shrinking and a number of small cytoplasm body masses when viewed under an inverted light microscope after 24 h. The incidence of apoptosis in MDA-MB-231 was further confirmed bythe DNA fragmentation analysis, with the formation of DNA fragments of oligonucleosomal size (180-200 base pairs, giving a ladder-like pattern on agarose gel electrophoresis. BA was more cytotoxic towards MDA-MB-231 than HL-60 cells, and induced apoptosis in MDA-MB-231 cells.

Conservation of myeloid surface antigens on primate granulocytes.

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Letvin, N L; Todd, R F; Palley, L S; Schlossman, S F; Griffin, J D

1983-02-01

Monoclonal antibodies reactive with myeloid cell surface antigens were used to study evolutionary changes in granulocyte surface antigens from primate species. Certain of these granulocyte membrane antigens are conserved in phylogenetically distant species, indicating the potential functional importance of these structures. The degree of conservation of these antigens reflects the phylogenetic relationship between primate species. Furthermore, species of the same genus show similar patterns of binding to this panel of anti-human myeloid antibodies. This finding of conserved granulocyte surface antigens suggests that non-human primates may provide a model system for exploring uses of monoclonal antibodies in the treatment of human myeloid disorders.

Effects of highly ripened cheeses on HL-60 human leukemia cells: antiproliferative activity and induction of apoptotic DNA damage.

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Yasuda, S; Ohkura, N; Suzuki, K; Yamasaki, M; Nishiyama, K; Kobayashi, H; Hoshi, Y; Kadooka, Y; Igoshi, K

2010-04-01

To establish cheese as a dairy product with health benefits, we examined the multifunctional role of cheeses. In this report, we clarify whether different types of commercial cheeses may possess antiproliferative activity using HL-60 human promyelocytic leukemia cell lines as a cancer model. Among 12 cheese extracts tested, 6 (Montagnard, Pont-l'Eveque, Brie, Camembert, Danablue, and Blue) revealed strong growth inhibition activity and induction of DNA fragmentation in HL-60 cells. Based on the quantification of nitrogen contents in different cheese samples, a positive correlation between the ripeness of various cheeses and their antiproliferative activity tested in HL-60 cells was displayed. Four varieties of Blue cheese ripened for 0, 1, 2, or 3 mo demonstrated that the Blue cheese ripened for a long term was capable of causing the strong suppression of the cell growth and the induction of apoptotic DNA damage as well as nucleic morphological change in HL-60 cells. Collectively, these results obtained suggest a potential role of highly ripened cheeses in the prevention of leukemic cell proliferation. Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

27 CFR 5.25 - Application.

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2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Application. 5.25 Section 5.25 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF DISTILLED SPIRITS Formulas § 5.25 Application. The...

Retroviruses As Myeloid Cell Riders: What Natural Human Siglec-1 “Knockouts” Tell Us About Pathogenesis

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Javier Martinez-Picado

2017-11-01

Full Text Available Myeloid cells initiate immune responses and are crucial to control infections. In the case of retroviruses, however, myeloid cells also promote pathogenesis by enabling viral dissemination; a process extensively studied in vitro using human immunodeficiency virus type 1 (HIV-1. This viral hijacking mechanism does not rely on productive myeloid cell infection but requires HIV-1 capture via Siglec-1/CD169, a receptor expressed on myeloid cells that facilitates the infection of bystander target cells. Murine retroviruses are also recognized by Siglec-1, and this interaction is required for robust retroviral infection in vivo. Yet, the relative contribution of Siglec-1-mediated viral dissemination to HIV-1 disease progression remains unclear. The identification of human null individuals lacking working copies of a particular gene enables studying how this loss affects disease progression. Moreover, it can reveal novel antiviral targets whose blockade might be therapeutically effective and safe, since finding null individuals in natura uncovers dispensable functions. We previously described a loss-of-function variant in SIGLEC-1. Analysis of a large cohort of HIV-1-infected individuals identified homozygous and heterozygous subjects, whose cells were functionally null or partially defective for Siglec-1 activity in HIV-1 capture and transmission ex vivo. Nonetheless, analysis of the effect of Siglec-1 truncation on progression to AIDS was not conclusive due to the limited cohort size, the lack of complete clinical records, and the restriction to study only off-therapy periods. Here, we review how the study of loss-of-function variants might serve to illuminate the role of myeloid cells in viral pathogenesis in vivo and the challenges ahead.

29 CFR 525.18 - Review.

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2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Review. 525.18 Section 525.18 Labor Regulations Relating to... DISABILITIES UNDER SPECIAL CERTIFICATES § 525.18 Review. Any person aggrieved by any action of the... allow, file with the Administrator a petition for review. Such review, if granted, shall be made by the...

The rate of spontaneous mutations in human myeloid cells

International Nuclear Information System (INIS)

Araten, David J.; Krejci, Ondrej; DiTata, Kimberly; Wunderlich, Mark; Sanders, Katie J.; Zamechek, Leah; Mulloy, James C.

2013-01-01

Highlights: • We provide the first measurement of the mutation rate (μ) in human myeloid cells. • μ is measured to be 3.6–23 × 10 −7 per cell division. • The AML-ETO and MLL-AF9 fusions do not seem to increase μ. • Cooperating mutations in NRAS, FLT3 and p53 not seem to increase μ. • Hypermutability may be required to explain leukemogenesis. - Abstract: The mutation rate (μ) is likely to be a key parameter in leukemogenesis, but historically, it has been difficult to measure in humans. The PIG-A gene has some advantages for the detection of spontaneous mutations because it is X-linked, and therefore only one mutation is required to disrupt its function. Furthermore, the PIG-A-null phenotype is readily detected by flow cytometry. Using PIG-A, we have now provided the first in vitro measurement of μ in myeloid cells, using cultures of CD34+ cells that are transduced with either the AML-ETO or the MLL-AF9 fusion genes and expanded with cytokines. For the AML-ETO cultures, the median μ value was ∼9.4 × 10 −7 (range ∼3.6–23 × 10 −7 ) per cell division. In contrast, few spontaneous mutations were observed in the MLL-AF9 cultures. Knockdown of p53 or introduction of mutant NRAS or FLT3 alleles did not have much of an effect on μ. Based on these data, we provide a model to predict whether hypermutability must occur in the process of leukemogenesis

Proteomic analysis of cell proliferation in a human hepatic cell line (HL-7702) induced by perfluorooctane sulfonate using iTRAQ

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Cui, Ruina; Zhang, Hongxia [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101 (China); Guo, Xuejiang [State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029 (China); Cui, Qianqian; Wang, Jianshe [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101 (China); Dai, Jiayin, E-mail: daijy@ioz.ac.cn [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101 (China)

2015-12-15

Highlights: • PFOS stimulates cell proliferation of human liver cell line (HL-7702). • Differential expressed proteins are identified by iTRAQ. • Most of differential proteins caused by PFOS are related to cell proliferation. • Up-regulation of cyclin/cdk by PFOS plays a role in driving cells into cell cycle. - Abstract: Perfluorooctane sulfonate (PFOS) is a commonly used and widely distributed perfluorinated compound proven to cause adverse health outcomes. However, how PFOS affects liver cell proliferation is not well understood. In this experiment, we exposed a human liver cell line (HL-7702) to 50 μM PFOS for 48 h and 96 h. We identified 52 differentially expressed proteins using a quantitative proteomic approach. Among them, 27 were associated with cell proliferation, including hepatoma-derived growth factor (Hdgf) and proliferation biomarkers Mk167 (Ki67) and Top2α. Results from MTT, cell counting, and cell cycle analysis showed low-dose PFOS (<200 μM) stimulated HL-7702 cell viability at 48 h and 96 h, reduced the G0/G1 percentage, and increased the S + G2/M percentage. Moreover, levels of Cyclin D1, Cyclin E2, Cyclin A2, Cyclin B1 and their partner Cdks were elevated, and the expression of regulating proteins like c-Myc, p53, p21 waf/cip1 and Myt1, as well as the phosphorylation levels of p-Wee1(S642), p-Chk1(S345) and p-Chk2(T68), were disturbed. We hypothesized that low-dose PFOS stimulated HL-7702 proliferation by driving cells into G1 through elevating cyclins/cdks expression, and by promoting cell cycle progression through altering other regulating proteins. This research will shed light on the mechanisms behind PFOS-mediated human hepatotoxicity.

Proteomic analysis of cell proliferation in a human hepatic cell line (HL-7702) induced by perfluorooctane sulfonate using iTRAQ

International Nuclear Information System (INIS)

Cui, Ruina; Zhang, Hongxia; Guo, Xuejiang; Cui, Qianqian; Wang, Jianshe; Dai, Jiayin

2015-01-01

Highlights: • PFOS stimulates cell proliferation of human liver cell line (HL-7702). • Differential expressed proteins are identified by iTRAQ. • Most of differential proteins caused by PFOS are related to cell proliferation. • Up-regulation of cyclin/cdk by PFOS plays a role in driving cells into cell cycle. - Abstract: Perfluorooctane sulfonate (PFOS) is a commonly used and widely distributed perfluorinated compound proven to cause adverse health outcomes. However, how PFOS affects liver cell proliferation is not well understood. In this experiment, we exposed a human liver cell line (HL-7702) to 50 μM PFOS for 48 h and 96 h. We identified 52 differentially expressed proteins using a quantitative proteomic approach. Among them, 27 were associated with cell proliferation, including hepatoma-derived growth factor (Hdgf) and proliferation biomarkers Mk167 (Ki67) and Top2α. Results from MTT, cell counting, and cell cycle analysis showed low-dose PFOS (<200 μM) stimulated HL-7702 cell viability at 48 h and 96 h, reduced the G0/G1 percentage, and increased the S + G2/M percentage. Moreover, levels of Cyclin D1, Cyclin E2, Cyclin A2, Cyclin B1 and their partner Cdks were elevated, and the expression of regulating proteins like c-Myc, p53, p21 waf/cip1 and Myt1, as well as the phosphorylation levels of p-Wee1(S642), p-Chk1(S345) and p-Chk2(T68), were disturbed. We hypothesized that low-dose PFOS stimulated HL-7702 proliferation by driving cells into G1 through elevating cyclins/cdks expression, and by promoting cell cycle progression through altering other regulating proteins. This research will shed light on the mechanisms behind PFOS-mediated human hepatotoxicity.

Differentiation-promoting activity of pomegranate (Punica granatum) fruit extracts in HL-60 human promyelocytic leukemia cells.

Science.gov (United States)

Kawaii, Satoru; Lansky, Ephraim P

2004-01-01

Differentiation refers to the ability of cancer cells to revert to their normal counterparts, and its induction represents an important noncytotoxic therapy for leukemia, and also breast, prostate, and other solid malignancies. Flavonoids are a group of differentiation-inducing chemicals with a potentially lower toxicology profile than retinoids. Flavonoid-rich polyphenol fractions from the pomegranate (Punica granatum) fruit exert anti-proliferative, anti-invasive, anti-eicosanoid, and pro-apoptotic actions in breast and prostate cancer cells and anti-angiogenic activities in vitro and in vivo. Here we tested flavonoid-rich fractions from fresh (J) and fermented (W) pomegranate juice and from an aqueous extraction of pomegranate pericarps (P) as potential differentiation-promoting agents of human HL-60 promyelocytic leukemia cells. Four assays were used to assess differentiation: nitro blue tetrazolium reducing activity, nonspecific esterase activity, specific esterase activity, and phagocytic activity. In addition, the effect of these extracts on HL-60 proliferation was evaluated. Extracts W and P were strong promoters of differentiation in all settings, with extract J showing only a relatively mild differentiation-promoting effect. The extracts had proportional inhibitory effects on HL-60 cell proliferation. The results highlight an important, previously unknown, mechanism of the cancer preventive and suppressive potential of pomegranate fermented juice and pericarp extracts.

Presence of estrogen receptors in human myeloid monocytic cells (THP-1 cell line).

Science.gov (United States)

Cutolo, M; Villaggio, B; Bisso, A; Sulli, A; Coviello, D; Dayer, J M

2001-01-01

To test THP-1 cells for the presence of estrogen receptors (ER) since studies have demonstrated in vivo and in vitro, the influence of estrogens on cells involved in immune response (i.e. macrophages), and since it has been demonstrated that human myeloid monocytic THP-1 cells acquire phenotypic and functional macrophage-like features after incubation with several cytokines or pharmacological agents. Stimulation of THP-1 cells with phorbol myristate acetate (PMA) to prompt their differentiation into macrophage-like cells and evaluation of the possible induction of ER. The expression of ER was analyzed by immunocytochemical assay, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis. After stimulation by PMA, the human myeloid monocytic THP-1 cells showed the presence of ER, together with markers of monocytic cell differentiation such as CD68, CD54 and HLA-DR. Estrogen effects may be exerted directly through ER on monocytes/macrophages. PMA-treated THP-1 cells may constitute a useful in vitro model to determine the effects of estrogens on macrophage-like cells and their implications in the inflammatory and immune processes.

Taraxinic acid, a hydrolysate of sesquiterpene lactone glycoside from the Taraxacum coreanum NAKAI, induces the differentiation of human acute promyelocytic leukemia HL-60 cells.

Science.gov (United States)

Choi, Jung-Hye; Shin, Kyung-Min; Kim, Na-Young; Hong, Jung-Pyo; Lee, Yong Sup; Kim, Hyoung Ja; Park, Hee-Juhn; Lee, Kyung-Tae

2002-11-01

The present work was performed to elucidate the active moiety of a sesquiterpene lactone, taraxinic acid-1'-O-beta-D-glucopyranoside (1). from Taraxacum coreanum NAKAI on the cytotoxicity of various cancer cells. Based on enzymatic hydrolysis and MTT assay, the active moiety should be attributed to the aglycone taraxinic acid (1a). rather than the glycoside (1). Taraxinic acid exhibited potent antiproliferative activity against human leukemia-derived HL-60. In addition, this compound was found to be a potent inducer of HL-60 cell differentiation as assessed by a nitroblue tetrazolium reduction test, esterase activity assay, phagocytic activity assay, morphology change, and expression of CD 14 and CD 66 b surface antigens. These results suggest that taraxinic acid induces the differentiation of human leukemia cells to monocyte/macrophage lineage. Moreover, the expression level of c-myc was down-regulated during taraxinic acid-dependent HL-60 cell differentiation, whereas p21(CIP1) and p27(KIP1) were up-regulated. Taken together, our results suggest that taraxinic acid may have potential as a therapeutic agent in human leukemia.

Drug screen in patient cells suggests quinacrine to be repositioned for treatment of acute myeloid leukemia

International Nuclear Information System (INIS)

Eriksson, A; Österroos, A; Hassan, S; Gullbo, J; Rickardson, L; Jarvius, M; Nygren, P; Fryknäs, M; Höglund, M; Larsson, R

2015-01-01

To find drugs suitable for repositioning for use against leukemia, samples from patients with chronic lymphocytic, acute myeloid and lymphocytic leukemias as well as peripheral blood mononuclear cells (PBMC) were tested in response to 1266 compounds from the LOPAC 1280 library (Sigma). Twenty-five compounds were defined as hits with activity in all leukemia subgroups (<50% cell survival compared with control) at 10 μM drug concentration. Only one of these compounds, quinacrine, showed low activity in normal PBMCs and was therefore selected for further preclinical evaluation. Mining the NCI-60 and the NextBio databases demonstrated leukemia sensitivity and the ability of quinacrine to reverse myeloid leukemia gene expression. Mechanistic exploration was performed using the NextBio bioinformatic software using gene expression analysis of drug exposed acute myeloid leukemia cultures (HL-60) in the database. Analysis of gene enrichment and drug correlations revealed strong connections to ribosomal biogenesis nucleoli and translation initiation. The highest drug–drug correlation was to ellipticine, a known RNA polymerase I inhibitor. These results were validated by additional gene expression analysis performed in-house. Quinacrine induced early inhibition of protein synthesis supporting these predictions. The results suggest that quinacrine have repositioning potential for treatment of acute myeloid leukemia by targeting of ribosomal biogenesis

49 CFR 25.525 - Fringe benefits.

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2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Fringe benefits. 25.525 Section 25.525... Employment in Education Programs or Activities Prohibited § 25.525 Fringe benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, fringe benefits means: Any medical, hospital...

10 CFR 52.5 - Employee protection.

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2010-01-01

... adverse action occurs because the employee has engaged in protected activities. An employee's engagement... 10 Energy 2 2010-01-01 2010-01-01 false Employee protection. 52.5 Section 52.5 Energy NUCLEAR... Provisions § 52.5 Employee protection. (a) Discrimination by a Commission licensee, holder of a standard...

29 CFR 525.6 - Compensable time.

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2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Compensable time. 525.6 Section 525.6 Labor Regulations... WITH DISABILITIES UNDER SPECIAL CERTIFICATES § 525.6 Compensable time. Individuals employed subject to this part must be compensated for all hours worked. Compensable time includes not only those hours...

22 CFR 229.525 - Fringe benefits.

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2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Fringe benefits. 229.525 Section 229.525... Employment in Education Programs or Activities Prohibited § 229.525 Fringe benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, fringe benefits means: Any medical, hospital...

32 CFR 196.525 - Fringe benefits.

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2010-07-01

... 32 National Defense 2 2010-07-01 2010-07-01 false Fringe benefits. 196.525 Section 196.525... Prohibited § 196.525 Fringe benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, fringe benefits means: Any medical, hospital, accident, life insurance, or retirement benefit...

22 CFR 146.525 - Fringe benefits.

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2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Fringe benefits. 146.525 Section 146.525... Employment in Education Programs or Activities Prohibited § 146.525 Fringe benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, fringe benefits means: Any medical, hospital...

28 CFR 54.525 - Fringe benefits.

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2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Fringe benefits. 54.525 Section 54.525... in Employment in Education Programs or Activities Prohibited § 54.525 Fringe benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, fringe benefits means: Any medical, hospital...

10 CFR 1042.525 - Fringe benefits.

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2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Fringe benefits. 1042.525 Section 1042.525 Energy... Education Programs or Activities Prohibited § 1042.525 Fringe benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, fringe benefits means: Any medical, hospital, accident, life...

43 CFR 41.525 - Fringe benefits.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Fringe benefits. 41.525 Section 41.525... in Employment in Education Programs or Activities Prohibited § 41.525 Fringe benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, fringe benefits means: Any medical, hospital...

14 CFR 1253.525 - Fringe benefits.

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2010-01-01

... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Fringe benefits. 1253.525 Section 1253.525... in Employment in Education Programs or Activities Prohibited § 1253.525 Fringe benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, fringe benefits means: Any medical, hospital...

6 CFR 17.525 - Fringe benefits.

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2010-01-01

... 6 Domestic Security 1 2010-01-01 2010-01-01 false Fringe benefits. 17.525 Section 17.525 Domestic... in Employment in Education Programs or Activities Prohibited § 17.525 Fringe benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, the term fringe benefits means any medical...

10 CFR 5.525 - Fringe benefits.

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2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Fringe benefits. 5.525 Section 5.525 Energy NUCLEAR... Activities Prohibited § 5.525 Fringe benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, fringe benefits means: Any medical, hospital, accident, life insurance, or retirement benefit...

40 CFR 5.525 - Fringe benefits.

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2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Fringe benefits. 5.525 Section 5.525... in Employment in Education Programs or Activities Prohibited § 5.525 Fringe benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, fringe benefits means: Any medical, hospital...

Cytotoxicity and cellular uptake of doxorubicin and its formamidine derivatives in HL60 sensitive and HL60/MX2 resistant cells.

Science.gov (United States)

Kik, Krzysztof; Wasowska-Lukawska, Malgorzata; Oszczapowicz, Irena; Szmigiero, Leszek

2009-04-01

In this work a comparison was made of the cytotoxicity and cellular uptake of doxorubicin (DOX) and two of its derivatives containing a formamidino group (-N=CH-N<) at the 3' position with morpholine (DOXM) or hexamethyleneimine (DOXH) ring. All tests were performed in doxorubicin-sensitive HL60 and -resistant HL60/MX2 cells which are known for the presence of altered topoisomerase II. Cytotoxic activity of DOX toward HL60/MX2 cells was about 195 times lower when compared with the sensitive HL60 cell line. DOXM and DOXH were approximately 20 times more active in resistant cells than DOX. It was found that the uptake of DOX was lower in resistant cells by about 16%, while that of DOXM and DOXH was lower by about 36% and 19%, respectively. Thus the changes in the cellular uptake of anthracyclines are not associated with the fact that cytotoxicity of DOXM and DOXH exceed the cytotoxicity of DOX. Experiments in cell-free system containing human topoisomerase II showed that topoisomerase II is not inhibited by DOXM and DOXH. Formamidinoanthracyclines may be more useful than parent drugs in therapy against tumor cells with altered topoisomerase II activity.

29 CFR 36.525 - Fringe benefits.

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Fringe benefits. 36.525 Section 36.525 Labor Office of the... Activities Prohibited § 36.525 Fringe benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, fringe benefits means: Any medical, hospital, accident, life insurance, or retirement benefit...

Preclinical evaluation of WYE-687, a mTOR kinase inhibitor, as a potential anti-acute myeloid leukemia agent

International Nuclear Information System (INIS)

Cheng, Feng; Wang, Lingling; Shen, Yunfeng; Xia, Jun; Chen, Heng; Jiang, Yuanqiang; Lu, Mize

2016-01-01

Mammalian target of rapamycin (mTOR) as a potential drug target for treatment of acute myeloid leukemia (AML). Here, we investigated the potential anti-leukemic activity by WYE-687, a potent mTOR kinase inhibitor. We demonstrated that WYE-687 potently inhibited survival and proliferation of established (HL-60, U937, AML-193 and THP-1 lines) and human AML progenitor cells. Yet, same WYE-687 treatment was non-cytotoxic to the primary peripheral blood mononuclear leukocytes (PBMCs) isolated from healthy donors. WYE-687 induced caspase-dependent apoptotic death in above AML cells/progenitor cells. On the other hand, the pan-caspase inhibitor (Z-VAD-FMK), the caspase-3 specific inhibitor (Z-DEVD-FMK) or the caspase-9 specific inhibitor (z-LEHD-fmk) attenuated WYE-687-induced cytotoxicity. At the molecular level, WYE-687 concurrently inhibited activation of mTORC1 (p70S6K1 and S6 phosphorylations) and mTORC2 (AKT Ser-473 and FoxO1/3a phosphorylations), whiling downregulating mTORC1/2-regulated genes (Bcl-xL and hypoxia-inducible factor 1/2α) in both HL-60/U937 cells and human AML progenitor cells. In vivo, oral administration of WYE-687 potently inhibited U937 leukemic xenograft tumor growth in severe combined immunodeficient (SCID) mice, without causing significant toxicities. In summary, our results demonstrate that targeting mTORC1/2 by WYE-687 leads to potent antitumor activity in preclinical models of AML. - Highlights: • WYE-687 inhibits survival and proliferation of human AML cells/progenitor cells. • WYE-687 induces apoptotic death of human AML cells/progenitor cells. • WYE-687 inhibits mTORC1/2 activation in human AML cells/progenitor cells. • WYE-687 inhibits U937 xenograft growth in SCID mice.

Preclinical evaluation of WYE-687, a mTOR kinase inhibitor, as a potential anti-acute myeloid leukemia agent

Energy Technology Data Exchange (ETDEWEB)

Cheng, Feng; Wang, Lingling; Shen, Yunfeng; Xia, Jun; Chen, Heng; Jiang, Yuanqiang, E-mail: jiangyuanqiangwuxi@163.com; Lu, Mize, E-mail: lumizewuxi9@sina.com

2016-02-05

Mammalian target of rapamycin (mTOR) as a potential drug target for treatment of acute myeloid leukemia (AML). Here, we investigated the potential anti-leukemic activity by WYE-687, a potent mTOR kinase inhibitor. We demonstrated that WYE-687 potently inhibited survival and proliferation of established (HL-60, U937, AML-193 and THP-1 lines) and human AML progenitor cells. Yet, same WYE-687 treatment was non-cytotoxic to the primary peripheral blood mononuclear leukocytes (PBMCs) isolated from healthy donors. WYE-687 induced caspase-dependent apoptotic death in above AML cells/progenitor cells. On the other hand, the pan-caspase inhibitor (Z-VAD-FMK), the caspase-3 specific inhibitor (Z-DEVD-FMK) or the caspase-9 specific inhibitor (z-LEHD-fmk) attenuated WYE-687-induced cytotoxicity. At the molecular level, WYE-687 concurrently inhibited activation of mTORC1 (p70S6K1 and S6 phosphorylations) and mTORC2 (AKT Ser-473 and FoxO1/3a phosphorylations), whiling downregulating mTORC1/2-regulated genes (Bcl-xL and hypoxia-inducible factor 1/2α) in both HL-60/U937 cells and human AML progenitor cells. In vivo, oral administration of WYE-687 potently inhibited U937 leukemic xenograft tumor growth in severe combined immunodeficient (SCID) mice, without causing significant toxicities. In summary, our results demonstrate that targeting mTORC1/2 by WYE-687 leads to potent antitumor activity in preclinical models of AML. - Highlights: • WYE-687 inhibits survival and proliferation of human AML cells/progenitor cells. • WYE-687 induces apoptotic death of human AML cells/progenitor cells. • WYE-687 inhibits mTORC1/2 activation in human AML cells/progenitor cells. • WYE-687 inhibits U937 xenograft growth in SCID mice.

42 CFR 426.525 - NCD review.

Science.gov (United States)

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false NCD review. 426.525 Section 426.525 Public Health... PROGRAM REVIEW OF NATIONAL COVERAGE DETERMINATIONS AND LOCAL COVERAGE DETERMINATIONS Review of an NCD § 426.525 NCD review. (a) Opportunity for the aggrieved party after his or her review of the NCD record...

Hans Pöhl - Estlandssvenskarnas hövding = Hans Pöhl - rannarootslaste eestvõitleja / Torkel Jansson

Index Scriptorium Estoniae

Jansson, Torkel, 1947-

2011-01-01

Raamatututvustus: Hans Pöhl - Estlandssvenskarnas hövding : en biografi över Hans Pöhl (1876-1930), estlandssvenskarnas främste företrädare och ledare = Hans Pöhl - rannarootslaste eestvõitleja : Hans Pöhli (1876-1930), Eesti rootslaste vaimse liidri ja valgustaja elulugu. (Stockholm ; Tallinn, 2010)

Anti-leukemic effect of a synthetic compound, (±) trans-dihydronarciclasine (HYU-01) via cell-cycle arrest and apoptosis in acute myeloid leukemia.

Science.gov (United States)

Kim, Seo Ju; Park, Hyun Ki; Kim, Ju Young; Yoon, Jin Sun; Kim, Eun Shil; Cho, Cheon-Gyu; Kim, Byoung Kook; Park, Byeong Bae; Lee, Young Yiul

2012-10-01

(±) trans-Dihydronarciclasine, isolated from Chinese medicinal plant Zephyranthes candida, has been shown to possess quite potent anti-tumoral effect against selected human cancer cell lines. However, little is known about the anti-tumoral effect of (±) trans-dihydronarciclasine in acute myeloid leukemia (AML). This study was performed to investigate the effect of a novel synthetic (±) trans-dihydronarciclasine (code name; HYU-01) in AML. The HYU-01 inhibited the proliferation of various AML cell lines including HL-60 as well as primary leukemic blasts in a dose-dependent manner. To investigate the mechanism of the anti-proliferative effect of HYU-01, cell-cycle analysis was attempted in HL-60 cells, resulting in G1 arrest. The expression levels of CDK2, CDK4, CDK6, cyclin E, and cyclin A were decreased in a time-dependent manner. In addition, HYU-01 up-regulated the expression of the p27, and markedly enhanced the binding of p27 with CDK2, 4, and 6, ultimately resulting in the decrease of their kinase activities. Furthermore, HYU-01 induced the apoptosis through the induction of proapoptotic molecules and reduction of antiapoptotic molecules in association with the activation of caspase-3, -8, and -9. These results suggest that HYU-01 may inhibit the proliferation of HL-60 cells, via apoptosis, as well as G1 block in association with the induction of p27. © 2012 The Authors APMIS © 2012 APMIS.

Vitamin K2 and cotylenin A synergistically induce monocytic differentiation and growth arrest along with the suppression of c-MYC expression and induction of cyclin G2 expression in human leukemia HL-60 cells.

Science.gov (United States)

Maniwa, Yasuhisa; Kasukabe, Takashi; Kumakura, Shunichi

2015-08-01

Although all-trans retinoic acid (ATRA) is a standard and effective drug used for differentiation therapy in acute promyelocytic leukemia, ATRA-resistant leukemia cells ultimately emerge during this treatment. Therefore, the development of new drugs or effective combination therapy is urgently needed. We demonstrate that the combined treatment of vitamin K2 and cotylenin A synergistically induced monocytic differentiation in HL-60 cells. This combined treatment also synergistically induced NBT-reducing activity and non-specific esterase-positive cells as well as morphological changes to monocyte/macrophage-like cells. Vitamin K2 and cotylenin A cooperatively inhibited the proliferation of HL-60 cells in short-term and long-term cultures. This treatment also induced growth arrest at the G1 phase. Although 5 µg/ml cotylenin A or 5 µM vitamin K2 alone reduced c-MYC gene expression in HL-60 cells to approximately 45% or 80% that of control cells, respectively, the combined treatment almost completely suppressed c-MYC gene expression. We also demonstrated that the combined treatment of vitamin K2 and cotylenin A synergistically induced the expression of cyclin G2, which had a positive effect on the promotion and maintenance of cell cycle arrest. These results suggest that the combination of vitamin K2 and cotylenin A has therapeutic value in the treatment of acute myeloid leukemia.

Modeling Myeloid Malignancies Using Zebrafish

Directory of Open Access Journals (Sweden)

Kathryn S. Potts

2017-12-01

Full Text Available Human myeloid malignancies represent a substantial disease burden to individuals, with significant morbidity and death. The genetic underpinnings of disease formation and progression remain incompletely understood. Large-scale human population studies have identified a high frequency of potential driver mutations in spliceosomal and epigenetic regulators that contribute to malignancies, such as myelodysplastic syndromes (MDS and leukemias. The high conservation of cell types and genes between humans and model organisms permits the investigation of the underlying mechanisms of leukemic development and potential therapeutic testing in genetically pliable pre-clinical systems. Due to the many technical advantages, such as large-scale screening, lineage-tracing studies, tumor transplantation, and high-throughput drug screening approaches, zebrafish is emerging as a model system for myeloid malignancies. In this review, we discuss recent advances in MDS and leukemia using the zebrafish model.

46 CFR 109.525 - Cranes: Working loads.

Science.gov (United States)

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Cranes: Working loads. 109.525 Section 109.525 Shipping... Cranes § 109.525 Cranes: Working loads. The master or person in charge shall ensure that tables... working the crane. ...

Von Hippel-Lindau disease (vHL)

DEFF Research Database (Denmark)

Binderup, Marie Louise Mølgaard; Bisgaard, Søs Marie Luise; Harbud, Vibeke

2013-01-01

These clinical guidelines outline the criteria and recommendations for diagnostic and genetic work-up of families suspected of von Hippel-Lindau disease (vHL), as well as recommendations for prophylactic surveillance for vHL patients. The guideline has been composed by the Danish Coordination Group...... for vHL which is comprised of Danish doctors and specialists interested in vHL. The recommendations are based on longstanding clinical experience, Danish original research, and extensive review of the international literature. vHL is a hereditary multi-tumour disease caused by germline mutations...... of the disease, and/or in individuals with a vHL-associated manifestation; i.e. a hemangioblastoma in the retina or the central nervous system, familial or bilateral pheochromocytomas, familial, multiple, or early onset renal cell carcinomas, and in individuals with an endolymphatic sac tumour in the inner ear...

Apoptosis and reduced cell proliferation of HL-60 cell line caused by human telomerase reverse transcriptase inhibition by siRNA.

Science.gov (United States)

Miri-Moghaddam, Ebrahim; Deezagi, Abdolkhaleg; Soheili, Zahra Sohaila; Shariati, Parvin

2010-01-01

The close correlation between telomerase activity and human telomerase reverse transcriptase (hTERT) expression has made hTERT to be considered as a selective molecular target for human cancer therapy. In this study, the ability of short-interfering RNA (siRNA) to downregulate hTERT expression and its correlation with cell growth and apoptosis in the promyelocytic cell line HL-60 was evaluated. hTERT siRNA was designed and transfected to HL-60. hTERT mRNA expression, cell proliferation and apoptotic cells were measured. The results indicated that hTERT siRNA resulted in 97.2 ± 0.6% downregulation of the hTERT mRNA content; inhibition of the cell proliferation rate was about 52.8 ± 2.3% and the apoptotic index of cells was 30.5 ± 1.5%. hTERT plays an essential role in cell proliferation and control of the viability of leukemic cells, thus promising the development of drugs for leukemia. Copyright © 2010 S. Karger AG, Basel.

Two Distinct Myeloid Subsets at the Term Human Fetal–Maternal Interface

Directory of Open Access Journals (Sweden)

Maria Laura Costa

2017-10-01

Full Text Available During pregnancy, immune cells infiltrate the placenta at different stages of fetal development. NK cells and macrophages are the most predominant cell types. These immune cells play pleiotropic roles, as they control spiral artery remodeling to ensure appropriate blood supply and maintain long-term tolerance to a true allograft; yet, they must be able to mount appropriate immune defenses to pathogens that may threaten the fetus. Whether the same cell type accomplishes all these tasks or if there are dedicated subsets remains controversial. Here, we identify and characterize two distinct subsets of myeloid cells that differ in their pro-inflammatory/regulatory capacity. While one subset predominantly produces the immune-modulating cytokine IL-10, the second subset has superior capacity to secrete pro-inflammatory mediators, such as IL-1β and IL-6. The putative regulatory myeloid cells also express high levels of inhibitory receptors and their ligands, including programmed cell death 1 (PD1 ligands. Importantly, a large fraction of CD8 and CD4 cells in normal term human placenta are PD1 positive, suggesting that the PD1/PD1 ligands axis might be critical to maintain tolerance during pregnancy.

Pilot Peter Hoag and HL-10

Science.gov (United States)

1969-01-01

Air Force Major Peter Hoag stands in front of the HL-10 Lifting Body. Maj. Hoag joined the HL-10 program in 1969 and made his first glide flight on June 6, 1969. He made a total of 8 flights in the HL-10. They included the fastest lifting-body flight, which reached Mach 1.861 on Feb. 18, 1970. The HL-10 was one of five heavyweight lifting-body designs flown at NASA's Flight Research Center (FRC--later Dryden Flight Research Center), Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the highest altitude reached in the program. Some new and different lessons were learned through the successful flight testing of the HL-10. These lessons, when combined with information from it's sister ship, the M2

[Expression of ICAT and Wnt signaling-related proteins in the monocytic differentiation of HL-60 cells induced by a new steroidal drug NSC67657].

Science.gov (United States)

Wang, J S; Wang, W J; Wang, T; Zhang, Y

2016-04-01

To investigate the expression of mRNA and proteins of β-catenin, TCF-4 (ICAT) and Wnt signaling pathway-related genes in the monocytic differentiation of acute myeloid leukemia HL-60 cells induced by a new steroidal drug NSC67657. Wright's staining and α-NBE staining were used to observe the differentiation of HL-60 cells after 5 days of 10 μmol/L NSC67657 treatment. Flow cytometry (FCM) was used to detect the differentiation and cell cycles. The expressions of mRNA and proteins of ICAT and Wnt signaling pathway-related factors, including β-catenin, TCF-4, c-myc, cyclin D1 and TCF-1 before and after differentiation, were detected by RT-PCR and Western blot. Morphological observation showed that NSC67657 induced monocytic differentiation of HL-60 cells. At 5 days after 10 μmol/L NSC67657 treatment, the number of CD14(+) HL-60 cells was (94.37±2.84)%, significantly higher than the (1.31±0.09)% in control group (Pcells were of (18.76±0.98)%, significantly lower than that of (34.38±2.61) % in the control group (Pprotein, and down-regulated the expression of β-catenin mRNA and protin (Pprotein and nuclear protein in the HL-60 cells (P>0.05 for all). The target genes of Wnt signaling pathway, including c-myc, cyclinD1 and TCF-1 mRNA and proteins in the HL-60 cells were significantly down-regulated after NSC67657 treatment (Pcells, and down-regulates the expression of β-catenin and target genes of Wnt signaling pathway. These results indicate that Wnt signaling pathway may be directly or indirectly involved in the monocytic differentiation process of HL-60 cells.

H/L transition time estimation in JET using conformal predictors

Energy Technology Data Exchange (ETDEWEB)

Gonzalez, S., E-mail: sergio.gonzalez@ciemat.es [Asociacion EURATOM/CIEMAT para Fusion, Madrid 28040 (Spain); Vega, J. [Asociacion EURATOM/CIEMAT para Fusion, Madrid 28040 (Spain); Murari, A. [Consorzio RFX, Associazione EURATOM/ENEA per la Fusione, Padova 4-25127 (Italy); Pereira, A. [Asociacion EURATOM/CIEMAT para Fusion, Madrid 28040 (Spain); Dormido-Canto, S.; Ramirez, J.M. [Departamento de Informatica y Automatica, UNED, Madrid 28040 (Spain)

2012-12-15

Highlights: Black-Right-Pointing-Pointer H/L transitions have been predicted using H/L and L/H models. Black-Right-Pointing-Pointer Models have been built using conformal predictors to hedge the prediction with confidence and credibility measures. Black-Right-Pointing-Pointer Models have been trained using linear and radial basis function kernels. Black-Right-Pointing-Pointer Conformal measures have proven their usefulness to validate data-driven models. - Abstract: Recent advances in data mining allow the automatic recognition of physical phenomena in the databases of fusion devices without human intervention. This is important to create large databases of physical events (thereby increasing the statistical relevance) in an unattended manner. Important examples are the L/H and H/L transitions. In this contribution, a novel technique is introduced to automatically locate H/L transitions in JET by using conformal predictors. The focus is on H/L transitions because typically there is not a clear signature in the time series of the most widely available signals to recognize the change of confinement. Conformal predictors hedge their prediction by means of two parameters: confidence and credibility. The technique has been based on binary supervised classifiers to separate the samples of the respective confinement modes. Results with several underlying classifiers are presented.

HL-A27 and anterior uveitis.

Science.gov (United States)

Woodrow, J C; Mapstone, R; Anderson, J; Usher, N

1975-09-01

HL-A types were determined in 90 successive patients with non-granulomatous uveitis. Fifty-one were HL-A27 positive (55.7%) compared to 8.2% of controls. Of 16 patients with ankylosing spondylitis, 13 were HL-A27 positive, as were two patients with a history of Reiter's syndrome. Twenty-eight patients were HL-A27 positive but had no evidence of rheumatic disease. The findings are discussed in relation to the possible pathogenesis of uveitis.

Cytotoxicity, Antiproliferative Effects, and Apoptosis Induction of Methanolic Extract of Cynometra cauliflora Linn. Whole Fruit on Human Promyelocytic Leukemia HL-60 Cells

Directory of Open Access Journals (Sweden)

T-Johari S. A. Tajudin

2012-01-01

Full Text Available Methanolic extract of Cynometra cauliflora whole fruit was assayed for cytotoxicity against the human promyelocytic leukemia HL-60 and the normal mouse fibroblast NIH/3T3 cell lines by using the MTT assay. The CD50 of the extract for 72 hours was 0.9 μg/mL whereas the value for the cytotoxic drug vincristine was 0.2 μg/mL. The viability of the NIH/3T3 cells was at 80.0% when treated at 15.0 μg/mL. The extract inhibited HL-60 cell proliferation with dose dependence. AO/PI staining of HL-60 cells treated with the extract revealed that majority of cells were in the apoptotic cell death mode. Flow cytometry analysis of HL-60 cells treated at CD50 of the extract showed that the early apoptotic cells were 31.0, 26.3 and 19.9% at 24, 48, and 72 hours treatment, respectively. The percentage of late apoptotic cells was increased from 62.0 at 24 hours to 64.1 and 70.2 at 48 and 72 hours, respectively. Meanwhile, percent of necrotic cells were 4.9, 6.6, and 8.5 at 24, 48, and 72 hours, respectively. This study has shown that the methanolic extract of C. cauliflora whole fruit was cytotoxic towards HL-60 cells and induced the cells into apoptotic cell death mode, but less cytotoxic towards NIH/3T3 cells.

Establishment of a humanized APL model via the transplantation of PML-RARA-transduced human common myeloid progenitors into immunodeficient mice.

Directory of Open Access Journals (Sweden)

Hiromichi Matsushita

Full Text Available Recent advances in cancer biology have revealed that many malignancies possess a hierarchal system, and leukemic stem cells (LSC or leukemia-initiating cells (LIC appear to be obligatory for disease progression. Acute promyelocytic leukemia (APL, a subtype of acute myeloid leukemia characterized by the formation of a PML-RARα fusion protein, leads to the accumulation of abnormal promyelocytes. In order to understand the precise mechanisms involved in human APL leukemogenesis, we established a humanized in vivo APL model involving retroviral transduction of PML-RARA into CD34(+ hematopoietic cells from human cord blood and transplantation of these cells into immunodeficient mice. The leukemia well recapitulated human APL, consisting of leukemic cells with abundant azurophilic abnormal granules in the cytoplasm, which expressed CD13, CD33 and CD117, but not HLA-DR and CD34, were clustered in the same category as human APL samples in the gene expression analysis, and demonstrated sensitivity to ATRA. As seen in human APL, the induced APL cells showed a low transplantation efficiency in the secondary recipients, which was also exhibited in the transplantations that were carried out using the sorted CD34- fraction. In order to analyze the mechanisms underlying APL initiation and development, fractionated human cord blood was transduced with PML-RARA. Common myeloid progenitors (CMP from CD34(+/CD38(+ cells developed APL. These findings demonstrate that CMP are a target fraction for PML-RARA in APL, whereas the resultant CD34(- APL cells may share the ability to maintain the tumor.

29 CFR 525.10 - Prevailing wage rates.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Prevailing wage rates. 525.10 Section 525.10 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS EMPLOYMENT OF WORKERS WITH DISABILITIES UNDER SPECIAL CERTIFICATES § 525.10 Prevailing wage rates. (a) A...

Keeping HL-LHC accountable

CERN Multimedia

2015-01-01

This week saw the cost and schedule of the High Luminosity LHC (HL-LHC) and LHC Injectors Upgrade (LIU) projects come under close scrutiny from the external review committee set up for the purpose.    HL-LHC, whose implementation requires an upgrade to the CERN injector complex, responds directly to one of the key recommendations of the updated European Strategy for Particle Physics, which urges CERN to prepare for a ‘major luminosity upgrade’, a recommendation that is also perfectly in line with the P5 report on the US strategy for the field. Responding to this recommendation, CERN set up the HL-LHC project in 2013, partially supported by FP7 funding through the HiLumi LHC Design Study (2011-2015), and coordinated with the American LARP project, which oversees the US contribution to the upgrade. A key element of HL-LHC planning is a mechanism for receiving independent expert advice on all aspects of the project.  To this end, several technical reviews h...

Effect of a 2.45-GHz radiofrequency electromagnetic field on neutrophil chemotaxis and phagocytosis in differentiated human HL-60 cells.

Science.gov (United States)

Koyama, Shin; Narita, Eijiro; Suzuki, Yoshihisa; Taki, Masao; Shinohara, Naoki; Miyakoshi, Junji

2015-01-01

The potential public health risks of radiofrequency (RF) fields have been discussed at length, especially with the use of mobile phones spreading extensively throughout the world. In order to investigate the properties of RF fields, we examined the effect of 2.45-GHz RF fields at the specific absorption rate (SAR) of 2 and 10 W/kg for 4 and 24 h on neutrophil chemotaxis and phagocytosis in differentiated human HL-60 cells. Neutrophil chemotaxis was not affected by RF-field exposure, and subsequent phagocytosis was not affected either compared with that under sham exposure conditions. These studies demonstrated an initial immune response in the human body exposed to 2.45-GHz RF fields at the SAR of 2 W/kg, which is the maximum value recommended by the International Commission for Non-Ionizing Radiation Protection (ICNIRP) guidelines. The results of our experiments for RF-field exposure at an SAR under 10 W/kg showed very little or no effects on either chemotaxis or phagocytosis in neutrophil-like human HL-60 cells. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

In vivo expansion of co-transplanted T cells impacts on tumor re-initiating activity of human acute myeloid leukemia in NSG mice.

Directory of Open Access Journals (Sweden)

Malte von Bonin

Full Text Available Human cells from acute myeloid leukemia (AML patients are frequently transplanted into immune-compromised mouse strains to provide an in vivo environment for studies on the biology of the disease. Since frequencies of leukemia re-initiating cells are low and a unique cell surface phenotype that includes all tumor re-initiating activity remains unknown, the underlying mechanisms leading to limitations in the xenotransplantation assay need to be understood and overcome to obtain robust engraftment of AML-containing samples. We report here that in the NSG xenotransplantation assay, the large majority of mononucleated cells from patients with AML fail to establish a reproducible myeloid engraftment despite high donor chimerism. Instead, donor-derived cells mainly consist of polyclonal disease-unrelated expanded co-transplanted human T lymphocytes that induce xenogeneic graft versus host disease and mask the engraftment of human AML in mice. Engraftment of mainly myeloid cell types can be enforced by the prevention of T cell expansion through the depletion of lymphocytes from the graft prior transplantation.

15 CFR 8a.525 - Fringe benefits.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Fringe benefits. 8a.525 Section 8a.525 Commerce and Foreign Trade Office of the Secretary of Commerce NONDISCRIMINATION ON THE BASIS OF SEX IN... in Employment in Education Programs or Activities Prohibited § 8a.525 Fringe benefits. (a) “Fringe...

Effect of citrus flavonoids on HL-60 cell differentiation.

Science.gov (United States)

Kawaii, S; Tomono, Y; Katase, E; Ogawa, K; Yano, M

1999-01-01

Twenty-seven Citrus flavonoids were examined for their activity of induction of terminal differentiation of human promyelocytic leukemia cells (HL-60) by nitro blue tetrazolium (NBT) reducing, nonspecific esterase, specific esterase, and phagocytic activities. 10 flavonoids were judged to be active (percentage of NBT reducing cells was more than 40% at a concentration of 40 microM), and the rank order of potency was natsudaidain, luteolin, tangeretin, quercetin, apigenin, 3, 3, '4, '5, 6, 7, 8-heptamethoxyflavone, nobiletin, acacetin, eriodictyol, and taxifolin. These flavonoids exerted their activity in a dose-dependent manner. HL-60 cells treated with these flavonoids differentiated into mature monocyte/macrophage. The structure-activity relationship established from comparison between flavones and flavanones revealed that ortho-catechol moiety in ring B and C2-C3 double bond had an important role for induction of differentiation of HL-60. In polymethoxylated flavones, hydroxyl group at C3 and methoxyl group at C8 enhanced the differentiation-inducing activity.

Tumor SHB gene expression affects disease characteristics in human acute myeloid leukemia.

Science.gov (United States)

Jamalpour, Maria; Li, Xiujuan; Cavelier, Lucia; Gustafsson, Karin; Mostoslavsky, Gustavo; Höglund, Martin; Welsh, Michael

2017-10-01

The mouse Shb gene coding for the Src Homology 2-domain containing adapter protein B has recently been placed in context of BCRABL1-induced myeloid leukemia in mice and the current study was performed in order to relate SHB to human acute myeloid leukemia (AML). Publicly available AML databases were mined for SHB gene expression and patient survival. SHB gene expression was determined in the Uppsala cohort of AML patients by qPCR. Cell proliferation was determined after SHB gene knockdown in leukemic cell lines. Despite a low frequency of SHB gene mutations, many tumors overexpressed SHB mRNA compared with normal myeloid blood cells. AML patients with tumors expressing low SHB mRNA displayed longer survival times. A subgroup of AML exhibiting a favorable prognosis, acute promyelocytic leukemia (APL) with a PMLRARA translocation, expressed less SHB mRNA than AML tumors in general. When examining genes co-expressed with SHB in AML tumors, four other genes ( PAX5, HDAC7, BCORL1, TET1) related to leukemia were identified. A network consisting of these genes plus SHB was identified that relates to certain phenotypic characteristics, such as immune cell, vascular and apoptotic features. SHB knockdown in the APL PMLRARA cell line NB4 and the monocyte/macrophage cell line MM6 adversely affected proliferation, linking SHB gene expression to tumor cell expansion and consequently to patient survival. It is concluded that tumor SHB gene expression relates to AML survival and its subgroup APL. Moreover, this gene is included in a network of genes that plays a role for an AML phenotype exhibiting certain immune cell, vascular and apoptotic characteristics.

Caffeine affects the biological responses of human hematopoietic cells of myeloid lineage via downregulation of the mTOR pathway and xanthine oxidase activity

Science.gov (United States)

Abooali, Maryam; Yasinska, Inna M.; Casely-Hayford, Maxwell A.; Berger, Steffen M.; Fasler-Kan, Elizaveta; Sumbayev, Vadim V.

2015-01-01

Correction of human myeloid cell function is crucial for the prevention of inflammatory and allergic reactions as well as leukaemia progression. Caffeine, a naturally occurring food component, is known to display anti-inflammatory effects which have previously been ascribed largely to its inhibitory actions on phosphodiesterase. However, more recent studies suggest an additional role in affecting the activity of the mammalian target of rapamycin (mTOR), a master regulator of myeloid cell translational pathways, although detailed molecular events underlying its mode of action have not been elucidated. Here, we report the cellular uptake of caffeine, without metabolisation, by healthy and malignant hematopoietic myeloid cells including monocytes, basophils and primary acute myeloid leukaemia mononuclear blasts. Unmodified caffeine downregulated mTOR signalling, which affected glycolysis and the release of pro-inflammatory/pro-angiogenic cytokines as well as other inflammatory mediators. In monocytes, the effects of caffeine were potentiated by its ability to inhibit xanthine oxidase, an enzyme which plays a central role in human purine catabolism by generating uric acid. In basophils, caffeine also increased intracellular cyclic adenosine monophosphate (cAMP) levels which further enhanced its inhibitory action on mTOR. These results demonstrate an important mode of pharmacological action of caffeine with potentially wide-ranging therapeutic impact for treating non-infectious disorders of the human immune system, where it could be applied directly to inflammatory cells. PMID:26384306

HL-LHC Accelerator

CERN Document Server

Zimmermann, F

2013-01-01

The tentative schedule, key ingredients, as well as progress of pertinent R&D and component prototypes for the LHC luminosity upgrade, "HL-LHC," are reviewed. Also alternative scenarios based on performance-improving consolidations (PICs) instead of a full upgrade are discussed. Tentative time schedules and expected luminosity evolutions for the different scenarios are sketched. The important role of HL-LHC development as a step towards a future HE-LHC or VHE-LHC is finally highlighted. Presented at "Higgs & Beyond" Conference Tohoku University, Sendai 7 June 2013.

HL-LHC parameter space and scenarios

International Nuclear Information System (INIS)

Bruning, O.S.

2012-01-01

The HL-LHC project aims at a total integrated luminosity of approximately 3000 fb -1 over the lifetime of the HL-LHC. Assuming an exploitation period of ca. 10 years this goal implies an annual integrated luminosity of approximately 200 fb -1 to 300 fb -1 per year. This paper looks at potential beam parameters that are compatible with the HL-LHC performance goals and discusses briefly potential variation in the parameter space. It is shown that the design goal of the HL-LHC project can only be achieved with a full upgrade of the injector complex and the operation with β* values close to 0.15 m. Significant margins for leveling can be achieved for β* values close to 0.15 m. However, these margins can only be harvested during the HL-LHC operation if the required leveling techniques have been demonstrated in operation

Structure-activity relationship studies of 5,7-dihydroxyflavones as naturally occurring inhibitors of cell proliferation in human leukemia HL-60 cells.

Science.gov (United States)

Ninomiya, Masayuki; Nishida, Kyohei; Tanaka, Kaori; Watanabe, Kunitomo; Koketsu, Mamoru

2013-07-01

Flavonoids are widely occurring polyphenols that are found in plants. The aim of this study was to investigate the structure-activity relationships of 5,7-dihydroxyflavones, with a focus on the effect of B ring structure substitution on the antiproliferative effects of the compounds in human leukemia HL-60 cells. We prepared a series of 5,7-dihydroxyflavones and evaluated their ability to inhibit the proliferation of HL-60 cells by using the MTT assay. The apoptosis- and cell differentiation-inducing ability of the most potent flavones were investigated using staining and morphological analyses. This study explored the antileukemic and chemopreventive potency of 5,7-dihydroxyflavones, particularly diosmetin and chrysoeriol, which have both hydroxy and methoxy groups on the B ring.

Biology and relevance of human acute myeloid leukemia stem cells.

Science.gov (United States)

Thomas, Daniel; Majeti, Ravindra

2017-03-23

Evidence of human acute myeloid leukemia stem cells (AML LSCs) was first reported nearly 2 decades ago through the identification of rare subpopulations of engrafting cells in xenotransplantation assays. These AML LSCs were shown to reside at the apex of a cellular hierarchy that initiates and maintains the disease, exhibiting properties of self-renewal, cell cycle quiescence, and chemoresistance. This cancer stem cell model offers an explanation for chemotherapy resistance and disease relapse and implies that approaches to treatment must eradicate LSCs for cure. More recently, a number of studies have both refined and expanded our understanding of LSCs and intrapatient heterogeneity in AML using improved xenotransplant models, genome-scale analyses, and experimental manipulation of primary patient cells. Here, we review these studies with a focus on the immunophenotype, biological properties, epigenetics, genetics, and clinical associations of human AML LSCs and discuss critical questions that need to be addressed in future research. © 2017 by The American Society of Hematology.

Effects of stem cell factor on hypoxia-inducible factor 1 alpha accumulation in human acute myeloid leukaemia and LAD2 mast cells.

Directory of Open Access Journals (Sweden)

Bernhard F Gibbs

Full Text Available Stem cell factor (SCF is a hematopoietic growth factor that exerts its activity by signalling through the tyrosine kinase receptor known as Kit or CD117. SCF-Kit signalling is crucial for the survival, proliferation and differentiation of hematopoietic cells of myeloid lineage. Furthermore, since myeloid leukaemia cells express the Kit receptor, SCF may play an important role in myeloid leukaemia progression too. However, the mechanisms of this pathophysiological effect remain unclear. Recent evidence shows that SCF triggers accumulation of the inducible alpha subunit of hypoxia-inducible factor 1 (HIF-1 in hematopoietic cells--a transcription complex that plays a pivotal role in cellular adaptation to low oxygen availability. However, it is unknown how SCF impacts on HIF-1α accumulation in human myeloid leukaemia and mast cells. Here we show that SCF induces HIF-1α accumulation in THP-1 human myeloid leukaemia cells but not in LAD2 mast cells. We demonstrated that LAD2 cells have a more robust glutathione (GSH-dependent antioxidative system compared to THP-1 cells and are therefore protected against the actions of ROS generated in an SCF-dependent manner. BSO-induced GSH depletion led to a significant decrease in HIF-1α prolyl hydroxylase (PHD activity in THP-1 cells and to near attenuation of it in LAD2 cells. In THP-1 cells, SCF-induced HIF-1α accumulation is controlled via ERK, PI3 kinase/PKC-δ/mTOR-dependent and to a certain extent by redox-dependent mechanisms. These results demonstrate for the first time an important cross-talk of signalling pathways associated with HIF-1 activation--an important stage of the myeloid leukaemia cell life cycle.

Allium compounds, dipropyl and dimethyl thiosulfinates as antiproliferative and differentiating agents of human acute myeloid leukemia cell lines

Directory of Open Access Journals (Sweden)

Faten Merhi

2008-08-01

Full Text Available Faten Merhi1, Jacques Auger2, Francine Rendu1, Brigitte Bauvois11UMR 7131 UPMC Paris Universitas/CNRS, Groupe Hospitalier Broussais-HEGP, Paris, France; 2University F. Rabelais, IRBI, UPRESA CNRS 6035, Tours, FranceAbstract: Epidemiologic studies support the premise that Allium vegetables may lower the risk of cancers. The beneficial effects appear related to the organosulfur products generated upon processing of Allium. Leukemia cells from patients with acute myeloid leukemia (AML display high proliferative capacity and have a reduced capacity of undergoing apoptosis and maturation. Whether the sulfur-containing molecules thiosulfinates (TS, diallyl TS (All2TS, dipropyl TS (Pr2TS and dimethyl TS (Me2TS, are able to exert chemopreventative activity against AML is presently unknown. The present study was an evaluation of proliferation, cytotoxicity, differentiation and secretion of AML cell lines (U937, NB4, HL-60, MonoMac-6 in response to treatment with these TS and their related sulfides (diallylsulfide, diallyl disulfide, dipropyl disulfide, dimethyl disulfide. As assessed by flow cytometry, ELISA, gelatin zymogaphy and RT-PCR, we showed that Pr2TS and Me2TS, but not All2TS and sulfides, 1 inhibited cell proliferation in dose- and time-dependent manner and this process was neither due to cytotoxicity nor apoptosis, 2 induced macrophage maturation, and 3 inhibited the levels of secreted MMP-9 (protein and activity and TNF-α protein, without altering mRNA levels. By establishing for the first time that Pr2TS and Me2TS affect proliferation, differentiation and secretion of leukemic cell lines, this study provides the opportunity to explore the potential efficiency of these molecules in AML.Keywords: acute myeloid leukemia, thiosulfinate, proliferation, differentiation, matrix metalloproteinase-9

Rannarootslaste suurmees Hans Pöhl / Olev Liivik

Index Scriptorium Estoniae

Liivik, Olev, 1975-

2011-01-01

Arvustus: Estlandssvenskarnas hövding. En biografi över Hans Pöhl (1876-1930), estlandssvenskarnas främste företrädare och ledare = Hans Pöhl - rannarootslaste eestvõileja : Hans Pöhl (1876-1930), Eesti rootslaste vaimse liidri ja valgustaja elulugu. Stockholm, 2010

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

Science.gov (United States)

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

2015-08-01

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

29 CFR 525.21 - Lowering of wage rates.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Lowering of wage rates. 525.21 Section 525.21 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS EMPLOYMENT OF WORKERS WITH DISABILITIES UNDER SPECIAL CERTIFICATES § 525.21 Lowering of wage rates. (a) No...

42 CFR 412.525 - Adjustments to the Federal prospective payment.

Science.gov (United States)

2010-10-01

... HUMAN SERVICES MEDICARE PROGRAM PROSPECTIVE PAYMENT SYSTEMS FOR INPATIENT HOSPITAL SERVICES Prospective Payment System for Long-Term Care Hospitals § 412.525 Adjustments to the Federal prospective payment. (a... its estimated costs for a patient exceed the adjusted LTC-MS-DRG payment plus a fixed-loss amount. For...

