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Sample records for chromium-induced growth arrest

  1. Bypass of hexavalent chromium-induced growth arrest by a protein tyrosine phosphatase inhibitor: Enhanced survival and mutagenesis

    International Nuclear Information System (INIS)

    Although the consequences of genotoxic injury include cell cycle arrest and apoptosis, cell survival responses after genotoxic injury can produce intrinsic death-resistance and contribute to the development of a transformed phenotype. Protein tyrosine phosphatases (PTPs) are integral components of key survival pathways, and are responsible for their inactivation, while PTP inhibition is often associated with enhanced cell proliferation. Our aim was to elucidate signaling events that modulate cell survival after genotoxin exposure. Diploid human lung fibroblasts (HLF) were treated with Cr(VI) (as Na2CrO4), the soluble oxyanionic dissolution product of certain particulate chromates, which are well-documented human respiratory carcinogens. In vitro soluble Cr(VI) induces a wide spectrum of DNA damage, in both the presence and absence of a broad-range PTP inhibitor, sodium orthovanadate (SOV). Notably, SOV abrogated Cr(VI)-induced clonogenic lethality. The enhanced survival of Cr(VI)-exposed cells after SOV treatment was predominantly due to a bypass of cell cycle arrest, as there was no effect of the PTP inhibitor on Cr-induced apoptosis. Moreover, the SOV effect was not due to decreased Cr uptake as evidenced by unchanged Cr-DNA adduct burden. Additionally, the bypass of Cr-induced growth arrest by SOV was accompanied by a decrease in Cr(VI)-induced expression of cell cycle inhibiting genes, and an increase in Cr(VI)-induced expression of cell cycle promoting genes. Importantly, SOV resulted in an increase in forward mutations at the HPRT locus, supporting the hypothesis that PTP inhibition in the presence of certain types of DNA damage may lead to increased genomic instability, via bypass of cell cycle checkpoints

  2. Bypass of hexavalent chromium-induced growth arrest by a protein tyrosine phosphatase inhibitor: Enhanced survival and mutagenesis

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Dongsoon; Camilli, Tura C. [Department of Pharmacology and Physiology, George Washington University Medical Center, Washington, DC (United States); Chun, Gina; Lal, Madhu; Wright, Kristen [Department of Pharmacology and Physiology, George Washington University Medical Center, Washington, DC (United States); Program in Molecular Medicine, George Washington University Medical Center, Washington, DC (United States); O' Brien, Travis J. [Department of Pharmacology and Physiology, George Washington University Medical Center, Washington, DC (United States); Program in Molecular Medicine, George Washington University Medical Center, Washington, DC (United States); GW Cancer Institute, George Washington University Medical Center, Washington, DC (United States); Patierno, Steven R. [Department of Pharmacology and Physiology, George Washington University Medical Center, Washington, DC (United States); Department of Medicine, George Washington University Medical Center, Washington, DC (United States); Program in Molecular Medicine, George Washington University Medical Center, Washington, DC (United States); GW Cancer Institute, George Washington University Medical Center, Washington, DC (United States); Ceryak, Susan [Department of Pharmacology and Physiology, George Washington University Medical Center, Washington, DC (United States); Department of Medicine, George Washington University Medical Center, Washington, DC (United States); Program in Molecular Medicine, George Washington University Medical Center, Washington, DC (United States); GW Cancer Institute, George Washington University Medical Center, Washington, DC (United States)], E-mail: phmsmc@gwumc.edu

    2009-01-15

    Although the consequences of genotoxic injury include cell cycle arrest and apoptosis, cell survival responses after genotoxic injury can produce intrinsic death-resistance and contribute to the development of a transformed phenotype. Protein tyrosine phosphatases (PTPs) are integral components of key survival pathways, and are responsible for their inactivation, while PTP inhibition is often associated with enhanced cell proliferation. Our aim was to elucidate signaling events that modulate cell survival after genotoxin exposure. Diploid human lung fibroblasts (HLF) were treated with Cr(VI) (as Na{sub 2}CrO{sub 4}), the soluble oxyanionic dissolution product of certain particulate chromates, which are well-documented human respiratory carcinogens. In vitro soluble Cr(VI) induces a wide spectrum of DNA damage, in both the presence and absence of a broad-range PTP inhibitor, sodium orthovanadate (SOV). Notably, SOV abrogated Cr(VI)-induced clonogenic lethality. The enhanced survival of Cr(VI)-exposed cells after SOV treatment was predominantly due to a bypass of cell cycle arrest, as there was no effect of the PTP inhibitor on Cr-induced apoptosis. Moreover, the SOV effect was not due to decreased Cr uptake as evidenced by unchanged Cr-DNA adduct burden. Additionally, the bypass of Cr-induced growth arrest by SOV was accompanied by a decrease in Cr(VI)-induced expression of cell cycle inhibiting genes, and an increase in Cr(VI)-induced expression of cell cycle promoting genes. Importantly, SOV resulted in an increase in forward mutations at the HPRT locus, supporting the hypothesis that PTP inhibition in the presence of certain types of DNA damage may lead to increased genomic instability, via bypass of cell cycle checkpoints.

  3. Chromium-induced modulation in the antioxidant defense system during phenological growth stages of Indian mustard.

    Science.gov (United States)

    Diwan, Hema; Ahmad, Altaf; Iqbal, Muhammad

    2010-02-01

    Chromium-induced modulation in the enzymes and metabolites of antioxidants was investigated at various phenological stages of Indian mustard (Brassica juncea (L.) Czern. & Coss. cv Pusa Jai Kisan)], grown with various levels of chromium (Cr) in pots under natural environmental conditions. Chromium accumulation in the root, stem and leaves increased with the advancement in the age of the plants. Growth of Indian mustard was not affected significantly by the supply of Cr up to the levels of 400 mg kg(-1) soil. Activities of superoxide dismutase (SOD), ascorbate peroxide (APX), catalase (CAT), and glutathione reductase (GR) increased in the leaves of Cr-treated plants, when compared with control. High activities of antioxidant enzymes supported by high Cr concentrations in roots and aerial parts (except seeds) established the Indian mustard as a potential hyperaccumulator anda hypertolerant species to Cr stress. For this study, an edible crop was chosen intentionally so as to tap maximum benefit by remediating the contaminated site on one hand and getting uncontaminated seeds to raise the next generation, on the other. PMID:20734612

  4. Growth arrest specific protein (GAS) 6

    DEFF Research Database (Denmark)

    Haase, T N; Rasmussen, Morten; Jaksch, C A M; Gaarn, L W; Petersen, Camilla K; Billestrup, N; Nielsen, Jens Høiriis

    2013-01-01

    Aims/hypothesis Maternal low-protein (LP) diet during gestation results in a reduced beta cell mass in the offspring at birth and this may hamper the ability to adapt to high-energy food and sedentary lifestyle later in life. To investigate the biology behind the LP-offspring phenotype, this study...... using RNA microarray and quantitative PCR. The role of a differentially expressed gene, growth arrest specific protein 6 (GAS6), was evaluated in vitro using neonatal rat islets. Results The mRNA level of Gas6, known to be mitogenic in other tissues, was reduced in LP offspring. The mRNA content of Mafa...... was increased in LP offspring suggesting an early maturation of beta cells. When applied in vitro, GAS6 increased proliferation of neonatal pancreatic beta cells, while reducing glucose-stimulated insulin secretion without changing the total insulin content of the islets. In addition, GAS6 decreased...

  5. MRI in the assessment of growth arrest

    Energy Technology Data Exchange (ETDEWEB)

    Lohman, Martina; Kivisaari, Arto; Kivisaari, Leena [Helsinki Univ. Central Hospital (Finland). Dept. of Radiology; Vehmas, Tapio [Finnish Institute of Occupational Health, Helsinki (Finland); Kallio, Pentti; Puntila, Juha [Department of Paediatric Surgery, Hospital for Children and Adolescents, University Central Hospital, Helsinki (Finland)

    2002-01-01

    Objective: To compare MRI with X-ray tomography in the assessment of bone bridges across the growth plate. Materials and methods: The investigation consisted of two parts. (1) Eleven children with 13 epiphyses suspected of physeal growth arrests were examined with conventional X-ray tomography and MRI. The bar was post-traumatic in eight children, postinfectious in two and due to a congenital, operated pes equinovarus in one. Three blinded radiologists separately evaluated the examinations retrospectively. (2) The images of four children with known physeal bars in the ankle were mixed with 36 normal examinations obtained 1-year after trauma and evaluated blindly by three radiologists. Results: In 5 of 13 epiphysis, the bony bridge was considered smaller on MRI than on X-ray tomography, in 7 of 13 it was considered equal, while it was larger only in one. The interobserver agreement (weighted kappa) was 0.8 (very good) for MRI, 0.76 (good) for X-ray tomography and 0.60 (moderate) for radiographs. The four bony bridges were easily detected on MRI. Conclusions: Compared to MRI, the size of bridges was estimated larger by tomography in about half of the patients. (orig.)

  6. Paclitaxel Arrests Growth of Intracellular Toxoplasma gondii

    OpenAIRE

    Estes, Randee; Vogel, Nicolas; Mack, Douglas; McLeod, Rima

    1998-01-01

    Addition of paclitaxel (Taxol) at a concentration of 1 μM to Toxoplasma gondii-infected human foreskin fibroblasts arrested parasite multiplication. Division of the T. gondii tachyzoite nucleus was inhibited, leading to syncytium-like parasite structures within the fibroblasts by 24 h after infection and treatment of the cultures. By 4 days after infection and treatment of the cultures with paclitaxel, this inhibition was irreversible, since the arrested intracellular form was incapable of le...

  7. Cellular Growth Arrest and Persistence from Enzyme Saturation

    Science.gov (United States)

    Ray, J. Christian J.; Wickersheim, Michelle L.; Jalihal, Ameya P.; Adeshina, Yusuf O.; Cooper, Tim F.; Balázsi, Gábor

    2016-01-01

    Metabolic efficiency depends on the balance between supply and demand of metabolites, which is sensitive to environmental and physiological fluctuations, or noise, causing shortages or surpluses in the metabolic pipeline. How cells can reliably optimize biomass production in the presence of metabolic fluctuations is a fundamental question that has not been fully answered. Here we use mathematical models to predict that enzyme saturation creates distinct regimes of cellular growth, including a phase of growth arrest resulting from toxicity of the metabolic process. Noise can drive entry of single cells into growth arrest while a fast-growing majority sustains the population. We confirmed these predictions by measuring the growth dynamics of Escherichia coli utilizing lactose as a sole carbon source. The predicted heterogeneous growth emerged at high lactose concentrations, and was associated with cell death and production of antibiotic-tolerant persister cells. These results suggest how metabolic networks may balance costs and benefits, with important implications for drug tolerance. PMID:27010473

  8. Total triterpenoids from Ganoderma Lucidum suppresses prostate cancer cell growth by inducing growth arrest and apoptosis.

    Science.gov (United States)

    Wang, Tao; Xie, Zi-ping; Huang, Zhan-sen; Li, Hao; Wei, An-yang; Di, Jin-ming; Xiao, Heng-jun; Zhang, Zhi-gang; Cai, Liu-hong; Tao, Xin; Qi, Tao; Chen, Di-ling; Chen, Jun

    2015-10-01

    In this study, one immortalized human normal prostatic epithelial cell line (BPH) and four human prostate cancer cell lines (LNCaP, 22Rv1, PC-3, and DU-145) were treated with Ganoderma Lucidum triterpenoids (GLT) at different doses and for different time periods. Cell viability, apoptosis, and cell cycle were analyzed using flow cytometry and chemical assays. Gene expression and binding to DNA were assessed using real-time PCR and Western blotting. It was found that GLT dose-dependently inhibited prostate cancer cell growth through induction of apoptosis and cell cycle arrest at G1 phase. GLT-induced apoptosis was due to activation of Caspases-9 and -3 and turning on the downstream apoptotic events. GLT-induced cell cycle arrest (mainly G1 arrest) was due to up-regulation of p21 expression at the early time and down-regulation of cyclin-dependent kinase 4 (CDK4) and E2F1 expression at the late time. These findings demonstrate that GLT suppresses prostate cancer cell growth by inducing growth arrest and apoptosis, which might suggest that GLT or Ganoderma Lucidum could be used as a potential therapeutic drug for prostate cancer. PMID:26489631

  9. Growth arrest and differentiation-associated phosphoproteins in mesenchymal stem cells

    International Nuclear Information System (INIS)

    Cancer is thought to result from the expression of defects in the control of both cell proliferation and differentiation. In murine mesenchymal stem cells they have established that differentiation and proliferation can be mediated at a variety of distinct states in the G1 phase of the cell cycle. In order to evaluate the role of cellular phosphoprotein (PP) expression in these regulatory processes, five different growth and differentiation-dependent states were compared. Cells in the following states were studied: (1) exponential growth; (2) arrest in serum-deficient medium; (3) arrest at the predifferentiation arrest state; (4) arrest at a state of nonterminal differentiation; and (5) arrest at a state of terminal differentiation. Whole cell lysates from each group were phosphorylated in vitro using [γ-32P]ATP and analyzed by SDS-polyacrylamide gel electrophoresis. Two most interesting observations were established. First, a distinct PP with a molecular weight of 37 kD was expressed in all growth arrested cells but was not evident in rapidly growing cells. Second, two distinct differentiation-associated PP with molecular weights of 72 kD and 29 kD were expressed exclusively in nonterminally and terminally differentiated cells. Since the identification of the 37 kD cell cycle-dependent growth arrest-associated PP could be of great significance, they plan to further investigate the functional role of this phosphoprotein in the control of cellular proliferation

  10. The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line

    DEFF Research Database (Denmark)

    Suzuki, Harukazu; Forrest, Alistair R R; van Nimwegen, Erik;

    2009-01-01

    Using deep sequencing (deepCAGE), the FANTOM4 study measured the genome-wide dynamics of transcription-start-site usage in the human monocytic cell line THP-1 throughout a time course of growth arrest and differentiation. Modeling the expression dynamics in terms of predicted cis-regulatory sites...

  11. Gene expression signature in organized and growth arrested mammaryacini predicts good outcome in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fournier, Marcia V.; Martin, Katherine J.; Kenny, Paraic A.; Xhaja, Kris; Bosch, Irene; Yaswen, Paul; Bissell, Mina J.

    2006-02-08

    To understand how non-malignant human mammary epithelial cells (HMEC) transit from a disorganized proliferating to an organized growth arrested state, and to relate this process to the changes that occur in breast cancer, we studied gene expression changes in non-malignant HMEC grown in three-dimensional cultures, and in a previously published panel of microarray data for 295 breast cancer samples. We hypothesized that the gene expression pattern of organized and growth arrested mammary acini would share similarities with breast tumors with good prognoses. Using Affymetrix HG-U133A microarrays, we analyzed the expression of 22,283 gene transcripts in two HMEC cell lines, 184 (finite life span) and HMT3522 S1 (immortal non-malignant), on successive days post-seeding in a laminin-rich extracellular matrix assay. Both HMECs underwent growth arrest in G0/G1 and differentiated into polarized acini between days 5 and 7. We identified gene expression changes with the same temporal pattern in both lines. We show that genes that are significantly lower in the organized, growth arrested HMEC than in their proliferating counterparts can be used to classify breast cancer patients into poor and good prognosis groups with high accuracy. This study represents a novel unsupervised approach to identifying breast cancer markers that may be of use clinically.

  12. p53-Induced Growth Arrest Is Regulated by the Mitochondrial SirT3 Deacetylase

    OpenAIRE

    SiDe Li; Michaela Banck; Shiraz Mujtaba; Ming-Ming Zhou; Mary M Sugrue; Walsh, Martin J

    2010-01-01

    A hallmark of p53 function is to regulate a transcriptional program in response to extracellular and intracellular stress that directs cell cycle arrest, apoptosis, and cellular senescence. Independent of the role of p53 in the nucleus, some of the anti-proliferative functions of p53 reside within the mitochondria [1]. p53 can arrest cell growth in response to mitochondrial p53 in an EJ bladder carcinoma cell environment that is naïve of p53 function until induced to express p53 [2]. TP53 can...

  13. Withaferin-A induces mitotic catastrophe and growth arrest in prostate cancer cells

    OpenAIRE

    Roy, Ram V; Suman, Suman; Das, Trinath P; Luevano, Joe; Damodaran, Chendil

    2013-01-01

    Cell cycle deregulation is strongly associated with the pathogenesis of prostate cancer (CaP). Clinical trials of cell cycle regulators that target either the G0/G1 or G2/M phase to inhibit the growth of cancers including CaP are increasing. In this study, we determined the cell-cycle regulatory potential of the herbal molecule Withaferin-A (WA) on CaP cells. WA induced irreversible G2/M arrest in both CaP cell lines (PC3 and DU145) for 48 h. The G2/M arrest was accompanied by upregulation of...

  14. Prolyl oligopeptidase inhibition-induced growth arrest of human gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Kanayo [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Sakaguchi, Minoru, E-mail: sakaguti@gly.oups.ac.jp [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Tanaka, Satoshi [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Yoshimoto, Tadashi [Department of Life Science, Setsunan University, 17-8 Ikeda-Nakamachi, Neyagawa, Osaka 572-8508 (Japan); Takaoka, Masanori [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan)

    2014-01-03

    Highlights: •We examined the effects of prolyl oligopeptidase (POP) inhibition on p53 null gastric cancer cell growth. •POP inhibition-induced cell growth suppression was associated with an increase in a quiescent G{sub 0} state. •POP might regulate the exit from and/or reentry into the cell cycle. -- Abstract: Prolyl oligopeptidase (POP) is a serine endopeptidase that hydrolyzes post-proline peptide bonds in peptides that are <30 amino acids in length. We recently reported that POP inhibition suppressed the growth of human neuroblastoma cells. The growth suppression was associated with pronounced G{sub 0}/G{sub 1} cell cycle arrest and increased levels of the CDK inhibitor p27{sup kip1} and the tumor suppressor p53. In this study, we investigated the mechanism of POP inhibition-induced cell growth arrest using a human gastric cancer cell line, KATO III cells, which had a p53 gene deletion. POP specific inhibitors, 3-((4-[2-(E)-styrylphenoxy]butanoyl)-L-4-hydroxyprolyl)-thiazolidine (SUAM-14746) and benzyloxycarbonyl-thioprolyl-thioprolinal, or RNAi-mediated POP knockdown inhibited the growth of KATO III cells irrespective of their p53 status. SUAM-14746-induced growth inhibition was associated with G{sub 0}/G{sub 1} cell cycle phase arrest and increased levels of p27{sup kip1} in the nuclei and the pRb2/p130 protein expression. Moreover, SUAM-14746-mediated cell cycle arrest of KATO III cells was associated with an increase in the quiescent G{sub 0} state, defined by low level staining for the proliferation marker, Ki-67. These results indicate that POP may be a positive regulator of cell cycle progression by regulating the exit from and/or reentry into the cell cycle by KATO III cells.

  15. Physeal growth arrest after tibial lengthening in achondroplasia

    OpenAIRE

    Song, Sang-Heon; Agashe, Mandar Vikas; Huh, Young-Jae; Hwang, Soon-Young; Song, Hae-Ryong

    2012-01-01

    Background and purpose Bilateral tibial lengthening has become one of the standard treatments for upper segment-lower segment disproportion and to improve quality of life in achondroplasia. We determined the effect of tibial lengthening on the tibial physis and compared tibial growth that occurred at the physis with that in non-operated patients with acondroplasia. Methods We performed a retrospective analysis of serial radiographs until skeletal maturity in 23 achondroplasia patients who und...

  16. Somatostatin receptor-1 induces cell cycle arrest and inhibits tumor growth in pancreatic cancer.

    Science.gov (United States)

    Li, Min; Wang, Xiaochi; Li, Wei; Li, Fei; Yang, Hui; Wang, Hao; Brunicardi, F Charles; Chen, Changyi; Yao, Qizhi; Fisher, William E

    2008-11-01

    Functional somatostatin receptors (SSTR) are lost in human pancreatic cancer. Transfection of SSTR-1 inhibited pancreatic cancer cell proliferation in vitro. We hypothesize that stable transfection of SSTR-1 may inhibit pancreatic cancer growth in vivo possibly through cell cycle arrest. In this study, we examined the expression of SSTR-1 mRNA in human pancreatic cancer tissue specimens, and investigated the effect of SSTR-1 overexpression on cell proliferation, cell cycle, and tumor growth in a subcutaneous nude mouse model. We found that SSTR-1 mRNA was downregulated in the majority of pancreatic cancer tissue specimens. Transfection of SSTR-1 caused cell cycle arrest at the G(0)/G(1) growth phase, with a corresponding decline of cells in the S (mitotic) phase. The overexpression of SSTR-1 significantly inhibited subcutaneous tumor size by 71% and 43% (n = 5, P < 0.05, Student's t-test), and inhibited tumor weight by 69% and 47% (n = 5, P < 0.05, Student's t-test), in Panc-SSTR-1 and MIA-SSTR-1 groups, respectively, indicating the potent inhibitory effect of SSTR-1 on pancreatic cancer growth. Our data demonstrate that overexpression of SSTR-1 significantly inhibits pancreatic cancer growth possibly through cell cycle arrest. This study suggests that gene therapy with SSTR-1 may be a potential adjuvant treatment for pancreatic cancer. PMID:18823376

  17. Physeal growth arrest after tibial lengthening in achondroplasia

    Science.gov (United States)

    2012-01-01

    Background and purpose Bilateral tibial lengthening has become one of the standard treatments for upper segment-lower segment disproportion and to improve quality of life in achondroplasia. We determined the effect of tibial lengthening on the tibial physis and compared tibial growth that occurred at the physis with that in non-operated patients with acondroplasia. Methods We performed a retrospective analysis of serial radiographs until skeletal maturity in 23 achondroplasia patients who underwent bilateral tibial lengthening before skeletal maturity (lengthening group L) and 12 achondroplasia patients of similar height and age who did not undergo tibial lengthening (control group C). The mean amount of lengthening of tibia in group L was 9.2 cm (lengthening percentage: 60%) and the mean age at the time of lengthening was 8.2 years. The mean duration of follow-up was 9.8 years. Results Skeletal maturity (fusion of physis) occurred at 15.2 years in group L and at 16.0 years in group C. The actual length of tibia (without distraction) at skeletal maturity was 238 mm in group L and 277 mm in group C (p = 0.03). The mean growth rates showed a decrease in group L relative to group C from about 2 years after surgery. Physeal closure was most pronounced on the anterolateral proximal tibial physis, with relative preservation of the distal physis. Interpretation Our findings indicate that physeal growth rate can be disturbed after tibial lengthening in achondroplasia, and a close watch should be kept for such an occurrence—especially when lengthening of more than 50% is attempted. PMID:22489887

  18. Die Rolle von growth arrest specific protein 6 im Aldosteron induzierten Endorganschaden

    OpenAIRE

    Theuer, Stefanie

    2013-01-01

    Growth arrest specific protein 6 (Gas 6) is involved in inflammatory kidney diseases, vascular remodeling, cell adhesion, and thrombus formation. We explored a role for Gas 6 in aldosterone-induced target organ damage. We observed that Gas 6 was upregulated in rats with high aldosterone levels. Mineralocorticoid receptor blockade prevented target organ damage and decreased the elevated Gas 6 expression. Vascular smooth muscle cells given aldosterone increased their Gas 6 expression in vitro. ...

  19. Growth arrest-specific protein 6 plasma concentrations during septic shock

    OpenAIRE

    Gibot, Sébastien; Massin, Frédéric; Cravoisy, Aurélie; Dupays, Rachel; Barraud, Damien; Nace, Lionel; Bollaert, Pierre-Edouard

    2007-01-01

    Introduction The product of growth arrest-specific gene 6 (Gas6) is a vitamin K dependent protein that is secreted by leucocytes and endothelial cells in response to injury and participates in cell survival, proliferation, migration and adhesion. Our purpose was to investigate plasma Gas6 concentration and its relation to organ dysfunction in patients with septic shock. Methods Forty-five patients with septic shock admitted to a medical adult intensive care unit were enrolled. Plasma Gas6 con...

  20. RRR-α-tocopheryl succinate inhibits human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesis arrest

    OpenAIRE

    Wu, Kun; ZHAO Yan; Liu, Bai-He; Li, Yao; Liu, Fang; Guo, Jian; Yu, Wei-Ping

    2002-01-01

    AIM: To investigate the effects of growth inhibition of human gastric cancer SGC-7901 cell with RRR-α-tocopheryl succinate (VES), a derivative of natural Vitamin E, via inducing apoptosis and DNA synthesis arrest.

  1. MR imaging of pituitary hyperplasia in a child with growth arrest and primary hypothyroidism

    International Nuclear Information System (INIS)

    Magnetic resonance imaging of pituitary hyperplasia has been rarely described in children with primary hypothyroidism. We report a case of pituitary hyperplasia in a child presented with significant growth arrest and laboratory evidence of hypothyroidism. Magnetic resonance imaging revealed symmetrical pituitary enlargement simulating macroadenoma. After thyroid hormone replacement therapy, the child's height increased and pituitary enlargement regressed to normal. Awareness of MRI appearance of pituitary hyperplasia in children with laboratory evidence of hypothyroidism might avoid misdiagnosis for pituitary tumor, which may also manifest as growth disorder, obviating unnecessary surgery. (orig.)

  2. Direct inhibition of Retinoblastoma phosphorylation by Nimbolide causes cell cycle arrest and suppresses glioblastoma growth

    Science.gov (United States)

    Anderson, Jane; Liu, Xiaona; Henry, Heather; Gasilina, Anjelika; Nassar, Nicholas; Ghosh, Jayeeta; Clark, Jason P; Kumar, Ashish; Pauletti, Giovanni M.; Ghosh, Pradip K; Dasgupta, Biplab

    2013-01-01

    Purpose Classical pharmacology allows the use and development of conventional phytomedicine faster and more economically than conventional drugs. This approach should be tested for their efficacy in terms of complementarity and disease control. The purpose of this study was to determine the molecular mechanisms by which nimbolide, a triterpenoid found in the well-known medicinal plant Azadirachta indica controls glioblastoma (GBM) growth. Experimental Design Using in vitro signaling, anchorage-independent growth, kinase assays, and xenograft models, we investigated the mechanisms of its growth inhibition in glioblastoma. Results We show that nimbolide or an ethanol soluble fraction of A. indica leaves (Azt) that contains nimbolide as the principal cytotoxic agent is highly cytotoxic against GBM in vitro and in vivo. Azt caused cell cycle arrest, most prominently at the G1-S stage in GBM cells expressing EGFRvIII, an oncogene present in about 20-25% of GBMs. Azt/nimbolide directly inhibited CDK4/CDK6 kinase activity leading to hypophosphorylation of the retinoblastoma (RB) protein, cell cycle arrest at G1-S and cell death. Independent of RB hypophosphorylation, Azt also significantly reduced proliferative and survival advantage of GBM cells in vitro and in tumor xenografts by downregulating Bcl2 and blocking growth factor induced phosphorylation of Akt, Erk1/2 and STAT3. These effects were specific since Azt did not affect mTOR or other cell cycle regulators. In vivo, Azt completely prevented initiation and inhibited progression of GBM growth. Conclusions Our preclinical findings demonstrate Nimbolide as a potent anti-glioma agent that blocks cell cycle and inhibits glioma growth in vitro and in vivo. PMID:24170547

  3. Necdin, a p53-target gene, is an inhibitor of p53-mediated growth arrest.

    Directory of Open Access Journals (Sweden)

    Julie Lafontaine

    Full Text Available In vitro, cellular immortalization and transformation define a model for multistep carcinogenesis and current ongoing challenges include the identification of specific molecular events associated with steps along this oncogenic pathway. Here, using NIH3T3 cells, we identified transcriptionally related events associated with the expression of Polyomavirus Large-T antigen (PyLT, a potent viral oncogene. We propose that a subset of these alterations in gene expression may be related to the early events that contribute to carcinogenesis. The proposed tumor suppressor Necdin, known to be regulated by p53, was within a group of genes that was consistently upregulated in the presence of PyLT. While Necdin is induced following p53 activation with different genotoxic stresses, Necdin induction by PyLT did not involve p53 activation or the Rb-binding site of PyLT. Necdin depletion by shRNA conferred a proliferative advantage to NIH3T3 and PyLT-expressing NIH3T3 (NIHLT cells. In contrast, our results demonstrate that although overexpression of Necdin induced a growth arrest in NIH3T3 and NIHLT cells, a growing population rapidly emerged from these arrested cells. This population no longer showed significant proliferation defects despite high Necdin expression. Moreover, we established that Necdin is a negative regulator of p53-mediated growth arrest induced by nutlin-3, suggesting that Necdin upregulation could contribute to the bypass of a p53-response in p53 wild type tumors. To support this, we characterized Necdin expression in low malignant potential ovarian cancer (LMP where p53 mutations rarely occur. Elevated levels of Necdin expression were observed in LMP when compared to aggressive serous ovarian cancers. We propose that in some contexts, the constitutive expression of Necdin could contribute to cancer promotion by delaying appropriate p53 responses and potentially promote genomic instability.

  4. Growth inhibitory effect of 4-phenyl butyric acid on human gastric cancer cells is associated with cell cycle arrest

    Institute of Scientific and Technical Information of China (English)

    Long-Zhu Li; Hong-Xia Deng; Wen-Zhu Lou; Xue-Yan Sun; Meng-Wan Song; Jing Tao; Bing-Xiu Xiao; Jun-Ming Guo

    2012-01-01

    AIM: To investigate the growth effects of 4-phenyl butyric acid (PBA) on human gastric carcinoma cells and their mechanisms. METHODS: Moderately-differentiated human gastric carcinoma SGC-7901 and lowly-differentiated MGC-803 cells were treated with 5, 10, 20, 40, and 60 μmol/L PBA for 1-4 d. Cell proliferation was detected using the MTT colorimetric assay. Cell cycle distributions were examined using flow cytometry. RESULTS: The proliferation of gastric carcinoma cells was inhibited by PBA in a dose- and time-dependent fashion. Flow cytometry showed that SGC-7901 cells treated with low concentrations of PBA were arrested at the G0/G1 phase, whereas cells treated with high concentrations of PBA were arrested at the G2/M phase. Although MGC-803 cells treated with low concentrations of PBA were also arrested at the G0/G1 phase, cells treated with high concentrations of PBA were arrested at the S phase. CONCLUSION: The growth inhibitory effect of PBA on gastric cancer cells is associated with alteration of the cell cycle. For moderately-differentiated gastric cancer cells, the cell cycle was arrested at the G0/G1 and G2/M phases. For lowly-differentiated gastric cancer cells, the cell cycle was arrested at the G0/G1 and S phases.