36 CFR 1211.525 - Fringe benefits.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Fringe benefits. 1211.525... Prohibited § 1211.525 Fringe benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, fringe benefits means: Any medical, hospital, accident, life insurance, or retirement benefit...

45 CFR 2555.525 - Fringe benefits.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Fringe benefits. 2555.525 Section 2555.525 Public... benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, fringe benefits means: Any medical, hospital, accident, life insurance, or retirement benefit, service, policy or plan, any...

45 CFR 618.525 - Fringe benefits.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 3 2010-10-01 2010-10-01 false Fringe benefits. 618.525 Section 618.525 Public... benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, fringe benefits means: Any medical, hospital, accident, life insurance, or retirement benefit, service, policy or plan, any...

44 CFR 19.525 - Fringe benefits.

Science.gov (United States)

2010-10-01

... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Fringe benefits. 19.525... Programs or Activities Prohibited § 19.525 Fringe benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, fringe benefits means: Any medical, hospital, accident, life insurance, or...

Effects of nicotine on cellular proliferation, cell cycle phase distribution, and macromolecular synthesis in human promyelocytic HL-60 leukaemia cells

International Nuclear Information System (INIS)

Konno, S.; Wu, J.M.; Chiao, J.W.

1986-01-01

Addition of nicotine causes a dose- and time-dependent inhibition of cell growth in the human promyelocytic HL-60 leukemia cells, with 4 mM nicotine resulting in a 50% inhibition of cellular proliferation after 48-50h. Accompanying the anticellular effect of nicotine is a significant change in the cell cycle distribution of HL-60 cells. For example, treatment with 4 mM nicotine for 20h causes an increase in the proportion of G1-phase cells (from 49% to 57%) and a significant decrease in the proportion of S-phase cells (from 41% to 32%). These results suggest that nicotine causes partial cell arrest in the G-1 phase which may in part account for its effects on cell growth. To determine whether nicotine changes the cellular uptake/transport to macromolecular precursors, HL-60 cells were treated with 216 mM nicotine for 30h, at the end of which time cells were labelled with ( 3 H)thymidine, ( 3 H)uridine, ( 14 C)lysine and( 35 S)methionine, the trichloroacetic acid soluble and insoluble radioactivities from each of the labelling conditions were determined. These studies show that nicotine mainly affects the ''de novo synthesis'' of proteins. (author)

Enhanced normal short-term human myelopoiesis in mice engineered to express human-specific myeloid growth factors.

Science.gov (United States)

Miller, Paul H; Cheung, Alice M S; Beer, Philip A; Knapp, David J H F; Dhillon, Kiran; Rabu, Gabrielle; Rostamirad, Shabnam; Humphries, R Keith; Eaves, Connie J

2013-01-31

Better methods to characterize normal human hematopoietic cells with short-term repopulating activity cells (STRCs) are needed to facilitate improving recovery rates in transplanted patients.We now show that 5-fold more human myeloid cells are produced in sublethally irradiated NOD/SCID-IL-2Receptor-γchain-null (NSG) mice engineered to constitutively produce human interleukin-3, granulocyte-macrophage colony-stimulating factor and Steel factor (NSG-3GS mice) than in regular NSG mice 3 weeks after an intravenous injection of CD34 human cord blood cells. Importantly, the NSG-3GS mice also show a concomitant and matched increase in circulating mature human neutrophils. Imaging NSG-3GS recipients of lenti-luciferase-transduced cells showed that human cells being produced 3 weeks posttransplant were heterogeneously distributed, validating the blood as a more representative measure of transplanted STRC activity. Limiting dilution transplants further demonstrated that the early increase in human granulopoiesis in NSG-3GS mice reflects an expanded output of differentiated cells per STRC rather than an increase in STRC detection. NSG-3GS mice support enhanced clonal outputs from human short-term repopulating cells (STRCs) without affecting their engrafting efficiency. Increased human STRC clone sizes enable their more precise and efficient measurement by peripheral blood monitoring.

Raman spectrum reveals Mesenchymal stem cells inhibiting HL60 cells growth

Science.gov (United States)

Su, Xin; Fang, Shaoyin; Zhang, Daosen; Zhang, Qinnan; Lu, Xiaoxu; Tian, Jindong; Fan, Jinping; Zhong, Liyun

2017-04-01

Though some research results reveals that Mesenchymal stem cells (MSCs) have the ability of inhibiting tumor cells proliferation, it remains controversial about the precise interaction mechanism during MSCs and tumor cells co-culture. In this study, combing Raman spectroscopic data and principle component analysis (PCA), the biochemical changes of MSCs or Human promyelocytic leukemia (HL60) cells during their co-culture were presented. The obtained results showed that some main Raman peaks of HL60 assigned to nucleic acids or proteins were greatly higher in intensity in the late stage of co-culture than those in the early stage of co-culture while they were still lower relative to the control group, implicating that the effect of MSCs inhibiting HL60 proliferation appeared in the early stage but gradually lost the inhibiting ability in the late stage of co-culture. Moreover, some other peaks of HL60 assigned to proteins were decreased in intensity in the early stage of co-culture relative to the control group but rebounded to the level similar to the control group in the late stage, showing that the content and structure changes of these proteins might be generated in the early stage but returned to the original state in the late stage of co-culture. As a result, in the early stage of MSCs-HL60 co-culture, along with the level of Akt phosphorylation of HL60 was lowered relative to its control group, the proliferation rate of HL60 cells was decreased. And in the late stage of co-culture, along with the level of Akt phosphorylation was rebounded, the reverse transfer of Raman peaks within 875-880 cm- 1 appeared, thus MSCs lost the ability to inhibit HL60 growth and HL60 proliferation was increased. In addition, it was observed that the peak at 811 cm- 1, which is a marker of RNA, was higher in intensity in the late stage than that in the control group, indicating that MSCs might be differentiated into myofibroblast-like MSCs. In addition, PCA results also exhibited

Radiation recall and radiosensitisation with alkylating agents

Energy Technology Data Exchange (ETDEWEB)

Kellie, S.J.; Plowman, P.N.; Malpas, J.S.

1987-05-16

This brief note records the results of experiments with Adriamycin, 1,2:5,6 dianhydrodulcit and hydroxyurea combined with an endogenous substance inhibiting myeloid proliferation selectively against target cells taken from normal rat, mouse or human haemopoietic lines, spontaneous human leukaemias and the HL-60 established promyelocytic cell line.

31 CFR 28.525 - Fringe benefits.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Fringe benefits. 28.525 Section 28... the Basis of Sex in Employment in Education Programs or Activities Prohibited § 28.525 Fringe benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, fringe benefits means: Any...

Berberine Induces Apoptotic Cell Death via Activation of Caspase-3 and -8 in HL-60 Human Leukemia Cells: Nuclear Localization and Structure-Activity Relationships.

Science.gov (United States)

Okubo, Shinya; Uto, Takuhiro; Goto, Aya; Tanaka, Hiroyuki; Nishioku, Tsuyoshi; Yamada, Katsushi; Shoyama, Yukihiro

2017-01-01

Berberine (BBR), an isoquinoline alkaloid, is a well-known bioactive compound contained in medicinal plants used in traditional and folk medicines. In this study, we investigated the subcellular localization and the apoptotic mechanisms of BBR were elucidated. First, we confirmed the incorporation of BBR into the cell visually. BBR showed antiproliferative activity and promptly localized to the nucleus from 5[Formula: see text]min to 15[Formula: see text]min after BBR treatment in HL-60 human promyelocytic leukemia cells. Next, we examined the antiproliferative activity of BBR (1) and its biosynthetically related compounds (2-7) in HL-60 cells. BBR exerted strongest antiproliferative activity among 1-7 and the results of structures and activity relation suggested that a methylenedioxyl group in ring A, an [Formula: see text]-alkyl group at C-9 position, and the frame of isoquinoline may be necessary for antiproliferative activity. Moreover, BBR showed the most potent antiproliferative activity in HL-60 cells among human cancer and normal cell lines tested. Next, we examined the effect of BBR on molecular events known as apoptosis induction. In HL-60 cells, BBR induced chromatin condensation and DNA fragmentation, and triggered the activation of PARP, caspase-3 and caspase-8 without the activation of caspase-9. BBR-induced DNA fragmentation was abolished by pretreatment with inhibitors against caspase-3 and caspase-8, but not against caspase-9. ERK and p38 were promptly phosphorylated after 15 min of BBR treatment, and this was correlated with time of localization to the nucleus of BBR. These results demonstrated that BBR translocated into nucleus immediately after treatments and induced apoptotic cell death by activation of caspase-3 and caspase-8.

HL7 Messaging Engine with Customizable Translation System

Directory of Open Access Journals (Sweden)

PRODAN, R.

2010-05-01

Full Text Available This paper introduces a new client-server messaging engine used to exchange clinical data between various medical software applications. Our portal uses the HL7 (Health Level Seven messaging standard to provide translated clinical data to HL7 and non-HL7 client applications. We used HL7 because this standard is worldwide used to facilitate the communication between clinical applications.

Myeloid Dysregulation in a Human Induced Pluripotent Stem Cell Model of PTPN11-Associated Juvenile Myelomonocytic Leukemia

Directory of Open Access Journals (Sweden)

Sonia Mulero-Navarro

2015-10-01

Full Text Available Somatic PTPN11 mutations cause juvenile myelomonocytic leukemia (JMML. Germline PTPN11 defects cause Noonan syndrome (NS, and specific inherited mutations cause NS/JMML. Here, we report that hematopoietic cells differentiated from human induced pluripotent stem cells (hiPSCs harboring NS/JMML-causing PTPN11 mutations recapitulated JMML features. hiPSC-derived NS/JMML myeloid cells exhibited increased signaling through STAT5 and upregulation of miR-223 and miR-15a. Similarly, miR-223 and miR-15a were upregulated in 11/19 JMML bone marrow mononuclear cells harboring PTPN11 mutations, but not those without PTPN11 defects. Reducing miR-223’s function in NS/JMML hiPSCs normalized myelogenesis. MicroRNA target gene expression levels were reduced in hiPSC-derived myeloid cells as well as in JMML cells with PTPN11 mutations. Thus, studying an inherited human cancer syndrome with hiPSCs illuminated early oncogenesis prior to the accumulation of secondary genomic alterations, enabling us to discover microRNA dysregulation, establishing a genotype-phenotype association for JMML and providing therapeutic targets.

Growth regulation on human acute myeloid leukemia effects of five recombinant hematopoietic factors in a serum-free culture system

NARCIS (Netherlands)

Delwel, E.; Salem, M.; Pellens, C.; Dorssers, L.; Wagemaker, G.; Clark, S.; Loewenberg, B

1988-01-01

The response of human acute myeloid leukemia (AML) cells to the distinct hematopoietic growth factors (HGFs), ie, recombinant interleukin-3 (IL-3), granulocyte-macrophage-CSF (GM-CSF), granulocyte-CSF (G-CSF), macrophage-CSF (M-CSF), and erythropoietin (Epo) was investigated under well-defined

Canthin-6-one induces cell death, cell cycle arrest and differentiation in human myeloid leukemia cells.

Science.gov (United States)

Vieira Torquato, Heron F; Ribeiro-Filho, Antonio C; Buri, Marcus V; Araújo Júnior, Roberto T; Pimenta, Renata; de Oliveira, José Salvador R; Filho, Valdir C; Macho, Antonio; Paredes-Gamero, Edgar J; de Oliveira Martins, Domingos T

2017-04-01

Canthin-6-one is a natural product isolated from various plant genera and from fungi with potential antitumor activity. In the present study, we evaluate the antitumor effects of canthin-6-one in human myeloid leukemia lineages. Kasumi-1 lineage was used as a model for acute myeloid leukemia. Cells were treated with canthin-6-one and cell death, cell cycle and differentiation were evaluated in both total cells (Lin + ) and leukemia stem cell population (CD34 + CD38 - Lin -/low ). Among the human lineages tested, Kasumi-1 was the most sensitive to canthin-6-one. Canthin-6-one induced cell death with apoptotic (caspase activation, decrease of mitochondrial potential) and necrotic (lysosomal permeabilization, double labeling of annexin V/propidium iodide) characteristics. Moreover, canthin-6-one induced cell cycle arrest at G 0 /G 1 (7μM) and G 2 (45μM) evidenced by DNA content, BrdU incorporation and cyclin B1/histone 3 quantification. Canthin-6-one also promoted differentiation of Kasumi-1, evidenced by an increase in the expression of myeloid markers (CD11b and CD15) and the transcription factor PU.1. Furthermore, a reduction of the leukemic stem cell population and clonogenic capability of stem cells were observed. These results show that canthin-6-one can affect Kasumi-1 cells by promoting cell death, cell cycle arrest and cell differentiation depending on concentration used. Canthin-6-one presents an interesting cytotoxic activity against leukemic cells and represents a promising scaffold for the development of molecules for anti-leukemic applications, especially by its anti-leukemic stem cell activity. Copyright © 2017 Elsevier B.V. All rights reserved.

HL60 human premyelocitic cell line as a model system for bystander response

International Nuclear Information System (INIS)

Dini, V.; Tabocchini, M.A.; Belli, M.; Simone, G.; Di Carlo, B.; Sapora, O.; Superiore di Sanita, Rome

2007-01-01

Complete text of publication follows. Objective: to evaluate HL60 human premyelocitic cell line as a model system to study bystander response. Methods: HL60 cell line, isolated from the blood of a patient affected by premyelocitic leukemia, has 45-46 chromosomes with abnormalities mainly on chromosomes 5, 8 and X and can undergo chemical-induced in vitro differentiation. Differentiation gives rise to granulocytes, monocytes or macrophages depending on the drug used. We define as proliferative (AP) cells those in log phase of growth with less than 10 passages from thawing and as differentiated (D) cells those treated with 10 nM TPA (phorbol ester) for 72 hours. Phorbol ester treatment induces differentiation to monocytes and macrophages. Differentiation has been evaluated through the expression of differentiation cluster membrane antigens (CD95, CD9 and CD14). Results: AP cells resulted positive for CD95 and negative for CD9 and CD14, while D cells resulted positive for CD9 and negative for CD95 and CD14. Our data on AP and D cells showed that: (i) the level of intracellular reactive oxygen and nitrogen species (ROS and RNS) is lower in D cells compared to AP cells; (ii) radiation induced DNA damage (single and double strand breaks, SSB and DSB, as measured with the comet assay technique) is lower in D cells than in AP cells. This different radiosensitivity can be related to the higher degree of compactness of nuclear structure in D cells. Radiation induced bystander effect (BE) was analyzed with the medium transfer technique. The medium from irradiated, with 0.5 Gy of γ-rays, AP cells was collected after 0, 2, 4 and 24 hours from irradiation and added to non irradiated log phase cells. The frequency of micronuclei formation in bystander cells was measured by using the cytokinesis block technique by adding cytochalasin B to the non irradiated culture together with the irradiated medium. Preliminary data indicate about 1.4-fold increase in micronuclei formation in

Rhein Elicits In Vitro Cytotoxicity in Primary Human Liver HL-7702 Cells by Inducing Apoptosis through Mitochondria-Mediated Pathway

Directory of Open Access Journals (Sweden)

Guy-Armel Bounda

2015-01-01

Full Text Available Objective. To study rhein-induced apoptosis signaling pathway and to investigate its molecular mechanisms in primary human hepatic cells. Results. Cell viability of HL-7702 cells treated with rhein showed significant decrease in dose-dependent manner. Following rhein treatment (25 μM, 50 μM, and 100 μM for 12 h, the detection of apoptotic cells was significantly analyzed by flow cytometry and nuclear morphological changes by Hoechst 33258, respectively. Fatty degeneration studies showed upregulation level of the relevant hepatic markers (P < 0.01. Caspase activities expressed significant upregulation of caspase-3, caspase-9, and caspase-8. Moreover, apoptotic cells by rhein were significantly inhibited by Z-LEHD-FMK and Z-DEVD-FMK, caspase-9 inhibitor, and caspase-3 inhibitor, respectively. Overproduction of reactive oxygen species, lipid peroxidation, and loss of mitochondrial membrane potential were detected by fluorometry. Additionally, NAC, a ROS scavenger, significantly attenuated rhein-induced oxidative damage in HL-7702 cells. Furthermore, real-time qPCR results showed significant upregulation of p53, PUMA, Apaf-1, and Casp-9 and Casp-3 mRNA, with no significant changes of Fas and Cytochrome-c. Immunoblotting revealed significant Cytochrome-c release from mitochondria into cytosol and no change in Fas expression. Conclusion. Taken together, these observations suggested that rhein could induce apoptosis in HL-7702 cells via mitochondria-mediated signal pathway with involvement of oxidative stress mechanism.

Von Hippel-Lindau disease (vHL)

DEFF Research Database (Denmark)

Binderup, Marie Louise Mølgaard; Bisgaard, Søs Marie Luise; Harbud, Vibeke

2013-01-01

for vHL which is comprised of Danish doctors and specialists interested in vHL. The recommendations are based on longstanding clinical experience, Danish original research, and extensive review of the international literature. vHL is a hereditary multi-tumour disease caused by germline mutations....../MRI of the abdomen, e) annual plasma-metanephrine, plasma-normetanephrine, and plasma-chromogranin A tests, and f) annual hearing examination at a department of audiology. It is advised that one doctor takes on the responsibility of coordination of and referral to the many examinations, and the communication...

The development of a three-dimensional scaffold for ex vivo biomimicry of human acute myeloid leukaemia.

Science.gov (United States)

Blanco, Teresa Mortera; Mantalaris, Athanasios; Bismarck, Alexander; Panoskaltsis, Nicki

2010-03-01

Acute myeloid leukaemia (AML) is a cancer of haematopoietic cells that develops in three-dimensional (3-D) bone marrow niches in vivo. The study of AML has been hampered by lack of appropriate ex vivo models that mimic this microenvironment. We hypothesised that fabrication and optimisation of suitable biomimetic scaffolds for culturing leukaemic cells ex vivo might facilitate the study of AML in its native 3-D niche. We evaluated the growth of three leukaemia subtype-specific cell lines, K-562, HL60 and Kasumi-6, on highly porous scaffolds fabricated from biodegradable and non-biodegradable polymeric materials, such as poly (L-lactic-co-glycolic acid) (PLGA), polyurethane (PU), poly (methyl-methacrylate), poly (D, L-lactade), poly (caprolactone), and polystyrene. Our results show that PLGA and PU supported the best seeding efficiency and leukaemic growth. Furthermore, the PLGA and PU scaffolds were coated with extracellular matrix (ECM) proteins, collagen type I (62.5 or 125 microg/ml) and fibronectin (25 or 50 microg/ml) to provide biorecognition signals. The 3 leukaemia subtype-specific lines grew best on PU scaffolds coated with 62.5 microg/ml collagen type I over 6 weeks in the absence of exogenous growth factors. In conclusion, PU-collagen scaffolds may provide a practical model to study the biology and treatment of primary AML in an ex vivo mimicry. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Time- and concentration-dependent effects of resveratrol in HL-60 and HepG2 cells

DEFF Research Database (Denmark)

Stervbo, Ulrik; Vang, Ole; Bonnesen, Christine

2006-01-01

Resveratrol, a phytochemical present in grapes, has been demonstrated to inhibit tumourigenesis in animal models. However, the specific mechanism by which resveratrol exerts its anticarcinogenic effect has yet to be elucidated. In the present study, the inhibitory effects of resveratrol on cell...... proliferation and apoptosis were evaluated in the human leukaemia cell line HL-60 and the human hepatoma derived cell line HepG2. We found that after a 2 h incubation period, resveratrol inhibited DNA synthesis in a concentration-dependent manner. The IC50 value was 15 μM in both HL-60 and HepG2 cells. When...... the time of treatment was extended, an increase in IC50 value was observed; for example, at 24 h the IC50 value was 30 μM for HL-60 cells and 60 μM for HepG2 cells. Flow cytometry revealed that cells accumulated in different phases of the cell cycle depending on the resveratrol concentration. Furthermore...

Modeling of C/EBPalpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells

DEFF Research Database (Denmark)

Kirstetter, Peggy; Schuster, Mikkel B; Bereshchenko, Oksana

2008-01-01

Mutations in the CEBPA gene are present in 7%-10% of human patients with acute myeloid leukemia (AML). However, no genetic models exist that demonstrate their etiological relevance. To mimic the most common mutations affecting CEBPA-that is, those leading to loss of the 42 kDa C/EBPalpha isoform (p...... penetrance. p42-deficient leukemia could be transferred by a Mac1+c-Kit+ population that gave rise only to myeloid cells in recipient mice. Expression profiling of this population against normal Mac1+c-Kit+ progenitors revealed a signature shared with MLL-AF9-transformed AML.......42) while retaining the 30kDa isoform (p30)-we modified the mouse Cebpa locus to express only p30. p30 supported the formation of granulocyte-macrophage progenitors. However, p42 was required for control of myeloid progenitor proliferation, and p42-deficient mice developed AML with complete...

Testicular myeloid sarcoma: case report.

Science.gov (United States)

Zago, Luzia Beatriz Ribeiro; Ladeia, Antônio Alexandre Lisbôa; Etchebehere, Renata Margarida; de Oliveira, Leonardo Rodrigues

2013-01-01

Myeloid sarcomas are extramedullary solid tumors composed of immature granulocytic precursor cells. In association with acute myeloid leukemia and other myeloproliferative disorders, they may arise concurrently with compromised bone marrow related to acute myeloid leukemia, as a relapsed presentation, or occur as the first manifestation. The testicles are considered to be an uncommon site for myeloid sarcomas. No therapeutic strategy has been defined as best but may include chemotherapy, radiotherapy and/or hematopoietic stem cell transplantation. This study reports the evolution of a patient with testicular myeloid sarcoma as the first manifestation of acute myeloid leukemia. The patient initially refused medical treatment and died five months after the clinical condition started.

20 CFR 404.525 - Suspension of offset.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Suspension of offset. 404.525 Section 404.525 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950....521, the overpaid individual notifies us that he or she is exercising a right described in § 404.522(a...

[Biologically active fragment of the differentiation factor from HL-60 cell line. Identification and properties].

Science.gov (United States)

Kostanian, I A; Astapova, M V; Navolotskaia, E V; Lepikhova, T N; Dranitsyna, S M; Telegin, G B; Rodionov, I L; Baĭdakova, L K; Zolotarev, Iu A; Molotkovskaia, I M; Lipkin, V M

2000-07-01

Six-membered peptide fragment TGENHR (HLDF-6) was identified in the HL-60 cell culture of human promyelocyte leukemia treated with retinoic acid when studying the differentiation factor HLDF of this cell line. HLDF-6 retains the ability of the full-size factor to induce the differentiation and arrest the proliferation of the starting HL-60 cells. It was shown that the synthetic peptide HLDF-6 has no specific receptors on the surface of the HL-60 cells but can affect the binding of interleukin IL-1 beta, a cytokine involved in proliferation, to the cell surface. It was found on a model of transplantable NSO myeloma that HLDF-6 has an antitumor activity.

Prevalence, birth incidence, and penetrance of von Hippel-Lindau disease (vHL) in Denmark

DEFF Research Database (Denmark)

Binderup, Marie Louise Mølgaard; Galanakis, Michael Carter Bisgaard; Budtz-Jørgensen, Esben

2017-01-01

the international diagnostic criteria. We found an overall penetrance of 87% at age 60 years. When considering only vHL patients who have not attended surveillance, 20% will still be asymptomatic at age 60 years. This should be considered in the context of genetic counselling, especially when assessing the risk...... of vHL in asymptomatic adult first-degree relatives who are often not genetically tested.European Journal of Human Genetics advance online publication, 14 December 2016; doi:10.1038/ejhg.2016.173....

Indole alkaloids from leaves and twigs of Rauvolfia verticillata.

Science.gov (United States)

Zhang, Bing-Jie; Peng, Lei; Wu, Zhi-Kun; Bao, Mei-Fen; Liu, Ya-Ping; Cheng, Gui-Guang; Luo, Xiao-Dong; Cai, Xiang-Hai

2013-01-01

Seven new indole alkaloids, rauverines A-G (1-7), and 19 known indole alkaloids were isolated from the leaves and twigs of Rauvolfia verticillata. All compounds showed no cytotoxicity against five human cancer cell lines, human myeloid leukemia (HL-60), hepatocellular carcinoma (SMMC-7721), lung cancer (A-549), breast cancer (MCF-7), and colon cancer (SW480) cells.

Cutaneous myeloid sarcoma: natural history and biology of an uncommon manifestation of acute myeloid leukemia.

Science.gov (United States)

Hurley, M Yadira; Ghahramani, Grant K; Frisch, Stephanie; Armbrecht, Eric S; Lind, Anne C; Nguyen, Tudung T; Hassan, Anjum; Kreisel, Friederike H; Frater, John L

2013-05-01

We conducted a retrospective study of patients with cutaneous myeloid sarcoma, from 2 tertiary care institutions. Eighty-three patients presented, with a mean age of 52 years. Diagnosis of myeloid sarcoma in the skin was difficult due to the low frequency of myeloperoxidase and/or CD34+ cases (56% and 19% of tested cases, respectively). Seventy-one of the 83 patients (86%) had ≥ 1 bone marrow biopsy. Twenty-eight (39%) had acute myeloid leukemia with monocytic differentiation. Twenty-three had other de novo acute myeloid leukemia subtypes. Thirteen patients had other myeloid neoplasms, of which 4 ultimately progressed to an acute myeloid leukemia. Seven had no bone marrow malignancy. Ninety-eight percent of the patients received chemotherapy, and approximately 89% died of causes related to their disease. Cutaneous myeloid sarcoma in most cases represents an aggressive manifestation of acute myeloid leukemia. Diagnosis can be challenging due to lack of myeloblast-associated antigen expression in many cases, and difficulty in distinguishing monocyte-lineage blasts from neoplastic and non-neoplastic mature monocytes.

The DNA Inflammasome in Human Myeloid Cells Is Initiated by a STING-Cell Death Program Upstream of NLRP3

Science.gov (United States)

Gaidt, Moritz M.; Ebert, Thomas S.; Chauhan, Dhruv; Ramshorn, Katharina; Pinci, Francesca; Zuber, Sarah; O’Duill, Fionan; Schmid-Burgk, Jonathan L.; Hoss, Florian; Buhmann, Raymund; Wittmann, Georg; Latz, Eicke; Subklewe, Marion; Hornung, Veit

2018-01-01

Summary Detection of cytosolic DNA constitutes a central event in the context of numerous infectious and sterile inflammatory conditions. Recent studies have uncovered a bipartite mode of cytosolic DNA recognition, in which the cGAS-STING axis triggers antiviral immunity, whereas AIM2 triggers inflammasome activation. Here, we show that AIM2 is dispensable for DNA-mediated inflammasome activation in human myeloid cells. Instead, detection of cytosolic DNA by the cGAS-STING axis induces a cell death program initiating potassium efflux upstream of NLRP3. Forward genetics identified regulators of lysosomal trafficking to modulate this cell death program, and subsequent studies revealed that activated STING traffics to the lysosome, where it triggers membrane permeabilization and thus lysosomal cell death (LCD). Importantly, the cGAS-STING-NLRP3 pathway constitutes the default inflammasome response during viral and bacterial infections in human myeloid cells. We conclude that targeting the cGAS-STING-LCD-NLRP3 pathway will ameliorate pathology in inflammatory conditions that are associated with cytosolic DNA sensing. PMID:29033128

Regulation of tumor necrosis factor gene expression by ionizing radiation in human myeloid leukemia cells and peripheral blood monocytes

International Nuclear Information System (INIS)

Sherman, M.L.; Datta, R.; Hallahan, D.E.; Weichselbaum, R.R.; Kufe, D.W.

1991-01-01

Previous studies have demonstrated that ionizing radiation induces the expression of certain cytokines, such as TNF alpha/cachectin. However, there is presently no available information regarding the molecular mechanisms responsible for the regulation of cytokine gene expression by ionizing radiation. In this report, we describe the regulation of the TNF gene by ionizing radiation in human myeloid leukemia cells. The increase in TNF transcripts by x rays was both time- and dose-dependent as determined by Northern blot analysis. Similar findings were obtained in human peripheral blood monocytes. Transcriptional run-on analyses have demonstrated that ionizing radiation stimulates the rate of TNF gene transcription. Furthermore, induction of TNF mRNA was increased in the absence of protein synthesis. In contrast, ionizing radiation had little effect on the half-life of TNF transcripts. These findings indicate that the increase in TNF mRNA observed after irradiation is regulated by transcriptional mechanisms and suggest that production of this cytokine by myeloid cells may play a role in the pathophysiologic effects of ionizing radiation

Preliminary results of MHD stability in HL-1 tokamak

International Nuclear Information System (INIS)

Zheng Yongzhen; Ma Tengcai; Xiao Zhenggui Cai Renfang

1987-01-01

In this paper, MHD activities of HL-1 tokamak plasma are studied with Fourier transform and correlatio analysis. The poloidal modes m = 1, 2, 3,4 and toroidal modes n of MHD magnetic fluctuation signals are detected. Methods for suppressing MHD instabilities are suggested and tested, after MHD instabilities are studied in HL-1. The effects of MHD characteristics in the beginning stage of discharge on the whole process of discharge are analyzed. The disruption, in HL-1 device could be divided into three kinds: internal disruption, minor disruption and major disruption. The result shows that HL-1 will have a better operation condition if internal disruption appears. In is end, the stable operation region of HL-1 tokamak is also given

Isolation of HL-60 cancer cells from the human serum sample using MnO2-PEI/Ni/Au/aptamer as a novel nanomotor and electrochemical determination of thereof by aptamer/gold nanoparticles-poly(3,4-ethylene dioxythiophene) modified GC electrode.

Science.gov (United States)

Amouzadeh Tabrizi, Mahmoud; Shamsipur, Mojtaba; Saber, Reza; Sarkar, Saeed

2018-07-01

Herein, aptamer-modified self-propelled nanomotors were used for transportation of human promyelocytic leukemia cells (HL-60) from a human serum sample. For this purpose, the fabricated manganese oxide nanosheets-polyethyleneimine decorated with nickel/gold nanoparticles (MnO 2 -PEI/Ni/Au) as nanomotors were added to a vial containing thiolated aptamer KH1C12 solution as a capture aptamer to attach to the gold nanoparticles on the surface of nanomotors covalently. The aptamer-modified self-propelled nanomotors (aptamer KH1C12 /nanomotors) were then separated by placing the vial in a magnetic stand. The aptamer-modified self-propelled nanomotors were rinsed three times with water to remove the non-attached aptamers. Then, the resulting aptamer KH1C12 /nanomotors were applied for the on-the-fly" transporting of HL-60 cancer cell from a human serum sample. To release of the captured HL-60 cancer cells, the complementary nucleotide sequences of KH1C12 aptamer solution (releasing aptamer) that has a with capture aptamer was added to phosphate buffer solution (1 M, pH 7.4) containing HL-60/aptamer KH1C12 /nanomotors. Because of the high affinity of capture aptamer to complementary nucleotide sequences of aptamer KH1C12 , the HL-60 cancer cells released on the surface of aptamer KH1C12 /nanomotors into the solution. The second goal of the present work was determining the concentration of HL-60 cancer cell in the human serum samples. The electrochemical impedance spectroscopy technique (EIS) was used for the determination of HL-60 cancer cell. The concentration of separated cancer cell was determined by aptamer/gold nanoparticles-poly(3,4-ethylene dioxythiophene) modified GC electrode (GC/PEDOT-Au nano /aptamer KH1C12 ). The proposed aptasensor exhibited a good response to the concentration of HL-60 cancer cells in the range of 2.5 × 10 1 to 5 × 10 5 cells mL -1 with a low limit of detection of 250 cells mL -1 . Copyright © 2018 Elsevier B.V. All rights reserved.

Uric acid disrupts hypochlorous acid production and the bactericidal activity of HL-60 cells.

Science.gov (United States)

Carvalho, Larissa A C; Lopes, João P P B; Kaihami, Gilberto H; Silva, Railmara P; Bruni-Cardoso, Alexandre; Baldini, Regina L; Meotti, Flavia C

2018-06-01

Uric acid is the end product of purine metabolism in humans and is an alternative physiological substrate for myeloperoxidase. Oxidation of uric acid by this enzyme generates uric acid free radical and urate hydroperoxide, a strong oxidant and potentially bactericide agent. In this study, we investigated whether the oxidation of uric acid and production of urate hydroperoxide would affect the killing activity of HL-60 cells differentiated into neutrophil-like cells (dHL-60) against a highly virulent strain (PA14) of the opportunistic pathogen Pseudomonas aeruginosa. While bacterial cell counts decrease due to dHL-60 killing, incubation with uric acid inhibits this activity, also decreasing the release of the inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF- α). In a myeloperoxidase/Cl - /H 2 O 2 cell-free system, uric acid inhibited the production of HOCl and bacterial killing. Fluorescence microscopy showed that uric acid also decreased the levels of HOCl produced by dHL-60 cells, while significantly increased superoxide production. Uric acid did not alter the overall oxidative status of dHL-60 cells as measured by the ratio of reduced (GSH) and oxidized (GSSG) glutathione. Our data show that uric acid impairs the killing activity of dHL-60 cells likely by competing with chloride by myeloperoxidase catalysis, decreasing HOCl production. Despite diminishing HOCl, uric acid probably stimulates the formation of other oxidants, maintaining the overall oxidative status of the cells. Altogether, our results demonstrated that HOCl is, indeed, the main relevant oxidant against bacteria and deviation of myeloperoxidase activity to produce other oxidants hampers dHL-60 killing activity. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Pharmacologic Targeting of Chromatin Modulators As Therapeutics of Acute Myeloid Leukemia

OpenAIRE

Rui Lu; Rui Lu; Gang Greg Wang; Gang Greg Wang

2017-01-01

Acute myeloid leukemia (AML), a common hematological cancer of myeloid lineage cells, generally exhibits poor prognosis in the clinic and demands new treatment options. Recently, direct sequencing of samples from human AMLs and pre-leukemic diseases has unveiled their mutational landscapes and significantly advanced the molecular understanding of AML pathogenesis. The newly identified recurrent mutations frequently “hit” genes encoding epigenetic modulators, a wide range of chromatin-modifyin...

Growth Factor-Activated Stem Cell Circuits and Stromal Signals Cooperatively Accelerate Non-Integrated iPSC Reprogramming of Human Myeloid Progenitors

Science.gov (United States)

Park, Tea Soon; Huo, Jeffrey S.; Peters, Ann; Talbot, C. Conover; Verma, Karan; Zimmerlin, Ludovic; Kaplan, Ian M.; Zambidis, Elias T.

2012-01-01

Nonviral conversion of skin or blood cells into clinically useful human induced pluripotent stem cells (hiPSC) occurs in only rare fractions (∼0.001%–0.5%) of donor cells transfected with non-integrating reprogramming factors. Pluripotency induction of developmentally immature stem-progenitors is generally more efficient than differentiated somatic cell targets. However, the nature of augmented progenitor reprogramming remains obscure, and its potential has not been fully explored for improving the extremely slow pace of non-integrated reprogramming. Here, we report highly optimized four-factor reprogramming of lineage-committed cord blood (CB) myeloid progenitors with bulk efficiencies of ∼50% in purified episome-expressing cells. Lineage-committed CD33+CD45+CD34− myeloid cells and not primitive hematopoietic stem-progenitors were the main targets of a rapid and nearly complete non-integrated reprogramming. The efficient conversion of mature myeloid populations into NANOG+TRA-1-81+ hiPSC was mediated by synergies between hematopoietic growth factor (GF), stromal activation signals, and episomal Yamanaka factor expression. Using a modular bioinformatics approach, we demonstrated that efficient myeloid reprogramming correlated not to increased proliferation or endogenous Core factor expressions, but to poised expression of GF-activated transcriptional circuits that commonly regulate plasticity in both hematopoietic progenitors and embryonic stem cells (ESC). Factor-driven conversion of myeloid progenitors to a high-fidelity pluripotent state was further accelerated by soluble and contact-dependent stromal signals that included an implied and unexpected role for Toll receptor-NFκB signaling. These data provide a paradigm for understanding the augmented reprogramming capacity of somatic progenitors, and reveal that efficient induced pluripotency in other cell types may also require extrinsic activation of a molecular framework that commonly regulates self

Expression of human kinase suppressor of Ras 2 (hKSR-2) gene in HL60 leukemia cells is directly upregulated by 1,25-dihydroxyvitamin D3 and is required for optimal cell differentiation

International Nuclear Information System (INIS)

Wang Xuening; Wang, T.-T.; White, John H.; Studzinski, George P.

2007-01-01

Induction of terminal differentiation of neoplastic cells offers potential for a novel approach to cancer therapy. One of the agents being investigated for this purpose in preclinical studies is 1,25-dihydroxyvitamin D 3 (1,25D), which can convert myeloid leukemia cells into normal monocyte-like cells, but the molecular mechanisms underlying this process are not fully understood. Here, we report that 1,25D upregulates the expression of hKSR-2, a new member of a small family of proteins that exhibit evolutionarily conserved function of potentiating ras signaling. The upregulation of hKSR-2 is direct, as it occurs in the presence of cycloheximide, and occurs primarily at the transcriptional level, via activation of vitamin D receptor, which acts as a ligand-activated transcription factor. Two VDRE-type motifs identified in the hKSR-2 gene bind VDR-RXR alpha heterodimers present in nuclear extracts of 1,25D-treated HL60 cells, and chromatin immunoprecipitation assays show that these VDRE motifs bind VDR in 1,25D-dependent manner in intact cells, coincident with the recruitment of RNA polymerase II to these motifs. Treatment of the cells with siRNA to hKSR-2 reduced the proportion of the most highly differentiated cells in 1,25D-treated cultures. These results demonstrate that hKSR-2 is a direct target of 1,25D in HL60 cells, and is required for optimal monocytic differentiation

Physics design of the HL-2A tokamak

International Nuclear Information System (INIS)

Gao Qingdi; Li Fangzhu; Zhang Jinhua; Pan Yudong; Jiao Yiming

2005-10-01

An overview report for the physics design of the HL-2A tokamak is presented. By numerically analyzing the plasma shaping and the vertical instability due to plasma elongation, the requirements for the currents of poloidal magnetic field coils and the control system are put forward. Controlling the plasma profile by using NBI (neutral beam injection) and LHCD (lower hybrid current drive) is investigated, and the high performance modes of operation in HL-2A and modeled and designed. The magnetohydrodynamic instabilities in improved confinement configuration (RS configuration) are studied so as to point out the way of plasma control to perform stationary high performance discharges in HL-2A. In order to offer data for updating the HL-2A divertor, performances of the divertor plasma are simulated. (authors)

Radiation response of haematopoietic cell lines of human origin

International Nuclear Information System (INIS)

Lehnert, S.; Rybka, W.B.; Suissa, S.; Giambattisto, D.

1986-01-01

Six human haematopoietic cell lines, five of leukaemic origin, including cells with myeloid, lymphoid and undifferentiated phenotype have been studied with respect to radiation response. The intrinsic radio-sensitivity of the cells varied widely, the D 0 s ranging from 0.53 to 1.39 Gy. Five of the cell lines showed some capacity to accumulate sublethal damage; in three of these, enhanced survival was demonstrated in split-dose experiments. One cell line (HL-60) was anomalous in that although little accumulation of sublethal damage was demonstrable, survival was enhanced by fractionation of the dose. Five of the six cell lines studied were of leukaemic origin. The results support the belief that, in contrast to the almost constant radiosensitivity of normal haematopoietic cell progenitors, leukaemic cell progenitors may show a wide range of radiosensitivities. (author)

Cytotoxic effect of betulinic acid and betulinic acid acetate isolated ...

African Journals Online (AJOL)

Cytotoxic effect of betulinic acid and betulinic acid acetate isolated from Melaleuca cajuput on human myeloid leukemia (HL-60) cell line. ... The cytotoxic effect of betulinic acid (BA), isolated from Melaleuca cajuput a Malaysian plant and its four synthetic derivatives were tested for their cytotoxicity in various cell line or ...

HL-LHC updates in Japan

CERN Multimedia

Antonella Del Rosso

2014-01-01

At a recent meeting in Japan, updates on the High Luminosity LHC (HL-LHC) project were presented, including the progress made so far and the deadlines still to be met for the upgraded machine to be operational from 2020.   New magnets made with advanced superconductor Nb3Sn in the framework of the HL-LHC project. These magnets are currently under construction at CERN by the TE-MSC group. The LHC is the world’s most powerful particle accelerator, and in 2015 it will reach yet another new record for the energy of its colliding beams. One key factor of its discovery potential is its ability to produce collisions described in mathematical terms by the parameter known as “luminosity”. In 2025, the HL-LHC project will allow the total number of collisions in the LHC to increase by a factor of 10. The first step in this rich upgrade programme is the delivery of the Preliminary Design Report (PDR), which is also a key milestone of the HiLumi LHC Design Study partly fund...

Hoxa9 and Hoxa10 induce CML myeloid blast crisis development through activation of Myb expression.

Science.gov (United States)

Negi, Vijay; Vishwakarma, Bandana A; Chu, Su; Oakley, Kevin; Han, Yufen; Bhatia, Ravi; Du, Yang

2017-11-17

Mechanisms underlying the progression of Chronic Myeloid Leukemia (CML) from chronic phase to myeloid blast crisis are poorly understood. Our previous studies have suggested that overexpression of SETBP1 can drive this progression by conferring unlimited self-renewal capability to granulocyte macrophage progenitors (GMPs). Here we show that overexpression of Hoxa9 or Hoxa10 , both transcriptional targets of Setbp1 , is also sufficient to induce self-renewal of primary myeloid progenitors, causing their immortalization in culture. More importantly, both are able to cooperate with BCR/ABL to consistently induce transformation of mouse GMPs and development of aggressive leukemias resembling CML myeloid blast crisis, suggesting that either gene can drive CML progression by promoting the self-renewal of GMPs. We further identify Myb as a common critical target for Hoxa9 and Hoxa10 in inducing self-renewal of myeloid progenitors as Myb knockdown significantly reduced colony-forming potential of myeloid progenitors immortalized by the expression of either gene. Interestingly, Myb is also capable of immortalizing primary myeloid progenitors in culture and cooperating with BCR/ABL to induce leukemic transformation of mouse GMPs. Significantly increased levels of MYB transcript also were detected in all human CML blast crisis samples examined over chronic phase samples, further suggesting the possibility that MYB overexpression may play a prevalent role in driving human CML myeloid blast crisis development. In summary, our results identify overexpression of HOXA9 , HOXA10 , and MYB as critical drivers of CML progression, and suggest MYB as a key therapeutic target for inhibiting the self-renewal of leukemia-initiating cells in CML myeloid blast crisis patients.

Up-Regulation of P21 Inhibits TRAIL-Mediated Extrinsic Apoptosis, Contributing Resistance to SAHA in Acute Myeloid Leukemia Cells

Directory of Open Access Journals (Sweden)

Xing Wu

2014-08-01

Full Text Available Background/Aim: P21, a multifunctional cell cycle-regulatory molecule, regulates apoptotic cell death. In this study we examined the effect of altered p21 expression on the sensitivity of acute myeloid leukemia cells in response to HDAC inhibitor SAHA treatment and investigated the underlying mechanism. Methods: Stably transfected HL60 cell lines were established in RPMI-1640 with supplementation of G-418. Cell viability was measured by MTT assay. Western blot was applied to assess the protein expression levels of target genes. Cell apoptosis was monitored by AnnexinV-PE/7AAD assay. Results: We showed HL60 cells that that didn't up-regulate p21 expression were more sensitive to SAHA-mediated apoptosis than NB4 and U937 cells that had increased p21 level. Enforced expression of p21 in HL60 cells reduced sensitivity to SAHA and blocked TRAIL-mediated apoptosis. Conversely, p21 silencing in NB4 cells enhanced SAHA-mediated apoptosis and lethality. Finally, we found that combined treatment with SAHA and rapamycin down-regulated p21 and enhanced apoptosis in AML cells. Conclusion: We conclude that up-regulated p21 expression mediates resistance to SAHA via inhibition of TRAIL apoptotic pathway. P21 may serve as a candidate biomarker to predict responsiveness or resistance to SAHA-based therapy in AML patients. In addition, rapamycin may be an effective agent to override p21-mediated resistance to SAHA in AML patients.

How Is Chronic Myeloid Leukemia Diagnosed?

Science.gov (United States)

... Myeloid Leukemia? More In Chronic Myeloid Leukemia About Chronic Myeloid Leukemia Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treatment After Treatment Back To Top Imagine a world ...

Social Cost Benefit Analysis of HL-LHC

CERN Document Server

Bastianin, Andrea

2018-01-01

We present a Social Cost–Benefit Analysis (CBA) of the High Luminosity upgrade of the Large Hadron Collider (HL-LHC), assessing its economic costs and benefits up to 2038. The Net Present Value (NPV) of the HL-LHC project is positive at the end of the observation period. The ratio between incremental benefits and incremental costs of the HL-LHC with respect to continue operating the LHC under normal consolidation (i.e. without high-luminosity upgrade) is slightly over 1.7, meaning that each Swiss Franc invested in the HL-LHC upgrade project pays back approximately 1.7 CHF in societal benefits. Simulations based on 50000 Monte Carlo rounds show that there is a 94% chance to observe a positive NPV (i.e. a quantifiable economic benefit for the society). The attractiveness of CERN for Early Stage Researchers (ESR) is key for a positive CBA result. Given that benefits to ESRs are the single most important societal benefit, CERN should invest more in activities facilitating the transition to the international job...

Dimethyl sulfoxide potentiates death receptor-mediated apoptosis in the human myeloid leukemia U937 cell line through enhancement of mitochondrial membrane depolarization

Czech Academy of Sciences Publication Activity Database

Vondráček, Jan; Souček, Karel; Sheard, M. A.; Chramostová, Kateřina; Andrysík, Zdeněk; Hofmanová, Jiřina; Kozubík, Alois

2006-01-01

Roč. 30, č. 1 (2006), s. 81-89 ISSN 0145-2126 R&D Projects: GA ČR(CZ) GA524/03/0766 Institutional research plan: CEZ:AV0Z50040507 Keywords : human myeloid leukemia * DMSO * apoptosis Subject RIV: BO - Biophysics Impact factor: 2.483, year: 2006

Kaempferol induces DNA damage and inhibits DNA repair associated protein expressions in human promyelocytic leukemia HL-60 cells.

Science.gov (United States)

Wu, Lung-Yuan; Lu, Hsu-Feng; Chou, Yu-Cheng; Shih, Yung-Luen; Bau, Da-Tian; Chen, Jaw-Chyun; Hsu, Shu-Chun; Chung, Jing-Gung

2015-01-01

Numerous evidences have shown that plant flavonoids (naturally occurring substances) have been reported to have chemopreventive activities and protect against experimental carcinogenesis. Kaempferol, one of the flavonoids, is widely distributed in fruits and vegetables, and may have cancer chemopreventive properties. However, the precise underlying mechanism regarding induced DNA damage and suppressed DNA repair system are poorly understood. In this study, we investigated whether kaempferol induced DNA damage and affected DNA repair associated protein expression in human leukemia HL-60 cells in vitro. Percentages of viable cells were measured via a flow cytometry assay. DNA damage was examined by Comet assay and DAPI staining. DNA fragmentation (ladder) was examined by DNA gel electrophoresis. The changes of protein levels associated with DNA repair were examined by Western blotting. Results showed that kaempferol dose-dependently decreased the viable cells. Comet assay indicated that kaempferol induced DNA damage (Comet tail) in a dose-dependent manner and DAPI staining also showed increased doses of kaempferol which led to increased DNA condensation, these effects are all of dose-dependent manners. Western blotting indicated that kaempferol-decreased protein expression associated with DNA repair system, such as phosphate-ataxia-telangiectasia mutated (p-ATM), phosphate-ataxia-telangiectasia and Rad3-related (p-ATR), 14-3-3 proteins sigma (14-3-3σ), DNA-dependent serine/threonine protein kinase (DNA-PK), O(6)-methylguanine-DNA methyltransferase (MGMT), p53 and MDC1 protein expressions, but increased the protein expression of p-p53 and p-H2AX. Protein translocation was examined by confocal laser microscopy, and we found that kaempferol increased the levels of p-H2AX and p-p53 in HL-60 cells. Taken together, in the present study, we found that kaempferol induced DNA damage and suppressed DNA repair and inhibited DNA repair associated protein expression in HL-60

38 CFR 41.525 - Criteria for Federal program risk.

Science.gov (United States)

2010-07-01

... control structures may have higher risk. When assessing risk in a large single audit, the auditor shall... also indicate risk. (2) Prior audit findings would indicate higher risk, particularly when the... program risk. 41.525 Section 41.525 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS...

Development and in vitro evaluations of new decitabine nanocarriers for the treatment of acute myeloid leukemia

Directory of Open Access Journals (Sweden)

Briot T

2017-11-01

Full Text Available Thomas Briot,1,2 Emilie Roger,1 Nolwenn Lautram,1 Alexis Verger,1 Anne Clavreul,3,4 Frederic Lagarce1,2 1Micro & Nanomédecines Translationelles – MINT, UNIV Angers, INSERM 1066, CNRS 6021, Université Bretagne Loire, MINT IBS-CHU, 2Pharmacy Department, University Hospital of Angers, 3Neurosurgery Department, University Hospital of Angers, 4CRCINA, INSERM, Université de Nantes, Université d’Angers, Angers, France Abstract: Decitabine is a hydrophilic drug that acts by hypomethylating DNA. Decitabine is used in Europe for the treatment of acute myeloid leukemia (AML in patients aged ≥65 years. However, it can only be administered intravenously due to very low oral bioavailability and a large distribution volume. Oral administration would allow outpatient treatment, improving quality of life and reducing treatment costs. The present study proposes to develop lipid nanocapsules (LNCs, originally designed for lipophilic drugs, to encapsulate decitabine. Two different formulations of LNCs were designed: LNCs based on a high proportion of Transcutol® HP (THP-LNCs and LNCs associated with a mixture of Transcutol® HP and Tween® 80 (THP-T80-LNCs. The second formulation had a diameter of 26.5±0.5 nm, high encapsulation efficiency (>85%, and a drug payload of 472±64 µg/mL. Decitabine-loaded THP-T80-LNC cytotoxicity was evaluated on two AML cell lines depending on their decitabine resistance: HEL (not resistant and HL-60 (resistant. The permeability of decitabine-loaded THP-T80-LNCs was also evaluated on Caco-2 cell monolayers. Decitabine cytotoxicity against HEL and HL-60 was higher when decitabine was loaded in THP-T80-LNCs than when free. Apparent permeability on Caco-2 cell monolayers was also increased, suggesting a potentially useful formulation to increase the oral bioavailability of decitabine. Keywords: lipid nanocapsules, acute myeloid leukemia, decitabine, nanomedicine, nanoparticles, oral administration, Caco2 cells

Induction of apoptosis by Citrus paradisi essential oil in human leukemic (HL-60) cells.

Science.gov (United States)

Hata, Tomona; Sakaguchi, Ikuyo; Mori, Masahiro; Ikeda, Norikazu; Kato, Yoshiko; Minamino, Miki; Watabe, Kazuhito

2003-01-01

Limonene is a primary component of citrus essential oils (EOs) and has been reported to induce apoptosis on tumor cells. Little is known about induction of apoptosis by citrus EOs. In this study, we examined induction of apoptosis by Citrus aurantium var. dulcis (sweet orange) EO, Citrus paradisi (grapefruit) EO and Citrus limon (lemon) EO. These EOs induced apoptosis in HL-60 cells and the apoptosis activities were related to the limonene content of the EOs. Moreover, sweet orange EO and grapefruit EO may contain components besides limonene that have apoptotic activity. To identify the components with apoptotic activity, grapefruit EO was fractionated using silica gel columns, and the components were analyzed by GC-MS. The n-hexane fraction contained limonene, and the dichloromethane fraction (DF) contained aldehyde compounds and nootkatone. Decanal, octanal and citral in the DF showed strong apoptotic activity, suggesting that the aldehyde compounds induced apoptosis strongly in HL-60 cells.

46 CFR 108.525 - Survival craft number and arrangement.

Science.gov (United States)

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Survival craft number and arrangement. 108.525 Section... UNITS DESIGN AND EQUIPMENT Lifesaving Equipment § 108.525 Survival craft number and arrangement. (a... arrangement of survival craft: (1) Lifeboats with an aggregate capacity to accommodate the total number of...

Relationship Between Structure and Antiproliferative Activity of Novel 5-amino-4-cyanopyrazole-1-formaldehydehydrazono Derivatives on HL-60RG Human Leukemia Cells.

Science.gov (United States)

Nagahara, Yukitoshi; Nagahara, Katsuhiko

2017-11-01

Pyrazole derivatives have been reported to have potent antimicrobial and anticancer activity. We recently synthesized and determined the effects of analogs, benzamidoxime derivatives, on mammalian cells and discovered that benzamidoximes had an antiproliferative effect. Here we synthesized and determined the anticancer effects of hydrazonopyrazole derivatives on a mammalian cancer cell line. We synthesized 12 hydrazonopyrazole derivatives with several constant alkyl chain length or branched chains at the side chain to investigate their anticancer cell activity, using the human myelogenous leukemia cell line HL-60RG. Among all hydrazonopyrazole derivatives we synthesized, the hydrazonopyrazole derivative with a branched chain at the side chain rather than a constant alkyl chain significantly inhibited cell viability. The strongest hydrazonopyrazole derivative, 5-amino-4-cyanopyrazole-1-formaldehydehydrazono-3'-pentanal, tended to damage cells dose-dependently. This cell growth attenuation was a result of apoptosis, activating caspase-3 and fragmented DNA. Hydrazonopyrazole derivatives induced apoptosis of HL-60RG leukemia cells. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Vav promotes differentiation of human tumoral myeloid precursors

International Nuclear Information System (INIS)

Bertagnolo, Valeria; Brugnoli, Federica; Mischiati, Carlo; Sereni, Alessia; Bavelloni, Alberto; Carini, Cinzia; Capitani, Silvano

2005-01-01

Vav is one of the genetic markers that correlate with the differentiation of hematopoietic cells. In T and B cells, it appears crucial for both development and functions, while, in non-lymphoid hematopoietic cells, Vav seems not involved in cell maturation, but rather in the response of mature cells to agonist-dependent proliferation and phagocytosis. We have previously demonstrated that the amount and the tyrosine phosphorylation of Vav are up-regulated in both whole cells and nuclei of tumoral promyelocytes induced to granulocytic maturation by ATRA and that tyrosine-phosphorylated Vav does not display any ATRA-induced GEF activity but contributes to the regulation of PI 3-K activity. In this study, we report that Vav accumulates in nuclei of ATRA-treated APL-derived cells and that the down-modulation of Vav prevents differentiation of tumoral promyelocytes, indicating that it is a key molecule in ATRA-dependent myeloid maturation. On the other hand, the overexpression of Vav induces an increased expression of surface markers of granulocytic differentiation without affecting the maturation-related changes of the nuclear morphology. Consistent with an effect of Vav on the transcriptional machinery, array profiling shows that the inhibition of the Syk-dependent tyrosine phosphorylation of Vav reduces the number of ATRA-induced genes. Our data support the unprecedented notion that Vav plays crucial functions in the maturation process of myeloid cells, and suggest that Vav can be regarded as a potential target for the therapeutic treatment of myeloproliferative disorders

Altered binding of human histone gene transcription factors during the shutdown of proliferation and onset of differentiation in HL-60 cells

International Nuclear Information System (INIS)

Stein, G.; Lian, J.; Stein, J.; Shalhoub, V.; Wright, K.; Pauli, U.; Van Wijnen, A.; Briggs, R.

1989-01-01

Two sites of protein-DNA interaction have been identified in vivo and in vitro in the proximal promoter regions of an H4 and an H3 human histone gene. In proliferating cells, these genes are transcribed throughout the cell cycle, and both the more distal site I and the proximal site II are occupied by promoter-binding factors. In this report the authors demonstrate that during the shutdown of proliferation and onset of differentiation of the human promyelocytic leukemia cell line HL-60 into cells that exhibit phenotypic properties of monocytes, histone gene expression is down-regulated at the level of transcription. In vivo occupancy of site I by promoter factors persists in the differentiated HL-60 cells, but protein-DNA interactions at site II are selectively lost. Furthermore, in vitro binding activity of the site II promoter factor HiNF-D is lost in differentiated cells, and nuclear extracts from differentiated cells do not support in vitro transcription of these histone genes. The results suggest that the interaction of HiNF-D with proximal promoter site II sequences plays a primary role in rendering cell growth-regulated histone genes transcribable in proliferating cells. It appears that while cell-cycle control of histone gene expression is mediated by both transcription and mRNA stability, with the shutdown of proliferation and onset of differentiation, histone gene expression is regulated at the transcriptional level

Vorinostat in Treating Patients With Acute Myeloid Leukemia

Science.gov (United States)

2014-04-30

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

Optics Measurements and Correction Challenges for the HL-LHC

CERN Document Server

Carlier, Felix Simon; Fartoukh, Stephane; Fol, Elena; Gamba, Davide; Garcia-Tabares Valdivieso, Ana; Giovannozzi, Massimo; Hofer, Michael; Langner, Andy Sven; Maclean, Ewen Hamish; Malina, Lukas; Medina Medrano, Luis Eduardo; Persson, Tobias Hakan Bjorn; Skowronski, Piotr Krzysztof; Tomas Garcia, Rogelio; Van Der Veken, Frederik; Wegscheider, Andreas

2017-01-01

Optics control in the HL-LHC will be challenged by a very small β* of 15 cm in the two main experiments. HL-LHC physics fills will keep a constant luminosity during several hours via β* leveling. This will require the commissioning of a large number of optical configurations, further challenging the efficiency of the optics measurements and correction tools. We report on the achieved level of optics control in the LHC with simulations and extrapolations for the HL-LHC.

Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia.

Directory of Open Access Journals (Sweden)

Carolyn Glass

Full Text Available The ecotropic virus integration site 1 (EVI1 transcription factor is associated with human myeloid malignancy of poor prognosis and is overexpressed in 8-10% of adult AML and strikingly up to 27% of pediatric MLL-rearranged leukemias. For the first time, we report comprehensive genomewide EVI1 binding and whole transcriptome gene deregulation in leukemic cells using a combination of ChIP-Seq and RNA-Seq expression profiling. We found disruption of terminal myeloid differentiation and cell cycle regulation to be prominent in EVI-induced leukemogenesis. Specifically, we identified EVI1 directly binds to and downregulates the master myeloid differentiation gene Cebpe and several of its downstream gene targets critical for terminal myeloid differentiation. We also found EVI1 binds to and downregulates Serpinb2 as well as numerous genes involved in the Jak-Stat signaling pathway. Finally, we identified decreased expression of several ATP-dependent P2X purinoreceptors genes involved in apoptosis mechanisms. These findings provide a foundation for future study of potential therapeutic gene targets for EVI1-induced leukemia.

Influence of DNA-methylation on zinc homeostasis in myeloid cells: Regulation of zinc transporters and zinc binding proteins.

Science.gov (United States)

Kessels, Jana Elena; Wessels, Inga; Haase, Hajo; Rink, Lothar; Uciechowski, Peter

2016-09-01

The distribution of intracellular zinc, predominantly regulated through zinc transporters and zinc binding proteins, is required to support an efficient immune response. Epigenetic mechanisms such as DNA methylation are involved in the expression of these genes. In demethylation experiments using 5-Aza-2'-deoxycytidine (AZA) increased intracellular (after 24 and 48h) and total cellular zinc levels (after 48h) were observed in the myeloid cell line HL-60. To uncover the mechanisms that cause the disturbed zinc homeostasis after DNA demethylation, the expression of human zinc transporters and zinc binding proteins were investigated. Real time PCR analyses of 14 ZIP (solute-linked carrier (SLC) SLC39A; Zrt/IRT-like protein), and 9 ZnT (SLC30A) zinc transporters revealed significantly enhanced mRNA expression of the zinc importer ZIP1 after AZA treatment. Because ZIP1 protein was also enhanced after AZA treatment, ZIP1 up-regulation might be the mediator of enhanced intracellular zinc levels. The mRNA expression of ZIP14 was decreased, whereas zinc exporter ZnT3 mRNA was also significantly increased; which might be a cellular reaction to compensate elevated zinc levels. An enhanced but not significant chromatin accessibility of ZIP1 promoter region I was detected by chromatin accessibility by real-time PCR (CHART) assays after demethylation. Additionally, DNA demethylation resulted in increased mRNA accumulation of zinc binding proteins metallothionein (MT) and S100A8/S100A9 after 48h. MT mRNA was significantly enhanced after 24h of AZA treatment also suggesting a reaction of the cell to restore zinc homeostasis. These data indicate that DNA methylation is an important epigenetic mechanism affecting zinc binding proteins and transporters, and, therefore, regulating zinc homeostasis in myeloid cells. Copyright © 2016 Elsevier GmbH. All rights reserved.

Fast crab cavity failures in HL-LHC

CERN Document Server

Yee-Rendon, B; Calaga, R; Tomas, R; Zimmermann, F; Barranco, J

2014-01-01

Crab cavities (CCs) are a key ingredient of the High-Luminosity Large Hadron Collider (HL-LHC) to ensure head on collisions at the main experiments (ATLAS and CMS) and fully profit from the smaller provided by the ATS optics [1]. At KEKB, CCs have exhibited abrupt changes of phase and voltage during a time period of few LHC turns and considering the large energy stored in the HL-LHC beam, CC failures represent a serious risk to the LHC machine protection. In this paper, we discuss the effect of CC voltage or phase changes on a time interval similar to, or longer than, the one needed to dump the beam. The simulations assume a realistic steady-state distribution to assess the beam losses for the HL-LHC. Additionally, some strategies are studied in order to reduce the damage caused by the CC failures.

Cytomegalovirus immune evasion of myeloid lineage cells.

Science.gov (United States)

Brinkmann, Melanie M; Dağ, Franziska; Hengel, Hartmut; Messerle, Martin; Kalinke, Ulrich; Čičin-Šain, Luka

2015-06-01

Cytomegalovirus (CMV) evades the immune system in many different ways, allowing the virus to grow and its progeny to spread in the face of an adverse environment. Mounting evidence about the antiviral role of myeloid immune cells has prompted the research of CMV immune evasion mechanisms targeting these cells. Several cells of the myeloid lineage, such as monocytes, dendritic cells and macrophages, play a role in viral control, but are also permissive for CMV and are naturally infected by it. Therefore, CMV evasion of myeloid cells involves mechanisms that qualitatively differ from the evasion of non-CMV-permissive immune cells of the lymphoid lineage. The evasion of myeloid cells includes effects in cis, where the virus modulates the immune signaling pathways within the infected myeloid cell, and those in trans, where the virus affects somatic cells targeted by cytokines released from myeloid cells. This review presents an overview of CMV strategies to modulate and evade the antiviral activity of myeloid cells in cis and in trans.

Identification of chimpanzee leukocyte antigens (ChL-A) and their relation to HL-A

NARCIS (Netherlands)

Balner, H.

1971-01-01

The identification of a number of leukocyte antigens of chimpanzees is described. Suggestive evidence was obtained that some of the isoantisera recognize specificities of a hypothetical genetic system of chimpanzee antigens which, in analogy with the human HL-A system, is tentatively called ChL-A.

JS-K, a nitric oxide prodrug, induces cytochrome c release and caspase activation in HL-60 myeloid leukemia cells.

Science.gov (United States)

Udupi, Vidya; Yu, Margaret; Malaviya, Swati; Saavedra, Joseph E; Shami, Paul J

2006-10-01

Nitric oxide (NO) induces differentiation and apoptosis in acute myelogenous leukemia (AML) cells. The NO prodrug O2-(2,4-dinitrophenyl)1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate, or JS-K, has potent antileukemic activity. JS-K induces apoptosis in HL-60 cells by a caspase-dependent mechanism. The purpose of this study was to determine the pathway through which JS-K induces apoptosis. We show that JS-K alters mitochondrial membrane potential (DeltaPsim) and induces cytochrome c release from mitochondria into the cytoplasm. Treatment with JS-K resulted in activation of Caspase (Casp) 9, Casp 3 and Casp 8. JS-K constitutes a promising lead for a new class of anti-leukemic agents.

T315 Decreases Acute Myeloid Leukemia Cell Viability through a Combination of Apoptosis Induction and Autophagic Cell Death

Directory of Open Access Journals (Sweden)

Chang-Fang Chiu

2016-08-01

Full Text Available T315, an integrin-linked kinase (ILK inhibitor, has been shown to suppress the proliferation of breast cancer, stomach cancer and chronic lymphocytic leukemia cells. Here we demonstrate that T315 decreases cell viability of acute myeloid leukemia (AML cell lines (HL-60 and THP-1 and primary leukemia cells from AML patients in a dose-responsive manner. Normal human bone marrow cells are less sensitive than leukemia cells to T315. T315 down regulates protein kinase B (Akt and p-Akt and induces caspase activation, poly-ADP-ribose polymerase (PARP cleavage, apoptosis and autophagy through an ILK-independent manner. Interestingly, pretreatment with autophagy inhibitors rescues cells from apoptosis and concomitant PARP cleavage, which implicates a key role of autophagic cell death in T315-mediated cytotoxicity. T315 also demonstrates efficacy in vivo, suppressing the growth of THP-1 xenograft tumors in athymic nude mice when administered intraperitoneally. This study shows that autophagic cell death and apoptosis cooperatively contribute to the anticancer activity of T315 in AML cells. In conclusion, the complementary roles of apoptotic and autophagic cell death should be considered in the future assessment of the translational value of T315 in AML therapy.

29 CFR 525.24 - Advisory Committee on Special Minimum Wages.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Advisory Committee on Special Minimum Wages. 525.24 Section 525.24 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR... Special Minimum Wages. The Advisory Committee on Special Minimum Wages, the members of which are appointed...

Acute myeloid leukemia (AML) - children

Science.gov (United States)

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

Immunomodulatory effects of testosterone evaluated in all-trans retinoic acid differentiated HL-60 cells, granulocytes, and monocytes

DEFF Research Database (Denmark)

Boje, Alex; Moesby, Lise; Timm, Michael

2012-01-01

The sex hormones are known to affect innate immunity in humans. In this study we evaluated the immunomodulatory effects of testosterone in a model system comprising of all-trans retinoic acid differentiated HL-60 cells, and confirmed the results in human granulocytes and monocytes. Results showed...... that testosterone at pharmacological doses reduced the production of interleukin-8 and reactive oxygen species from differentiated HL-60 cells in a concentration dependent manner without affecting phagocytosis. The cells were stimulated with zymosan, lipopolysaccharide, or Bacillus subtilis. At the highest...... concentration of testosterone (120 µM), interleukin-8 secretion was reduced 42-80%, and production of reactive oxygen species was reduced 32-46%. Flutamide, an antagonist of the classical intracellular androgen receptor, was unable to antagonize the immunosuppressive effect of testosterone. We further...

7 CFR 1944.525 - Targeting of TSA funds to States.

Science.gov (United States)

2010-01-01

... 7 Agriculture 13 2010-01-01 2009-01-01 true Targeting of TSA funds to States. 1944.525 Section... § 1944.525 Targeting of TSA funds to States. (a) The Administrator will determine, based on the most... portion of the available funds for TSA to these States, leaving the balance available for national...

Spontaneous release of soluble HL-A antigens from platelets during conservation.

Science.gov (United States)

Dautigny, A; Bernier, I; Colombani, J; Jollès, P

1975-01-01

Experiments with the aim of studying the solubilisation of HL-A antigens from blood platelets by methods which do not involve any biologically active processes (moderate, discontinuous agitation of a low concentration of platelets suspended in a saline medium, in the presence of an antiseptic; supernatants collected at frequent intervals) have shown that platelets release membrane proteins, including HL-A antigens, spontaneously. Optimal conditions for the treatment of membrane proteins have been perfected. The great stability of HL-A antigens under these conditions permits prolonged treatment. The products extracted are soluble and extremely complex. The molecular weight of the HL-A antigens is between 40,000 and 70,000.

Utilization of the human cell line HL-60 for chemiluminescence based detection of microorganisms and related substances

DEFF Research Database (Denmark)

Timm, Michael; Hansen, Erik W; Moesby, Lise

2006-01-01

species (ROS) when challenged with pyrogenic substances. In a luminol enhanced chemilumimetric assay the responsiveness of differentiated HL-60 cells is tested towards Salmonella typhimurium, Bacillus subtilis, Saccharomyces cerevisiae, Candida albicans, lipopolysaccharide (LPS) and lipoteichoic acid (LTA......). The results show a poor sensitivity to S. typhimurium but displays good sensitivity towards B. subtilis, LTA and LPS. Furthermore, the sensitivity towards the yeasts C. albicans and S. cerevisiae is considerably better than obtained in other in vitro cell systems. Overall these results indicate that the HL-60...... cell assay possibly could be evolved to a supplementary assay for the known pyrogenic detection assays. Furthermore, the utilization of the assay for pyrogenic examination of recombinant drugs derived from yeast expression systems would be relevant to examine....

Comparative evaluation of the cytotoxicity of 5.25% sodium hypochlorite, 2% chlorhexidine and mixture of a tetracycline isomer, an acid and a detergent on human red blood corpuscles: An in-vitro study

Directory of Open Access Journals (Sweden)

Krishna Prasad Shetty

2014-01-01

Full Text Available Aim: The aim of this study was to analyze the cytotoxicity of various volumes of 5.25% of sodium hypochlorite, 2% of chlorhexidine gluconate and mixture of a tetracycline isomer, an acid and a detergent (MTAD by checking for hemolysis of human red blood corpuscles. Materials and Methods: A total volume of 100 μl of diluted red blood corpuscles obtained through centrifugation was added to three irrigating solutions (5.25% of sodium hypochlorite, 2% of chlorhexidine and MTAD of six test tubes each. Individual irrigants per group were added in increasing volume starting from the second test tube keeping the first one as the control. After incubation for 3 min hemoglobin content was measured using an automated hemoanalyzer data was analyzed using one sample t-test. Results: Sodium hypochlorite is the most cytotoxic solution followed by MTAD and chlorhexidine. Conclusions: This study suggests that the three irrigating solutions do cause detrimental effects on the diluted red blood corpuscles. A great deal of care should therefore be exercised when using 5.25% sodium hypochlorite during endodontic irrigation.

Compound K, a metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells

International Nuclear Information System (INIS)

Cho, Sung-Hee; Chung, Kyung-Sook; Choi, Jung-Hye; Kim, Dong-Hyun; Lee, Kyung-Tae

2009-01-01

Compound K [20-O-β-(D-glucopyranosyl)-20(S)-protopanaxadiol], a metabolite of the protopanaxadiol-type saponins of Panax ginseng C.A. Meyer, has been reported to possess anti-tumor properties to inhibit angiogenesis and to induce tumor apoptosis. In the present study, we investigated the effect of Compound K on apoptosis and explored the underlying mechanisms involved in HL-60 human leukemia cells. We examined the effect of Compound K on the viabilities of various cancer cell lines using MTT assays. DAPI assay, Annexin V and PI double staining, Western blot assay and immunoprecipitation were used to determine the effect of Compound K on the induction of apoptosis. Compound K was found to inhibit the viability of HL-60 cells in a dose- and time-dependent manner with an IC 50 of 14 μM. Moreover, this cell death had typical features of apoptosis, that is, DNA fragmentation, DNA ladder formation, and the externalization of Annexin V targeted phosphatidylserine residues in HL-60 cells. In addition, compound-K induced a series of intracellular events associated with both the mitochondrial- and death receptor-dependent apoptotic pathways, namely, (1) the activation of caspases-3, -8, and -9; (2) the loss of mitochondrial membrane potential; (3) the release of cytochrome c and Smac/DIABLO to the cytosol; (4) the translocation of Bid and Bax to mitochondria; and (5) the downregulations of Bcl-2 and Bcl-xL. Furthermore, a caspase-8 inhibitor completely abolished caspase-3 activation, Bid cleavage, and subsequent DNA fragmentation by Compound K. Interestingly, the activation of caspase-3 and -8 and DNA fragmentation were significantly prevented in the presence of cycloheximide, suggesting that Compound K-induced apoptosis is dependent on de novo protein synthesis. The results indicate that caspase-8 plays a key role in Compound K-stimulated apoptosis via the activation of caspase-3 directly or indirectly through Bid cleavage, cytochrome c release, and caspase-9 activation

Compound K, a metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells

Directory of Open Access Journals (Sweden)

Choi Jung-Hye

2009-12-01

Full Text Available Abstract Background Compound K [20-O-β-(D-glucopyranosyl-20(S-protopanaxadiol], a metabolite of the protopanaxadiol-type saponins of Panax ginseng C.A. Meyer, has been reported to possess anti-tumor properties to inhibit angiogenesis and to induce tumor apoptosis. In the present study, we investigated the effect of Compound K on apoptosis and explored the underlying mechanisms involved in HL-60 human leukemia cells. Methods We examined the effect of Compound K on the viabilities of various cancer cell lines using MTT assays. DAPI assay, Annexin V and PI double staining, Western blot assay and immunoprecipitation were used to determine the effect of Compound K on the induction of apoptosis. Results Compound K was found to inhibit the viability of HL-60 cells in a dose- and time-dependent manner with an IC50 of 14 μM. Moreover, this cell death had typical features of apoptosis, that is, DNA fragmentation, DNA ladder formation, and the externalization of Annexin V targeted phosphatidylserine residues in HL-60 cells. In addition, compound-K induced a series of intracellular events associated with both the mitochondrial- and death receptor-dependent apoptotic pathways, namely, (1 the activation of caspases-3, -8, and -9; (2 the loss of mitochondrial membrane potential; (3 the release of cytochrome c and Smac/DIABLO to the cytosol; (4 the translocation of Bid and Bax to mitochondria; and (5 the downregulations of Bcl-2 and Bcl-xL. Furthermore, a caspase-8 inhibitor completely abolished caspase-3 activation, Bid cleavage, and subsequent DNA fragmentation by Compound K. Interestingly, the activation of caspase-3 and -8 and DNA fragmentation were significantly prevented in the presence of cycloheximide, suggesting that Compound K-induced apoptosis is dependent on de novo protein synthesis. Conclusions The results indicate that caspase-8 plays a key role in Compound K-stimulated apoptosis via the activation of caspase-3 directly or indirectly through

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

Science.gov (United States)

2018-03-12

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

Cancer progression by reprogrammed BCAA metabolism in myeloid leukaemia.

Science.gov (United States)

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

2017-05-25

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

Evidence for Transfer of Membranes from Mesenchymal Stem Cells to HL-1 Cardiac Cells.

Science.gov (United States)

Boomsma, Robert A; Geenen, David L

2014-01-01

This study examined the interaction of mouse bone marrow mesenchymal stem cells (MSC) with cardiac HL-1 cells during coculture by fluorescent dye labeling and then flow cytometry. MSC were layered onto confluent HL-1 cell cultures in a 1 : 4 ratio. MSC gained gap junction permeant calcein from HL-1 cells after 4 hours which was partially reduced by oleamide. After 20 hours, 99% MSC gained calcein, unaffected by oleamide. Double-labeling HL-1 cells with calcein and the membrane dye DiO resulted in transfer of both calcein and DiO to MSC. When HL-1 cells were labeled with calcein and MSC with DiO, MSC gained calcein while HL-1 cells gained DiO. Very little fusion was observed since more than 90% Sca-1 positive MSC gained DiO from HL-1 cells while less than 9% gained gap junction impermeant CMFDA after 20 hours with no Sca-1 transfer to HL-1 cells. Time dependent transfer of membrane DiD was observed from HL-1 cells to MSC (100%) and vice versa (50%) after 20 hours with more limited transfer of CMFDA. These results demonstrate that MSC and HL-1 cells exchange membrane components which may account for some of the beneficial effect of MSC in the heart after myocardial infarction.

Initial analysis of the HL-2A tokamak visible light measurements

International Nuclear Information System (INIS)

Shi Le; Zheng Yinjia

2005-01-01

Measurement of H α radial distribution is an important part in a plasma experiment. During the HL-2A experiment, CCD photos recorded the plasma radiation information using a plasma imaging system, particularly the H α line emission information (with H α filter in front of the camera). Since the line of light radiation measurement involves a line integral of the radiating region, data handling and analysis are necessary. The H α radial distribution along an HL-2A tokamak radial radius can be obtained by using an Abel inversion transformation with plasma imaging on the HL-2A tokamak. This paper provides a reliable measurement method on the HL-2A tokamak. (authors)

Microarray analysis reveals genetic pathways modulated by tipifarnib in acute myeloid leukemia

International Nuclear Information System (INIS)

Raponi, Mitch; Belly, Robert T; Karp, Judith E; Lancet, Jeffrey E; Atkins, David; Wang, Yixin

2004-01-01

Farnesyl protein transferase inhibitors (FTIs) were originally developed to inhibit oncogenic ras, however it is now clear that there are several other potential targets for this drug class. The FTI tipifarnib (ZARNESTRA™, R115777) has recently demonstrated clinical responses in adults with refractory and relapsed acute leukemias. This study was conducted to identify genetic markers and pathways that are regulated by tipifarnib in acute myeloid leukemia (AML). Tipifarnib-mediated gene expression changes in 3 AML cell lines and bone marrow samples from two patients with AML were analyzed on a cDNA microarray containing approximately 7000 human genes. Pathways associated with these expression changes were identified using the Ingenuity Pathway Analysis tool. The expression analysis identified a common set of genes that were regulated by tipifarnib in three leukemic cell lines and in leukemic blast cells isolated from two patients who had been treated with tipifarnib. Association of modulated genes with biological functional groups identified several pathways affected by tipifarnib including cell signaling, cytoskeletal organization, immunity, and apoptosis. Gene expression changes were verified in a subset of genes using real time RT-PCR. Additionally, regulation of apoptotic genes was found to correlate with increased Annexin V staining in the THP-1 cell line but not in the HL-60 cell line. The genetic networks derived from these studies illuminate some of the biological pathways affected by FTI treatment while providing a proof of principle for identifying candidate genes that might be used as surrogate biomarkers of drug activity

Connecting HL Tau to the observed exoplanet sample

Science.gov (United States)

Simbulan, Christopher; Tamayo, Daniel; Petrovich, Cristobal; Rein, Hanno; Murray, Norman

2017-08-01

The Atacama Large Millimeter/submilimeter Array (ALMA) recently revealed a set of nearly concentric gaps in the protoplanetary disc surrounding the young star HL Tauri (HL Tau). If these are carved by forming gas giants, this provides the first set of orbital initial conditions for planets as they emerge from their birth discs. Using N-body integrations, we have followed the evolution of the system for 5 Gyr to explore the possible outcomes. We find that HL Tau initial conditions scaled down to the size of typically observed exoplanet orbits naturally produce several populations in the observed exoplanet sample. First, for a plausible range of planetary masses, we can match the observed eccentricity distribution of dynamically excited radial velocity giant planets with eccentricities >0.2. Secondly, we roughly obtain the observed rate of hot Jupiters around FGK stars. Finally, we obtain a large efficiency of planetary ejections of ≈2 per HL Tau-like system, but the small fraction of stars observed to host giant planets makes it hard to match the rate of free-floating planets inferred from microlensing observations. In view of upcoming Gaia results, we also provide predictions for the expected mutual inclination distribution, which is significantly broader than the absolute inclination distributions typically considered by previous studies.

Peroxisome Proliferator-Activated Receptor Ligands and Their Role in Chronic Myeloid Leukemia: Therapeutic Strategies.

Science.gov (United States)

Yousefi, Bahman; Samadi, Nasser; Baradaran, Behzad; Shafiei-Irannejad, Vahid; Zarghami, Nosratollah

2016-07-01

Imatinib therapy remains the gold standard for treatment of chronic myeloid leukemia; however, the acquired resistance to this therapeutic agent in patients has urged the scientists to devise modalities for overcoming this chemoresistance. For this purpose, initially therapeutic agents with higher tyrosine kinase activity were introduced, which had the potential for inhibiting even mutant forms of Bcr-Abl. Furthermore, coupling imatinib with peroxisome proliferator-activated receptor ligands also showed beneficial effects in chronic myeloid leukemia cell proliferation. These combination protocols inhibited cell growth and induced apoptosis as well as differentiation in chronic myeloid leukemia cell lines. In addition, peroxisome proliferator-activated receptors ligands increased imatinib uptake by upregulating the expression of human organic cation transporter 1. Taken together, peroxisome proliferator-activated receptors ligands are currently being considered as novel promising therapeutic candidates for chronic myeloid leukemia treatment, because they can synergistically enhance the efficacy of imatinib. In this article, we reviewed the potential of peroxisome proliferator-activated receptors ligands for use in chronic myeloid leukemia treatment. The mechanism of action of these therapeutics modalities are also presented in detail. © 2016 John Wiley & Sons A/S.

Responses of the Murine Myeloid Colony-Forming Cell to Ansamycin Antibiotics

Science.gov (United States)

Horoszewicz, Julius S.; Carter, William A.

1974-01-01

The in vitro susceptibility of murine myeloid colony-forming cells to the antiproliferative activities of three ansamycin antibiotics was determined. These cells were found to be 10- to 40-fold more susceptible than the corresponding human ones. PMID:4151701

CAR-T cells targeting CLL-1 as an approach to treat acute myeloid leukemia

OpenAIRE

Wang, Jinghua; Chen, Siyu; Xiao, Wei; Li, Wende; Wang, Liang; Yang, Shuo; Wang, Weida; Xu, Liping; Liao, Shuangye; Liu, Wenjian; Wang, Yang; Liu, Nawei; Zhang, Jianeng; Xia, Xiaojun; Kang, Tiebang

2018-01-01

Background Acute myeloid leukemia (AML) is one of the most common types of adult acute leukemia. Standard chemotherapies can induce complete remission in selected patients; however, a majority of patients eventually relapse and succumb to the disease. Thus, the development of novel therapeutics for AML is urgently needed. Human C-type lectin-like molecule-1 (CLL-1) is a type II transmembrane glycoprotein, and its expression is restricted to myeloid cells and the majority of AML blasts. Moreov...

[Drug resistance reversal of HL-60/ADR cells by simultaneous suppression of XIAP and MRP].

Science.gov (United States)

Wang, Xiao-Fang; Wang, Chun; Qin, You-Wen; Yan, Shi-Ke; Gao, Yan-Rong

2006-12-01

This study was purposed to explore the mechanisms of drug resistance of HL-60/ADR cells and to compare the reversal drug-resistance effects of antisense oligonucleotides (AS ODN) of XIAP (X-linked inhibitor of apoptosis protein) and AS ODNs of MRP (multidrug resistance-associated protein) by use alone or in combination. Reverse transcription-PCR and Western blot were applied to detect the expression of XIAP, BCL-2, MRP and MDR1 in mRNA and protein levels of HL-60 cells and HL-60/ADR cells, respectively. Fully phosphorothioated AS ODN of XIAP and MRP was delivered into HL-60/ADR cells with Lipofectamine 2000 in the form of liposome-ODN complexes alone or in combination. CCK-8 cell viability assay was used to determine the effect of AS ODN of XIAP and MRP used alone or in combination on the chemotherapy sensitivity of HL-60/ADR cells to daunorubicin (DNR). Reverse transcription-PCR and Western blot were applied to examine the changes of XIAP, MRP in mRNA and protein levels respectively. The results showed that MRP and XIAP were both significantly higher in HL-60/ADR cells than those in HL-60 cells. AS ODN of XIAP and MRP down-regulated the expression of XIAP and MRP in HL-60/ADR cells and increased the sensitivity of HL-60/ADR cells to DNR, respectively. AS ODN of XIAP + MRP did not enhance the inhibition expression of XIAP in HL-60/ADR cells but increased the sensitivity of HL-60/ADR cells to DNR significantly as compared with AS ODN of XIAP (P MRP did not increase the concentration of DNR nor enhanced the inhibition expression of MRP in HL-60/ADR cells but increased the sensitivity of HL-60/ADR cells to DNR significantly (P MRP. It is concluded that both XIAP and MRP may be involved in the drug resistance mechanisms of HL-60/ADR cells. Drug-resistance of HL-60/ADR cells can be reversed significantly when antisense oligonucleotides of XIAP and MRP were used in combination.

Tissue factor expression by myeloid cells contributes to protective immune response against Mycobacterium tuberculosis infection.

Science.gov (United States)

Venkatasubramanian, Sambasivan; Tripathi, Deepak; Tucker, Torry; Paidipally, Padmaja; Cheekatla, Satyanarayana; Welch, Elwyn; Raghunath, Anjana; Jeffers, Ann; Tvinnereim, Amy R; Schechter, Melissa E; Andrade, Bruno B; Mackman, Nizel; Idell, Steven; Vankayalapati, Ramakrishna

2016-02-01

Tissue factor (TF) is a transmembrane glycoprotein that plays an essential role in hemostasis by activating coagulation. TF is also expressed by monocytes/macrophages as part of the innate immune response to infections. In the current study, we determined the role of TF expressed by myeloid cells during Mycobacterium tuberculosis (M. tb) infection by using mice lacking the TF gene in myeloid cells (TF(Δ) ) and human monocyte derived macrophages (MDMs). We found that during M. tb infection, a deficiency of TF in myeloid cells was associated with reduced inducible nitric oxide synthase (iNOS) expression, enhanced arginase 1 (Arg1) expression, enhanced IL-10 production and reduced apoptosis in infected macrophages, which augmented M. tb growth. Our results demonstrate that a deficiency of TF in myeloid cells promotes M2-like phenotype in M .tb infected macrophages. A deficiency in TF expression by myeloid cells was also associated with reduced fibrin deposition and increased matrix metalloproteases (MMP)-2 and MMP-9 mediated inflammation in M. tb infected lungs. Our studies demonstrate that TF expressed by myeloid cells has newly recognized abilities to polarize macrophages and to regulate M. tb growth. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

49 CFR 525.11 - Termination of exemption; amendment of alternative average fuel economy standard.

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2010-10-01

... average fuel economy standard. 525.11 Section 525.11 Transportation Other Regulations Relating to... EXEMPTIONS FROM AVERAGE FUEL ECONOMY STANDARDS § 525.11 Termination of exemption; amendment of alternative average fuel economy standard. (a) Any exemption granted under this part for an affected model year does...

The CMS Outer Tracker for HL-LHC

CERN Document Server

Dierlamm, Alexander Hermann

2018-01-01

The LHC is planning an upgrade program, which will bring the luminosity to about $5-7\\times10^{34}$~cm$^{-2}$s$^{-1}$ in 2026, with a goal of an integrated luminosity of 3000 fb$^{-1}$ by the end of 2037. This High Luminosity LHC scenario, HL-LHC, will require a preparation program of the LHC detectors known as Phase-2 Upgrade. The current CMS Tracker is already running beyond design specifications and will not be able to cope with the HL-LHC radiation conditions. CMS will need a completely new Tracker in order to fully exploit the highly demanding operating conditions and the delivered luminosity. The new Outer Tracker system is designed to provide robust tracking as well as Level-1 trigger capabilities using closely spaced modules composed of silicon macro-pixel and/or strip sensors. Research and development activities are ongoing to explore options and develop module components and designs for the HL-LHC environment. The design choices for the CMS Outer Tracker Upgrade are discussed along with some highlig...

Effect of dioxin on normal and leukemic human hematopoietic cells

Energy Technology Data Exchange (ETDEWEB)

Lambertenghi-Deliliers, G.; Soligo, D. [Univ. degli Studi, Milan (Italy). Dipt. die Ematologia, Ospedale Maggiore Policlinico IRCCS; Fracchiolla, N.S. [Ospedale Maggiore Policlinico IRCCS, Milan (Italy). Dipt. di Ematologia; Servida, F. [Fondazione Matarelli, Milan (Italy); Bertazzi, P.A. [Istituti Clinici di Perfezionamento, Milan (Italy). Dipt. di Medicina del Lavoro

2004-09-15

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) arises from chlorination of phenolic substrates or from partial combustion of organic materials in the presence of chlorine sources. TCDD has a large number of biological effects such as long-lasting skin disease, cardiovascular disease, diabete and cancer. TCDD is the prototypical agonist of the aryl hydrocarbon receptor (AhR), a member of the erb-A family that also includes the receptors for steroids, thyroid hormones, peroxisome proliferators and retinoids. When bound to dioxin, the AhR can bind to DNA and alter the expression of some genes including cytokines and growth factors. In this study, we analyzed the effect of escalating doses of TCDD on human CD34{sup +} progenitor cells from the leukapheresis of normal donors stimulated with G-CSF as well as the human myeloid leukemic cell lines HL60 (promyelocytic leukemia) and K562 (chronic myelogenous leukemia). The possible specific modulation of gene expression induced by the TCDD exposure was then tested by means of microarray analyses.

An experimental study of 99Tcm-HL91 in detection of myocardial viability

International Nuclear Information System (INIS)

Xu Tao; Liu Baoping; Meng Yubao; Sun Bingqi; Niu Guangjun; Han Xingmin; Yuan Qiao

2005-01-01

Objective: To investigate whether 99 Tc m -4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime (HL91) can be used to distinguish ischemic myocardium segments from infarction segments. Methods: Twenty-five acute myocardial infarction patients (≤6 weeks) and 5 old myocardial infarction patients (> 6 weeks) were included in the study. All the study patients underwent 99 Tc m -HL91 and 99 Tc m -methoxyisobutylisonitrile (MIBI) imaging intervented and unintervented with nitroglycerin, and the myocardium segments were divided into three groups according to 99 Tc m -MIBI imaging results: normal, ischemic, and infarction myocardium segments. The difference of the radial counts of 99 Tc m -HL91 in three groups were analyzed after the imaging with 99 Tc m -HL91. Results: 1) In acute myocardial infarction patients, the accumulation rates of 99 Tc m -HL91 was 95% in normal segment group, 157% in ischemic group, 93% in infarction group. The accumulation rates of 99 Tc m -HL91 in the ischemic group was higher than that in the normal group and infarction group. 2)In old myocardial infarction patients, the accumulation rates of 99 Tc m -HL91 were of no difference among the normal, ischemic, and infarction groups. Conclusion: 99 Tc m -HL91 is a potential marker for detecting the ischemic myocardial tissue. (authors)

Sacral Myeloid Sarcoma Manifesting as Radiculopathy in a Pediatric Patient: An Unusual Form of Myeloid Leukemia Relapse

Directory of Open Access Journals (Sweden)

Joana Ruivo Rodrigues

2018-01-01

Full Text Available Myeloid sarcoma (MS, granulocytic sarcoma or chloroma, is defined as a localized extramedullary mass of blasts of granulocytic lineage with or without maturation, occurring outside the bone marrow. MS can be diagnosed concurrently with acute myeloid leukemia (AML or myelodysplastic syndrome (MDS. The authors report a case of sacral MS occurring as a relapse of myeloid leukemia in a 5-year-old girl who was taken to the emergency department with radiculopathy symptoms.

Physics Prospects at the HL-LHC with ATLAS

CERN Document Server

Duncan, Anna Kathryn; The ATLAS collaboration

2017-01-01

The High-Luminosity LHC aims to provide a total integrated luminosity of 3000 fb-1 from p-p collisions at $\\sqrt{s}$ = 14 TeV over the course of $\\sim$ 10 years, reaching instantaneous luminosities of up to L = 7.5 $\\times$ 1034cm$^{-2}$s$^{-1}$, corresponding to an average ($\\mu$) of 200 inelastic p-p collisions per bunch crossing. The upgraded ATLAS detector must be able to cope well with increased occupancies and data rates. The performance of the upgrade has been estimated in full simulation studies, assuming expected HL-LHC conditions and a detector configuration intended to maximise physics performance and discovery potential at the HL-LHC. The performance is expected to be similar to what we have now. Simulation studies have been carried out to evaluate the prospects of various benchmark physics analyses to be performed using the upgraded ATLAS detector with the full HL-LHC dataset.

Preliminary applied study of assessment ischemic/viable myocardium by 99Tcm-HL91

International Nuclear Information System (INIS)

Liu Gang; Wu Hua

2004-01-01

Objective: To investigate the representation of 99 Tc m -HL91 in the ischemic myocardium, evaluate the diagnosis value of 99 Tc m -HL91 on hypoxic but viable myocardium. Methods: Six patients with cardiac infarction all underwent 99 Tc m -MIBI SPECT and 99 Tc m -HL91 SPECT. Average radioactivity of ischemic area and normal area were respectively obtained by ROI (2 x 2 pixels) on heart minor axis of images, And the radioactivity ratios of target (ischemic area)-to-non target(normal area)were calculated. Results: In image of 99 Tc m -HL91 SPECT, two patients who's radioactivity coloboma of 99 Tc m -MIBI image could be filled with 99 Tc m -HL91, four patients were not caught sight of obvious filling up. Conclusion 99 Tc m -HL91 can be selectively uptaken by ischemic and hypoxic but viable myocardium. it combination of 99 Tc m -MIBI SPECT may be good for accurate diagnosis and differentiation of viable myocardium. (authors)

Effects of CD44 Ligation on Signaling and Metabolic Pathways in Acute Myeloid Leukemia

KAUST Repository

Madhoun, Nour Y.

2017-04-01

Acute myeloid leukemia (AML) is characterized by a blockage in the differentiation of myeloid cells at different stages. CD44-ligation using anti-CD44 monoclonal antibodies (mAbs) has been shown to reverse the blockage of differentiation and to inhibit the proliferation of blasts in most AML-subtypes. However, the molecular mechanisms underlying this property have not been fully elucidated. Here, we sought to I) analyze the effects of anti-CD44 mAbs on downstream signaling pathways, including the ERK1/2 (extracellular signal-regulated kinase 1 and 2) and mTOR (mammalian target of rapamycin) pathways and II) use state-of-the-art Nuclear Magnetic Resonance (NMR) technology to determine the global metabolic changes during differentiation induction of AML cells using anti-CD44 mAbs and other two previously reported differentiation agents. In the first objective (Chapter 4), our studies provide evidence that CD44-ligation with specific mAbs in AML cells induced an increase in ERK1/2 phosphorylation. The use of the MEK inhibitor (U0126) significantly inhibited the CD44-induced differentiation of HL60 cells, suggesting that ERK1/2 is critical for the CD44-triggered differentiation in AML. In addition, this was accompanied by a marked decrease in the phosphorylation of the mTORC1 and mTORC2 complexes, which are strongly correlated with the inhibition of the PI3K/Akt pathway. In the second objective (Chapter 5), 1H NMR experiments demonstrated that considerable changes in the metabolic profiles of HL60 cells were induced in response to each differentiation agent. These most notable metabolites that significantly changed upon CD44 ligation were involved in the tricarboxylic acid (TCA) cycle and glycolysis such as, succinate, fumarate and lactate. Therefore, we sought to analyze the mechanisms underlying their alterations. Our results revealed that anti-CD44 mAbs treatment induced upregulation in fumarate hydratase (FH) expression and its activity which was accompanied by a

Tracking in Dense Environments for the HL-LHC ATLAS Detector

CERN Document Server

Cormier, Felix; The ATLAS collaboration

2018-01-01

Tracking in dense environments, such as in the cores of high-energy jets, will be key for new physics searches as well as measurements of the Standard Model at the High Luminosity LHC (HL-LHC). The HL-LHC will operate in challenging conditions with large radiation doses and high pile-up (up to $\\mu=200$). The current tracking detector will be replaced with a new all-silicon Inner Tracker for the Phase II upgrade of the ATLAS detector. In this talk, characterization of the HL-LHC tracker performance for collimated, high-density charged particles arising from high-momentum decays is presented. In such decays the charged-particle separations are of the order of the tracking detector granularity, leading to challenging reconstruction. The ability of the HL-LHC ATLAS tracker to reconstruct the tracks in such dense environments is discussed and compared to ATLAS Run-2 performance for a variety of relevant physics processes.

Clonal evolution of pre-leukemic hematopoietic stem cells precedes human acute myeloid leukemia.

Science.gov (United States)

Majeti, Ravindra

2014-01-01

Massively parallel DNA sequencing has uncovered recurrent mutations in many human cancers. In acute myeloid leukemia (AML), cancer genome/exome resequencing has identified numerous recurrently mutated genes with an average of 5 mutations in each case of de novo AML. In order for these multiple mutations to accumulate in a single lineage of cells, they are serially acquired in clones of self-renewing hematopoietic stem cells (HSC), termed pre-leukemic HSC. Isolation and characterization of pre-leukemic HSC have shown that their mutations are enriched in genes involved in regulating DNA methylation, chromatin modifications, and the cohesin complex. On the other hand, genes involved in regulating activated signaling are generally absent. Pre-leukemic HSC have been found to persist in clinical remission and may ultimately give rise to relapsed disease through the acquisition of novel mutations. Thus, pre-leukemic HSC may constitute a key cellular reservoir that must be eradicated for long-term cures. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dynamics of myeloid cell populations during relapse-preventive immunotherapy in acute myeloid leukemia.

Science.gov (United States)

Rydström, Anna; Hallner, Alexander; Aurelius, Johan; Sander, Frida Ewald; Bernson, Elin; Kiffin, Roberta; Thoren, Fredrik Bergh; Hellstrand, Kristoffer; Martner, Anna

2017-08-01

Relapse of leukemia in the postchemotherapy phase contributes to the poor prognosis and survival in patients with acute myeloid leukemia (AML). In an international phase IV trial (ClinicalTrials.gov; NCT01347996), 84 patients with AML in first complete remission who had not undergone transplantation received immunotherapy with histamine dihydrochloride (HDC) and low-dose IL-2 with the aim of preventing relapse. The dynamics of myeloid cell counts and expression of activation markers was assessed before and after cycles of immunotherapy and correlated with clinical outcome in terms of relapse risk and survival. During cycles, a pronounced increase in blood eosinophil counts was observed along with a reduction in monocyte and neutrophil counts. A strong reduction of blood monocyte counts during the first HDC/IL-2 treatment cycle predicted leukemia-free survival. The HDC component of the immunotherapy exerts agonist activity at histamine type 2 receptors (H2Rs) that are expressed by myeloid cells. It was observed that the density of H 2 R expression in blood monocytes increased during cycles of immunotherapy and that high monocyte H 2 R expression implied reduced relapse risk and improved overall survival. Several other activation markers, including HLA-DR, CD86, and CD40, were induced in monocytes and dendritic cells during immunotherapy but did not predict clinical outcome. In addition, expression of HLA-ABC increased in all myeloid populations during therapy. A low expression of HLA-ABC was associated with reduced relapse risk. These results suggest that aspects of myeloid cell biology may impact clinical benefit of relapse-preventive immunotherapy in AML. © Society for Leukocyte Biology.

Genital ulcers as diagnostic clue for acute myeloid leukaemia.

Science.gov (United States)

Schröder, Sina D; Krause, Stefan W; Erfurt-Berge, Cornelia

2018-04-23

Acute myeloid leukaemia is a myeloid neoplasm with an extremely varying clinical appearance. Skin lesions are common for specific subtypes of acute myeloid leukaemia but are often misinterpreted. Here, we present a case of acute myeloid leukaemia in a young woman exhibiting genital ulcerations and gingival erosions. © 2018 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Selections from 2016: Gaps in HL Tau's Protoplanetary Disk

Science.gov (United States)

Kohler, Susanna

2016-12-01

Editors note:In these last two weeks of 2016, well be looking at a few selections that we havent yet discussed on AAS Nova from among the most-downloaded paperspublished in AAS journals this year. The usual posting schedule will resume after the AAS winter meeting.Gas Gaps in the Protoplanetary Disk Around the Young Protostar HL TauPublished March 2016The dust (left) and gas (right) emission from HL Tau show that the gaps in its disk match up. [Yen et al. 2016]Main takeaway:At the end of last year, the Atacama Large Millimeter/Submillimeter Array released some of its first data including a spectacular observation of a dusty protoplanetary disk around the young star HL Tau. In this follow-up study, a team led by Hsi-Wei Yen (Academia Sinica Institute of Astronomy and Astrophysics, Taiwan) analyzed the ALMA data and confirmed the presence of two gaps in the gas of HL Taus disk, at radii of 28 and 69 AU.Why its interesting:The original ALMA image of HL Taus disk suggests the presence of gaps in disk, but scientists werent sure if they were caused by effects like gravitational instabilities or dust clumping, or if the gaps were created by the presence of young planets. Yen and collaborators showed that gaps in the disks gas line up with gaps in its dust, supporting the model in which these gaps have been carved out by newly formed planets.Added intrigue:The evidence for planets in this disk came as a bit of a surprise, since it was originally believed that it takes tens of millions of years to form planets from the dust of protoplanetary disks but HL Tau is only a million years old. These observations therefore suggest that planets start to form much earlier than we thought.CitationHsi-Wei Yen et al 2016 ApJL 820 L25. doi:10.3847/2041-8205/820/2/L25

Physics prospects at the HL-LHC with ATLAS

CERN Document Server

Duncan, Anna Kathryn

2017-01-01

The High-Luminosity LHC aims to provide a total integrated luminosity of 3000 fb$^{-1}$ from proton-proton collisions at $\\sqrt{s}$ = 14 TeV over the course of $\\sim$ 10 years, reaching instantaneous luminosities of up to $L = 7.5 \\times 10^{34} cm^{-2} s^{-1}$, corresponding to an average of 200 inelastic p-p collisions per bunch crossing ($\\mu = 200)$. The upgraded ATLAS detector and trigger system must be able to cope well with increased occupancies and data rates. The performance of the upgrade has been estimated in full simulation studies, assuming expected HL-LHC conditions and a detector configuration intended to maximise physics performance and discovery potential at the HL-LHC, and is expected to be similar to current performance. Fast simulation studies have been carried out to evaluate the prospects of various benchmark physics analyses to be performed using the upgraded ATLAS detector with the full HL-LHC dataset.

13 CFR 113.525 - Fringe benefits.

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Fringe benefits. 113.525 Section... benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, fringe benefits means: Any medical, hospital, accident, life insurance, or retirement benefit, service, policy or plan, any...

38 CFR 23.525 - Fringe benefits.

Science.gov (United States)

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Fringe benefits. 23.525... benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, fringe benefits means: Any medical, hospital, accident, life insurance, or retirement benefit, service, policy or plan, any...

24 CFR 3.525 - Fringe benefits.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Fringe benefits. 3.525 Section 3... benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, fringe benefits means: Any medical, hospital, accident, life insurance, or retirement benefit, service, policy or plan, any...

Integration of IEEE 1451 and HL7 exchanging information for patients' sensor data.

Science.gov (United States)

Kim, Wooshik; Lim, Suyoung; Ahn, Jinsoo; Nah, Jiyoung; Kim, Namhyun

2010-12-01

HL7 (Health Level 7) is a standard developed for exchanging incompatible healthcare information generated from programs or devices among heterogenous medical information systems. At present, HL7 is growing as a global standard. However, the HL7 standard does not support effective methods for treating data from various medical sensors, especially from mobile sensors. As ubiquitous systems are growing, HL7 must communicate with various medical transducers. In the area of sensor fields, IEEE 1451 is a group of standards for controlling transducers and for communicating data from/to various transducers. In this paper, we present the possibility of interoperability between the two standards, i.e., HL7 and IEEE 1451. After we present a method to integrate them and show the preliminary results of this approach.

HSP10 selective preference for myeloid and megakaryocytic precursors in normal human bone marrow

Directory of Open Access Journals (Sweden)

F Cappello

2009-06-01

Full Text Available Heat shock proteins (HSPs constitute a heterogeneous family of proteins involved in cell homeostasis. During cell life they are involved in harmful insults, as well as in immune and inflammatory reactions. It is known that they regulate gene expression, and cell proliferation, differentiation and death. HSP60 is a mitochondrial chaperonin, highly preserved during evolution, responsible of protein folding. Its function is strictly dependent on HSP10 in both prokaryotic and eukaryotic elements. We investigated the presence and the expression of HSP60 and HSP10 in a series of 20 normal human bone marrow specimens (NHBM by the means of immunohistochemistry. NHBM showed no expression of HSP60, probably due to its being below the detectable threshold, as already demonstrated in other normal human tissues. By contrast, HSP10 showed a selective positivity for myeloid and megakaryocytic lineages. The positivity was restricted to precursor cells, while mature elements were constantly negative.We postulate that HSP10 plays a role in bone marrow cell differentiation other than being a mitochondrial co-chaperonin. The present data emphasize the role of HSP10 during cellular homeostasis and encourage further investigations in this field.

Overview of HL-2A experiment results

International Nuclear Information System (INIS)

Yang, Q.W.; Yong Liu; Ding, X.T.

2007-01-01

Recent experiment results from the HL-2A tokamak are presented in this paper. Supersonic molecular beam injection (SMBI) with liquid nitrogen temperature propellant is used. Low temperature SMBI can form hydrogen clusters that penetrate into the plasma more deeply and efficiently. Particle diffusion coefficient and convection velocity (D = 0.5-1.5 m 2 s -1 and V conv -1 , respectively) are obtained at the plasma periphery using modulated SMBI. Multi-probe measurements reveal the m = 0-1, n = 0 symmetries of directly measured low frequency (7-9 kHz) electric potential and field are simultaneously observed for the first time. Impurity transport is determined with the laser blow-off system and transport code. A disruption predictor has been derived based on MHD activity observations and statistical analysis. Sawtooth characteristics during ECRH are investigated and coupling between m = 1 and m/n = 2/1 modes is studied. Detachment features of HL-2A divertor are numerically and experimentally studied using the code SOLPS5.0 and measured data. The long divertor legs and thin divertor throats in HL-2A pose MHD shaping problems resulting in momentum losses even at low densities and strongly enhanced main chamber losses

20 CFR 411.525 - What payments are available under each of the EN payment systems?

Science.gov (United States)

2010-04-01

... EN payment systems? 411.525 Section 411.525 Employees' Benefits SOCIAL SECURITY ADMINISTRATION THE TICKET TO WORK AND SELF-SUFFICIENCY PROGRAM Employment Network Payment Systems § 411.525 What payments are available under each of the EN payment systems? (a) For payments for outcome payment months, both...

Vildagliptin and its metabolite M20.7 induce the expression of S100A8 and S100A9 in human hepatoma HepG2 and leukemia HL-60 cells.

Science.gov (United States)

Asakura, Mitsutoshi; Karaki, Fumika; Fujii, Hideaki; Atsuda, Koichiro; Itoh, Tomoo; Fujiwara, Ryoichi

2016-10-19

Vildagliptin is a potent, orally active inhibitor of dipeptidyl peptidase-4 (DPP-4) for the treatment of type 2 diabetes mellitus. It has been reported that vildagliptin can cause hepatic dysfunction in patients. However, the molecular-mechanism of vildagliptin-induced liver dysfunction has not been elucidated. In this study, we employed an expression microarray to determine hepatic genes that were highly regulated by vildagliptin in mice. We found that pro-inflammatory S100 calcium-binding protein (S100) a8 and S100a9 were induced more than 5-fold by vildagliptin in the mouse liver. We further examined the effects of vildagliptin and its major metabolite M20.7 on the mRNA expression levels of S100A8 and S100A9 in human hepatoma HepG2 and leukemia HL-60 cells. In HepG2 cells, vildagliptin, M20.7, and sitagliptin - another DPP-4 inhibitor - induced S100A9 mRNA. In HL-60 cells, in contrast, S100A8 and S100A9 mRNAs were significantly induced by vildagliptin and M20.7, but not by sitagliptin. The release of S100A8/A9 complex in the cell culturing medium was observed in the HL-60 cells treated with vildagliptin and M20.7. Therefore, the parental vildagliptin- and M20.7-induced release of S100A8/A9 complex from immune cells, such as neutrophils, might be a contributing factor of vildagliptin-associated liver dysfunction in humans.

Genetics Home Reference: chronic myeloid leukemia

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... Central Quintás-Cardama A, Cortes JE. Chronic myeloid leukemia: diagnosis and treatment. Mayo Clin Proc. 2006 Jul;81(7):973-88. Review. Citation on PubMed Skorski T. Genetic mechanisms of chronic myeloid leukemia blastic transformation. Curr Hematol Malig Rep. 2012 Jun; ...

29 CFR 525.4 - Patient workers.

Science.gov (United States)

2010-07-01

..., as defined in § 525.3(e), a major factor in determining if an employment relationship exists is... become an employee if he or she merely performs personal housekeeping chores, such as maintaining his or... possible for patients in family-like settings such as group homes to rotate or share household tasks or...

The preparation and biological characterization of a new HL91-derivative for hypoxic imaging on stroke mice

Energy Technology Data Exchange (ETDEWEB)

Hsia, C.-C. [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taiwan (China); Institute of Nuclear Energy Research, Taiwan (China); Huang, F.-L.; Lin, C.-H.; Shen, L.-H. [Institute of Nuclear Energy Research, Taiwan (China); Wang, H.-E., E-mail: hewang@ym.edu.t [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taiwan (China)

2010-09-15

Aim: {sup 99m}Tc-HL91 (Prognox, GE-Healthcare) was the first nonnitro-aryl-based radiotracer for evaluating hypoxic fraction in neoplasm, stroke and myocardium infarction regions. However, the high hydrophilicity of {sup 99m}Tc-HL91 might hamper its penetration into cells. In this study, we prepared a new ligand 4,4,11,11-tetramethyl- 5,10-diazatetradecane- 3,12-dionedioxime (HL91-ET) with higher lipophilicity but structurally similar compared with that of HL91. The chemical and biological characterizations of {sup 99m}Tc-HL91-ET as a scintigraphic probe for hypoxia were performed with a stroke-bearing mouse model. Materials and Methods: HL91-ET was synthesized and formulated with stannous chloride and buffer to afford kits. After mixing with {sup 99m}Tc-pertechnetate, {sup 99m}Tc-HL91-ET can be prepared in high yield and high radiochemical purity (both >96%). The partition coefficient of {sup 99m}Tc-HL91-ET was determined in n-octanol/PBS system. Cellular uptake assays under normoxic and hypoxic conditions were performed in an oxygen-controlled CO{sub 2} incubator. Brain stroke in the mouse model was induced by the electrocautery of the middle cerebral artery. After intravenous injection of {sup 99m}Tc-HL91-ET into the Balb/c mouse suffering brain stroke, small-animal SPECT images were acquired at designated time points and autoradiography of the brain slides was conducted. Parallel studies of {sup 99m}Tc-HL91 were also conducted at the same conditions for comparison. Results: The higher partition coefficient of {sup 99m}Tc-HL91-ET (0.294{+-}0.007) indicated higher lipophlicity compared with that of {sup 99m}Tc-HL91 (0.089{+-}0.005). The {sup 99m}Tc-HL91-ET preparation was stable at ambient temperature for 24 h. Cellular uptake assay showed that {sup 99m}Tc-HL91-ET was less selectively retained in hypoxic cells than {sup 99m}Tc-HL91. The target-to-normal brain ratios derived from the autoradiograms of the brains of stroke mice were 1.31{+-}0.02 and 17

The preparation and biological characterization of a new HL91-derivative for hypoxic imaging on stroke mice

International Nuclear Information System (INIS)

Hsia, C.-C.; Huang, F.-L.; Lin, C.-H.; Shen, L.-H.; Wang, H.-E.

2010-01-01

Aim: 99m Tc-HL91 (Prognox, GE-Healthcare) was the first nonnitro-aryl-based radiotracer for evaluating hypoxic fraction in neoplasm, stroke and myocardium infarction regions. However, the high hydrophilicity of 99m Tc-HL91 might hamper its penetration into cells. In this study, we prepared a new ligand 4,4,11,11-tetramethyl- 5,10-diazatetradecane- 3,12-dionedioxime (HL91-ET) with higher lipophilicity but structurally similar compared with that of HL91. The chemical and biological characterizations of 99m Tc-HL91-ET as a scintigraphic probe for hypoxia were performed with a stroke-bearing mouse model. Materials and Methods: HL91-ET was synthesized and formulated with stannous chloride and buffer to afford kits. After mixing with 99m Tc-pertechnetate, 99m Tc-HL91-ET can be prepared in high yield and high radiochemical purity (both >96%). The partition coefficient of 99m Tc-HL91-ET was determined in n-octanol/PBS system. Cellular uptake assays under normoxic and hypoxic conditions were performed in an oxygen-controlled CO 2 incubator. Brain stroke in the mouse model was induced by the electrocautery of the middle cerebral artery. After intravenous injection of 99m Tc-HL91-ET into the Balb/c mouse suffering brain stroke, small-animal SPECT images were acquired at designated time points and autoradiography of the brain slides was conducted. Parallel studies of 99m Tc-HL91 were also conducted at the same conditions for comparison. Results: The higher partition coefficient of 99m Tc-HL91-ET (0.294±0.007) indicated higher lipophlicity compared with that of 99m Tc-HL91 (0.089±0.005). The 99m Tc-HL91-ET preparation was stable at ambient temperature for 24 h. Cellular uptake assay showed that 99m Tc-HL91-ET was less selectively retained in hypoxic cells than 99m Tc-HL91. The target-to-normal brain ratios derived from the autoradiograms of the brains of stroke mice were 1.31±0.02 and 17.47±0.10 (n=3), respectively, at 2 h post injection of 99m Tc-HL91-ET and 99m Tc-HL91

Omacetaxine Mepesuccinate for Chronic Myeloid Leukemia.

Science.gov (United States)

Rosshandler, Yasmin; Shen, Ann Q; Cortes, Jorge; Khoury, Hanna Jean

2016-05-01

Omacetaxine mepesuccinate is approved by the Food and Drug Administration in the United States for the treatment of chronic myeloid leukemia in chronic or accelerated phase resistant to two or more tyrosine kinase inhibitors. This review summarizes the mode of action, pharmacokinetics, efficacy and safety of omacetaxine mepesuccinate. Omacetaxine mepesuccinate has activity in chronic myeloid leukemia, especially in the chronic phase, regardless of the presence of ABL1 kinase domain mutations. Omacetaxine mepesuccinate has distinct but manageable adverse events profile. Omacetaxine mepesuccinate is a treatment option for a subset of patients with refractory chronic myeloid leukemia.

Stage-Specific Human Induced Pluripotent Stem Cells Map the Progression of Myeloid Transformation to Transplantable Leukemia.

Science.gov (United States)

Kotini, Andriana G; Chang, Chan-Jung; Chow, Arthur; Yuan, Han; Ho, Tzu-Chieh; Wang, Tiansu; Vora, Shailee; Solovyov, Alexander; Husser, Chrystel; Olszewska, Malgorzata; Teruya-Feldstein, Julie; Perumal, Deepak; Klimek, Virginia M; Spyridonidis, Alexandros; Rampal, Raajit K; Silverman, Lewis; Reddy, E Premkumar; Papaemmanuil, Elli; Parekh, Samir; Greenbaum, Benjamin D; Leslie, Christina S; Kharas, Michael G; Papapetrou, Eirini P

2017-03-02

Myeloid malignancy is increasingly viewed as a disease spectrum, comprising hematopoietic disorders that extend across a phenotypic continuum ranging from clonal hematopoiesis to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In this study, we derived a collection of induced pluripotent stem cell (iPSC) lines capturing a range of disease stages encompassing preleukemia, low-risk MDS, high-risk MDS, and secondary AML. Upon their differentiation, we found hematopoietic phenotypes of graded severity and/or stage specificity that together delineate a phenotypic roadmap of disease progression culminating in serially transplantable leukemia. We also show that disease stage transitions, both reversal and progression, can be modeled in this system using genetic correction or introduction of mutations via CRISPR/Cas9 and that this iPSC-based approach can be used to uncover disease-stage-specific responses to drugs. Our study therefore provides insight into the cellular events demarcating the initiation and progression of myeloid transformation and a new platform for testing genetic and pharmacological interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

THERAPY-RELATED MYELOID MALIGNANCIES IN MYELOMA

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Xenofon Papanikolaou

2011-10-01

Full Text Available Therapy related myeloid malignancies are an increasingly recognized treatment complication in patients undergoing therapy for multiple myeloma. The main predisposing factors are the alkylating agents, topoisomerase II inhibitors and radiotherapy, but recently questions have been raised regarding the immunomodulatory agent lenalidomide. Little is known about the new antimyeloma agents in the context of therapy related myeloid malignanices. The duration of treatment and the time from diagnosis are the main contributing factors in alkylating induced myeloid malignancies which occur 5-10 years after treatment, chromosome 5 and 7 abnormalities being the characteristic finding. High dose therapy (HDT does not seem to be a major contributing factor per se in multiple myeloma. In a number of large published series, all the factors related with therapy-induced myelodysplasia were defined prior to HDT. Topoisomerase II inhibitors induce mainly acute leukemias which invariably correlate with dysregulation of the MLL gene. Radiotherapy causes therapy related myelodysplasia if applied in bone marrow producing areas, especially if combined with chemotherapy. Therapy related myeloid malignancies generally herald a poor prognosis. Karyotypic abnormalities seem to be the main prognostic factor. In all cases the risk for therapy related myeloid malignancies drops sharply by 10 years after the treatment.

THERAPY-RELATED MYELOID MALIGNANCIES IN MYELOMA

Directory of Open Access Journals (Sweden)

Bart Barlogie

2011-01-01

Full Text Available

Therapy related myeloid malignancies are an increasingly recognized treatment complication in patients undergoing therapy for multiple myeloma. The main predisposing factors are the alkylating agents, topoisomerase II inhibitors and radiotherapy, but recently questions have been raised regarding the immunomodulatory agent lenalidomide. Little is known about the new antimyeloma agents in the context of therapy related myeloid malignanices. The duration of treatment and the time from diagnosis are the main contributing factors in alkylating induced myeloid malignancies which occur 5-10 years after treatment, chromosome 5 and 7 abnormalities being the characteristic finding. High dose therapy (HDT does not seem to be a major contributing factor per se in multiple myeloma. In a number of large published series, all the factors related with therapy-induced myelodysplasia were defined prior to HDT. Topoisomerase II inhibitors induce mainly acute leukemias which invariably correlate with dysregulation of the MLL gene. Radiotherapy causes therapy related myelodysplasia if applied in bone marrow producing areas, especially if combined with chemotherapy. Therapy related myeloid malignancies generally herald a poor prognosis. Karyotypic abnormalities seem to be the main prognostic factor. In all cases the risk for therapy related myeloid malignancies drops sharply by 10 years after the treatment.