  5. Arrested chain growth during magnetic directed particle assembly in yield stress matrix fluids.

    Science.gov (United States)

    Rich, Jason P; McKinley, Gareth H; Doyle, Patrick S

    2012-02-28

    The process of assembling particles into organized functional structures is influenced by the rheological properties of the matrix fluid in which the assembly takes place. Therefore, tuning these properties represents a viable and as yet unexplored approach for controlling particle assembly. In this Letter, we examine the effect of the matrix fluid yield stress on the directed assembly of polarizable particles into linear chains under a uniform external magnetic field. Using particle-level simulations with a simple yield stress model, we find that chain growth follows the same trajectory as in Newtonian matrix fluids up to a critical time that depends on the balance between the yield stress and the strength of magnetic interactions between particles; subsequently, the system undergoes structural arrest. Appropriate dimensionless groups for characterizing the arresting behavior are determined and relationships between these groups and the resulting structural properties are presented. Since field-induced structures can be indefinitely stabilized by the matrix fluid yield stress and "frozen" into place as desired, this approach may facilitate the assembly of more complex and sophisticated structures. PMID:22335399

  6. Withaferin-A induces mitotic catastrophe and growth arrest in prostate cancer cells

    Science.gov (United States)

    Roy, Ram V; Suman, Suman; Das, Trinath P.; Luevano, Joe; Damodaran, Chendil

    2014-01-01

    Cell cycle deregulation is strongly associated with the pathogenesis of prostate cancer (CaP). Clinical trials of cell cycle regulators that target either the G0/G1 or G2/M phase to inhibit the growth of cancers including CaP are increasing. In this study, we determined the cell-cycle regulatory potential of the herbal molecule Withaferin-A (WA) on CaP cells. WA induced irreversible G2/M arrest in both CaP cell lines (PC3 and DU145) for 48 h. The G2/M arrest was accompanied by upregulation of phosphorylated Wee1, phophorylated histone H3, p21 and Aurora-B. On the other hand, downregulation of cyclins (E2, A, and B1) and phorphorylated Cdc2 (Tyr15) was observed in WA-treated CaP cells. In addition, decreased levels of phosphorylated Chk1 (Ser345) and Chk2 (Thr68) were evident in WA-treated CaP cells. Our results suggest that activation of Cdc2 leads to accumulation in M-phase, with abnormal duplication, and initiation of mitotic catastrophe that results in cell death. In conclusion, these results clearly highlight the potential of WA as a regulator of the G2/M phase of the cell cycle and as a therapeutic agent for CaP. PMID:24079846

  7. Type-1-cytokines synergize with oncogene inhibition to induce tumor growth arrest

    Science.gov (United States)

    Acquavella, Nicolas; Clever, David; Yu, Zhiya; Roelke-Parker, Melody; Palmer, Douglas C.; Xi, Liqiang; Pflicke, Holger; Ji, Yun; Gros, Alena; Hanada, Ken-ichi; Goldlust, Ian S.; Mehta, Gautam U.; Klebanoff, Christopher A.; Crompton, Joseph G.; Sukumar, Madhusudhanan; Morrow, James J.; Franco, Zulmarie; Gattinoni, Luca; Liu, Hui; Wang, Ena; Marincola, Francesco; Stroncek, David F.; Lee, Chyi-Chia R.; Raffeld, Mark; Bosenberg, Marcus W.; Roychoudhuri, Rahul; Restifo, Nicholas P.

    2014-01-01

    Both targeted inhibition of oncogenic driver mutations and immune-based therapies show efficacy in treatment of patients with metastatic cancer but responses can be either short-lived or incompletely effective. Oncogene inhibition can augment the efficacy of immune-based therapy but mechanisms by which these two interventions might cooperate are incompletely resolved. Using a novel transplantable BRAFV600E-mutant murine melanoma model (SB-3123), we explore potential mechanisms of synergy between the selective BRAFV600E inhibitor vemurafenib and adoptive cell transfer (ACT)-based immunotherapy. We found that vemurafenib cooperated with ACT to delay melanoma progression without significantly affecting tumor infiltration or effector function of endogenous or adoptively transferred CD8+ T cells as previously observed. Instead, we found that the T-cell cytokines IFNγ and TNFα synergized with vemurafenib to induce cell-cycle arrest of tumor cells in vitro. This combinatorial effect was recapitulated in human melanoma-derived cell lines and was restricted to cancers bearing a BRAFV600E-mutation. Molecular profiling of treated SB-3123 indicated that the provision of vemurafenib promoted the sensitization of SB-3123 to the anti-proliferative effects of T-cell effector cytokines. The unexpected finding that immune cytokines synergize with oncogene inhibitors to induce growth arrest have major implications for understanding cancer biology at the intersection of oncogenic and immune signaling and provides a basis for design of combinatorial therapeutic approaches for patients with metastatic cancer. PMID:25358764

  8. Chromium-induced membrane damage: protective role of ascorbic acid

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Importance of chromium as environmental toxicant is largely due to impact on the body to produce cellular toxicity. The impact of chromium and their supplementation with ascorbic acid was studied on plasma membrane of liver and kidney in male Wistar rats (80 - 100gbody weight). It has been observed that the intoxication with chromium ( i. p. ) at the dose of 0.8 mg/100g body weight per day for a period of 28 days causes significant increase in the level of cholesterol and decrease in the level of phospbolipid of both liver and kidney. The alkaline pbosphatase, total ATPase and Na + -K + -ATPase activities were significantly decreased in both liver and kidney after chromium treatment,except total ATPase activity of kidney. It is suggested that chromium exposure at the present dose and duration induce for the alterations of structure and function of both liver and kidney plasma membrane. Ascorbic acid ( i.p. at the dose of 0.5 mg,/100g body weight per day for period of 28 days) supplementation can reduce these structural changes in the plasma membrane of liver and kidney. But the functional changes can not be completely replenished by the ascorbic acid supplementation in response to chromium exposure. So it is also suggested that ascorbic acid (nutritional antioxidant) is useful free radical scavenger to restrain the chromium-induced membrane damage.

  9. The Role of Telomere Maintenance in the Spontaneous Growth Arrest of Pediatric Low-Grade Gliomas

    Directory of Open Access Journals (Sweden)

    Uri Tabori

    2006-02-01

    Full Text Available Spontaneous tumor regression is a unique feature of pediatric low-grade gliomas (PLGG. We speculated that lack of telomere maintenance is responsible for this behavior. We first looked for evidence of telomerase activity and alternative-lengthening telomeres (ALT in 56 PLGG. Telomerase activity was observed in 0 of 11 PLGG in contrast to 10 of 13 high-grade pediatric brain tumors. There was no ALT in 45 of 45 samples. We applied Q-FISH to eight patients whose indolent PLGG underwent two metachronous biopsies over a lag of several years. Telomere shortening was observed in the second biopsy in all tumors but not in a normal brain control (P 8.0 conferred a high likelihood of late recurrences in PLGG. Our findings provide a plausible biological mechanism to explain the tendency of PLGG to exhibit growth arrest and spontaneous regression. Telomere maintenance may therefore represent the first known biologic prognostic marker in PLGG.

  10. Parafibromin inhibits cancer cell growth and causes G1 phase arrest

    International Nuclear Information System (INIS)

    The HRPT2 (hereditary hyperparathyroidism type 2) tumor suppressor gene encodes a ubiquitously expressed 531 amino acid protein termed parafibromin. Inactivation of parafibromin predisposes one to the development of HPT-JT syndrome. To date, the role of parafibromin in tumorigenesis is largely unknown. Here, we report that parafibromin is a nuclear protein that possesses anti-proliferative properties. We show that overexpression of parafibromin inhibits colony formation and cellular proliferation, and induces cell cycle arrest in the G1 phase. Moreover, HPT-JT syndrome-derived mutations in HRPT2 behave in a dominant-negative manner by abolishing the ability of parafibromin to suppress cell proliferation. These findings suggest that parafibromin has a critical role in cell growth, and mutations in HRPT2 can directly inhibit this role

  11. Silencing NOTCH signaling causes growth arrest in both breast cancer stem cells and breast cancer cells

    Science.gov (United States)

    Suman, S; Das, T P; Damodaran, C

    2013-01-01

    Background: Breast cancer stem cells (BCSCs) are characterized by high aldehyde dehydrogenase (ALDH) enzyme activity and are refractory to current treatment modalities, show a higher risk for metastasis, and influence the epithelial to mesenchymal transition (EMT), leading to a shorter time to recurrence and death. In this study, we focused on examination of the mechanism of action of a small herbal molecule, psoralidin (Pso) that has been shown to effectively suppress the growth of BSCSs and breast cancer cells (BCCs), in breast cancer (BC) models. Methods: ALDH− and ALDH+ BCCs were isolated from MDA-MB-231 cells, and the anticancer effects of Pso were measured using cell viability, apoptosis, colony formation, invasion, migration, mammosphere formation, immunofluorescence, and western blot analysis. Results: Psoralidin significantly downregulated NOTCH1 signaling, and this downregulation resulted in growth inhibition and induction of apoptosis in both ALDH− and ALDH+ cells. Molecularly, Pso inhibited NOTCH1 signaling, which facilitated inhibition of EMT markers (β-catenin and vimentin) and upregulated E-cadherin expression, resulting in reduced migration and invasion of both ALDH− and ALDH+ cells. Conclusion: Together, our results suggest that inhibition of NOTCH1 by Pso resulted in growth arrest and inhibition of EMT in BCSCs and BCCs. Psoralidin appears to be a novel agent that targets both BCSCs and BCCs. PMID:24129237

  12. Understanding the functional difference between growth arrest-specific protein 6 and protein S : an evolutionary approach

    NARCIS (Netherlands)

    Studer, Romain A.; Opperdoes, Fred R.; Nicolaes, Gerry A. F.; Mulder, Andre B.; Mulder, Rene

    2014-01-01

    Although protein S (PROS1) and growth arrest-specific protein 6 (GAS6) proteins are homologous with a high degree of structural similarity, they are functionally different. The objectives of this study were to identify the evolutionary origins from which these functional differences arose. Bioinform

  13. Analysis of HIV-1 Vpr determinants responsible for cell growth arrest in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Yao Xiao-Jian

    2004-08-01

    Full Text Available Abstract Background The HIV-1 genome encodes a well-conserved accessory gene product, Vpr, that serves multiple functions in the retroviral life cycle, including the enhancement of viral replication in nondividing macrophages, the induction of G2 cell-cycle arrest, and the modulation of HIV-1-induced apoptosis. We previously reported the genetic selection of a panel of di-tryptophan (W-containing peptides capable of interacting with HIV-1 Vpr and inhibiting its cytostatic activity in Saccharomyces cerevisiae (Yao, X.-J., J. Lemay, N. Rougeau, M. Clément, S. Kurtz, P. Belhumeur, and E. A. Cohen, J. Biol. Chem. v. 277, p. 48816–48826, 2002. In this study, we performed a mutagenic analysis of Vpr to identify sequence and/or structural determinants implicated in the interaction with di-W-containing peptides and assessed the effect of mutations on Vpr-induced cytostatic activity in S. cerevisiae. Results Our data clearly shows that integrity of N-terminal α-helix I (17–33 and α-helix III (53–83 is crucial for Vpr interaction with di-W-containing peptides as well as for the protein-induced cytostatic effect in budding yeast. Interestingly, several Vpr mutants, mainly in the N- and C-terminal domains, which were previously reported to be defective for cell-cycle arrest or apoptosis in human cells, still displayed a cytostatic activity in S. cerevisiae and remained sensitive to the inhibitory effect of di-W-containing peptides. Conclusions Vpr-induced growth arrest in budding yeast can be effectively inhibited by GST-fused di-W peptide through a specific interaction of di-W peptide with Vpr functional domain, which includes α-helix I (17–33 and α-helix III (53–83. Furthermore, the mechanism(s underlying Vpr-induced cytostatic effect in budding yeast are likely to be distinct from those implicated in cell-cycle alteration and apoptosis in human cells.

  14. Three-dimensional MR imaging in the assessment of physeal growth arrest

    Energy Technology Data Exchange (ETDEWEB)

    Sailhan, Frederic; Chotel, Franck; Gollogly, Sohrab; Adam, Philippe; Berard, Jerome [Department of Orthopaedics, Hopital Bebrousse, 29 rue Soeur Bouvier, 69005, Lyon (France); Guibal, Anne-Laure; Guibaud, Laurent [Department of Radiology, Hopital Bebrousse, 29 rue Soeur Bouvier, 69005, Lyon (France)

    2004-09-01

    The purpose of this study is to describe an imaging method for identifying and characterising physeal growth arrest following physeal plate aggression. The authors describe the use of three-dimensional MRI performed with fat-suppressed three-dimensional spoiled gradient-recalled echo sequences followed by manual image reconstruction to create a 3D model of the physeal plate. This retrospective series reports the analysis of 33 bony physeal bridges in 28 children (mean age 10.5 years) with the use of fat-suppressed three-dimensional spoiled gradient-recalled echo imaging and 3D reconstructions from the source images. 3D reconstructions were obtained after the outlining was done manually on each source image. Files of all patients were reviewed for clinical data at the time of MRI, type of injury, age at MRI and bone bridge characteristics on reconstructions. Twenty-one (63%) of the 33 bridges were post-traumatic and were mostly situated in the lower extremities (19/21). The distal tibia was involved in 66% (14/21) of the cases. Bridges due to causes other than trauma were located in the lower extremities in 10/12 cases, and the distal femur represented 60% of these cases. Of the 28 patients, five presented with two bridges involving two different growth plates making a total of 33 physeal bone bars. The location and shape of each bridge was accurately identified in each patient, and in post-traumatic cases, 89% of bone bars were of Ogden type III (central) or I (peripheral). Reconstructions were obtained in 15 min and are easy to interpret. Volumes of the physeal bone bridge(s) and of the remaining normal physis were calculated. The bone bridging represented less than 1% to 47% of the total physeal plate volume. The precise shape and location of the bridge can be visualised on the 3D reconstructions. This information is useful in the surgical management of these deformities; as for the eight patients who underwent bone bar resection, an excellent correspondence was

  15. Indole-3-carbinol inhibits nasopharyngeal carcinoma growth through cell cycle arrest in vivo and in vitro.

    Directory of Open Access Journals (Sweden)

    Zhe Chen

    Full Text Available Nasopharyngeal carcinoma is a common malignant tumor in the head and neck. Because of frequent recurrence and distant metastasis which are the main causes of death, better treatment is needed. Indole-3-carbinol (I3C, a natural phytochemical found in the vegetables of the cruciferous family, shows anticancer effect through various signal pathways. I3C induces G1 arrest in NPC cell line with downregulation of cell cycle-related proteins, such as CDK4, CDK6, cyclin D1 and pRb. In vivo, nude mice receiving I3C protectively or therapeutically exhibited smaller tumors than control group after they were inoculated with nasopharyngeal carcinoma cells. The expression of CDK4, CDK6, cyclin D1 and pRb in preventive treatment group and drug treatment group both decreased compared with the control group. We conclude that I3C can inhibit the growth of NPC in vitro and in vivo by suppressing the expression of CDK and cyclin families. The drug was safe and had no toxic effects on normal tissues and organs.

  16. Growth arrest specific protein 6 participates in DOCA-induced target-organ damage.

    Science.gov (United States)

    Park, Joon-Keun; Theuer, Stefanie; Kirsch, Torsten; Lindschau, Carsten; Klinge, Uwe; Heuser, Arnd; Plehm, Ralph; Todiras, Mihai; Carmeliet, Peter; Haller, Hermann; Luft, Friedrich C; Muller, Dominik N; Fiebeler, Anette

    2009-08-01

    Growth arrest-specific protein 6 (Gas 6) is involved in inflammatory kidney diseases, vascular remodeling, cell adhesion, and thrombus formation. We explored a role for Gas 6 in aldosterone-induced target organ damage. We observed that Gas 6 was upregulated in rats with high aldosterone levels. Mineralocorticoid receptor blockade prevented target organ damage and decreased the elevated Gas 6 expression. Vascular smooth muscle cells given aldosterone increased their Gas 6 expression in vitro. To test the pathophysiological relevance, we investigated the effects of deoxycorticosterone acetate (DOCA) on Gas 6 gene-deleted ((-/-)) mice. After 6 weeks DOCA, Gas 6(-/-) mice developed similar telemetric blood pressure elevations compared to wild-type mice but were protected from cardiac hypertrophy. Cardiac expression of interleukin 6 and collagen IV was blunted in Gas 6(-/-) mice, indicating reduced inflammation and fibrosis. Gas 6(-/-) mice also had an improved renal function with reduced albuminuria, compared to wild-type mice. Renal fibrosis and fibronectin deposition in the kidney were also reduced. Gas 6 deficiency reduces the detrimental effects of aldosterone on cardiac and renal remodeling independent of blood pressure reduction. Gas 6 appears to play a role in mineralocorticoid receptor-mediated target organ damage. Furthermore, because warfarin interferes with Gas 6 protein expression, the findings could be of clinical relevance for anticoagulant choices. PMID:19564549

  17. Postmortem serum protein growth arrest-specific 6 levels in sepsis-related deaths.

    Science.gov (United States)

    Palmiere, Cristian; Augsburger, Marc

    2015-09-01

    Growth arrest-specific 6 (Gas6) is widely expressed in leukocytes, platelets, endothelial cells, and monocytes. It regulates various processes including granulocyte adhesion to the endothelium, cell migration, thrombus stabilization, and cytokine release. In humans, increased plasma Gas6 levels have been described in patients with sepsis and septic shock. In this study, Gas6 concentrations were measured in postmortem serum from femoral blood in a series of sepsis-related fatalities and control cases. The aims were twofold: first, to determine whether Gas6 can be reliably determined in postmortem serum; and second, to assess its diagnostic potential in identifying sepsis-related deaths. Two study groups were prospectively formed, a sepsis-related fatalities group (24 cases) and a control group (24 cases) including cases of deep vein thrombosis and fatal pulmonary embolism, cases of systemic inflammatory response syndrome in severe trauma, cases of end-stage renal failure, and cases of hanging (non-septic, non-SIRS, non-end stage renal failure cases). The preliminary results of this study seem to indicate that Gas6 can be effectively measured in postmortem serum. However, Gas6 levels in sepsis-related fatalities do not appear to be clearly distinguishable from concentrations in pulmonary embolism, severe trauma, and end-stage renal failure cases. These findings tend to support previous reports that indicated that Gas6 behaves as an acute phase reactant and can be considered a general marker of inflammation rather than a specific biomarker of sepsis. PMID:26233610

  18. A novel peptide sansalvamide analogue inhibits pancreatic cancer cell growth through G0/G1 cell-cycle arrest

    International Nuclear Information System (INIS)

    Patients with pancreatic cancer have little hope for cure because no effective therapies are available. Sansalvamide A is a cyclic depsipeptide produced by a marine fungus. We investigated the effect of a novel sansalvamide A analogue on growth, cell-cycle phases, and induction of apoptosis in human pancreatic cancer cells in vitro. The sansalvamide analogue caused marked time- and concentration-dependent inhibition of DNA synthesis and cell proliferation of two human pancreatic cancer cell lines (AsPC-1 and S2-013). The analogue induced G0/G1 phase cell-cycle arrest and morphological changes suggesting induction of apoptosis. Apoptosis was confirmed by annexin V binding. This novel sansalvamide analogue inhibits growth of pancreatic cancer cells through G0/G1 arrest and induces apoptosis. Sansalvamide analogues may be valuable for the treatment of pancreatic cancer

  19. Mutation of Growth Arrest Specific 8 Reveals a Role in Motile Cilia Function and Human Disease.

    Science.gov (United States)

    Lewis, Wesley R; Malarkey, Erik B; Tritschler, Douglas; Bower, Raqual; Pasek, Raymond C; Porath, Jonathan D; Birket, Susan E; Saunier, Sophie; Antignac, Corinne; Knowles, Michael R; Leigh, Margaret W; Zariwala, Maimoona A; Challa, Anil K; Kesterson, Robert A; Rowe, Steven M; Drummond, Iain A; Parant, John M; Hildebrandt, Friedhelm; Porter, Mary E; Yoder, Bradley K; Berbari, Nicolas F

    2016-07-01

    Ciliopathies are genetic disorders arising from dysfunction of microtubule-based cellular appendages called cilia. Different cilia types possess distinct stereotypic microtubule doublet arrangements with non-motile or 'primary' cilia having a 9+0 and motile cilia have a 9+2 array of microtubule doublets. Primary cilia are critical sensory and signaling centers needed for normal mammalian development. Defects in their structure/function result in a spectrum of clinical and developmental pathologies including abnormal neural tube and limb patterning. Altered patterning phenotypes in the limb and neural tube are due to perturbations in the hedgehog (Hh) signaling pathway. Motile cilia are important in fluid movement and defects in motility result in chronic respiratory infections, altered left-right asymmetry, and infertility. These features are the hallmarks of Primary Ciliary Dyskinesia (PCD, OMIM 244400). While mutations in several genes are associated with PCD in patients and animal models, the genetic lesion in many cases is unknown. We assessed the in vivo functions of Growth Arrest Specific 8 (GAS8). GAS8 shares strong sequence similarity with the Chlamydomonas Nexin-Dynein Regulatory Complex (NDRC) protein 4 (DRC4) where it is needed for proper flagella motility. In mammalian cells, the GAS8 protein localizes not only to the microtubule axoneme of motile cilia, but also to the base of non-motile cilia. Gas8 was recently implicated in the Hh signaling pathway as a regulator of Smoothened trafficking into the cilium. Here, we generate the first mouse with a Gas8 mutation and show that it causes severe PCD phenotypes; however, there were no overt Hh pathway phenotypes. In addition, we identified two human patients with missense variants in Gas8. Rescue experiments in Chlamydomonas revealed a subtle defect in swim velocity compared to controls. Further experiments using CRISPR/Cas9 homology driven repair (HDR) to generate one of these human missense variants in

  20. Overexpression of a novel gene, Cms1, can rescue the growth arrest of a Saccharomyces cerevisiae mcm10 suppressor

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    MCM10 protein is an essential replication factor involved in the initiation of DNA replication. A mcm10 mutant (mcm10-1) of budding yeast shows a growth arrest at 37℃. In the present work, we have isolated a mcm10-1 suppressor strain, which grows at 37℃. Interestingly, this mcm10-1 suppressor undergoes cell cycle arrest at 14℃. A novel gene, YLR003c, is identified by high-copy complementation of this suppressor. We called it as Cmsl (Complementation of Mcm 10 Suppressor). Furthermore, the experiments of transformation show that cells of mcm10-1 suppressor with high-copy plasmid but not low-copy plasmid grow at 14℃, indicating that overexpression of Cmsl can rescue the growth arrest of this mcm10 suppressor at non-permissive temperature. These results suggest that CMS1 protein may functionally interact with MCM10 protein and play a role in the regulation of DNA replication and cell cycle control.

  1. The SWI/SNF chromatin-remodeling gene AtCHR12 mediates temporary growth arrest in Arabidopsis thaliana upon perceiving environmental stress.

    Science.gov (United States)

    Mlynárová, Ludmila; Nap, Jan-Peter; Bisseling, Ton

    2007-09-01

    One of the earliest responses of plants to environmental stress is establishing a temporary growth arrest that allows adaptation to adverse conditions. The response to abiotic stress requires the modulation of gene expression, which may be mediated by the alteration of chromatin structures. This alteration can be accomplished with the help of chromatin-remodeling enzymes, such as the various SWI/SNF classes of ATPases. Here, we investigate the role of the Arabidopsis SNF2/Brahma-type AtCHR12 chromatin-remodeling gene in plant growth and development in reaction to adverse environmental conditions. We show that the AtCHR12 chromatin-remodeling gene plays a vital role in mediating the temporary growth arrest of Arabidopsis that is induced upon perception of stress. Exposing an AtCHR12 overexpressing mutant to stress conditions leads to growth arrest of normally active primary buds, as well as to reduced growth of the primary stem. In contrast, the AtCHR12 knockout mutant shows less growth arrest than the wild-type when exposed to moderate stress. Without stress, mutant plants are indistinguishable from the wild-type, and the growth arrest response seems to depend on the severity of the stress applied. Modulation of AtCHR12 expression correlates with changes in expression of dormancy-associated genes. This is in agreement with the concept of AtCHR12 participation in priming the plants for the growth arrest response. Our data indicate that AtCHR12-associated growth arrest differs from DELLA-mediated growth restraint. This establishes AtCHR12 as a novel gene involved in the response repertoire of plants that permits flexible modulation of growth in adverse and/or otherwise limiting environments. PMID:17605754

  2. Airway Delivery of Mesenchymal Stem Cells Prevents Arrested Alveolar Growth in Neonatal Lung Injury in Rats

    OpenAIRE

    van Haaften, Timothy; Byrne, Roisin; Bonnet, Sebastien; Rochefort, Gael Y.; Akabutu, John; Bouchentouf, Manaf; Rey-Parra, Gloria J.; Galipeau, Jacques; Haromy, Alois; Eaton, Farah; Chen, Ming; Hashimoto, Kyoko; Abley, Doris; Korbutt, Greg; Archer, Stephen L.

    2009-01-01

    Rationale: Bronchopulmonary dysplasia (BPD) and emphysema are characterized by arrested alveolar development or loss of alveoli; both are significant global health problems and currently lack effective therapy. Bone marrow–derived mesenchymal stem cells (BMSCs) prevent adult lung injury, but their therapeutic potential in neonatal lung disease is unknown.

  3. RUNX1 and its fusion oncoprotein derivative RUNX1-ETO induce senescence-like growth arrest independently of replicative stress

    Science.gov (United States)

    Wolyniec, Kamil; Wotton, Sandy; Kilbey, Anna; Jenkins, Alma; Terry, Anne; Peters, Gordon; Stocking, Carol; Cameron, Ewan; Neil, James C.

    2016-01-01

    A role for the RUNX genes in cancer failsafe processes has been suggested by their induction of senescence-like growth arrest in primary murine fibroblasts and the failure of RAS-induced senescence in Runx2 deficient cells. We now show that RUNX1 induces senescence in human primary fibroblasts. High affinity DNA binding is necessary but not sufficient, as shown by the functional attenuation of the truncated RUNX1/AML1a isoform and the TEL-RUNX1 fusion oncoprotein. However, a similar phenotype was potently induced by the RUNX1-ETO (AML1-ETO) oncoprotein, despite its dominant negative potential. Detailed comparison of H-RASV12, RUNX1 and RUNX1-ETO senescent phenotypes showed that the RUNX effectors induce earlier growth stasis with only low levels of DNA damage signalling and a lack of chromatin condensation, a marker of irreversible growth arrest. In human fibroblasts, all effectors induced p53 in the absence of detectable p14ARF, while only RUNX1-ETO induced senescence in p16INK4a null cells. Correlation was noted between induction of p53, reactive oxygen species and phospho-p38, while p38MAPK inhibition rescued cell growth markedly. These findings reveal a role for replication-independent pathways in RUNX and RUNX1-ETO senescence, and show that the context-specific oncogenic activity of RUNX1 fusion proteins are mirrored in their distinctive interactions with failsafe responses. PMID:19448675

  4. Dynamic analysis of crack growth and arrest in a pressure vessel subjected to thermal and pressure loading

    International Nuclear Information System (INIS)

    Predictions of crack arrest behaviour are performed for a cracked reactor pressure vessel under both thermal and pressure loading. The object is to compare static and dynamic calculations. The dynamic calculations are made using an explicit finite-element technique where crack growth is simulated by gradual nodal release. Three different load cases and the effect of different velocity dependence on the crack-propagation toughness are studied. It is found that for the analysed cases the static analysis is slightly conservative, thus justifying its use for these problems. (author)

  5. Interaction of E-cadherin and PTEN regulates morphogenesis and growth arrest in human mammary epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Fournier, Marcia V.; Fata, Jimmie E.; Martin, Katherine J.; Yaswen, Paul; Bissell, Mina J.

    2009-06-03

    PTEN is a dual function phosphatase with tumor suppressor function compromised in a wide spectrum of cancers. Because tissue polarity and architecture are crucial modulators of normal and malignant behavior, we postulated that PTEN may play a role in maintenance of tissue integrity. We used two non-malignant human mammary epithelial cell lines (HMECs) that form polarized, growth-arrested structures (acini) when cultured in 3-dimensional laminin-rich extracellular matrix gels (3D lrECM). As acini begin to form, PTEN accumulates in both the cytoplasm, and at cell-cell contacts where it colocalizes with E-cadherin/{beta}-catenin complex. Reduction of PTEN levels by shRNA in lrECM prevents formation of organized breast acini and disrupts growth arrest. Importantly, disruption of acinar polarity and cell-cell contact by E-cadherin function-blocking antibodies reduces endogenous PTEN protein levels and inhibits its accumulation at cell-cell contacts. Conversely, in SKBR3 breast cancer cells lacking endogenous E-cadherin expression, exogenous introduction of E-cadherin gene causes induction of PTEN expression and its accumulation at sites of cell interactions. These studies provide evidence that E-cadherin regulates both the PTEN protein levels and its recruitment to cell-cell junctions in 3D lrECM indicating a dynamic reciprocity between architectural integrity and the levels and localization of PTEN. This interaction thus appears to be a critical integrator of proliferative and morphogenetic signaling in breast epithelial cells.