29 CFR 525.11 - Issuance of certificates.

Science.gov (United States)

2010-07-01

... consideration of the criteria cited in these regulations, a special certificate may be issued. (b) If a special... notified in writing and told the reasons for the denial, as well as the right to petition under § 525.18. ...

49 CFR 214.525 - Towing with on-track roadway maintenance machines or hi-rail vehicles.

Science.gov (United States)

2010-10-01

... or hi-rail vehicles. 214.525 Section 214.525 Transportation Other Regulations Relating to... SAFETY On-Track Roadway Maintenance Machines and Hi-Rail Vehicles § 214.525 Towing with on-track roadway maintenance machines or hi-rail vehicles. (a) When used to tow pushcars or other maintenance-of-way equipment...

spib is required for primitive myeloid development in Xenopus.

Science.gov (United States)

Costa, Ricardo M B; Soto, Ximena; Chen, Yaoyao; Zorn, Aaron M; Amaya, Enrique

2008-09-15

Vertebrate blood formation occurs in 2 spatially and temporally distinct waves, so-called primitive and definitive hematopoiesis. Although definitive hematopoiesis has been extensively studied, the development of primitive myeloid blood has received far less attention. In Xenopus, primitive myeloid cells originate in the anterior ventral blood islands, the equivalent of the mammalian yolk sac, and migrate out to colonize the embryo. Using fluorescence time-lapse video microscopy, we recorded the migratory behavior of primitive myeloid cells from their birth. We show that these cells are the first blood cells to differentiate in the embryo and that they are efficiently recruited to embryonic wounds, well before the establishment of a functional vasculature. Furthermore, we isolated spib, an ETS transcription factor, specifically expressed in primitive myeloid precursors. Using spib antisense morpholino knockdown experiments, we show that spib is required for myeloid specification, and, in its absence, primitive myeloid cells retain hemangioblast-like characteristics and fail to migrate. Thus, we conclude that spib sits at the top of the known genetic hierarchy that leads to the specification of primitive myeloid cells in amphibians.

Preliminary clinical study of 99Tcm-HL91 imaging in bone metastasis

International Nuclear Information System (INIS)

Liu Baoping; Mao Ronghu; Han Xingmin

2008-01-01

Objective: 99 Tc m -4, 9-diaza-3, 3, 10, 10-tetramethyldodecan-2, 11-dione dioxime (HL91), a new type of hypoxic agents, accumulates in tumor hypoxic tissue specifically. The aim of this study was to evaluate the value of 99 Tc m -HL91 imaging in the diagnosis of bone metastasis. Methods: Nine- teen cases with bone metastasis (without any treatment) and 8 cases with benign lesions underwent SPECT imaging at 4 h after injection of 740 MBq of 99 Tc m -HL91 along with 99 Tc m -methylene diphosphonic acid (MDP) imaging. Regions of interest (ROIs) were drawn in tumor tissue and contralateral normal tissue respectively, and the radioactivity ratios of tumor-to-normal (T/N) were calculated. The t-test was used for data analysis with SPSS 11.0. Results: There were visible uptake of 99 Tc m -HL91 in 79 out of 85 focuses in 19 patients of bone metastasis; however, there was no obvious uptake of 99 Tc m -HL91 in 12 focuses of 8 patients of benign lesions. Significant difference existed between the T/N values of malignant (1.877 ± 0.288) and benign lesions [(0.735 ± 0.236); t=13.065, P 0.05). Conclusion: The results indicated that 99 Tc m -HL91 was useful in diagnosing the malignant and benign bone lesions. (authors)

Neurological Complications Of Chronic Myeloid Leukaemia: Any ...

African Journals Online (AJOL)

, of the neurological deficits complicating chronic myeloid leukaemia. Method: Using patients\\' case folders and haematological malignancy register all cases of chronic myeloid leukaemia seen in Jos University Teaching Hospital between July ...

Genetics Home Reference: core binding factor acute myeloid leukemia

Science.gov (United States)

... binding factor acute myeloid leukemia Core binding factor acute myeloid leukemia Printable PDF Open All Close All Enable Javascript ... on PubMed (1 link) PubMed OMIM (1 link) LEUKEMIA, ACUTE MYELOID Sources for This Page Goyama S, Mulloy JC. Molecular ...

Pixel DAQ and trigger for HL-LHC

International Nuclear Information System (INIS)

Morettini, P.

2017-01-01

The read-out is one of the challenges in the design of a pixel detector for the High Luminosity upgrade of the Large Hadron Collider (HL-LHC), that is expected to operate from 2026 at a leveled luminosity of 5 × 10 34  cm −2  s −1 . This is especially true if tracking information is needed in a low latency trigger system. The difficulties of a fast read-out will be reviewed, and possible strategies explained. The solutions that are being evaluated by the ATLAS and CMS collaborations for the upgrade of their trackers will be outlined and ideas on possible development beyond HL-LHC will be presented.

HL-LHC alternatives

CERN Document Server

Tomás, R; White, S

2014-01-01

The HL-LHC parameters assume unexplored regimes for hadron colliders in various aspects of accelerator beam dynamics and technology. This paper reviews three alternatives that could potentially improve the LHC performance: (i) the alternative filling scheme 8b+4e, (ii) the use of a 200 MHz RF system in the LHC and (iii) the use of proton cooling methods to reduce the beam emittance (at top energy and at injection). The alternatives are assessed in terms of feasibility, pros and cons, risks versus benefits and the impact on beam availability.

Expected performance of tracking and vertexing with the HL-LHC ATLAS detector

CERN Document Server

Calace, Noemi; The ATLAS collaboration

2018-01-01

The High Luminosity LHC (HL-LHC) aims to increase the LHC data-set by an order of magnitude in order to increase its potential for discoveries. Starting from the middle of 2026, the HL-LHC is expected to reach the peak instantaneous luminosity of $7.5 \\cdot 10^{34} cm^{-2}s^{-1}$ which corresponds to about 200 inelastic proton-proton collisions per beam crossing. To cope with the large radiation doses and high pileup, the current ATLAS Inner Detector will be replaced with a new all-silicon Inner Tracker. In this talk the expected performance of tracking and vertexing with the HL-LHC tracker is presented. Comparison is made to the performance with the Run2 detector. Ongoing developments of the track reconstruction for the HL-LHC are also discussed.

Extramedullary leukemia in children with acute myeloid leukemia

DEFF Research Database (Denmark)

Støve, Heidi Kristine; Sandahl, Julie Damgaard; Abrahamsson, Jonas

2017-01-01

BACKGROUND: The prognostic significance of extramedullary leukemia (EML) in childhood acute myeloid leukemia is not clarified. PROCEDURE: This population-based study included 315 children from the NOPHO-AML 2004 trial. RESULTS: At diagnosis, 73 (23%) patients had EML: 39 (12%) had myeloid sarcoma...... the OS. No patients relapsed at the primary site of the myeloid sarcoma despite management without radiotherapy....

The HL-LHC accelerator physics challenges

CERN Document Server

Fartoukh, S

2014-01-01

We review the conceptual baseline of the HL-LHC project, putting into perspective the main beam physics challenges of this new collider in comparison with the existing LHC, and the series of solutions and possible mitigation measures presently envisaged.

The HL-LHC Accelerator Physics Challenges

Science.gov (United States)

Fartoukh, S.; Zimmermann, F.

The conceptual baseline of the HL-LHC project is reviewed, putting into perspective the main beam physics challenges of this new collider in comparison with the existing LHC, and the series of solutions and possible mitigation measures presently envisaged.

The HL-LHC accelerator physics challenges

CERN Document Server

Fartoukh, S

2015-01-01

The conceptual baseline of the HL-LHC project is reviewed, putting into perspective the main beam physics challenges of this new collider in comparison with the existing LHC, and the series of solutions and possible mitigation measures presently envisaged.

The CNGRC-GG-D(KLAKLAK)2 peptide induces a caspase-independent, Ca2+-dependent death in human leukemic myeloid cells by targeting surface aminopeptidase N/CD13.

Science.gov (United States)

Bouchet, Sandrine; Tang, Ruoping; Fava, Fanny; Legrand, Ollivier; Bauvois, Brigitte

2016-04-12

The CD13 antigen's binding site for the Asn-Gly-Arg (NGR) motif enables NGR-containing chemotherapeutic drugs to be delivered to CD13-positive tumours. Human CD13-positive acute myeloid leukemia (AML) cells proliferate abnormally and escape death. Here, we show that the CNGRC-GG-D(KLAKLAK)2 peptide induces death in AML cell lines (U937, THP-1, NB4, HL-60) and primary blood cells from AML patients. Cell death was characterized as a caspase-independent mechanism, without DNA fragmentation, but phosphatidylserine externalization and membrane disruption. Our results demonstrate in U937 cells that (i) the NGR-peptide triggers the loss of mitochondrial potential(ΔΨm) and generates superoxide anion (O2-), (ii) N-acetyl-L-cysteine (NAC) and extra/intracellular Ca2+ chelators (BAPTA) prevent both O2- production and cell death, (iii) the Ca2+-channel blocker nifedipine prevents cell death (indicating that Ca2+ influx is the initial death trigger), and (iv) BAPTA, but not NAC, prevents ΔΨm loss (suggesting O2- is a mitochondrial downstream effector). AML cell lines and primary blasts responding to the lethal action of NGR-peptide express promatrix metalloproteinase-12 (proMMP-12) and its substrate progranulin (an 88 kDa cell survival factor). A cell-free assay highlighted proMMP-12 activation by O2-. Accordingly, NGR-peptide's downregulation of 88 kDa progranulin protein was prevented by BAPTA and NAC. Conversely, AML blast resistance to NGR-peptide is associated with the expression of a distinct, 105 kDa progranulin isoform. These results indicate that CNGRC-GG-D(KLAKLAK)2 induces death in AML cells through the Ca2+-mitochondria-O2.-pathway, and support the link between proMMP-12 activation and progranulin cleavage during cell death. Our findings may have implications for the understanding of tumour biology and treatment.

Isolation of furocoumarins from bergamot fruits as HL-60 differentiation-inducing compounds.

Science.gov (United States)

Kawaii, S; Tomono, Y; Katase, E; Ogawa, K; Yano, M

1999-10-01

The HL-60 differentiation-inducing compounds in bergamot fruits were isolated with column chromatography and identified as bergamottin, bergapten, and citropten by (1)H and (13)C NMR. Their HL-60 differentiation-inducing activity was measured by examining nitro blue tetrazolium (NBT) reducing, nonspecific acid esterase (NSE), specific esterase (SE), and phagocytic activities, and bergamottin showed the strongest activity among the coumarins isolated from bergamot fruits. The structure-activity relationship obtained from HL-60 differentiation assay suggests that hydrophobicity of furocoumarins is correlated with their activity.

Diagnostic confusion resulting from CD56 expression by cutaneous myeloid sarcoma

Directory of Open Access Journals (Sweden)

Sheeja T. Pullarkat

2009-12-01

Full Text Available Myeloid sarcomas are tumor masses composed of aggregates of malignant myeloid precursors in extramedullary sites including the skin. We report a case of myeloid sarcoma in a patient who presented with an ear lobe mass and facial nerve paralysis. Expression of CD56 by the malignant cells led to an initial misdiagnosis as Merkel cell tumor. Comprehensive pathological evaluation confirmed the diagnosis of myeloid sarcoma with aberrant expression of CD56 and carrying the translocation t(8;21 (q22;q22. Aberrant antigen expression by cutaneous myeloid sarcomas can cause diagnostic confusion with other cutaneous neoplasms. This is especially relevant when myeloid sarcoma is the sole manifestation of acute myeloid leukemia.

A Novel Dual HDAC6 and Tubulin Inhibitor, MPT0B451, Displays Anti-tumor Ability in Human Cancer Cells in Vitro and in Vivo

Directory of Open Access Journals (Sweden)

Yi-Wen Wu

2018-03-01

Full Text Available The combination cancer therapy is a new strategy to circumvent drug resistance for the treatment of high metastasis and advanced malignancies. Herein, we developed a synthesized compound MPT0B451 that display inhibitory effect against histone deacetylase (HDAC 6 and tubulin assembly. Our data demonstrated that MPT0B451 significantly inhibited cancer cell growths in HL-60 and PC-3 cells due to inhibition of HDAC activity. MPT0B451 also markedly increased caspase-mediated apoptosis in these cells. The cell cycle analysis showed mitotic arrest induced by MPT0B451 with enhanced expression of G2/M transition proteins. Moreover, molecular docking analysis supported MPT0B451 as a dual HDAC6 and tubulin inhibitor. Finally, MPT0B451 led to tumor growth inhibition (TGI in HL-60 and PC-3 xenograft models. These findings indicated that MPT0B451 has dual inhibition effects for HDAC6 and tubulin, and also contributed to G2/M arrest followed by apoptotic induction. Together, our results suggested that MPT0B451 may serve as a potent anti-cancer treatment regimen in human prostate cancer and acute myeloid leukemia.

HL-LHC kicker magnet (MKI)

CERN Multimedia

Brice, Maximilien

2018-01-01

HL-LHC kicker magnet (MKI): last vacuum test, preparation for transport to LHC transfer line in underground tunnel.The LHC injection kicker systems (MKIs) generate fast field pulses to inject the clockwise rotating beam at Point 2 and the anti-clockwise rotating beam at Point 8: there are eight MKI magnets installed in total. Each MKI magnet contains a high purity alumina tube: if an MKI magnet is replaced this tube requires conditioning with LHC beam: until it is properly conditioned, there can be high vacuum pressure due to the beam. This high pressure can also cause electrical breakdowns in the MKI magnets. A special coating (Cr2O3) has been applied to the inside of the alumina tube of an upgraded MKI magnet – this is expected to greatly reduce the pressure rise with beam. In addition, HL-LHC beam would result in excessive heating of the MKI magnets: the upgraded design includes modifications that will reduce heating, and move the power deposition to parts that will be easier to cool. Experience during 2...

Childhood Acute Myeloid Leukemia Treatment (PDQ®)—Health Professional Version

Science.gov (United States)

Acute myeloid leukemia (AML), juvenile myelomonocytic leukemia (JMML), acute promyelocytic leukemia (APL) and chronic myeloid leukemia (CML) account for about 20% of childhood myeloid leukemias. Other myeloid malignancies include transient abnormal myelopoiesis and myelodysplastic syndrome. Get detailed information about the classification, clinical presentation, diagnostic and molecular evaluation, prognosis, and treatment of newly diagnosed and recurrent disease in this summary for clinicians.

Myeloid Sarcoma after Allogenic Stem Cell Transplantation for Acute Myeloid Leukemia: Successful Consolidation Treatment Approaches in Two Patients

Directory of Open Access Journals (Sweden)

Silje Johansen

2018-01-01

Full Text Available Myeloid sarcoma is an extramedullary (EM manifestation (i.e., manifestation outside the bone marrow of acute myeloid leukemia (AML; it is assumed to be relatively uncommon and can be the only manifestation of leukemia relapse after allogenic stem cell transplantation (allo-SCT. An EM sarcoma can manifest in any part of the body, although preferentially manifesting in immunological sanctuary sites as a single or multiple tumors. The development of myeloid sarcoma after allo-SCT is associated with certain cytogenetic abnormalities, developing of graft versus host disease (GVHD, and treatment with donor lymphocytes infusion (DLI. It is believed that posttransplant myeloid sarcomas develop because the EM sites evade immune surveillance. We present two patients with EM myeloid sarcoma in the breast and epipharynx, respectively, as the only manifestation of leukemia relapse. Both patients were treated with a combination of local and systemic therapy, with successfully longtime disease-free survival. Based on these two case reports, we give an updated review of the literature and discuss the pathogenesis, diagnosis, and treatment of EM sarcoma as the only manifestation of AML relapse after allo-SCT. There are no standard guidelines for the treatment of myeloid sarcomas in allotransplant recipients. In our opinion, the treatment of these patients needs to be individualized and should include local treatment (i.e., radiotherapy combined with systemic therapy (i.e., chemotherapy, immunotherapy, DLI, or retransplantation. The treatment has to consider both the need for sufficient antileukemic efficiency versus the risk of severe complications due to cumulative toxicity.

29 CFR 5.25 - Rate of contribution or cost for fringe benefits.

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Rate of contribution or cost for fringe benefits. 5.25... Fringe Benefits Provisions of the Davis-Bacon Act § 5.25 Rate of contribution or cost for fringe benefits... contribution or cost of fringe benefits. Only the amount of contributions or costs for fringe benefits which...

An experimental study on cerebral ischemic penumbra imaging with 99Tcm-HL91

International Nuclear Information System (INIS)

Zhu Cansheng; Jiang Ningyi

2002-01-01

Objective: To investigate the biodistribution of 99 Tc m -4,9-diaza-3,3,10,10-tetramethyl dodecan-2,11-dione dioxime (HL91) in rat model of middle cerebral artery occlusion (MCAO). Methods: Thirty-one MCAO rats were established. Fourteen rats were used to study the biodistribution of 99 Tc m -HL91 and 15 rats were used to study the distribution of 99 Tc m -HL91 in the brain of MCAO model rats. Autoradiographic study of brain was also done in 16 MCAO model rats. Results: The liver and kidney retention were higher than that in other tissues. At 1 h after injection, small intestine retention was also high. But radioactivity in normal brain was low. Retention in target site was higher than that in non-target site. Difference between subgroups of operation and that of pseudo operation was significant (P 99 Tc m -HL91 at the target-ischemic area was shown in the autoradiograph. By using computer-enhanced image analysis, difference between target site and non-target site in the same autoradiograph and the differences between operation subgroups and that of pseudo-subgroups were all significant via Dunnett t-test and One-Way ANOVA. Conclusions: 99 Tc m -HL91 can be avidly taken up by ischemic penumbra and target/non-target ratio is high. 99 Tc m -HL91 is a potential agent for hypoxic tissue imaging, and 99 Tc m -HL91 SPECT is a promising modality in detecting the ischemic penumbra

Application of 99Tcm-HL-91 in the hypoxia study of malignant lymphoma

International Nuclear Information System (INIS)

Li Li; Han Peizhen; Yan Yujun; Wang Yueying; Wang Junqi; Li Meijia

2002-01-01

Objective: 99 Tc m -HL91 is a putative hypoxic tracer probing hypoxia in solid tumors. This study was aimed at investigating the property of the spontaneous IRM-2-ML malignant lymphoma in homozygotic IRM-2 mice, and at testing the applicability of 99 Tc m -HL91 to the imaging of hypoxia in tumors. Methods: Biodistribution of 99 Tc m -HL91 after intravenously injection into normal and tumor-bearing IRM-2 mice was studied by determining blood and tissue levels of radioactivity from 20 to 360 min after injection. Nicotinamide was used to reduce the extent of hypoxia in the tumors. Planar SPECT imaging on normal and tumor-bearing IRM-2 mice was also performed. Results: Tumor load did not significantly influence the retention of 99 Tc m -HL91 in normal organs. 99 Tc m -HL91 was metabolized mainly via the liver and kidney, and was cleared fast from the blood. The tumor-to-blood ratio and tumor-to-muscle ratio continued to increase until 360 min (2.63 +- 0.25 and 3.37 +- 0.22 at 120 min, 3.51 +- 0.17 and 6.44 +- 0.29 at 360 min, respectively). The retention of 99 Tc m -HL91 in the tumor was reduced in mice by treatment with nicotinamide. Planar SPECT imaging showed that tumor could be observed clearly. Conclusion: These results confirm that IRM-2-ML malignant lymphoma possesses the common property of solid tumors,and also indicate that 99 Tc m -HL91 could be used to detect tumor hypoxia

Modification of steel 35 HL surge current during crystallization

Directory of Open Access Journals (Sweden)

Zhbanova O.M.

2017-04-01

Full Text Available The method of electro steel melt modification 35 HL variable polarity current pulses with a duration of more 10-3s frequency within the 5–33 Hz, 5–24 porosity meanders, strength 30–40 A at a voltage of 180–240 V during crystallization, which allows to obtain high-quality castings 35 HL steel grade. Show that electro melt processing improves the structure and reduces the physical heterogeneity of castings and increases the rate of dissolution of metallic impurities and other components in the melt, providing fine-grained structure and increases the homogeneity of metal carbides reduces the amount of manganese reduces gases and nonmetallic inclusions. Modifying steel 35 HL pulse current during crystallization of the melt increases the physical and mechanical properties of tempered steel, increasing yield strength by 30 %, the tensile strength at 7 % elongation of 1,5 % relative narrowing by 2 %, toughness at 20 %.

A novel application of furazolidone: anti-leukemic activity in acute myeloid leukemia.

Directory of Open Access Journals (Sweden)

Xueqing Jiang

Full Text Available Acute myeloid leukemia (AML is the most common malignant myeloid disorder of progenitor cells in myeloid hematopoiesis and exemplifies a genetically heterogeneous disease. The patients with AML also show a heterogeneous response to therapy. Although all-trans retinoic acid (ATRA has been successfully introduced to treat acute promyelocytic leukemia (APL, it is rather ineffective in non-APL AML. In our present study, 1200 off-patent marketed drugs and natural compounds that have been approved by the Food and Drug Administration (FDA were screened for anti-leukemia activity using the retrovirus transduction/transformation assay (RTTA. Furazolidone (FZD was shown to inhibit bone marrow transformation mediated by several leukemia fusion proteins, including AML1-ETO. Furazolidone has been used in the treatment of certain bacterial and protozoan infections in human and animals for more than sixty years. We investigated the anti-leukemic activity of FZD in a series of AML cells. FZD displayed potent antiproliferative properties at submicromolar concentrations and induced apoptosis in AML cell lines. Importantly, FZD treatment of certain AML cells induced myeloid cell differentiation by morphology and flow cytometry for CD11b expression. Furthermore, FZD treatment resulted in increased stability of tumor suppressor p53 protein in AML cells. Our in vitro results suggest furazolidone as a novel therapeutic strategy in AML patients.

Myeloid malignancies: mutations, models and management

International Nuclear Information System (INIS)

Murati, Anne; Brecqueville, Mandy; Devillier, Raynier; Mozziconacci, Marie-Joelle; Gelsi-Boyer, Véronique; Birnbaum, Daniel

2012-01-01

Myeloid malignant diseases comprise chronic (including myelodysplastic syndromes, myeloproliferative neoplasms and chronic myelomonocytic leukemia) and acute (acute myeloid leukemia) stages. They are clonal diseases arising in hematopoietic stem or progenitor cells. Mutations responsible for these diseases occur in several genes whose encoded proteins belong principally to five classes: signaling pathways proteins (e.g. CBL, FLT3, JAK2, RAS), transcription factors (e.g. CEBPA, ETV6, RUNX1), epigenetic regulators (e.g. ASXL1, DNMT3A, EZH2, IDH1, IDH2, SUZ12, TET2, UTX), tumor suppressors (e.g. TP53), and components of the spliceosome (e.g. SF3B1, SRSF2). Large-scale sequencing efforts will soon lead to the establishment of a comprehensive repertoire of these mutations, allowing for a better definition and classification of myeloid malignancies, the identification of new prognostic markers and therapeutic targets, and the development of novel therapies. Given the importance of epigenetic deregulation in myeloid diseases, the use of drugs targeting epigenetic regulators appears as a most promising therapeutic approach

Systemic agonistic anti-CD40 treatment of tumor bearing mice modulates hepatic myeloid suppressive cells and causes immune-mediated liver damage

Science.gov (United States)

Medina-Echeverz, José; Ma, Chi; Duffy, Austin; Eggert, Tobias; Hawk, Nga; Kleiner, David E.; Korangy, Firouzeh; Greten, Tim F.

2015-01-01

Immune stimulatory monoclonal antibodies are currently evaluated as anti tumor agents. Although overall toxicity appears to be moderate, liver toxicities have been reported and are not completely understood. We studied the effect of systemic CD40 antibody treatment on myeloid cells in spleen and liver. Naïve and tumor-bearing mice were treated systemically with agonistic anti-CD40 antibody. Immune cell subsets in liver and spleen, serum transaminases and liver histologies were analyzed after antibody administration. Nox2−/−, Cd40−/− as well as bone marrow chimeric mice were used to study the mechanism by which agonistic anti-CD40 mediates its effects in vivo. Suppressor function of murine and human tumor-induced myeloid derived suppressive cells was studied upon CD40 ligation. Agonistic CD40 antibody caused liver damage within 24 hours after injection in two unrelated tumor models and mice strains. Using bone marrow chimeras we demonstrated that CD40 antibody-induced hepatitis in tumor-bearing mice was dependent on the presence of CD40-expressing hematopoietic cells. Agonistic CD40 ligation-dependent liver damage was induced by the generation of reactive oxygen species. Furthermore, agonistic CD40 antibody resulted in increased CD80 and CD40 positive liver CD11b+Gr-1+ immature myeloid cells. CD40 ligation on tumor-induced murine and human CD14+HLA-DRlow PBMC from cancer patients reduced their immune suppressor function. Collectively, agonistic CD40 antibody treatment activated tumor-induced, myeloid cells, caused myeloid dependent hepatotoxicity and ameliorated the suppressor function of murine and human MDSC. Collectively, our data suggests that CD40 may mature immunosuppressive myeloid cells and thereby cause liver damage in mice with an accumulation of tumor-induced hepatic MDSC. PMID:25637366

Down-regulation of procaspase-8 expression by focal adhesion kinase protects HL-60 cells from TRAIL-induced apoptosis

International Nuclear Information System (INIS)

Tamagiku, Yuji; Sonoda, Yoshiko; Kunisawa, Mari; Ichikawa, Daiju; Murakami, Yayoi; Aizu-Yokota, Eriko; Kasahara, Tadashi

2004-01-01

We have demonstrated that focal adhesion kinase (FAK)-overexpressed (HL-60/FAK) cells have marked resistance against various apoptotic stimuli such as hydrogen peroxide, etoposide, and ionizing radiation compared with the vector-transfected (HL-60/Vect) cells. HL-60/FAK cells are highly resistant to TRAIL-induced apoptosis, while original HL-60 or HL-60/Vect cells were sensitive. TRAIL at 500 ng/ml induced significant DNA fragmentation, activation of caspase-8 and 3, the processing of a proapoptotic BID, and mitochondrial release of cytochrome c in HL-60/Vect cells, whereas no such events were observed in the HL-60/FAK cells. In particular, the expression of procaspase-8 gene and subsequent cleavage of caspase-8 were markedly reduced in HL-60/FAK cells, while expression of TRAIL-receptor 2 and 3, TRADD, and FADD was equivalent in both types of cells. In HL-60/FAK cells, the phosphoinositide 3 (PI3)-kinase/Akt survival pathway was constitutively activated, accompanied by significant induction of inhibitor-of-apoptosis proteins, XIAP, RIP, and Bcl-XL. The introduction of FAK siRNA in HL-60/FAK cells sensitized them against TRAIL-induced apoptosis, confirming that overexpressed FAK downregulates procaspase-8 expression, which subsequently inhibits downstream apoptosis pathway in the HL-60/FAK cells

Myeloid-Related Protein 14 Promotes Inflammation and Injury in Meningitis

DEFF Research Database (Denmark)

Wache, Christina; Klein, Matthias; Andersen, Christian Østergaard

2015-01-01

BACKGROUND:  Neutrophilic inflammation often persists for days despite effective antibiotic treatment and contributes to brain damage in bacterial meningitis. We propose here that myeloid-related protein 14 (MRP14), an abundant cytosolic protein in myeloid cells, acts as an endogenous danger signal......, driving inflammation and aggravating tissue injury. METHODS:  The release pattern of MRP14 was analyzed in human and murine cerebrospinal fluid (CSF), as well as in isolated neutrophils. Its functional role was assessed in a mouse meningitis model, using MRP14-deficient mice. RESULTS:  We detected large...... quantities of MRP14 in CSF specimens from patients and mice with pneumococcal meningitis. Immunohistochemical analyses and a cell-depletion approach indicated neutrophils as the major source of MRP14. In a meningitis model, MRP14-deficient mice showed a better resolution of inflammation during antibiotic...

Epigenetics targeted protein-vorinostat nanomedicine inducing apoptosis in heterogeneous population of primary acute myeloid leukemia cells including refractory and relapsed cases.

Science.gov (United States)

Chandran, Parwathy; Kavalakatt, Anu; Malarvizhi, Giridharan Loghanathan; Vasanthakumari, Divya Rani Vikraman Nair; Retnakumari, Archana Payickattu; Sidharthan, Neeraj; Pavithran, Keechilat; Nair, Shantikumar; Koyakutty, Manzoor

2014-05-01

Aberrant epigenetics play a key role in the onset and progression of acute myeloid leukemia (AML). Herein we report in silico modelling based development of a novel, protein-vorinostat nanomedicine exhibiting selective and superior anti-leukemic activity against heterogeneous population of AML patient samples (n=9), including refractory and relapsed cases, and three representative cell lines expressing CD34(+)/CD38(-) stem cell phenotype (KG-1a), promyelocytic phenotype (HL-60) and FLT3-ITD mutation (MV4-11). Nano-vorinostat having ~100nm size exhibited enhanced cellular uptake rendering significantly lower IC50 in AML cell lines and patient samples, and induced enhanced HDAC inhibition, oxidative injury, cell cycle arrest and apoptosis compared to free vorinostat. Most importantly, nanomedicine showed exceptional single-agent activity against the clonogenic proliferative capability of bone marrow derived leukemic progenitors, while remaining non-toxic to healthy bone marrow cells. Collectively, this epigenetics targeted nanomedicine appears to be a promising therapeutic strategy against various French-American-British (FAB) classes of AML. Through the use of a protein-vorinostat agent, exceptional single-agent activity was demonstrated against the clonogenic proliferative capability of bone marrow derived leukemic progenitors, while remaining non-toxic to healthy bone marrow cells. The studied epigenetics targeted nanomedicine approach is a promising therapeutic strategy against various French-American-British classes of acute myeloid leukemia. © 2014 Elsevier Inc. All rights reserved.

Differentiation Therapy of Acute Myeloid Leukemia

International Nuclear Information System (INIS)

Gocek, Elzbieta; Marcinkowska, Ewa

2011-01-01

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

Differentiation Therapy of Acute Myeloid Leukemia

Energy Technology Data Exchange (ETDEWEB)

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

2011-05-16

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

Regulatory Myeloid Cells in Transplantation

Science.gov (United States)

Rosborough, Brian R.; Raïch-Regué, Dàlia; Turnquist, Heth R.; Thomson, Angus W.

2013-01-01

Regulatory myeloid cells (RMC) are emerging as novel targets for immunosuppressive (IS) agents and hold considerable promise as cellular therapeutic agents. Herein, we discuss the ability of regulatory macrophages (Mreg), regulatory dendritic cells (DCreg) and myeloid-derived suppressor cells (MDSC) to regulate alloimmunity, their potential as cellular therapeutic agents and the IS agents that target their function. We consider protocols for the generation of RMC and the selection of donor- or recipient-derived cells for adoptive cell therapy. Additionally, the issues of cell trafficking and antigen (Ag) specificity following RMC transfer are discussed. Improved understanding of the immunobiology of these cells has increased the possibility of moving RMC into the clinic to reduce the burden of current IS agents and promote Ag-specific tolerance. In the second half of this review, we discuss the influence of established and experimental IS agents on myeloid cell populations. IS agents believed historically to act primarily on T cell activation and proliferation are emerging as important regulators of RMC function. Better insights into the influence of IS agents on RMC will enhance our ability to develop cell therapy protocols to promote the function of these cells. Moreover, novel IS agents may be designed to target RMC in situ to promote Ag-specific immune regulation in transplantation and usher in a new era of immune modulation exploiting cells of myeloid origin. PMID:24092382

Do We Know What Causes Chronic Myeloid Leukemia?

Science.gov (United States)

... Be Prevented? More In Chronic Myeloid Leukemia About Chronic Myeloid Leukemia Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treatment After Treatment Back To Top Imagine a world ...

Multi-channel time-division integrator in HL-2A

International Nuclear Information System (INIS)

Yan Ji

2008-01-01

HL-2A is China's first Tokamak device with divertor configuration (magnetic confinement controlled nuclear fusion device). To find out the details of on-going fusion reaction at different times is of important significance in achieving controlled nuclear fusion. We developed a new type multi-channel time-division integrator for HL-2A. It has functions of automatic cutting off negative pulse of the input signals, optional integrating time division spacing 0.2-1 ms, TTL starting trigger signal, automatic regularly work 20 s, and integrating 10 channel at the same time. (authors)

Introduction to the HL-LHC Project

CERN Document Server

Rossi , L

2015-01-01

The Large Hadron Collider (LHC) is one of largest scientific instruments ever built. It has been exploring the new energy frontier since 2010, gathering a global user community of 7,000 scientists. To extend its discovery potential, the LHC will need a major upgrade in the 2020s to increase its luminosity (rate of collisions) by a factor of five beyond its design value and the integrated luminosity by a factor of ten. As a highly complex and optimized machine, such an upgrade of the LHC must be carefully studied and requires about ten years to implement. The novel machine configuration, called High Luminosity LHC (HL-LHC), will rely on a number of key innovative technologies, representing exceptional technological challenges, such as cutting-edge 11–12 tesla superconducting magnets, very compact superconducting cavities for beam rotation with ultra-precise phase control, new technology for beam collimation and 300-meter-long high-power superconducting links with negligible energy dissipation. HL-LHC federa...

Genetics Home Reference: familial acute myeloid leukemia with mutated CEBPA

Science.gov (United States)

... Familial acute myeloid leukemia with mutated CEBPA Familial acute myeloid leukemia with mutated CEBPA Printable PDF Open All Close ... on PubMed (1 link) PubMed OMIM (1 link) LEUKEMIA, ACUTE MYELOID Sources for This Page Carmichael CL, Wilkins EJ, ...

41 CFR 101-4.525 - Fringe benefits.

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Fringe benefits. 101-4... in Employment in Education Programs or Activities Prohibited § 101-4.525 Fringe benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, fringe benefits means: Any medical, hospital...

The role of peptide and DNA vaccines in myeloid leukemia immunotherapy

Directory of Open Access Journals (Sweden)

Lin Chen

2013-02-01

Full Text Available Abstract While chemotherapy and targeted therapy are successful in inducing the remission of myeloid leukemia as acute myeloid leukemia (AML and chronic myeloid leukemia (CML, the disease remains largely incurable. This observation is likely due to the drug resistance of leukemic cells, which are responsible for disease relapse. Myeloid leukemia vaccines may most likely be beneficial for eradicating minimal residual disease after treatment with chemotherapy or targeted therapy. Several targeted immunotherapies using leukemia vaccines have been heavily investigated in clinical and preclinical trials. This review will focus on peptides and DNA vaccines in the context of myeloid leukemias, and optimal strategies for enhancing the efficacy of vaccines based on myeloid leukemia immunization are also summarized.

The CMS ECAL Upgrade for Precision Crystal Calorimetry at the HL-LHC

CERN Document Server

Petyt, David Anthony

2018-01-01

The electromagnetic calorimeter (ECAL) of the Compact Muon Solenoid Experiment (CMS) is operating at the Large Hadron Collider (LHC) in 2016 with proton-proton collisions at 13 TeV center-of-mass energy and at a bunch spacing of 25 ns. Challenging running conditions for CMS are expected after the High-Luminosity upgrade of the LHC (HL-LHC). We review the design and R and D studies for the CMS ECAL crystal calorimeter upgrade and present first test beam studies. Particular challenges at HL-LHC are the harsh radiation environment, the increasing data rates and the extreme level of pile-up events, with up to 200 simultaneous proton-proton collisions. We present test beam results of hadron irradiated PbWO$_{4}$ crystals up to fluences expected at the HL-LHC. We also report on the R and D for the new readout and trigger electronics, which must be upgraded due to the increased trigger and latency requirements at the HL-LHC.

HL-LHC and HE-LHC Upgrade Plans and Opportunities for US Participation

Science.gov (United States)

Apollinari, Giorgio

2017-01-01

The US HEP community has identified the exploitation of physics opportunities at the High Luminosity-LHC (HL-LHC) as the highest near-term priority. Thanks to multi-year R&D programs, US National Laboratories and Universities have taken the leadership in the development of technical solutions to increase the LHC luminosity, enabling the HL-LHC Project and uniquely positioning this country to make critical contributions to the LHC luminosity upgrade. This talk will describe the shaping of the US Program to contribute in the next decade to HL-LHC through newly developed technologies such as Nb3Sn focusing magnets or superconducting crab cavities. The experience gained through the execution of the HL-LHC Project in the US will constitute a pool of knowledge and capabilities allowing further developments in the future. Opportunities for US participations in proposed hadron colliders, such as a possible High Energy-LHC (HE-LHC), will be described as well.

Will ALICE run in the HL-LHC era?

International Nuclear Information System (INIS)

Wessels, J.P.

2012-01-01

We will present the perspectives for ion running in the HL-LHC era. In particular, ALICE is preparing a significant upgrade of its rate capabilities and is further extending its particle identification potential. This paves the way for heavy ion physics at unprecedented luminosities, which are expected in the HL-LHC era with the heaviest ions. Here, we outline a scenario, in which ALICE will be taking data at a luminosity of L > 6*10 27 cm -2 *s -1 for Pb-Pb with the aim of collecting at least 10 nb -1 . The potential interest of data-taking during high luminosity proton runs for ATLAS and CMS will also be commented. (author)

Genetics Home Reference: cytogenetically normal acute myeloid leukemia

Science.gov (United States)

... Testing (1 link) Genetic Testing Registry: Acute myeloid leukemia Other Diagnosis and Management Resources (3 links) Fred Hutchinson Cancer Research Center National Cancer Institute: Acute Myeloid Leukemia Treatment St. Jude Children's Research Hospital General Information ...

Overexpression of the Large-Conductance, Ca2+-Activated K+ (BK) Channel Shortens Action Potential Duration in HL-1 Cardiomyocytes.

Science.gov (United States)

Stimers, Joseph R; Song, Li; Rusch, Nancy J; Rhee, Sung W

2015-01-01

Long QT syndrome is characterized by a prolongation of the interval between the Q wave and the T wave on the electrocardiogram. This abnormality reflects a prolongation of the ventricular action potential caused by a number of genetic mutations or a variety of drugs. Since effective treatments are unavailable, we explored the possibility of using cardiac expression of the large-conductance, Ca2+-activated K+ (BK) channel to shorten action potential duration (APD). We hypothesized that expression of the pore-forming α subunit of human BK channels (hBKα) in HL-1 cells would shorten action potential duration in this mouse atrial cell line. Expression of hBKα had minimal effects on expression levels of other ion channels with the exception of a small but significant reduction in Kv11.1. Patch-clamped hBKα expressing HL-1 cells exhibited an outward voltage- and Ca2+-sensitive K+ current, which was inhibited by the BK channel blocker iberiotoxin (100 nM). This BK current phenotype was not detected in untransfected HL-1 cells or in HL-1 null cells sham-transfected with an empty vector. Importantly, APD in hBKα-expressing HL-1 cells averaged 14.3 ± 2.8 ms (n = 10), which represented a 53% reduction in APD compared to HL-1 null cells lacking BKα expression. APD in the latter cells averaged 31.0 ± 5.1 ms (n = 13). The shortened APD in hBKα-expressing cells was restored to normal duration by 100 nM iberiotoxin, suggesting that a repolarizing K+ current attributed to BK channels accounted for action potential shortening. These findings provide initial proof-of-concept that the introduction of hBKα channels into a cardiac cell line can shorten APD, and raise the possibility that gene-based interventions to increase hBKα channels in cardiac cells may hold promise as a therapeutic strategy for long QT syndrome.

21 CFR 111.525 - What requirements apply to a returned dietary supplement that quality control personnel approve...

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What requirements apply to a returned dietary supplement that quality control personnel approve for reprocessing? 111.525 Section 111.525 Food and Drugs... FOR DIETARY SUPPLEMENTS Returned Dietary Supplements § 111.525 What requirements apply to a returned...

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

Directory of Open Access Journals (Sweden)

Shanmin Zhao

2014-01-01

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

A discussion on practicable scheme for machine control system of HL-2A tokamak

International Nuclear Information System (INIS)

Li Qiang; Song Xianming; Jiang Chao

2001-01-01

This is the modified version of The Preliminary Design on the Hardware and Nets of HL-2A Tokamak. In this version, centralized control as well as the field bus communication on HL-2A Tokamak is used. The hardware components and the operational theory are introduced. The questions of practice program, extensibility, centralized control, cooperation with other subsystems and the continuous adaptation of present device are all discussed. The budget of the system is detailed. To keep the step with the overall engineering constructions of HL-2A, suggestions of the time program are presented for the system design, instrument purchases, installation, construction, user program development and the final operation processes for the machine control system of HL-2A Tokamak

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

DEFF Research Database (Denmark)

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

1998-01-01

The Brown Norwegian rat transplanted with promyelocytic leukaemic cells (BNML) has been used as a model for human acute myeloid leukaemia. We have previously shown that both the blood supply to the bone marrow and the metabolic rate decrease in relation to the leukaemic development in these rats....

Phenotype-gene: 525 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 525 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u3ria224u1522i lethal (sensu gen...Sci. U.S.A. 101(20):7821-6. http://metadb.riken.jp/db/SciNetS_ria224i/cria224u4ria224u15136745i lethal (sensu gen

Ageing studies of resistive Micromegas detectors for the HL-LHC

CERN Document Server

Galán, J; Ferrer-Ribas, E; Giganon, A; Giomataris, I; Herlant, S; Jeanneau, F; Peyaud, A; Schune, Ph; Alexopoulos, T; Byszewski, M; Iakovidis, G; Iengo, P; Ntekas, K; Leontsinis, S; de Oliveira, R; Tsipolitis, Y; Wotschack, J

2013-01-01

Resistive-anode Micromegas detectors are in development since several years, in an effort to solve the problem of sparks when working in high flux and high radiations environment like in the HL-LHC (ten times the luminosity of the LHC). They have been chosen as one of the technologies that will be part of the ATLAS New Small Wheel project (forward muon system). An ageing study is mandatory to assess their capabilities to handle the HL-LHC environment on a long-term period. A prototype has been exposed to several types of irradiations (X-rays, cold neutrons, 60 Co gammas) up to an equivalent HL-LHC time of more than five years without showing any degradation of the performances in terms of gain and energy resolution. Beam test studies took place in October 2012 to assess the tracking performances (efficiency, spatial resolution,...). Results of ageing studies and beam test performances are reported in this paper.

Super and ferric: the first HL-LHC component is ready

CERN Multimedia

Antonella Del Rosso

2016-01-01

Although the actual installation phase in the tunnel will only start in 2024, the first magnet – a sextupole – of the High-Luminosity LHC (HL-LHC) is ready and working according to specifications. This first component is also rather unique as, unlike the superconducting magnets currently used in the LHC, it relies on a “superferric” heart.   An expert in the LASA Laboratory (INFN Milan, Italy) works on assembling the first sextupole corrector of the HL-LHC. (Image: INFN Milan) Although the name might sound completely unfamiliar, superferric magnets were first proposed in the 1980s as a possible solution for high-energy colliders. However, many technical problems had to be overcome before the use of superferric magnets could become a reality. In its final configuration, the HL-LHC will have 36 superferric corrector magnets, of which 4 will be quadrupoles, 8 sextupoles and 24 higher order magnets. In superferric (or “iron-dominated”) magne...

Synthesis and Structures of Two Lanthanide Complexes Containing a Mixed Ligand System: [Ln(Phen)2(L)3(HL)]·H2O [Ln = La, Ce; Phen = Phenanthroline; HL = Salicylic Acid

International Nuclear Information System (INIS)

Iravani, Effat; Nami, Navabeh; Nabizadeh, Fatemeh; Bayani, Elham; Neumueller, Bernhard

2013-01-01

The reaction of LnCl 3 ·7H 2 O [Ln = La (1), Ce (2)] with salicylic acid (HL) and 1,10-phenanthroline (Phen) at 20 .deg. C in H 2 O/ethanol gave after work-up and recrystallization two novel lanthanide complexes with general formula [Ln(Phen) 2 (L) 3 (HL)]·H 2 O. Compounds 1 and 2 were characterized by IR and UV-Vis spectroscopy, TGA, CHN as well as by X-ray analysis. According to these results, compounds 1 and 2 are isostructural and contain Ln 3+ ions with coordination number nine. Complexes 1 and 2 consist of two Phen, one neutral HL and three L anions (two L anions act as monodentate ligands and the third one is chelating to Ln 3+ ). Thermal decomposition led to primary loss of the Phen molecules. Then HL molecules and finally L moieties left the material to give Ln 2 O 3

24 CFR 232.525 - Note and security form.

Science.gov (United States)

2010-04-01

... URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES MORTGAGE INSURANCE FOR NURSING HOMES, INTERMEDIATE CARE FACILITIES, BOARD AND CARE HOMES, AND ASSISTED... Fire Safety Equipment Eligible Security Instruments § 232.525 Note and security form. The lender shall...

Differential contribution of complement receptor C5aR in myeloid and non-myeloid cells in chronic ethanol-induced liver injury in mice.

Science.gov (United States)

McCullough, Rebecca L; McMullen, Megan R; Das, Dola; Roychowdhury, Sanjoy; Strainic, Michael G; Medof, M Edward; Nagy, Laura E

2016-07-01

Complement is implicated in the development of alcoholic liver disease. C3 and C5 contribute to ethanol-induced liver injury; however, the role of C5a receptor (C5aR) on myeloid and non-myeloid cells to progression of injury is not known. C57BL/6 (WT), global C5aR-/-, myeloid-specific C5aR-/-, and non-myeloid-specific C5aR-/- mice were fed a Lieber-DeCarli diet (32%kcal EtOH) for 25 days. Cultured hepatocytes were challenged with ethanol, TNFα, and C5a. Chronic ethanol feeding increased expression of pro-inflammatory mediators in livers of WT mice; this response was completely blunted in C5aR-/- mice. However, C5aR-/- mice were not protected from other measures of hepatocellular damage, including ethanol-induced increases in hepatic triglycerides, plasma alanine aminotransferase and hepatocyte apoptosis. CYP2E1 and 4-hydroxynonenal protein adducts were induced in WT and C5aR-/- mice. Myeloid-specific C5aR-/- mice were protected from ethanol-induced increases in hepatic TNFα, whereas non-myeloid-specific C5aR-/- displayed increased hepatocyte apoptosis and inflammation after chronic ethanol feeding. In cultured hepatocytes, cytotoxicity induced by challenge with ethanol and TNFα was completely eliminated by treatment with C5a in cells from WT, but not C5aR-/- mice. Further, treatment with C5a enhanced activation of pro-survival signal AKT in hepatocytes challenged with ethanol and TNFα. Taken together, these data reveal a differential role for C5aR during ethanol-induced liver inflammation and injury, with C5aR on myeloid cells contributing to ethanol-induced inflammatory cytokine expression, while non-myeloid C5aR protects hepatocytes from death after chronic ethanol feeding. Copyright © 2016 Elsevier Ltd. All rights reserved.

Performance and Operational Aspects of HL-LHC Scenarios

CERN Document Server

Medina Medrano, Luis

2016-01-01

Several alternatives to the present HL-LHC baseline configuration have been proposed, aiming either to improve the potential performance, reduce its risks, or to provide options for addressing possible limitations or changes in its parameters. In this paper we review and compare the performance of the HL-LHC baseline and the main alternatives with the latest parameters set. The results are obtained using refined simulations of the evolution of the luminosity with β^{*}-levelling, for which new criteria have been introduced, such as improved calculation of the intrabeam scattering and the addition of penalty steps to take into account the necessary time to move between consecutive optics during the process. The features of the set of optics are discussed for the nominal baseline.

Performances of the HL (Hyperloop) transport system

NARCIS (Netherlands)

van Goeverden, C.D.; Milakis, D.; Janic, M.; Konings, J.W.; Cools, M.; Limbourg, S.

2017-01-01

This paper deals with an analysis of performances of the HL (Hyperloop) transport system considered as an advanced transport alternative to the existing APT (Air Passenger Transport) and HSR (High Speed Rail) systems. The considered performances are operational, financial, social and environmental.

Loss of mitochondrial transmembrane potential and caspase-9 activation during apoptosis induced by the novel styryl-lactone goniothalamin in HL-60 leukemia cells.

Science.gov (United States)

Inayat-Hussain, S H; Annuar, B O; Din, L B; Ali, A M; Ross, D

2003-08-01

Styryl-lactones such as goniothalamin represent a new class of compounds with potential anti-cancer properties. In this study, we investigated the mechanisms of goniothalamin (GTN), a plant styryl-lactone induced apoptosis in human promyelocytic leukemia HL-60 cells. This plant extract resulted in apoptosis in HL-60 cells as assessed by the externalisation of phosphatidylserine. Using the mitochondrial membrane dye (DIOC(6)) in conjunction with flow cytometry, we found that GTN treated HL-60 cells demonstrated a loss of mitochondrial transmembrane potential (Deltapsi(m)). Further immunoblotting on these cells showed activation of initiator caspase-9 and the executioner caspases-3 and -7. Pretreatment with the pharmacological caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone (Z-VAD.FMK) abrogated apoptosis as assessed by all of the apoptotic features in this study. In summary, our results demonstrate that goniothalamin-induced apoptosis occurs via the mitochondrial pathway in a caspase dependent manner.

Concept design for the central control system of HL-2A

International Nuclear Information System (INIS)

Song Xianming; Li Qiang; Jiang Chao

2001-01-01

The design principle and basic structure of the central control system for HL-2A Tokamak are introduced. Having been limited by manpower and money, the central control system should not be too expensive and too advanced. On the other hand, because of the complexity of the machine and the difficulty the author will encounter when operating the machine, the central control system should be advanced enough. If use the same technology for HL-1M to control HL-2A, the author would fail to fulfill authors' experiment goal. The central control system consists of software and hardware. The software mainly includes: (a) system monitor and control software; (b) discharge monitor and control software; (c) network and communication software. Hardware includes: (a) PLC for machine control, personnel protection and machine protection; and (b) VME computer, for the feedback control of the discharge

Vorinostat induces apoptosis and differentiation in myeloid malignancies: genetic and molecular mechanisms.

Directory of Open Access Journals (Sweden)

Gabriela Silva

Full Text Available BACKGROUND: Aberrant epigenetic patterns are central in the pathogenesis of haematopoietic diseases such as myelodysplastic syndromes (MDS and acute myeloid leukaemia (AML. Vorinostat is a HDACi which has produced responses in these disorders. The purpose of this study was to address the functional effects of vorinostat in leukemic cell lines and primary AML and MDS myeloid cells and to dissect the genetic and molecular mechanisms by which it exerts its action. METHODOLOGY/PRINCIPAL FINDINGS: Functional assays showed vorinostat promoted cell cycle arrest, inhibited growth, and induced apoptosis and differentiation of K562, HL60 and THP-1 and of CD33(+ cells from AML and MDS patients. To explore the genetic mechanism for these effects, we quantified gene expression modulation by vorinostat in these cells. Vorinostat increased expression of genes down-regulated in MDS and/or AML (cFOS, COX2, IER3, p15, RAI3 and suppressed expression of genes over-expressed in these malignancies (AXL, c-MYC, Cyclin D1 and modulated cell cycle and apoptosis genes in a manner which would favor cell cycle arrest, differentiation, and apoptosis of neoplastic cells, consistent with the functional assays. Reporter assays showed transcriptional effect of vorinostat on some of these genes was mediated by proximal promoter elements in GC-rich regions. Vorinostat-modulated expression of some genes was potentiated by mithramycin A, a compound that interferes with SP1 binding to GC-rich DNA sequences, and siRNA-mediated SP1 reduction. ChIP assays revealed vorinostat inhibited DNA binding of SP1 to the proximal promoter regions of these genes. These results suggest vorinostat transcriptional action in some genes is regulated by proximal promoter GC-rich DNA sequences and by SP1. CONCLUSION: This study sheds light on the effects of vorinostat in AML and MDS and supports the implementation of clinical trials to explore the use of vorinostat in the treatment of these diseases.

Vorinostat induces apoptosis and differentiation in myeloid malignancies: genetic and molecular mechanisms.

Science.gov (United States)

Silva, Gabriela; Cardoso, Bruno A; Belo, Hélio; Almeida, António Medina

2013-01-01

Aberrant epigenetic patterns are central in the pathogenesis of haematopoietic diseases such as myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). Vorinostat is a HDACi which has produced responses in these disorders. The purpose of this study was to address the functional effects of vorinostat in leukemic cell lines and primary AML and MDS myeloid cells and to dissect the genetic and molecular mechanisms by which it exerts its action. Functional assays showed vorinostat promoted cell cycle arrest, inhibited growth, and induced apoptosis and differentiation of K562, HL60 and THP-1 and of CD33(+) cells from AML and MDS patients. To explore the genetic mechanism for these effects, we quantified gene expression modulation by vorinostat in these cells. Vorinostat increased expression of genes down-regulated in MDS and/or AML (cFOS, COX2, IER3, p15, RAI3) and suppressed expression of genes over-expressed in these malignancies (AXL, c-MYC, Cyclin D1) and modulated cell cycle and apoptosis genes in a manner which would favor cell cycle arrest, differentiation, and apoptosis of neoplastic cells, consistent with the functional assays. Reporter assays showed transcriptional effect of vorinostat on some of these genes was mediated by proximal promoter elements in GC-rich regions. Vorinostat-modulated expression of some genes was potentiated by mithramycin A, a compound that interferes with SP1 binding to GC-rich DNA sequences, and siRNA-mediated SP1 reduction. ChIP assays revealed vorinostat inhibited DNA binding of SP1 to the proximal promoter regions of these genes. These results suggest vorinostat transcriptional action in some genes is regulated by proximal promoter GC-rich DNA sequences and by SP1. This study sheds light on the effects of vorinostat in AML and MDS and supports the implementation of clinical trials to explore the use of vorinostat in the treatment of these diseases.

Characterized the pattern of the material deposition in the HL-2A tokamak

Energy Technology Data Exchange (ETDEWEB)

Cai, Laizhong, E-mail: cailz@swip.ac.cn [Southwestern Institute of Physics, P.O.Box 432, Chengdu, Sichuan 610041 (China); Wang, Jianbao; Wu, Ting; Zeng, Xiaoxiao [Southwestern Institute of Physics, P.O.Box 432, Chengdu, Sichuan 610041 (China); Hai, Ran; Ding, Hongbin [Dalian University of Technology, Dalian, Liaoning 116024 (China)

2017-03-15

Since the divertor geometry of a tokamak has a strong impact on the material erosion and deposition on the wall and HL-2A has a unique divertor configuration, it is necessary to investigate the material deposition pattern in HL-2A although a few results on other tokamaks have already been published. In this paper, tiles retrieved from the vessel are analyzed ex-situ by SIMS, SEM and laser-induced breakdown spectroscopy (LIBS). And deposition behind the lower divertor is in-situ measured by a quartz crystal microbalance (QMB). The deposition in HL-2A displays a complex pattern and clear localization characteristic. The thickness of the deposition layer varies in the range of 0-4μm. And in-situ diagnostic of QMB indicates that the average thickness of the deposition layer per pulse is over ten nanometers. In addition, the results imply that Si, Fe and D have different behaviors during the material deposition in HL-2A.

Phenotypical difference in deamination of cytarabine is not evident in induction therapy for acute myeloid leukemia

DEFF Research Database (Denmark)

Krogh-Madsen, Mikkel; Hansen, Steen Honore'; Jensen, Morten Krogh

2013-01-01

Objective To investigate the uracil arabinoside/cytarabine (Ara-U/Ara-C) ratios with the lower dose in adult acute myeloid leukaemia (AML) induction therapy (100 mg/m2 Ara-C) where no enzyme saturation is expected. Methods A precise and robust high-performance liquid chromatography (HPLC) method...... for simultaneous determination of Ara-C and its main inactive metabolite Ara-U in human plasma was developed and validated. Nineteen patients with acute myeloid leukaemia were treated with Ara-C in a dose of 100 mg/m2 together with daunorubicin and etoposide. Plasma concentrations were used to construct...

CD30 ligand is frequently expressed in human hematopoietic malignancies of myeloid and lymphoid origin.

Science.gov (United States)

Gattei, V; Degan, M; Gloghini, A; De Iuliis, A; Improta, S; Rossi, F M; Aldinucci, D; Perin, V; Serraino, D; Babare, R; Zagonel, V; Gruss, H J; Carbone, A; Pinto, A

1997-03-15

CD30 ligand (CD30L) is a type-II membrane glycoprotein capable of transducing signals leading to either cell death or proliferation through its specific counterstructure CD30. Although several lines of evidence indicate that CD30L plays a key role as a paracrine- or autocrine-acting surface molecule in the deregulated cytokine cascade of Hodgkin's disease, little is known regarding its distribution and biologic significance in other human hematopoietic malignancies. By analyzing tumor cells from 181 patients with RNA studies and immunostaining by the anti-CD30L monoclonal antibody M80, we were able to show that human hematopoietic malignancies of different lineage and maturation stage display a frequent and broad expression of the ligand. CD30L mRNA and surface protein were detected in 60% of acute myeloid leukemias (AMLs), 54% of B-lineage acute lymphoblastic leukemias (ALLs), and in a consistent fraction (68%) of B-cell lymphoproliferative disorders. In this latter group, hairy cell leukemia and high-grade B-cell non-Hodgkin's lymphoma (B-NHL) expressed a higher surface density of CD30L as compared with B-cell chronic lymphocytic leukemia and low-grade B-NHL. Purified plasmacells from a fraction of multiple myeloma patients also displayed CD30L mRNA and protein. A more restricted expression of CD30L was found in T-cell tumors that was mainly confined to neoplasms with an activated peripheral T-cell phenotype, such as T-cell prolymphocytic leukemia, peripheral T-NHL, and adult T-cell leukemia/lymphoma. In contrast, none of the T-lineage ALLs analyzed expressed the ligand. In AML, a high cellular density of CD30L was detected in French-American-British M3, M4, and M5 phenotypes, which are directly associated with the presence on tumor cells of certain surface structures, including the p55 interleukin-2 receptor alpha-chain, the alpha(M) (CD11b) chain of beta2 integrins, and the intercellular adhesion molecule-1 (CD54). Analysis of normal hematopoietic cells

Daunorubicin Hydrochloride, Cytarabine and Oblimersen Sodium in Treating Patients With Previously Untreated Acute Myeloid Leukemia

Science.gov (United States)

2013-06-04

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); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Activity of Bruton's tyrosine-kinase inhibitor ibrutinib in patients with CD117-positive acute myeloid leukaemia: a mechanistic study using patient-derived blast cells.

Science.gov (United States)

Rushworth, Stuart A; Pillinger, Genevra; Abdul-Aziz, Amina; Piddock, Rachel; Shafat, Manar S; Murray, Megan Y; Zaitseva, Lyubov; Lawes, Matthew J; MacEwan, David J; Bowles, Kristian M

2015-05-01

Roughly 80% of patients with acute myeloid leukaemia have high activity of Bruton's tyrosine-kinase (BTK) in their blast cells compared with normal haemopoietic cells, rendering the cells sensitive to the oral BTK inhibitor ibrutinib in vitro. We aimed to develop the biological understanding of the BTK pathway in acute myeloid leukaemia to identify clinically relevant diagnostic information that might define a subset of patients that should respond to ibrutinib treatment. We obtained acute myeloid leukaemia blast cells from unselected patients attending our UK hospital between Feb 19, 2010, and Jan 20, 2014. We isolated primary acute myeloid leukaemia blast cells from heparinised blood and human peripheral blood mononuclear cells to establish the activity of BTK in response to CD117 activation. Furthermore, we investigated the effects of ibrutinib on CD117-induced BTK activation, downstream signalling, adhesion to primary bone-marrow mesenchymal stromal cells, and proliferation of primary acute myeloid leukaemia blast cells. We used the Mann-Whitney U test to compare results between groups. We obtained acute myeloid leukaemia blast cells from 29 patients. Ibrutinib significantly inhibited CD117-mediated proliferation of primary acute myeloid leukaemia blast cells (p=0·028). CD117 activation increased BTK activity by inducing phosphorylated BTK in patients with CD117-positive acute myeloid leukaemia. Furthermore, ibrutinib inhibited CD117-induced activity of BTK and downstream kinases at a concentration of 100 nM or more. CD117-mediated adhesion of CD117-expressing blast cells to bone-marrow stromal cells was significantly inhibited by Ibrutinib at 500 nM (p=0·028) INTERPRETATION: As first-in-man clinical trials of ibrutinib in patients with acute myeloid leukaemia commence, the data suggest not all patients will respond. Our findings show that BTK has specific pro-tumoural biological actions downstream of surface CD117 activation, which are inhibited by ibrutinib

Stromal cells expressing hedgehog-interacting protein regulate the proliferation of myeloid neoplasms

International Nuclear Information System (INIS)

Kobune, M; Iyama, S; Kikuchi, S; Horiguchi, H; Sato, T; Murase, K; Kawano, Y; Takada, K; Ono, K; Kamihara, Y; Hayashi, T; Miyanishi, K; Sato, Y; Takimoto, R; Kato, J

2012-01-01

Aberrant reactivation of hedgehog (Hh) signaling has been described in a wide variety of human cancers including cancer stem cells. However, involvement of the Hh-signaling system in the bone marrow (BM) microenvironment during the development of myeloid neoplasms is unknown. In this study, we assessed the expression of Hh-related genes in primary human CD34 + cells, CD34 + blastic cells and BM stromal cells. Both Indian Hh (Ihh) and its signal transducer, smoothened (SMO), were expressed in CD34 + acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)-derived cells. However, Ihh expression was relatively low in BM stromal cells. Remarkably, expression of the intrinsic Hh-signaling inhibitor, human Hh-interacting protein (HHIP) in AML/MDS-derived stromal cells was markedly lower than in healthy donor-derived stromal cells. Moreover, HHIP expression levels in BM stromal cells highly correlated with their supporting activity for SMO + leukemic cells. Knockdown of HHIP gene in stromal cells increased their supporting activity although control cells marginally supported SMO + leukemic cell proliferation. The demethylating agent, 5-aza-2′-deoxycytidine rescued HHIP expression via demethylation of HHIP gene and reduced the leukemic cell-supporting activity of AML/MDS-derived stromal cells. This indicates that suppression of stromal HHIP could be associated with the proliferation of AML/MDS cells

HL-217, a new topical anti-angiogenic agent, inhibits retinal vascular leakage and pathogenic subretinal neovascularization in Vldlr−/− mice

International Nuclear Information System (INIS)

Kim, Junghyun; Kim, Chan-Sik; Jo, Kyuhyung; Cho, Yun-Seok; Kim, Hyun-Gyu; Lee, Geun-Hyeog; Lee, Yun Mi; Sohn, Eunjin; Kim, Jin Sook

2015-01-01

Highlights: • HL-217 is a new synthetic topical anti-angiogenic agent. • HL-217 attenuated subretinal neovascularization in Vldlr −/− mice. • HL-217 blocked the binding of PDGF-BB to PDGFRβ. - Abstract: HL-217 is a new synthetic angiogenesis inhibitor. Platelet derived growth factor (PDGF) is a vasoactive factor and has been implicated in proliferative retinopathies. In this study, we examined the mechanism of action and efficacy of topical application of HL-217 on subretinal neovascularization in very low-density lipoprotein receptor knockout (Vldlr −/− ) mice. In three-week-old male Vldlr −/− mice, HL-217 (1.5 or 3 mg/ml) was administered twice per day for 4 weeks by topical eye drop instillation. Neovascular areas were then measured. We used a protein array to evaluate the expression levels of angiogenic factors. The inhibitory effect of HL-217 on the PDGF-BB/PDGFRβ interaction was evaluated in vitro. The neovascular area in the Vldlr −/− mice was significantly reduced by HL-217. Additionally, HL-217 decreased the expression levels of PDGF-BB protein and VEGF mRNA. Moreover, HL-217 dose-dependently inhibited the PDGF-BB/PDGFRβ interaction (IC 50 = 38.9 ± 0.7 μM). These results suggest that HL-217 is a potent inhibitor of PDGF-BB. HL-217, when applied topically, is an effective inhibitor of subretinal neovascularization due to its ability to inhibit the pro-angiogenic effects of PDGF-BB

Outcomes following splenectomy in patients with myeloid neoplasms.

Science.gov (United States)

Rialon, Kristy L; Speicher, Paul J; Ceppa, Eugene P; Rendell, Victoria R; Vaslef, Steven N; Beaven, Anne; Tyler, Douglas S; Blazer, Dan G

2015-03-15

Myeloid neoplasms are classified into five major categories. These patients may develop splenomegaly and require splenectomy to alleviate mechanical symptoms, to ameliorate transfusion-dependent cytopenias, or to enhance stem cell transplantation. The objective of this study was to determine which clinical variables significantly impacted morbidity, mortality, and survival in patients with myeloid neoplasms undergoing splenectomy, and to determine if operative outcomes have improved over time. The records of all patients with myeloid neoplasms undergoing splenectomy from 1993 to 2010 were retrospectively reviewed. Eighty-nine patients (n = 89) underwent splenectomy for myeloid neoplasms. Over half of patients who had symptoms preoperatively had resolution of their symptoms post-splenectomy. The morbidity rate was 38%, with the most common complications being bleeding (14%) or infection (20%). Thirty-day mortality rate was 18% and median survival after splenectomy was 278 days. Decreased survival was associated with a diagnosis of myelodysplastic syndrome/myeloproliferative neoplasm, anemia, abnormal white blood cell count, and hypoalbuminemia. Patients who underwent stem cell transplantation did not show an increased risk for morbidity or mortality. Patients with myeloid neoplasms have a poor prognosis after splenectomy and the decision to operate is a difficult one, associated with high morbidity and mortality. © 2014 Wiley Periodicals, Inc.

Modeling of Chronic Myeloid Leukemia : An Overview of In Vivo Murine and Human Xenograft Models

NARCIS (Netherlands)

Sontakke, Pallavi; Jaques, Jenny; Vellenga, Edo; Schuringa, Jan Jacob

2016-01-01

Over the past years, a wide variety of in vivo mouse models have been generated in order to unravel the molecular pathology of Chronic Myeloid Leukemia (CML) and to develop and improve therapeutic approaches. These models range from (conditional) transgenic models, knock-in models, and murine bone

HLA-DRB1*16-restricted recognition of myeloid cells, including CD34+ CML progenitor cells

NARCIS (Netherlands)

Ebeling, Saskia B.; Ivanov, Roman; Hol, Samantha; Aarts, Tineke I.; Hagenbeek, Anton; Verdonck, Leo F.; Petersen, Eefke J.

2003-01-01

The therapeutic effect of a human leucocyte antigen (HLA)-identical allogeneic stem cell transplantation (allo-SCT) for the treatment of haematological malignancies is mediated partly by the allogeneic T cells that are administered together with the stem cell graft. Chronic myeloid leukaemia (CML)

Autoradiographic imaging of cerebral ischemia using hypoxic marker: Tc-99m-HL91 in animal models

International Nuclear Information System (INIS)

Jiang, N.Y.; Zhu, C.S.; Hu, X.K.

2002-01-01

Objective: To explore the possibility of Tc-99m-HL91 imaging in detecting the ischemic penumbra during acute stoke. Methods: 16 Sprague-Dawley (SD) rats were divided into operation group (n=12) and pseudo-operation group (n=4) randomly. In operation group, 12 middle cerebral artery occlusion animal (MCAO) models were established by electrocautery. 4 rats in pseudo-operation group were treated as a control without occlusion. All animals were injected Tc-99m-HL91 intravenously 2 hours after occlusion. Animals were killed at different time after injection and brains were removed rapidly from the skull to do the autoradiographic study. Result: The ischemic territory accumulated more Tc-99m-HL91 than the opposite site in the autoradiogram at 1 hour after injection. The ischemic cerebral tissue can be visualized clearly. At 2, 4 hours after injection, the difference of accumulation of Tc-99m-HL91 in target and non-target site became more obvious. By using computer-enhanced imaging analysis, the optical density (OD) ratio differences between each subgroup of operation group and pseudo-operation group were all significant. Conclusion : Tc-99m-HL91 can be avidly taken up by ischemic penumbra. Tc-99m-HL91 is a potential agent for imaging hypoxic tissue, and Tc-99m-HL91 SPECT may be a promising imaging method in detecting the ischemic penumbra

Autoradiographic imaging of cerebral ischaemia using hypoxic marker: 99mTc-HL91 in animal models

International Nuclear Information System (INIS)

Ningyi, J.; Cansheng, Z.; Xiaoke, H.

2002-01-01

Objective: To explore the possibility of 99mTc-HL91 imaging in detecting the ischemic penumbra during acute stoke. Methods 16 Sprague-Dawley (SD) rats were divided into operation group (n=12) and pseudo-operation group (n=4) randomly. In operation group, 12 middle cerebral artery occlusion animal (MCAO) models were established by electrocautery. 4 rats in pseudo-operation group were treated as a control without occlusion. All animals were injected 99mTc-HL91 intravenously 2 hours after occlusion. Animals were killed at different time after injection and brains were removed rapidly from the skull to do the autoradiographic study. Result The ischemic territory accumulated more 99mTc-HL91 than the opposite site in the autoradiogram at 1 hour after injection. The ischemic cerebral tissue can be visualized clearly. At 2, 4 hours after injection, the difference of accumulation of 99mTc-HL91 in target and non-target site became more obvious. By using computer-enhanced imaging analysis, the optical density (OD) ratio differences between each subgroup of operation group and pseudo-operation group were all significant. Conclusion 99mTc-HL91 can be avidly taken up by ischemic penumbra. 99mTc-HL91 is a potential agent for imaging hypoxic tissue, and 99mTc-HL91 SPECT may be a promising imaging method in detecting the ischemic penumbra

Childhood Acute Myeloid Leukemia Treatment (PDQ®)—Patient Version

Science.gov (United States)

Childhood acute myeloid leukemia and other myeloid malignancies treatment may include chemotherapy, radiation therapy, stem cell transplant, and targeted therapy. Learn more about AML and myelodysplastic/myeloproliferative diseases in this expert-reviewed summary.

HL-1 tokamak data acquisition system and its initial application in the physical experiment

International Nuclear Information System (INIS)

Deng Huichen; Fu Bo; Dong Jiafu

1989-11-01

A HL-1 tokamak data acquisition system has been developed and has been used in the physical experiment. The hardware and software configuration of the system, as well as the typical acquired data in the HL-1 experiment are introduced

The CMS Tracker upgrade for HL-LHC

CERN Document Server

Ahuja, Sudha

2017-01-01

The LHC machine is planning an upgrade program which will smoothly bring the luminosity to about 5 $\\times$ $10^{34} $cm$^{-2}$s$^{-1}$ in 2028, to possibly reach an integrated luminosity of 3000 fb$^{-1}$ by the end of 2037. This High Luminosity LHC scenario, HL-LHC, will require a preparation program of the LHC detectors known as Phase-2 upgrade. The current CMS Outer Tracker, already running beyond design specifications, and CMS Phase1 Pixel Detector will not be able to survive HL-LHC radiation conditions and CMS will need completely new devices, in order to fully exploit the high-demanding operating conditions and the delivered luminosity. The new Outer Tracker should have also trigger capabilities. To achieve such goals, R$\\&$D activities are ongoing to explore options both for the Outer Tracker, and for the pixel Inner Tracker. Solutions are being developed that would allow including tracking information at Level-1. The design choices for the Tracker upgrades are discussed along with some highlights...

Design for effective development and prototyping of the HL-20

Science.gov (United States)

Urie, David M.; Floreck, Paul A.; McMorris, John A.; Elvin, John D.

1993-10-01

A feasibility study of the HL-20 personnel launch system (PLS) concept was conducted by a team which focused on creating a PLS design approach and an accelerated development plan consistent with the historical 'Skunk Works' approach to rapid prototyping. Technical design, manufacturing, system testing, and operations and support elements of the predefined baseline concept were evaluated. An initial phase program, featuring a concurrent system test during design and development, leading to the orbital flight of an unmanned HL-20 prototype on a Titan III launch system, was prescribed. A second-phase development and manufacturing plan leading to system operational status was also formulated. Baseline design feature modifications were made when necessary, without compromise to performance, to satisfy the prototype development plan. Technical design details and off-the-shelf hardware candidates were also identified for several subsystems, including the launch-system interface adapter/emergency escape system. The technical feasibility of the system and applicability of the Skunk Works approach to development of the HL-20/PLS were verified.

Myeloid clusters are associated with a pro-metastatic environment and poor prognosis in smoking-related early stage non-small cell lung cancer.

Directory of Open Access Journals (Sweden)

Wang Zhang

Full Text Available This study aimed to understand the role of myeloid cell clusters in uninvolved regional lymph nodes from early stage non-small cell lung cancer patients.Uninvolved regional lymph node sections from 67 patients with stage I-III resected non-small cell lung cancer were immunostained to detect myeloid clusters, STAT3 activity and occult metastasis. Anthracosis intensity, myeloid cluster infiltration associated with anthracosis and pSTAT3 level were scored and correlated with patient survival. Multivariate Cox regression analysis was performed with prognostic variables. Human macrophages were used for in vitro nicotine treatment.CD68+ myeloid clusters associated with anthracosis and with an immunosuppressive and metastasis-promoting phenotype and elevated overall STAT3 activity were observed in uninvolved lymph nodes. In patients with a smoking history, myeloid cluster score significantly correlated with anthracosis intensity and pSTAT3 level (P<0.01. Nicotine activated STAT3 in macrophages in long-term culture. CD68+ myeloid clusters correlated and colocalized with occult metastasis. Myeloid cluster score was an independent prognostic factor (P = 0.049 and was associated with survival by Kaplan-Maier estimate in patients with a history of smoking (P = 0.055. The combination of myeloid cluster score with either lymph node stage or pSTAT3 level defined two populations with a significant difference in survival (P = 0.024 and P = 0.004, respectively.Myeloid clusters facilitate a pro-metastatic microenvironment in uninvolved regional lymph nodes and associate with occult metastasis in early stage non-small cell lung cancer. Myeloid cluster score is an independent prognostic factor for survival in patients with a history of smoking, and may present a novel method to inform therapy choices in the adjuvant setting. Further validation studies are warranted.

Dynamical Stability of Imaged Planetary Systems in Formation: Application to HL Tau

Science.gov (United States)

Tamayo, D.; Triaud, A. H. M. J.; Menou, K.; Rein, H.

2015-06-01

A recent Atacama Large Millimeter/Submillimeter Array image revealed several concentric gaps in the protoplanetary disk surrounding the young star HL Tau. We consider the hypothesis that these gaps are carved by planets, and present a general framework for understanding the dynamical stability of such systems over typical disk lifetimes, providing estimates for the maximum planetary masses. We collect these easily evaluated constraints into a workflow that can help guide the design and interpretation of new observational campaigns and numerical simulations of gap opening in such systems. We argue that the locations of resonances should be significantly shifted in massive disks like HL Tau, and that theoretical uncertainties in the exact offset, together with observational errors, imply a large uncertainty in the dynamical state and stability in such disks. This presents an important barrier to using systems like HL Tau as a proxy for the initial conditions following planet formation. An important observational avenue to breaking this degeneracy is to search for eccentric gaps, which could implicate resonantly interacting planets. Unfortunately, massive disks like HL Tau should induce swift pericenter precession that would smear out any such eccentric features of planetary origin. This motivates pushing toward more typical, less massive disks. For a nominal non-resonant model of the HL Tau system with five planets, we find a maximum mass for the outer three bodies of approximately 2 Neptune masses. In a resonant configuration, these planets can reach at least the mass of Saturn. The inner two planets’ masses are unconstrained by dynamical stability arguments.

Autoradiographic imaging of cerebral ischemia using hypoxic marker: 99mTc-HL91 in animal models

International Nuclear Information System (INIS)

Zhu Cansheng; Jiang Ningyi; Hu Xiaoke

2001-01-01

Objective: To explore the possibility of 99m Tc-HL91 imaging in detecting the ischemic penumbra during acute stoke. Methods; 16 Sprague-Dawley (SD) rats were divided into operation group (n=12) and pseudo-operation group (n=4) randomly. In operation group, 12 middle cerebral artery occlusion animal (MCAO) models were established by electrocautery. 4 rats in pseudo-operation group were treated as a control without occlusion. All animals were injected 99m Tc-HL91 intravenously 2 hours after occlusion. Animals were killed at different time after injection and brains were removed rapidly from the skull to do the autoradiographic study. Results: The ischemic territory accumulated more 99m Tc-HL91 than the opposite site in the autoradiogram at 1 hour after injection. The ischemic cerebral tissue can be visualized clearly. At 2, 4 hours after injection, the difference of accumulation of 99m Tc-HL91 in target and non-target site became more obvious. By using computer-enhanced imaging analysis, the optical density (OD) ratio differences between each subgroup of operation group and pseudo-operation group were all significant. The OD ratios (T/N) were 1.2691±0.0189, 1.3542±0.0119, 2.1201±0.0616, 2.5369±0.1214 respectively at 1, 2, 4 hours after 99m Tc-HL91 injection. Conclusion: 99m Tc-HL91 can be avidly taken up by ischemic penumbra. 99m Tc-HL91 is a potential agent for imaging hypoxic tissue, and 99m Tc-HL91 SPECT may be a promising imaging method in detecting the ischemic penumbra

Human prosthetic joint infections are associated with myeloid-derived suppressor cells (MDSCs): Implications for infection persistence.

Science.gov (United States)

Heim, Cortney E; Vidlak, Debbie; Odvody, Jessica; Hartman, Curtis W; Garvin, Kevin L; Kielian, Tammy

2017-11-15

Prosthetic joint infection (PJI) is a devastating complication of joint arthroplasty surgery typified by biofilm formation. Currently, mechanisms whereby biofilms persist and evade immune-mediated clearance in immune competent patients remain largely ill-defined. Therefore, the current study characterized leukocyte infiltrates and inflammatory mediator expression in tissues from patients with PJI compared to aseptic loosening. CD33 + HLA-DR - CD66b + CD14 -/low granulocytic myeloid-derived suppressor cells (G-MDSCs) were the predominant leukocyte population at sites of human PJI compared to aseptic tissues. MDSCs inhibit T cell proliferation, which coincided with reduced T cells in PJIs compared to aseptic tissues. IL-10, IL-6, and CXCL1 were significantly elevated in PJI tissues and have been implicated in MDSC inhibitory activity, expansion, and recruitment, respectively, which may account for their preferential increase in PJIs. This bias towards G-MDSC accumulation during human PJI could account for the chronicity of these infections by preventing the pro-inflammatory, antimicrobial actions of immune effector cells. Animal models of PJI have revealed a critical role for MDSCs and IL-10 in promoting infection persistence; however, whether this population is prevalent during human PJI and across distinct bacterial pathogens remains unknown. This study has identified that granulocytic-MDSC infiltrates are unique to human PJIs caused by distinct bacteria, which are not associated with aseptic loosening of prosthetic joints. Better defining the immune status of human PJIs could lead to novel immune-mediated approaches to facilitate PJI clearance in combination with conventional antibiotics. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Two-dimensional analysis of metabolically and cell surface radiolabeled proteins of some human lymphoid and myeloid leukemia cell lines. II. Glycosylated and phosphorylated proteins

Energy Technology Data Exchange (ETDEWEB)

Chorvath, B; Duraj, J; Sedlak, J; Pleskova, I

1986-01-01

Cell surface glycoproteins, radiolabelled by the sodium metaperiodate/tritiated borohydride technique, and cell phosphoproteins, metabolically radiolabelled with /sup 32/P-orthophosphate were analyzed by two-dimensional electrophoretic analysis in some myeloid and lymphoid leukemia cell lines. Some markedly expressed major glycoproteins were predominant in some of the cell lines (such as 95k and 100k glycoproteins with marked charge heterogeneity in non-T, non-B acute lymphoblastic leukemia cell lines NALM 6 and NALM 16), but markedly quantitatively reduced in other examined cell lines, such as lymphoblastoid cell line UHKT 34/2. /sup 32/P-orthophosphate radiolabelled phosphoprotein two-dimensional patterns of the examined lymphoid leukemia cell lines were essentially similar, with some minor differences, in examined lymphoid and myeloid leukemia cell lines, such as marked expression of a series of large phosphoproteins in the molecular weight range 80-100k in lymphoid cell lines and almost complete absence of these phosphoproteins on the examined myeloid leukemia cell lines. Another configuration of acidic phosphoproteins (30-35k) exhibited individual cell line variability and differences between both individual myeloid leukemia cell lines and between the lymphoid and myeloid cell lines examined. (author) 2 figs., 15 refs.

Formal methods impact on ANSI standard HL7/IM: filling gaps in MSC theory

NARCIS (Netherlands)

W. Wesselink; N. Goga (Nicolae); A.J. Mooij (Arjan); R. Spronk

2005-01-01

htmlabstractHealth level seven (HL7) is an ANSI standard that provides a comprehensive framework for electronic health information. The most-widely used HL7 specification is called infrastructure management, which facilitates health-care applications to exchange key sets of clinical and

Commissioning and preliminary operation of HL-2A tokamak

International Nuclear Information System (INIS)

Liu Dequan; Liu Yong; Yan Jianchen; Cao Zeng; Yang Qingwei; Zhou Caipin; Li Xiaodong

2005-01-01

HL-2A is a divertor tokamak located at new site of Southwestern Institute of Physics (SWIP), Chengdu, China. It can be operated in double-null and single-null divertor with closed configurations. The effects of the divertor on impurity behaviors, MHD instabilities, transport, wall conditioning and divertor physics are key issues to be studied during the first step operation on HL-2A. Preliminary experiments with limiter and single null divertor configurations were carried out in 2003. Main parameters achieved are the plasma current 168 KA, duration time of 920 ms and plasma linear-averaged density of 1.7 x 10 19 m -3 . The impurities, especially of low Z, are clearly decreased during the divertor experiments

Human monoclonal antibodies reactive with human myelomonocytic leukemia cells.

Science.gov (United States)

Posner, M R; Santos, D J; Elboim, H S; Tumber, M B; Frackelton, A R

1989-04-01

Peripheral blood mononuclear cells from a patient with chronic myelogenous leukemia (CML), in remission, were depleted of CD8-positive T-cells and cultured with Epstein-Barr virus. Four of 20 cultures (20%) secreted human IgG antibodies selectively reactive with the cell surfaces of certain human leukemia cell lines. Three polyclonal, Epstein-Barr virus-transformed, B-cell lines were expanded and fused with the human-mouse myeloma analogue HMMA2.11TG/O. Antibody from secreting clones HL 1.2 (IgG1), HL 2.1 (IgG3), and HL 3.1 (IgG1) have been characterized. All three react with HL-60 (promyelocytic), RWLeu4 (CML promyelocytic), and U937 (monocytic), but not with KG-1 (myeloblastic) or K562 (CML erythroid). There is no reactivity with T-cell lines, Burkitt's cell lines, pre-B-leukemia cell lines, or an undifferentiated CML cell line, BV173. Leukemic cells from two of seven patients with acute myelogenous leukemia and one of five with acute lymphocytic leukemia react with all three antibodies. Normal lymphocytes, monocytes, polymorphonuclear cells, red blood cells, bone marrow cells, and platelets do not react. Samples from patients with other diverse hematopoietic malignancies showed no reactivity. Immunoprecipitations suggest that the reactive antigen(s) is a lactoperoxidase iodinatable series of cell surface proteins with molecular weights of 42,000-54,000 and a noniodinatable protein with a molecular weight of 82,000. Based on these data these human monoclonal antibodies appear to react with myelomonocytic leukemic cells and may detect a leukemia-specific antigen or a highly restricted differentiation antigen.

Study on fast ion loss in HL-2A tokamak

International Nuclear Information System (INIS)

Liu Yi; Sun Tengfei; Ji Xiaoquan

2012-01-01

Experiments with a high-energy deuterium neutral beam (NB) injection (30 keV, about 0.6 MW) were performed on the HL-2A tokamak. Analysis of neutron decay following the NB 'blip' injection indicates that tangentially injected beam ions are well confined, slowing down classically in the HL-2A. Anomalous losses of beam ions were observed when a beta-induced Alfven acoustic (BAAE) mode was present in the plasma. Such a high energetic particle driven mode led to fast-ion loss, showing a strong influence of the energetic particle driven mode on the fast-ion transport. (authors)

Introduction to the HL-LHC Project

Science.gov (United States)

Rossi, L.; Brüning, O.

The Large Hadron Collider (LHC) is one of largest scientific instruments ever built. It has been exploring the new energy frontier since 2010, gathering a global user community of 7,000 scientists. To extend its discovery potential, the LHC will need a major upgrade in the 2020s to increase its luminosity (rate of collisions) by a factor of five beyond its design value and the integrated luminosity by a factor of ten. As a highly complex and optimized machine, such an upgrade of the LHC must be carefully studied and requires about ten years to implement. The novel machine configuration, called High Luminosity LHC (HL-LHC), will rely on a number of key innovative technologies, representing exceptional technological challenges, such as cutting-edge 11-12 tesla superconducting magnets, very compact superconducting cavities for beam rotation with ultra-precise phase control, new technology for beam collimation and 300-meter-long high-power superconducting links with negligible energy dissipation. HL-LHC federates efforts and R&D of a large community in Europe, in the US and in Japan, which will facilitate the implementation of the construction phase as a global project.

A comparative study of 99mTc-HL91 and 99mTc-MIBI imaging in experimental tumor and inflammatory models

International Nuclear Information System (INIS)

Cao, W.; Zhang, X.Y.; An, R.

2002-01-01

Aim: 99m Tc-HL91 is a newly developed hypoxic imaging agent for ischemic myocardium and tumor imaging. 99m Tc-MIBI is one of imaging agent for mammary tumor imaging. The aim of this experiment is to evaluate the diagnostic value of 99m Tc-HL91 in detection of solid tumor in experimental tumor and inflammatory models, via comparative study with 99m Tc-MIBI. Material and Methods: HL91 kits was provided by China Nine Star Co. Three kinds of bearing solid neoplasm mice groups (bearing Ehrlich carcinoma mice, bearing H 22 carcinoma mice and bearing human ovarian COC 1 neoplasm nude mice) and two inflammatory model groups (chemical and bacterial inflammation) underwent static whole body planar images at 1 and 4 hours post injection of 99m Tc-HL91. Two kinds of bearing neoplasm mice groups (bearing Ehrlich carcinoma mice, bearing H 22 carcinoma mice) and two inflammatory model groups (chemical and bacterial inflammation) underwent static planar images post injection of 99m Tc-MIBI, at early phase (10∼20 minutes) and delayed phase (2 hrs). All of mice were sacrificed at 4 hrs. The tumors, or inflammatory lesions, blood and contralateral muscles were removed, weighed and the radioactivity was measured. Regions of interesting (ROIs) were drawn around tumor, inflammatory lesions and contralateral muscles in planar images, and the radioactivity ratios of target (tumor or inflammatory lesions)-to-blood (T/B), target-to-non target (contralateral muscles) i. e. T/NT was calculated. Results: Neoplasm can be clearly visible in planar images at 1hr and 4 hrs post injection of 99m Tc-HL91 in all tumor models. At same time inflammatory lesions cannot be seen clearly. Neoplasm can be seen in delayed phase in 99m Tc-MIBI groups, but not easy to distinguish them from inflammation. Conclusion: Compared with 99m Tc-MIBI imaging, 99m Tc-HL91 has much more diagnostic value in detection of solid neoplasm, and can distinguish neoplasm from inflammation

An ageing study of resistive micromegas for the HL-LHC environment

CERN Document Server

Galan, J.; Ferrer-Ribas, E.; Giganon, A.; Giomataris, I.; Herlant, S.; Jeanneau, F.; Peyaud, A.; Schune, Ph; Alexopoulos, T.; Byszewski, M.; Iakovidis, G.; Iengo, P.; Ntekas, K.; Leontsinis, S.; de Oliveira, R.; Tsipolitis, Y.; Wotschack, J.

2013-01-01

Resistive-anode micromegas detectors are in development since several years, in an effort to solve the problem of sparks when working at high flux and high ionizing radiation like in the HL-LHC (up to ten times the luminosity of the LHC). They have been chosen as one of the technologies that will be part of the ATLAS New Small Wheel project (forward muon system). An ageing study is mandatory to assess their capabilities to handle the HL-LHC environment on a long-term period. A prototype has been exposed to several types of irradiation (X-rays, cold neutrons, $^{60}$Co gammas and alphas) above the equivalent charge produced at the detector in five HL-LHC running years without showing any degradation of the performances in terms of gain and energy resolution. This study has been completed with the characterization of the tracking performances in terms of efficiency and spatial resolution, verifying the compatibility of results obtained with both resistive micromegas detectors, irradiated and non-irradiated one.

The conceptual design for the modification of HL-2A tokamak

International Nuclear Information System (INIS)

Dequan Liu

2006-01-01

The medium-sized tokamak HL-2A, based on the former ASDEX's main components has approached its rating operational parameters with I p = 450 kA and B T =2.8 T so far. The HL-2A was originally designed to operate under an axisymmetrical double-null configuration by two triplets of shaping coils located in the vacuum vessel. Because the shaping coils were set very close to the plasma column, the nulls are normally fixed and the plasma has a nearly circular cross-section. It is difficult to increase the parameters further and obtain a preferable plasma shape with certain values of triangularity and elongation. Due to the defects on upper shaping coils' electrical insulation, the HL-2A is presently just operated with lower single null divertor configuration. Additionally, the experiment has to occasionally terminate due to incidental damages of the weak parts. With the experimental progress on HL-2A, the plasma stored energy and auxiliary heating power is being increased, a more efficient, compact and tight divertor is needed. Based on present status of HL-2A tokamak and for satisfying the requirements of the experiment, the modification of HL-2A tokamak device will be carried out. The modification design of HL-2A intents to obtain optimized plasma parameters, e.g., aspect ratio, I p , b, plasma volume, certain plasma shaping with preferable elongation and triangularity, a stable vacuum vessel easy to be maintained and an advanced divertor. The primary consideration of the modification is to take all of the shaping coils out of the vessel to enlarge the plasma volume. The elongated and triangular cross section with double null of plasma is to be obtained by composite distribution of eight sets of poloidal coils. Because all poloidal coils will be located between the TF coil and the vessel, the vacuum vessel will be remade with a smaller size to make rooms for the poloidal coil system. With an optimized operation mode, the volt-second of the plasma may be increased a

Monocytic myeloid-derived suppressor cells as prognostic factor in chronic myeloid leukaemia patients treated with dasatinib.

Science.gov (United States)

Giallongo, Cesarina; Parrinello, Nunziatina L; La Cava, Piera; Camiolo, Giuseppina; Romano, Alessandra; Scalia, Marina; Stagno, Fabio; Palumbo, Giuseppe A; Avola, Roberto; Li Volti, Giovanni; Tibullo, Daniele; Di Raimondo, Francesco

2018-02-01

Myeloid suppressor cells are a heterogeneous group of myeloid cells that are increased in patients with chronic myeloid leukaemia (CML) inducing T cell tolerance. In this study, we found that therapy with tyrosine kinase inhibitors (TKI) decreased the percentage of granulocytic MDSC, but only patients treated with dasatinib showed a significant reduction in the monocytic subset (M-MDSC). Moreover, a positive correlation was observed between number of persistent M-MDSC and the value of major molecular response in dasatinib-treated patients. Serum and exosomes from patients with CML induced conversion of monocytes from healthy volunteers into immunosuppressive M-MDSC, suggesting a bidirectional crosstalk between CML cells and MDSC. Overall, we identified M-MDSC as prognostic factors in patients treated with dasatinib. It might be of interest to understand whether MDSC may be a candidate predictive markers of relapse risk following TKI discontinuation, suggesting their potential significance as practice of precision medicine. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

The Discharge Design of HL-2M with the Tokamak Simulation Code (TSC)

International Nuclear Information System (INIS)

Yudong Pan; Jardin, S.C.; Kes, C.

2007-01-01

We present results on the discharge design of the HL-2M tokamak, which is to be an upgrade to the existing HL-2A tokamak. We present simulation results for complete 5-sec. discharges, both double null and lower single null, for both ohmic and auxiliary heated discharges. We also discuss the vertical stability properties of the device

The Hellenic National Tsunami Warning Centre (HL-NTWC): Recent updates and future developments

Science.gov (United States)

Melis, Nikolaos S.; Charalampakis, Marinos

2014-05-01

The Hellenic NTWC (HL-NTWC) was established officially by Greek Law in September 2010. HL-NTWC is hosted at the National Observatory of Athens, Institute of Geodynamics (NOA-IG), which also operates a 24/7 earthquake monitoring service in Greece and coordinates the newly established Hellenic Unified National Seismic Network. NOA-IG and HL-NTWC Operational Centre is linked to the Civil Protection Operational Centre and serves as the official alerting agency to the General Secretariat for Civil Protection in Greece, regarding earthquake events and tsunami watch. Since August 2012, HL-NTWC acts as Candidate Tsunami Watch Provider (CTWP) under the UNESCO IOC - ICG NEAMTWS tsunami warning system (NEAM: North-Eastern Atlantic, the Mediterranean and connected seas) and offers its services to the NEAMTWS system. HL-NTWC has participated in all Communication Test Exercises (CTE) under NEAMTWS and also it has provided tsunami scenarios for extended system testing exercises such as NEAMWAVE12. Some of the recent developments at HL-NTWC in Greece include: deployment of new tide gauge stations for tsunami watch purposes, computation of tsunami scenarios and extending the database in use, improving alerting response times, earthquake magnitude estimation and testing newly established software modules for tsunami and earthquake alerting (i.e. Early-Est, SeisComP3 etc.) in Greece and the Eastern Mediterranean. Although funding today is limited, an advantage of the participation in important EC funded research projects, i.e. NERIES, NERA, TRANSFER, NEAMTIC and ASTARTE, demonstrates that collaboration of top class Research Institutions that care to produce important and useful results in the research front in Europe, can facilitate towards developing and operating top class Operational Centers, useful for Civil Protection purposes in regions in need. Last, it is demonstrated that HL-NTWC collaboration with important key role Research Centers in the Security and Safety issues (e

Chronic myeloid leukemia: reminiscences and dreams

Science.gov (United States)

Mughal, Tariq I.; Radich, Jerald P.; Deininger, Michael W.; Apperley, Jane F.; Hughes, Timothy P.; Harrison, Christine J.; Gambacorti-Passerini, Carlo; Saglio, Giuseppe; Cortes, Jorge; Daley, George Q.

2016-01-01

With the deaths of Janet Rowley and John Goldman in December 2013, the world lost two pioneers in the field of chronic myeloid leukemia. In 1973, Janet Rowley, unraveled the cytogenetic anatomy of the Philadelphia chromosome, which subsequently led to the identification of the BCR-ABL1 fusion gene and its principal pathogenetic role in the development of chronic myeloid leukemia. This work was also of major importance to support the idea that cytogenetic changes were drivers of leukemogenesis. John Goldman originally made seminal contributions to the use of autologous and allogeneic stem cell transplantation from the late 1970s onwards. Then, in collaboration with Brian Druker, he led efforts to develop ABL1 tyrosine kinase inhibitors for the treatment of patients with chronic myeloid leukemia in the late 1990s. He also led the global efforts to develop and harmonize methodology for molecular monitoring, and was an indefatigable organizer of international conferences. These conferences brought together clinicians and scientists, and accelerated the adoption of new therapies. The abundance of praise, tributes and testimonies expressed by many serve to illustrate the indelible impressions these two passionate and affable scholars made on so many people’s lives. This tribute provides an outline of the remarkable story of chronic myeloid leukemia, and in writing it, it is clear that the historical triumph of biomedical science over this leukemia cannot be considered without appreciating the work of both Janet Rowley and John Goldman. PMID:27132280

Interferon in chronic myeloid leukaemia: past and future.

Science.gov (United States)

Guilhot, François; Roy, Lydia; Saulnier, Pierre-Jean; Guilhot, Joëlle

2009-09-01

Imatinib has revolutionized the therapy of chronic myeloid leukaemia. However the complete eradication of leukaemic stem cells is still a matter of discussion. Interferon (IFN) has been used in the past with success. However the proportion of patients who achieved sustained complete cytogenetic response was small. Recently, in addition to its direct antineoplastic effect and immunomodulatory activity, IFN has been shown to stimulate the quiescent leukaemic stem cells. Thus there is now a rational for combining Imatinib and IFN. Large prospective phase III trials are in good progress to demonstrate in humans the usefullness of a combination therapy using Imatinib and IFN.

Myeloid leukemias and virally induced lymphomas in miniature inbred swine; development of a large animal tumor model

Directory of Open Access Journals (Sweden)

RAIMON eDURAN-STRUUCK

2015-11-01

Full Text Available The lack of a large animal transplantable tumor model has limited the study of novel therapeutic strategies for the treatment of liquid cancers. Swine as a species provide a natural option based on their similarities with humans and their already extensive use in biomedical research. Specifically, the MGH miniature swine herd retains unique genetic characteristics that facilitate the study of hematopoietic cell and solid organ transplantation. Spontaneously arising liquid cancers in these swine, specifically myeloid leukemias and B cell lymphomas, closely resemble human malignancies. The ability to establish aggressive tumor cell lines in vitro from these naturally occurring malignancies makes a transplantable tumor model a close reality. Here, we discuss our experience with myeloid and lymphoid tumors in MHC characterized miniature swine and future approaches regarding the development of a large animal transplantable tumor model.

Synthesis and Structures of Two Lanthanide Complexes Containing a Mixed Ligand System: [Ln(Phen){sub 2}(L){sub 3}(HL)]·H{sub 2}O [Ln = La, Ce; Phen = Phenanthroline; HL = Salicylic Acid

Energy Technology Data Exchange (ETDEWEB)

Iravani, Effat [UNiv. of Applied Science and Technology, Tehran (Iran, Islamic Republic of); Nami, Navabeh; Nabizadeh, Fatemeh; Bayani, Elham [Islamic Azad Univ., Mazandaran (Iran, Islamic Republic of); Neumueller, Bernhard [Philipps-Universitat Marburg, Marburg (Germany)

2013-11-15

The reaction of LnCl{sub 3}·7H{sub 2}O [Ln = La (1), Ce (2)] with salicylic acid (HL) and 1,10-phenanthroline (Phen) at 20 .deg. C in H{sub 2}O/ethanol gave after work-up and recrystallization two novel lanthanide complexes with general formula [Ln(Phen){sub 2}(L){sub 3}(HL)]·H{sub 2}O. Compounds 1 and 2 were characterized by IR and UV-Vis spectroscopy, TGA, CHN as well as by X-ray analysis. According to these results, compounds 1 and 2 are isostructural and contain Ln{sup 3+} ions with coordination number nine. Complexes 1 and 2 consist of two Phen, one neutral HL and three L anions (two L anions act as monodentate ligands and the third one is chelating to Ln{sup 3+}). Thermal decomposition led to primary loss of the Phen molecules. Then HL molecules and finally L moieties left the material to give Ln{sub 2}O{sub 3}.

40 CFR 1065.525 - Engine starting, restarting, shutdown, and optional repeating of void discrete modes.

Science.gov (United States)

2010-07-01

..., and optional repeating of void discrete modes. 1065.525 Section 1065.525 Protection of Environment... repeating of void discrete modes. (a) Start the engine using one of the following methods: (1) Start the... during one of the modes of a discrete-mode test, you may void the results only for that individual mode...

The Supervisory Control System for the HL-2A Neutral Beam Injector

Science.gov (United States)

Li, Bo; Li, Li; Feng, Kun; Wang, Xueyun; Yang, Jiaxing; Huang, Zhihui; Kang, Zihua; Wang, Mingwei; Zhang, Guoqing; Lei, Guangjiu; Rao, Jun

2009-06-01

Supervisory control and protection system of the neutral beam injector (NBI) in the HL-2A tokamak is presented. The system is used for a safe coordination of all the main NBI subsystems. Because the system is based on computer networks with its transmission medium of optical fiber, its advantages in high operational stability, reliability, security and flexible functional expandability are clearly shown during the NBI commissioning and heating experiment in HL-2A.

99MTC-HL91 spect image versus 18F-FDG PET for detection of head and neck carcinoma

International Nuclear Information System (INIS)

Chu, L.S.; Liu, R.S.; Chou, K.L.; Yang, B.H.; Liao, S.Q.; Yeh, S.H.

2004-01-01

Objective: Tumor hypoxia is a major complication of oncologic cell switch for chemotherapy(C/T) and / or radiotherapy(R/T). Such lesions detected by selective modem conventional examination remains difficult. 99mTc-HL91 is a potential agent for imaging hypoxic tissue in vivo. This study aimed to assess efficacy of 99mTc- HL91 in imaging of head and neck cancer and compared the result with 18F-fluorodeoxyglucose(FDG)PET. Methods: Sixteen pts with head and neck cancers (7 hypopharyngeal cancers, 4 laryngeal cancers, 5 tongue base cancers) were enrolled in this study. Primary tumors and suspicious local,regional metastases were diagnosed by clinical examination, CT/MRI , and biopsy. After intravenous injection of 740 MBq of 99mTc-HL91, whole body planar scan and regional SPECT at 2hr postinjection were performed. Tumor lesion -to- normal background(T/N) ratios with 3x3 pixels of background ROI were also measured. The reference range of T/N ratio greater 3.0 defined +, close to 2.4 defined +/- and less than 1.5 defined as -. The FDG images with dedicated PET system was performed at 4hr after completion of 99mTc-HL91 study. The visualized tumors uptake with ratio of standardized uptake value (SUV) greater than 2.5 defined as +.. less than 2.5 defined -. Results: In 7 hypopharyngeal cancers, there are 2FDG+/HL91+, 3FDG+/HL91-, 2FDG+/HL91+/-, In 4 laryngeal cancers, there are 3FDG+/HL91-, 1FDG+/HL91 +/-. In 5 tongue base cancers, there are 5FDG+/HL91-.(Table 1). The T/N ratios of all head and neck cancers in primary tumor and regional lymph nodes were ranged from l.3/1.5 and 1.1/1.2 respectively. The frequency of FDG + in hypopharyngeal cancers is 1.0,in laryngeal cancers is 1.0 and in tongue base cancers is 1.0. The frequency of HL91+/+/- in hypopharyngeal cancers is 0..58,in laryngeal cancers is 0.25.and in tongue base cancers is 0. The overall detection rate of head and neck cancer by FDG+ in this study is 100% and overall detection rate of local-regional hypoxia, by

Inhibition of autophagy as a treatment strategy for p53 wild-type acute myeloid leukemia

NARCIS (Netherlands)

Folkerts, Hendrik; Hilgendorf, Susan; Wierenga, Albertus T J; Jaques, Jennifer; Mulder, André B; Coffer, Paul J; Schuringa, Jan Jacob; Vellenga, Edo

2017-01-01

Here we have explored whether inhibition of autophagy can be used as a treatment strategy for acute myeloid leukemia (AML). Steady-state autophagy was measured in leukemic cell lines and primary human CD34(+) AML cells with a large variability in basal autophagy between AMLs observed. The autophagy

On the HL-1M tokamak plasma confinement time

International Nuclear Information System (INIS)

Qin Yunwen

2001-01-01

Emphasizing that the tokamak plasma confinement time is the plasma particle or thermal energy loss characteristic time, the relevant physical concept and HL-1M tokamak experimental data analyses are reviewed

Myeloid Sarcoma of the Uterine Cervix as Presentation of Acute Myeloid Leukaemia after Treatment with Low-Dose Radioiodine for Thyroid Cancer: A Case Report and Review of the Literature

Directory of Open Access Journals (Sweden)

Anne Sophie Weingertner

2009-01-01

Full Text Available The development of acute myeloid leukaemia after low-dose radioiodine therapy and its presentation as a myeloid sarcoma of the uterine cervix are both rare events. We report a case of acute myeloid leukaemia revealed by a myeloid sarcoma of the uterine cervix in a 48-year-old woman, 17 months after receiving a total dose of 100 mCi 131I for papillary thyroid cancer. A strict hematological follow-up of patients treated with any dose of 131I is recommended to accurately detect any hematological complications which might have been underestimated. Unusual presentations, such as chloroma of the uterine cervix, may reveal myeloid malignancy and should be kept in mind.

Development of a USB-based multi-channel time division scaler for HL-2A

International Nuclear Information System (INIS)

Liang Ping

2008-01-01

HL-2A is China's first Tokamak device with divertor configuration. Mastering the process and plasma parameter changes with time are of great significance to achieve controlled nuclear fusion. In the recent upgrading of HL-2A, for which a higher and faster electronic equipment was required, we developed a new type USB multi-channel time division scaler for HL-2A including functions: USB interface, PC graphical user interface, simultaneously calibrating more than five channel signals, optional time division spacing 2-50 ms, count rate up to over 2 MHz, accessing all the information 20 s after a activated signal, and processing data and displaying off-line. (authors)

Physics potential of ATLAS upgrades at HL-LHC

CERN Document Server

Testa, Marianna; The ATLAS collaboration

2017-01-01

The High Luminosity-Large Hadron Collider (HL-LHC) is expected to start in 2026 and to pro- vide an integrated luminosity of 3000 fb−1 in ten years, a factor 10 more than what will be collected by 2023. This high statistics will allow ATLAS to perform precise measurements in the Higgs sector and improve searches for new physics at the TeV scale. The luminosity needed is L ∼ 7.51034 cm−2 s−1, corresponding to ∼200 additional proton-proton pile- up interactions. To face such harsh environment some sub-detectors of the ATLAS experiment will be upgraded or completely substituted. The performances of the new or upgraded ATLAS sub-detectors are presented, focusing in particular on the new inner tracker and a proposed high granularity time device. The impact of those upgrades on crucial physics measurements for HL-LHC program is also shown.

RBE of tritium beta rays for causes of death other than myeloid leukemia in male CBA/H mice

International Nuclear Information System (INIS)

Myers, D.K.; Jackson, J.S.; Dunford, D.W.

1991-05-01

Causes of death were examined for 5,206 male CBA/H mice which had previously been treated with tritiated water or with X rays at comparable doses and comparable dose rates. Data on induced myeloid leukemia had been examined in detail in a previous report. The purpose of the present study was to examine the relative biological effectiveness of tritium beta rays for causes of death other than mye-loid leukemia. However, no consistent values for the tritium relative biological effectiveness were obtained. The values were spread over a wide range for different endpoints and were generally less reliable than those for induction of myeloid leukemia. A surprising decrease in time to death of animals without tumours was observed in the irradiated groups of mice. This observation suggests that a detailed review of recent data on non-specific life shortening in irradiated animals and humans might be useful

29 CFR 99.525 - Criteria for Federal program risk.

Science.gov (United States)

2010-07-01

... Auditors § 99.525 Criteria for Federal program risk. (a) General. The auditor's determination should be... Federal program. The auditor shall use auditor judgment and consider criteria, such as described in... analysis, the auditor may wish to discuss a particular Federal program with auditee management and the...

7 CFR 3052.525 - Criteria for Federal program risk.

Science.gov (United States)

2010-01-01

... ORGANIZATIONS Auditors § 3052.525 Criteria for Federal program risk. (a) General. The auditor's determination... to the Federal program. The auditor shall use auditor judgment and consider criteria, such as... part of the risk analysis, the auditor may wish to discuss a particular Federal program with auditee...

Modeling chronic myeloid leukemia in immunodeficient mice reveals expansion of aberrant mast cells and accumulation of pre-B cells

International Nuclear Information System (INIS)

Askmyr, M; Ågerstam, H; Lilljebjörn, H; Hansen, N; Karlsson, C; Palffy, S von; Landberg, N; Högberg, C; Lassen, C; Rissler, M; Richter, J; Ehinger, M; Järås, M; Fioretos, T

2014-01-01

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that, if not treated, will progress into blast crisis (BC) of either myeloid or B lymphoid phenotype. The BCR-ABL1 fusion gene, encoding a constitutively active tyrosine kinase, is thought to be sufficient to cause chronic phase (CP) CML, whereas additional genetic lesions are needed for progression into CML BC. To generate a humanized CML model, we retrovirally expressed BCR-ABL1 in the cord blood CD34 + cells and transplanted these into NOD-SCID (non-obese diabetic/severe-combined immunodeficient) interleukin-2-receptor γ-deficient mice. In primary mice, BCR-ABL1 expression induced an inflammatory-like state in the bone marrow and spleen, and mast cells were the only myeloid lineage specifically expanded by BCR-ABL1. Upon secondary transplantation, the pronounced inflammatory phenotype was lost and mainly human mast cells and macrophages were found in the bone marrow. Moreover, a striking block at the pre-B-cell stage was observed in primary mice, resulting in an accumulation of pre-B cells. A similar block in B-cell differentiation could be confirmed in primary cells from CML patients. Hence, this humanized mouse model of CML reveals previously unexplored features of CP CML and should be useful for further studies to understand the disease pathogenesis of CML

Detection of an Abnormal Myeloid Clone by Flow Cytometry in Familial Platelet Disorder With Propensity to Myeloid Malignancy.

Science.gov (United States)

Ok, Chi Young; Leventaki, Vasiliki; Wang, Sa A; Dinardo, Courtney; Medeiros, L Jeffrey; Konoplev, Sergej

2016-02-01

To report aberrant myeloblasts detected by flow cytometry immunophenotypic studies in an asymptomatic patient with familial platelet disorder with propensity to myeloid malignancy, a rare autosomal dominant disease caused by germline heterozygous mutations in Runt-related transcription factor 1. Morphologic evaluation, flow cytometry immunophenotypic studies, nanofluidics-based qualitative multiplex reverse transcriptase polymerase chain reaction, Sanger sequencing, and next-generation sequencing-based mutational hotspot analysis of 53 genes were performed on bone marrow biopsy and aspirate samples. Flow cytometry immunophenotypic analysis showed 0.6% CD34+ blasts with an abnormal immunophenotype: CD13 increased, CD33+, CD38 decreased, CD117 increased, and CD123 increased. The acquisition of new phenotypic aberrancies in myeloblasts as detected by flow cytometry immunophenotypic studies might be a harbinger of impending myelodysplastic syndrome or acute myeloid leukemia in a patient with familial platelet disorder with propensity to myeloid malignancy. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

HL-217, a new topical anti-angiogenic agent, inhibits retinal vascular leakage and pathogenic subretinal neovascularization in Vldlr{sup −/−} mice

Energy Technology Data Exchange (ETDEWEB)

Kim, Junghyun; Kim, Chan-Sik; Jo, Kyuhyung [Korean Medicine Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon (Korea, Republic of); Cho, Yun-Seok; Kim, Hyun-Gyu; Lee, Geun-Hyeog [Research and Development Center, Hanlim Pharm. Co. Ltd., 1656-10, Seocho-dong, Seocho-gu, Seoul (Korea, Republic of); Lee, Yun Mi; Sohn, Eunjin [Korean Medicine Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon (Korea, Republic of); Kim, Jin Sook, E-mail: jskim@kiom.re.kr [Korean Medicine Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon (Korea, Republic of)

2015-01-02

Highlights: • HL-217 is a new synthetic topical anti-angiogenic agent. • HL-217 attenuated subretinal neovascularization in Vldlr{sup −/−} mice. • HL-217 blocked the binding of PDGF-BB to PDGFRβ. - Abstract: HL-217 is a new synthetic angiogenesis inhibitor. Platelet derived growth factor (PDGF) is a vasoactive factor and has been implicated in proliferative retinopathies. In this study, we examined the mechanism of action and efficacy of topical application of HL-217 on subretinal neovascularization in very low-density lipoprotein receptor knockout (Vldlr{sup −/−}) mice. In three-week-old male Vldlr{sup −/−} mice, HL-217 (1.5 or 3 mg/ml) was administered twice per day for 4 weeks by topical eye drop instillation. Neovascular areas were then measured. We used a protein array to evaluate the expression levels of angiogenic factors. The inhibitory effect of HL-217 on the PDGF-BB/PDGFRβ interaction was evaluated in vitro. The neovascular area in the Vldlr{sup −/−} mice was significantly reduced by HL-217. Additionally, HL-217 decreased the expression levels of PDGF-BB protein and VEGF mRNA. Moreover, HL-217 dose-dependently inhibited the PDGF-BB/PDGFRβ interaction (IC{sub 50} = 38.9 ± 0.7 μM). These results suggest that HL-217 is a potent inhibitor of PDGF-BB. HL-217, when applied topically, is an effective inhibitor of subretinal neovascularization due to its ability to inhibit the pro-angiogenic effects of PDGF-BB.

Diverse Brain Myeloid Expression Profiles Reveal Distinct Microglial Activation States and Aspects of Alzheimer’s Disease Not Evident in Mouse Models

Directory of Open Access Journals (Sweden)

Brad A. Friedman

2018-01-01

Full Text Available Microglia, the CNS-resident immune cells, play important roles in disease, but the spectrum of their possible activation states is not well understood. We derived co-regulated gene modules from transcriptional profiles of CNS myeloid cells of diverse mouse models, including new tauopathy model datasets. Using these modules to interpret single-cell data from an Alzheimer’s disease (AD model, we identified microglial subsets—distinct from previously reported “disease-associated microglia”—expressing interferon-related or proliferation modules. We then analyzed whole-tissue RNA profiles from human neurodegenerative diseases, including a new AD dataset. Correcting for altered cellular composition of AD tissue, we observed elevated expression of the neurodegeneration-related modules, but also modules not implicated using expression profiles from mouse models alone. We provide a searchable, interactive database for exploring gene expression in all these datasets (http://research-pub.gene.com/BrainMyeloidLandscape. Understanding the dimensions of CNS myeloid cell activation in human disease may reveal opportunities for therapeutic intervention.

Evaluation of Antiradical and Anti-Inflammatory Activities of Ethyl Acetate and Butanolic Subfractions of Agelanthus dodoneifolius (DC. Polhill & Wiens (Loranthaceae Using Equine Myeloperoxidase and Both PMA-Activated Neutrophils and HL-60 Cells

Directory of Open Access Journals (Sweden)

Rainatou Boly

2015-01-01

Full Text Available The ethyl acetate and n-butanolic subfractions of Agelanthus dodoneifolius were investigated for their antioxidant and antimyeloperoxidase (MPO activities. The reactive oxygen species (ROS generation was assessed by lucigenin-enhanced chemiluminescence (CL and dichlorofluorescein- (DCF- induced fluorescence techniques from phorbol myristate acetate- (PMA- stimulated equine neutrophils and human myeloid cell line HL-60, respectively. In parallel, the effects of the tested subfractions were evaluated on the total MPO release by stimulated neutrophils and on the specific MPO activity by means of immunological assays. The results showed the potent activity of the butanolic subfraction, at least in respect of the chemiluminescence test (IC50 = 0.3±0.1 µg/mL and the ELISA and SIEFED assays (IC50 = 2.8±1.2 µg/mL and 1.3±1.0 µg/mL, respectively. However, the ethyl acetate subfraction was found to be the most potent in the DCF assay as at the highest concentration, DCF fluorescence intensity decreases of about 50%. Moreover, we demonstrated that the ethyl acetate subfraction was rich in catechin (16.51% while it was not easy to identify the main compounds in the butanolic subfraction using the UPLC-MS/MS technique. Nevertheless, taken together, our results provide evidence that Agelanthus dodoneifolius subfractions may represent potential sources of natural antioxidants and of antimyeloperoxidase compounds.

The CMS ECAL Upgrade for Precision Crystal Calorimetry at the HL-LHC

CERN Document Server

Jofrehei, Arash

2017-01-01

The Compact Muon Solenoid Experiment (CMS) is operating at the Large Hadron Collider (LHC) with proton-proton collisions at 13 TeV center-of-mass energy and at a bunch spacing of 25 ns. Challenging running conditions for CMS are expected after the High-Luminosity upgrade of the LHC (HL-LHC). We review the CMS ECAL crystal calorimeter upgrade and present results from the first test beam studies. Particular challenges at HL-LHC are the harsh radiation environment, the increasing data rates and the extreme level of pile-up events, with up to 200 simultaneous proton-proton collisions. Precision timing can be exploited to reduce the effect of the pile-up. We report on the timing resolution studies performed with test-beams. We discuss the new readout and trigger electronics, which must be upgraded due to the increased trigger and latency requirements at the HL-LHC.

Phospholipase D catalyzes phospholipid metabolism in chemotactic peptide-stimulated HL-60 granulocytes

International Nuclear Information System (INIS)

Pai, J.K.; Siegel, M.I.; Egan, R.W.; Billah, M.M.