  6. Pharmacologic inhibition of cdk4/6 arrests the growth of glioblastoma multiforme intracranial xenografts

    OpenAIRE

    Michaud, Karine; Solomon, David A.; Oermann, Eric; Kim, Jung-Sik; Zhong, Wei-Zhu; Prados, Michael D.; Ozawa, Tomoko; James, C. David; Waldman, Todd

    2010-01-01

    Activation of cyclin-dependent kinases 4 and 6 (cdk4/6) occurs in the majority of glioblastoma multiforme (GBM) tumors, and represents a promising molecular target for the development of small molecule inhibitors. In the current study we investigated the molecular determinants and in vivo response of diverse GBM cell lines and xenografts to PD-0332991, a cdk4/6 specific inhibitor. In vitro testing of PD-0332991 against a panel of GBM cell lines revealed a potent G1 cell cycle arrest and induc...

  7. Using growth and arrest of Richtmyer-Meshkov instabilities and Lagrangian simulations to study high-rate material strength

    International Nuclear Information System (INIS)

    Experiments applying a supported shock through mating surfaces (Atwood number = 1) with geometrical perturbations have been proposed for studying strength at strain rates up to 107/s using Richtmyer-Meshkov (RM) instabilities. Buttler et al. recently reported experimental results for RM instability growth in copper but with an unsupported shock applied by high explosives and the geometrical perturbations on the opposite free surface (Atwood number = −1). This novel configuration allowed detailed experimental observation of the instability growth and arrest. We present results and interpretation from numerical simulations of the Buttler RM instability experiments. Highly-resolved, two-dimensional simulations were performed using a Lagrangian hydrocode and the Preston-Tonks-Wallace (PTW) strength model. The model predictions show good agreement with the data. The numerical simulations are used to examine various assumptions previously made in an analytical model and to estimate the sensitivity of such experiments to material strength.

  8. CHROMIUM INDUCED CYTOTOXICITY IN BLACKGRAM (VIGNA MUNGO L.)

    OpenAIRE

    A. Chidambaram ، P. Sundaramoorthy ، A. Murugan ، K. Sankar Ganesh ، L. Baskaran

    2009-01-01

    Chromium is known to be highly toxic to biological systems. This study was designed to determine the mutagenic effects of different concentrations (0, 10, 25, 50, 100 and 200 mg/L) of hexavalent chromium on root tip cells of blackgram (Vigna mungo L. Hepper). The blackgram seeds were equi-spacially arranged in sterilized petriplates lined with filter paper and they were treated with different concentrations of chromium solution. In germination studies, the morphological growth parameters such...

  9. Platycodin D Induces Tumor Growth Arrest by Activating FOXO3a Expression in Prostate Cancer in vitro and in vivo

    Science.gov (United States)

    Zhou, Rui; Lu, Zongliang; Liu, Kai; Guo, Jing; Liu, Jie; Zhou, Yong; Yang, Jian; Mi, Mantian; Xu, Hongxia

    2014-01-01

    Platycodin D (PD), a major saponin derived from Platycodin grandiflorum, exerted cytotoxicity against prostate cancer cell lines (PC3, DU145 and LNCaP cells) with IC50 values in the range of 11.17 to 26.13μmol/L, whereas RWPE-1cells (a non-malignant human prostate epithelial cell line) were not significantly affected. A further study in these cell lines showed that PD could potently affect cell proliferation (indicated by the bromodeoxyuridine assay), induce cell apoptosis (determined by Annexin V-FITC flow cytometry) and cause cell cycle arrest (indicated by PI staining). After being treated with PD for 48 hours, DU145 and LNCaP cells were arrested in the G0 /G1 phase, and PC3 cells were arrested in the G2/M phase. A Western blotting analysis indicated that PD increased the expression of the FOXO3a transcription factor, decreased the expression of p-FOXO3a and MDM2 and increased the expression of FOXO-responsive genes, p21 and p27. MDM2 silencing (transiently by siRNA-MDM2) increased the PD-induced FOXO3a protein expression, while MDM2 overexpression (in cells transiently transfected with a pcDNA3-MDM2 plasmid) decreased the PD-induced expression of the FOXO3a protein. Moreover, PD dose-dependently inhibited the growth of PC3 xenograft tumors in BALB/c nude mice. A Western blotting analysis of the excised xenograft tumors indicated that similar changes in protein expression also occurred in vivo. These results suggest that PD exhibits significant activity against prostate cancer in vitro and in vivo. The FOXO3a transcription factor appears to be involved in the activity of PD. Together, all of these findings provide a basis for the future development of this agent for human prostate cancer therapy. PMID:25431082

  10. A low-dose hypersensitive keratinocyte loss in response to fractionated radiotherapy is associated with growth arrest and apoptosis

    International Nuclear Information System (INIS)

    Background and purpose: The existence of a hypersensitive radiation response to doses below 0.5 Gy is well established for many normal and tumour cell lines. There is also evidence for hypersensitive tissue responses in acute skin damage and kidney function in mice. Recently, we have identified that a hypersensitive γH2AX response exists in human epidermis. The aim of this study was to investigate the dose-response of basal clonogenic keratinocytes in normal skin to fractionated radiotherapy with low dose fractions. Materials: Skin punch biopsies were taken before and during radiotherapy from prostate cancer patients undergoing radiotherapy with a curative intent. Areas of epidermis receiving daily fractions of approximately 0.1, 0.2, 0.45 and 1.1 Gy were biopsied on the same occasion to determine dose-response for each individual patient. In total, 89 cases were assessed either at 1, 2.5, 3, 4, 5 or 6.5 weeks in the treatment course. Biopsy sampling of another 25 patients was performed from areas receiving 0.45 and 1.1 Gy per fraction at regular intervals throughout the 7-week treatment period. The number of basal keratinocytes per mm of the interfollicular epidermis was determined. The DNA damage response of the basal keratinocytes was investigated by immunohistochemical staining for molecular markers of growth arrest, mitosis and cell death, using p21, phospho-H3 and γH2AX, respectively. The number of stained keratinocytes in the basal layer was counted manually. The p21 staining was also quantified by digital image analysis. Results: The individual dose-response relationships revealed a low-dose hypersensitivity for reduction of basal keratinocytes throughout 7 weeks of radiotherapy (p < 0.01). Growth arrest and cell proliferation assessed at 1 week and 6.5 weeks showed, in both cases, hypersensitive increase of p21 (p < 0.01) and hypersensitive depression of mitosis (p < 0.01). Manual counting and digital image analysis of p21 showed good agreement. Cell

  11. Differential regulation of vitamin D receptor expression in distinct leukemic cell lines upon phorbol ester-induced growth arrest

    Directory of Open Access Journals (Sweden)

    Folgueira M.A.A.K.

    2000-01-01

    Full Text Available A close correlation between vitamin D receptor (VDR abundance and cell proliferation rate has been shown in NIH-3T3 fibroblasts, MCF-7 breast cancer and in HL-60 myeloblastic cells. We have now determined if this association occurs in other leukemic cell lines, U937 and K562, and if VDR content is related to c-myc expression, which is also linked to cell growth state. Upon phorbol myristate acetate (PMA treatment, cells from the three lineages (HL-60, U937 and K562 differentiated and expressed specific surface antigens. All cell lines analyzed were growth inhibited by PMA and the doubling time was increased, mainly due to an increased fraction of cells in the G0/G1 phase, as determined by flow cytometry measurements of incorporated bromodeoxyuridine and cell DNA content. C-myc mRNA expression was down-regulated and closely correlated to cell growth arrest. However, VDR expression in leukemic cell lines, as determined by immunofluorescence and Northern blot assays, was not consistently changed upon inhibition of cell proliferation since VDR levels were down-regulated only in HL-60 cells. Our data suggest that VDR expression cannot be explained simply as a reflection of the leukemic cell growth state.

  12. NBM-T-BBX-OS01, Semisynthesized from Osthole, Induced G1 Growth Arrest through HDAC6 Inhibition in Lung Cancer Cells.

    Science.gov (United States)

    Pai, Jih-Tung; Hsu, Chia-Yun; Hua, Kuo-Tai; Yu, Sheng-Yung; Huang, Chung-Yang; Chen, Chia-Nan; Liao, Chiung-Ho; Weng, Meng-Shih

    2015-01-01

    Disrupting lung tumor growth via histone deacetylases (HDACs) inhibition is a strategy for cancer therapy or prevention. Targeting HDAC6 may disturb the maturation of heat shock protein 90 (Hsp90) mediated cell cycle regulation. In this study, we demonstrated the effects of semisynthesized NBM-T-BBX-OS01 (TBBX) from osthole on HDAC6-mediated growth arrest in lung cancer cells. The results exhibited that the anti-proliferative activity of TBBX in numerous lung cancer cells was more potent than suberoylanilide hydroxamic acid (SAHA), a clinically approved pan-HDAC inhibitor, and the growth inhibitory effect has been mediated through G1 growth arrest. Furthermore, the protein levels of cyclin D1, CDK2 and CDK4 were reduced while cyclin E and CDK inhibitor, p21Waf1/Cip1, were up-regulated in TBBX-treated H1299 cells. The results also displayed that TBBX inhibited HDAC6 activity via down-regulation HDAC6 protein expression. TBBX induced Hsp90 hyper-acetylation and led to the disruption of cyclin D1/Hsp90 and CDK4/Hsp90 association following the degradation of cyclin D1 and CDK4 proteins through proteasome. Ectopic expression of HDAC6 rescued TBBX-induced G1 arrest in H1299 cells. Conclusively, the data suggested that TBBX induced G1 growth arrest may mediate HDAC6-caused Hsp90 hyper-acetylation and consequently increased the degradation of cyclin D1 and CDK4. PMID:25946558

  13. The Forkhead Transcription Factor FOXP2 Is Required for Regulation of p21WAF1/CIP1 in 143B Osteosarcoma Cell Growth Arrest.

    Directory of Open Access Journals (Sweden)

    Duncan M Gascoyne

    Full Text Available Mutations of the forkhead transcription factor FOXP2 gene have been implicated in inherited speech-and-language disorders, and specific Foxp2 expression patterns in neuronal populations and neuronal phenotypes arising from Foxp2 disruption have been described. However, molecular functions of FOXP2 are not completely understood. Here we report a requirement for FOXP2 in growth arrest of the osteosarcoma cell line 143B. We observed endogenous expression of this transcription factor both transiently in normally developing murine osteoblasts and constitutively in human SAOS-2 osteosarcoma cells blocked in early osteoblast development. Critically, we demonstrate that in 143B osteosarcoma cells with minimal endogenous expression, FOXP2 induced by growth arrest is required for up-regulation of p21WAF1/CIP1. Upon growth factor withdrawal, FOXP2 induction occurs rapidly and precedes p21WAF1/CIP1 activation. Additionally, FOXP2 expression could be induced by MAPK pathway inhibition in growth-arrested 143B cells, but not in traditional cell line models of osteoblast differentiation (MG-63, C2C12, MC3T3-E1. Our data are consistent with a model in which transient upregulation of Foxp2 in pre-osteoblast mesenchymal cells regulates a p21-dependent growth arrest checkpoint, which may have implications for normal mesenchymal and osteosarcoma biology.

  14. Natural variation in small molecule-induced TIR-NB-LRR signaling induces root growth arrest via EDS1- and PAD4-complexed R protein VICTR in Arabidopsis.

    Science.gov (United States)

    Kim, Tae-Houn; Kunz, Hans-Henning; Bhattacharjee, Saikat; Hauser, Felix; Park, Jiyoung; Engineer, Cawas; Liu, Amy; Ha, Tracy; Parker, Jane E; Gassmann, Walter; Schroeder, Julian I

    2012-12-01

    In a chemical genetics screen we identified the small-molecule [5-(3,4-dichlorophenyl)furan-2-yl]-piperidine-1-ylmethanethione (DFPM) that triggers rapid inhibition of early abscisic acid signal transduction via PHYTOALEXIN DEFICIENT4 (PAD4)- and ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1)-dependent immune signaling mechanisms. However, mechanisms upstream of EDS1 and PAD4 in DFPM-mediated signaling remain unknown. Here, we report that DFPM generates an Arabidopsis thaliana accession-specific root growth arrest in Columbia-0 (Col-0) plants. The genetic locus responsible for this natural variant, VICTR (VARIATION IN COMPOUND TRIGGERED ROOT growth response), encodes a TIR-NB-LRR (for Toll-Interleukin1 Receptor-nucleotide binding-Leucine-rich repeat) protein. Analyses of T-DNA insertion victr alleles showed that VICTR is necessary for DFPM-induced root growth arrest and inhibition of abscisic acid-induced stomatal closing. Transgenic expression of the Col-0 VICTR allele in DFPM-insensitive Arabidopsis accessions recapitulated the DFPM-induced root growth arrest. EDS1 and PAD4, both central regulators of basal resistance and effector-triggered immunity, as well as HSP90 chaperones and their cochaperones RAR1 and SGT1B, are required for the DFPM-induced root growth arrest. Salicylic acid and jasmonic acid signaling pathway components are dispensable. We further demonstrate that VICTR associates with EDS1 and PAD4 in a nuclear protein complex. These findings show a previously unexplored association between a TIR-NB-LRR protein and PAD4 and identify functions of plant immune signaling components in the regulation of root meristematic zone-targeted growth arrest. PMID:23275581

  15. Growth arrest and apoptosis of human hepatocellular carcinoma cells induced by hexamethylene bisacetamide

    OpenAIRE

    Ouyang, Gao-Liang; Cai, Qiu-Feng; Min LIU; Chen, Rui-Chuan; Huang, Zhi; Jiang, Rui-Sheng; Chen, Fu; Hong, Shui-Gen; Bao, Shi-Deng

    2004-01-01

    AIM: To investigate the cellular effects of hybrid polar compound hexamethylene bisacetamide (HMBA) on the growth and apoptosis of human hepatocellular carcinoma cells and to provide the molecular mechanism for potential application of HMBA in the treatment of liver cancer.

  16. Cellular Iron Depletion and the Mechanisms Involved in the Iron-dependent Regulation of the Growth Arrest and DNA Damage Family of Genes*

    OpenAIRE

    Saletta, Federica; Rahmanto, Yohan Suryo; Siafakas, Aritee R.; Richardson, Des R.

    2011-01-01

    Iron plays a crucial part in proliferation while iron deficiency results in G1/S arrest, DNA damage, and apoptosis. However, the precise role of iron in cell cycle control remains unclear. We showed that iron depletion using the iron chelators, desferrioxamine (DFO), or 2-hydroxy-1-napthylaldehyde isonicotinoyl hydrazone (311), increased the mRNA levels of the growth arrest and DNA damage 45α gene, GADD45α (Darnell, G. and Richardson, D. R. (1999) Blood 94, 781–792). In this study, we examine...

  17. H4 histamine receptors mediate cell cycle arrest in growth factor-induced murine and human hematopoietic progenitor cells.

    Directory of Open Access Journals (Sweden)

    Anne-France Petit-Bertron

    Full Text Available The most recently characterized H4 histamine receptor (H4R is expressed preferentially in the bone marrow, raising the question of its role during hematopoiesis. Here we show that both murine and human progenitor cell populations express this receptor subtype on transcriptional and protein levels and respond to its agonists by reduced growth factor-induced cell cycle progression that leads to decreased myeloid, erythroid and lymphoid colony formation. H4R activation prevents the induction of cell cycle genes through a cAMP/PKA-dependent pathway that is not associated with apoptosis. It is mediated specifically through H4R signaling since gene silencing or treatment with selective antagonists restores normal cell cycle progression. The arrest of growth factor-induced G1/S transition protects murine and human progenitor cells from the toxicity of the cell cycle-dependent anticancer drug Ara-C in vitro and reduces aplasia in a murine model of chemotherapy. This first evidence for functional H4R expression in hematopoietic progenitors opens new therapeutic perspectives for alleviating hematotoxic side effects of antineoplastic drugs.

  18. CSBF/C10orf99, a novel potential cytokine, inhibits colon cancer cell growth through inducing G1 arrest.

    Science.gov (United States)

    Pan, Wen; Cheng, Yingying; Zhang, Heyu; Liu, Baocai; Mo, Xiaoning; Li, Ting; Li, Lin; Cheng, Xiaojing; Zhang, Lianhai; Ji, Jiafu; Wang, Pingzhang; Han, Wenling

    2014-01-01

    Cytokines are soluble proteins that exert their functions by binding specific receptors. Many cytokines play essential roles in carcinogenesis and have been developed for the treatment of cancer. In this study, we identified a novel potential cytokine using immunogenomics designated colon-derived SUSD2 binding factor (CSBF), also known as chromosome 10 open reading frame 99 (C10orf99). CSBF/C10orf99 is a classical secreted protein with predicted molecular mass of 6.5 kDa, and a functional ligand of Sushi Domain Containing 2 (SUSD2). CSBF/C10orf99 has the highest expression level in colon tissue. Both CSBF/C10orf99 and SUSD2 are down-regulated in colon cancer tissues and cell lines with different regulation mechanisms. CSBF/C10orf99 interacts with SUSD2 to inhibit colon cancer cell growth and induce G1 cell cycle arrest by down-regulating cyclin D and cyclin-dependent kinase 6 (CDK6). CSBF/C10orf99 displays a bell-shaped activity curve with the optimal effect at ~10 ng/ml. Its growth inhibitory effects can be blocked by sSUSD2-Fc soluble protein. Our results suggest that CSBF/C10orf99 is a novel potential cytokine with tumor suppressor functions. PMID:25351403

  19. Higher order nuclear organization in growth arrest of humanmammary epithelial cells: A novel role for telomere-associated proteinTIN2

    Energy Technology Data Exchange (ETDEWEB)

    Kaminker, Patrick; Plachot, Cedric; Kim, Sahn-Ho; Chung, Peter; Crippen, Danielle; Petersen, Ole W.; Bissell, Mina J.; Campisi, Judith; Lelievre, Sophie A.

    2004-12-15

    Nuclear organization, such as the formation of specific nuclear subdomains, is generally thought to be involved in the control of cellular phenotype; however, there are relatively few specific examples of how mammalian nuclei organize during radical changes in phenotype, such as those which occur during differentiation and growth arrest. Using human mammary epithelial cells (HMECs) in which growth arrest is essential for morphological differentiation, we show that the arrest of cell proliferation is accompanied by a reorganization of the telomere-associated protein, TIN2, into one to three large nuclear subdomains. The large TIN2 domains do not contain telomeres and occur concomitant with the continued presence of TIN2 at telomeres. The TIN2 domains were sensitive to DNAse, but not RNAse, occurred frequently, but not exclusively near nucleoli, and overlapped often with dense domains containing heterochromatin protein l{gamma}. Expression of truncated forms of TIN2 simultaneously prevented the formation of TIN2 domains and relaxed the stringent morphogenesis-induced growth arrest in HMECs. Our findings reveal a novel extra-telomeric organization of TIN2 associated with the control of cell proliferation and identify TIN2 as an important regulator of mammary epithelial differentiation.

  20. Live-Cell Imaging Visualizes Frequent Mitotic Skipping During Senescence-Like Growth Arrest in Mammary Carcinoma Cells Exposed to Ionizing Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Masatoshi, E-mail: msuzuki@nagasaki-u.ac.jp [Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki (Japan); Yamauchi, Motohiro; Oka, Yasuyoshi; Suzuki, Keiji; Yamashita, Shunichi [Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki (Japan)

    2012-06-01

    Purpose: Senescence-like growth arrest in human solid carcinomas is now recognized as the major outcome of radiotherapy. This study was designed to analyze cell cycle during the process of senescence-like growth arrest in mammary carcinoma cells exposed to X-rays. Methods and Materials: Fluorescent ubiquitination-based cell cycle indicators were introduced into the human mammary carcinoma cell line MCF-7. Cell cycle was sequentially monitored by live-cell imaging for up to 5 days after exposure to 10 Gy of X-rays. Results: Live-cell imaging revealed that cell cycle transition from G2 to G1 phase without mitosis, so-called mitotic skipping, was observed in 17.1% and 69.8% of G1- and G2-irradiated cells, respectively. Entry to G1 phase was confirmed by the nuclear accumulation of mKO{sub 2}-hCdt1 as well as cyclin E, which was inversely correlated to the accumulation of G2-specific markers such as mAG-hGeminin and CENP-F. More than 90% of cells skipping mitosis were persistently arrested in G1 phase and showed positive staining for the senescent biochemical marker, which is senescence-associated ss-galactosidase, indicating induction of senescence-like growth arrest accompanied by mitotic skipping. While G2 irradiation with higher doses of X-rays induced mitotic skipping in approximately 80% of cells, transduction of short hairpin RNA (shRNA) for p53 significantly suppressed mitotic skipping, suggesting that ionizing radiation-induced mitotic skipping is associated with p53 function. Conclusions: The present study found the pathway of senescence-like growth arrest in G1 phase without mitotic entry following G2-irradiation.

  1. Live-Cell Imaging Visualizes Frequent Mitotic Skipping During Senescence-Like Growth Arrest in Mammary Carcinoma Cells Exposed to Ionizing Radiation

    International Nuclear Information System (INIS)

    Purpose: Senescence-like growth arrest in human solid carcinomas is now recognized as the major outcome of radiotherapy. This study was designed to analyze cell cycle during the process of senescence-like growth arrest in mammary carcinoma cells exposed to X-rays. Methods and Materials: Fluorescent ubiquitination-based cell cycle indicators were introduced into the human mammary carcinoma cell line MCF-7. Cell cycle was sequentially monitored by live-cell imaging for up to 5 days after exposure to 10 Gy of X-rays. Results: Live-cell imaging revealed that cell cycle transition from G2 to G1 phase without mitosis, so-called mitotic skipping, was observed in 17.1% and 69.8% of G1- and G2-irradiated cells, respectively. Entry to G1 phase was confirmed by the nuclear accumulation of mKO2-hCdt1 as well as cyclin E, which was inversely correlated to the accumulation of G2-specific markers such as mAG-hGeminin and CENP-F. More than 90% of cells skipping mitosis were persistently arrested in G1 phase and showed positive staining for the senescent biochemical marker, which is senescence-associated ß-galactosidase, indicating induction of senescence-like growth arrest accompanied by mitotic skipping. While G2 irradiation with higher doses of X-rays induced mitotic skipping in approximately 80% of cells, transduction of short hairpin RNA (shRNA) for p53 significantly suppressed mitotic skipping, suggesting that ionizing radiation-induced mitotic skipping is associated with p53 function. Conclusions: The present study found the pathway of senescence-like growth arrest in G1 phase without mitotic entry following G2-irradiation.

  2. Arrest of Myelination and Reduced Axon Growth when Schwann Cells Lack mTOR

    OpenAIRE

    Sherman, Diane L.; Krols, Michiel; Wu, Lai-Man N.; Grove, Matthew; Nave, Klaus-Armin; Gangloff, Yann-Gaël; Brophy, Peter J.

    2012-01-01

    In developing peripheral nerves differentiating Schwann cells sort individual axons from bundles and ensheath them to generate multiple layers of myelin. In recent years there has been an increasing understanding of the extracellular and intracellular factors that initiate and stimulate Schwann cell myelination together with a growing appreciation of some of the signalling pathways involved. However, our knowledge of how Schwann cell growth is regulated during myelination is still incomplete....

  3. Nanotechnology and mesenchymal stem cells with chondrocytes in prevention of partial growth plate arrest in pigs

    Czech Academy of Sciences Publication Activity Database

    Plánka, L.; Srnec, R.; Rauser, P.; Starý, D.; Filová, Eva; Jančář, J.; Juhásová, Jana; Křen, J.; Nečas, A.; Gál, P.

    2012-01-01

    Roč. 156, č. 2 (2012), s. 128-134. ISSN 1213-8118 R&D Projects: GA MZd(CZ) NS9896 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50450515 Institutional support: RVO:68378041 ; RVO:67985904 Keywords : mesenchymal stem cells * growth plate defect * bone bridge Subject RIV: FI - Traumatology, Orthopedics Impact factor: 0.990, year: 2012

  4. Resistance to ultraviolet-induced apoptosis in DNA repair deficient growth arrested human fibroblasts is not related to recovery from RNA transcription blockage

    International Nuclear Information System (INIS)

    The impact of ultraviolet (UV-C) photoproducts on apoptosis induction was investigated in growth arrested (confluent) and proliferating human primary fibroblasts. Confluent fibroblasts were more resistant to UV-C-induced apoptosis than proliferating cells, and this was observed for normal human cells and for cells from patients with Cockayne and trichothiodystrophy syndromes, deficient in transcription coupled repair. This resistance was sustained for at least seven days and was not due to DNA repair efficiency, as the removal of CPDs in the genome was similar under both growth conditions. There was no correlation between reduced apoptosis and RNA synthesis recovery. Following UV-C treatment, proliferating and confluent fibroblasts showed a similar level of RNA synthesis inhibition and recovery from transcription blockage. These results support the hypothesis that the decrease of DNA replication, in growth arrested cells, protects cell from UV-C-induced apoptosis, even in the presence of DNA lesions

  5. Linear Growth Arrest Without Weight Gain Due to Overuse of Topical Clobetasol

    OpenAIRE

    Zahra Razavi; Milad Sanginabadi

    2014-01-01

    Prolonged potent topical glucocorticoid therapy in infants can cause iatrogenic Cushing’s syndrome. This case highlights the rarity of poor weight gain in iatrogenic Cushing’s syndrome. A 17-month-old boy was referred to outpatients pediatric endocrine clinic for evaluation of growth failure. On presentation his weight was 9.7kg (5th percentile) and height was 72cm (-3.6 SD below mean for age and sex). Systemic examination revealed grossly moon-like face, hypertrichosis and thin skin in the g...

  6. Linear Growth Arrest Without Weight Gain Due to Overuse of Topical Clobetasol

    Directory of Open Access Journals (Sweden)

    Zahra Razavi

    2014-11-01

    Full Text Available Prolonged potent topical glucocorticoid therapy in infants can cause iatrogenic Cushing’s syndrome. This case highlights the rarity of poor weight gain in iatrogenic Cushing’s syndrome. A 17-month-old boy was referred to outpatients pediatric endocrine clinic for evaluation of growth failure. On presentation his weight was 9.7kg (5th percentile and height was 72cm (-3.6 SD below mean for age and sex. Systemic examination revealed grossly moon-like face, hypertrichosis and thin skin in the genital area. His mother reported using local clobetasol for the previous seven months for his diaper dermatitis. Baseline plasma cortisol was low (0.3ng/ml, normal range: 60 to 280ng/ml. During standard dose of synthetic adrenocorticotropic hormone test, the peak cortisol level was 0.4ng/ml (N>180ng/ml and was consistent with hypothalamic–pituitary–adrenal axis suppression. The patient’s clinical presentation and laboratory investigations confirmed the diagnosis of secondary adrenal insufficiency and iatrogenic Cushing’s syndrome. He was treated successfully by discontinuing use of clobetasol. His appearance and growth returned to normal within two months. Morning cortisol was 101.2ng/ml after stopping the oral physiologic dose of hydrocortisone. Our case differed from other reports of iatrogenic Cushing’s syndrome by presenting in poor weight gain rather than obesity.

  7. Linear growth arrest without weight gain due to overuse of topical clobetasol.

    Science.gov (United States)

    Razavi, Zahra; Sanginabadi, Milad

    2014-11-01

    Prolonged potent topical glucocorticoid therapy in infants can cause iatrogenic Cushing's syndrome. This case highlights the rarity of poor weight gain in iatrogenic Cushing's syndrome. A 17-month-old boy was referred to outpatients pediatric endocrine clinic for evaluation of growth failure. On presentation his weight was 9.7kg (5th percentile) and height was 72cm (-3.6 SD below mean for age and sex). Systemic examination revealed grossly moon-like face, hypertrichosis and thin skin in the genital area. His mother reported using local clobetasol for the previous seven months for his diaper dermatitis. Baseline plasma cortisol was low (0.3ng/ml, normal range: 60 to 280ng/ml). During standard dose of synthetic adrenocorticotropic hormone test, the peak cortisol level was 0.4ng/ml (N>180ng/ml) and was consistent with hypothalamic-pituitary-adrenal axis suppression. The patient's clinical presentation and laboratory investigations confirmed the diagnosis of secondary adrenal insufficiency and iatrogenic Cushing's syndrome. He was treated successfully by discontinuing use of clobetasol. His appearance and growth returned to normal within two months. Morning cortisol was 101.2ng/ml after stopping the oral physiologic dose of hydrocortisone. Our case differed from other reports of iatrogenic Cushing's syndrome by presenting in poor weight gain rather than obesity. PMID:25584165

  8. Silica Nanoparticles Sensitize Human Multiple Myeloma Cells to Snake (Walterinnesia aegyptia Venom-Induced Apoptosis and Growth Arrest

    Directory of Open Access Journals (Sweden)

    Douaa Sayed

    2012-01-01

    Full Text Available Background. Multiple myeloma (MM, an almost incurable disease, is the second most common blood cancer. Initial chemotherapeutic treatment could be successful; however, resistance development urges the use of higher toxic doses accompanied by hematopoietic stem cell transplantation. The establishment of more effective treatments that can overcome or circumvent chemoresistance has become a priority. We recently demonstrated that venom extracted from Walterinnesia aegyptia (WEV either alone or in combination with silica nanoparticles (WEV+NPs mediated the growth arrest and apoptosis of prostate cancer cells. In the present study, we evaluated the impact of WEV alone and WEV+NP on proliferation and apoptosis of MM cells. Methods. The impacts of WEV alone and WEV+NP were monitored in MM cells from 70 diagnosed patients. The influences of WEV and WEV+NP were assessed with flow cytometry analysis. Results. WEV alone and WEV+NP decreased the viability of MM cells. Using a CFSE proliferation assay, we found that WEV+NP strongly inhibited MM cell proliferation. Furthermore, analysis of the cell cycle using the propidium iodide (PI staining method indicated that WEV+NP strongly altered the cell cycle of MM cells and enhanced the induction of apoptosis. Conclusions. Our data reveal the biological effects of WEV and WEV+NP on MM cells that enable these compounds to function as effective treatments for MM.

  9. Resveratrol oligomers isolated from Carex species inhibit growth of human colon tumorigenic cells mediated by cell cycle arrest.

    Science.gov (United States)

    González-Sarrías, Antonio; Gromek, Samantha; Niesen, Daniel; Seeram, Navindra P; Henry, Geneive E

    2011-08-24

    Research has shown that members of the Carex genus produce biologically active stilbenoids including resveratrol oligomers. This is of great interest to the nutraceutical industry given that resveratrol, a constituent of grape and red wine, has attracted immense research attention due to its potential human health benefits. In the current study, five resveratrol oligomers (isolated from Carex folliculata and Carex gynandra ), along with resveratrol, were evaluated for antiproliferative effects against human colon cancer (HCT-116, HT-29, Caco-2) and normal human colon (CCD-18Co) cells. The resveratrol oligomers included one dimer, two trimers, and two tetramers: pallidol (1); α-viniferin (2) and trans-miyabenol C (3); and kobophenols A (4) and B (5), respectively. Although not cytotoxic, the resveratrol oligomers (1-5), as well as resveratrol, inhibited growth of the human colon cancer cells. Among the six stilbenoids, α-viniferin (2) was most active against the colon cancer cells with IC(50) values of 6-32 μM (>2-fold compared to normal colon cells). Moreover, α-viniferin (at 20 μM) did not induce apoptosis but arrested cell cycle (in the S-phase) for the colon cancer but not the normal colon cells. This study adds to the growing body of knowledge supporting the anticancer effects of resveratrol and its oligomers. Furthermore, Carex species should be investigated for their nutraceutical potential given that they produce biologically active stilbenoids such as α-viniferin. PMID:21761862

  10. Antisense oligonucleotide targeting at the initiator of hTERT arrests growth of hepatoma cells

    Institute of Scientific and Technical Information of China (English)

    Su-Xia Liu; Wen-Sheng Sun; Ying-Lin Cao; Chun-Hong Ma; Li-Hui Han; Li-Ning Zhang; Zhen-Guang Wang; Fa-Liang Zhu

    2004-01-01

    AIM: To evaluate the inhibitory effect of antisense phosphorothioate oligonucleotide (asON) complementary to the initiator of human telomerase catalytic subunit (hTERT)on the growth of hepatoma cells.METHODS: The as-hTERT was synthesized by using a DNA synthesizer. HepG2.2.15 cells were treated with ashTERT at the concentration of 10 μmol/L. After 72 h, these cells were obtained for detecting growth inhibition,telomerase activity using the methods of MTT, TRAP-PCR-ELISA, respectively. BALB/c(nu/nu) mice were injected HepG2.2.15 cells and a human-nude mice model was obtained. There were three groups for anti-tumor activity study. Once tumors were established, these animals in the first group were administered as-hTERT and saline.Apoptosis of tumor cells was detected by FCM. In the 2nd group, the animals were injected HepG2.2.15 cells together with as-hTERT. In the third group, the animals were given as-hTERT 24 hours postinjection of HepG2.2.15 cells. The anti-HBV effects were assayed with ELISA ih vitro and in vivo.RESULTS: Growth inhibition was observed in cells treated with as-hTERT ih vitro. A significant different in the value of A570-A630 was found between cells treated with as-hTERT and control (P<0.01) by MTT method. The telomerase activity of tumor cells treated with as-hTERT was reduced,the value of A450 nm was 0.42 compared to control (1,49)with TRAP-PCR-ELISA. The peak of apoptosis in tumor cells given as-hTERT was 21. 12%, but not seen in saline-treated control. A prolonged period of carcinogenesis was observed in the second and third group animals. There was inhibitory effect on the expression of HBsAg and HBeAg ih vivo and in vitro.CONCLUSION: As-hTERT has an anti-tumor activity, which may be useful for gene therapy of tumors.

  11. Growth arrest of lung carcinoma cells (A549) by polyacrylate-anchored peroxovanadate by activating Rac1-NADPH oxidase signalling axis.

    Science.gov (United States)

    Chatterjee, Nirupama; Anwar, Tarique; Islam, Nashreen S; Ramasarma, T; Ramakrishna, Gayatri

    2016-09-01

    Hydrogen peroxide is often required in sublethal, millimolar concentrations to show its oxidant effects on cells in culture as it is easily destroyed by cellular catalase. Previously, we had shown that diperoxovanadate, a physiologically stable peroxovanadium compound, can substitute H2O2 effectively in peroxidation reactions. We report here that peroxovanadate when anchored to polyacrylic acid (PAPV) becomes a highly potent inhibitor of growth of lung carcinoma cells (A549). The early events associated with PAPV treatment included cytoskeletal modifications, increase in GTPase activity of Rac1, accumulation of the reactive oxygen species, and also increase in phosphorylation of H2AX (γH2AX), a marker of DNA damage. These effects persisted even at 24 h after removal of the compound and culminated in increased levels of p53 and p21 together with growth arrest. The PAPV-mediated growth arrest was significantly abrogated in cells pre-treated with the N-acetylcysteine, Rac1 knocked down by siRNA and DPI an inhibitor of NADPH oxidase. In conclusion, our results show that polyacrylate derivative of peroxovanadate efficiently arrests growth of A549 cancerous cells by activating the axis of Rac1-NADPH oxidase leading to oxidative stress and DNA damage. PMID:27435854

  12. Tris(2-chloroethyl)phosphate-induced cell growth arrest via attenuation of SIRT1-independent PI3K/Akt/mTOR pathway.

    Science.gov (United States)

    Zhang, Wenjuan; Zhang, Youjian; Wang, Zhiyuan; Xu, Tian; Huang, Cheng; Yin, Wenjun; Wang, Jing; Xiong, Wei; Lu, Wenhong; Zheng, Hongyan; Yuan, Jing

    2016-07-01

    Tris(2-chloroethyl)phosphate (TCEP) as an organophosphorus flame retardant and plasticizer has been widely used in industrial and household products. It not only was detected in residential indoor air and dust, surface and drinking water, but also in human plasma and breast milk, and tissue samples of liver, kidneys and brain from rodents. TCEP is classified as carcinogenic category 2 and toxic for reproduction category 1B. Sufficient evidence from experimental animals indicated carcinogenicity of TCEP in the liver, and kidneys as well as cell loss in the brain. However, the underlying mechanisms of TCEP-induced hepatotoxicity are mostly unknown. We investigated the in vitro effects of TCEP as well as TCEP-induced cell growth in the L02 and HepG2 cells through the PI3K/Akt/mTOR pathway. We found that TCEP reduced cell viability of these cell lines, induced the cell growth arrest, upregulated mRNA and protein levels of SIRT1, and attenuated the PI3K/Akt/mTOR pathway. However, growth arrest of the L02 and HepG2 cells were aggravated after inhibiting the SIRT1 expression with EX-527. The findings above suggested that TCEP induced the cell growth arrest of L02 and HepG2 cells via attenuation of the SIRT1-independent PI3K/Akt/mTOR pathway. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26378621

  13. Peptide nucleic acids arrest the growth of gastric cancer cells SGC7901

    Institute of Scientific and Technical Information of China (English)

    王宽; 张岂凡; 王锡山; 薛英威; 庞达; 傅松滨

    2004-01-01

    Background Peptide nucleic acid (PNA) has many characteristics useful in molecular biology. This paper described an effective way to raise the cell ingestion rate of PNA so as to kill gastric cancer cells.Methods Heteroduplexes of PNAs and oligonucleotides, wrapped by Lipofectamine 2000, were used to infect SGC7901 cells. The inhibitive effect of heteroduplexes was evaluated by analyzing cell clone forming and cell growth rate. Telomerase activity of SGC7901 cells was detected by polymerase chain reaction enzyme-linked immunosorbent assay (PCR-ELISA) and silver staining assay.Results PNAs showed a dose-dependent inhibition of cell proliferation. The percentage of proliferation inhibition was 99.4% after 7 days; the rate of cloning inhibition was 98.2% after 8 days;whereas for oligonucleotide groups, at the same concentration, the percentages were 50. 1% and 67. 5% respectively. Antisense PNA-DNA-Lipofectamine 2000 group (AP-D-L group) exhibited significantly different percentages from the control groups (P<0.05). The test result indicated that telomerase activity of the AP-D-L group was inhibited (P<0.05). At the same time, the impact on cell morphology was observed.Conclusions The results showed that PNAs are potent antisense reagents. The telomeraseassociated therapies are very promising for the treatment of malignant tumours.

  14. Daily Arrests

    Data.gov (United States)

    Montgomery County of Maryland — This dataset provides the public with arrest information from the Montgomery County Central Processing Unit (CPU) systems. The data presented is derived from every...

  15. Evaluation and prediction of the HIV-1 central polypurine tract influence on foamy viral vectors to transduce dividing and growth-arrested cells.

    Science.gov (United States)

    Shityakov, Sergey; Förster, Carola; Rethwilm, Axel; Dandekar, Thomas

    2014-01-01

    Retroviral vectors are potent tools for gene delivery and various biomedical applications. To accomplish a gene transfer task successfully, retroviral vectors must effectively transduce diverse cell cultures at different phases of a cell cycle. However, very promising retroviral vectors based on the foamy viral (FV) backbone lack the capacity to efficiently transduce quiescent cells. It is hypothesized that this phenomenon might be explained as the inability of foamy viruses to form a pre-integration complex (PIC) with nuclear import activity in growth-arrested cells, which is the characteristic for lentiviruses (HIV-1). In this process, the HIV-1 central polypurine tract (cPPT) serves as a primer for plus-strand synthesis to produce a "flap" element and is believed to be crucial for the subsequent double-stranded cDNA formation of all retroviral RNA genomes. In this study, the effects of the lentiviral cPPT element on the FV transduction potential in dividing and growth-arrested (G1/S phase) adenocarcinomic human alveolar basal epithelial (A549) cells are investigated by experimental and theoretical methods. The results indicated that the HIV-1 cPPT element in a foamy viral vector background will lead to a significant reduction of the FV transduction and viral titre in growth-arrested cells due to the absence of PICs with nuclear import activity. PMID:25009830

  16. A class of DNA-binding peptides from wheat bud causes growth inhibition, G2 cell cycle arrest and apoptosis induction in HeLa cells

    Directory of Open Access Journals (Sweden)

    Elgjo Kjell

    2009-07-01

    Full Text Available Abstract Background Deproteinized DNA from eukaryotic and prokaryotic cells still contains a low-molecular weight peptidic fraction which can be dissociated by alkalinization of the medium. This fraction inhibits RNA transcription and tumor cell growth. Removal from DNA of normal cells causes amplification of DNA template activity. This effect is lower or absent in several cancer cell lines. Likewise, the amount of active peptides in cancer cell DNA extracts is lower than in DNA preparation of the corresponding normal cells. Such evidence, and their ubiquitous presence, suggests that they are a regulatory, conserved factor involved in the control of normal cell growth and gene expression. Results We report that peptides extracted from wheat bud chromatin induce growth inhibition, G2 arrest and caspase-dependent apoptosis in HeLa cells. The growth rate is decreased in cells treated during the S phase only and it is accompanied by DNA damage and DNA synthesis inhibition. In G2 cells, this treatment induces inactivation of the CDK1-cyclin B1 complex and an increase of active chk1 kinase expression. Conclusion The data indicate that the chromatin peptidic pool inhibits HeLa cell growth by causing defective DNA replication which, in turn, arrests cell cycle progression to mitosis via G2 checkpoint pathway activation.

  17. Effects of gamma-radiation on cell growth, cycle arrest, death, and superoxide dismutase expression by DU 145 human prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Vucic V.

    2006-01-01

    Full Text Available Gamma-irradiation (gamma-IR is extensively used in the treatment of hormone-resistant prostate carcinoma. The objective of the present study was to investigate the effects of 60Co gamma-IR on the growth, cell cycle arrest and cell death of the human prostate cancer cell line DU 145. The viability of DU 145 cells was measured by the Trypan blue exclusion assay and the 3(4,5-dimethylthiazol-2-yl-2,5,diphenyltetrazolium bromide test. Bromodeoxyuridine incorporation was used for the determination of cell proliferation. Cell cycle arrest and cell death were analyzed by flow cytometry. Superoxide dismutase (SOD, specifically CuZnSOD and MnSOD protein expression, after 10 Gy gamma-IR, was determined by Western immunoblotting analysis. gamma-IR treatment had a significant (P < 0.001 antiproliferative and cytotoxic effect on DU 145 cells. Both effects were time and dose dependent. Also, the dose of gamma-IR which inhibited DNA synthesis and cell proliferation by 50% was 9.7 Gy. Furthermore, gamma-IR induced cell cycle arrest in the G2/M phase and the percentage of cells in the G2/M phase was increased from 15% (control to 49% (IR cells, with a nonsignificant induction of apoptosis. Treatment with 10 Gy gamma-IR for 24, 48, and 72 h stimulated CuZnSOD and MnSOD protein expression in a time-dependent manner, approximately by 3- to 3.5-fold. These data suggest that CuZnSOD and MnSOD enzymes may play an important role in the gamma-IR-induced changes in DU 145 cell growth, cell cycle arrest and cell death.

  18. Sarsaparilla (Smilax Glabra Rhizome) Extract Inhibits Cancer Cell Growth by S Phase Arrest, Apoptosis, and Autophagy via Redox-Dependent ERK1/2 Pathway.

    Science.gov (United States)

    She, Tiantian; Qu, Like; Wang, Lixin; Yang, Xingxin; Xu, Shuo; Feng, Junnan; Gao, Yujing; Zhao, Chuanke; Han, Yong; Cai, Shaoqing; Shou, Chengchao

    2015-05-01

    Cancer is still the major cause of death across the world. Regular approaches cannot effectively solve the emerging problems, including drug/radiation resistance, side effects, and therapeutic ineffectiveness. Natural dietary supplements have shown effectiveness in the prevention and treatment of cancer. Sarsaparilla (Smilax Glabra Rhizome) has growth-inhibitory effects on several cancer cell lines in vitro and in vivo, with little toxicity on normal cells. However, the mechanism underlying its function remains elusive. In the present study, we examined the anticancer activity of the supernatant of the water-soluble extract (SW) from sarsaparilla. Liquid chromatography/mass spectrometry-ion trap-time-of-flight (LC/MS-IT-TOF) analysis identified flavonoids, alkaloids, and phenylpropanoids as the major bioactive components of SW. SW was shown to markedly inhibit the growth of a broad spectrum of cancer cell lines in the in vitro and in vivo assays. S phase arrest, autophagy, or/and apoptosis were partly responsible for SW-induced growth inhibition. Results of microarray analysis and validation by quantitative RT-PCR indicated the involvement of oxidative stress and the MAPK1 pathway in SW-treated cells. We further found that SW destroyed intracellular-reduced glutathione/oxidized glutathione (GSH/GSSG) balance, and supplement with N-acetylcysteine (NAC) or glutathione (GSH) significantly antagonized SW-induced S phase arrest, apoptosis, and autophagy. In addition, SW-induced GSH/GSSG imbalance activated the ERK1/2 pathway, which contributed to SW-induced S phase arrest, apoptosis, autophagy, and resultant growth-inhibitory effect. Together, our results provide a molecular basis for sarsaparilla as an anticancer agent. PMID:25732255

  19. Curcumin induces growth-arrest and apoptosis in association with the inhibition of constitutively active JAK-STAT pathway in T cell leukemia

    International Nuclear Information System (INIS)

    Adult T cell leukemia is an aggressive and frequently fatal malignancy that expressess constitutively activated growth-signaling pathways in association with deregulated growth and resistance to apoptosis. Curcumin (diferuloylmethane) is a naturally occurring yellow pigment, isolated from the rhizomes of the plant Curcuma longa that has traditionally been used in the treatment of injury and inflammation. But the effect and mechanism of action of curcumin on T cell leukemia is not known. To investigate the antitumor activity of curcumin in T cell leukemia, we examined its effect on constitutive phosphorylation of JAK and STAT proteins, proliferation, and apoptosis in HTLV-I-transformed T cell lines. HTLV-I-transformed T cell leukemia lines, MT-2, HuT-102, and SLB-1, express constitutively phosphorylated JAK3, TYK2, STAT3, and STAT5 signaling proteins. In vitro treatment with curcumin induced a dose-dependent decrease in JAK and STAT phosphorylation resulting in the induction of growth-arrest and apoptosis in T cell leukemia. The induction of growth-arrest and apoptosis in association with the blockade of constitutively active JAK-STAT pathway suggests this be a mechanism by which curcumin induces antitumor activity in T cell leukemia

  20. Multivariate modeling of chromium-induced oxidative stress and biochemical changes in plants of Pistia stratiotes L.

    OpenAIRE

    Sinha, Sarita; Basant, Ankita; Malik, Amrita; Singh, Kunwar P.

    2009-01-01

    Biochemical changes in the plants of Pistia stratiotes L., a free floating macrophyte exposed to different concentrations of hexavalent chromium (0, 10, 40, 60, 80 and 160 μM) for 48, 96 and 144 h were studied. Chromium-induced oxidative stress in macrophyte was investigated using the multivariate modeling approaches. Cluster analysis rendered two fairly distinct clusters (roots and shoots) of similar characteristics in terms of their biochemical responses. Discriminant analysis identified as...

  1. Vitamin D Arrests Thyroid Carcinoma Cell Growth and Induces p27 Dephosphorylation and Accumulation through PTEN/Akt-Dependent and -Independent Pathways

    OpenAIRE

    Wei LIU; Asa, Sylvia L.; Fantus, I. George; Walfish, Paul G.; Ezzat, Shereen

    2002-01-01

    We investigated the effects of 1,25-dihydroxycholecalciferol vitamin D3 (VD) and its noncalciomimetic analog EB1089 on thyroid carcinoma cell growth. VD and EB1089 exhibited anti-proliferative effects in a dose-dependent manner as determined by [3H]thymidine incorporation and MIB-1 immunolabeling. VD or EB1089 resulted in similar G1-phase arrest. Neither apoptosis nor differentiation was affected. VD and EB1089 induced increased nuclear protein expression of the cyclin-dependent kinase inhibi...

  2. A role for transcriptional repression of p21CIP1 by c-Myc in overcoming transforming growth factor β-induced cell-cycle arrest

    OpenAIRE

    Claassen, Gisela F.; Hann, Stephen R.

    2000-01-01

    c-Myc plays a vital role in cell-cycle progression. Deregulated expression of c-Myc can overcome cell-cycle arrest in order to promote cellular proliferation. Transforming growth factor β (TGFβ) treatment of immortalized human keratinocyte cells inhibits cell-cycle progression and is characterized by down-regulation of c-Myc followed by up-regulation of p21CIP1. A direct role of c-Myc in this pathway was demonstrated by the observation that ectopic expression of c-Myc overcame the cell-cycle ...

  3. Resistance to ursodeoxycholic acid-induced growth arrest can also result in resistance to deoxycholic acid-induced apoptosis and increased tumorgenicity

    International Nuclear Information System (INIS)

    There is a large body of evidence which suggests that bile acids increase the risk of colon cancer and act as tumor promoters, however, the mechanism(s) of bile acids mediated tumorigenesis is not clear. Previously we showed that deoxycholic acid (DCA), a tumorogenic bile acid, and ursodeoxycholic acid (UDCA), a putative chemopreventive agent, exhibited distinct biological effects, yet appeared to act on some of the same signaling molecules. The present study was carried out to determine whether there is overlap in signaling pathways activated by tumorogenic bile acid DCA and chemopreventive bile acid UDCA. To determine whether there was an overlap in activation of signaling pathways by DCA and UDCA, we mutagenized HCT116 cells and then isolated cell lines resistant to UDCA induced growth arrest. These lines were then tested for their response to DCA induced apoptosis. We found that a majority of the cell lines resistant to UDCA-induced growth arrest were also resistant to DCA-induced apoptosis, implying an overlap in DCA and UDCA mediated signaling. Moreover, the cell lines which were the most resistant to DCA-induced apoptosis also exhibited a greater capacity for anchorage independent growth. We conclude that UDCA and DCA have overlapping signaling activities and that disregulation of these pathways can lead to a more advanced neoplastic phenotype

  4. Platelet-derived growth factor stimulation of [3H]-glucosamine incorporation in density-arrested BALB/c-3T3 cells

    International Nuclear Information System (INIS)

    G0/G1 traverse in density-arrested BALB/c-3T3 cells is controlled by multiple serum-derived growth factors. Platelet-derived growth factor (PDGF) initiates a proliferative response, whereas factors present in plasma facilitate progression through G0/G1. In the absence of competence formation, progression factors are unable to stimulate cell cycle traverse. The authors have identified the stimulation of a biochemical process specific to competence formation in BALB/c-3T3 cells. PDGF treated BALB/c-3T3 cells incorporated 5-10 fold more [3H]-glucosamine (GlcN) into acid-insoluble material as compared to platelet-poor plasma (PPP) treated cultures. Increased GlcN incorporation occurred in density-arrested BALB/c-3T3 cells in response to treatment with other competence factors, fibroblast growth factor, and Ca3 (PO4)2 and was not due to cell-cycle traverse. Stimulation of [3H]-GlcN incorporation by PDGF was time dependent, and increased incorporation of [3H]-GlcN into protein required de novo protein synthesis. Several mechanisms through which PDGF could increase GlcN incorporation into cellular material were examined. Results of these studies suggest an increase in the cellular capacity to glycosylate proteins is a response to or a part of competence formation

  5. The click-compatible sugar 6-deoxy-alkynyl glucose metabolically incorporates into Arabidopsis root hair tips and arrests their growth.

    Science.gov (United States)

    McClosky, Daniel D; Wang, Bo; Chen, Gong; Anderson, Charles T

    2016-03-01

    Plant cell walls are dynamic structures whose polysaccharide components are rearranged and recycled during growth and morphogenesis. Covalent fluorescent tagging of these polysaccharides following a metabolic labeling approach can help elucidate these changes. Herein reported are the synthesis and seedling-incorporation of a plant polysaccharide chemical reporter, 6-deoxy-alkynyl glucose (6dAG), that is modeled on D-glucose. Whereas fucose-alkyne, a previously reported chemical reporter for pectin, incorporates diffusely throughout growing cell walls, 6dAG incorporated specifically into root hair tips. This incorporation occurs in a time- and concentration-dependent manner. 6dAG exposure both induces and colocalizes with callose deposition in this tissue, and arrests both root hair and root growth. These results show that plants can incorporate an additional alkynyl-modified sugar analog into their metabolism, and into a discrete subcellular location. PMID:26833385

  6. Expression of the bacterial type III effector DspA/E in Saccharomyces cerevisiae down-regulates the sphingolipid biosynthetic pathway leading to growth arrest.

    Science.gov (United States)

    Siamer, Sabrina; Guillas, Isabelle; Shimobayashi, Mitsugu; Kunz, Caroline; Hall, Michael N; Barny, Marie-Anne

    2014-06-27

    Erwinia amylovora, the bacterium responsible for fire blight, relies on a type III secretion system and a single injected effector, DspA/E, to induce disease in host plants. DspA/E belongs to the widespread AvrE family of type III effectors that suppress plant defense responses and promote bacterial growth following infection. Ectopic expression of DspA/E in plant or in Saccharomyces cerevisiae is toxic, indicating that DspA/E likely targets a cellular process conserved between yeast and plant. To unravel the mode of action of DspA/E, we screened the Euroscarf S. cerevisiae library for mutants resistant to DspA/E-induced growth arrest. The most resistant mutants (Δsur4, Δfen1, Δipt1, Δskn1, Δcsg1, Δcsg2, Δorm1, and Δorm2) were impaired in the sphingolipid biosynthetic pathway. Exogenously supplied sphingolipid precursors such as the long chain bases (LCBs) phytosphingosine and dihydrosphingosine also suppressed the DspA/E-induced yeast growth defect. Expression of DspA/E in yeast down-regulated LCB biosynthesis and induced a rapid decrease in LCB levels, indicating that serine palmitoyltransferase (SPT), the first and rate-limiting enzyme of the sphingolipid biosynthetic pathway, was repressed. SPT down-regulation was mediated by dephosphorylation and activation of Orm proteins that negatively regulate SPT. A Δcdc55 mutation affecting Cdc55-PP2A protein phosphatase activity prevented Orm dephosphorylation and suppressed DspA/E-induced growth arrest. PMID:24828506

  7. Identification of MicroRNAs Involved in Growth Arrest and Apoptosis in Hydrogen Peroxide-Treated Human Hepatocellular Carcinoma Cell Line HepG2

    Directory of Open Access Journals (Sweden)

    Yuan Luo

    2016-01-01

    Full Text Available Although both oxidative stress and microRNAs (miRNAs play vital roles in physiological and pathological processes, little is known about the interactions between them. In this study, we first described the regulation of H2O2 in cell viability, proliferation, cycle, and apoptosis of human hepatocellular carcinoma cell line HepG2. Then, miRNAs expression was profiled after H2O2 treatment. The results showed that high concentration of H2O2 (600 μM could decrease cell viability, inhibit cell proliferation, induce cell cycle arrest, and finally promote cell apoptosis. Conversely, no significant effects could be found under treatment with low concentration (30 μM. miRNAs array analysis identified 131 differentially expressed miRNAs (125 were upregulated and 6 were downregulated and predicted 13504 putative target genes of the deregulated miRNAs. Gene ontology (GO analysis revealed that the putative target genes were associated with H2O2-induced cell growth arrest and apoptosis. The subsequent bioinformatics analysis indicated that H2O2-response pathways, including MAPK signaling pathway, apoptosis, and pathways in cancer and cell cycle, were significantly affected. Overall, these results provided comprehensive information on the biological function of H2O2 treatment in HepG2 cells. The identification of miRNAs and their putative targets may offer new diagnostic and therapeutic strategies for liver cancer.

  8. A novel muscarinic antagonist R2HBJJ inhibits non-small cell lung cancer cell growth and arrests the cell cycle in G0/G1.

    Directory of Open Access Journals (Sweden)

    Nan Hua

    Full Text Available Lung cancers express the cholinergic autocrine loop, which facilitates the progression of cancer cells. The antagonists of mAChRs have been demonstrated to depress the growth of small cell lung cancers (SCLCs. In this study we intended to investigate the growth inhibitory effect of R2HBJJ, a novel muscarinic antagonist, on non-small cell lung cancer (NSCLC cells and the possible mechanisms. The competitive binding assay revealed that R2HBJJ had a high affinity to M3 and M1 AChRs. R2HBJJ presented a strong anticholinergic activity on carbachol-induced contraction of guinea-pig trachea. R2HBJJ markedly suppressed the growth of NSCLC cells, such as H1299, H460 and H157. In H1299 cells, both R2HBJJ and its leading compound R2-PHC displayed significant anti-proliferative activity as M3 receptor antagonist darifenacin. Exogenous replenish of ACh could attenuate R2HBJJ-induced growth inhibition. Silencing M3 receptor or ChAT by specific-siRNAs resulted in a growth inhibition of 55.5% and 37.9% on H1299 cells 96 h post transfection, respectively. Further studies revealed that treatment with R2HBJJ arrested the cell cycle in G0/G1 by down-regulation of cyclin D1-CDK4/6-Rb. Therefore, the current study reveals that NSCLC cells express an autocrine and paracrine cholinergic system which stimulates the growth of NSCLC cells. R2HBJJ, as a novel mAChRs antagonist, can block the local cholinergic loop by antagonizing predominantly M3 receptors and inhibit NSCLC cell growth, which suggest that M3 receptor antagonist might be a potential chemotherapeutic regimen for NSCLC.

  9. A novel muscarinic antagonist R2HBJJ inhibits non-small cell lung cancer cell growth and arrests the cell cycle in G0/G1.

    Science.gov (United States)

    Hua, Nan; Wei, Xiaoli; Liu, Xiaoyan; Ma, Xiaoyun; He, Xinhua; Zhuo, Rengong; Zhao, Zhe; Wang, Liyun; Yan, Haitao; Zhong, Bohua; Zheng, Jianquan

    2012-01-01

    Lung cancers express the cholinergic autocrine loop, which facilitates the progression of cancer cells. The antagonists of mAChRs have been demonstrated to depress the growth of small cell lung cancers (SCLCs). In this study we intended to investigate the growth inhibitory effect of R2HBJJ, a novel muscarinic antagonist, on non-small cell lung cancer (NSCLC) cells and the possible mechanisms. The competitive binding assay revealed that R2HBJJ had a high affinity to M3 and M1 AChRs. R2HBJJ presented a strong anticholinergic activity on carbachol-induced contraction of guinea-pig trachea. R2HBJJ markedly suppressed the growth of NSCLC cells, such as H1299, H460 and H157. In H1299 cells, both R2HBJJ and its leading compound R2-PHC displayed significant anti-proliferative activity as M3 receptor antagonist darifenacin. Exogenous replenish of ACh could attenuate R2HBJJ-induced growth inhibition. Silencing M3 receptor or ChAT by specific-siRNAs resulted in a growth inhibition of 55.5% and 37.9% on H1299 cells 96 h post transfection, respectively. Further studies revealed that treatment with R2HBJJ arrested the cell cycle in G0/G1 by down-regulation of cyclin D1-CDK4/6-Rb. Therefore, the current study reveals that NSCLC cells express an autocrine and paracrine cholinergic system which stimulates the growth of NSCLC cells. R2HBJJ, as a novel mAChRs antagonist, can block the local cholinergic loop by antagonizing predominantly M3 receptors and inhibit NSCLC cell growth, which suggest that M3 receptor antagonist might be a potential chemotherapeutic regimen for NSCLC. PMID:23285263

  10. Curcumin-treated cancer cells show mitotic disturbances leading to growth arrest and induction of senescence phenotype.