1988-01-01

There exists circumstantial evidence for activation of phospholipase D (PLD) in intact cells. However, because of the complexity of phospholipid remodeling processes, it is essential to distinguish PLD clearly from other phospholipases and phospholipid remodeling enzymes. Therefore, to establish unequivocally PLD activity in dimethyl sulfoxide-differentiated HL-60 granulocytes, to demonstrate the relative contribution of PLD to phospholipid turnover, and to validate the hypothesis that the formation of phosphatidylethanol is an expression of PLD-catalyzed transphosphatidylation, we have developed methodologies to label HL-60 granulocytes in 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine (alkyl-PC) with 32P without labeling cellular ATP. These methodologies involve (a) synthesis of alkyl-lysoPC containing 32P by a combination of enzymatic and chemical procedures and (b) incubation of HL-60 granulocytes with this alkyl-[32P] lysoPC which enters the cell and becomes acylated into membrane-associated alkyl-[32P]PC. Upon stimulation of these 32P-labeled cells with the chemotactic peptide, N-formyl-Met-Leu-Phe (fMLP), alkyl-[32P]phosphatidic acid (alkyl-[32P]PA) is formed rapidly. Because, under these conditions, cellular ATP has not been labeled with 32P, alkyl-[32P]PA must be formed via PLD-catalyzed hydrolysis of alkyl-[32P]PC at the terminal phosphodiester bond. This result conclusively demonstrates fMLP-induced activation of PLD in HL-60 granulocytes. These 32P-labeled HL-60 granulocytes have also been stimulated in the presence of ethanol to produce alkyl-[32P]phosphatidylethanol (alkyl-[32P]PEt). Formation of alkyl-[32P]PEt parallels that of alkyl-[32P]PA with respect to time course, fMLP concentration, inhibition by a specific fMLP antagonist (t-butoxycarbonyl-Met-Leu-Phe), and Ca2+ concentration

Human algorithmic stability and human Rademacher complexity

NARCIS (Netherlands)

Vahdat, Mehrnoosh; Oneto, L.; Ghio, A; Anguita, D.; Funk, M.; Rauterberg, G.W.M.

2015-01-01

In Machine Learning (ML), the learning process of an algo- rithm given a set of evidences is studied via complexity measures. The way towards using ML complexity measures in the Human Learning (HL) domain has been paved by a previous study, which introduced Human Rademacher Complexity (HRC): in this

Characterization of plasma current quench during disruptions at HL-2A

Science.gov (United States)

Zhu, Jinxia; Zhang, Yipo; Dong, Yunbo; HL-2A Team

2017-05-01

The most essential assumptions of physics for the evaluation of electromagnetic forces on the plasma-facing components due to a disruption-induced eddy current are characteristics of plasma current quenches including the current quench rate or its waveforms. The characteristics of plasma current quenches at HL-2A have been analyzed during spontaneous disruptions. Both linear decay and exponential decay are found in the disruptions with the fastest current quenches. However, there are two stages of current quench in the slow current quench case. The first stage with an exponential decay and the second stage followed by a rapid linear decay. The faster current quench rate corresponds to the faster movement of plasma displacement. The parameter regimes on the current quench time and the current quench rates have been obtained from disruption statistics at HL-2A. There exists no remarkable difference for distributions obtained between the limiter and the divertor configuration. This data from HL-2A provides basic data of the derivation of design criteria for a large-sized machine during the current decay phase of the disruptions.

Synthesis and Biological Activity of Diastereomeric and Geometric Analogs of Calcipotriol, PRI-2202 and PRI-2205, Against Human HL-60 Leukemia and MCF-7 Breast Cancer Cells.

Science.gov (United States)

Milczarek, Magdalena; Chodyński, Michał; Filip-Psurska, Beata; Martowicz, Agnieszka; Krupa, Małgorzata; Krajewski, Krzysztof; Kutner, Andrzej; Wietrzyk, Joanna

2013-10-31

Diastereomeric and geometric analogs of calcipotriol, PRI-2202 and PRI-2205, were synthesized as advanced intermediates from vitamin D C-22 benzothiazoyl sulfones and side-chain aldehydes using our convergent strategy. Calcitriol, calcipotriol (PRI-2201) and tacalcitol (PRI-2191) were used as the reference compounds. Among a series of tested analogs the diastereomeric analog PRI-2202 showed the strongest antiproliferative activity on the human breast cancer cell line MCF-7, whereas the geometric analog PRI-2205 was the weakest. Both analogs were less potent in antiproliferative activity against HL-60 cells compared to the reference compounds. The ability to potentiate antiproliferative effect of cisplatin or doxorubicin against HL-60 cells or that of tamoxifen against the MCF-7 cell line was observed at higher doses of PRI-2202 or PRI-2205 than those of the reference compounds. The proapoptotic activity of tamoxifen, expressed as the diminished mitochondrial membrane potential, as well as the increased phosphatidylserine expression, was partially attenuated by calcitriol, PRI-2191, PRI-2201 and PRI-2205. The treatment of the MCF-7 cells with tamoxifen alone resulted in an increase in VDR expression. Moreover, a further increase in VDR expression was observed when the analogs PRI-2201 or PRI-2205, but not PRI-2191, were used in combination with tamoxifen. This observation could partially explain the potentiation of the antiproliferative effect of tamoxifen by vitamin D analogs.

Radiation hard silicon particle detectors for HL-LHC—RD50 status report

Energy Technology Data Exchange (ETDEWEB)

Terzo, S., E-mail: Stefano.Terzo@mpp.mpg.de

2017-02-11

It is foreseen to significantly increase the luminosity of the LHC by upgrading towards the HL-LHC (High Luminosity LHC). The Phase-II-Upgrade scheduled for 2024 will mean unprecedented radiation levels, way beyond the limits of the silicon trackers currently employed. All-silicon central trackers are being studied in ATLAS, CMS and LHCb, with extremely radiation hard silicon sensors to be employed on the innermost layers. Within the RD50 Collaboration, a massive R&D program is underway across experimental boundaries to develop silicon sensors with sufficient radiation tolerance. We will present results of several detector technologies and silicon materials at radiation levels corresponding to HL-LHC fluences. Based on these results, we will give recommendations for the silicon detectors to be used at the different radii of tracking systems in the LHC detector upgrades. In order to complement the measurements, we also perform detailed simulation studies of the sensors. - Highlights: • The RD50 collaboration investigates the radiation hardness of silicon sensors. • Different approaches to simulate the detector response after irradiation are shown. • HV-CMOS are cost-effective solution for the outer pixel layers at HL-LHC. • 3D and thin planar sensors with slim edges are solutions for innermost layers at HL-LHC. • Sensors with intrinsic gain are investigated to develop ultra-fast silicon detectors.

Leishmania Hijacks Myeloid Cells for Immune Escape

Directory of Open Access Journals (Sweden)

María Martínez-López

2018-05-01

Full Text Available Protozoan parasites of the Leishmania genus are the causative agents of leishmaniasis, a group of neglected tropical diseases whose clinical manifestations vary depending on the infectious Leishmania species but also on host factors. Recognition of the parasite by host myeloid immune cells is a key to trigger an effective Leishmania-specific immunity. However, the parasite is able to persist in host myeloid cells by evading, delaying and manipulating host immunity in order to escape host resistance and ensure its transmission. Neutrophils are first in infiltrating infection sites and could act either favoring or protecting against infection, depending on factors such as the genetic background of the host or the parasite species. Macrophages are the main host cells where the parasites grow and divide. However, macrophages are also the main effector population involved in parasite clearance. Parasite elimination by macrophages requires the priming and development of an effector Th1 adaptive immunity driven by specific subtypes of dendritic cells. Herein, we will provide a comprehensive outline of how myeloid cells regulate innate and adaptive immunity against Leishmania, and the mechanisms used by the parasites to promote their evasion and sabotage. Understanding the interactions between Leishmania and the host myeloid cells may lead to the development of new therapeutic approaches and improved vaccination to leishmaniases, an important worldwide health problem in which current therapeutic or preventive approaches are limited.

Recent advances in the HL-2A tokamak experiments

International Nuclear Information System (INIS)

Liu, Y.; Ding, X.T.; Yang, Q.W.; Yan, L.W.; Liu, D.Q.; Xuan, W.M.; Chen, L.Y.; Song, X.M.; Cao, Z.; Zhang, J.H.; Mao, W.C.; Zhou, C.P.; Li, X.D.; Wang, S.J.; Yan, J.C.; Bu, M.N.; Chen, Y.H.; Cui, C.H.; Cui, Z.Y.; Deng, Z.C.; Hong, W.Y.; Hu, H.T.; Huang, Y.; Kang, Z.H.; Li, B.; Li, W.; Li, F.Z.; Li, G.S.; Li, H.J.; Li, Q.; Li, Y.G.; Li, Z.J.; Liu, Yi; Liu, Z.T.; Luo, C.W.; Mao, X.H.; Pan, Y.D.; Rao, J.; Shao, K.; Song, X.Y.; Wang, M.; Wang, M.X.; Wang, Q.M.; Xiao, Z.G.; Xie, Y.F.; Yao, L.H.; Yao, L.Y.; Zheng, Y.J.; Zhong, G.W.; Zhou, Y.; Pan, C.H.

2005-01-01

Two experiment campaigns were conducted on the HL-2A tokamak in 2003 and 2004 after the first plasma was obtained at the end of 2002. Progresses in many aspects have been made, especially in the divertor discharge and feedback control of plasma configuration. Up to now, the following operation parameters have been achieved: I p = 320 kA, B t = 2.2 T and discharge duration T d = 1580 ms. With the feedback control of plasma current and horizontal position, an excellent repeatability of the discharge has been achieved. The tokamak has been operated at both limiter configuration and single null (SN) divertor configuration. The HL-2A SN divertor configuration is simulated with the MHD equilibrium code SWEQU. When the divertor configuration is formed, the impurity radiation in the main plasma decreases remarkably

Magnetically Induced Disk Winds and Transport in the HL Tau Disk

International Nuclear Information System (INIS)

Hasegawa, Yasuhiro; Flock, Mario; Turner, Neal J.; Okuzumi, Satoshi

2017-01-01

The mechanism of angular momentum transport in protoplanetary disks is fundamental to understanding the distributions of gas and dust in the disks. The unprecedented ALMA observations taken toward HL Tau at high spatial resolution and subsequent radiative transfer modeling reveal that a high degree of dust settling is currently achieved in the outer part of the HL Tau disk. Previous observations, however, suggest a high disk accretion rate onto the central star. This configuration is not necessarily intuitive in the framework of the conventional viscous disk model, since efficient accretion generally requires a high level of turbulence, which can suppress dust settling considerably. We develop a simplified, semi-analytical disk model to examine under what condition these two properties can be realized in a single model. Recent, non-ideal MHD simulations are utilized to realistically model the angular momentum transport both radially via MHD turbulence and vertically via magnetically induced disk winds. We find that the HL Tau disk configuration can be reproduced well when disk winds are properly taken into account. While the resulting disk properties are likely consistent with other observational results, such an ideal situation can be established only if the plasma β at the disk midplane is β 0 ≃ 2 × 10 4 under the assumption of steady accretion. Equivalently, the vertical magnetic flux at 100 au is about 0.2 mG. More detailed modeling is needed to fully identify the origin of the disk accretion and quantitatively examine plausible mechanisms behind the observed gap structures in the HL Tau disk.

Magnetically Induced Disk Winds and Transport in the HL Tau Disk

Energy Technology Data Exchange (ETDEWEB)

Hasegawa, Yasuhiro; Flock, Mario; Turner, Neal J. [Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109 (United States); Okuzumi, Satoshi, E-mail: yasuhiro@caltech.edu [Department of Earth and Planetary Sciences, Tokyo Institute of Technology, Meguro-ku, Tokyo 152-8551 (Japan)

2017-08-10

The mechanism of angular momentum transport in protoplanetary disks is fundamental to understanding the distributions of gas and dust in the disks. The unprecedented ALMA observations taken toward HL Tau at high spatial resolution and subsequent radiative transfer modeling reveal that a high degree of dust settling is currently achieved in the outer part of the HL Tau disk. Previous observations, however, suggest a high disk accretion rate onto the central star. This configuration is not necessarily intuitive in the framework of the conventional viscous disk model, since efficient accretion generally requires a high level of turbulence, which can suppress dust settling considerably. We develop a simplified, semi-analytical disk model to examine under what condition these two properties can be realized in a single model. Recent, non-ideal MHD simulations are utilized to realistically model the angular momentum transport both radially via MHD turbulence and vertically via magnetically induced disk winds. We find that the HL Tau disk configuration can be reproduced well when disk winds are properly taken into account. While the resulting disk properties are likely consistent with other observational results, such an ideal situation can be established only if the plasma β at the disk midplane is β {sub 0} ≃ 2 × 10{sup 4} under the assumption of steady accretion. Equivalently, the vertical magnetic flux at 100 au is about 0.2 mG. More detailed modeling is needed to fully identify the origin of the disk accretion and quantitatively examine plausible mechanisms behind the observed gap structures in the HL Tau disk.

Section 525(a) of the bankruptcy code plainly does not apply to Medicare provider agreements.

Science.gov (United States)

Sperow, E H

2001-01-01

Section 525(a) of the Bankruptcy Code prevents government entities from discriminating against debtors based on the debtor's bankruptcy filing. This Article analyzes how this provision is applied to healthcare providers who file for bankruptcy. Some commentators have expressed concerns that because of Section 525, the federal government is unable to deny a bankrupt provider a new Medicare provider agreement due to the debtor's failure to pay debts discharged during bankruptcy. This Article, however, argues that Section 525 does not apply to a provider agreements because it is not a "license, permit, charter, franchise, or other similar grant" as defined by the statute. Therefore, the author concludes that debtor healthcare providers should not be allowed back into the Medicare program without first paying their statutorily required debts.

5-Fluoro-2'-Deoxycytidine and Tetrahydrouridine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

Science.gov (United States)

2015-06-03

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

The CMS HGCAL detector for HL-LHC upgrade

CERN Document Server

Martelli, Arabella

2017-01-01

The High Luminosity LHC (HL-LHC) will integrate 10 times more luminosity than the LHC, posing significant challenges for radiation tolerance and event pileup on detectors, especially for forward calorimetry, and hallmarks the issue for future colliders. As part of its HL-LHC upgrade program, the CMS collaboration is designing a High Granularity Calorimeter to replace the existing endcap calorimeters. It features unprecedented transverse and longitudinal segmentation for both electromagnetic (ECAL) and hadronic (HCAL) compartments. This will facilitate particle-flow calorimetry, where the fine structure of showers can be measured and used to enhance pileup rejection and particle identification, whilst still achieving good energy resolution. The ECAL and a large fraction of HCAL will be based on hexagonal silicon sensors of 0.5 - 1 cm$^2$ cell size, with the remainder of the HCAL based on highly-segmented scintillators with SiPM readout. The intrinsic high-precision timing capabilities of the silicon sensors wi...

The CMS High Granularity Calorimeter for HL-LHC

CERN Document Server

Mastrolorenzo, Luca

2017-01-01

The High Luminosity LHC (HL-LHC) will integrate 10 times more luminosity than the LHC, posing significant challenges for radiation tolerance and event pileup on detectors, especially for forward calorimetry, and hallmarks the issue for future colliders. As part of its HL-LHC upgrade program, the CMS collaboration is designing a High Granularity Calorimeter to replace the existing endcap calorimeters. It features unprecedented transverse and longitudinal segmentation for both electromagnetic (ECAL) and hadronic (HCAL) compartments. This will facilitate particle-flow calorimetry, where the fine structure of showers can be measured and used to enhance pileup rejection and particle identification, whilst still achieving good energy resolution. The ECAL and a large fraction of HCAL will be based on hexagonal silicon sensors of 0.5 - 1 cm$^2$ cell size, with the remainder of the HCAL based on highly-segmented scintillators with SiPM readout. The intrinsic high-precision timing capabilities of the silicon sensors wi...

CAR-T cells targeting CLL-1 as an approach to treat acute myeloid leukemia.

Science.gov (United States)

Wang, Jinghua; Chen, Siyu; Xiao, Wei; Li, Wende; Wang, Liang; Yang, Shuo; Wang, Weida; Xu, Liping; Liao, Shuangye; Liu, Wenjian; Wang, Yang; Liu, Nawei; Zhang, Jianeng; Xia, Xiaojun; Kang, Tiebang; Chen, Gong; Cai, Xiuyu; Yang, Han; Zhang, Xing; Lu, Yue; Zhou, Penghui

2018-01-10

Acute myeloid leukemia (AML) is one of the most common types of adult acute leukemia. Standard chemotherapies can induce complete remission in selected patients; however, a majority of patients eventually relapse and succumb to the disease. Thus, the development of novel therapeutics for AML is urgently needed. Human C-type lectin-like molecule-1 (CLL-1) is a type II transmembrane glycoprotein, and its expression is restricted to myeloid cells and the majority of AML blasts. Moreover, CLL-1 is expressed in leukemia stem cells (LSCs), but absent in hematopoietic stem cells (HSCs), which may provide a potential therapeutic target for AML treatment. We tested the expression of CLL-1 antigen on peripheral blood cells and bone marrow cells in healthy donor and AML patients. Then, we developed a chimeric antigen receptor (CAR) containing a CLL1-specific single-chain variable fragment, in combination with CD28, 4-1BB costimulatory domains, and CD3-ζ signaling domain. We further investigate the function of CLL-1 CAR-T cells. The CLL-1 CAR-T cells specifically lysed CLL-1 + cell lines as well as primary AML patient samples in vitro. Strong anti-leukemic activity was observed in vivo by using a xenograft model of disseminated AML. Importantly, CLL-1 + myeloid progenitor cells and mature myeloid cells were specifically eliminated by CLL-1 CAR-T cells, while normal HSCs were not targeted due to the lack of CLL-1 expression. CLL-1 CAR-T represents a promising immunotherapy for the treatment of AML.

Cucurbitane-type triterpenes from Citrullus lanatus (watermelon) seeds.

Science.gov (United States)

Kikuchi, Takashi; Okada, Rina; Harada, Yu; Ikushima, Kenji; Yamakawa, Takahiro; Yamada, Takeshi; Tanaka, Reiko

2013-10-01

Two new cucurbitane-type triterpenes, 24-hydroperoxycucurbita-5,25-dien-3beta-ol (1) and 25-hydroperoxycucurbita-5,23-dien-3beta-ol (2), were isolated from a MeOH extract of Citrullus lanatus seeds. Compounds 1 and 2 exhibited moderate cytotoxic activities with IC50 values of 33.4-52.4 microM against HL-60 (human leukemia), P388 (murine leukemia), and L1210 (murine leukemia) cells. Compound 1 showed melanogenesis inhibitory activity (melanin content 80.0 %) with low cytotoxicity (cell viability 97.6%) at a low concentration (10 microM).

Induction of apoptosis by hydrolyzable tannins from Eugenia jambos L. on human leukemia cells.

Science.gov (United States)

Yang, L L; Lee, C Y; Yen, K Y

2000-08-31

Eugenia jambos L. (Myrtaceae) is an antipyretic and anti-inflammatory herb of Asian folk medicine. A 70% acetone extract exerted the strongest cytotoxic effects on human leukemia cells (HL-60) from a preliminary screening of 15 plants. The cytotoxic principles were separated by bio-assay-guided fractionation to HL-60 cells; two hydrolyzable tannins (1-O-galloyl castalagin and casuarinin) were isolated from the 70% acetone extract. All significantly inhibited human promyelocytic leukemia cell line HL-60 and showed less cytotoxicity to human adenocarcinoma cell line SK-HEP-1 and normal cell lines of human lymphocytes and Chang liver cells. Thus, these compounds were exhibited the dose-dependent manner in HL-60 cells and the IC(50) were 10.8 and 12.5 microM, respectively. Flow cytometric analysis demonstrated the presence of apoptotic cells with low DNA content, a decrease of cell population at G(2)/M phase, and a concomitant increase of cell population at G(1) phase. The apoptosis induced by these two compounds was also demonstrated by DNA fragmentation assay and microscopic observation. These results suggest that the cytotoxic mechanism of both antitumor principle constituents might be the induction of apoptosis in HL-60 cells.

Power supply for plasma generator of HL-1M neutral beam injector

International Nuclear Information System (INIS)

Wang Detai; Qian Jiamei; Lei Guangjiu; Shun Mengda; Jiang Shaofeng; Wang Enyao; Lu Xuejun; Yang Tiehai; Wang Xuehua; Zhao Zhimin; Hao Ming; Huang Jianrong; Yu Yanqiu; Cheng Baoqiang; Wu Zhige; Sheng Ning; Hu Qingtao

1999-01-01

The diagram of the HL-1M Neutral Beam Injector (NBI) and the power supply (PS) system is shown. The NBI consists of ion source, beam line and power supply system etc. The ion source includes plasma generator and three-electrode extraction system. The power supply for plasma generator consists of a filament PS, an arc PS and gas valve PS. Testing has shown that the PS for plasma generator of the HL-1M NBI has excellent stability and obtain good plasma heating effect

miR-181a promotes G1/S transition and cell proliferation in pediatric acute myeloid leukemia by targeting ATM.

Science.gov (United States)

Liu, Xiaodan; Liao, Wang; Peng, Hongxia; Luo, Xuequn; Luo, Ziyan; Jiang, Hua; Xu, Ling

2016-01-01

Abnormal expression of miRNAs is intimately related to a variety of human cancers. The purpose of this study is to confirm the expression of miR-181a and elucidate its physiological function and mechanism in pediatric acute myeloid leukemia (AML). Pediatric AML patients and healthy controls were enrolled, and the expression of miR-181a and ataxia telangiectasia mutated (ATM) in tissues were examined using quantitative PCR. Moreover, cell proliferation and cell cycle were evaluated in several cell lines (HL60, NB4 and K562) by using flow cytometry after transfected with miR-181a mimics and inhibitors, or ATM siRNA and control siRNA. Finally, ATM as the potential target protein of miR-181a was examined. We found that miR-181a was significantly increased in pediatric AML, which showed an inverse association with ATM expression. Overexpressed miR-181a in cell lines significantly enhanced cell proliferation, as well as increased the ratio of S-phase cells by miR-181a mimics transfection in vitro. Luciferase activity of the reporter construct identified ATM as the direct molecular target of miR-181a. ATM siRNA transfection significantly enhanced cell proliferation and increased the ratio of S-phase cells in vitro. The results revealed novel mechanism through which miR-181a regulates G1/S transition and cell proliferation in pediatric AML by regulating the tumor suppressor ATM, providing insights into the molecular mechanism in pediatric AML.

Lumbar Myeloid Cell Trafficking into Locomotor Networks after Thoracic Spinal Cord Injury

Science.gov (United States)

Hansen, Christopher N.; Norden, Diana M.; Faw, Timothy D.; Deibert, Rochelle; S.Wohleb, Eric; Sheridan, John F.; P.Godbout, Jonathan; Basso, D. Michele

2016-01-01

Spinal cord injury (SCI) promotes inflammation along the neuroaxis that jeopardizes plasticity, intrinsic repair and recovery. While inflammation at the injury site is well-established, less is known within remote spinal networks. The presence of bone marrow-derived immune (myeloid) cells in these areas may further impede functional recovery. Previously, high levels of the gelatinase, matrix metalloproteinase-9 (MMP-9) occurred within the lumbar enlargement after thoracic SCI and impeded activity-dependent recovery. Since SCI-induced MMP-9 potentially increases vascular permeability, myeloid cell infiltration may drive inflammatory toxicity in locomotor networks. Therefore, we examined neurovascular reactivity and myeloid cell infiltration in the lumbar cord after thoracic SCI. We show evidence of region-specific recruitment of myeloid cells into the lumbar but not cervical region. Myeloid infiltration occurred with concomitant increases in chemoattractants (CCL2) and cell adhesion molecules (ICAM-1) around lumbar vasculature 24 hours and 7 days post injury. Bone marrow GFP chimeric mice established robust infiltration of bone marrow-derived myeloid cells into the lumbar gray matter 24 hours after SCI. This cell infiltration occurred when the blood-spinal cord barrier was intact, suggesting active recruitment across the endothelium. Myeloid cells persisted as ramified macrophages at 7 days post injury in parallel with increased inhibitory GAD67 labeling. Importantly, macrophage infiltration required MMP-9. PMID:27191729

History of myeloid-derived suppressor cells.

Science.gov (United States)

Talmadge, James E; Gabrilovich, Dmitry I

2013-10-01

Tumour-induced granulocytic hyperplasia is associated with tumour vasculogenesis and escape from immunity via T cell suppression. Initially, these myeloid cells were identified as granulocytes or monocytes; however, recent studies have revealed that this hyperplasia is associated with populations of multipotent progenitor cells that have been identified as myeloid-derived suppressor cells (MDSCs). The study of MDSCs has provided a wealth of information regarding tumour pathobiology, has extended our understanding of neoplastic progression and has modified our approaches to immune adjuvant therapy. In this Timeline article, we discuss the history of MDSCs, their influence on tumour progression and metastasis, and the crosstalk between tumour cells, MDSCs and the host macroenvironment.

Signaling by myeloid C-type lectin receptors in immunity and homeostasis.

Science.gov (United States)

Sancho, David; Reis e Sousa, Caetano

2012-01-01

Myeloid cells are key drivers of physiological responses to pathogen invasion or tissue damage. Members of the C-type lectin receptor (CLR) family stand out among the specialized receptors utilized by myeloid cells to orchestrate these responses. CLR ligands include carbohydrate, protein, and lipid components of both pathogens and self, which variably trigger endocytic, phagocytic, proinflammatory, or anti-inflammatory reactions. These varied outcomes rely on a versatile system for CLR signaling that includes tyrosine-based motifs that recruit kinases, phosphatases, or endocytic adaptors as well as nontyrosine-based signals that modulate the activation of other pathways or couple to the uptake machinery. Here, we review the signaling properties of myeloid CLRs and how they impact the role of myeloid cells in innate and adaptive immunity.

Myeloid-derived suppressor cells in breast cancer.

Science.gov (United States)

Markowitz, Joseph; Wesolowski, Robert; Papenfuss, Tracey; Brooks, Taylor R; Carson, William E

2013-07-01

Myeloid-derived suppressor cells (MDSCs) are a population of immature myeloid cells defined by their suppressive actions on immune cells such as T cells, dendritic cells, and natural killer cells. MDSCs typically are positive for the markers CD33 and CD11b but express low levels of HLADR in humans. In mice, MDSCs are typically positive for both CD11b and Gr1. These cells exert their suppressive activity on the immune system via the production of reactive oxygen species, arginase, and cytokines. These factors subsequently inhibit the activity of multiple protein targets such as the T cell receptor, STAT1, and indoleamine-pyrrole 2,3-dioxygenase. The numbers of MDSCs tend to increase with cancer burden while inhibiting MDSCs improves disease outcome in murine models. MDSCs also inhibit immune cancer therapeutics. In light of the poor prognosis of metastatic breast cancer in women and the correlation of increasing levels of MDSCs with increasing disease burden, the purposes of this review are to (1) discuss why MDSCs may be important in breast cancer, (2) describe model systems used to study MDSCs in vitro and in vivo, (3) discuss mechanisms involved in MDSC induction/function in breast cancer, and (4) present pre-clinical and clinical studies that explore modulation of the MDSC-immune system interaction in breast cancer. MDSCs inhibit the host immune response in breast cancer patients and diminishing MDSC actions may improve therapeutic outcomes.

Efficient 525 nm laser generation in single or double resonant cavity

Science.gov (United States)

Liu, Shilong; Han, Zhenhai; Liu, Shikai; Li, Yinhai; Zhou, Zhiyuan; Shi, Baosen

2018-03-01

This paper reports the results of a study into highly efficient sum frequency generation from 792 and 1556 nm wavelength light to 525 nm wavelength light using either a single or double resonant ring cavity based on a periodically poled potassium titanyl phosphate crystal (PPKTP). By optimizing the cavity's parameters, the maximum power achieved for the resultant 525 nm laser was 263 and 373 mW for the single and double resonant cavity, respectively. The corresponding quantum conversion efficiencies were 8 and 77% for converting 1556 nm photons to 525 nm photons with the single and double resonant cavity, respectively. The measured intra-cavity single pass conversion efficiency for both configurations was about 5%. The performances of the sum frequency generation in these two configurations was studied and compared in detail. This work will provide guidelines for optimizing the generation of sum frequency generated laser light for a variety of configurations. The high conversion efficiency achieved in this work will help pave the way for frequency up-conversion of non-classical quantum states, such as the squeezed vacuum and single photon states. The proposed green laser source will be used in our future experiments, which includes a plan to generate two-color entangled photon pairs and achieve the frequency down-conversion of single photons carrying orbital angular momentum.

[Clinical and biological prognostic factors in relapsed acute myeloid leukemia patients].

Science.gov (United States)

Yébenes-Ramírez, Manuel; Serrano, Josefina; Martínez-Losada, Carmen; Sánchez-García, Joaquín

2016-09-02

Acute myeloid leukemia (AML) is the most frequent type of acute leukemia in adults. Despite recent advances in the characterization of pathogenesis of AML, the cure rates are under 40%, being leukemia relapse the most common cause of treatment failure. Leukaemia relapse occurs due to clonal evolution or clonal escape. In this study, we aimed to analyze the clinical and biological factors influencing outcomes in patients with AML relapse. We included a total of 75 AML patients who experienced leukaemia relapse after achieving complete remission. We performed complete immunophenotyping and conventional karyotyping in bone marrow aspirates obtained at diagnosis and at leukemia relapse. Overall survival (OS) of the series was 3.7%±2.3, leukaemia progression being the most common cause of death. Patients relapsing before 12 months and those with adverse cytogenetic-molecular risk had statistically significant worse outcomes. A percentage of 52.5 of patients showed phenotypic changes and 50% cytogenetic changes at relapse. We did not find significant clinical factors predicting clonal evolution. The presence of clonal evolution at relapse did not have a significant impact on outcome. Patients with relapsed AML have a dismal prognosis, especially those with early relapse and adverse cytogenetic-molecular risk. Clonal evolution with phenotypic and cytogenetic changes occurred in half of the patients without predictive clinical factors or impact on outcome. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Human Placenta Extract Therapy for Feline Hepatic Lipidosis

OpenAIRE

2018-01-01

Feline hepatic lipidosis (HL), the most common hepatobiliary disease in cats, is characterized by the accumulation of excessive triglycerides (TGs) in more than 80% of hepatocytes. Forced oral feeding is recommended as the only therapy for this disease but the prognosis is often poor. As human placenta extract (Laennec) has been used to improve hepatic metabolism, we investigated the efficacy of this drug for the treatment of cats with HL. Ten cats diagnosed with HL in this study were treated...

Use of hypoxia imaging agent 99mTc-HL91 in rat cerebral ischemia models

International Nuclear Information System (INIS)

Zhou Ying; Qu Wanying; Li Meng; Chen Fang; Yao Zhiming; Zhu Ming; Zhu Lin

1999-01-01

Objective: To explore the possibility of diagnosis for cerebrovascular disease by a novel synthetic hypoxia agent 99m Tc-HL91 used in rat cerebral ischemia models. Methods: Pharmacological experiments of 99m Tc-HL91 were carried out including common properties, radiochemical purity, stability in vitro, anomalous toxicity test and biodistribution in mice. Fifteen cerebral ischemic rat models were established and received 99m Tc-HL91 scintigraphy. Results: 1) HL91 kits were labelled with 99m Tc easily and showed high radiochemical purity and stability. 2) Rapid clearance in blood, heart and lungs and high activity in liver, kidneys and intestines were observed. Relatively low uptake in brain was identified. 3) The radioactivity in ischemic brain tissue increased significantly at 4h postinjection in both rat images and isolated brain images. 4) The radioactivity ratios of lesion to normal brain tissue by drawing ROIs in isolated brain planar images were 0.98 +- 0.06, 0.99 +- 0.05, 1.29 +- 0.03, 1.56 +- 0.14 and 1.66 +- 0.06 at 1,2,4,8 and 12 h postinjection, respectively. There were significant differences among all groups except for 1 h and 2 h, 8 h and 12 h postinjection (P 99m Tc-HL91 in the hypoxic, ischemic brain tissue have been proved. It is appropriate to perform imaging at 4 h postinjection

24 CFR 891.525 - Amount and terms of financing.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Amount and terms of financing. 891... Handicapped-Section 8 Assistance § 891.525 Amount and terms of financing. (a) The amount of financing approved... financing provided shall not exceed the lesser of: (1) The dollar amounts stated in paragraphs (b) through...

Experimental study of 99Tcm-HL91 and 99Tcm-MIBI in mice bearing Lewis lung cancer

International Nuclear Information System (INIS)

Han Chunqi; Li Yaming; Ren Yangang; Yi Lijie

2000-01-01

Objective: To evaluate the ability of detecting lung cancer by 99 Tc m -HL91 and 99 Tc m -MIBI in mice bearing Lewis lung cancer. Methods: Four model mice underwent whole body planar imaging at 2 h, 4 h after injection of 99 Tc m -MIBI; four mice underwent whole body planar imaging at 2 h and 4 h after injection of 99 Tc m -HL91, and the mice of the 99 Tc m -HL91 group were then killed, the tumor, blood and organs were removed, weighted and the radioactivity was measured. ROIs were drawn around the tumor, head and chest in whole body planar images, and radioactivity ratios of tumor to head (T/H), chest (T/C) and contralateral limbs (T/L) were calculated. Results: No significant tumor radioactivity in 2 h and 4 h images of 99 Tc m -MIBI mice (T/C: 0.20 +- 0.08 and 0.14 +- 0.07) was found; increased tumor radioactivity was identified in images of 99 Tc m -HL91 mice (T/C: 3.25 +- 1.25 and 2.44 +- 1.07), and there was significant difference (t = 4.8 - 7.5, P 99 Tc m -HL91 in tumor tissue of mice is higher and clearance rate is slower. 99 Tc m -HL91 is a valuable tumor imaging agent for clinical diagnosis for the cancer

Colony stimulating factor 1 receptor inhibition delays recurrence of glioblastoma after radiation by altering myeloid cell recruitment and polarization

Science.gov (United States)

Stafford, Jason H.; Hirai, Takahisa; Deng, Lei; Chernikova, Sophia B.; Urata, Kimiko; West, Brian L.; Brown, J. Martin

2016-01-01

Background Glioblastoma (GBM) may initially respond to treatment with ionizing radiation (IR), but the prognosis remains extremely poor because the tumors invariably recur. Using animal models, we previously showed that inhibiting stromal cell–derived factor 1 signaling can prevent or delay GBM recurrence by blocking IR-induced recruitment of myeloid cells, specifically monocytes that give rise to tumor-associated macrophages. The present study was aimed at determining if inhibiting colony stimulating factor 1 (CSF-1) signaling could be used as an alternative strategy to target pro-tumorigenic myeloid cells recruited to irradiated GBM. Methods To inhibit CSF-1 signaling in myeloid cells, we used PLX3397, a small molecule that potently inhibits the tyrosine kinase activity of the CSF-1 receptor (CSF-1R). Combined IR and PLX3397 therapy was compared with IR alone using 2 different human GBM intracranial xenograft models. Results GBM xenografts treated with IR upregulated CSF-1R ligand expression and increased the number of CD11b+ myeloid-derived cells in the tumors. Treatment with PLX3397 both depleted CD11b+ cells and potentiated the response of the intracranial tumors to IR. Median survival was significantly longer for mice receiving combined therapy versus IR alone. Analysis of myeloid cell differentiation markers indicated that CSF-1R inhibition prevented IR-recruited monocyte cells from differentiating into immunosuppressive, pro-angiogenic tumor-associated macrophages. Conclusion CSF-1R inhibition may be a promising strategy to improve GBM response to radiotherapy. PMID:26538619

Hollow Electron Beam Collimation for HL-LHC - Effects on the Beam Core

Energy Technology Data Exchange (ETDEWEB)

Fitterer, M. [Fermilab; Stancari, G. [Fermilab; Valishev, A. [Fermilab; Bruce, R. [CERN; Papotti, G [CERN; Redaelli, S. [CERN; Valentino, G. [Malta U.; Valentino, G. [CERN; Valuch, D. [CERN; Xu, C. [CERN

2017-06-13

Collimation with hollow electron beams is currently one of the most promising concepts for active halo control in the High Luminosity Large Hadron Collider (HL-LHC). To ensure the successful operation of the hollow beam collimator the unwanted effects on the beam core, which might arise from the operation with a pulsed electron beam, must be minimized. This paper gives a summary of the effect of hollow electron lenses on the beam core in terms of sources, provides estimates for HL-LHC and discusses the possible mitigation methods.

Future Plans of the ATLAS Collaboration for the HL-LHC

CERN Document Server

Hristova, Ivana; The ATLAS collaboration

2018-01-01

These proceedings report the current plans to upgrade the ATLAS detector at CERN for the High Luminosity LHC (HL-LHC). The HL-LHC is expected to start operations in the middle of 2026, aiming to reach an ultimate peak instantaneous luminosity of 7.5$\\times10^{34}$cm$^{-2}$s$^{-1}$, corresponding to approximately 200 inelastic proton-proton collisions per bunch crossing, and to deliver over a period of twelve years more than ten times the integrated luminosity of the large hadron collider (LHC) Runs 1-3 combined (up to $4000$ fb$^{-1}$). This is a huge challenge to all sub-systems of the detector which will need extensive upgrades to allow the experiment to pursue a rich and interesting physics programme in the future.

Cellular uptake of 99mTcN-NOET in human leukaemic HL-60 cells is related to calcium channel activation and cell proliferation

International Nuclear Information System (INIS)

Guillermet, Stephanie; Vuillez, Jean-Philippe; Caravel, Jean-Pierre; Marti-Batlle, Daniele; Fagret, Daniel; Fontaine, Eric; Pasqualini, Roberto

2006-01-01

A major goal of nuclear oncology is the development of new radiolabelled tracers as proliferation markers. Intracellular calcium waves play a fundamental role in the course of the cell cycle. These waves occur in non-excitable tumour cells via store-operated calcium channels (SOCCs). Bis(N-ethoxy, N-ethyldithiocarbamato) nitrido technetium (V)-99m ( 99m TcN-NOET) has been shown to interact with L-type voltage-operated calcium channels (VOCCs) in cultured cardiomyocytes. Considering the analogy between VOCCs and SOCCs, we sought to determine whether 99m TcN-NOET also binds to activated SOCCs in tumour cells in order to clarify the potential value of this tracer as a proliferation marker. Uptake kinetics of 99m TcN-NOET were measured in human leukaemic HL-60 cells over 60 min and the effect of several calcium channel modulators on 1-min tracer uptake was studied. The uptake kinetics of 99m TcN-NOET were compared both with the variations of cytosolic free calcium concentration measured by indo-1/AM and with the variations in the SG 2 M cellular proliferation index. All calcium channel inhibitors significantly decreased the cellular uptake of 99m TcN-NOET whereas the activator thapsigargin induced a significant 10% increase. In parallel, SOCC activation by thapsigargin, as measured using the indo-1/AM probe, was inhibited by nicardipine. These results indicate that the uptake of 99m TcN-NOET is related to the activation of SOCCs. Finally, a correlation was observed between the tracer uptake and variations in the proliferation index SG 2 M. The uptake of 99m TcN-NOET seems to be related to SOCC activation and to cell proliferation in HL-60 cells. These results indicate that 99m TcN-NOET might be a marker of cell proliferation. (orig.)

Myeloid cells in circulation and tumor microenvironment of breast cancer patients.

Science.gov (United States)

Toor, Salman M; Syed Khaja, Azharuddin Sajid; El Salhat, Haytham; Faour, Issam; Kanbar, Jihad; Quadri, Asif A; Albashir, Mohamed; Elkord, Eyad

2017-06-01

Pathological conditions including cancers lead to accumulation of a morphological mixture of highly immunosuppressive cells termed as myeloid-derived suppressor cells (MDSC). The lack of conclusive markers to identify human MDSC, due to their heterogeneous nature and close phenotypical and functional proximity with other cell subsets, made it challenging to identify these cells. Nevertheless, expansion of MDSC has been reported in periphery and tumor microenvironment of various cancers. The majority of studies on breast cancers were performed on murine models and hence limited literature is available on the relation of MDSC accumulation with clinical settings in breast cancer patients. The aim of this study was to investigate levels and phenotypes of myeloid cells in peripheral blood (n = 23) and tumor microenvironment of primary breast cancer patients (n = 7), compared with blood from healthy donors (n = 21) and paired non-tumor normal breast tissues from the same patients (n = 7). Using multicolor flow cytometric assays, we found that breast cancer patients had significantly higher levels of tumor-infiltrating myeloid cells, which comprised of granulocytes (P = 0.022) and immature cells that lack the expression of markers for fully differentiated monocytes or granulocytes (P = 0.016). Importantly, this expansion was not reflected in the peripheral blood. The immunosuppressive potential of these cells was confirmed by expression of Arginase 1 (ARG1), which is pivotal for T-cell suppression. These findings are important for developing therapeutic modalities to target mechanisms employed by immunosuppressive cells that generate an immune-permissive environment for the progression of cancer.

Dasatinib-Induced Rhabdomyolysis in a 33-Year-Old Patient with Chronic Myeloid Leukemia

Directory of Open Access Journals (Sweden)

Andrew Stevenson Joel Chandranesan

2018-01-01

Full Text Available Rhabdomyolysis is a life-threatening syndrome due to breakdown of the skeletal muscle. It can be caused by massive trauma and crush injuries or occur as a side effect of medications. Here, we describe a case of a 33-year-old male with human immunodeficiency virus (HIV and newly diagnosed chronic myeloid leukemia (CML with severe life-threatening rhabdomyolysis due to a rare offending agent.

H-L transition caused by irregular probe insertion in the JFT-2M tokamak

International Nuclear Information System (INIS)

Hanada, K.; Hasegawa, M.; Shinohara, K.

1996-01-01

A pair of probe pins whose lengths differ by 5 mm are inserted into the separatrix of H-mode plasmas. When the long pin is biased positively against the short one, the H-L transition takes place and the current through the resistor making a connection between these pins increases for 10 μs and the potential of the pin increases for 100 μs. The energy dissipated by the resistor during the H-L transition is comparable to the energy of the radial electric field in H-mode plasma. When the long pin is biased negatively, the H-L transition also occurs; however, it takes 1 ms to change the potential of the pin and the plasma returns to H-mode after the extraction of the probe. (author)

Synthesis and Biological Activity of Diastereomeric and Geometric Analogs of Calcipotriol, PRI-2202 and PRI-2205, Against Human HL-60 Leukemia and MCF-7 Breast Cancer Cells

Directory of Open Access Journals (Sweden)

Andrzej Kutner

2013-10-01

Full Text Available Diastereomeric and geometric analogs of calcipotriol, PRI-2202 and PRI-2205, were synthesized as advanced intermediates from vitamin D C-22 benzothiazoyl sulfones and side-chain aldehydes using our convergent strategy. Calcitriol, calcipotriol (PRI-2201 and tacalcitol (PRI-2191 were used as the reference compounds. Among a series of tested analogs the diastereomeric analog PRI-2202 showed the strongest antiproliferative activity on the human breast cancer cell line MCF-7, whereas the geometric analog PRI-2205 was the weakest. Both analogs were less potent in antiproliferative activity against HL-60 cells compared to the reference compounds. The ability to potentiate antiproliferative effect of cisplatin or doxorubicin against HL-60 cells or that of tamoxifen against the MCF-7 cell line was observed at higher doses of PRI-2202 or PRI-2205 than those of the reference compounds. The proapoptotic activity of tamoxifen, expressed as the diminished mitochondrial membrane potential, as well as the increased phosphatidylserine expression, was partially attenuated by calcitriol, PRI-2191, PRI-2201 and PRI-2205. The treatment of the MCF-7 cells with tamoxifen alone resulted in an increase in VDR expression. Moreover, a further increase in VDR expression was observed when the analogs PRI-2201 or PRI-2205, but not PRI-2191, were used in combination with tamoxifen. This observation could partially explain the potentiation of the antiproliferative effect of tamoxifen by vitamin D analogs.

The ohmic heating power supply for HL-1 tokamak

International Nuclear Information System (INIS)

Mingrui, Z.; Jiashun, C.

1986-01-01

A combination of capacitor banks, inductor and DC Fly wheel-Generator sets are used as ohmic heating power supply (OHPS) for HL-1, which is the largest tokamak in China. This system can give changeable waveform of current in a simple way, because of the use of protection for capacitor banks by changeable connection in easy way. Since the technology of forced zero current in the commutating breaker and synchronous self-triggering crowbar are used, the smooth conversion between the wave front provided by discharge of the capacitor banks and the flat top sustained by the inductor and flywheel realized. The performance of the system was tested by a dummy load and the system has been used in the HL-1 experiments. It is confirmed that this system is sufficiently available for the ohmic heating and has important effects on the long plasma lasting time on the order of 1 sec

The CMS ECAL Upgrade for Precision Crystal Calorimetry at the HL-LHC

CERN Document Server

Marinelli, Nancy

2017-01-01

The Compact Muon Solenoid Experiment (CMS) is operating at the Large Hadron Collider (LHC) with proton-proton collisions at 13 TeV center-of-mass energy and at a bunch spacing of 25 ns. New further challenging running conditions for CMS are expected after the High-Luminosity upgrade of the LHC (HL--LHC). The CMS electromagnetic calorimeter (ECAL) will need to be upgraded to substain the hardned environment.The design and R\\ and D studies for the ECAL upgrade are presented together with first test beam studies. Particular challenges at HL--LHC are the harsh radiation environment, the increasing data rates and the extreme level of pile-up events, with up to 200 simultaneous proton-proton collisions. Precision timing can be exploited to reduce the effect of the pile-up. Time resolution measurementscarried out during test-beams are shown. Plans are also shown for R\\ and D for the new readout and trigger electronics, which must be upgraded due to the increased trigger and latency requirements at the HL--LHC

Hierarchical Recognition Scheme for Human Facial Expression Recognition Systems

Directory of Open Access Journals (Sweden)

Muhammad Hameed Siddiqi

2013-12-01

Full Text Available Over the last decade, human facial expressions recognition (FER has emerged as an important research area. Several factors make FER a challenging research problem. These include varying light conditions in training and test images; need for automatic and accurate face detection before feature extraction; and high similarity among different expressions that makes it difficult to distinguish these expressions with a high accuracy. This work implements a hierarchical linear discriminant analysis-based facial expressions recognition (HL-FER system to tackle these problems. Unlike the previous systems, the HL-FER uses a pre-processing step to eliminate light effects, incorporates a new automatic face detection scheme, employs methods to extract both global and local features, and utilizes a HL-FER to overcome the problem of high similarity among different expressions. Unlike most of the previous works that were evaluated using a single dataset, the performance of the HL-FER is assessed using three publicly available datasets under three different experimental settings: n-fold cross validation based on subjects for each dataset separately; n-fold cross validation rule based on datasets; and, finally, a last set of experiments to assess the effectiveness of each module of the HL-FER separately. Weighted average recognition accuracy of 98.7% across three different datasets, using three classifiers, indicates the success of employing the HL-FER for human FER.

Hierarchical Recognition Scheme for Human Facial Expression Recognition Systems

Science.gov (United States)

Siddiqi, Muhammad Hameed; Lee, Sungyoung; Lee, Young-Koo; Khan, Adil Mehmood; Truc, Phan Tran Ho

2013-01-01

Over the last decade, human facial expressions recognition (FER) has emerged as an important research area. Several factors make FER a challenging research problem. These include varying light conditions in training and test images; need for automatic and accurate face detection before feature extraction; and high similarity among different expressions that makes it difficult to distinguish these expressions with a high accuracy. This work implements a hierarchical linear discriminant analysis-based facial expressions recognition (HL-FER) system to tackle these problems. Unlike the previous systems, the HL-FER uses a pre-processing step to eliminate light effects, incorporates a new automatic face detection scheme, employs methods to extract both global and local features, and utilizes a HL-FER to overcome the problem of high similarity among different expressions. Unlike most of the previous works that were evaluated using a single dataset, the performance of the HL-FER is assessed using three publicly available datasets under three different experimental settings: n-fold cross validation based on subjects for each dataset separately; n-fold cross validation rule based on datasets; and, finally, a last set of experiments to assess the effectiveness of each module of the HL-FER separately. Weighted average recognition accuracy of 98.7% across three different datasets, using three classifiers, indicates the success of employing the HL-FER for human FER. PMID:24316568

29 CFR 525.9 - Criteria for employment of workers with disabilities under certificates at special minimum wage...

Science.gov (United States)

2010-07-01

... certificates at special minimum wage rates. 525.9 Section 525.9 Labor Regulations Relating to Labor (Continued... special minimum wage rates. (a) In order to determine that special minimum wage rates are necessary in... at the special minimum wage rate; (3) The productivity of the workers with disabilities compared to...

Analysis of myelomonocytic leukemic differentiation by a cell surface marker panel including a fucose-binding lectin from Lotus tetragonolobus.

Science.gov (United States)

Elias, L; Van Epps, D E

1984-06-01

The fucose-binding lectin from Lotus tetragonolobus ( FBL -L) has been previously shown to bind specifically to normal cells of the myeloid and monocytic lineages. The purpose of this study was to explore the utility of fluoresceinated FBL -L as a leukemia differentiation marker in conjunction with a panel of other frequently used surface markers (Fc receptor, HLA-DR, OKM1, and antimonocyte antibody). FBL -L reacted with leukemic cells in 8/9 cases of clinically recognized acute myeloid leukemia, including myeloid blast crisis of chronic granulocytic leukemia, 3/3 cases of chronic phase chronic myelogenous leukemia, and in 2/7 cases of clinically undifferentiated acute leukemia. Correlations were noted between reactivity with FBL -L, and DR and Fc receptor expression. Among continuous cell lines, FBL -L bound with high intensity to a majority of HL-60 and U937 cells. The less well differentiated myeloblast cell lines, KG-1, KG1a , and HL-60 blast II, exhibited less FBL -L binding than HL-60 and U937. A moderate proportion of K562 cells exhibited low level binding of FBL -L. Several lymphoblastic cell lines exhibited a pattern of low intensity binding that was distinguishable from the high intensity binding pattern of the myeloblastic lines. FBL -L reactivity of U937 was enhanced by induction of differentiation with leukocyte conditioned medium, but not dimethylsulfoxide. Such treatments induced contrasting patterns of change of HL-60 and U937 when labeled with OKM1, alpha-Mono, and HLA-DR. These studies demonstrate the application of FBL -L to analysis and quantitation of myelomonocytic leukemic differentiation.

Instrumentation for silicon tracking at the HL-LHC

CERN Document Server

AUTHOR|(INSPIRE)INSPIRE-00524651; Strandberg, Sara; Garcia-Sciveres, Maurice

2017-06-14

In 2027 the Large Hadron Collider (LHC) at CERN will enter a high luminosity phase, deliver- ing 3000 fb 1 over the course of ten years. The High Luminosity LHC (HL-LHC) will increase the instantaneous luminosity delivered by a factor of 5 compared to the current operation pe- riod. This will impose significant technical challenges on all aspects of the ATLAS detector but particularly the Inner Detector, trigger, and data acquisition systems. In addition, many of the components of the Inner Detector are reaching the end of their designed lifetime and will need to be exchanged. As such, the Inner Detector will be entirely replaced by an all silicon tracker, known as the Inner Tracker (ITk). The layout of the Pixel and strip detectors will be optimised for the upgrade and will extend their forward coverage. To reduce the per-pixel hit rate and explore novel techniques for deal- ing with the conditions in HL-LHC, an inter-experiment collaboration called RD53 has been formed. RD53 is tasked with producing a front...

The synthesis of phosphatidylalcohols in HL-60 cells

International Nuclear Information System (INIS)

Tettenborn, C.S.

1988-01-01

This study focuses upon the phenomenon that 12-O-tetradecanoyl-phorbol-13-acetate (TPA) stimulates a pathway for the synthesis of phosphatidylalcohols in HL-60 cells during the differentiation of these cells to macrophages. Using exogenous ethanol as a substrate for this pathway, the synthesis of phosphatidylethanol is induced by TPA well before full expression of differentiation. Experiments done in whole cell cultures demonstrated that this pathway could utilize a wide range of other alcohols as substrates, including glycerol, a potential endogenous substrate. Using radiolabeling and iodine-staining as criteria, this TPA-inducible pathway was shown to result in a dramatic alteration of phospholipid composition, depending on the availability of the alcohol headgroup. A cell-free system was developed to explore the enzymatic reactions involved in phosphatidylalcohol synthesis, a main goal of these studies. For this purpose, the lipid pools of HL-60 cells were prelabeled with [ 3 H]arachidonic acid in the absence of ethanol and total cell homogenates were prepared by sonication. The ability of the cell lysates to synthesize phosphatidylethanol was assayed after addition of ethanol to the system

The ATLAS tracker strip detector for HL-LHC

CERN Document Server

Cormier, Kyle James Read; The ATLAS collaboration

2016-01-01

As part of the ATLAS upgrades for the High Luminsotiy LHC (HL-LHC) the current ATLAS Inner Detector (ID) will be replaced by a new Inner Tracker (ITk). The ITk will consist of two main components: semi-conductor pixels at the innermost radii, and silicon strips covering larger radii out as far as the ATLAS solenoid magnet including the volume currently occupied by the ATLAS Transition Radiation Tracker (TRT). The primary challenges faced by the ITk are the higher planned read out rate of ATLAS, the high density of charged particles in HL-LHC conditions for which tracks need to be resolved, and the corresponding high radiation doses that the detector and electronics will receive. The ITk strips community is currently working on designing and testing all aspects of the sensors, readout, mechanics, cooling and integration to meet these goals and a Technical Design Report is being prepared. This talk is an overview of the strip detector component of the ITk, highlighting the current status and the road ahead.

The ATLAS tracker strip detector for HL-LHC

CERN Document Server

AUTHOR|(INSPIRE)INSPIRE-00512833; The ATLAS collaboration

2017-01-01

As part of the ATLAS upgrades for the High Luminsotiy LHC (HL-LHC) the current ATLAS Inner Detector (ID) will be replaced by a new Inner Tracker (ITk). The ITk will consist of two main components: semi-conductor pixels at the innermost radii, and silicon strips covering larger radii out as far as the ATLAS solenoid magnet including the volume currently occupied by the ATLAS Transition Radiation Tracker (TRT). The primary challenges faced by the ITk are the higher planned read out rate of ATLAS, the high density of charged particles in HL-LHC conditions for which tracks need to be resolved, and the corresponding high radiation doses that the detector and electronics will receive. The ITk strips community is currently working on designing and testing all aspects of the sensors, readout, mechanics, cooling and integration to meet these goals and a Technical Design Report is being prepared. This talk is an overview of the strip detector component of the ITk, highlighting the current status and the road ahead.

Biologico-clinical significance of DNMT3A variants expression in acute myeloid leukemia.

Science.gov (United States)

Lin, Na; Fu, Wei; Zhao, Chen; Li, Bixin; Yan, Xiaojing; Li, Yan

2017-12-09

DNA methyltransferase 3A (DNMT3A) catalyzes de novo DNA methylation and plays important roles in the pathogenesis of acute myeloid leukemia. However, the expression status of DNMT3A variants in acute myeloid leukemia remains obscure. This study aimed to assess the expression levels of alternative splicing of DNMT3A variants and explore their roles in acute myeloid leukemia (AML). DNMT3A variants gene expression were assessed, measuring their effects on cell proliferation. In addition, the expression of DNMT3A variants were evaluated in acute myeloid leukemia patients. Four DNMT3A variants were identified, with DNMT3A1 and DNMT3A2V found to be dominant in acute myeloid leukemia cell lines. Moreover, DNMT3A2V overexpression delayed cell proliferation; while, DNMT3A2V R882H mutation promoted cell proliferation. Further, DNMT3A1 and DNMT3A2V were detected in newly diagnosed acute myeloid leukemia (AML) patients and controls with non-malignant hematological disease, with DNMT3A2V significantly up-regulated in AML patients. The main transcript switched from DNMT3A1 to DNMT3A2V in some patients, especially the low risk group based on the NCCN 2016 guidelines. These findings suggest that DNMT3A1 and DNMT3A2V are the main variants in acute myeloid leukemia with different clinical association, and might play important roles in the pathophysiology of acute myeloid leukemia. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Heat dissipation research on the water-cooling channel of HL-2M in-vessel coils

Energy Technology Data Exchange (ETDEWEB)

Jiang, J., E-mail: jiangjiaming@swip.ac.cn; Liu, Y.; Chen, Q.; Ji, X.Q.

2017-04-15

Highlights: • The joule heat of in-vessel coils is very difficult to dissipate inside HL-2M vacuum vessel. • Heat dissipation model of the coil includes the joule heat model, the heat conduction model and the heat transfer model. • The CFD analysis has been done for the coil-water cooling, with comparison with the date of theoretical analysis and experiment. • The result shows water-cooling channel is good for the joule heat transfer and taken away. - Abstract: HL-2M in-vessel coils are positioned in high vacuum circumstance, and they will generate joule heat when they carry 15 kA electrical current, but joule heat is very difficult to dissipate in vacuum, so a hollow cable with 8 mm inner diameter is design as water-cooling channel for heat convection. By using the methods of the theoretical derivation, together with CFD numeric simulation method and the experiment of the heat transfer, the water channel of HL-2M in-vessel coils has been studied, and the temperature of HL-2M in-vessel coils under different cooling water flow rates is obtained and acceptable. Simultaneously, the external cooling water supply system parameters for the water-cooling channel of the coils are estimated. Three methods’ results are in good agreement; the theoretical model is verified and could be popularized for predicting the temperature rise of HL-2M in-vessel coils.

A Rapid Culture Technique Produces Functional Dendritic-Like Cells from Human Acute Myeloid Leukemia Cell Lines

Directory of Open Access Journals (Sweden)

Jian Ning

2011-01-01

Full Text Available Most anti-cancer immunotherapeutic strategies involving dendritic cells (DC as vaccines rely upon the adoptive transfer of DC loaded with exogenous tumour-peptides. This study utilized human acute myeloid leukemia (AML cells as progenitors from which functional dendritic-like antigen presenting cells (DLC were generated, that constitutively express tumour antigens for recognition by CD8+ T cells. DLC were generated from AML cell lines KG-1 and MUTZ-3 using rapid culture techniques and appropriate cytokines. DLC were evaluated for their cell-surface phenotype, antigen uptake and ability to stimulate allogeneic responder cell proliferation, and production of IFN-γ; compared with DC derived from normal human PBMC donors. KG-1 and MUTZ-3 DLC increased expression of CD80, CD83, CD86, and HLA-DR, and MUTZ-3 DLC downregulated CD14 and expressed CD1a. Importantly, both KG-1 and MUTZ-3-derived DLC promoted proliferation of allogeneic responder cells more efficiently than unmodified cells; neither cells incorporated FITC-labeled dextran, but both stimulated IFN-γ production from responding allogeneic CD8+ T cells. Control DC produced from PBMC using the FastDC culture also expressed high levels of critical cell surface ligands and demonstrated good APC function. This paper indicates that functional DLC can be cultured from the AML cell lines KG-1 and MUTZ-3, and FastDC culture generates functional KG-1 DLC.

HL7 and DICOM based integration of radiology departments with healthcare enterprise information systems.