    Science.gov (United States)

    Mosieniak, Grażyna; Sliwinska, Małgorzata A; Przybylska, Dorota; Grabowska, Wioleta; Sunderland, Piotr; Bielak-Zmijewska, Anna; Sikora, Ewa

    2016-05-01

    Cellular senescence is recognized as a potent anticancer mechanism that inhibits carcinogenesis. Cancer cells can also undergo senescence upon chemo- or radiotherapy. Curcumin, a natural polyphenol derived from the rhizome of Curcuma longa, shows anticancer properties both in vitro and in vivo. Previously, we have shown that treatment with curcumin leads to senescence of human cancer cells. Now we identified the molecular mechanism underlying this phenomenon. We observed a time-dependent accumulation of mitotic cells upon curcumin treatment. The time-lapse analysis proved that those cells progressed through mitosis for a significantly longer period of time. A fraction of cells managed to divide or undergo mitotic slippage and then enter the next phase of the cell cycle. Cells arrested in mitosis had an improperly formed mitotic spindle and were positive for γH2AX, which shows that they acquired DNA damage during prolonged mitosis. Moreover, the DNA damage response pathway was activated upon curcumin treatment and the components of this pathway remained upregulated while cells were undergoing senescence. Inhibition of the DNA damage response decreased the number of senescent cells. Thus, our studies revealed that the induction of cell senescence upon curcumin treatment resulted from aberrant progression through the cell cycle. Moreover, the DNA damage acquired by cancer cells, due to mitotic disturbances, activates an important molecular mechanism that determines the potential anticancer activity of curcumin. PMID:26916504

  11. Notch Signaling Activation in Cervical Cancer Cells Induces Cell Growth Arrest with the Involvement of the Nuclear Receptor NR4A2

    Science.gov (United States)

    Sun, Lichun; Liu, Mingqiu; Sun, Guang-Chun; Yang, Xu; Qian, Qingqing; Feng, Shuyu; Mackey, L. Vienna; Coy, David H.

    2016-01-01

    Cervical cancer is a second leading cancer death in women world-wide, with most cases in less developed countries. Notch signaling is highly conserved with its involvement in many cancers. In the present study, we established stable cervical cell lines with Notch activation and inactivation and found that Notch activation played a suppressive role in cervical cancer cells. Meanwhile, the transient overexpression of the active intracellular domain of all four Notch receptors (ICN1, 2, 3, and 4) also induced the suppression of cervical cancer Hela cell growth. ICN1 also induced cell cycle arrest at phase G1. Notch1 signaling activation affected the expression of serial genes, especially the genes associated with cAMP signaling, with an increase of genes like THBS1, VCL, p63, c-Myc and SCG2, a decrease of genes like NR4A2, PCK2 and BCL-2. Particularly, The nuclear receptor NR4A2 was observed to induce cell proliferation via MTT assay and reduce cell apoptosis via FACS assay. Furthermore, NR4A2's activation could reverse ICN1-induced suppression of cell growth while erasing ICN1-induced increase of tumor suppressor p63. These findings support that Notch signaling mediates cervical cancer cell growth suppression with the involvement of nuclear receptor NR4A2. Notably, Notch/NR4A2/p63 signaling cascade possibly is a new signling pathway undisclosed. PMID:27471554

  12. Using quantitative PCR to Identify Kinesin-3 Genes that are Upregulated During Growth Arrest in MouseNIH3T3 Cells

    DEFF Research Database (Denmark)

    Thorsteinsson, Rikke; Christensen, Søren Tvorup; Pedersen, Lotte Bang

    2009-01-01

    mouse NIH3T3 cells and those that might have cilia-related functions. We employed this method to specifically search for mouse kinesin-3 genes that are upregulated during growth arrest and identified three such genes (Kif13A, Kif13B, and Kif16A). In principle, however, the method can be extended to...

  13. Herbal diterpenoids induce growth arrest and apoptosis in colon cancer cells with increased expression of the nonsteroidal anti-inflammatory drug-activated gene.

    Science.gov (United States)

    Ko, Joshua K S; Leung, Wan C; Ho, Wai K; Chiu, Pauline

    2007-03-15

    Novel chemotherapeutic agents derived from active phytochemicals could be used as adjuvants and improve the anti-carcinogenicity of standard drug treatments. However, their precise mechanisms of action are sometimes unclear. In this study, the anti-carcinogenic effect of the herbal diterpenoid pseudolaric acid B (PAB) on the growth and apoptosis of colon cancer cells was investigated, and to compare that with the more toxic compound triptolide. PAB induced growth inhibition and apoptosis in HT-29 cells, which were associated with cell cycle arrest at the G(2)/M phase, modulation of cyclin expression and downregulation of the protooncogene c-myc. In addition, PAB also inhibited bcl-x(L) expression, induced cleavage of procaspase-3 and its substrate poly(ADP-ribose) polymerase (PARP), which together caused DNA fragmentation and nuclear chromatin condensation. Concomitantly, the modulation of the growth-related and apoptotic factors by PAB was accompanied by the increased protein and gene expression of the nonsteroidal anti-inflammatory drug-activated gene (NAG-1), which occurred along with cyclooxygenase-2 inhibition. The effects of PAB on PARP cleavage and NAG-1 overexpression were not reversible upon removal of the drug from the culture medium. Similar cytotoxic and pro-apoptotic effects were also attained by treating the HT-29 cells with another diterpenoid triptolide, but its actions on cell cycle progression and on the upstream transcriptional regulation of NAG-1 both took place in a less coherent manner. These findings exemplify the potential of herbal terpenoids, particularly PAB, in modulating colon cancer carcinogenesis through known molecular targets and precise mechanism of action. PMID:17258704

  14. Upregulation of the growth arrest-specific-2 in recurrent colorectal cancers, and its susceptibility to chemotherapy in a model cell system.

    Science.gov (United States)

    Huang, Chi-Jung; Lee, Chia-Long; Yang, Shung-Haur; Chien, Chih-Cheng; Huang, Chi-Cheng; Yang, Ruey-Neng; Chang, Chun-Chao

    2016-07-01

    Colorectal cancer (CRC) is one of the most common life-threatening malignances worldwide. CRC relapse markedly decreases the 5-year survival of patients following surgery. Aberrant expression of genes involved in pathways regulating the cell cycle, cell proliferation, or cell death are frequently reported in CRC tumorigenesis. We hypothesized that genes involved in CRC relapse might serve as prognostic indicators. We first evaluated the significance of gene sequences in the feces of patients with CRC relapse by consulting a public database. Tumorigenesis of target tissues was tested through tumor cell growth, cell cycle regulation, and chemotherapeutic efficacy. We found a highly significant correlation between CRC relapse and growth arrest-specific 2 (GAS2) gene expression. Based on cell models, the overexpressed GAS2 was associated with cellular growth rate, cell cycle regulation, and with chemotherapeutic sensitivity. Cell division was impaired by treating cells with 2-[4-(7-chloro-2-quinoxalinyloxy)phenoxy]-propionic acid (XK469), even when the cells were overexpressing GAS2. Thus, downregulation of GAS2 expression might control CRC relapse after curative resection. GAS2 could serve as a noninvasive marker from the feces of patients with prediagnosed CRC. Our findings suggest that GAS2 could have potential clinical applications for predicting early CRC relapse after radical resection, and that XK469 might impair tumor cell division by reducing GAS2 expression or blocking its cellular translocation. This will help in selecting the best therapeutic option, 5-fluorouracil in combination with XK469, for patients overexpressing GAS2 in CRC cells. Thus, GAS2 might act as a prognostic biomolecule and potential therapeutic target in patients with CRC relapse. PMID:27085973

  15. Induction of reactive oxygen species generation inhibits epithelial-mesenchymal transition and promotes growth arrest in prostate cancer cells.

    Science.gov (United States)

    Das, Trinath P; Suman, Suman; Damodaran, Chendil

    2014-07-01

    Oxidative stress is one causative factor of the pathogenesis and aggressiveness of most of the cancer types, including prostate cancer (CaP). A moderate increase in reactive oxygen species (ROS) induces cell proliferation whereas excessive amounts of ROS promote apoptosis. In this study, we explored the pro-oxidant property of 3,9-dihydroxy-2-prenylcoumestan (psoralidin [pso]), a dietary agent, on CaP (PC-3 and C4-2B) cells. Pso greatly induced ROS generation (more than 20-fold) that resulted in the growth inhibition of CaP cells. Overexpression of anti-oxidant enzymes superoxide dismutase 1 (SOD1), SOD2, and catalase, or pretreatment with the pharmacological inhibitor N-acetylcysteine (NAC) significantly attenuated both pso-mediated ROS generation and pso-mediated growth inhibition in CaP cells. Furthermore, pso administration significantly inhibited the migratory and invasive property of CaP cells by decreasing the transcription of β-catenin, and slug, which promote epithelial-mesenchymal transition (EMT), and by concurrently inducing E-cadherin expression in CaP cells. Pso-induced ROS generation in CaP cells resulted in loss of mitochondrial membrane potential, cytochrome-c release, and activation of caspase-3 and -9 and poly (ADP-ribose) polymerase (PARP), which led to apoptosis. On the other hand, overexpression of anti-oxidants rescued pso-mediated effects on CaP cells. These findings suggest that increasing the threshold of intracellular ROS could prevent or treat CaP growth and metastasis. PMID:23475579

  16. On arresting the complex growth rates in ferromagnetic convection with magnetic field dependent viscosity in a rotating ferrofluid layer

    Energy Technology Data Exchange (ETDEWEB)

    Prakash, Jyoti, E-mail: jpsmaths67@gmail.com; Gupta, Sanjay

    2013-11-15

    It is proved analytically that the complex growth rate ω=ω{sub r}+iω{sub i} (ω{sub r}andω{sub i} are respectively the real and imaginary parts of ω) of an arbitrary oscillatory motion of growing amplitude in ferromagnetic convection, with magnetic field dependent viscosity, in a rotating ferrofluid layer for the case of free boundaries, must lie inside a semicircle in the right half of the ω{sub r}ω{sub i}- plane whose center is at the origin and (radius){sup 2}=max{(RM_1/P_r),T_a}, where R is the Rayleigh number, M{sub 1} is the magnetic number, P{sub r} is the Prandtl number and T{sub a} is the Taylor number. Further, bounds for the case of rigid boundaries are also derived separately. - Highlights: • The linear stability analysis for a rotating ferrofluid layer with magnetic field dependent viscosity heated from below is made. • Upper bounds for the complex growth rates are obtained for free and rigid boundaries. • Bounds are important mainly when atleast one boundary is rigid so that exact solutions in closed form are not obtainable. • Results derived involve only nondimensional quantities and are independent of the wave number; are, thus, of uniform validity and applicability.

  17. On arresting the complex growth rates in ferromagnetic convection with magnetic field dependent viscosity in a rotating ferrofluid layer

    International Nuclear Information System (INIS)

    It is proved analytically that the complex growth rate ω=ωr+iωi (ωrandωi are respectively the real and imaginary parts of ω) of an arbitrary oscillatory motion of growing amplitude in ferromagnetic convection, with magnetic field dependent viscosity, in a rotating ferrofluid layer for the case of free boundaries, must lie inside a semicircle in the right half of the ωrωi- plane whose center is at the origin and (radius)2=max{(RM1/Pr),Ta}, where R is the Rayleigh number, M1 is the magnetic number, Pr is the Prandtl number and Ta is the Taylor number. Further, bounds for the case of rigid boundaries are also derived separately. - Highlights: • The linear stability analysis for a rotating ferrofluid layer with magnetic field dependent viscosity heated from below is made. • Upper bounds for the complex growth rates are obtained for free and rigid boundaries. • Bounds are important mainly when atleast one boundary is rigid so that exact solutions in closed form are not obtainable. • Results derived involve only nondimensional quantities and are independent of the wave number; are, thus, of uniform validity and applicability

  18. Translational arrest due to cytoplasmic redox stress delays adaptation to growth on methanol and heterologous protein expression in a typical fed-batch culture of Pichia pastoris.

    Directory of Open Access Journals (Sweden)

    Bryn Edwards-Jones

    Full Text Available We have followed a typical fed-batch induction regime for heterologous protein production under the control of the AOX1 promoter using both microarray and metabolomic analysis. The genetic constructs involved 1 and 3 copies of the TRY1 gene, encoding human trypsinogen. In small-scale laboratory cultures, expression of the 3 copy-number construct induced the unfolded protein response (UPR sufficiently that titres of extracellular trypsinogen were lower in the 3-copy construct than with the 1-copy construct. In the fed-batch-culture, a similar pattern was observed, with higher expression from the 1-copy construct, but in this case there was no significant induction of UPR with the 3-copy strain. Analysis of the microarray and metabolomic information indicates that the 3-copy strain was undergoing cytoplasmic redox stress at the point of induction with methanol. In this Crabtree-negative yeast, this redox stress appeared to delay the adaptation to growth on methanol and supressed heterologous protein production, probably due to a block in translation.Although redox imbalance as a result of artificially imposed hypoxia has previously been described, this is the first time that it has been characterised as a result of a transient metabolic imbalance and shown to involve a stress response which can lead to translational arrest. Without detailed analysis of the underlying processes it could easily have been mis-interpreted as secretion stress, transmitted through the UPR.

  19. Arrest of cell cycle by inhibition of ribonucleotide reductase induces accumulation of NAD+ by Mn2+-supplemented growth of Corynebacterium ammoniagenes.

    Science.gov (United States)

    Abbouni, Bouziane; Elhariry, Hesham M; Auling, Georg

    2003-01-01

    Cell division of the wild type strain Corynebacterium (formerly Brevibacterium) ammoniagenes ATCC 6872 which requires 1 microM Mn2+ for balanced growth was inhibited by addition of 20 mM hydroxyurea (HU) or 10 mM p-methoxyphenol (MP) to a Mn2+-supplemented fermentation medium at an appropriate time. Scanning electron microscopy (SEM) showed a restricted elongation characteristic of arrest of the cell cycle in coryneform bacteria. The cultures treated with HU or MP had, respectively, a fourfold or sixfold enhanced accumulation of NAD+ by a salvage biosynthetic pathway. An assay of nucleotide-permeable cells for ribonucleotide reductase activity using [3H-CDP] as substrate revealed a pre-early and complete decline of DNA precursor biosynthesis not found in the untreated control. Overproduction of NAD+ is an alternative to the conventional fermentation process using Mn2+ deficiency. A simple model is presented to discuss the metabolic regulation of the new process based on the presence of a manganese ribonucleotide reductase (Mn-RNR) in the producing strain. PMID:12882290

  20. Ability of Group IVB metallocene polyethers containing dienestrol to arrest the growth of selected cancer cell lines

    International Nuclear Information System (INIS)

    Monomeric Group IVB (Ti, Zr and Hf) metallocenes represent a new class of antitumor compounds. There is literature on the general biological activities of some organotin compounds. Unfortunately, there is little information with respect to the molecular level activity of these organotin compounds. We recently started focusing on the anti-cancer activity of organotin polymers that we had made for other purposes and as part of our platinum anti-cancer effort. For this study, we synthesized a new series of metallocene-containing compounds coupling the metallocene unit with dienestrol, a synthetic, nonsteroidal estrogen. This is part of our effort to couple known moieties that offer antitumor activity with biologically active units hoping to increase the biological activity of the combination. The materials were confirmed to be polymeric using light scattering photometry and the structural repeat unit was verified employing matrix assisted laser desorption ionization mass spectrometry and infrared spectroscopy results. The polymers demonstrated the ability to suppress the growth of a series of tumor cell lines originating from breast, colon, prostrate, and lung cancers at concentrations generally lower than those required for inhibition of cell growth by the commonly used antitumor drug cisplatin. These drugs show great promise in vitro against a number of cancer cell lines and due to their polymeric nature will most likely be less toxic than currently used metal-containing drugs such as cisplatin. These drugs also offer several addition positive aspects. First, the reactants are commercially available so that additional synthetic steps are not needed. Second, synthesis of the polymer is rapid, occurring within about 15 seconds. Third, the interfacial synthetic system is already industrially employed in the synthesis of aromatic nylons and polycarbonates. Thus, the ability to synthesize large amounts of the drugs is straight forward

  1. Plant HDAC inhibitor chrysin arrest cell growth and induce p21WAF1 by altering chromatin of STAT response element in A375 cells

    Directory of Open Access Journals (Sweden)

    Pal-Bhadra Manika

    2012-05-01

    Full Text Available Abstract Background Chrysin and its analogues, belongs to flavonoid family and possess potential anti-tumour activity. The aim of this study is to determine the molecular mechanism by which chrysin controls cell growth and induce apoptosis in A375 cells. Methods Effect of chrysin and its analogues on cell viability and cell cycle analysis was determined by MTT assay and flowcytometry. A series of Western blots was performed to determine the effect of chrysin on important cell cycle regulatory proteins (Cdk2, cyclin D1, p53, p21, p27. The fluorimetry and calorimetry based assays was conducted for characterization of chrysin as HDAC inhibitor. The changes in histone tail modification such as acetylation and methylation was studied after chrysin treatment was estimated by immuno-fluorescence and western blot analysis. The expression of Bcl-xL, survivin and caspase-3 was estimated in chrysin treated cells. The effect of chrysin on p21 promoter activity was studied by luciferase and ChIP assays. Results Chrysin cause G1 cell cycle arrest and found to inhibit HDAC-2 and HDAC-8. Chrysin treated cells have shown increase in the levels of H3acK14, H4acK12, H4acK16 and decrease in H3me2K9 methylation. The p21 induction by chrysin treatment was found to be independent of p53 status. The chromatin remodelling at p21WAF1 promoter induces p21 activity, increased STAT-1 expression and epigenetic modifications that are responsible for ultimate cell cycle arrest and apoptosis. Conclusion Chrysin shows in vitro anti-cancer activity that is correlated with induction of histone hyperacetylation and possible recruitment of STAT-1, 3, 5 proteins at STAT (−692 to −684 region of p21 promoter. Our results also support an unexpected action of chrysin on the chromatin organization of p21WAF1 promoter through histone methylation and hyper-acetylation. It proposes previously unknown sequence specific chromatin modulations in the STAT responsive elements for regulating

  2. Plant HDAC inhibitor chrysin arrest cell growth and induce p21WAF1 by altering chromatin of STAT response element in A375 cells

    International Nuclear Information System (INIS)

    Chrysin and its analogues, belongs to flavonoid family and possess potential anti-tumour activity. The aim of this study is to determine the molecular mechanism by which chrysin controls cell growth and induce apoptosis in A375 cells. Effect of chrysin and its analogues on cell viability and cell cycle analysis was determined by MTT assay and flowcytometry. A series of Western blots was performed to determine the effect of chrysin on important cell cycle regulatory proteins (Cdk2, cyclin D1, p53, p21, p27). The fluorimetry and calorimetry based assays was conducted for characterization of chrysin as HDAC inhibitor. The changes in histone tail modification such as acetylation and methylation was studied after chrysin treatment was estimated by immuno-fluorescence and western blot analysis. The expression of Bcl-xL, survivin and caspase-3 was estimated in chrysin treated cells. The effect of chrysin on p21 promoter activity was studied by luciferase and ChIP assays. Chrysin cause G1 cell cycle arrest and found to inhibit HDAC-2 and HDAC-8. Chrysin treated cells have shown increase in the levels of H3acK14, H4acK12, H4acK16 and decrease in H3me2K9 methylation. The p21 induction by chrysin treatment was found to be independent of p53 status. The chromatin remodelling at p21WAF1 promoter induces p21 activity, increased STAT-1 expression and epigenetic modifications that are responsible for ultimate cell cycle arrest and apoptosis. Chrysin shows in vitro anti-cancer activity that is correlated with induction of histone hyperacetylation and possible recruitment of STAT-1, 3, 5 proteins at STAT (−692 to −684) region of p21 promoter. Our results also support an unexpected action of chrysin on the chromatin organization of p21WAF1 promoter through histone methylation and hyper-acetylation. It proposes previously unknown sequence specific chromatin modulations in the STAT responsive elements for regulating cell cycle progression negatively via the induction of the CDK

  3. Treatment of mouse melanoma cells with phorbol 12-myristate 13-acetate counteracts mannosylerythritol lipid-induced growth arrest and apoptosis.

    Science.gov (United States)

    Zhao, X; Geltinger, C; Kishikawa, S; Ohshima, K; Murata, T; Nomura, N; Nakahara, T; Yokoyama, K K

    2000-07-01

    Mannosylerythritol lipid (MEL), an extracellularglycolipid from yeast, induces the differentiation ofHL-60 promyelocytic leukemia cells towardsgranulocytes. We show here that MEL is also a potentinhibitor of the proliferation of mouse melanoma B16cells. Flow-cytometric analysis of the cell cycle ofMEL-treated B16 cells revealed the accumulation ofcells in the sub-G(0)/G(1) phase, which is a hallmark ofcells undergoing apoptosis. Treatment of B16 cellsfor 24 h with phorbol 12-myristate 13-acetate (PMA),an activator of protein kinase C (PKC), did notinterfere with the growth and survival of the cells,but it effectively counteracted the MEL-induced growtharrest and apoptosis. The activity of PKC was reducedin B16 cells treated with MEL at a concentration atwhich MEL induced apoptosis. However, incubation withPMA in addition to MEL reversed this reduction in theactivity of PKC. These results suggest thatconverging signaling pathways are triggeredindependently by MEL and PMA and that the signalsmight both be mediated by PKC. PMID:19002819

  4. Dual involvement of growth arrest-specific gene 6 in the early phase of human IgA nephropathy.

    Directory of Open Access Journals (Sweden)

    Kojiro Nagai

    Full Text Available BACKGROUND: Gas6 is a growth factor that causes proliferation of mesangial cells in the development of glomerulonephritis. Gas6 can bind to three kinds of receptors; Axl, Dtk, and Mer. However, their expression and functions are not entirely clear in the different glomerular cell types. Meanwhile, representative cell cycle regulatory protein p27 has been reported to be expressed in podocytes in normal glomeruli with decreased expression in proliferating glomeruli, which inversely correlated with mesangial proliferation in human IgA nephropathy (IgAN. METHODS: The aim of this study is to clarify Gas6 involvement in the progression of IgAN. Expression of Gas6/Axl/Dtk was examined in 31 biopsy proven IgAN cases. We compared the expression levels with histological severity or clinical data. Moreover, we investigated the expression of Gas6 and its receptors in cultured podocytes. RESULTS: In 28 of 31 cases, Gas6 was upregulated mainly in podocytes. In the other 3 cases, Gas6 expression was induced in endothelial and mesangial cells, which was similar to animal nephritis models. Among 28 podocyte type cases, the expression level of Gas6 correlated with the mesangial hypercellularity score of IgAN Oxford classification and urine protein excretion. It also inversely correlated with p27 expression in glomeruli. As for the receptors, Axl was mainly expressed in endothelial and mesangial cells, while Dtk was expressed in podocytes. In vitro, Dtk was expressed in cultured murine podocytes, and the expression of p27 was decreased by Gas6 stimulation. CONCLUSIONS: Gas6 was uniquely upregulated in either endothelial/mesangial cells or podocytes in IgAN. The expression pattern can be used as a marker to classify IgAN. Gas6 has a possibility to be involved in not only mesangial proliferation via Axl, but also podocyte injury via Dtk in IgAN.

  5. Dehydroleucodine inhibits tumor growth in a preclinical melanoma model by inducing cell cycle arrest, senescence and apoptosis.

    Science.gov (United States)

    Costantino, Valeria V; Lobos-Gonzalez, Lorena; Ibañez, Jorge; Fernandez, Dario; Cuello-Carrión, F Darío; Valenzuela, Manuel A; Barbieri, Manuel A; Semino, Silvana N; Jahn, Graciela A; Quest, Andrew F G; Lopez, Luis A

    2016-03-01

    Malignant melanoma represents the fastest growing public health risk of all cancer types worldwide. Several strategies and anti-cancer drugs have been used in an effort to improve treatments, but the development of resistance to anti-neoplastic drugs remains the major cause of chemotherapy failure in melanomas. Previously, we showed that the sesquiterpene lactone, dehydroleucodine (DhL), promotes the accumulation of DNA damage markers, such as H2AX and 53BP1, in human tumor cells. Also DhL was shown to trigger either cell senescence or apoptosis in a concentration-dependent manner in HeLa and MCF7 cells. Here, we evaluated the effects of DhL on B16F0 mouse melanoma cells in vitro and in a pre-clinical melanoma model. DhL inhibited the proliferation of B16F0 cells by inducing senescence or apoptosis in a concentration-dependent manner. Also, DhL reduced the expression of the cell cycle proteins cyclin D1 and B1 and the inhibitor of apoptosis protein, survivin. In melanomas generated by subcutaneous injection of B16F0 cells into C57/BL6 mice, the treatment with 20 mg DhL /Kg/day in preventive, simultaneous and therapeutic protocols reduced tumor volumes by 70%, 60% and 50%, respectively. DhL treatments reduced the number of proliferating, while increasing the number of senescent and apoptotic tumor cells. To estimate the long-term effects of DhL, a mathematical model was applied to fit experimental data. Extrapolation beyond experimental time points revealed that DhL administration following preventive and therapeutic protocols is predicted to be more effective than simultaneous treatments with DhL in restricting tumor growth. PMID:26718258

  6. Prediction of solution structures of the Ca2+-bound gamma-carboxyglutamic acid domains of protein S and homolog growth arrest specific protein 6: use of the particle mesh Ewald method.

    OpenAIRE

    Perera, L; Li, L.; Darden, T.; Monroe, D M; Pedersen, L G

    1997-01-01

    The solution structures of the N-terminal domains of protein S, a plasma vitamin K-dependent glycoprotein, and its homolog growth arrest specific protein 6 (Gas6) were predicted by molecular dynamics computer simulations. The initial structures were based on the x-ray crystallographic structure of the corresponding region of bovine prothrombin fragment 1. The subsequent molecular dynamics trajectories were calculated using the second-generation AMBER force field. The long-range electrostatic ...

  7. Growth arrest-specific transcript 5 associated snoRNA levels are related to p53 expression and DNA damage in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Jonathan Krell

    Full Text Available The growth arrest-specific transcript 5 gene (GAS5 encodes a long noncoding RNA (lncRNA and hosts a number of small nucleolar RNAs (snoRNAs that have recently been implicated in multiple cellular processes and cancer. Here, we investigate the relationship between DNA damage, p53, and the GAS5 snoRNAs to gain further insight into the potential role of this locus in cell survival and oncogenesis both in vivo and in vitro.We used quantitative techniques to analyse the effect of DNA damage on GAS5 snoRNA expression and to assess the relationship between p53 and the GAS5 snoRNAs in cancer cell lines and in normal, pre-malignant, and malignant human colorectal tissue and used biological techniques to suggest potential roles for these snoRNAs in the DNA damage response.GAS5-derived snoRNA expression was induced by DNA damage in a p53-dependent manner in colorectal cancer cell lines and their levels were not affected by DICER. Furthermore, p53 levels strongly correlated with GAS5-derived snoRNA expression in colorectal tissue.In aggregate, these data suggest that the GAS5-derived snoRNAs are under control of p53 and that they have an important role in mediating the p53 response to DNA damage, which may not relate to their function in the ribosome. We suggest that these snoRNAs are not processed by DICER to form smaller snoRNA-derived RNAs with microRNA (miRNA-like functions, but their precise role requires further evaluation. Furthermore, since GAS5 host snoRNAs are often used as endogenous controls in qPCR quantifications we show that their use as housekeeping genes in DNA damage experiments can lead to inaccurate results.

  8. Hwanggeumchal sorghum induces cell cycle arrest, and suppresses tumor growth and metastasis through Jak2/STAT pathways in breast cancer xenografts.

    Directory of Open Access Journals (Sweden)

    Jin Hee Park

    Full Text Available BACKGROUND: Cancer is one of the highly virulent diseases known to humankind with a high mortality rate. Breast cancer is the most common cancer in women worldwide. Sorghum is a principal cereal food in many parts of the world, and is critical in folk medicine of Asia and Africa. In the present study, we analyzed the effects of HSE in metastatic breast cancer. METHODOLOGY/PRINCIPAL FINDINGS: Preliminary studies conducted on MDA-MB 231 and MCF-7 xenograft models showed tumor growth suppression by HSE. Western blotting studies conducted both in vivo and in vitro to check the effect of HSE in Jak/STAT pathways. Anti-metastatic effects of HSE were confirmed using both MDA-MB 231 and MCF-7 metastatic animal models. These studies showed that HSE can modulate Jak/STAT pathways, and it hindered the STAT5b/IGF-1R and STAT3/VEGF pathways not only by down-regulating the expression of these signal molecules and but also by preventing their phosphorylation. The expression of angiogenic factors like VEGF, VEGF-R2 and cell cycle regulators like cyclin D, cyclin E, and pRb were found down-regulated by HSE. In addition, it also targets Brk, p53, and HIF-1α for anti-cancer effects. HSE induced G1 phase arrest and migration inhibition in MDA-MB 231 cells. The metastasis of breast cancer to the lungs also found blocked by HSE in the metastatic animal model. CONCLUSIONS/SIGNIFICANCE: Usage of HS as a dietary supplement is an inexpensive natural cancer therapy, without any side effects. We strongly recommend the use of HS as an edible therapeutic agent as it possesses tumor suppression, migration inhibition, and anti-metastatic effects on breast cancer.

  9. N-Methyl-N'-nitro-N-nitrosoguanidine-induced senescence-like growth arrest in colon cancer cells is associated with loss of adenomatous polyposis coli protein, microtubule organization, and telomeric DNA

    Directory of Open Access Journals (Sweden)

    Narayan Satya

    2004-01-01

    Full Text Available Abstract Background Cellular senescence is a state in which mammalian cells enter into an irreversible growth arrest and altered biological functions. The senescence response in mammalian cells can be elicited by DNA-damaging agents. In the present study we report that the DNA-damaging agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG is able to induce senescence in the HCT-116 colon cancer cell line. Results Cells treated with lower concentrations of MNNG (0–25 microM for 50 h showed a dose-dependent increase in G2/M phase arrest and apoptosis; however, cells treated with higher concentrations of MNNG (50–100 microM showed a senescence-like G0/G1 phase arrest which was confirmed by increased expression of β-galactosidase, a senescence induced marker. The G2/M phase arrest and apoptosis were found to be associated with increased levels of p53 protein, but the senescence-like G0/G1 phase arrest was dissociated with p53 protein levels, since the p53 protein levels decreased in senescence-like arrested cells. We further, determined whether the decreased level of p53 was a transcriptional or a translational phenomenon. The results revealed that the decreased level of p53 protein in senescence-like arrested cells was a transcriptional phenomenon since p53 mRNA levels simultaneously decreased after treatment with higher concentrations of MNNG. We also examined the effect of MNNG treatment on other cell cycle-related proteins such as p21, p27, cyclin B1, Cdc2, c-Myc and max. The expression levels of these proteins were increased in cells treated with lower concentrations of MNNG, which supported the G2/M phase arrest. However, cells treated with higher concentrations of MNNG showed decreased levels of these proteins, and hence, may not play a role in cell cycle arrest. We then examined a possible association of the expression of APC protein and telomeric DNA signals with cellular senescence in MNNG-treated cells. We found that protein and m

  10. Growth arrest by the antitumor steroidal lactone withaferin A in human breast cancer cells is associated with down-regulation and covalent binding at cysteine 303 of β-tubulin.

    Science.gov (United States)

    Antony, Marie L; Lee, Joomin; Hahm, Eun-Ryeong; Kim, Su-Hyeong; Marcus, Adam I; Kumari, Vandana; Ji, Xinhua; Yang, Zhen; Vowell, Courtney L; Wipf, Peter; Uechi, Guy T; Yates, Nathan A; Romero, Guillermo; Sarkar, Saumendra N; Singh, Shivendra V

    2014-01-17

    Withaferin A (WA), a C5,C6-epoxy steroidal lactone derived from a medicinal plant (Withania somnifera), inhibits growth of human breast cancer cells in vitro and in vivo and prevents mammary cancer development in a transgenic mouse model. However, the mechanisms underlying the anticancer effect of WA are not fully understood. Herein, we report that tubulin is a novel target of WA-mediated growth arrest in human breast cancer cells. The G2 and mitotic arrest resulting from WA exposure in MCF-7, SUM159, and SK-BR-3 cells was associated with a marked decrease in protein levels of β-tubulin. These effects were not observed with the naturally occurring C6,C7-epoxy analogs of WA (withanone and withanolide A). A non-tumorigenic normal mammary epithelial cell line (MCF-10A) was markedly more resistant to mitotic arrest by WA compared with breast cancer cells. Vehicle-treated control cells exhibited a normal bipolar spindle with chromosomes aligned along the metaphase plate. In contrast, WA treatment led to a severe disruption of normal spindle morphology. NMR analyses revealed that the A-ring enone in WA, but not in withanone or withanolide A, was highly reactive with cysteamine and rapidly succumbed to irreversible nucleophilic addition. Mass spectrometry demonstrated direct covalent binding of WA to Cys(303) of β-tubulin in MCF-7 cells. Molecular docking indicated that the WA-binding pocket is located on the surface of β-tubulin and characterized by a hydrophobic floor, a hydrophobic wall, and a charge-balanced hydrophilic entrance. These results provide novel insights into the mechanism of growth arrest by WA in breast cancer cells. PMID:24297176

  11. Multivariate modeling of chromium-induced oxidative stress and biochemical changes in plants of Pistia stratiotes L.

    Science.gov (United States)

    Sinha, Sarita; Basant, Ankita; Malik, Amrita; Singh, Kunwar P

    2009-07-01

    Biochemical changes in the plants of Pistia stratiotes L., a free floating macrophyte exposed to different concentrations of hexavalent chromium (0, 10, 40, 60, 80 and 160 microM) for 48, 96 and 144 h were studied. Chromium-induced oxidative stress in macrophyte was investigated using the multivariate modeling approaches. Cluster analysis rendered two fairly distinct clusters (roots and shoots) of similar characteristics in terms of their biochemical responses. Discriminant analysis identified ascorbate peroxidase (APX) as discriminating variable between the root and shoot tissues. Principal components analysis results suggested that malondialdehyde (MDA), superoxide dismutase (SOD), APX, non-protein thiols (NP-SH), cysteine, ascorbic acid, and Cr-accumulation are dominant in root tissues, whereas, protein and guaiacol peroxidase (GPX) in shoots of the plant. Discriminant partial least squares analysis results further confirmed that MDA, SOD, NP-SH, cysteine, GPX, APX, ascorbic acid and Cr-accumulation dominated in the root tissues, while protein in the shoot. Three-way analysis helped in visualizing simultaneous influence of metal concentration and exposure duration on biochemical variables in plant tissues. The multivariate approaches, thus, allowed for the interpretation of the induced biochemical changes in the plant tissues exposed to chromium, which otherwise using the conventional approaches is difficult. PMID:19396544

  12. The mitigative effect of Raphanus sativus oil on chromium-induced geno- and hepatotoxicity in male rats.

    Science.gov (United States)

    Elshazly, M O; Morgan, Ashraf M; Ali, Merhan E; Abdel-Mawla, Essam; Abd El-Rahman, Sahar S

    2016-05-01

    To study the impact of radish oil on the possible genotoxic and hepatotoxic effects of hexavalent chromium, male rats were divided into 4 groups. Group 1 served as control, group 2 received radish oil at the recommended human therapeutic dose (0.07 mL/kg) by gavage, group 3 received sodium dichromate dihydrate (SDD) 520 mg/L in drinking water, and group 4 received both SDD and radish oil as previously mentioned in groups 2 and 3. All treatments were continued for six months. The results revealed that chromium exposure promoted oxidative stress with a consequently marked hepatic histopathological alterations, increased serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities, alfa fetoprotein (AFP) levels, and micronucleated erythrocytes (MNE) % in peripheral blood. Moreover, COMET assay of hepatic DNA revealed that SDD exposure significantly decreased the intact cells %, head diameter, and head DNA % compared to control, indicating DNA damage. However, radish oil co-administration with SDD resulted in marked amendment in the altered parameters as detected by improved liver function markers (ALT and ALP) and AFP level, decreased lipid peroxidation, increased antioxidant markers, inhibited hepatic DNA damage and restored the hepatic histology by preventing the appearance of the altered hepatocytes' foci and decreasing chromium induced histopathological lesions. It could be concluded that radish oil was able to provide a convergent complete protection against the geno- and hepatotoxicity of chromium by its potent antioxidant effect. PMID:27222746

  13. Sonic Hedgehog Opposes Epithelial Cell Cycle Arrest

    OpenAIRE

    Fan, Hongran; Khavari, Paul A

    1999-01-01

    Stratified epithelium displays an equilibrium between proliferation and cell cycle arrest, a balance that is disrupted in basal cell carcinoma (BCC). Sonic hedgehog (Shh) pathway activation appears sufficient to induce BCC, however, the way it does so is unknown. Shh-induced epidermal hyperplasia is accompanied by continued cell proliferation in normally growth arrested suprabasal cells in vivo. Shh-expressing cells fail to exit S and G2/M phases in response to calcium-induced differentiation...

  14. Deterrence and arrest ratios.

    Science.gov (United States)

    Carmichael, Stephanie E; Piquero, Alex R

    2006-02-01

    In the limited research on the origins of sanction threat perceptions, researchers have focused on either the effects of actively engaging in crime or the effects of formal sanctioning but rarely on both (i.e., the arrest ratio or the number of arrests relative to the number of crimes committed). This article extends this line of research by using a sample of Colorado inmates and measures arrest ratios and sanction perceptions for eight different crime types. Analyses reveal that the offenders report both significant experiential and arrest ratio effects. Theoretical and policy implications, limitations, and directions for future research are outlined. PMID:16397123

  15. High-density growth arrest in Ras-transformed cells: low Cdk kinase activities in spite of absence of p27Kip Cdk-complexes

    DEFF Research Database (Denmark)

    Groth, Anja; Willumsen, Berthe Marie

    2005-01-01

    and Cdk2 complexes, as these kinases were inactivated. Ras-transformed cells failed to arrest at normal saturation density and showed no significant alterations in cell control complexes at this point. Yet, at an elevated density the Ras-transformed cells ceased to proliferate and entered a quiescent......-like state with low Cdk4 and Cdk2 activity. Surprisingly, this delayed arrest was molecularly distinct from contact inhibition of normal cells, as it occurred in the absence of p27Kip1 induction and cyclin D1 levels remained high. This demonstrates that although oncogenic Ras efficiently disabled the normal...

  16. A novel site contributing to growth-arrest-specific gene 6 binding to its receptors as revealed by a human monoclonal antibody

    Science.gov (United States)

    2004-01-01

    Gas6 (growth-arrest-specific gene 6) is a vitamin K-dependent protein known to activate the Axl family of receptor tyrosine kinases. It is an important regulator of thrombosis and many other biological functions. The C-terminus of Gas6 binds to receptors and consists of two laminin-like globular domains LG1 and LG2. It has been reported that a Ca2+-binding site at the junction of LG1 and LG2 domains and a hydrophobic patch at the LG2 domain are important for receptor binding [Sasaki, Knyazev, Cheburkin, Gohring, Tisi, Ullrich, Timpl and Hohenester (2002) J. Biol. Chem. 277, 44164–44170]. In the present study, we developed a neutralizing human monoclonal antibody, named CNTO300, for Gas6. The antibody was generated by immunization of human IgG-expressing transgenic mice with recombinant human Gas6 protein and the anti-Gas6 IgG sequences were rescued from an unstable hybridoma clone. Binding of Gas6 to its receptors was partially inhibited by the CNTO300 antibody in a dose-dependent manner. To characterize further the interaction between Gas6 and this antibody, the binding kinetics of CNTO300 for recombinant Gas6 were compared with independently expressed LG1 and LG2. The CNTO300 antibody showed comparable binding affinity, yet different dependence on Ca2+, to Gas6 and LG1. No binding to LG2 was detected. In the presence of EDTA, binding of the antibody to Gas6 was disrupted, but no significant effect of EDTA on LG1 binding was evident. Further epitope mapping identified a Gas6 peptide sequence recognized by the CNTO300 antibody. This peptide sequence was found to be located at the LG1 domain distant from the Ca2+-binding site and the hydrophobic patch. Co-interaction of Gas6 with its receptor and CNTO300 antibody was detected by BIAcore analysis, suggesting a second receptor-binding site on the LG1 domain. This hypothesis was further supported by direct binding of Gas6 receptors to an independently expressed LG1 domain. Our results revealed, for the first time, a

  17. Chromium-Induced Ultrastructural Changes and Oxidative Stress in Roots of Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Eleftherios P. Eleftheriou

    2015-07-01

    Full Text Available Chromium (Cr is an abundant heavy metal in nature, toxic to living organisms. As it is widely used in industry and leather tanning, it may accumulate locally at high concentrations, raising concerns for human health hazards. Though Cr effects have extensively been investigated in animals and mammals, in plants they are poorly understood. The present study was then undertaken to determine the ultrastructural malformations induced by hexavalent chromium [Cr(VI], the most toxic form provided as 100 μM potassium dichromate (K2Cr2O7, in the root tip cells of the model plant Arabidopsis thaliana. A concentration-dependent decrease of root growth and a time-dependent increase of dead cells, callose deposition, hydrogen peroxide (H2O2 production and peroxidase activity were found in Cr(VI-treated seedlings, mostly at the transition root zone. In the same zone, nuclei remained ultrastructurally unaffected, but in the meristematic zone some nuclei displayed bulbous outgrowths or contained tubular structures. Endoplasmic reticulum (ER was less affected under Cr(VI stress, but Golgi bodies appeared severely disintegrated. Moreover, mitochondria and plastids became spherical and displayed translucent stroma with diminished internal membranes, but noteworthy is that their double-membrane envelopes remained structurally intact. Starch grains and electron dense deposits occurred in the plastids. Amorphous material was also deposited in the cell walls, the middle lamella and the vacuoles. Some vacuoles were collapsed, but the tonoplast appeared integral. The plasma membrane was structurally unaffected and the cytoplasm contained opaque lipid droplets and dense electron deposits. All electron dense deposits presumably consisted of Cr that is sequestered from sensitive sites, thus contributing to metal tolerance. It is concluded that the ultrastructural changes are reactive oxygen species (ROS-correlated and the malformations observed are organelle specific.

  18. Chromium-Induced Ultrastructural Changes and Oxidative Stress in Roots of Arabidopsis thaliana.

    Science.gov (United States)

    Eleftheriou, Eleftherios P; Adamakis, Ioannis-Dimosthenis S; Panteris, Emmanuel; Fatsiou, Maria

    2015-01-01

    Chromium (Cr) is an abundant heavy metal in nature, toxic to living organisms. As it is widely used in industry and leather tanning, it may accumulate locally at high concentrations, raising concerns for human health hazards. Though Cr effects have extensively been investigated in animals and mammals, in plants they are poorly understood. The present study was then undertaken to determine the ultrastructural malformations induced by hexavalent chromium [Cr(VI)], the most toxic form provided as 100 μM potassium dichromate (K2Cr2O7), in the root tip cells of the model plant Arabidopsis thaliana. A concentration-dependent decrease of root growth and a time-dependent increase of dead cells, callose deposition, hydrogen peroxide (H2O2) production and peroxidase activity were found in Cr(VI)-treated seedlings, mostly at the transition root zone. In the same zone, nuclei remained ultrastructurally unaffected, but in the meristematic zone some nuclei displayed bulbous outgrowths or contained tubular structures. Endoplasmic reticulum (ER) was less affected under Cr(VI) stress, but Golgi bodies appeared severely disintegrated. Moreover, mitochondria and plastids became spherical and displayed translucent stroma with diminished internal membranes, but noteworthy is that their double-membrane envelopes remained structurally intact. Starch grains and electron dense deposits occurred in the plastids. Amorphous material was also deposited in the cell walls, the middle lamella and the vacuoles. Some vacuoles were collapsed, but the tonoplast appeared integral. The plasma membrane was structurally unaffected and the cytoplasm contained opaque lipid droplets and dense electron deposits. All electron dense deposits presumably consisted of Cr that is sequestered from sensitive sites, thus contributing to metal tolerance. It is concluded that the ultrastructural changes are reactive oxygen species (ROS)-correlated and the malformations observed are organelle specific. PMID:26204828

  19. Growth arrest- and DNA-damage-inducible 45beta gene inhibits c-Jun N-terminal kinase and extracellular signal-regulated kinase and decreases IL-1beta-induced apoptosis in insulin-producing INS-1E cells

    DEFF Research Database (Denmark)

    Larsen, Claus Morten; Døssing, M G; Papa, S;

    2006-01-01

    IL-1beta is a candidate mediator of apoptotic beta cell destruction, a process that leads to type 1 diabetes and progression of type 2 diabetes. IL-1beta activates beta cell c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38, all of which are members of the mitogen......-activated protein kinase (MAPK) family. Inhibition of JNK prevents IL-1beta-mediated beta cell destruction. In mouse embryo fibroblasts and 3DO T cells, overexpression of the gene encoding growth arrest and DNA-damage-inducible 45beta (Gadd45b) downregulates pro-apoptotic JNK signalling. The aim of this study...

  20. Sudden Cardiac Arrest

    Science.gov (United States)

    ... scan, or MUGA, which shows how well your heart is pumping blood. Magnetic resonance imaging (MRI) which gives doctors detailed pictures of your heart. How is SCA treated? Sudden cardiac arrest should ...

  1. Cardiac arrest in children

    Directory of Open Access Journals (Sweden)

    Tress Erika

    2010-01-01

    Full Text Available Major advances in the field of pediatric cardiac arrest (CA were made during the last decade, starting with the publication of pediatric Utstein guidelines, the 2005 recommendations by the International Liaison Committee on Resuscitation, and culminating in multicenter collaborations. The epidemiology and pathophysiology of in-hospital and out-of-hospital CA are now well described. Four phases of CA are described and the term "post-cardiac arrest syndrome" has been proposed, along with treatment goals for each of its four phases: immediate post-arrest, early post-arrest, intermediate and recovery phase. Hypothermia is recommended to be considered as a therapy for post-CA syndrome in comatose patients after CA, and large multicenter prospective studies are underway. We reviewed landmark articles related to pediatric CA published during the last decade. We present the current knowledge of epidemiology, pathophysiology and treatment of CA relevant to pre-hospital and acute care health practitioners.

  2. Cardiac arrest in children.

    Science.gov (United States)

    Tress, Erika E; Kochanek, Patrick M; Saladino, Richard A; Manole, Mioara D

    2010-07-01

    Major advances in the field of pediatric cardiac arrest (CA) were made during the last decade, starting with the publication of pediatric Utstein guidelines, the 2005 recommendations by the International Liaison Committee on Resuscitation, and culminating in multicenter collaborations. The epidemiology and pathophysiology of in-hospital and out-of-hospital CA are now well described. Four phases of CA are described and the term "post-cardiac arrest syndrome" has been proposed, along with treatment goals for each of its four phases: immediate post-arrest, early post-arrest, intermediate and recovery phase. Hypothermia is recommended to be considered as a therapy for post-CA syndrome in comatose patients after CA, and large multicenter prospective studies are underway. We reviewed landmark articles related to pediatric CA published during the last decade. We present the current knowledge of epidemiology, pathophysiology and treatment of CA relevant to pre-hospital and acute care health practitioners. PMID:20930971

  3. Sudden Cardiac Arrest

    Science.gov (United States)

    ... Heart Risk Factors & Prevention Heart Diseases & Disorders Atrial Fibrillation (AFib) Sudden Cardiac Arrest (SCA) SCA: Who's At Risk? Prevention of SCA What Causes SCA? SCA Awareness Atrial Flutter Heart Block Heart Failure Sick Sinus Syndrome Substances & Heart Rhythm Disorders Symptoms & ...

  4. Sudden Cardiac Arrest

    Science.gov (United States)

    ... often are found in public places, such as shopping malls, golf courses, businesses, airports, airplanes, casinos, ... arrest In a study published online today in the New England Journal of Medicine , ...

  5. Cardiac arrest - cardiopulmonary resuscitation

    Institute of Scientific and Technical Information of China (English)

    Basri Lenjani; Besnik Elshani; Nehat Baftiu; Kelmend Pallaska; Kadir Hyseni; Njazi Gashi; Nexhbedin Karemani; Ilaz Bunjaku; Taxhidin Zaimi; Arianit Jakupi

    2014-01-01

    Objective:To investigate application of cardiopulmonary resuscitation(CPR) measures within the golden minutes inEurope.Methods:The material was taken from theUniversityClinical Center ofKosovo -EmergencyCentre inPristina, during the two(2) year period(2010-2011).The collected date belong to the patients with cardiac arrest have been recorded in the patients' log book protocol at the emergency clinic.Results:During the2010 to2011 in the emergency center of theCUCK inPristina have been treated a total of269 patients with cardiac arrest, of whom159 or59.1% have been treated in2010, and110 patients or40.9% in2011.Of the269 patients treated in the emergency centre,93 or34.6% have exited lethally in the emergency centre, and176 or 65.4% have been transferred to other clinics.In the total number of patients with cardiac arrest, males have dominated with186 cases, or69.1%.The average age of patients included in the survey was56.7 year oldSD±16.0 years.Of the269 patients with cardiac arrest, defibrillation has been applied for93 or34.6% of patients.In the outpatient settings defibrillation has been applied for3 or3.2% of patients.Patients were defibrillated with application of one to four shocks. Of27 cases with who have survived cardiac arrest, none of them have suffered cardiac arrest at home,3 or11.1% of them have suffered cardiac arrest on the street, and24 or88.9% of them have suffered cardiac arrest in the hospital.5 out of27 patients survived have ended with neurological impairment.Cardiac arrest cases were present during all days of the week, but frequently most reported cases have been onMonday with32.0% of cases, and onFriday with24.5% of cases. Conclusions:All survivors from cardiac arrest have received appropriate medical assistance within10 min from attack, which implies that if cardiac arrest occurs near an institution health care(with an opportunity to provide the emergent health care) the rate of survival is higher.

  6. The prospective protective effect of selenium nanoparticles against chromium-induced oxidative and cellular damage in rat thyroid

    Directory of Open Access Journals (Sweden)

    Hassanin KMA

    2013-05-01

    Full Text Available Kamel MA Hassanin,1 Samraa H Abd El-Kawi,2 Khalid S Hashem1 1Department of Biochemistry, Faculty of Veterinary Medicine, 2Department of Histology, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt Background: Nanotechnology has enabled researchers to synthesize nanosize particles that possess increased surface areas. Compared to conventional microparticles, it has resulted in increased interactions with biological targets. Objective: The objective of this study was to determine the protective ability of selenium nanoparticles against hexavalent chromium-induced thyrotoxicity. Design: Twenty male rats were used in the study, and arbitrarily assigned to four groups. Group 1 was the control group, and was given phosphate-buffered saline. Group 2 was the chromium-treated group and was given K2Cr2O7 60 µg/kg body weight intraperitoneally as a single dose on the third day of administration. Group 3 was the nano-selenium-treated group and was given selenium nanoparticles (size 3–20 nm 0.5 mg/kg body weight intraperitoneally daily for 5 consecutive days. Group 4 was the nano-selenium chromium-treated group, which received selenium nanoparticles for 5 days and a single dose of K2Cr2O7 on the third day of administration. Materials and methods: Blood samples were collected from rats for measuring thyroid hormones (free triiodothyronine [T3] and free thyroxine [T4] and oxidative and antioxidant parameters (malondialdehyde [MDA], reduced glutathione [GSH], catalase, and superoxide dismutase [SOD]. Upon dissection, thyroid glands were taken for histopathological examination by using paraffin preparations stained with hematoxylin and eosin (H&E and Masson’s trichrome. Immunohistochemical staining was performed for detecting cellular proliferation using Ki67 antibodies. Results: The present study shows that K2Cr2O7 has a toxic effect on the thyroid gland as a result of inducing a marked oxidative damage and release of reactive oxygen species

  7. 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. PMID:26046133

  8. 4β-Hydroxywithanolide E from Physalis peruviana (golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest

    International Nuclear Information System (INIS)

    The crude extract of the fruit bearing plant, Physalis peruviana (golden berry), demonstrated anti-hepatoma and anti-inflammatory activities. However, the cellular mechanism involved in this process is still unknown. Herein, we isolated the main pure compound, 4β-Hydroxywithanolide (4βHWE) derived from golden berries, and investigated its antiproliferative effect on a human lung cancer cell line (H1299) using survival, cell cycle, and apoptosis analyses. An alkaline comet-nuclear extract (NE) assay was used to evaluate the DNA damage due to the drug. It was shown that DNA damage was significantly induced by 1, 5, and 10 μg/mL 4βHWE for 2 h in a dose-dependent manner (p < 0.005). A trypan blue exclusion assay showed that the proliferation of cells was inhibited by 4βHWE in both dose- and time-dependent manners (p < 0.05 and 0.001 for 24 and 48 h, respectively). The half maximal inhibitory concentrations (IC50) of 4βHWE in H1299 cells for 24 and 48 h were 0.6 and 0.71 μg/mL, respectively, suggesting it could be a potential therapeutic agent against lung cancer. In a flow cytometric analysis, 4βHWE produced cell cycle perturbation in the form of sub-G1 accumulation and slight arrest at the G2/M phase with 1 μg/mL for 12 and 24 h, respectively. Using flow cytometric and annexin V/propidium iodide immunofluorescence double-staining techniques, these phenomena were proven to be apoptosis and complete G2/M arrest for H1299 cells treated with 5 μg/mL for 24 h. In this study, we demonstrated that golden berry-derived 4βHWE is a potential DNA-damaging and chemotherapeutic agent against lung cancer

  9. 4β-Hydroxywithanolide E from Physalis peruviana (golden berry inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest

    Directory of Open Access Journals (Sweden)

    Guo Zong-Lun

    2010-02-01

    Full Text Available Abstract Background The crude extract of the fruit bearing plant, Physalis peruviana (golden berry, demonstrated anti-hepatoma and anti-inflammatory activities. However, the cellular mechanism involved in this process is still unknown. Methods Herein, we isolated the main pure compound, 4β-Hydroxywithanolide (4βHWE derived from golden berries, and investigated its antiproliferative effect on a human lung cancer cell line (H1299 using survival, cell cycle, and apoptosis analyses. An alkaline comet-nuclear extract (NE assay was used to evaluate the DNA damage due to the drug. Results It was shown that DNA damage was significantly induced by 1, 5, and 10 μg/mL 4βHWE for 2 h in a dose-dependent manner (p p 50 of 4βHWE in H1299 cells for 24 and 48 h were 0.6 and 0.71 μg/mL, respectively, suggesting it could be a potential therapeutic agent against lung cancer. In a flow cytometric analysis, 4βHWE produced cell cycle perturbation in the form of sub-G1 accumulation and slight arrest at the G2/M phase with 1 μg/mL for 12 and 24 h, respectively. Using flow cytometric and annexin V/propidium iodide immunofluorescence double-staining techniques, these phenomena were proven to be apoptosis and complete G2/M arrest for H1299 cells treated with 5 μg/mL for 24 h. Conclusions In this study, we demonstrated that golden berry-derived 4βHWE is a potential DNA-damaging and chemotherapeutic agent against lung cancer.

  10. Crack-arrest technology

    International Nuclear Information System (INIS)

    Over the last several years, the Heavy Section Steel Technology (HSST) Program has conducted several fracture mechanics experiments on large specimens that produced crack-arrest fracture-toughness values above 220 MPa·√m, which is the limit imposed by the ASME Code and the limit included in the Issues on Pressurized Thermal Shock studies. It is therefore appropriate and timely to investigate the influence that these high crack-arrest data have on the integrity assessment of nuclear Reactor Pressure Vessels (RPVs). A review of the evolution of the Pressurized Thermal Shock (PTS) issue and current methods of analysis provides insight into the motivation for the HSST Program performing the large-specimen fracture mechanics experiments. During the early 1970s, it was recognized that RPVs could be subjected to severe thermal shock as the result of a large-break loss-of-coolant accident (LBLOCA). Analyses performed at that time indicated that thermal shock alone would not result in failure (through-wall cracking) of the vessel. However, a combination of pressure and a less severe thermal shock, the result of some postulated transients, could result in vessel failure. In March 1978, such a transient occurred at the Rancho Seco nuclear power plant. As a result of these events, parametric PTS studies were undertaken. Because of the apparent need for and the existence of high-temperature crack-arrest capability, the NRC HSST Program and others began to investigate the effect of higher crack-arrest values on the probability of failure and to determine if these values actually exist for prototypical RPV materials. This report describes the results of HSST Program large-specimen crack-arrest testing

  11. Resveratrol analogue 3,4,4′,5-tetramethoxystilbene inhibits growth, arrests cell cycle and induces apoptosis in ovarian SKOV‐3 and A-2780 cancer cells

    International Nuclear Information System (INIS)

    In the screening studies, cytotoxicity of 12 methylated resveratrol analogues on 11 human cancer cell lines was examined. The most active compound 3,4,4′5-tetramethoxystilbene (DMU-212) and two ovarian cancer cell lines A-2780 (IC50 = 0.71 μM) and SKOV-3 (IC50 = 11.51 μM) were selected for further investigation. To determine the mechanism of DMU-212 cytotoxicity, its ability to induce apoptosis was examined. DMU-212 arrested cell cycle in the G2/M or G0/G1 phase which resulted in apoptosis of both cell lines. The expression level of 84 apoptosis-related genes was investigated. In SKOV-3 cells DMU-212 caused up-regulation of pro-apoptotic Bax, Apaf-1 and p53 genes, specific to intrinsic pathway of apoptosis, and a decrease in Bcl-2 and Bcl 2110 mRNA expressions. Conversely, in A-2780 cells an increased expression of pro-apoptotic genes Fas, FasL, TNF, TNFRSF10A, TNFRSF21, TNFRSF16 specific to extracellular mechanism of apoptosis was observed. There are no data published so far regarding the receptor mediated apoptosis induced by DMU-212. The activation of caspase-3/7 was correlated with decreased TRAF-1 and BIRC-2 expression level in A-2780 cells exposed to DMU-212. DMU-212 caused a decrease in CYP1A1 and CYP1B1 mRNA levels in A-2780 by 50% and 75%, and in SKOV-3 cells by 15% and 45%, respectively. The protein expression was also reduced in both cell lines. It is noteworthy that the expression of CYP1B1 protein was entirely inhibited in A-2780 cells treated with DMU-212. It can be suggested that different CYP1B1 expression patterns in either ovarian cell line may affect their sensitivity to cytotoxic activity of DMU-212. -- Highlights: ► DMU-212 was the most cytotoxic among 12 O-methylated resveratrol analogues. ► DMU-212 arrested cell cycle at G2/M and G0/G1phase ► DMU-212 triggered mitochondria- and receptor‐mediated apoptosis. ► DMU-212 entirely inhibited CYP1B1 protein expression in A-2780 cells.

  12. Resveratrol analogue 3,4,4′,5-tetramethoxystilbene inhibits growth, arrests cell cycle and induces apoptosis in ovarian SKOV‐3 and A-2780 cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Piotrowska, Hanna; Myszkowski, Krzysztof; Ziółkowska, Alicja [Department of Toxicology, Poznan University of Medical Sciences, Poznan (Poland); Kulcenty, Katarzyna [Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan (Poland); Wierzchowski, Marcin [Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Poznan (Poland); Kaczmarek, Mariusz [Department of Clinical Immunology, Poznan University of Medical Sciences, Poznan (Poland); Murias, Marek [Department of Toxicology, Poznan University of Medical Sciences, Poznan (Poland); Kwiatkowska-Borowczyk, Eliza [Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan (Poland); Department of Cancer Diagnostics and Immunology, Greater Poland Cancer Centre, Poznan (Poland); Jodynis-Liebert, Jadwiga, E-mail: liebert@ump.edu.pl [Department of Toxicology, Poznan University of Medical Sciences, Poznan (Poland)

    2012-08-15

    In the screening studies, cytotoxicity of 12 methylated resveratrol analogues on 11 human cancer cell lines was examined. The most active compound 3,4,4′5-tetramethoxystilbene (DMU-212) and two ovarian cancer cell lines A-2780 (IC{sub 50} = 0.71 μM) and SKOV-3 (IC{sub 50} = 11.51 μM) were selected for further investigation. To determine the mechanism of DMU-212 cytotoxicity, its ability to induce apoptosis was examined. DMU-212 arrested cell cycle in the G2/M or G0/G1 phase which resulted in apoptosis of both cell lines. The expression level of 84 apoptosis-related genes was investigated. In SKOV-3 cells DMU-212 caused up-regulation of pro-apoptotic Bax, Apaf-1 and p53 genes, specific to intrinsic pathway of apoptosis, and a decrease in Bcl-2 and Bcl 2110 mRNA expressions. Conversely, in A-2780 cells an increased expression of pro-apoptotic genes Fas, FasL, TNF, TNFRSF10A, TNFRSF21, TNFRSF16 specific to extracellular mechanism of apoptosis was observed. There are no data published so far regarding the receptor mediated apoptosis induced by DMU-212. The activation of caspase-3/7 was correlated with decreased TRAF-1 and BIRC-2 expression level in A-2780 cells exposed to DMU-212. DMU-212 caused a decrease in CYP1A1 and CYP1B1 mRNA levels in A-2780 by 50% and 75%, and in SKOV-3 cells by 15% and 45%, respectively. The protein expression was also reduced in both cell lines. It is noteworthy that the expression of CYP1B1 protein was entirely inhibited in A-2780 cells treated with DMU-212. It can be suggested that different CYP1B1 expression patterns in either ovarian cell line may affect their sensitivity to cytotoxic activity of DMU-212. -- Highlights: ► DMU-212 was the most cytotoxic among 12 O-methylated resveratrol analogues. ► DMU-212 arrested cell cycle at G2/M and G0/G1phase ► DMU-212 triggered mitochondria- and receptor‐mediated apoptosis. ► DMU-212 entirely inhibited CYP1B1 protein expression in A-2780 cells.