Science.gov (United States)

Blazona, Bojan; Koncar, Miroslav

2007-12-01

Integration based on open standards, in order to achieve communication and information interoperability, is one of the key aspects of modern health care information systems. However, this requirement represents one of the major challenges for the Information and Communication Technology (ICT) solutions, as systems today use diverse technologies, proprietary protocols and communication standards which are often not interoperable. One of the main producers of clinical information in healthcare settings represent Radiology Information Systems (RIS) that communicate using widely adopted DICOM (Digital Imaging and COmmunications in Medicine) standard, but in very few cases can efficiently integrate information of interest with other systems. In this context we identified HL7 standard as the world's leading medical ICT standard that is envisioned to provide the umbrella for medical data semantic interoperability, which amongst other things represents the cornerstone for the Croatia's National Integrated Healthcare Information System (IHCIS). The aim was to explore the ability to integrate and exchange RIS originated data with Hospital Information Systems based on HL7's CDA (Clinical Document Architecture) standard. We explored the ability of HL7 CDA specifications and methodology to address the need of RIS integration HL7 based healthcare information systems. We introduced the use of WADO service interconnection to IHCIS and finally CDA rendering in widely used Internet explorers. The outcome of our pilot work proves our original assumption of HL7 standard being able to adopt radiology data into the integrated healthcare systems. Uniform DICOM to CDA translation scripts and business processes within IHCIS is desired and cost effective regarding to use of supporting IHCIS services aligned to SOA.

Human Immunodeficiency Virus Infection and Hodgkin's Lymphoma in South Africa: An Emerging Problem

Directory of Open Access Journals (Sweden)

Moosa Patel

2011-01-01

Full Text Available Hodgkin's lymphoma (HL occurs with increasing frequency in human-immunodeficiency-virus-(HIV- infected individuals. The natural history and behaviour of HIV-HL is different, being more atypical and aggressive. The association between HIV and HL appears to be primarily EBV driven. HAART use does not significantly impact on the incidence of HL. Indeed, the risk of HL has increased in the post-HAART era. However, the advent of HAART has brought renewed hope, allowing standard therapeutic options to be used more optimally, with better treatment outcomes. Despite the renewed optimism, the overall survival of HIV-HL patients remains less favourable than that in HIV-seronegative patients. This is particularly true in sub-Saharan Africa, where there is a significant burden of HIV/AIDS and where more than half the patients are HAART naive at diagnosis of HL. The similarities and differences of a South African cohort of HIV-HL are presented in this paper.

Preliminary study of energy confinement data with a statistical analysis system in HL-2A tokamak

International Nuclear Information System (INIS)

Xu Yuan; Cui Zhengying; Ji Xiaoquan; Dong Chunfeng; Yang Qingwei; O J W F Kardaun

2010-01-01

Taking advantage of the HL-2A experimental data,an energy confinement database facing ITERL DB2.0 version has been originally established. As for this database,a world widely used statistical analysis system (SAS) has been adopted for the first time to analyze and evaluate the confinement data from HL-2A and the research on scaling laws of energy confinement time corresponding to plasma density is developed, some preliminary results having been achieved. Finally, through comparing with both ITER scaling law and previous ASDEX database, the investigation about L-mode confinement quality on HL-2A and influence of temperature on Spitzer resistivity will be discussed. (authors)

In memoriam Dieter Möhl his life as a scientist, mentor and friend

CERN Document Server

Caspers, Fritz

2013-01-01

The scientific life of Dieter Möhl can be split up into four major categories; namely accelerators where he made major contributions, theory and teaching, advice to the management and human relations including human rights. Regarding the first point it should be recalled that Dieter is one of the founding fathers of LEAR and in parallel worked a lot on ICE, the PS as well as the AAC until it became the AD. The list of other machines (not always built) which have profited from his contributions is very long and include the RCS, SuperLEAR, Tau-charm and neutrino factories and also various rings of FAIR. Dieter was one of leading theorists in accelerator physics making fundamental contributions to stochastic cooling, ordered beam issues, electron cooling, polarized beams and beam stability problems. He was very often called in for advice by the management, not only at CERN but in numerous advisory committees. His excellent human qualities are known worldwide and they are held in the highest esteem in particular...

Disinfectant Efficacy of 0.525% Sodium Hypochlorite and Epimax on Alginate Impression Material.

Science.gov (United States)

Choudhury, Gopal Krishna; Chitumalla, Rajkiran; Manual, Litto; Rajalbandi, Santosh Kumar; Chauhan, Mahinder Singh; Talukdar, Pratim

2018-01-01

Species of Streptococcus, Escherichia coli, Staphylococcus, Actinomyces, Pseudomonas, Klebsiella, and Candida are commonly seen in the oral cavity. Impression materials are commonly contaminated with microorganisms. The present study was conducted to assess the disinfection efficacy of Epimax and 0.525% sodium hypochlorite on alginate impression over a period of 10 minutes. This study was conducted in the Department of Prosthodontics in the year 2015. An alginate impression material was prepared. For each bacteria species, 15 samples were used. Out of 15 samples, 3 were used by 0.525% sodium hypochlorite for disinfection for 5 minutes and 3 others for 10 minutes. Similarly, 3 samples were used by Epimax for 5 minutes and other 3 for 10 minutes. Three samples were used as controls. Each sample was polluted with Candida albicans, Pseudomonas aeruginosa, and Staphylococcus aureus strains. There was no statistical difference in P. aeruginosa and C. albicans after 5 minutes, whereas S. aureus showed significant difference (p alginate impression material against C. albicans, P. aeruginosa, and S. aureus strains. However, Epimax was found to be more effective against S. aureus as compared with 0.525% sodium hypochlorite. Efficacy of disinfection of sodium hypo-chlorite and Epimax on alginate impression.

29 CFR 525.13 - Renewal of special minimum wage certificates.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Renewal of special minimum wage certificates. 525.13... minimum wage certificates. (a) Applications may be filed for renewal of special minimum wage certificates.... (c) Workers with disabilities may not continue to be paid special minimum wages after notice that an...

The CMS HGCAL detector for the HL-LHC upgrade

CERN Document Server

Steen, Arnaud

2017-01-01

The High Luminosity LHC (HL-LHC) will integrate 10 times more luminosity than the LHC, posing significant challenges for radiation tolerance and event pileup on detectors, especially for forward calorimetry, and hallmarks the issue for future colliders. As part of its HL-LHC upgrade program, the CMS collaboration is designing a High Granularity Calorimeter to replace the existing endcap calorimeters. It features unprecedented transverse and longitudinal segmentation for both electromagnetic (ECAL) and hadronic (HCAL) compartments. This will facilitate particle-flow calorimetry, where the fine structure of showers can be measured and used to enhance pileup rejection and particle identification, whilst still achieving good energy resolution. The ECAL and a large fraction of HCAL will be based on hexagonal silicon sensors of 0.5 - 1 cm$^2$ cell size, with the remainder of the HCAL based on highly-segmented scintillators with SiPM readout. The intrinsic high-precision timing capabilities of the silicon sensors wi...

Upgrades of the CMS Outer Tracker for HL-LHC

CERN Document Server

AUTHOR|(CDS)2067159

2016-01-01

The LHC machine is planning an upgrade program which will smoothly bring the luminosity to about 5×1034cm$^{−2}$s$^{−1}$ around 2028, to possibly reach an integrated luminosity of 3000 fb$^{−1}$ in the following decade. This High Luminosity LHC scenario, HL-LHC, will require a preparation program of the LHC detectors known as Phase-2 upgrade. The current CMS Outer Tracker, already running close to its design limits, will not be able to survive HL-LHC radiation conditions and CMS will need a completely new device, in order to fully exploit the highly demanding operating conditions and the delivered luminosity. The new Tracker should have also L1 trigger capabilities. To achieve such goals, R&D; activities are ongoing to explore options and develop solutions that would allow including tracking information at Level-1. The design choices for the CMS Outer Tracker upgrades are discussed along with some highlights of the R&D; activities.

Roles of different forms of cytochrome P450 in the activation of the promutagen 6-aminochrysene to genotoxic metabolites in human liver microsomes.

Science.gov (United States)

Yamazaki, H; Mimura, M; Oda, Y; Inui, Y; Shiraga, T; Iwasaki, K; Guengerich, F P; Shimada, T

1993-07-01

We reported previously that the potent mutagen 6-aminochrysene is catalyzed principally by rat liver microsomal P4501A and P4502B enzymes to reactive metabolites that induce umu gene expression in O-acetyltransferase-over-expressing strain Salmonella typhimurium NM2009; the proposal was made that there are different mechanisms in the formation of reactive N-hydroxylated and diolepoxide metabolites by P450 enzymes (Yamazaki, H. and Shimada, T., Biochem. Pharmacol., 44, 913-920, 1992). Here we further examined the roles of human liver P450 enzymes and the mechanism of activation of 6-aminochrysene by rat and human P450 enzymes in the Salmonella tester strains. Liver microsomes from 18 different human samples catalyzed activation of 6-aminochrysene more efficiently in S. typhimurium NM2009 than in the original strain of S. typhimurium TA1535/pSK1002. The rates of 6-aminochrysene activation in 18 human liver samples showed good correlation to the contents of P4502B6 as well as contents of P4503A4 and the respective mono-oxygenase activities catalyzed by P4503A4. Among purified P450 enzymes examined, P4501A2 as well as P4503A4 were highly active in transforming 6-amino-chrysene to reactive metabolites, suggesting the involvement of different human P450 enzymes in the reaction. Four human samples that contained relatively high levels of particular P450 enzymes in their microsomes were selected and used for further characterization. Liver microsomes from human samples HL-13 and HL-4 that contained the highest levels of P4502B6 and P4503A4 respectively, were sensitive to the respective antibodies raised against monkey P4502B and human P4503A4; the activity in sample HL-16 having the highest level of P4501A2 was inhibited by anti-P4501A2 IgG. alpha-Naphthoflavone enhanced the activation of 6-aminochrysene very significantly in human liver microsomes enriched in P4503A4 and P4502B6 enzymes. Pentachlorophenol, an inhibitor of acetyltransferase activity, suppressed the

Performances of the HL (Hyperloop) transport system

OpenAIRE

van Goeverden, C.D.; Milakis, D.; Janic, M.; Konings, J.W.; Cools, M.; Limbourg, S.

2017-01-01

This paper deals with an analysis of performances of the HL (Hyperloop) transport system considered as an advanced transport alternative to the existing APT (Air Passenger Transport) and HSR (High Speed Rail) systems. The considered performances are operational, financial, social and environmental. The operational performance include capacity and quality of service provided to the system’s users-passengers with attributes such as door-to-door travel time consisting of the access and egress ti...

The Development of a Graphical User Interface Engine for the Convenient Use of the HL7 Version 2.x Interface Engine.

Science.gov (United States)

Kim, Hwa Sun; Cho, Hune; Lee, In Keun

2011-12-01

The Health Level Seven Interface Engine (HL7 IE), developed by Kyungpook National University, has been employed in health information systems, however users without a background in programming have reported difficulties in using it. Therefore, we developed a graphical user interface (GUI) engine to make the use of the HL7 IE more convenient. The GUI engine was directly connected with the HL7 IE to handle the HL7 version 2.x messages. Furthermore, the information exchange rules (called the mapping data), represented by a conceptual graph in the GUI engine, were transformed into program objects that were made available to the HL7 IE; the mapping data were stored as binary files for reuse. The usefulness of the GUI engine was examined through information exchange tests between an HL7 version 2.x message and a health information database system. Users could easily create HL7 version 2.x messages by creating a conceptual graph through the GUI engine without requiring assistance from programmers. In addition, time could be saved when creating new information exchange rules by reusing the stored mapping data. The GUI engine was not able to incorporate information types (e.g., extensible markup language, XML) other than the HL7 version 2.x messages and the database, because it was designed exclusively for the HL7 IE protocol. However, in future work, by including additional parsers to manage XML-based information such as Continuity of Care Documents (CCD) and Continuity of Care Records (CCR), we plan to ensure that the GUI engine will be more widely accessible for the health field.

Heavy-ion operation of HL-LHC

CERN Document Server

Jowett, J M; Versteegen, R

2015-01-01

The heavy-ion physics programme of the LHC will continue during the HL-LHC period with upgraded detectors capable of exploiting several times the design luminosity for nucleus–nucleus (Pb–Pb) collisions. For proton–nucleus (p–Pb) collisions, unforeseen in the original design of the LHC, a comparable increase beyond the 2013 luminosity should be attainable. We present performance projections and describe the operational strategies and relatively modest upgrades to the collider hardware that will be needed to achieve these very significant extensions to the physics potential of the High Luminosity LHC.

Synthesis IR spectra and crystal structure of N-(4-bromophenyl)-1,1,1-trifluoroacetyl-acetonimine HN(C6H4Br)xC(Me)xCHxC(CF3)xO(HL) and its molecular complex with tungstene(4) oxotetrachloride WOCl4xHL

International Nuclear Information System (INIS)

Sergienko, V.S.; Ilyukhin, A.B.; Abramenko, V.L.

1997-01-01

Synthesis, IR spectroscopic and X-ray diffraction studies of compound HN(C 6 H 4 Br)xC(Me)xCHxC(CF 3 )xO(HL) (1) and of molecular complex WOCl 4 xHL(2) have been conducted. In 1 and 2 HL molecule exists in ketoamine tautomeric form (acid proton is localized at nitrogen atom). The results of 1 and 2 study are compared with literature data on structures of HL type molecules and Mo(6) molecular complexes with β-enaminevinylketone, as well as with the structure of chelate compound WOCl 3 L 1 , where L 1 - anion of N-phenylacetylacetonimine

Cyclosporine, Pravastatin Sodium, Etoposide, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Science.gov (United States)

2017-06-27

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

Cyclic AMP-dependent protein kinase interferes with GTP γS stimulated IP3 formation in differentiated HL-60 cell membranes

International Nuclear Information System (INIS)

Misaki, Naoyuki; Imaizumi, Taro; Watanabe, Yashuiro

1989-01-01

The effects of addition of activated cyclic AMP-dependent protein kinase (PKA) on the function of islet-activating protein (IAP)-sensitive GTP-binding (G) protein were studied in the plasma membranes of 3 H-inositol-labeled differentiated human leukemic (HL-60) cells. Pretreatment of the membranes with activated PKA in the presence of MgATP for 15 min. at 37 degree C decreased GTP γS-stimulated inositol trisphosphate (IP 3 ) formation by about 30%, but had no influence on Ca 2+ -stimulated IP 3 formation. And autoradiography in the phosphorylation experiments of solubilized HL-60 cell membranes by PKA showed some 32 P incorporated bands, and among them one of the major bands showed the migration at 40 kDa supporting that the G protein coupling with PI response was phosphorylated by PKA. These results showed that pretreatment with activated PKA inhibited the mediating function of the G protein between the fMLP receptor and phospholipase C by its phosphorylation

Acute myeloid leukaemia presenting as bilateral proptosis in a young child

Directory of Open Access Journals (Sweden)

Charudutt Kalamkar

2016-06-01

Full Text Available Myeloid sarcoma is an extramedullary manifestation of acute myeloid leukaemia (AML. Aims We are reporting a paediatric case presenting with bilateral proptosis, which we were able to diagnose with peripheral blood smear (PBS examination. Methods Case Report Results This case highlights the utility of simple routinely available PBS test in diagnosing this rare disease. Conclusion Our case highlights the importance of haemogram and peripheral blood smear in the initial evaluation of proptosis. Correct diagnosis of this rare entity is vital especially in cases where (myeloid sarcoma MS is the presenting feature of AML.

Apoptotic and antiproliferative properties of 3β-hydroxy-Δ5-steroidal congeners from a partially purified column fraction of Dendronephthya gigantea against HL-60 and MCF-7 cancer cells.

Science.gov (United States)

Fernando, I P Shanura; Sanjeewa, K K Asanka; Kim, Hyun-Soo; Wang, Lei; Lee, Won Woo; Jeon, You-Jin

2018-04-01

Organisms belonging to the genus Dendronephthya are among a group of marine invertebrates that produce a variety of terpenoids with biofunctional properties. Many of these terpenoids have been proven effective as anticancer drugs. Here, we report the antiproliferative effect of 3β-hydroxy-Δ5-steroidal congeners against the proliferation of HL-60 human leukemia cells and MCF-7 human breast cancer cells. The sterol-rich fraction (DGEHF2-1) inhibited the growth of HL-60 and MCF-7 cells with IC 50 values of 13.59 ± 1.40 and 29.41 ± 0.87 μg ml -1 respectively. Treatment with DGEHF2-1 caused a dose-dependent increase in apoptotic body formation, DNA damage and the sub-G 1 apoptotic cell population. Moreover, DGEHF2-1 downregulated the expression of Bcl-xL while upregulating Bax, caspase-9, and PARP cleavage in both HL-60 and MCF-7 cells. The steroid fraction was found to act via the mitochondria-mediated apoptosis pathway. Identification of the sterols was performed via gas chromatography-tandem mass spectrometry analysis. Studying the mechanism of the anticancer effect caused by these sterol derivatives could lead to the identification of other natural products with anticancer properties. Copyright © 2017 John Wiley & Sons, Ltd.

Cytokine Networks between Innate Lymphoid Cells and Myeloid Cells.

Science.gov (United States)

Mortha, Arthur; Burrows, Kyle

2018-01-01

Innate lymphoid cells (ILCs) are an essential component of the innate immune system in vertebrates. They are developmentally rooted in the lymphoid lineage and can diverge into at least three transcriptionally distinct lineages. ILCs seed both lymphoid and non-lymphoid tissues and are locally self-maintained in tissue-resident pools. Tissue-resident ILCs execute important effector functions making them key regulator in tissue homeostasis, repair, remodeling, microbial defense, and anti-tumor immunity. Similar to T lymphocytes, ILCs possess only few sensory elements for the recognition of non-self and thus depend on extrinsic cellular sensory elements residing within the tissue. Myeloid cells, including mononuclear phagocytes (MNPs), are key sentinels of the tissue and are able to translate environmental cues into an effector profile that instructs lymphocyte responses. The adaptation of myeloid cells to the tissue state thus influences the effector program of ILCs and serves as an example of how environmental signals are integrated into the function of ILCs via a tissue-resident immune cell cross talks. This review summarizes our current knowledge on the role of myeloid cells in regulating ILC functions and discusses how feedback communication between ILCs and myeloid cells contribute to stabilize immune homeostasis in order to maintain the healthy state of an organ.

Simvastatin Inhibits IL-5-Induced Chemotaxis and CCR3 Expression of HL-60-Derived and Human Primary Eosinophils.

Science.gov (United States)

Fu, Chia-Hsiang; Tsai, Wan-Chun; Lee, Ta-Jen; Huang, Chi-Che; Chang, Po-Hung; Su Pang, Jong-Hwei

2016-01-01

IL-5-induced chemotaxis of eosinophils is an important feature of allergic airway inflammatory diseases. Simvastatin, a lipid lowering agent, has been shown to exhibit anti-inflammatory and anti-allergic effects. Our aim was to investigate the effect of simvastatin on IL-5-induced eosinophil chemotaxis and its regulatory mechanisms. Eosinophils were derived by treating HL-60 clone 15 (HC15) cells with butyric acid (BA) in an alkaline condition or through direct isolation from human peripheral blood. The expressions of CC chemokine receptor 3 (CCR3) and interleukin (IL)-5 receptors (IL5Rα and β) were analyzed using RT/real-time PCR. The granular proteins were stained using fast green. Eotaxin-induced chemotaxis was measured using a transwell migration assay. CCR3 protein expression was revealed by immunocytochemistry. An animal model of allergic rhinitis was established by challenging Sprague-Dawley® rats repeatedly with ovalbumin. Butyric acid significantly increased the expression of IL5Rα and IL5Rβ, CCR3 and granular proteins in HC15 cells, indicating the maturation of eosinophils (BA-E cells). IL-5 further enhanced the CCR3 expression at both the mRNA and protein levels and the eotaxin-induced chemotaxis of BA-E cells. Simvastatin inhibited the effects of IL-5 on BA-E cells, but not in the presence of mevalonate. Similar results were also exhibited in human primary eosinophils. In vivo animal studies further confirmed that oral simvastatin could significantly suppress the infiltration of eosinophils into turbinate tissues of allergic rats. Therefore, simvastatin was demonstrated to inhibit IL-5-induced CCR3 expression and chemotaxis of eosinophils mediated via the mevalonate pathway. We confirmed that simvastatin also reduced eosinophilic infiltration in allergic rhinitis.

Beam Cleaning in Experimental IRs in HL-LHC for the Incoming Beam

CERN Document Server

Garcia-Morales, H; Bruce, Roderik; Redaelli, Stefano

2015-01-01

The HL-LHC will store 675 MJ of energy per beam, about 300 MJ more than the nominal LHC. Due to the increase in stored energy and a different interaction region (IR) optics layout, the collimation system for the incoming beam must be revisited in order to avoid dangerous losses that could cause quenches or machine damage. This paper studies the effectiveness of the current LHC collimation system in intercepting cleaning losses close to the experiments in the HL-LHC. The study reveals that additional tertiary collimators would be beneficial in order to protect not only the final focusing triplets but also the two quadrupoles further upstream.

Beam cleaning of the incoming beam in experimental IRs in HL-LHC

CERN Document Server

Garcia Morales, Hector; Redaelli, Stefano; De Maria, Riccardo; CERN. Geneva. ATS Department

2017-01-01

The HL-LHC will store 675 MJ of energy per beam, about 300 MJ more than the nominal LHC. Due to the increase in stored energy and a different interaction region (IR) layout and optics design, the collimation system for the incoming beam must be revisited in order to avoid dangerous losses that could cause quenches and machine damage. This paper studies the effectiveness of the current LHC collimation system in intercepting cleaning losses close to the experiments in the HL-LHC. The study reveals that in addition to the triplet also the Q4 needs local protection, which could be provided by an additional pair of TCTs.

The skin as a window to the blood: Cutaneous manifestations of myeloid malignancies.

Science.gov (United States)

Li, Alvin W; Yin, Emily S; Stahl, Maximilian; Kim, Tae Kon; Panse, Gauri; Zeidan, Amer M; Leventhal, Jonathan S

2017-11-01

Cutaneous manifestations of myeloid malignancies are common and have a broad range of presentations. These skin findings are classified as specific, due to direct infiltration by malignant hematopoietic cells, or non-specific. Early recognition and diagnosis can have significant clinical implications, as skin manifestations may be the first indication of underlying hematologic malignancy, can reflect the immune status and stage of disease, and cutaneous reactions may occur from conventional and targeted agents used to treat myeloid disease. In addition, infections with cutaneous involvement are common in immunocompromised patients with myeloid disease. Given the varying presentations, dermatologic findings associated with myeloid malignancies can pose diagnostic challenges for hematologists and dermatologists. In this clinical review intended for the practicing hematologist/oncologist, we discuss the presentation, diagnosis, treatment, and prognostic value of the most common cutaneous manifestations associated with myeloid malignancies using illustrative macro- and microscopic figures and with a special emphasis on practical considerations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Experiment of laser thomson scattering at HL-1 tokamak device

International Nuclear Information System (INIS)

Zuo Henian; Chen Jiafu; Yan Derong; Liu Aiping; Shi Peilan; Wang Wei; Liu Xiaomei

1989-05-01

The structure and performance of the Ruby Laser Thomson Scattering apparatus for HL-1 tokamak device is described. The method of acquisition and calibration of multichannel scattered signals are presented. Examples of measured electron temperature T. with experimental error are given

Analysis of the plasma magnetohydrodynamic equilibrium in iron core transformer Tokamak HL-1M

International Nuclear Information System (INIS)

Chen Xiaoguang; Yuan Baoshan

1992-01-01

The physical and mathematical model are presented on the problem of MHD equilibrium with the self consistent in iron core transformer HL-1M. Calculation and analysis for the plasma equilibrium of the stable boundary and free boundary are shown respectively, in an axisymmetric equilibrium model of two dimensions. First, a variation formulation of the problem is written and the equations of the poloided flux ψ are solved by a finite element method; the Picard and Newton algorithms are tested for the non-linearities. The plasma boundary and the magnetic surfaces are being simulated, with the currents in the coils, the total plasma current, its current density function and the magnetic permeability of the iron being the data for the problem; a certain number of the characteristic parameter of the equilibrium configuration is calculated. Secondly, a simple method of calculation is adopted in the determination of equilibrium fields and currents in iron core HL-1M tokamak device. In the plasma equilibrium, the magnetic effect of the air gaps in the iron core and the iron magnetic shielded plate are considered in HL-1M device. Reliable data are provided for designing and constructing the poloidal field system of HL-1M device. A good computer code is constructed, which may be useful in operating on analysis for the future device

Isocitrate dehydrogenase 1 mutations prime the all-trans retinoic acid myeloid differentiation pathway in acute myeloid leukemia

Science.gov (United States)

Boutzen, Héléna; Saland, Estelle; Larrue, Clément; de Toni, Fabienne; Gales, Lara; Castelli, Florence A.; Cathebas, Mathilde; Zaghdoudi, Sonia; Stuani, Lucille; Kaoma, Tony; Riscal, Romain; Yang, Guangli; Hirsch, Pierre; David, Marion; De Mas-Mansat, Véronique; Delabesse, Eric; Vallar, Laurent; Delhommeau, François; Jouanin, Isabelle; Ouerfelli, Ouathek; Le Cam, Laurent; Linares, Laetitia K.; Junot, Christophe; Portais, Jean-Charles; Vergez, François; Récher, Christian

2016-01-01

Acute myeloid leukemia (AML) is characterized by the accumulation of malignant blasts with impaired differentiation programs caused by recurrent mutations, such as the isocitrate dehydrogenase (IDH) mutations found in 15% of AML patients. These mutations result in the production of the oncometabolite (R)-2-hydroxyglutarate (2-HG), leading to a hypermethylation phenotype that dysregulates hematopoietic differentiation. In this study, we identified mutant R132H IDH1-specific gene signatures regulated by key transcription factors, particularly CEBPα, involved in myeloid differentiation and retinoid responsiveness. We show that treatment with all-trans retinoic acid (ATRA) at clinically achievable doses markedly enhanced terminal granulocytic differentiation in AML cell lines, primary patient samples, and a xenograft mouse model carrying mutant IDH1. Moreover, treatment with a cell-permeable form of 2-HG sensitized wild-type IDH1 AML cells to ATRA-induced myeloid differentiation, whereas inhibition of 2-HG production significantly reduced ATRA effects in mutant IDH1 cells. ATRA treatment specifically decreased cell viability and induced apoptosis of mutant IDH1 blasts in vitro. ATRA also reduced tumor burden of mutant IDH1 AML cells xenografted in NOD–Scid–IL2rγnull mice and markedly increased overall survival, revealing a potent antileukemic effect of ATRA in the presence of IDH1 mutation. This therapeutic strategy holds promise for this AML patient subgroup in future clinical studies. PMID:26951332

Checkpoints to the Brain: Directing Myeloid Cell Migration to the Central Nervous System

Directory of Open Access Journals (Sweden)

Meredith Harrison-Brown

2016-12-01

Full Text Available Myeloid cells are a unique subset of leukocytes with a diverse array of functions within the central nervous system during health and disease. Advances in understanding of the unique properties of these cells have inspired interest in their use as delivery vehicles for therapeutic genes, proteins, and drugs, or as “assistants” in the clean-up of aggregated proteins and other molecules when existing drainage systems are no longer adequate. The trafficking of myeloid cells from the periphery to the central nervous system is subject to complex cellular and molecular controls with several ‘checkpoints’ from the blood to their destination in the brain parenchyma. As important components of the neurovascular unit, the functional state changes associated with lineage heterogeneity of myeloid cells are increasingly recognized as important for disease progression. In this review, we discuss some of the cellular elements associated with formation and function of the neurovascular unit, and present an update on the impact of myeloid cells on central nervous system (CNS diseases in the laboratory and the clinic. We then discuss emerging strategies for harnessing the potential of site-directed myeloid cell homing to the CNS, and identify promising avenues for future research, with particular emphasis on the importance of untangling the functional heterogeneity within existing myeloid subsets.

Characterization of the binding of [3H]-(+/-)-L-364,718: a new potent, nonpeptide cholecystokinin antagonist radioligand selective for peripheral receptors

International Nuclear Information System (INIS)

Chang, R.S.; Lotti, V.J.; Chen, T.B.; Kunkel, K.A.

1986-01-01

[3H]-(+/-)-L-364,718 a new, potent and selective nonpeptide peripheral cholecystokinin (CCK) antagonist bound saturably and reversibly to rat pancreatic membranes. The radioligand recognized a single class of binding sites with a high affinity (Kd = 0.23 nM). The binding of [ 3 H]-(+/-)-L-364,718 was stereospecific in that the more biologically active (-)-enantiomer demonstrated greater potency than the (+)-enantiomer. The rank order of potency of various CCK agonists and antagonists in displacing [ 3 H]-(+/-)-L-364,718 correlated with their ability to displace [ 125 I]CCK-8 and their known pharmacological activities in peripheral tissues. However, the absolute potencies of agonists were greater in displacing [ 125 I]CCK-8 than [ 3 H]-(+/-)-L-364,718. As described for other physiologically relevant receptor systems, the potency for displacement of [ 3 H]-(+/-)-L-364,718 binding by CCK agonists, but not antagonists, was reduced by guanosine 5'-(beta, gamma-imido)triphosphate and NaCl and enhanced by MgCl 2 . [ 3 H]-(+/-)-L-364,718 also demonstrated specific binding to bovine gall bladder tissue but not guinea pig brain or gastric glands, consistent with its selectivity as a peripheral CCK antagonist. [ 3 H]-(+/-)-L-364,718 binding to pancreatic membranes was not affected by various pharmacological agents known to interact with other common peptide and nonpeptide receptor systems. These data indicate that [ 3 H]-(+/-)-L-364,718 represents a new potent nonpeptide antagonist radioligand for the study of peripheral CCK receptors which may allow differentiation of agonist and antagonist interactions

Intelligent plasma operation and control system for HL-2M

International Nuclear Information System (INIS)

Xia, F.; Chen, L.Y.; Wang, C.; Zhang, G.; Song, X.M.; Song, X.; Pan, L.; Zhao, L.; Pan, W.; Lan, J.T.

2015-01-01

Full text of publication follows. The Intelligent Plasma Operation and Control System (IPOCS) for HL-2M is under construction based on the current actual situation of HL-2A control system in SWIP. The purpose of IPOCS is to replace the routine processes before, during and post discharge with the automatic process algorithms and give various information, for example, status, warning, reason, instruction, suggestion, physics phenomenon etc. to staff who can access the intranet. In this case, the core research objectives can be focused on and the related operations can be carried out referring to the information. The ultimate goal of IPOCS is to improve the efficiency of plant operation and control and physics research for HL-2M and for the fusion reactor in the future. There are three layers in IPOCS, which are named the information collection layer, the data processing layer and the presentation layer respectively. Information collection layer consists of data acquisition system, EPICS system, Audio and Video system, discharge scheduling system, data storage system etc. All raw data are collected and stored in this layer. The data processing layer is the core of IPOCS. Most algorithms are executed here. The basic computation platform is based on cluster (56 cores at present) and Parallel Computing Toolbox provided by Matlab. The physics database for SWIP based on HDF5 and offline EFIT also locate at this layer. All the operations can be finished during the time interval between two shots. The last layer is to present the information from the former two layers. The typical hardware including the large display screen system in the control room, the voice broadcasting system, personal monitors and smart phones, etc.. Several applications has being developed such as Control System Studio (CSS) in SWIP version, WebOPI, Automatic Alarm Display system and so on. IPOCS for HL-2M is at the very beginning phase at present. With more and more systems and algorithms got

B-physics studies for HL-LHC ATLAS upgrade

CERN Document Server

Jakoubek, Tomas; The ATLAS collaboration

2017-01-01

Simulation studies were made to estimate ATLAS HL-LHC upgrade performance for B-physics. In particular, the decay of $B_s^0 \\to J/\\psi\\phi$ is studied in order to measures the $CP$ violating mixing phase and the width difference between the $B_s^0$ eigenstates. The increased sensitivity is related mainly to the improved decay time resolution obtained with the upgraded ITk inner tracking detector.

12 CFR 308.525 - Form, filing, and service of papers.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Form, filing, and service of papers. 308.525... service of papers. (a) Form. (1) Documents filed with the ALJ must include an original and two copies. (2) Every pleading and paper filed in the proceeding must contain a caption setting forth the title of the...

Leukomogenic factors downregulate heparanase expression in acute myeloid leukemia cells

International Nuclear Information System (INIS)

Eshel, Rinat; Ben-Zaken, Olga; Vainas, Oded; Nadir, Yona; Minucci, Saverio; Polliack, Aaron; Naparstek, Ella; Vlodavsky, Israel; Katz, Ben-Zion

2005-01-01

Heparanase is a heparan sulfate-degrading endoglycosidase expressed by mature monocytes and myeloid cells, but not by immature hematopoietic progenitors. Heparanase gene expression is upregulated during differentiation of immature myeloid cells. PML-RARα and PLZF-RARα fusion gene products associated with acute promyelocytic leukemia abrogate myeloid differentiation and heparanase expression. AML-Eto, a translocation product associated with AML FAB M2, also downregulates heparanase gene expression. The common mechanism that underlines the activity of these three fusion gene products involves the recruitment of histone deacetylase complexes to specific locations within the DNA. We found that retinoic acid that dissociates PML-RARα from the DNA, and which is used to treat acute promyelocytic leukemia patients, restores heparanase expression to normal levels in an acute promyelocytic leukemia cell line. The retinoic acid effects were also observed in primary acute promyelocytic leukemia cells and in a retinoic acid-treated acute promyelocytic leukemia patient. Histone deacetylase inhibitor reverses the downregulation of heparanase expression induced by the AML-Eto fusion gene product in M2 type AML. In summary, we have characterized a link between leukomogenic factors and the downregulation of heparanase in myeloid leukemic cells

Antimicrobial Properties of an Oxidizer Produced by Burkholderia cenocepacia P525

Science.gov (United States)

A compound with both oxidizing properties and antibiotic properties was extracted and purified from broth cultures of Burkholderia cenocepacia strain P525. A four step purification procedure was used to increase its specific activity ~ 400 fold and to yield a HPLC- UV chromatogram containing a sing...

[An immunological approach to acute myeloid leukaemia].

Science.gov (United States)

González, B; Bueno, D; Rubio, P M; San Román, S; Plaza, D; Sastre, A; García-Miguel, P; Fernández, L; Valentín, J; Martínez, I; Pérez-Martínez, A

2016-04-01

Acute myeloid leukaemia (AML) is the second haematological malignancy in the paediatric population, and one of the leading causes of childhood cancer mortality. Survival is currently around 60%, with no improvement in last decades, suggesting that new therapeutic approaches are needed. The anti-leukaemia effect mediated by the lymphocytes and natural killer (NK) cells of the immune system has been established in haematopoietic stem cell transplantation, and also as adoptive immunotherapy after consolidation chemotherapy schemes. A retrospective study was conducted on the clinical characteristics of patients diagnosed and treated for AML in our centre during 1996-2014. The mean fluorescence intensities of HLA-I, MICA/B and ULBP1-4, ligands for NK cell receptors, were also analysed in ten new diagnosed leukaemia cases, five myeloid and five lymphoid. A total of 67 patients were used in this analysis. With a median follow up of 25 months, the event-free survival was 62% (95% CI: 55-67). Secondary AML, non-M3 phenotype, and the absence of favourable cytogenetic markers had a lower survival. The probability of relapse was 38% (95% CI: 31-45). The expression of HLA-I and ULBP-4 was significantly lower in myeloid than in lymphoid blast cells. Our clinical results are similar to those described in the literature. Survival did not significantly change in recent decades, and the likelihood of relapse remains high. Myeloid blasts might be more susceptible to the cytotoxicity of NK cells through their lower expression of HLA-I. NK therapy strategies in minimal disease situation could be effective, as reported by other groups. Copyright © 2015 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

Simulation of the MHD stabilities of the experiment on HL-2A tokamak by GATO code

International Nuclear Information System (INIS)

Pan Wei; Chen Liaoyuan; Dong Jiaqi; Shen Yong; Zhang Jinhua

2009-01-01

The ideal two-dimensional MHD stabilities code, GATO, has been successfully immigrated to the high-performance computing system of HL-2A and used to the simulation study of the ideal MHD stabilities of the plasmas produced by one of the pellets injection experiments on HL-2A tokamak. The EFIT code was used to reconstruct the equilibrium configures firstly and the GATO was used to compute their MHD stabilities secondly whose source data were obtained by the NO.4050 discharge of the experiments on HL-2A, and finally by analyzing these results the preliminary conclusion was devised that the confinement performance of the plasma was improved because of the stabilization effect of the anti-sheared configures created by the pellets injection. (authors)

Inward rectifier potassium channels in the HL-1 cardiomyocyte-derived cell line.

Science.gov (United States)

Goldoni, Dana; Zhao, YouYou; Green, Brian D; McDermott, Barbara J; Collins, Anthony

2010-11-01

HL-1 is a line of immortalized cells of cardiomyocyte origin that are a useful complement to native cardiomyocytes in studies of cardiac gene regulation. Several types of ion channel have been identified in these cells, but not the physiologically important inward rectifier K(+) channels. Our aim was to identify and characterize inward rectifier K(+) channels in HL-1 cells. External Ba(2+) (100 µM) inhibited 44 ± 0.05% (mean ± s.e.m., n = 11) of inward current in whole-cell patch-clamp recordings. The reversal potential of the Ba(2+)-sensitive current shifted with external [K(+)] as expected for K(+)-selective channels. The slope conductance of the inward Ba(2+)-sensitive current increased with external [K(+)]. The apparent Kd for Ba(2+) was voltage dependent, ranging from 15 µM at -150  mV to 148 µM at -75  mV in 120  mM external K(+). This current was insensitive to 10 µM glybenclamide. A component of whole-cell current was sensitive to 150 µM 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), although it did not correspond to the Ba(2+)-sensitive component. The effect of external 1 mM Cs(+) was similar to that of Ba(2+). Polymerase chain reaction using HL-1 cDNA as template and primers specific for the cardiac inward rectifier K(ir)2.1 produced a fragment of the expected size that was confirmed to be K(ir)2.1 by DNA sequencing. In conclusion, HL-1 cells express a current that is characteristic of cardiac inward rectifier K(+) channels, and express K(ir)2.1 mRNA. This cell line may have use as a system for studying inward rectifier gene regulation in a cardiomyocyte phenotype. © 2010 Wiley-Liss, Inc.

Low dose perfluorooctanoate exposure promotes cell proliferation in a human non-tumor liver cell line

Energy Technology Data Exchange (ETDEWEB)

Zhang, Hongxia; Cui, Ruina [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101 (China); Guo, Xuejiang [State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029 (China); Hu, Jiayue [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101 (China); Dai, Jiayin, E-mail: daijy@ioz.ac.cn [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101 (China)

2016-08-05

Highlights: • Differential expression of proteins induced by PFOA in HL-7702 was identified. • Most of the differentially expressed proteins are related to cell proliferation. • A low dose of PFOA stimulates HL-7702 cell proliferation. • A high dose of PFOA inhibits HL-7702 cell proliferation. - Abstract: Perfluorooctanoate (PFOA) is a well-known persistent organic pollutant widely found in the environment, wildlife and humans. Medical surveillance and experimental studies have investigated the potential effects of PFOA on human livers, but the hepatotoxicity of PFOA on humans and its underlying mechanism remain to be clarified. We exposed a human liver cell line (HL-7702) to 50 μM PFOA for 48 h and 96 h, and identified 111 significantly differentially expressed proteins by iTRAQ analysis. A total of 46 proteins were related to cell proliferation and apoptosis. Through further analysis of the cell cycle, apoptosis and their related proteins, we found that low doses of PFOA (50–100 μM) promoted cell proliferation and numbers by promoting cells from the G1 to S phases, whereas high doses of PFOA (200–400 μM) led to reduced HL-7702 cell numbers compared with that of the control mainly due to cell cycle arrest in the G0/G1 phase. To our knowledge, this is the first report on the promotion of cell cycle progression in human cells following PFOA exposure.

Low dose perfluorooctanoate exposure promotes cell proliferation in a human non-tumor liver cell line

International Nuclear Information System (INIS)

Zhang, Hongxia; Cui, Ruina; Guo, Xuejiang; Hu, Jiayue; Dai, Jiayin

2016-01-01

Highlights: • Differential expression of proteins induced by PFOA in HL-7702 was identified. • Most of the differentially expressed proteins are related to cell proliferation. • A low dose of PFOA stimulates HL-7702 cell proliferation. • A high dose of PFOA inhibits HL-7702 cell proliferation. - Abstract: Perfluorooctanoate (PFOA) is a well-known persistent organic pollutant widely found in the environment, wildlife and humans. Medical surveillance and experimental studies have investigated the potential effects of PFOA on human livers, but the hepatotoxicity of PFOA on humans and its underlying mechanism remain to be clarified. We exposed a human liver cell line (HL-7702) to 50 μM PFOA for 48 h and 96 h, and identified 111 significantly differentially expressed proteins by iTRAQ analysis. A total of 46 proteins were related to cell proliferation and apoptosis. Through further analysis of the cell cycle, apoptosis and their related proteins, we found that low doses of PFOA (50–100 μM) promoted cell proliferation and numbers by promoting cells from the G1 to S phases, whereas high doses of PFOA (200–400 μM) led to reduced HL-7702 cell numbers compared with that of the control mainly due to cell cycle arrest in the G0/G1 phase. To our knowledge, this is the first report on the promotion of cell cycle progression in human cells following PFOA exposure.

Effects of Ligusticum porteri (Osha) Root Extract on Human Promyelocytic Leukemia Cells

OpenAIRE

Nguyen, Khanh; Sparks, Jean; Omoruyi, Felix

2017-01-01

Background: Ligusticum porteri roots have been traditionally used in folk medicine, but the scientific basis is unclear. Objective: To investigate the cytotoxicity, antioxidant, and immunomodulatory effects of L. porteri root extract on human promyelocytic leukemia (HL-60) cells and H2O2-induced oxidative damaged HL-60 cells. Materials and Methods: HL-60 cells were incubated with different concentrations of root extract, and cells were harvested for viability assays on day 3 and 7. Cytokine l...

Myeloid HIF-1 is protective in Helicobacter pylori-mediated gastritis.

Science.gov (United States)

Matak, Pavle; Heinis, Mylène; Mathieu, Jacques R R; Corriden, Ross; Cuvellier, Sylvain; Delga, Stéphanie; Mounier, Rémi; Rouquette, Alexandre; Raymond, Josette; Lamarque, Dominique; Emile, Jean-François; Nizet, Victor; Touati, Eliette; Peyssonnaux, Carole

2015-04-01

Helicobacter pylori infection triggers chronic inflammation of the gastric mucosa that may progress to gastric cancer. The hypoxia-inducible factors (HIFs) are the central mediators of cellular adaptation to low oxygen levels (hypoxia), but they have emerged recently as major transcriptional regulators of immunity and inflammation. No studies have investigated whether H. pylori affects HIF signaling in immune cells and a potential role for HIF in H. pylori-mediated gastritis. HIF-1 and HIF-2 expression was examined in human H. pylori-positive gastritis biopsies. Subsequent experiments were performed in naive and polarized bone marrow-derived macrophages from wild-type (WT) and myeloid HIF-1α-null mice (HIF-1(Δmyel)). WT and HIF-1(Δmyel) mice were inoculated with H. pylori by oral gavage and sacrificed 6 mo postinfection. HIF-1 was specifically expressed in macrophages of human H. pylori-positive gastritis biopsies. Macrophage HIF-1 strongly contributed to the induction of proinflammatory genes (IL-6, IL-1β) and inducible NO synthase in response to H. pylori. HIF-2 expression and markers of M2 macrophage differentiation were decreased in response to H. pylori. HIF-1(Δmyel) mice inoculated with H. pylori for 6 mo presented with a similar bacterial colonization than WT mice but, surprisingly, a global increase of inflammation, leading to a worsening of the gastritis, measured by an increased epithelial cell proliferation. In conclusion, myeloid HIF-1 is protective in H. pylori-mediated gastritis, pointing to the complex counterbalancing roles of innate immune and inflammatory phenotypes in driving this pathology. Copyright © 2015 by The American Association of Immunologists, Inc.

Creation of miniature pig model of human Waardenburg syndrome type 2A by ENU mutagenesis.

Science.gov (United States)

Hai, Tang; Guo, Weiwei; Yao, Jing; Cao, Chunwei; Luo, Ailing; Qi, Meng; Wang, Xianlong; Wang, Xiao; Huang, Jiaojiao; Zhang, Ying; Zhang, Hongyong; Wang, Dayu; Shang, Haitao; Hong, Qianlong; Zhang, Rui; Jia, Qitao; Zheng, Qiantao; Qin, Guosong; Li, Yongshun; Zhang, Tao; Jin, Weiwu; Chen, Zheng-Yi; Wang, Hongmei; Zhou, Qi; Meng, Anming; Wei, Hong; Yang, Shiming; Zhao, Jianguo

2017-11-01

Human Waardenburg syndrome 2A (WS2A) is a dominant hearing loss (HL) syndrome caused by mutations in the microphthalmia-associated transcription factor (MITF) gene. In mouse models with MITF mutations, WS2A is transmitted in a recessive pattern, which limits the study of hearing loss (HL) pathology. In the current study, we performed ENU (ethylnitrosourea) mutagenesis that resulted in substituting a conserved lysine with a serine (p. L247S) in the DNA-binding domain of the MITF gene to generate a novel miniature pig model of WS2A. The heterozygous mutant pig (MITF +/L247S ) exhibits a dominant form of profound HL and hypopigmentation in skin, hair, and iris, accompanied by degeneration of stria vascularis (SV), fused hair cells, and the absence of endocochlear potential, which indicate the pathology of human WS2A. Besides hypopigmentation and bilateral HL, the homozygous mutant pig (MITF L247S/L247S ) and CRISPR/Cas9-mediated MITF bi-allelic knockout pigs both exhibited anophthalmia. Three WS2 patients carrying MITF mutations adjacent to the corresponding region were also identified. The pig models resemble the clinical symptom and molecular pathology of human WS2A patients perfectly, which will provide new clues for better understanding the etiology and development of novel treatment strategies for human HL.

Protective Effect of Prolactin against Methylmercury-Induced Mutagenicity and Cytotoxicity on Human Lymphocytes

Directory of Open Access Journals (Sweden)

Liz Carmem Silva-Pereira

2014-09-01

Full Text Available Mercury exhibits cytotoxic and mutagenic properties as a result of its effect on tubulin. This toxicity mechanism is related to the production of free radicals that can cause DNA damage. Methylmercury (MeHg is one of the most toxic of the mercury compounds. It accumulates in the aquatic food chain, eventually reaching the human diet. Several studies have demonstrated that prolactin (PRL may be differently affected by inorganic and organic mercury based on interference with various neurotransmitters involved in the regulation of PRL secretion. This study evaluated the cytoprotective effect of PRL on human lymphocytes exposed to MeHg in vitro, including observation of the kinetics of HL-60 cells (an acute myeloid leukemia lineage treated with MeHg and PRL at different concentrations, with both treatments with the individual compounds and combined treatments. All treatments with MeHg produced a significant increase in the frequency of chromatid gaps, however, no significant difference was observed in the chromosomal breaks with any treatment. A dose-dependent increase in the mitotic index was observed for treatments with PRL, which also acts as a co-mitogenic factor, regulating proliferation by modulating the expression of genes that are essential for cell cycle progression and cytoskeleton organization. These properties contribute to the protective action of PRL against the cytotoxic and mutagenic effects of MeHg.

Protective Effect of Prolactin against Methylmercury-Induced Mutagenicity and Cytotoxicity on Human Lymphocytes

Science.gov (United States)

Silva-Pereira, Liz Carmem; da Rocha, Carlos Alberto Machado; Cunha, Luiz Raimundo Campos da Silva e; da Costa, Edmar Tavares; Guimarães, Ana Paula Araújo; Pontes, Thais Brilhante; Diniz, Domingos Luiz Wanderley Picanço; Leal, Mariana Ferreira; Moreira-Nunes, Caroline Aquino; Burbano, Rommel Rodríguez

2014-01-01

Mercury exhibits cytotoxic and mutagenic properties as a result of its effect on tubulin. This toxicity mechanism is related to the production of free radicals that can cause DNA damage. Methylmercury (MeHg) is one of the most toxic of the mercury compounds. It accumulates in the aquatic food chain, eventually reaching the human diet. Several studies have demonstrated that prolactin (PRL) may be differently affected by inorganic and organic mercury based on interference with various neurotransmitters involved in the regulation of PRL secretion. This study evaluated the cytoprotective effect of PRL on human lymphocytes exposed to MeHg in vitro, including observation of the kinetics of HL-60 cells (an acute myeloid leukemia lineage) treated with MeHg and PRL at different concentrations, with both treatments with the individual compounds and combined treatments. All treatments with MeHg produced a significant increase in the frequency of chromatid gaps, however, no significant difference was observed in the chromosomal breaks with any treatment. A dose-dependent increase in the mitotic index was observed for treatments with PRL, which also acts as a co-mitogenic factor, regulating proliferation by modulating the expression of genes that are essential for cell cycle progression and cytoskeleton organization. These properties contribute to the protective action of PRL against the cytotoxic and mutagenic effects of MeHg. PMID:25247425

Optical data transmission ASICs for the high-luminosity LHC (HL-LHC) experiments

International Nuclear Information System (INIS)

Li, X; Huang, G; Sun, X; Liu, G; Deng, B; Gong, D; Guo, D; Liu, C; Liu, T; Xiang, A C; Ye, J; Zhao, X; Chen, J; You, Y; He, M; Hou, S; Teng, P-K; Jin, G; Liang, H; Liang, F

2014-01-01

We present the design and test results of two optical data transmission ASICs for the High-Luminosity LHC (HL-LHC) experiments. These ASICs include a two-channel serializer (LOCs2) and a single-channel Vertical Cavity Surface Emitting Laser (VCSEL) driver (LOCld1V2). Both ASICs are fabricated in a commercial 0.25-μm Silicon-on-Sapphire (SoS) CMOS technology and operate at a data rate up to 8 Gbps per channel. The power consumption of LOCs2 and LOCld1V2 are 1.25 W and 0.27 W at 8-Gbps data rate, respectively. LOCld1V2 has been verified meeting the radiation-tolerance requirements for HL-LHC experiments

Nenápadné významy Hlávkova mostu

Czech Academy of Sciences Publication Activity Database

Hnídková, Vendula

2015-01-01

Roč. 94, č. 12 (2015), s. 722-724 ISSN 0042-4544 Institutional support: RVO:68378033 Keywords : Czech modern architecture * Pavel Janák * Hlávka bridge Subject RIV: AL - Art, Architecture , Cultural Heritage

The Danish National Chronic Myeloid Neoplasia Registry

Directory of Open Access Journals (Sweden)

Bak M

2016-10-01

Full Text Available Marie Bak,1 Else Helene Ibfelt,2 Thomas Stauffer Larsen,3 Dorthe Rønnov-Jessen,4 Niels Pallisgaard,5 Ann Madelung,6 Lene Udby,1 Hans Carl Hasselbalch,1 Ole Weis Bjerrum,7 Christen Lykkegaard Andersen1,7 1Department of Hematology, Zealand University Hospital, University of Copenhagen, Roskilde, 2Research Centre for Prevention and Health, Rigshospitalet Glostrup, University of Copenhagen, Glostrup, 3Department of Hematology, Odense University Hospital, Odense, 4Department of Hematology, Vejle Hospital, Vejle, 5Department of Surgical Pathology, Zealand University Hospital, University of Copenhagen, Roskilde, 6Department of Surgical Pathology, Zealand University Hospital, University of Copenhagen, Næstved, 7Department of Hematology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Aim: The Danish National Chronic Myeloid Neoplasia Registry (DCMR is a population-based clinical quality database, introduced to evaluate diagnosis and treatment of patients with chronic myeloid malignancies. The aim is to monitor the clinical quality at the national, regional, and hospital departmental levels and serve as a platform for research. Study population: The DCMR has nationwide coverage and contains information on patients diagnosed at hematology departments from January 2010 onward, including patients with essential thrombocythemia, polycythemia vera, myelofibrosis, unclassifiable myeloproliferative neoplasms, chronic myelomonocytic leukemia, and chronic myeloid leukemia. Main variables: Data are collected using standardized registration forms (so far up to four forms per patient, which are consecutively filled out online at time of diagnosis, after 2-year and 5-year follow-ups, and at end of follow-up. The forms include variables that describe clinical/paraclinical assessments, treatment, disease progression, and survival – disease-specific variables – as well as variables that are identical for all chronic myeloid malignancies. Descriptive

[Primary study on fluro [ 19F] berberine derivative for human hepatocellular carcinoma targetting in vitro].

Science.gov (United States)

Zhang, Tong; Wu, Xiaoai; Cai, Huawei; Liang, Meng; Fan, Chengzhong

2017-04-01

[ 18 F]HX-01, a Fluorine-18 labeled berberine derivative, is a potential positron emission tomography (PET) tumor imaging agent, while [ 19 F]HX-01 is a nonradioactive reference substance with different energy state and has the same physical and chemical properties. In order to collect data for further study of [ 18 F]HX-01 PET imaging of hepatocellular carcinoma in vivo , this study compared the uptake of [ 19 F]HX-01 by human hepatocellular carcinoma and normal hepatocytes in vitro . The target compound, [ 19 F]HX-01, was synthesized in one step using berberrubine and 3-fluoropropyl 4-methylbenzenesulfonate. Cellular uptake and localization of [ 19 F]HX-01 were performed by a fluorescence microscope in human hepatocellular carcinoma HepG2, SMMC-7721 and human normal hepatocyte HL-7702. Cellular proliferation inhibition and cell cytotoxicity assay of the [ 19 F]HX-01 were conducted using cell counting kit-8 (CCK-8) on HepG2, SMMC-7721 and HL-7702 cells. Fluorescent microscopy showed that the combining ability of [ 19 F]HX-01 to the carcinoma SMMC-7721 and HepG2 was higher than that to the normal HL-7702. Cellular proliferation inhibition assay demonstrated that [ 19 F]HX-01 leaded to a dose-dependent inhibition on SMMC-7721, HepG2, and HL-7702 proliferation. Cell cytotoxicity assay presented that the cytotoxicity of [ 19 F]HX-01 to SMMC-7721 and HepG2 was obviously higher than that to HL-7702. This in vitro study showed that [ 19 F]HX-01 had a higher selectivity on human hepatocellular carcinoma cells (SMMC-7721, HepG2) but has less toxicity to normal hepatocytes (HL-7702). This could set up the idea that the radioactive reference substance [ 18 F]HX-01 may be worthy of further development as a potential molecular probe targeting human hepatocellular carcinoma using PET.

Towards Optimum Material Choices for HL-LHC Collimator Upgrade

CERN Document Server

Quaranta, E.; Biancacci, N.; Bruce, R.; Carra, F.; Métral, E.; Redaelli, S.; Rossi, A.; Salvant, B.

2016-01-01

properties that address different limitations of the present collimation system, solutions have been found to fulfil various upgrade challenges. This paper describes the proposed staged approach to deploy new materials in the upgraded HL-LHC collimation system. Beam tests at the CERN HiRadMat facility were also performed to benchmark simulation methods and constitutive material models.

Myeloid-Derived Suppressor Cells and Therapeutic Strategies in Cancer

Directory of Open Access Journals (Sweden)

Hiroshi Katoh

2015-01-01

Full Text Available Development of solid cancer depends on escape from host immunosurveillance. Various types of immune cells contribute to tumor-induced immune suppression, including tumor associated macrophages, regulatory T cells, type 2 NKT cells, and myeloid-derived suppressor cells (MDSCs. Growing body of evidences shows that MDSCs play pivotal roles among these immunosuppressive cells in multiple steps of cancer progression. MDSCs are immature myeloid cells that arise from myeloid progenitor cells and comprise a heterogeneous immune cell population. MDSCs are characterized by the ability to suppress both adaptive and innate immunities mainly through direct inhibition of the cytotoxic functions of T cells and NK cells. In clinical settings, the number of circulating MDSCs is associated with clinical stages and response to treatment in several cancers. Moreover, MDSCs are reported to contribute to chemoresistant phenotype. Collectively, targeting MDSCs could potentially provide a rationale for novel treatment strategies in cancer. This review summarizes recent understandings of MDSCs in cancer and discusses promissing clinical approaches in cancer patients.

Myeloid leukaemia/osteosarcoma ratio in CBA/H mice given radium 224

International Nuclear Information System (INIS)

Humphreys, E.R.; Stones, V.A.

1989-01-01

Four groups of 400 12-week-old CBA/H mice were injected intraperitoneally with mean amounts of 69, 139, 280 and 550 Bq/g -1 radium 224. A further group of 400 mice were injected intraperitoneally with diluting solution only. The mice were allowed unrestricted access to food and water until they died or were killed. To date (September 1988) about 40% of the mice are dead, and 28 cases of myeloid leukaemia and four cases of osteosarcoma have been diagnosed in the animals given radium 224. The relationship between the yield of myeloid leukaemia and the amount of radium 224 injected was found to be curvilinear. The determined value of the myeloid leukaemia:osteosarcoma ratio is discussed. (author)

Plasma electron density measurement with multichannel microwave interferometer on the HL-1 tokamak device

International Nuclear Information System (INIS)

Xu Deming; Zhang Hongyin; Liu Zetian; Ding Xuantong; Li Qirui; Wen Yangxi

1989-11-01

A multichannel microwave interferometer which is composed of different microwave interferometers (one 2 mm band, one 4 mm band and two 8 mm band) has been used to measure the plasma electron density on HL-1 tokamak device. The electron density approaching to 5 x 10 13 cm -3 is measured by a 2 mm band microwave interferometer. In the determinable range, the electron density profile in the cross-section on HL-1 device has been measured by this interferometer. A microcomputer data processing system is also developed

Bounding the HL-index of a graph: a majorization approach.

Science.gov (United States)

Clemente, Gian Paolo; Cornaro, Alessandra

2016-01-01

In mathematical chemistry, the median eigenvalues of the adjacency matrix of a molecular graph are strictly related to orbital energies and molecular orbitals. In this regard, the difference between the occupied orbital of highest energy (HOMO) and the unoccupied orbital of lowest energy (LUMO) has been investigated (see Fowler and Pisansky in Acta Chim. Slov. 57:513-517, 2010). Motivated by the HOMO-LUMO separation problem, Jaklič et al. in (Ars Math. Contemp. 5:99-115, 2012) proposed the notion of HL -index that measures how large in absolute value are the median eigenvalues of the adjacency matrix. Several bounds for this index have been provided in the literature. The aim of the paper is to derive alternative inequalities to bound the HL -index. By applying majorization techniques and making use of some known relations, we derive new and sharper upper bounds for this index. Analytical and numerical results show the performance of these bounds on different classes of graphs.

The CMS Tracker Upgrade for HL-LHC\\\\ Sensor R$\\&$D

CERN Document Server

Naseri, Mohsen

2014-01-01

At an instantaneous luminosity of 5~$\\times10^{34}~cm^{-2}~s^{-1}$, the high-luminosity phase of the Large Hadron Collider (HL-LHC) is expected to deliver a total of 3000~fb$^{-1}$ of collisions, hereby increasing the discovery potential of the LHC experiments significantly. However, the radiation environment of the tracking system will be severe, requiring new radiation hard sensors for the CMS tracker. Focusing on the upgrade of the outer tracker region, the CMS tracker collaboration has almost completed a large material investigation and irradiation campaign to identify the silicon material and design that fulfils all requirements of a new tracking detector at HL-LHC. Focusing on the upgrade of the outer tracker region, pad diodes as well as fully functional strip sensors have been implemented on silicon wafers with different material properties and thicknesses. The samples were irradiated with a mixture of neutrons and protons corresponding to fluences as expected for various positions in the future track...

Rare myeloid sarcoma/acute myeloid leukemia with adrenal mass after allogeneic mobilization peripheral blood stem cell transplantation

International Nuclear Information System (INIS)

Wang, Ya-Fei; Li, Qian; Xu, Wen-Gui; Xiao, Jian-Yu; Pang, Qing-Song; Yang, Qing; Zhang, Yi-Zuo

2013-01-01

Myeloid sarcoma (MS) is a rare hematological neoplasm that develops either de novo or concurrently with acute myeloid leukemia (AML). This neoplasm can also be an initial manifestation of relapse in a previously treated AML that is in remission. A 44-year-old male patient was diagnosed with testis MS in a local hospital in August 2010. After one month, bone marrow biopsy and aspiration confirmed the diagnosis of AML. Allogeneic mobilization peripheral blood stem cell transplantation was performed, with the sister of the patient as donor, after complete remission (CR) was achieved by chemotherapy. Five months after treatment, an adrenal mass was detected by positron emission tomography-computed tomography (PET-CT). Radiotherapy was performed for the localized mass after a multidisciplinary team (MDT) discussion. The patient is still alive as of May 2013, with no evidence of recurrent MS or leukemia

Induction of cytosine arabinoside-resistant human myeloid leukemia cell death through autophagy regulation by hydroxychloroquine.

Science.gov (United States)

Kim, Yundeok; Eom, Ju-In; Jeung, Hoi-Kyung; Jang, Ji Eun; Kim, Jin Seok; Cheong, June-Won; Kim, Young Sam; Min, Yoo Hong

2015-07-01

We investigated the effects of the autophagy inhibitor hydroxychloroquine (HCQ) on cell death of cytosine arabinoside (Ara-C)-resistant human acute myeloid leukemia (AML) cells. Ara-C-sensitive (U937, AML-2) and Ara-C-resistant (U937/AR, AML-2/AR) human AML cell lines were used to evaluate HCQ-regulated cytotoxicity, autophagy, and apoptosis as well as effects on cell death-related signaling pathways. We found that HCQ-induced dose- and time-dependent cell death in Ara-C-resistant cells compared to Ara-C-sensitive cell lines. The extent of cell death and features of HCQ-induced autophagic markers including increase in microtubule-associated protein light chain 3 (LC3) I conversion to LC3-II, beclin-1, ATG5, as well as green fluorescent protein-LC3 positive puncta and autophagosome were remarkably greater in U937/AR cells. Also, p62/SQSTM1 was increased in response to HCQ. p62/SQSTM1 protein interacts with both LC3-II and ubiquitin protein and is degraded in autophagosomes. Therefore, a reduction of p62/SQSTM1 indicates increased autophagic degradation, whereas an increase of p62/SQSTM1 by HCQ indicates inhibited autophagic degradation. Knock down of p62/SQSTM1 using siRNA were prevented the HCQ-induced LC3-II protein level as well as significantly reduced the HCQ-induced cell death in U937/AR cells. Also, apoptotic cell death and caspase activation in U937/AR cells were increased by HCQ, provided evidence that HCQ-induced autophagy blockade. Taken together, our data show that HCQ-induced apoptotic cell death in Ara-C-resistant AML cells through autophagy regulation. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia

DEFF Research Database (Denmark)

Saglio, Giuseppe; Kim, Dong-Wook; Issaragrisil, Surapol

2010-01-01

Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib. We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase.......Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib. We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase....

Prevention of Resistance in Chronic Myeloid Leukemia: the role of combination therapy

NARCIS (Netherlands)

W. Deenik (Wendy)

2010-01-01

textabstractChronic myeloid leukemia (CML) is a rare disease with a worldwide incidence of approximately 1-2 cases per 100,000 individuals. Chronic myeloid leukemia occurs slightly more frequently in men than in women. The median age at diagnosis is approximately 60 years, and although the incidence

Magnetic Frequency Response of HL-LHC Beam Screens

Energy Technology Data Exchange (ETDEWEB)

Morrone, M. [CERN; Martino, M. [CERN; De Maria, R. [CERN; Fitterer, M. [Fermilab; Garion, C. [CERN

2017-10-12

Magnetic fields used to control particle beams in accelerators are usually controlled by regulating the electrical current of the power converters. In order to minimize lifetime degradation and ultimately luminosity loss in circular colliders, current-noise is a highly critical figure of merit of power converters, in particular for magnets located in areas with high beta-function, like the High Luminosity Large Hadron Collider (HL-LHC) insertions. However, what is directly acting upon the beam is the magnetic field and not the current of the power converter, which undergoes several frequency-dependent transformations until the desired magnetic field, seen by the beam, is obtained. Beam screens are very rarely considered when assessing or specifying the noise figure of merit, but their magnetic frequency response is such that they realize relatively effective low pass filtering of the magnetic field produced by the system magnet-power converter. This work aims at filling this gap by quantifying the expected impact of different beam screen layouts for the most relevant HL-LHC insertion magnets. A welldefined post-processing technique is used to derive the frequency response of the different multipoles from multi-physics Finite Element Method (FEM) simulation results. In addition, a well approximated analytical formula for the low-frequency range of multi-layered beam screens is presented.

A typical presentation of acute myeloid leukemia

Directory of Open Access Journals (Sweden)

Udayakumar N

2006-01-01

Full Text Available A young man who presented with fever, altered sensorium and sudden onset tachypnea, is described. Arterial blood gas analysis, revealed the presence of severe high anion gap metabolic acidosis, with compensatory respiratory alkalosis and normal oxygen saturation. A detailed neurological, nephrological, biochemical and hematological evaluation, revealed the presence of Acute myeloid leukemia, with lactic acidosis and hyponatremia. There are very few reports of presentation of leukemia as lactic acidosis. This case report highlights the need for emergency room physicians, to consider the possibility of lactic acidosis, as one of the causes of high anion gap acidosis and to meticulously investigate the cause of lactic acidosis. We describe a rare clinical instance of lactic acidosis as the presenting manifestation of Acute myeloid leukemia.

Performances and ageing study of resistive-anodes Micromegas detectors for HL-LHC environment

CERN Document Server

Jeanneau, F; Attié, D; Boyer, M; Derré, J; Fanourakis, G; Ferrer-Ribas, E; Galán, J; Gazis, E; Geralis, T; Giganon, A; Giomataris, I; Herlant, S; Manjarrés, J; Ntomari, E; Schune, Ph; Titov, M; Tsipolitis, G

2012-01-01

With the tenfold luminosity increase envisaged at the HL-LHC, the background (photons, neutrons, ...) and the event pile-up probability are expected to increase in proportion in the different experiments, especially in the forward regions like, for instance, the muons chambers of the ATLAS detector. Detectors based on the Micromegas principle should be good alternatives for the detector upgrade in the HL-LHC framework because of a good spatial ( 98%) can be achieved with resistive-anode micromegas detector. An X-rays irradiation has been also performed, showing no ageing effect after more than 21 days exposure and an integrated charge of almost 1C.

Granulocytic sarcoma in a patient with chronic myeloid leukaemia in complete haematological, cytogenetic and molecular remission.

Science.gov (United States)

Kittai, Adam; Yu, Eun-Mi; Tabbara, Imad

2014-12-23

Granulocytic sarcoma, also known as myeloid sarcoma, is an extramedullary tumour composed of immature myeloid cells. Granulocytic sarcoma is typically found in patients with acute myeloid leukaemia, accelerated phase or blast crisis of chronic myeloid leukaemia, myelodysplastic syndrome, or as an isolated event without bone marrow involvement. We present a case of granulocytic sarcoma in a patient with chronic myeloid leukaemia in the setting of complete haematological, molecular and cytogenetic remission. Our patient was first treated with imatinib for chronic-phase chronic myeloid leukaemia. After maintaining remission for 42 months, he developed a granulocytic sarcoma in his spine. In this case report, we describe our case, along with the three other cases reported in the literature. In addition to being a rare diagnosis, this case demonstrates the importance of being vigilant in diagnosing the cause of back pain and atypical symptoms in patients with a history of leukaemia. 2014 BMJ Publishing Group Ltd.

Cyanobacteria from Terrestrial and Marine Sources Contain Apoptogens Able to Overcome Chemoresistance in Acute Myeloid Leukemia Cells

Science.gov (United States)

Liu, Liwei; Herfindal, Lars; Jokela, Jouni; Shishido, Tania Keiko; Wahlsten, Matti; Døskeland, Stein Ove; Sivonen, Kaarina

2014-01-01

In this study, we investigated forty cyanobacterial isolates from biofilms, gastropods, brackish water and symbiotic lichen habitats. Their aqueous and organic extracts were used to screen for apoptosis-inducing activity against acute myeloid leukemia cells. A total of 28 extracts showed cytotoxicity against rat acute myeloid leukemia (IPC-81) cells. The design of the screen made it possible to eliminate known toxins, such as microcystins and nodularin, or known metabolites with anti-leukemic activity, such as adenosine and its analogs. A cytotoxicity test on human embryonic kidney (HEK293T) fibroblasts indicated that 21 of the 28 extracts containing anti-acute myeloid leukemia (AML) activity showed selectivity in favor of leukemia cells. Extracts L26-O and L30-O were able to partly overcome the chemotherapy resistance induced by the oncogenic protein Bcl-2, whereas extract L1-O overcame protection from the deletion of the tumor suppressor protein p53. In conclusion, cyanobacteria are a prolific resource for anti-leukemia compounds that have potential for pharmaceutical applications. Based on the variety of cellular responses, we also conclude that the different anti-leukemic compounds in the cyanobacterial extracts target different elements of the death machinery of mammalian cells. PMID:24705501

Cyanobacteria from Terrestrial and Marine Sources Contain Apoptogens Able to Overcome Chemoresistance in Acute Myeloid Leukemia Cells

Directory of Open Access Journals (Sweden)

Liwei Liu

2014-04-01

Full Text Available In this study, we investigated forty cyanobacterial isolates from biofilms, gastropods, brackish water and symbiotic lichen habitats. Their aqueous and organic extracts were used to screen for apoptosis-inducing activity against acute myeloid leukemia cells. A total of 28 extracts showed cytotoxicity against rat acute myeloid leukemia (IPC-81 cells. The design of the screen made it possible to eliminate known toxins, such as microcystins and nodularin, or known metabolites with anti-leukemic activity, such as adenosine and its analogs. A cytotoxicity test on human embryonic kidney (HEK293T fibroblasts indicated that 21 of the 28 extracts containing anti-acute myeloid leukemia (AML activity showed selectivity in favor of leukemia cells. Extracts L26-O and L30-O were able to partly overcome the chemotherapy resistance induced by the oncogenic protein Bcl-2, whereas extract L1-O overcame protection from the deletion of the tumor suppressor protein p53. In conclusion, cyanobacteria are a prolific resource for anti-leukemia compounds that have potential for pharmaceutical applications. Based on the variety of cellular responses, we also conclude that the different anti-leukemic compounds in the cyanobacterial extracts target different elements of the death machinery of mammalian cells.

Involvement of the histamine H4 receptor in clozapine-induced hematopoietic toxicity: Vulnerability under granulocytic differentiation of HL-60 cells

International Nuclear Information System (INIS)

Goto, Aya; Mouri, Akihiro; Nagai, Tomoko; Yoshimi, Akira; Ukigai, Mako; Tsubai, Tomomi; Hida, Hirotake; Ozaki, Norio; Noda, Yukihiro

2016-01-01

Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but can cause fatal hematopoietic toxicity as agranulocytosis. To elucidate the mechanism of hematopoietic toxicity induced by clozapine, we developed an in vitro assay system using HL-60 cells, and investigated the effect on hematopoiesis. HL-60 cells were differentiated by all-trans retinoic acid (ATRA) into three states according to the following hematopoietic process: undifferentiated HL-60 cells, those undergoing granulocytic ATRA-differentiation, and ATRA-differentiated granulocytic cells. Hematopoietic toxicity was evaluated by analyzing cell survival, cell proliferation, granulocytic differentiation, apoptosis, and necrosis. In undifferentiated HL-60 cells and ATRA-differentiated granulocytic cells, both clozapine (50 and 100 μM) and doxorubicin (0.2 µM) decreased the cell survival rate, but olanzapine (1–100 µM) did not. Under granulocytic differentiation for 5 days, clozapine, even at a concentration of 25 μM, decreased survival without affecting granulocytic differentiation, increased caspase activity, and caused apoptosis rather than necrosis. Histamine H 4 receptor mRNA was expressed in HL-60 cells, whereas the expression decreased under granulocytic ATRA-differentiation little by little. Both thioperamide, a histamine H 4 receptor antagonist, and DEVD-FMK, a caspase-3 inhibitor, exerted protection against clozapine-induced survival rate reduction, but not of live cell counts. 4-Methylhistamine, a histamine H 4 receptor agonist, decreased the survival rate and live cell counts, as did clozapine. HL-60 cells under granulocytic differentiation are vulnerable under in vitro assay conditions to hematopoietic toxicity induced by clozapine. Histamine H 4 receptor is involved in the development of clozapine-induced hematopoietic toxicity through apoptosis, and may be a potential target for preventing its occurrence through granulocytic differentiation. - Highlights: • HL-60

Differentiation-inducing effects of small fruit juices on HL-60 leukemic cells.

Science.gov (United States)

Yoshizawa, Y; Kawaii, S; Urashima, M; Fukase, T; Sato, T; Murofushi, N; Nishimura, H

2000-08-01

Epidemiological studies indicate that high intakes of fruits and vegetables are associated with a reduced risk of cancer, and several plant-derived drugs have been developed in medical oncology. Since only a small part of the flora has been tested for any kind of bioactivity, we chose small fruits as sources of differentiation-inducing activity against HL-60 leukemic cells. We have prepared juices from various small fruits that grow mainly in the northern part of Japan. Screening of 43 samples indicated that juices of Actinidia polygama Maxim., Rosa rugosa Thunb., Vaccinium smallii A. Gray, and Sorbus sambucifolia Roem. strongly induced differentiation of HL-60 cells to monocyte/macrophage characteristics in a concentration-dependent manner as indicated by histochemical and biochemical examinations.

Discovery of novel inducers of cellular differentiation using HL-60 promyelocytic cells.

Science.gov (United States)

Mata-Greenwood, E; Ito, A; Westenburg, H; Cui, B; Mehta, R G; Kinghorn, A D; Pezzuto, J M

2001-01-01

Non-physiological inducers of terminal differentiation have been used as novel therapies for the prevention and therapy of cancer. We have used cultured HL-60 promyelocytic cells to monitor differentiation, proliferation and cell death events as induced by a large set of extracts derived from plants. Screening of more than 1400 extracts led to the discovery of 34 with potent activity (ED50 Petiveria alliacea, and desmethylrocaglamide from Aglaia ponapensis. Zapotin demonstrated the most favorable biological profile in that induction of differentiation correlated with proliferation arrest, and a lack of cytotoxicity. We conclude that the HL-60 cell model is a useful system for the discovery of novel pharmacophores with potential to suppress the process of carcinogenesis, and that flavonoids may be especially useful in this capacity.

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

Science.gov (United States)

2018-02-16

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

MicroRNA expression changes during human leukemic HL-60 cell differentiation induced by 4-hydroxynonenal, a product of lipid peroxidation.

Science.gov (United States)

Pizzimenti, Stefania; Ferracin, Manuela; Sabbioni, Silvia; Toaldo, Cristina; Pettazzoni, Piergiorgio; Dianzani, Mario Umberto; Negrini, Massimo; Barrera, Giuseppina

2009-01-15

4-Hydroxynonenal (HNE) is one of several lipid oxidation products that may have an impact on human pathophysiology. It is an important second messenger involved in the regulation of various cellular processes and exhibits antiproliferative and differentiative properties in various tumor cell lines. The mechanisms by which HNE affects cell growth and differentiation are only partially clarified. Because microRNAs (miRNAs) have the ability to regulate several cellular processes, we hypothesized that HNE, in addition to other mechanisms, could affect miRNA expression. Here, we present the results of a genome-wide miRNA expression profiling of HNE-treated HL-60 leukemic cells. Among 470 human miRNAs, 10 were found to be differentially expressed between control and HNE-treated cells (at p<0.05). Six miRNAs were down-regulated (miR-181a*, miR-199b, miR-202, miR-378, miR-454-3p, miR-575) and 4 were up-regulated (miR-125a, miR-339, miR-663, miR-660). Three of these regulated miRNAs (miR-202, miR-339, miR-378) were further assayed and validated by quantitative real-time RT-PCR. Moreover, consistent with the down-regulation of miR-378, HNE also induced the expression of the SUFU protein, a tumor suppressor recently identified as a target of miR-378. The finding that HNE could regulate the expression of miRNAs and their targets opens new perspectives on the understanding of HNE-controlled pathways. A functional analysis of 191 putative gene targets of miRNAs modulated by HNE is discussed.

A fragment of alpha-actinin promotes monocyte/macrophage maturation in vitro.

Science.gov (United States)

Luikart, S; Wahl, D; Hinkel, T; Masri, M; Oegema, T

1999-02-01

Conditioned media (CM) from cultures of HL-60 myeloid leukemia cells grown on extracellular bone marrow matrix contains a factor that induces macrophage-like maturation of HL-60 cells. This factor was purified from the CM of HL-60 cells grown on bone marrow stroma by ammonium sulfate precipitation, then sequential chromatography on DEAE, affi-gel blue affinity, gel exclusion, and wheat germ affinity columns, followed by C-4 reverse phase HPLC, and SDS-PAGE. The maturation promoting activity of the CM was identified in a single 31 kD protein. Amino acid sequence analysis of four internal tryptic peptides of this protein confirmed significant homology with amino acid residues 48-60, 138-147, 215-220, and 221-236 of human cytoskeletal alpha-actinin. An immunoaffinity purified rabbit polyclonal anti-chicken alpha-actinin inhibited the activity of HL-60 conditioned media. A 27 kD amino-terminal fragment of alpha-actinin produced by thermolysin digestion of chicken gizzard alpha-actinin, but not intact alpha-actinin, had maturation promoting activity on several cell types, including blood monocytes, as measured by lysozyme secretion and tartrate-resistant acid phosphatase staining. We conclude that an extracellular alpha-actinin fragment can promote monocyte/macrophage maturation. This represents the first example of a fragment of a cytoskeletal component, which may be released during tissue remodeling and repair, playing a role in phagocyte maturation.

Preliminary design of HL-2A discharge control system

International Nuclear Information System (INIS)

Jiang Chao; Song Xianming; Li Qiang

2001-01-01

HL-2A Discharge Control System consists of one or more VXI work stations so as to compose an all digital control system. The DCS are used to measure and control the poloidal coils, the main tasks of the poloidal coils are exploding, keeping and controlling the current of plasma. These coils explode plasma and keep it in the determined position

Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission

Science.gov (United States)

2018-05-24

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; 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

Optics of ion beams for the neutral beam injection system on HL-2A Tokamak

Energy Technology Data Exchange (ETDEWEB)

Zou, G. Q.; Lei, G. J.; Cao, J. Y.; Duan, X. R. [Southwestern Institute of Physics, Chengdu, 610041 (China)

2012-07-15

The ion beam optics for the neutral beam injection system on HL-2A Tokomak is studied by two- dimensional numerical simulation program firstly, where the emitting surface is taken at 100 Debye lengths from the plasma electrode. The mathematical formulation, computation techniques are described. Typical ion orbits, equipotential contours, and emittance diagram are shown. For a fixed geometry electrode, the effect of plasma density, plasma potential and plasma electron temperature on ion beam optics is examined, and the calculation reliability is confirmed by experimental results. In order to improve ion beam optics, the application of a small pre-acceleration voltage ({approx}100 V) between the plasma electrode and the arc discharge anode is reasonable, and a lower plasma electron temperature is desired. The results allow optimization of the ion beam optics in the neutral beam injection system on HL-2A Tokomak and provide guidelines for designing future neutral beam injection system on HL-2M Tokomak.

Optics of ion beams for the neutral beam injection system on HL-2A Tokamak.

Science.gov (United States)

Zou, G Q; Lei, G J; Cao, J Y; Duan, X R

2012-07-01

The ion beam optics for the neutral beam injection system on HL-2A Tokomak is studied by two- dimensional numerical simulation program firstly, where the emitting surface is taken at 100 Debye lengths from the plasma electrode. The mathematical formulation, computation techniques are described. Typical ion orbits, equipotential contours, and emittance diagram are shown. For a fixed geometry electrode, the effect of plasma density, plasma potential and plasma electron temperature on ion beam optics is examined, and the calculation reliability is confirmed by experimental results. In order to improve ion beam optics, the application of a small pre-acceleration voltage (∼100 V) between the plasma electrode and the arc discharge anode is reasonable, and a lower plasma electron temperature is desired. The results allow optimization of the ion beam optics in the neutral beam injection system on HL-2A Tokomak and provide guidelines for designing future neutral beam injection system on HL-2M Tokomak.

AN ORIGIN OF MULTIPLE RING STRUCTURE AND HIDDEN PLANETS IN HL TAU: A UNIFIED PICTURE BY SECULAR GRAVITATIONAL INSTABILITY

International Nuclear Information System (INIS)

Takahashi, Sanemichi Z.; Inutsuka, Shu-ichiro

2016-01-01

Recent ALMA observation has revealed multiple ring structures formed in a protoplanetary disk around HL Tau. Prior to the ALMA observation of HL Tau, theoretical analysis of secular gravitational instability (GI) described a possible formation of multiple ring structures with separations of 13 au around a radius of 100 au in protoplanetary disks under certain conditions. In this article, we reanalyze the viability of secular GI by adopting the physical values inferred from the observations. We derive the radial distributions of the most unstable wavelength and the growth timescale of secular GI and verify that secular GI can form the ring structures observed in HL Tau. When a turbulent viscosity coefficient α remains small in the inner region of the disk, secular GI grows in the whole disk. Thus, the formation of planetary mass objects should occur first in the inner region as a result of gravitational fragmentation after the nonlinear growth of secular GI. In this case, the resulting objects are expected to create gaps at r  ∼ 10 au and ∼30 au. As a result, all ring structures in HL Tau can be created by secular GI. If this scenario is realized in HL Tau, the outer region corresponds to the earlier growth phase of the most unstable mode of secular GI, and the inner region corresponds to the outcome of the nonlinear growth of secular GI. Therefore, this interpretation suggests that we are possibly witnessing both the beginning and the end of planet formation in HL Tau.

AN ORIGIN OF MULTIPLE RING STRUCTURE AND HIDDEN PLANETS IN HL TAU: A UNIFIED PICTURE BY SECULAR GRAVITATIONAL INSTABILITY

Energy Technology Data Exchange (ETDEWEB)

Takahashi, Sanemichi Z. [Astronomical Institute, Tohoku University, 6-3 Aoba, Aramaki-aza, Aoba-ku, Sendai, Miyagi (Japan); Inutsuka, Shu-ichiro, E-mail: sanemichi@astr.tohoku.ac.jp, E-mail: inutsuka@nagoya-u.jp [Department of Physics, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8602 (Japan)

2016-12-01

Recent ALMA observation has revealed multiple ring structures formed in a protoplanetary disk around HL Tau. Prior to the ALMA observation of HL Tau, theoretical analysis of secular gravitational instability (GI) described a possible formation of multiple ring structures with separations of 13 au around a radius of 100 au in protoplanetary disks under certain conditions. In this article, we reanalyze the viability of secular GI by adopting the physical values inferred from the observations. We derive the radial distributions of the most unstable wavelength and the growth timescale of secular GI and verify that secular GI can form the ring structures observed in HL Tau. When a turbulent viscosity coefficient α remains small in the inner region of the disk, secular GI grows in the whole disk. Thus, the formation of planetary mass objects should occur first in the inner region as a result of gravitational fragmentation after the nonlinear growth of secular GI. In this case, the resulting objects are expected to create gaps at r  ∼ 10 au and ∼30 au. As a result, all ring structures in HL Tau can be created by secular GI. If this scenario is realized in HL Tau, the outer region corresponds to the earlier growth phase of the most unstable mode of secular GI, and the inner region corresponds to the outcome of the nonlinear growth of secular GI. Therefore, this interpretation suggests that we are possibly witnessing both the beginning and the end of planet formation in HL Tau.

Evolution of our understanding of myeloid regulatory cells: from MDSCs to Mregs

Directory of Open Access Journals (Sweden)

Masoud H Manjili

2014-07-01

Full Text Available The term Myeloid-Derived Suppressor Cells (MDSCs was first suggested in 2007 in order to reflect on the origin and function of myeloid cells during immunosuppression in cancer and other pathologic conditions. Emerging evidence suggest that MDSCs suppress CTL and Th1 responses in malignant diseases while they regulate effective immune responses in parasitic and helminth infections as well as Th17 inflammatory response during autoimmune diseases. Based on these data the term myeloid regulatory cells (Mregs more accurately reflects their function and interactions with different cells of the immune system during diseased conditions. Here, we provide evidence on the multifaceted function of Mregs during diseased states.

SUMOylation of sPRDM16 promotes the progression of acute myeloid leukemia

International Nuclear Information System (INIS)

Dong, Song; Chen, Jieping

2015-01-01

In addition to genetic and epigenetic alteration, post-translational modification of proteins plays a critical role in the initiation, progression and maturation of acute myeloid leukemia (AML). The SUMOylation site of sPRDM16 at K568 was mutated to arginine by site-directed mutagenesis. THP-1 acute myeloid leukemia cells were transduced with a lentivirus containing wild type or K568 mutant sPRDM16. Proliferation, self-renewal and differentiation of transduced THP-1 cells were analyzed both in vitro cell culture and in mouse xenografts. Gene expression profiles were analyzed by RNA-seq. Overexpression of sPRDM16 promoted proliferation, enhanced self-renewal capacity, but inhibited differentiation of THP-1 acute myeloid leukemia cells. We further confirmed that K568 is a bona fide SUMOylation site on sPRDM16. Mutation of the sPRDM16 SUMOylation site at K568 partially abolished the capacity of sPRDM16 to promote proliferation and inhibit differentiation of acute myeloid leukemia cells both in vitro and in mouse xenografts. Furthermore, THP-1 cells overexpressing sPRDM16-K568R mutant exhibited a distinct gene expression profile from wild type sPRDM16 following incubation with PMA. Our results suggest that K568 SUMOylation of sPRDM16 plays an important role in the progression of acute myeloid leukemia

Cellular uptake of {sup 99m}TcN-NOET in human leukaemic HL-60 cells is related to calcium channel activation and cell proliferation

Energy Technology Data Exchange (ETDEWEB)

Guillermet, Stephanie; Vuillez, Jean-Philippe; Caravel, Jean-Pierre; Marti-Batlle, Daniele; Fagret, Daniel [Universite de Grenoble, Radiopharmaceutiques Biocliniques, La Tronche (France); Fontaine, Eric [Universite de Grenoble, Laboratoire de Bioenergetique Fondamentale et Appliquee, Grenoble (France); Pasqualini, Roberto [Cis Bio International Schering SA, Gif-sur-Yvette (France)

2006-01-01

A major goal of nuclear oncology is the development of new radiolabelled tracers as proliferation markers. Intracellular calcium waves play a fundamental role in the course of the cell cycle. These waves occur in non-excitable tumour cells via store-operated calcium channels (SOCCs). Bis(N-ethoxy, N-ethyldithiocarbamato) nitrido technetium (V)-99m ({sup 99m}TcN-NOET) has been shown to interact with L-type voltage-operated calcium channels (VOCCs) in cultured cardiomyocytes. Considering the analogy between VOCCs and SOCCs, we sought to determine whether {sup 99m}TcN-NOET also binds to activated SOCCs in tumour cells in order to clarify the potential value of this tracer as a proliferation marker. Uptake kinetics of {sup 99m}TcN-NOET were measured in human leukaemic HL-60 cells over 60 min and the effect of several calcium channel modulators on 1-min tracer uptake was studied. The uptake kinetics of {sup 99m}TcN-NOET were compared both with the variations of cytosolic free calcium concentration measured by indo-1/AM and with the variations in the SG{sub 2}M cellular proliferation index. All calcium channel inhibitors significantly decreased the cellular uptake of {sup 99m}TcN-NOET whereas the activator thapsigargin induced a significant 10% increase. In parallel, SOCC activation by thapsigargin, as measured using the indo-1/AM probe, was inhibited by nicardipine. These results indicate that the uptake of {sup 99m}TcN-NOET is related to the activation of SOCCs. Finally, a correlation was observed between the tracer uptake and variations in the proliferation index SG{sub 2}M. The uptake of {sup 99m}TcN-NOET seems to be related to SOCC activation and to cell proliferation in HL-60 cells. These results indicate that {sup 99m}TcN-NOET might be a marker of cell proliferation. (orig.)

Secondary Leukemia in a non-Hodgkin's Lymphoma Patient Presenting as Myeloid Sarcoma of the Breast

Directory of Open Access Journals (Sweden)

Vincenzo Pitini

2011-01-01

Full Text Available As defined by the World Health Organization classification of tumors of hematopoietic and lymphoid tissue, myeloid sarcoma (MS is a tumor mass of myeloblasts or immature myeloid cells that can arise before, concurrent with, or following acute myeloid leukaemia. We describe a case of secondary leukemia presenting itself as MS of the breast in a patient previously treated for a non-Hodgkin's Lymphoma.

A stratified myeloid system, the challenge of understanding macrophage diversity.

Science.gov (United States)

Geissmann, F; Mass, E

2015-12-01

The present issue of 'Seminars in Immunology' addresses the topic of macrophage biology, 100 years after the death of Elie Metchnikoff (May 1845-July 1916). As foreseen by Metchnikoff, the roles of macrophages in the maintenance of homeostasis and immunity against pathogens have become a broad and active area of investigation. We now start to realize that the myeloid system includes a multiplicity of cell types with diverse developmental origins and functions. Therefore, the textbook picture of a plastic and multifunctional macrophage does not meet the requirements of our current knowledge anymore. Further development toward a quantitative and molecular understanding of myeloid cell biology in vivo and their roles in tissue homeostasis and remodeling will benefit from taking this complexity into account. A tentative model to help in this pursuit and account for myeloid cell and macrophage diversity is discussed below. Copyright © 2016. Published by Elsevier Ltd.

GRAIN SIZE CONSTRAINTS ON HL TAU WITH POLARIZATION SIGNATURE

International Nuclear Information System (INIS)

Kataoka, Akimasa; Dullemond, Cornelis P; Muto, Takayuki; Momose, Munetake; Tsukagoshi, Takashi

2016-01-01

The millimeter-wave polarization of the protoplanetary disk around HL Tau has been interpreted as the emission from elongated dust grains aligned with the magnetic field in the disk. However, the self-scattering of thermal dust emission may also explain the observed millimeter-wave polarization. In this paper, we report a modeling of the millimeter-wave polarization of the HL Tau disk with the self-polarization. Dust grains are assumed to be spherical and to have a power-law size distribution. We change the maximum grain size with a fixed dust composition in a fixed disk model to find the grain size to reproduce the observed signature. We find that the direction of the polarization vectors and the polarization degree can be explained with the self-scattering. Moreover, the polarization degree can be explained only if the maximum grain size is ∼150 μm. The obtained grain size from the polarization is different from that which has been previously expected from the spectral index of the dust opacity coefficient (a millimeter or larger) if the emission is optically thin. We discuss that porous dust aggregates may solve the inconsistency of the maximum grain size between the two constraints

GRAIN SIZE CONSTRAINTS ON HL TAU WITH POLARIZATION SIGNATURE

Energy Technology Data Exchange (ETDEWEB)

Kataoka, Akimasa; Dullemond, Cornelis P [Zentrum für Astronomie der Universität Heidelberg, Institut für Theoretische Astrophysik, Albert-Ueberle-Str. 2, D-69120 Heidelberg (Germany); Muto, Takayuki [Division of Liberal Arts, Kogakuin University, 1-24-2 Nishi-Shinjuku, Shinjuku-ku, Tokyo 163-8677 (Japan); Momose, Munetake; Tsukagoshi, Takashi, E-mail: kataoka@uni-heidelberg.de [College of Science, Ibaraki University, 2-1-1 Bunkyo, Mito, Ibaraki 310-8512 (Japan)

2016-03-20

The millimeter-wave polarization of the protoplanetary disk around HL Tau has been interpreted as the emission from elongated dust grains aligned with the magnetic field in the disk. However, the self-scattering of thermal dust emission may also explain the observed millimeter-wave polarization. In this paper, we report a modeling of the millimeter-wave polarization of the HL Tau disk with the self-polarization. Dust grains are assumed to be spherical and to have a power-law size distribution. We change the maximum grain size with a fixed dust composition in a fixed disk model to find the grain size to reproduce the observed signature. We find that the direction of the polarization vectors and the polarization degree can be explained with the self-scattering. Moreover, the polarization degree can be explained only if the maximum grain size is ∼150 μm. The obtained grain size from the polarization is different from that which has been previously expected from the spectral index of the dust opacity coefficient (a millimeter or larger) if the emission is optically thin. We discuss that porous dust aggregates may solve the inconsistency of the maximum grain size between the two constraints.

A study on apoptotic signaling pathway in HL-60 cells induced by radiation

International Nuclear Information System (INIS)

Kim, Hye Jung; Moon, Sung Keun; Lee, Jae Hoon; Moon, Sun Rock

2001-01-01

The mechanical insights of death at cancer cells by ionizing radiation are not yet clearly defined. Recent evidences have demonstrated that radiation therapy may induce cell death via activation of signaling pathway for apoptosis in target cells. This study is designed whether ionizing radiation may activate the signaling cascades of apoptosis including caspase family cysteine proteases, Bcl2/Bax, cytochrome c and Fas/Fas-L in target cells. HL-60 cells were irradiated in vitro with 6 MV X-ray at dose ranges from 2 Gy to 32 Gy. The cell viability was tested by MTT assay and the extent of apoptosis was determined using agarose gel electrophoresis. The activities of caspase proteases were measured by proteolytic cleavages of substrates. Western blot analysis was used to monitor PARP, caspase-3, Cytochrome-c, BcI-2, Bax, Fas and Fas-L. Ionizing radiation decreases the viability of HL -60 cells in a time and dose dependent manner. Ionizing radiation-induced death in HL- 60 cells is an apoptotic death which is revealed as characteristic ladder-pattern fragmentation at genomic DNA over 16 Gy at 4 hours. Ionizing radiation induces the activation of caspase-2, 3, 6, 8 and 9 of HL --60 cells in a time-dependent manner. The activation of caspase- 3 protease is also evidenced by the digestion of poly (ADP-ribose) polymerase and procaspase 3 with 16Gy ionizing irradiation. Anti-apoptotic Bcl2 expression is decreased but apoptotic Bax expression is increased with mitochondrial cytochrome c release in a time- dependent manner. In addition, expression of Fas and Fas-L is also increased in a time dependent manner. These data suggest that ionizing radiation-induced apoptosis is mediated by the activation of various signaling pathways including caspase family cysteine proteases, BcI 2 /Bax, Fas and Fas-L in a time and dose dependent manner

JAK and MPL mutations in myeloid malignancies.

Science.gov (United States)

Tefferi, Ayalew

2008-03-01

The Janus family of non-receptor tyrosine kinases (JAK1, JAK2, JAK3 and tyrosine kinase 2) transduces signals downstream of type I and II cytokine receptors via signal transducers and activators of transcription (STATs). JAK3 is important in lymphoid and JAK2 in myeloid cell proliferation and differentiation. The thrombopoietin receptor MPL is one of several JAK2 cognate receptors and is essential for myelopoiesis in general and megakaryopoiesis in particular. Germline loss-of-function (LOF) JAK3 and MPL mutations cause severe combined immunodeficiency and congenital amegakaryocytic thrombocytopenia, respectively. Germline gain-of-function (GOF) MPL mutation (MPLS505N) causes familial thrombocytosis. Somatic JAK3 (e.g. JAK3A572V, JAK3V722I, JAK3P132T) and fusion JAK2 (e.g. ETV6-JAK2, PCM1-JAK2, BCR-JAK2) mutations have respectively been described in acute megakaryocytic leukemia and acute leukemia/chronic myeloid malignancies. However, current attention is focused on JAK2 (e.g. JAK2V617F, JAK2 exon 12 mutations) and MPL (e.g. MPLW515L/K/S, MPLS505N) mutations associated with myeloproliferative neoplasms (MPNs). A JAK2 mutation, primarily JAK2V617F, is invariably associated with polycythemia vera (PV). The latter mutation also occurs in the majority of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). MPL mutational frequency in MPNs is substantially less (<10%). In general, despite a certain degree of genotype - phenotype correlations, the prognostic relevance of harbouring one of these mutations, or their allele burden when present, remains dubious. Regardless, based on the logical assumption that amplified JAK-STAT signalling is central to the pathogenesis of PV, ET and PMF, several anti-JAK2 tyrosine kinase inhibitors have been developed and are currently being tested in humans with these disorders.

Enhancing Natural Killer Cell Mediated Targeting and Responses to Myeloid Leukemias

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-16-1-0380 TITLE: Enhancing Natural Killer Cell Mediated Targeting and Responses to Myeloid Leukemias PRINCIPAL...2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Enhancing Natural Killer Cell Mediated Targeting and Responses to Myeloid Leukemias 5b. GRANT NUMBER...leukemias still have poor prognosis, particularly in the elderly, and require hematopoietic cell transplants to fully kill the tumor, which is both

33 CFR 80.525 - Cape Lookout, NC to Cape Fear, NC.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Cape Lookout, NC to Cape Fear, NC... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Fifth District § 80.525 Cape Lookout, NC to Cape Fear... southeast side of the Inlet. (g) Except as provided elsewhere in this section from Cape Lookout to Cape Fear...

Neutral pressure measured by fast ionization gauge in HL-2A

International Nuclear Information System (INIS)

Wang, M.X.; Yan, L.W.; Hong, W.Y.; Cui, Z.Y.; Pan, Y.D.; Yao, L.H.; Cao, Z.; Yang, Q.W.; Liu, Y.

2007-01-01

A fast ionization gauge capable of working in a strong magnetic field and noisy environment is developed for the pressure measurement in the main chamber and the divertor chamber of the HL-2A tokamak. The neutral pressure in the main chamber evidently decreases after in-situ siliconization. Improvement of boundary plasma confinement is observed with SMBI or PI fueling after siliconization. The neutral pressure in the main chamber for divertor configuration is 50% lower than that for limiter one. The pressure in the divertor chamber rises when the strike point moves toward the bottom of the vertical target plates. The maximum pressure compression of is 24. The relative high pressure in the main chamber is contributed primarily by plasma limiter interaction due to the short distance from separatrix to limiter and secondly by neutral flux from the divertor chamber to the main chamber by leaks in HL-2A

Dual effect of LPS on murine myeloid leukemia cells: Pro-proliferation and anti-proliferation

International Nuclear Information System (INIS)

Yu, Lingling; Zhao, Yingmin; Gu, Xin; Wang, Jijun; Pang, Lei; Zhang, Yanqing; Li, Yaoyao; Jia, Xiaoqin; Wang, Xin; Gu, Jian; Yu, Duonan

2016-01-01

Modification of the bone marrow microenvironment is considered as a promising strategy to control leukemic cell proliferation, diseases progression and relapse after treatment. However, due to the diversity and complexity of the cellular and molecular compartments in the leukemic microenvironment, it is extremely difficult to dissect the role of each individual molecule or cell type in vivo. Here we established an in vitro system to dissect the role of lipopolysaccharide (LPS), stromal cells and endothelial cells in the growth of mouse myeloid tumor cells and B-lymphoma cells. We found that either LPS or bone marrow stromal cells as a feeder layer in culture is required for the proliferation of myeloid tumor cells. Surprisingly, the growth of myeloid leukemic cells on stromal cells is strongly inhibited when coupled with LPS in culture. This opposing effect of LPS, a complete switch from pro-proliferation to antitumor growth is due, at least in part, to the rapidly increased production of interleukin 12, Fas ligand and tissue inhibitor of metalloproteinases-2 from stromal cells stimulated by LPS. These results demonstrate that LPS can either facilitate or attenuate tumor cell proliferation, thus changing the disease course of myeloid leukemias through its direct effect or modulation of the tumor microenvironment. - Highlights: • LPS alone in culture is required for the proliferation of murine myeloid tumor cells. • Bone marrow stromal cells as a feeder layer is also required for the proliferation of myeloid tumor cells. • However, the growth of myeloid tumor cells is inhibited when LPS and stromal cells are both available in culture. • Thus LPS can either facilitate or attenuate tumor growth through its direct effect or modulation of tumor microenvironment.

Dual effect of LPS on murine myeloid leukemia cells: Pro-proliferation and anti-proliferation

Energy Technology Data Exchange (ETDEWEB)

Yu, Lingling [Department of Pediatrics, Jingjiang People' s Hospital, Yangzhou University, Jingjiang 214500 (China); Noncoding RNA Center, Yangzhou University, Yangzhou 225001 (China); Zhao, Yingmin [Department of Pediatrics, Jingjiang People' s Hospital, Yangzhou University, Jingjiang 214500 (China); Gu, Xin; Wang, Jijun; Pang, Lei; Zhang, Yanqing; Li, Yaoyao; Jia, Xiaoqin; Wang, Xin [Noncoding RNA Center, Yangzhou University, Yangzhou 225001 (China); Gu, Jian [Department of Hematology, Yangzhou University School of Clinical Medicine, Yangzhou 225001 (China); Yu, Duonan, E-mail: duonan@yahoo.com [Department of Pediatrics, Jingjiang People' s Hospital, Yangzhou University, Jingjiang 214500 (China); Noncoding RNA Center, Yangzhou University, Yangzhou 225001 (China); Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Disease, Yangzhou 225001 (China); Institute of Comparative Medicine, Yangzhou University, Yangzhou 225001 (China); Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonosis, Yangzhou 225001 (China)

2016-06-10

Modification of the bone marrow microenvironment is considered as a promising strategy to control leukemic cell proliferation, diseases progression and relapse after treatment. However, due to the diversity and complexity of the cellular and molecular compartments in the leukemic microenvironment, it is extremely difficult to dissect the role of each individual molecule or cell type in vivo. Here we established an in vitro system to dissect the role of lipopolysaccharide (LPS), stromal cells and endothelial cells in the growth of mouse myeloid tumor cells and B-lymphoma cells. We found that either LPS or bone marrow stromal cells as a feeder layer in culture is required for the proliferation of myeloid tumor cells. Surprisingly, the growth of myeloid leukemic cells on stromal cells is strongly inhibited when coupled with LPS in culture. This opposing effect of LPS, a complete switch from pro-proliferation to antitumor growth is due, at least in part, to the rapidly increased production of interleukin 12, Fas ligand and tissue inhibitor of metalloproteinases-2 from stromal cells stimulated by LPS. These results demonstrate that LPS can either facilitate or attenuate tumor cell proliferation, thus changing the disease course of myeloid leukemias through its direct effect or modulation of the tumor microenvironment. - Highlights: • LPS alone in culture is required for the proliferation of murine myeloid tumor cells. • Bone marrow stromal cells as a feeder layer is also required for the proliferation of myeloid tumor cells. • However, the growth of myeloid tumor cells is inhibited when LPS and stromal cells are both available in culture. • Thus LPS can either facilitate or attenuate tumor growth through its direct effect or modulation of tumor microenvironment.

BCR-ABL1 tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia.

Science.gov (United States)

Cuellar, Sandra; Vozniak, Michael; Rhodes, Jill; Forcello, Nicholas; Olszta, Daniel

2017-01-01

The management of chronic myeloid leukemia with BCR-ABL1 tyrosine kinase inhibitors has evolved chronic myeloid leukemia into a chronic, manageable disease. A patient-centered approach is important for the appropriate management of chronic myeloid leukemia and optimization of long-term treatment outcomes. The pharmacist plays a key role in treatment selection, monitoring drug-drug interactions, identification and management of adverse events, and educating patients on adherence. The combination of tyrosine kinase inhibitors with unique safety profiles and individual patients with unique medical histories can make managing treatment difficult. This review will provide up-to-date information regarding tyrosine kinase inhibitor-based treatment of patients with chronic myeloid leukemia. Management strategies for adverse events and considerations for drug-drug interactions will not only vary among patients but also across tyrosine kinase inhibitors. Drug-drug interactions can be mild to severe. In instances where co-administration of concomitant medications cannot be avoided, it is critical to understand how drug levels are impacted and how subsequent dose modifications ensure therapeutic drug levels are maintained. An important component of patient-centered management of chronic myeloid leukemia also includes educating patients on the significance of early and regular monitoring of therapeutic milestones, emphasizing the importance of adhering to treatment in achieving these targets, and appropriately modifying treatment if these clinical goals are not being met. Overall, staying apprised of current research, utilizing the close pharmacist-patient relationship, and having regular interactions with patients, will help achieve successful long-term treatment of chronic myeloid leukemia in the age of BCR-ABL1 tyrosine kinase inhibitors.

Genes encoded within 8q24 on the amplicon of a large extrachromosomal element are selectively repressed during the terminal differentiation of HL-60 cells

OpenAIRE

Hirano, Tetsuo; Ike, Fumio; Murata, Takehide; Obata, Yuichi; Utiyama, Hiroyasu; Yokoyama, Kazunari K.

2008-01-01

Human acute myeloblastic leukemia HL-60 cells become resistant to differentiation during long­term cultivation. After 150 passages, double minute chromosomes (dmins) found in early­-passaged cells are replaced by large extrachromosomal elements (LEEs). In a DNA library derived from a purified fraction of LEEs, 12.6% (23/183) of clones were assigned to 8q24 and 9.2% (17/183) were assigned to 14q11 in the human genome. Fluorescence in situ hybridization (FISH) revealed a small aberrant chromos...

The molecular biology of radiation-induced carcinogenesis: thymic lymphoma, myeloid leukaemia and osteosarcoma

Energy Technology Data Exchange (ETDEWEB)

Janowski, M [Centre d' Etude de l' Energie Nucleaire, Mol (Belgium); Cox, R [Medical Research Council, Harwell (UK). Radiobiological Research Unit; Strauss, P G [GSF, Neuherberg (Germany, F.R.). Abt. fuer Molekulare Zellpathologie

1990-04-01

In mice, external X- or {gamma}-irradiation may induce thymic lymphomas or myeloid leukaemias, while bone-seeking {alpha}-emitters may induce osteosarcomas, and to a lesser extent acute myeloid leukaemia. The paper reviews briefly some experimental data in respect to molecular mechanisms underlying these radio-carcinogenic processes. Thymic lymphomagenesis proceeds by an indirect mechanism in which recombinant proviruses could be involved. Myeloid leukaemogenesis is characterized by a very early putative initiating event, consisting of non-random rearrangements and/or deletions of chromosome 2. Osteosarcomagenesis in mice is often associated with the expression of proviruses, and the tumors often contain somatically acquired proviruses. (UK).

Modifying factors of radiation induced myeloid leukemia of C3H/He mouse

International Nuclear Information System (INIS)

Yoshida, Kazuko; Nishimura, Mayumi; Nemoto, Kumie; Seki, Masatoshi

1989-01-01

The first experiment examined modifying factors, such as adrenocortical hormones, inflammatory reaction, and surgical stress, for radiation induced myeloid leukemia in C3H/He mice. The incidence of myeloid leukemia was not affected by a solitary subcutaneous injection of one mg of prednisolone acetate (predonine), but increased significantly by whole body irradiation, immediately followed by predonine. Augumentated effects of predonine was found in the 0.47 Gy, 1.42 Gy, and 2.84 Gy irradiated groups, but not found in the 4.73 Gy irradiated group. These results suggest that predonine itself did not have any effect on initiation of leukemogenesis, but promoted the incidence of radiation-induced myeloid leukemia. In the next experiment determining whether the incidence of myeloid leukemia was increased with stimulation of hematopoietic tissues, mice were inserted a piece of cellulose acetate membrane (CAM) into the peritoneal cavity. In the non-irradiated group of mice, CAM insertion did not affect the incidence of myeloid leukemia at all. The incidence of leukemia increased significantly by CAM insertion combined with irradiation of 2.84 Gy. Mice suffered from both surgical stress and inflammatory reaction after CAM insertion. Therefore, surgical stress was considered responsible for the development of radiation-induced leukemia. (Namekawa, K)

Involvement of the histamine H{sub 4} receptor in clozapine-induced hematopoietic toxicity: Vulnerability under granulocytic differentiation of HL-60 cells

Energy Technology Data Exchange (ETDEWEB)

Goto, Aya; Mouri, Akihiro; Nagai, Tomoko; Yoshimi, Akira; Ukigai, Mako; Tsubai, Tomomi; Hida, Hirotake [Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503 (Japan); Ozaki, Norio [Department of Psychiatry, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Noda, Yukihiro, E-mail: ynoda@meijo-u.ac.jp [Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503 (Japan)

2016-09-01

Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but can cause fatal hematopoietic toxicity as agranulocytosis. To elucidate the mechanism of hematopoietic toxicity induced by clozapine, we developed an in vitro assay system using HL-60 cells, and investigated the effect on hematopoiesis. HL-60 cells were differentiated by all-trans retinoic acid (ATRA) into three states according to the following hematopoietic process: undifferentiated HL-60 cells, those undergoing granulocytic ATRA-differentiation, and ATRA-differentiated granulocytic cells. Hematopoietic toxicity was evaluated by analyzing cell survival, cell proliferation, granulocytic differentiation, apoptosis, and necrosis. In undifferentiated HL-60 cells and ATRA-differentiated granulocytic cells, both clozapine (50 and 100 μM) and doxorubicin (0.2 µM) decreased the cell survival rate, but olanzapine (1–100 µM) did not. Under granulocytic differentiation for 5 days, clozapine, even at a concentration of 25 μM, decreased survival without affecting granulocytic differentiation, increased caspase activity, and caused apoptosis rather than necrosis. Histamine H{sub 4} receptor mRNA was expressed in HL-60 cells, whereas the expression decreased under granulocytic ATRA-differentiation little by little. Both thioperamide, a histamine H{sub 4} receptor antagonist, and DEVD-FMK, a caspase-3 inhibitor, exerted protection against clozapine-induced survival rate reduction, but not of live cell counts. 4-Methylhistamine, a histamine H{sub 4} receptor agonist, decreased the survival rate and live cell counts, as did clozapine. HL-60 cells under granulocytic differentiation are vulnerable under in vitro assay conditions to hematopoietic toxicity induced by clozapine. Histamine H{sub 4} receptor is involved in the development of clozapine-induced hematopoietic toxicity through apoptosis, and may be a potential target for preventing its occurrence through granulocytic differentiation

Upgrade Plans for ATLAS Forward Calorimetry for the HL-LHC

CERN Document Server

Krieger, P; The ATLAS collaboration

2013-01-01

The ATLAS detector was designed and built to study proton-proton (pp) collisions produced by the Large Hadron Collider (LHC) at centre-of-mass energies up to 14 TeV and instantaneous luminosities up to $10^{34}{\\rm cm}^{-2}{\\rm s}^{-1}$. At the higher instantaneous luminosity ($5\\times 10^{34}{\\rm cm}^{-2}{\\rm s}^{-1}$) proposed for the High-Luminosity LHC (HL-LHC), some components of ATLAS will not operate properly, while others may not survive the dose that will be accumulated while collecting the proposed 3000 fb$^{-1}$ of pp collision data. For the ATLAS liquid argon (LAr) calorimeter, problems are anticipated in the forward region where the particle flux is particularly high. The existing Forward Calorimeter (FCal) was designed with very narrow LAr gaps (250-500 $\\mu$m) in order to avoid problems due to ion build-up that would distort the electric field. At HL-LHC luminosities, these gaps are no longer sufficiently narrow. The resulting distortions of the electric field in the gaps would be exacerbated b...

Upgrade of the ATLAS Muon Barrel Trigger for HL-LHC

CERN Document Server

Romano, Marino; The ATLAS collaboration

2015-01-01

The present ATLAS muon trigger in the barrel region (|eta|<1.05) is based on three layers of RPC chambers. It was designed to run for 10 years at the LHC luminosity of 10^{34} cm^{-2}s^{-1} and operated successfully and with high selectivity during the first run of the LHC. In order to ensure a stable performance of the RPCs until 2035 at the higher rates and at luminosities of 5-7x10^{34} cm^{-2}s^{-1} provided by HL-LHC, the chambers will have to be operated with reduced gas gain to respect the original design limits on currents and integrated charge. The ATLAS muon collaboration proposes an upgrade of the system by installing an inner layer of new generation RPCs during the LHC shutdown expected for the year 2023. This new layer will increase the system redundancy and therefore allow operation with high efficiency and high selectivity during the HL-LHC phase. The insertion of this new layer will also increase the geometrical acceptance in the barrel region from 75% to 95%. Moreover, the additional measu...

Upgrade of the ATLAS Muon Barrel Trigger for HL-LHC.

CERN Document Server

Biondi, Silvia; The ATLAS collaboration

2015-01-01

The present ATLAS muon trigger in the barrel region (|η | < 1.05) is based on three layers of RPC chambers. It was designed to run for 10 years at the LHC luminosity of 1034cm−2s−1 and operated successfully and with high selectivity during the first run of the LHC. In order to ensure a stable performance of the RPCs until 2035 at the higher rates and at luminosities of 5−7x1034cm−2s−1 provided by HL-LHC, the chambers will have to be operated with reduced gas gain to respect the original design limits on currents and integrated charge. The ATLAS muon collaboration proposes an upgrade of the system by installing an inner layer of new generation RPCs during the LHC shutdown expected for the year 2023. This new layer will increase the system redundancy and therefore allow operation with high efficiency and high selectivity during the HL-LHC phase. The insertion of this new layer will also increase the geometrical acceptance in the barrel region from 75% to 95%. Moreover, the additional measurements ...

Breaching the Phase I Optics Limitations for the HL-LHC

CERN Document Server

Fartoukh, S

2011-01-01

This paper scrutinizes the performance goal of the HL-LHC Project and proposes a solution to reach it. This solution is based on an Achromatic Telescopic Squeezing (ATS) principle which can push beta* well below the limits which were identified in the context of the so-called Phase I Upgrade studies. The novel optics scheme is described, with its main weak points, possible mitigation measures and hardware modifications needed in the LHC ring in order to implement it. Other implications or by-products are also highlighted. Some of them are rather exotic and are worth to be mentioned in the abstract even if not completely developed in the paper: the possibility to run with a third low-beta experiment installed in IR3 or IR7 (which is an interesting direction for a smooth co-habitation between the HL-LHC and the LHeC), a notable reduction of the IBS growth rate in the longitudinal plane (generally the most critical plane), or a boost by more than one order of magnitude for the efficiency of the Landau octupoles,...

Breaching the Phase I optics limitations for the HL-LHC

CERN Document Server

Fartoukh, S

2011-01-01

This paper scrutinizes the performance goal of the HL-LHC Project and proposes a solution to reach it. This solution is based on an Achromatic Telescopic Squeezing (ATS) principle which can push β ∗ well below the limits which were identified in the context of the so-called Phase I Upgrade studies. The novel optics scheme is described, with its main weak points, possible mitigation measures and hardware modifications needed in the LHC ring in order to implement it. Other implications or by-products are also highlighted. Some of them are rather exotic and are worth to be mentioned in the abstract even if not completely developed in the paper: the possibility to run with a third low-β experiment installed in IR3 or IR7 (which is an interesting direction for a smooth co-habitation between the HL-LHC and the LHeC), a notable reduction of the IBS growth rate in the longitudinal plane (generally the most critical plane), or a boost by more than one order of magnitude for the efficiency of the Landau octupoles, ...

Expected performance of the upgrade ATLAS experiment for HL-LHC

CERN Document Server

Liu, Peilian; The ATLAS collaboration

2018-01-01

The Large Hadron Collider (LHC) has been successfully delivering proton-proton collision data at the unprecedented center of mass energy of 13 TeV. An upgrade is planned to increase the instantaneous luminosity delivered by the LHC in what is called the HL-LHC, aiming to deliver a total of up 3000/fb to 4000/fb of data per experiment. To cope with the expected data-taking conditions ATLAS is planning major upgrades of the detector. It is now a critical time for these upgrade projects and during the last year and a half, six Technical Design Reports (TDR) were produced by the ATLAS Collaboration. In these TDRs the physics motivation and benefits of such upgrades are discussed together with details on the upgrade project itself. In this contribution we review the expected performance of the upgraded ATLAS detector and the expected reach for physics measurements as well as the discovery potential for new physics that is expected by the end of the HL-LHC data-taking. The performance of object reconstruction under...

Upgrade plans for ATLAS Forward Calorimetry for the HL-LHC

CERN Document Server

Turner, J; The ATLAS collaboration

2011-01-01

Even though data taking has just started with the LHC, plans are being developed to operate the machine and its detectors at up to 10 times the original design luminosity. This has an impact on many components of the ATLAS detector, particularly the Forward calorimeter, which is exposed to some of the highest radiation rates in ATLAS. The FCal detector and its associated components were designed for operation at the maximum LHC luminosity of 1034 cm2s-1. However at the higher luminosities (HL), which are projected for the HL-LHC, operation of the FCal will be compromised. Beam heating in the FCal which is located on a liquid argon filled cryostat could lead to the formation of argon bubbles in the detector, the ionization rate will result in space charge effects that will reduce the signal and the current draw will result in a voltage drop across the HV current limiting resistors. The space charge and ionization rates will result in the FCal becoming insensitive to particles at its inner edge and the insensit...

Upgrade Plans for ATLAS Forward Calorimetry for the HL-LHC

CERN Document Server

Turner, J

2012-01-01

Even though data-taking has just started with the LHC, plans are being developed to operate the machine and its detectors at up to 10 times the original design luminosity. This has a major impact on the Forward Calorimeter (FCal), which is exposed to some of the highest radiation rates in ATLAS. The FCal detector and its associated components were designed for operation at the maximum LHC luminosity of \\(\\text{10}^{\\text{34}} \\text{ cm}^{-2}\\text{s}^{-1}\\). However at the higher luminosities projected for the HL-LHC, operation of the FCal may be compromised. Beam heating in the FCal could lead to the formation of argon bubbles in the detector, the ionization rate will result in space charge effects that will reduce the signal and the current draw will result in a voltage drop across the HV current limiting resistors. Two possible solutions are being considered to maintain FCal operation at HL-LHC. One is a complete replacement of the FCal system. A replacement FCal would have a similar design to the current c...

Upgrade Plans for ATLAS Forward Calorimetry for the HL-LHC

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