  13. CARI III Inhibits Tumor Growth in a Melanoma-Bearing Mouse Model through Induction of G0/G1 Cell Cycle Arrest

    Directory of Open Access Journals (Sweden)

    Hye-Jin Park

    2014-09-01

    Full Text Available Mushroom-derived natural products have been used to prevent or treat cancer for millennia. In this study, we evaluated the anticancer effects of CARI (Cell Activation Research Institute III, which consists of a blend of mushroom mycelia from Phellinus linteus grown on germinated brown rice, Inonotus obliquus grown on germinated brown rice, Antrodia camphorata grown on germinated brown rice and Ganoderma lucidum. Here, we showed that CARI III exerted anti-cancer activity, which is comparable to Dox against melanoma in vivo. B16F10 cells were intraperitoneally injected into C57BL6 mice to develop solid intra-abdominal tumors. Three hundred milligrams of the CARI III/kg/day p.o. regimen reduced tumor weight, comparable to the doxorubicin (Dox-treated group. An increase in life span (ILS% = 50.88% was observed in the CARI III-administered group, compared to the tumor control group. CARI III demonstrates anti-proliferative activity against B16F10 melanoma cells through inducing G0/G1 cell cycle arrest. CARI III inhibits the expression of cyclin D1, CDK4 and CDK2 and induces p21. Therefore, CARI III could be a potential chemopreventive supplement to melanoma patients.

  14. CARI III inhibits tumor growth in a melanoma-bearing mouse model through induction of G0/G1 cell cycle arrest.

    Science.gov (United States)

    Park, Hye-Jin

    2014-01-01

    Mushroom-derived natural products have been used to prevent or treat cancer for millennia. In this study, we evaluated the anticancer effects of CARI (Cell Activation Research Institute) III, which consists of a blend of mushroom mycelia from Phellinus linteus grown on germinated brown rice, Inonotus obliquus grown on germinated brown rice, Antrodia camphorata grown on germinated brown rice and Ganoderma lucidum. Here, we showed that CARI III exerted anti-cancer activity, which is comparable to Dox against melanoma in vivo. B16F10 cells were intraperitoneally injected into C57BL6 mice to develop solid intra-abdominal tumors. Three hundred milligrams of the CARI III/kg/day p.o. regimen reduced tumor weight, comparable to the doxorubicin (Dox)-treated group. An increase in life span (ILS% = 50.88%) was observed in the CARI III-administered group, compared to the tumor control group. CARI III demonstrates anti-proliferative activity against B16F10 melanoma cells through inducing G0/G1 cell cycle arrest. CARI III inhibits the expression of cyclin D1, CDK4 and CDK2 and induces p21. Therefore, CARI III could be a potential chemopreventive supplement to melanoma patients. PMID:25221864

  15. Dactylone inhibits epidermal growth factor-induced transformation and phenotype expression of human cancer cells and induces G1-S arrest and apoptosis.

    Science.gov (United States)

    Fedorov, Sergey N; Shubina, Larisa K; Bode, Ann M; Stonik, Valentin A; Dong, Zigang

    2007-06-15

    The marine natural chamigrane-type sesquiterpenoid, dactylone, is closely related to secondary metabolites of some edible species of red algae. In the present study, the effect of dactylone was tested on the mouse skin epidermal JB6 P+ Cl41 cell line and its stable transfectants as well as on several human tumor cell lines, including lung (H460), colon (HCT-116), and skin melanomas (SK-MEL-5 and SK-MEL-28). This natural product was effective at nontoxic doses as a cancer-preventive agent, which exerted its actions, at least in part, through the inhibition of cyclin D3 and Cdk4 expression and retinoblastoma tumor suppressor protein (Rb) phosphorylation. The inhibition of these cell cycle components was followed by cell cycle arrest at the G1-S transition with subsequent p53-independent apoptosis. Therefore, these data showed that application of dactylone and related compounds may lead to decreased malignant cell transformation and/or decreased tumor cell proliferation. PMID:17575161

  16. Lentivirus-mediated knockdown of TSP50 suppresses the growth of non-small cell lung cancer cells via G0/G1 phase arrest.

    Science.gov (United States)

    Qiao, Wen-Liang; Hu, Hai-Yang; Shi, Bo-Wen; Zang, Li-Juan; Jin, Wei; Lin, Qiang

    2016-06-01

    Non-small cell lung cancer (NSCLC) as the most frequently diagnosed lethal cancer remains the major cause of overall cancer-related death worldwide. Testes-specific protease 50 (TSP50) has been proved as a critical biomarker in various cancers, and we previously reported that TSP50 protein expression is overexpressed in clinical resected NSCLC tumor tissues and related to poor prognosis in NSCLC patients. Hence, the present study was designed to further investigate the potential oncogenesis mechanism of TSP50 in NSCLC cells. Real-time quantitative PCR, immunohistochemical assay and western blot analysis were used to analyze the TSP50 mRNA and protein expression in 20 NSCLC cases, and TSP50 expression was observed to have high levels in the NSCLC specimens and paired metastatic lymph node tissues when compared to the levels in corresponding normal lung tissues and normal lymph nodes. In the experiments in NSCLC cell lines, lentiviral short hairpin RNA (shRNA) delivery system was applied to knock down TSP50 in 95D cells, and the following investigations revealed that downregulation of TSP50 expression markedly reduced cell proliferation, colony formation and migration ability in vitro. Furthermore, the inhibition of TSP50 induced G0/G1-phase arrest and decreased expression levels of cell cycle relative markers CDK4, CDK6, and CyclinD1 and increased expression of p21 and p53 in 95D cells. In conclusion, this study indicates that TSP50 plays a significant role in NSCLC cell proliferation and may act as a novel oncogene in the development and progression of NSCLC, offering a potential cancer therapeutic target for the treatment of NSCLC. PMID:27109614

  17. Direct targeting of MEK1/2 and RSK2 by silybin induces cell cycle arrest and inhibits melanoma cell growth

    OpenAIRE

    Lee, Mee-Hyun; Huang, Zunnan; Kim, Dong Joon; Kim, Sung-Hyun; Kim, Myoung Ok; Lee, Sung-Young; Xie, Hua; Park, Si Jun; Kim, Jae Young; Kundu, Joydeb Kumar; Bode, Ann M.; Surh, Young-Joon; Dong, Zigang

    2013-01-01

    Abnormal functioning of multiple gene products underlies the neoplastic transformation of cells. Thus, chemopreventive and/or chemotherapeutic agents with multigene targets hold promise in the development of effective anticancer drugs. Silybin, a component of milk thistle, is a natural anticancer agent. In the present study, we investigated the effect of silybin on melanoma cell growth and elucidated its molecular targets. Our study revealed that silybin attenuated the growth of melanoma xeno...

  18. Simultaneous changes in the function and expression of beta 1 integrins during the growth arrest of poorly differentiated colorectal cells (LISP-1

    Directory of Open Access Journals (Sweden)

    R.A. Roela

    2003-08-01

    Full Text Available Cells usually lose adhesion and increase proliferation and migration during malignant transformation. Here, we studied how proliferation can affect the other two characteristics, which ultimately lead to invasion and metastasis. We determined the expression of ß1 integrins, as well as adhesion and migration towards laminin-1, fibronectin, collagens type I and type IV presented by LISP-1 colorectal cancer cells exposed to 2.5% dimethyl sulfoxide (DMSO, an agent capable of decreasing proliferation in this poorly differentiated colorectal cell line. Untreated cells (control, as shown by flow cytometry and monoclonal antibodies, expressed alpha2 (63.8 ± 11.3% positive cells, alpha3 (93.3 ± 7.0%, alpha5 (50.4 ± 12.0% and alpha6 (34.1 ± 4.9% integrins but not alpha1, alpha4, alphav or ß4. Cells adhered well to laminin-1 (73.4 ± 6.0% and fibronectin (40.0 ± 2.0% substrates but very little to collagens. By using blocking monoclonal antibodies, we showed that alpha2, alpha3 and alpha6 mediated laminin-1 adhesion, but neither alpha3 nor alpha5 contributed to fibronectin adherence. DMSO arrested cells at G0/G1 (control: 55.0 ± 2.4% vs DMSO: 70.7 ± 2.5% while simultaneously reducing alpha5 (24.2 ± 19% and alpha6 (14.3 ± 10.8% expression as well as c-myc mRNA (7-fold, the latter shown by Northern blotting. Although the adhesion rate did not change after exposure to DMSO, alpha3 and alpha5 played a major role in laminin-1 and fibronectin adhesion, respectively. Migration towards laminin-1, which was clearly increased upon exposure to DMSO (control: 6 ± 2 cells vs DMSO: 64 ± 6 cells, was blocked by an antibody against alpha6. We conclude that the effects of DMSO on LISP-1 proliferation were accompanied by concurrent changes in the expression and function of integrins, consequently modulating adhesion/migration, and revealing a complex interplay between function/expression and the proliferative state of cells.

  19. A Novel Muscarinic Antagonist R2HBJJ Inhibits Non-Small Cell Lung Cancer Cell Growth and Arrests the Cell Cycle in G0/G1

    OpenAIRE

    Hua, Nan; Wei, Xiaoli; Liu, Xiaoyan; Ma, Xiaoyun; He, Xinhua; Zhuo, Rengong; Zhao, Zhe; Wang, Liyun; Yan, Haitao; Zhong, Bohua; Zheng, Jianquan

    2012-01-01

    Lung cancers express the cholinergic autocrine loop, which facilitates the progression of cancer cells. The antagonists of mAChRs have been demonstrated to depress the growth of small cell lung cancers (SCLCs). In this study we intended to investigate the growth inhibitory effect of R2HBJJ, a novel muscarinic antagonist, on non-small cell lung cancer (NSCLC) cells and the possible mechanisms. The competitive binding assay revealed that R2HBJJ had a high affinity to M3 and M1 AChRs. R2HBJJ pre...

  20. WIF1, a Wnt pathway inhibitor, regulates SKP2 and c-myc expression leading to G1 arrest and growth inhibition ofhuman invasive urinary bladder cancer cells

    OpenAIRE

    Tang, Yaxiong; Simoneau, Anne R; Liao, Wu-Xiang; Yi, Guo; Hope, Christopher; Liu, Feng; Li, Shunqiang; Xie, Jun; Holcombe, Randall F; Jurnak, Frances A.; Mercola, Dan; Hoang, Bang H.; Zi, Xiaolin

    2009-01-01

    Epigenetic silencing of secreted wingless-type (Wnt) antagonists through hypermethylation is associated with tobacco smoking and with invasive bladder cancer. The secreted Wnt inhibitory factor-1 (WIF1) has shown consistent growth-inhibitory effect on various cancer cell lines. Therefore,we assessed the mechanisms of action of WIF1 by either restoring WIF1 expression in invasive bladder cancer cell lines (T24 and TSU-PR1) or using a recombinant protein containing functional WIF1 domain. Both ...

  1. The stringent response and cell cycle arrest in Escherichia coli.

    OpenAIRE

    Daniel J Ferullo; Lovett, Susan T.

    2008-01-01

    The bacterial stringent response, triggered by nutritional deprivation, causes an accumulation of the signaling nucleotides pppGpp and ppGpp. We characterize the replication arrest that occurs during the stringent response in Escherichia coli. Wild type cells undergo a RelA-dependent arrest after treatment with serine hydroxamate to contain an integer number of chromosomes and a replication origin-to-terminus ratio of 1. The growth rate prior to starvation determines the number of chromosomes...

  2. The Stringent Response and Cell Cycle Arrest in Escherichia coli

    OpenAIRE

    Daniel J Ferullo; Lovett, Susan T.

    2008-01-01

    The bacterial stringent response, triggered by nutritional deprivation, causes an accumulation of the signaling nucleotides pppGpp and ppGpp. We characterize the replication arrest that occurs during the stringent response in Escherichia coli. Wild type cells undergo a RelA-dependent arrest after treatment with serine hydroxamate to contain an integer number of chromosomes and a replication origin-to-terminus ratio of 1. The growth rate prior to starvation determines the number of chromosomes...

  3. Antibodies to Placental Immunoregulatory Ferritin with Transfer of Polyclonal Lymphocytes Arrest MCF-7 Human Breast Cancer Growth in a Nude Mouse Model

    Directory of Open Access Journals (Sweden)

    Marisa Halpern

    2007-06-01

    Full Text Available The recently cloned human gene named “placental immunoregulatory ferritin” (PLIF is a pregnancyrelated immunomodulator. Recombinant PLIF and its bioactive domain C48 are immune-suppressive and induce pronounced IL-10 production by immune cells. PLIF is expressed in the placenta and breast cancer cells. Blocking PLIF in pregnant mice by anti-C48 antibodies inhibited placental and fetal growth and modulated the cytokine network. It has been revealed that anti-C48 treatment inhibited MCF-7 tumor growth in nude mice. However, this significant effect was observed only in those transfused with human peripheral blood mononuclear cells. Blocking PLIF in tumor-engrafted human immune cell transfused mice resulted in massive infiltration of human CD45+ cells (mainly CD8+ T cells, both intratumorally and in the tumor periphery, and a significant number of caspase-3+ cells. In vitro, antiC48 treatment of MCF-7 tumor cells cocultured with human lymphocytes induced a significant increase in interferon-γ secretion. We conclude that blocking PLIF inhibits breast cancer growth, possibly by an effect on the cytokine network in immune cells and on breakdown of immunosuppression.

  4. Cardiac arrest – cardiopulmonary resuscitation

    Directory of Open Access Journals (Sweden)

    Basri Lenjani

    2014-01-01

    Conclusions: All survivors from cardiac arrest have received appropriate medical assistance within 10 min from attack, which implies that if cardiac arrest occurs near an institution health care (with an opportunity to provide the emergent health care the rate of survival is higher.

  5. Proteasomal degradation of sphingosine kinase 1 and inhibition of dihydroceramide desaturase by the sphingosine kinase inhibitors, SKi or ABC294640, induces growth arrest in androgen-independent LNCaP-AI prostate cancer cells

    Science.gov (United States)

    McNaughton, Melissa; Pitman, Melissa; Pitson, Stuart M.; Pyne, Nigel J.; Pyne, Susan

    2016-01-01

    Sphingosine kinases (two isoforms termed SK1 and SK2) catalyse the formation of the bioactive lipid sphingosine 1-phosphate. We demonstrate here that the SK2 inhibitor, ABC294640 (3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amide) or the SK1/SK2 inhibitor, SKi (2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole)) induce the proteasomal degradation of SK1a (Mr = 42 kDa) and inhibit DNA synthesis in androgen-independent LNCaP-AI prostate cancer cells. These effects are recapitulated by the dihydroceramide desaturase (Des1) inhibitor, fenretinide. Moreover, SKi or ABC294640 reduce Des1 activity in Jurkat cells and ABC294640 induces the proteasomal degradation of Des1 (Mr = 38 kDa) in LNCaP-AI prostate cancer cells. Furthermore, SKi or ABC294640 or fenretinide increase the expression of the senescence markers, p53 and p21 in LNCaP-AI prostate cancer cells. The siRNA knockdown of SK1 or SK2 failed to increase p53 and p21 expression, but the former did reduce DNA synthesis in LNCaP-AI prostate cancer cells. Moreover, N-acetylcysteine (reactive oxygen species scavenger) blocked the SK inhibitor-induced increase in p21 and p53 expression but had no effect on the proteasomal degradation of SK1a. In addition, siRNA knockdown of Des1 increased p53 expression while a combination of Des1/SK1 siRNA increased the expression of p21. Therefore, Des1 and SK1 participate in regulating LNCaP-AI prostate cancer cell growth and this involves p53/p21-dependent and -independent pathways. Therefore, we propose targeting androgen-independent prostate cancer cells with compounds that affect Des1/SK1 to modulate both de novo and sphingolipid rheostat pathways in order to induce growth arrest. PMID:26934645

  6. Mangrove dolabrane-type of diterpenes tagalsins suppresses tumor growth via ROS-mediated apoptosis and ATM/ATR-Chk1/Chk2-regulated cell cycle arrest.

    Science.gov (United States)

    Neumann, Jennifer; Yang, Yi; Köhler, Rebecca; Giaisi, Marco; Witzens-Harig, Mathias; Liu, Dong; Krammer, Peter H; Lin, Wenhan; Li-Weber, Min

    2015-12-01

    Natural compounds are an important source for drug development. With an increasing cancer rate worldwide there is an urgent quest for new anti-cancer drugs. In this study, we show that a group of dolabrane-type of diterpenes, collectively named tagalsins, isolated from the Chinese mangrove genus Ceriops has potent cytotoxicity on a panel of hematologic cancer cells. Investigation of the molecular mechanisms by which tagalsins kill malignant cells revealed that it induces a ROS-mediated damage of DNA. This event leads to apoptosis induction and blockage of cell cycle progression at S-G2 phase via activation of the ATM/ATR-Chk1/Chk2 check point pathway. We further show that tagalsins suppress growth of human T-cell leukemia xenografts in vivo. Tagalsins show only minor toxicity on healthy cells and are well tolerated by mice. Our study shows a therapeutic potential of tagalsins for the treatment of hematologic malignancies and a new source of anticancer drugs. PMID:26061604

  7. Inhibition of in vitro growth and arrest in the G0/G1 phase of HCT8 line human colon cancer cells by kaempferide triglycoside from Dianthus caryophyllus.

    Science.gov (United States)

    Martineti, Valentina; Tognarini, Isabella; Azzari, Chiara; Carbonell Sala, Silvia; Clematis, Francesca; Dolci, Marcello; Lanzotti, Virginia; Tonelli, Francesco; Brandi, Maria Luisa; Curir, Paolo

    2010-09-01

    The effects of phytoestrogens have been studied in the hypothalamic-pituitary-gonadal axis and in various non-gonadal targets. Epidemiologic and experimental evidence indicates a protective effect of phytoestrogens also in colorectal cancer. The mechanism through which estrogenic molecules control colorectal cancer tumorigenesis could possibly involve estrogen receptor beta, the predominantly expressed estrogen receptor subtype in colon mucosa.To validate this hypothesis, we therefore used an engineered human colon cancer cell line induced to overexpress estrogen receptor beta, beside its native cell line, expressing very low levels of ERbeta and not expressing ERalpha; as a phytoestrogenic molecule, we used kaempferide triglycoside, a glycosylated flavonol from a Dianthus caryophyllus cultivar. The inhibitory properties of this molecule toward vegetal cell growth have been previously demonstrated: however, no data on its activity on animal cell or information about the mechanism of this activity are available. Kaempferide triglycoside proved to inhibit the proliferation of native and estrogen receptor beta overexpressing colon cancer cells through a mechanism not mediated by ligand binding dependent estrogen receptor activation. It affected HCT8 cell cycle progression by increasing the G(0)/G(1) cell fraction and in estrogen receptor beta overexpressing cells increased two antioxidant enzymes. Interestingly, the biological effects of this kaempferide triglycoside were strengthened by the presence of high levels of estrogen receptor beta.Pleiotropic molecular effects of phytoestrogens may explain their protective activity against colorectal cancer and may represent an interesting area for future investigation with potential clinical applications. PMID:20104502

  8. The Pseudomonas aeruginosa antimetabolite L-2-amino-4-methoxy-trans-3-butenoic acid inhibits growth of Erwinia amylovora and acts as a seed germination-arrest factor.

    Science.gov (United States)

    Lee, Xiaoyun; Azevedo, Mark D; Armstrong, Donald J; Banowetz, Gary M; Reimmann, Cornelia

    2013-02-01

    The Pseudomonas aeruginosa antimetabolite L-2-amino-4-methoxy-trans-3-butenoic acid (AMB) shares biological activities with 4-formylaminooxyvinylglycine, a related molecule produced by Pseudomonas fluorescens WH6. We found that culture filtrates of a P. aeruginosa strain overproducing AMB weakly interfered with seed germination of the grassy weed Poa annua and strongly inhibited growth of Erwinia amylovora, the causal agent of the devastating orchard crop disease known as fire blight. AMB was active against a 4-formylaminooxyvinylglycine-resistant isolate of E. amylovora, suggesting that the molecular targets of the two oxyvinylglycines in Erwinia do not, or not entirely, overlap. The AMB biosynthesis and transport genes were shown to be organized in two separate transcriptional units, ambA and ambBCDE, which were successfully expressed from IPTG-inducible tac promoters in the heterologous host P. fluorescens CHA0. Engineered AMB production enabled this model biocontrol strain to become inhibitory against E. amylovora and to weakly interfere with the germination of several graminaceous seeds. We conclude that AMB production requires no additional genes besides ambABCDE and we speculate that their expression in marketed fire blight biocontrol strains could potentially contribute to disease control. PMID:23757135

  9. Metoclopramide-induced cardiac arrest

    Directory of Open Access Journals (Sweden)

    Martha M. Rumore

    2011-11-01

    Full Text Available The authors report a case of cardiac arrest in a patient receiving intravenous (IV metoclopramide and review the pertinent literature. A 62-year-old morbidly obese female admitted for a gastric sleeve procedure, developed cardiac arrest within one minute of receiving metoclopramide 10 mg via slow intravenous (IV injection. Bradycardia at 4 beats/min immediately appeared, progressing rapidly to asystole. Chest compressions restored vital function. Electrocardiogram (ECG revealed ST depression indicative of myocardial injury. Following intubation, the patient was transferred to the intensive care unit. Various cardiac dysrrhythmias including supraventricular tachycardia (SVT associated with hypertension and atrial fibrillation occurred. Following IV esmolol and metoprolol, the patient reverted to normal sinus rhythm. Repeat ECGs revealed ST depression resolution without pre-admission changes. Metoclopramide is a non-specific dopamine receptor antagonist. Seven cases of cardiac arrest and one of sinus arrest with metoclopramide were found in the literature. The metoclopramide prescribing information does not list precautions or adverse drug reactions (ADRs related to cardiac arrest. The reaction is not dose related but may relate to the IV administration route. Coronary artery disease was the sole risk factor identified. According to Naranjo, the association was possible. Other reports of cardiac arrest, severe bradycardia, and SVT were reviewed. In one case, five separate IV doses of 10 mg metoclopramide were immediately followed by asystole repeatedly. The mechanism(s underlying metoclopramide’s cardiac arrest-inducing effects is unknown. Structural similarities to procainamide may play a role. In view of eight previous cases of cardiac arrest from metoclopramide having been reported, further elucidation of this ADR and patient monitoring is needed. Our report should alert clinicians to monitor patients and remain diligent in surveillance and

  10. Ethyl-2-amino-pyrrole-3-carboxylates are novel potent anticancer agents that affect tubulin polymerization, induce G2/M cell-cycle arrest, and effectively inhibit soft tissue cancer cell growth in vitro.

    Science.gov (United States)

    Boichuk, Sergei; Galembikova, Aigul; Zykova, Svetlana; Ramazanov, Bulat; Khusnutdinov, Ramil; Dunaev, Pavel; Khaibullina, Svetlana; Lombardi, Vincent

    2016-08-01

    Microtubules are known to be one of the most attractive and validated targets in cancer therapy. However, the clinical use of drugs that affect the dynamic state of microtubules has been hindered by chemoresistance and toxicity issues. Accordingly, the development of novel agents that target microtubules is needed. Here, we report the identification of novel compounds with pirrole and carboxylate structures: ethyl-2-amino-pyrrole-3-carboxylates (EAPCs) that provide potent cytotoxic activities against multiple soft tissue cancer cell lines in vitro. Using the MTS cell proliferation assay, we assessed the activity of EAPCs on various cancer cell lines including leiomyosarcoma SK-LMS-1, rhabdomyosarcoma RD, gastrointestinal stromal tumor GIST-T1, A-673 Ewing's sarcoma, and U-2 OS osteosarcoma. We found that in the majority of cases, two EAPC compounds (EAPC-20 and EAPC-24) considerably inhibited cancer cell proliferation in vitro. The growth-inhibitory effects of EAPC-20 and EAPC-24 were time and dose dependent. The molecular mechanisms of action of these compounds were because of the inhibition of tubulin polymerization and induction of a robust G2/M cell-cycle arrest, leading to considerable accumulation of tumor cells in the M-phase. Finally, EAPCs induced tumor cell death by apoptotic pathways. The above-mentioned effects were also observed in most soft tissue tumor cell lines and the gastrointestinal stromal tumor cell line investigated. Taken together, our data identify potent antitumor activity of EAPCs in vitro, thus providing a novel scaffold with which to develop potent chemotherapeutic agents for cancer therapy. PMID:27129079

  11. Juvenile Arrests, 1998. Juvenile Justice Bulletin.

    Science.gov (United States)

    Snyder, Howard N.

    This report provides a summary and analysis of national and state juvenile arrest data in the United States. In 1998, law enforcement agencies made an estimated 2.6 million arrests of persons under age 18. Federal Bureau of Investigations statistics indicate that juveniles account for 18% of all arrests, and 17% of all violent crime arrests in…

  12. 33 CFR 154.822 - Detonation arresters, flame arresters, and flame screens.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Detonation arresters, flame... BULK Vapor Control Systems § 154.822 Detonation arresters, flame arresters, and flame screens. (a) Each detonation arrester required by this part must: (1) Be capable of arresting a detonation from either side...

  13. Inhibition of the phosphoinositide 3-kinase pathway induces a senescence-like arrest mediated by p27Kip1

    NARCIS (Netherlands)

    Collado, M.; Medema, R.H.; Garcia-Cao, I.; Dubuisson, M.L.N.; Barradas, M.; Glassford, J.; Rivas, C.; Burgering, B.M.T.; Serrano, M.; Lam, E.W.-F.

    2000-01-01

    A senescence-like growth arrest is induced in mouse primary embryo fibroblasts by inhibitors of phosphoinositide 3-kinase (PI3K). We observed that senescence-like growth arrest is correlated with an increase in p27Kip1 but that down-regulation of other cyclin-dependent kinase (CDK) inhibitors, inclu

  14. The stringent response and cell cycle arrest in Escherichia coli.

    Science.gov (United States)

    Ferullo, Daniel J; Lovett, Susan T

    2008-12-01

    The bacterial stringent response, triggered by nutritional deprivation, causes an accumulation of the signaling nucleotides pppGpp and ppGpp. We characterize the replication arrest that occurs during the stringent response in Escherichia coli. Wild type cells undergo a RelA-dependent arrest after treatment with serine hydroxamate to contain an integer number of chromosomes and a replication origin-to-terminus ratio of 1. The growth rate prior to starvation determines the number of chromosomes upon arrest. Nucleoids of these cells are decondensed; in the absence of the ability to synthesize ppGpp, nucleoids become highly condensed, similar to that seen after treatment with the translational inhibitor chloramphenicol. After induction of the stringent response, while regions corresponding to the origins of replication segregate, the termini remain colocalized in wild-type cells. In contrast, cells arrested by rifampicin and cephalexin do not show colocalized termini, suggesting that the stringent response arrests chromosome segregation at a specific point. Release from starvation causes rapid nucleoid reorganization, chromosome segregation, and resumption of replication. Arrest of replication and inhibition of colony formation by ppGpp accumulation is relieved in seqA and dam mutants, although other aspects of the stringent response appear to be intact. We propose that DNA methylation and SeqA binding to non-origin loci is necessary to enforce a full stringent arrest, affecting both initiation of replication and chromosome segregation. This is the first indication that bacterial chromosome segregation, whose mechanism is not understood, is a step that may be regulated in response to environmental conditions. PMID:19079575

  15. The stringent response and cell cycle arrest in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Daniel J Ferullo

    2008-12-01

    Full Text Available The bacterial stringent response, triggered by nutritional deprivation, causes an accumulation of the signaling nucleotides pppGpp and ppGpp. We characterize the replication arrest that occurs during the stringent response in Escherichia coli. Wild type cells undergo a RelA-dependent arrest after treatment with serine hydroxamate to contain an integer number of chromosomes and a replication origin-to-terminus ratio of 1. The growth rate prior to starvation determines the number of chromosomes upon arrest. Nucleoids of these cells are decondensed; in the absence of the ability to synthesize ppGpp, nucleoids become highly condensed, similar to that seen after treatment with the translational inhibitor chloramphenicol. After induction of the stringent response, while regions corresponding to the origins of replication segregate, the termini remain colocalized in wild-type cells. In contrast, cells arrested by rifampicin and cephalexin do not show colocalized termini, suggesting that the stringent response arrests chromosome segregation at a specific point. Release from starvation causes rapid nucleoid reorganization, chromosome segregation, and resumption of replication. Arrest of replication and inhibition of colony formation by ppGpp accumulation is relieved in seqA and dam mutants, although other aspects of the stringent response appear to be intact. We propose that DNA methylation and SeqA binding to non-origin loci is necessary to enforce a full stringent arrest, affecting both initiation of replication and chromosome segregation. This is the first indication that bacterial chromosome segregation, whose mechanism is not understood, is a step that may be regulated in response to environmental conditions.

  16. Wide plate crack arrest testing

    International Nuclear Information System (INIS)

    To predict the behavior of a nuclear pressure vessel undergoing pressurized thermal shock, certain information on dynamic crack propagation and arrest is required. The purpose of the work described is to provide such data on wide plates fracturing at temperatures up to the upper shelf region. Four tests have been completed on the 26 MN Universal Testing Machine at NBS. The specimens are to be fractured in a thermal gradient that, in the most extreme case, might extend from -1000C to 2000 across the 1 meter specimen width. This is done so that the crack will initiate in a cold, brittle region and arrest in a hot, tough region. An important part of this study is data acquisition from the numerous strain gages, thermocouples, timing wires, crack mouth opening displacement gages, and acoustic emission transducers that are mounted on the specimen. Each test has been different with respect to conditions of testing, specimen configuration, and instrumentation used. The progressive changes in test procedure represent attempts to obtain the desired crack run and arrest behavior and to improve upon the quality of the data collected. In particular, efforts were made to initiate crack propagation at lower stress intensity factors. Also, strain gage combinations and locations were optimized to better deduce the crack position as a function of time. Another result of great interest that can be deduced from these tests is the initiation of fracture toughness and the arrest toughness

  17. Sudden Cardiac Arrest (SCA) Risk Assessment

    Science.gov (United States)

    ... Find a Specialist Share Twitter Facebook SCA Risk Assessment Sudden Cardiac Arrest (SCA) occurs abruptly and without ... of all ages and health conditions. Start Risk Assessment The Sudden Cardiac Arrest (SCA) Risk Assessment Tool ...

  18. Cardiac arrest: resuscitation and reperfusion.

    Science.gov (United States)

    Patil, Kaustubha D; Halperin, Henry R; Becker, Lance B

    2015-06-01

    The modern treatment of cardiac arrest is an increasingly complex medical procedure with a rapidly changing array of therapeutic approaches designed to restore life to victims of sudden death. The 2 primary goals of providing artificial circulation and defibrillation to halt ventricular fibrillation remain of paramount importance for saving lives. They have undergone significant improvements in technology and dissemination into the community subsequent to their establishment 60 years ago. The evolution of artificial circulation includes efforts to optimize manual cardiopulmonary resuscitation, external mechanical cardiopulmonary resuscitation devices designed to augment circulation, and may soon advance further into the rapid deployment of specially designed internal emergency cardiopulmonary bypass devices. The development of defibrillation technologies has progressed from bulky internal defibrillators paddles applied directly to the heart, to manually controlled external defibrillators, to automatic external defibrillators that can now be obtained over-the-counter for widespread use in the community or home. But the modern treatment of cardiac arrest now involves more than merely providing circulation and defibrillation. As suggested by a 3-phase model of treatment, newer approaches targeting patients who have had a more prolonged cardiac arrest include treatment of the metabolic phase of cardiac arrest with therapeutic hypothermia, agents to treat or prevent reperfusion injury, new strategies specifically focused on pulseless electric activity, which is the presenting rhythm in at least one third of cardiac arrests, and aggressive post resuscitation care. There are discoveries at the cellular and molecular level about ischemia and reperfusion pathobiology that may be translated into future new therapies. On the near horizon is the combination of advanced cardiopulmonary bypass plus a cocktail of multiple agents targeted at restoration of normal metabolism and

  19. Crack propagation and arrest in CFRP materials with strain softening regions

    Science.gov (United States)

    Dilligan, Matthew Anthony

    Understanding the growth and arrest of cracks in composite materials is critical for their effective utilization in fatigue-sensitive and damage susceptible applications such as primary aircraft structures. Local tailoring of the laminate stack to provide crack arrest capacity intermediate to major structural components has been investigated and demonstrated since some of the earliest efforts in composite aerostructural design, but to date no rigorous model of the crack arrest mechanism has been developed to allow effective sizing of these features. To address this shortcoming, the previous work in the field is reviewed, with particular attention to the analysis methodologies proposed for similar arrest features. The damage and arrest processes active in such features are investigated, and various models of these processes are discussed and evaluated. Governing equations are derived based on a proposed mechanistic model of the crack arrest process. The derived governing equations are implemented in a numerical model, and a series of simulations are performed to ascertain the general characteristics of the proposed model and allow qualitative comparison to existing experimental results. The sensitivity of the model and the arrest process to various parameters is investigated, and preliminary conclusions regarding the optimal feature configuration are developed. To address deficiencies in the available material and experimental data, a series of coupon tests are developed and conducted covering a range of arrest zone configurations. Test results are discussed and analyzed, with a particular focus on identification of the proposed failure and arrest mechanisms. Utilizing the experimentally derived material properties, the tests are reproduced with both the developed numerical tool as well as a FEA-based implementation of the arrest model. Correlation between the simulated and experimental results is analyzed, and future avenues of investigation are identified

  20. Carbamazepine induces mitotic arrest in mammalian Vero cells

    International Nuclear Information System (INIS)

    We reported recently that the anticonvulsant drug carbamazepine, at supratherapeutic concentrations, exerts antiproliferative effects in mammalian Vero cells, but the underlying mechanism has not been elucidated. This motivates us to examine rigorously whether growth arrest was associated with structural changes in cellular organization during mitosis. In the present work, we found that exposure of the cells to carbamazepine led to an increase in mitotic index, mainly due to the sustained block at the metaphase/anaphase boundary, with the consequent inhibition of cell proliferation. Indirect immunofluorescence, using antibodies directed against spindle apparatus proteins, revealed that mitotic arrest was associated with formation of monopolar spindles, caused by impairment of centrosome separation. The final consequence of the spindle defects induced by carbamazepine, depended on the duration of cell cycle arrest. Following the time course of accumulation of metaphase and apoptotic cells during carbamazepine treatments, we observed a causative relationship between mitotic arrest and induction of cell death. Conversely, cells released from the block of metaphase by removal of the drug, continued to progress through mitosis and resume normal proliferation. Our results show that carbamazepine shares a common antiproliferative mechanism with spindle-targeted drugs and contribute to a better understanding of the cytostatic activity previously described in Vero cells. Additional studies are in progress to extend these initial findings that define a novel mode of action of carbamazepine in cultured mammalian cells

  1. Carbamazepine induces mitotic arrest in mammalian Vero cells

    Energy Technology Data Exchange (ETDEWEB)

    Perez Martin, J.M.; Fernandez Freire, P.; Labrador, V. [Departamento de Biologia, Facultad de Ciencias, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain); Hazen, M.J. [Departamento de Biologia, Facultad de Ciencias, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain)], E-mail: mariajose.hazen@uam.es

    2008-01-01

    We reported recently that the anticonvulsant drug carbamazepine, at supratherapeutic concentrations, exerts antiproliferative effects in mammalian Vero cells, but the underlying mechanism has not been elucidated. This motivates us to examine rigorously whether growth arrest was associated with structural changes in cellular organization during mitosis. In the present work, we found that exposure of the cells to carbamazepine led to an increase in mitotic index, mainly due to the sustained block at the metaphase/anaphase boundary, with the consequent inhibition of cell proliferation. Indirect immunofluorescence, using antibodies directed against spindle apparatus proteins, revealed that mitotic arrest was associated with formation of monopolar spindles, caused by impairment of centrosome separation. The final consequence of the spindle defects induced by carbamazepine, depended on the duration of cell cycle arrest. Following the time course of accumulation of metaphase and apoptotic cells during carbamazepine treatments, we observed a causative relationship between mitotic arrest and induction of cell death. Conversely, cells released from the block of metaphase by removal of the drug, continued to progress through mitosis and resume normal proliferation. Our results show that carbamazepine shares a common antiproliferative mechanism with spindle-targeted drugs and contribute to a better understanding of the cytostatic activity previously described in Vero cells. Additional studies are in progress to extend these initial findings that define a novel mode of action of carbamazepine in cultured mammalian cells.

  2. Retinoids arrest breast cancer cell proliferation: retinoic acid selectively reduces the duration of receptor tyrosine kinase signaling

    OpenAIRE

    Tighe, Ann P.; Talmage, David A

    2004-01-01

    Retinoic acid (RA) induces cell cycle arrest of hormone-dependent human breast cancer (HBC) cells. Previously, we demonstrated that RA-induced growth arrest of T-47D HBC cells required the activity of the RA-induced protein kinase, protein kinase Cα (PKCα) [J. Cell Physiol. 172 (1997) 306]. Here, we demonstrate that RA treatment of T-47D cells interfered with growth factor signaling to downstream, cytoplasmic and nuclear targets. RA treatment did not inhibit epidermal growth factor (EGF) rece...

  3. Simultaneous Radial Lengthening and Ulnar Shortening for a Delayed Presentation of Radius Distal Physeal Arrest: A Case Report

    Directory of Open Access Journals (Sweden)

    Erdal Uzun

    2014-12-01

    Full Text Available Distal radius fractures are common injuries in both children and in the elderly (25%; 18%. Distal radius physeal fractures have a high incidence, but physeal growth arrest occurs at a low rate. As a main deformity, radial shortening occurs with relative ulnar overgrowth leading to significant complaints of pain and functional limitations after distal radial growth arrest. In this paper we aim to report on the restoration of the wrist mechanics attained by performing a surgical technique of simultaneous radial lengthening and ulnar shortening procedures in an adolescent with a significant ulnar overgrowth deformity due to a posttraumatic growth arrest of distal radius.

  4. Cognitive and Functional Consequence of Cardiac Arrest.

    Science.gov (United States)

    Perez, Claudia A; Samudra, Niyatee; Aiyagari, Venkatesh

    2016-08-01

    Cardiac arrest is associated with high morbidity and mortality. Better-quality bystander cardiopulmonary resuscitation training, cardiocerebral resuscitation principles, and intensive post-resuscitation hospital care have improved survival. However, cognitive and functional impairment after cardiac arrest remain areas of concern. Research focus has shifted beyond prognostication in the immediate post-arrest period to identification of mechanisms for long-term brain injury and implementation of promising protocols to reduce neuronal injury. These include therapeutic temperature management (TTM), as well as pharmacologic and psychological interventions which also improve overall neurological function. Comprehensive assessment of cognitive function post-arrest is hampered by heterogeneous measures among studies. However, the domains of attention, long-term memory, spatial memory, and executive function appear to be affected. As more patients survive cardiac arrest for longer periods of time, there needs to be a greater focus on interventions that can enhance cognitive and psychosocial function post-arrest. PMID:27311306

  5. Simulated Cardiopulmonary Arrests in a Hospital Setting.

    Science.gov (United States)

    Mishkin, Barbara H.; And Others

    1982-01-01

    Describes a simulated interdisciplinary role rehearsal for cardiopulmonary arrest to prepare nurses to function effectively. Includes needs analysis, program components, and responses of program participants. (Author)

  6. [Out-of-hospital cardiac arrest].

    Science.gov (United States)

    Virkkunen, Ilkka; Hoppu, Sanna; Kämäräinen, Antti

    2011-01-01

    Cardiac arrest as the first symptom of coronary artery disease is not uncommon. Some of previously healthy people with sudden cardiac arrest may be saved by effective resuscitation and post-resuscitative therapy. The majority of cardiac arrest patients experience the cardiac arrest outside of the hospital, in which case early recognition of lifelessness, commencement of basic life support and entry to professional care without delay are the prerequisites for recovery. After the heart has started beating again, the clinical picture of post-resuscitation syndrome must be recognized and appropriate treatment utilized. PMID:22204143

  7. Ent-11α-Hydroxy-15-oxo-kaur-16-en-19-oic-acid Inhibits Growth of Human Lung Cancer A549 Cells by Arresting Cell Cycle and Triggering Apoptosis

    Institute of Scientific and Technical Information of China (English)

    Li Li; George G Chen; Ying-nian Lu; Yi Liu; Ke-feng Wu; Xian-ling Gong; Zhan-ping Gou; Ming-yue Li; Nian-ci Liang

    2012-01-01

    Objective:To examine the apoptotic effect of ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F),a compound isolated from Pteris semipinnata L(PsL),in human lung cancer A549 cells.Methods:A549 cells were treated with 5F (0-80 μg/ml) for different time periods.Cytotoxicity was examined using a MTT method.Cell cycle was examined using propidium iodide staining.Apoptosis was examined using Hoechst 33258 staining,enzyme-linked immunosorbent assay (ELISA) and caspase-3 activity analysis.Expression of representative apoptosis-related proteins was evaluated by Western blot analysis.Reactive oxygen species (ROS) level was measured using standard protocols.Potential interaction of 5F with cisplatin was also examined.Results:5F inhibited the proliferation of A549 cells in a concentration- and time-dependent manner.5F increased the accumulation of cells in sub-G1 phase and arrested the cells in the G2 phase.Exposure to 5F induced morphological changes and DNA fragmentation that are characteristic of apoptosis.The expression of p21 was increased.5F exposure also increased Bax expression,release of cytochrome c and apoptosis inducing factor (AIF),and activation of caspase-3.5F significantly sensitized the cells to cisplatin toxicity Interestingly,treatment with 5F did not increase ROS,but reduced ROS production induced by cisplatin.Conclusion:SF could inhibit the proliferation of A549 cells by arresting the cells in G2 phase and by inducing mitochondrial-mediated apoptosis.

  8. Psychopathology in Women Arrested for Domestic Violence

    Science.gov (United States)

    Stuart, Gregory L.; Moore, Todd M.; Gordon, Kristina Coop; Ramsey, Susan E.; Kahler, Christopher W.

    2006-01-01

    This study examined the prevalence of psychopathology among women arrested for violence and whether the experience of intimate partner violence (IPV) was associated with Axis I psychopathology. Women who were arrested for domestic violence perpetration and court referred to violence intervention programs (N=103) completed measures of IPV…

  9. The course of circulatory and cerebral recovery after circulatory arrest: influence of pre-arrest, arrest and post-arrest factors.

    Science.gov (United States)

    Jørgensen, E O; Holm, S

    1999-11-01

    We evaluated the influence of pre-arrest, arrest and post-arrest factors on circulatory and neurological recovery for up to 1 year following circulatory arrest of cardio-pulmonary aetiology in 231 patients. Initially, all patients were unconscious and 106 had some cortical activity recorded in the immediate post-resuscitation EEG (Group I), while 125 had no such activity initially (Group II). The following variables were explored: age, sex, medical history, cause and location of arrest, initial cardiac dysrhythmia, duration of life support, metabolic acidosis, pulse-pressure product and heart pump function capacity early after resuscitation. Outcome measures were duration and quality of circulatory survival, cause of death, neurological recovery and ultimate outcome. First year survival was 33% in Group I and 16% in Group II. Severe heart failure and brain death occurred mainly in Group II. Circulatory recovery was negatively influenced by out-of-hospital arrest, metabolic acidosis and pulse-pressure products below 150. Neurological recovery was negatively influenced by initial dysrhythmias other than ventricular fibrillation, pulse-pressure products below 150, post-arrest heart failure and/or pulmonary complications. It seems that circulatory and cerebral outcomes are mainly determined by the global ischaemic insults sustained during the circulatory arrest period. PMID:10625157

  10. 2-D gel electrophoresis-based proteomic analysis reveals that ormeloxifen induces G0-G1 growth arrest and ERK-mediated apoptosis in chronic myeloid leukemia cells K562.

    Science.gov (United States)

    Pal, Pooja; Kanaujiya, Jitendra K; Lochab, Savita; Tripathi, Shashi B; Bhatt, Madan L B; Singh, Pradhyumna K; Sanyal, Sabyasachi; Trivedi, Arun K

    2011-04-01

    Ormeloxifen is a nonsteroidal selective estrogen receptor modulator (SERM) and has been shown to possess anticancer activities in breast and uterine cancer. Here, we show that ormeloxifen induces apoptosis in dose-dependent manner in a variety of leukemia cells, more strikingly in K562. 2-DE-gel electrophoresis of K562 cells induced with ormeloxifen showed that 57 and 30% of proteins belong to apoptosis and cell-cycle pathways, respectively. Our data demonstrate that ormeloxifen-induced apoptosis in K562 cells involves activation of extracellular signal-regulated kinases (ERKs) and subsequent cytochrome c release, leading to mitochondria-mediated caspase-3 activation. Ormeloxifen-induced apoptosis via ERK activation was drastically inhibited by prior treatment of K562 cells with ERK inhibitor PD98059. Ormeloxifen also inhibits proliferation of K562 cells by blocking them in G0-G1 phase by inhibiting c-myc promoter via ormeloxifen-induced MBP-1 (c-myc promoter-binding protein) and upregulation of p21 expression. We further show that ormeloxifen-induced apoptosis in K562 is translatable to mononuclear cells isolated from chronic myeloid leukemia (CML) patients. Thus, ormeloxifen induces apoptosis in K562 cells via phosphorylation of ERK and arrests them in G0-G1 phase by reciprocal regulation of p21 and c-myc. Therefore, inclusion of ormeloxifen in the therapy of chronic myeloid leukemia can be of potential utility. PMID:21360677

  11. Carnosol, a dietary diterpene, displays growth inhibitory effects in human prostate cancer PC3 cells leading to G2-phase cell cycle arrest and targets the 5'-AMP-activated protein kinase (AMPK) pathway

    Science.gov (United States)

    Johnson, Jeremy J.; Syed, Deeba N.; Heren, Chenelle R.; Suh, Yewseok; Adhami, Vaqar M.; Mukhtar, Hasan

    2010-01-01

    Purpose The anti-cancer effect of carnosol was investigated in human prostate cancer PC3 cells. Methods Biochemical analysis and protein array data of carnosol treated PC3 cells were analyzed. Results We evaluated carnosol for its potential anti-cancer properties in the PC3 cells. Using an MTT assay we found that carnosol (10 – 70 µM) decreases cell viability in a time and dose dependent manner. Next, we evaluated the effect of carnosol (20–60 uM) effect using flow cytometry as well as biochemical analysis and found induction of G2-phase cell cycle arrest. To establish a more precise mechanism, we performed a protein array that evaluated 638 proteins involved in cell signaling pathways. The protein array identified 5'-AMP-activated protein kinase (AMPK), a serine/threonine protein kinase involved in the regulation of cellular energy balance as a potential target. Further downstream effects consistent with cancer inhibition included the modulation of the mTOR/HSP70S6k/4E-BP1 pathway. Additionally, we found that carnosol targeted the PI3K/Akt pathway in a dose dependent manner. Conclusions These results suggest that carnosol targets multiple signaling pathways that include the AMPK pathway. The ability of carnosol to inhibit prostate cancer in vitro suggests carnosol may be a novel agent for the management of PCa. PMID:18286356

  12. Soft Semicrystalline Thermoplastic Elastomers by Arrested Crystallization

    Science.gov (United States)

    Burns, Adam; Register, Richard

    2014-03-01

    Thermoplastic elastomers (TPEs) marry the solid-state behavior of vulcanized rubbers with the melt processability of thermoplastics. Archetypal soft TPEs consist of triblock copolymers comprising a rubbery mid-block flanked by two identical glassy end-blocks. Incorporating crystalline blocks into TPEs can confer solvent resistance as well as reduce the processing costs by giving access to single-phase melts. However, simply substituting crystalline for glassy end-blocks dramatically degrades the solid-state mechanical properties, particularly at large strains. We seek to integrate the benefits of crystallinity into TPEs, while maintaining the desired mechanical properties, using the block architecture: crystalline-glassy-rubbery-glassy-crystalline. Methods have been developed to synthesize highly symmetric, narrow-distribution block copolymers with this architecture using anionic polymerization of butadiene, styrene, and isoprene followed by hydrogenation. Judicious choices of block molecular weights indeed yield homogeneous melts above the melting point of the crystalline component. Upon cooling, crystallization--rather than interblock repulsion--establishes the solid-state microstructure which physically crosslinks the rubbery mid-block, ultimately conferring elasticity. Subsequent vitrification of the adjacent glassy blocks arrests the growth of the crystallites, and protects them from yielding under applied load. As a result, our materials show low initial moduli, strain hardening, and high extensibility, typical of commercial TPEs.

  13. Chromosomal Aneuploidies and Early Embryonic Developmental Arrest

    Directory of Open Access Journals (Sweden)

    Maria Maurer

    2015-07-01

    Full Text Available Background: Selecting the best embryo for transfer, with the highest chance of achieving a vital pregnancy, is a major goal in current in vitro fertilization (IVF technology. The high rate of embryonic developmental arrest during IVF treatment is one of the limitations in achieving this goal. Chromosomal abnormalities are possibly linked with chromosomal arrest and selection against abnormal fertilization products. The objective of this study was to evaluate the frequency and type of chromosomal abnormalities in preimplantation embryos with developmental arrest. Materials and Methods: This cohort study included blastomeres of embryos with early developmental arrest that were biopsied and analyzed by fluorescence in-situ hybridization (FISH with probes for chromosomes 13, 16, 18, 21 and 22. Forty-five couples undergoing IVF treatment were included, and 119 arrested embryos were biopsied. All probes were obtained from the Kinderwunsch Zentrum, Linz, Austria, between August 2009 and August 2011. Results: Of these embryos, 31.6% were normal for all chromosomes tested, and 68.4% were abnormal. Eleven embryos were uniformly aneuploid, 20 were polyploid, 3 were haploid, 11 displayed mosaicism and 22 embryos exhibited chaotic chromosomal complement. Conclusion: Nearly 70% of arrested embryos exhibit chromosomal errors, making chromosomal abnormalities a major cause of embryonic arrest and may be a further explanation for the high developmental failure rates during culture of the embryos in the IVF setting.

  14. Aqueous Extracts of the Edible Gracilaria tenuistipitata are Protective Against H2O2-Induced DNA Damage, Growth Inhibition, and Cell Cycle Arrest

    Directory of Open Access Journals (Sweden)

    Chi-Chen Yeh

    2012-06-01

    Full Text Available Potential antioxidant properties of an aqueous extract of the edible red seaweed Gracilaria tenuistipitata (AEGT against oxidative DNA damage were evaluated. The AEGT revealed several antioxidant molecules, including phenolics, flavonoids and ascorbic acid. In a cell-free assay, the extract exhibited 1,1-diphenyl-2-picrylhydrazyl (DPPH radical scavenging activity that significantly reduced H2O2-induced plasmid DNA breaks in a dose-response manner (P < 0.001. The AEGT also suppressed H2O2-induced oxidative DNA damage in H1299 cells by reducing the percentage of damaged DNA in a dose-response manner (P < 0.001 as measured by a modified alkaline comet-nuclear extract (comet-NE assay. The MTT assay results showed that AEGT confers significant protection against H2O2-induced cytotoxicity and that AEGT itself is not cytotoxic (P < 0.001. Moreover, H2O2-induced cell cycle G2/M arrest was significantly released when cells were co-treated with different concentrations of AEGT (P < 0.001. Taken together, these findings suggest that edible red algae Gracilaria water extract can prevent H2O2-induced oxidative DNA damage and its related cellular responses.

  15. Crack arrest saturation model under combined electrical and mechanical loadings

    Directory of Open Access Journals (Sweden)

    R.R. Bhargava

    2009-12-01

    Full Text Available Purpose: The investigation aims at proposing a model for cracked piezoelectric strip which is capable to arrest the crack.Design/methodology/approach: Under the combined effect of electrical and mechanical loadings applied at the edges of the strip, the developed saturation zone is produced at each tip of the crack. To arrest further opening of the crack, the rims of the developed saturation zones are subjected to in-plane cohesive, normal uniform constant saturation point electrical displacement. The problem is solved using Fourier integral transform method which reduces the problem to the solution of Fredholm integral equation of the second kind. This integral equation in turn is solved numerically.Findings: The expressions are derived for different intensity factors and energy release rate. A qualitative analysis of the parameters affecting the arrest of opening of the crack and fatigue crack growth with respect to strip thickness and material constants are presented graphically.Research limitations/implications: The investigations are carried out by considering the material electrical brittle. Consequently, the zones protrude along the straight lines ahead of the crack tips. And further, the small scale electrical yielding conditions are used.Practical implications: Piezoelectric materials are widely getting used nowadays, even in day to day life like piezoelectric cigarette lighter, children toys etc. And, its advance used in technology like transducers, actuators has been already in progress. So, the aspect of cracking of piezoelectric materials are of great practical importance.Originality/value: The piezoelectric material under the combined effect of electrical and mechanical loadings gives the assessment of electrical displacement which is required to arrest the crack. The various useful interpretations are also drawn from the graphs.

  16. Composite Pressure Vessel Including Crack Arresting Barrier

    Science.gov (United States)

    DeLay, Thomas K. (Inventor)

    2013-01-01

    A pressure vessel includes a ported fitting having an annular flange formed on an end thereof and a tank that envelopes the annular flange. A crack arresting barrier is bonded to and forming a lining of the tank within the outer surface thereof. The crack arresting barrier includes a cured resin having a post-curing ductility rating of at least approximately 60% through the cured resin, and further includes randomly-oriented fibers positioned in and throughout the cured resin.

  17. Surviving out-of-hospital cardiac arrest.

    Science.gov (United States)

    Evans, Nick

    2016-05-01

    Emergency care nurses have been urged to play their part in Scotland's push to revolutionise care for cardiac arrest patients - by teaching others how to save a life. This article discusses the Scottish out-of-hospital cardiac arrest strategy, with particular focus on the drive to increase bystander cardiopulmonary resuscitation (CPR) rates, and on how emergency nurses are being enlisted to help promote the training of members of the public. PMID:27165393

  18. Predicting crack arrest in reactor pressure vessels

    International Nuclear Information System (INIS)

    The pressurized thermal shock (PTS) issue has provided increased motivation for the search for a reasonably accurate crack arrest prediction methodology. This issue has assumed greater significance recently as a consequence of the imposition of Regulatory Guide 1.99 Revision 2 procedures for determining the effects of radiation embrittlement in the context of the screening criteria in the PTS rule that is used by the United States Nuclear Regulatory Commission to assess the integrity of reactor pressure vessels. The currently accepted procedure for predicting crack arrest is the so-called KIa procedure, which is based on static linear elastic fracture mechanics principles, with a crack being presumed to arrest when the crack tip stress intensity factor KIST falls below a value KIa. The present paper reviews recent EPRI sponsored research, which shows that the static procedure is overly conservative when it is applied to the first arrest of a deep crack in the thickness of a reactor vessel. This conclusion is clearly important when assessing the consequences of the imposition of the procedures of Regulatory Guide 1.99 Revision 2. A more accurate crack arrest prediction procedure, i.e. the Combustion Engineering constrained static procedure or the reflectionless stress intensity factor procedure which are very similar in concept and their arrest prediction, should be considered to assess the impact of its use in the context of the screening criteria limits in the PTS rule. (orig.)

  19. THE RACE/ETHNICITY DISPARITY IN MISDEMEANOR MARIJUANA ARRESTS IN NEW YORK CITY.

    Science.gov (United States)

    Golub, Andrew; Johnson, Bruce D; Dunlap, Eloise

    2007-01-01

    RESEARCH SUMMARY: This article examines the growth in marijuana misdemeanor arrests in New York City (NYC) from 1980 to 2003 and its differential impact on blacks and Hispanics. Since 1980, the New York City Police Department (NYPD) expanded its use of arrest and detention for minor offenses under its quality-of-life (QOL) policing initiative. Arrest data indicate that during the 1990s the primary focus of QOL policing became smoking marijuana in public view (MPV). By 2000, MPV had become the most common misdemeanor arrest, accounting for 15% of all NYC adult arrests and rivaling controlled substance arrests as the primary focus of drug abuse control. Of note, most MPV arrestees have been black or Hispanic. Furthermore, black and Hispanic MPV arrestees have been more likely to be detained prior to arraignment, convicted, and sentenced to jail than their white counterparts. POLICY IMPLICATIONS: In light of the disparities, we recommend that the NYPD consider scaling back on MPV enforcement and reducing the harshness of treatment by routinely issuing Desk Appearance Tickets when the person is not wanted on other charges, so that most MPV arrestees would not be detained. Furthermore, we recommend that legislators should consider making smoking marijuana in public a violation and not a misdemeanor. Lastly, we suggest ways that NYC could monitor the effectiveness of these policy modifications to assure that the city continues to meet its goals for order maintenance. PMID:18841246

  20. Sex Disparities in Arrest Outcomes for Domestic Violence

    Science.gov (United States)

    Hamilton, Melissa; Worthen, Meredith G. F.

    2011-01-01

    Domestic violence arrests have been historically focused on protecting women and children from abusive men. Arrest patterns continue to reflect this bias with more men arrested for domestic violence compared to women. Such potential gender variations in arrest patterns pave the way to the investigation of disparities by sex of the offender in…

  1. Canopy shade causes a rapid and transient arrest in leaf development through auxin-induced cytokinin oxidase activity.

    Science.gov (United States)

    Carabelli, Monica; Possenti, Marco; Sessa, Giovanna; Ciolfi, Andrea; Sassi, Massimiliano; Morelli, Giorgio; Ruberti, Ida

    2007-08-01

    A plant grown under canopies perceives the reduction in the ratio of red (R) to far-red (FR) light as a warning of competition, and enhances elongation growth in an attempt to overgrow its neighbors. Here, we report that the same low R/FR signal that induces hypocotyl elongation also triggers a rapid arrest of leaf primordium growth, ensuring that plant resources are redirected into extension growth. The growth arrest induced by low R/FR depends on auxin-induced cytokinin breakdown in incipient vein cells of developing primordia, thus demonstrating the existence of a previously unrecognized regulatory circuit underlying plant response to canopy shade. PMID:17671088

  2. Reversible cryo-arrest for imaging molecules in living cells at high spatial resolution.

    Science.gov (United States)

    Masip, Martin E; Huebinger, Jan; Christmann, Jens; Sabet, Ola; Wehner, Frank; Konitsiotis, Antonios; Fuhr, Günther R; Bastiaens, Philippe I H

    2016-08-01

    The dynamics of molecules in living cells hampers precise imaging of molecular patterns by functional and super-resolution microscopy. We developed a method that circumvents lethal chemical fixation and allows on-stage cryo-arrest for consecutive imaging of molecular patterns within the same living, but arrested, cells. The reversibility of consecutive cryo-arrests was demonstrated by the high survival rate of different cell lines and by intact growth factor signaling that was not perturbed by stress response. Reversible cryo-arrest was applied to study the evolution of ligand-induced receptor tyrosine kinase activation at different scales. The nanoscale clustering of epidermal growth factor receptor (EGFR) in the plasma membrane was assessed by single-molecule localization microscopy, and endosomal microscale activity patterns of ephrin receptor A2 (EphA2) were assessed by fluorescence lifetime imaging microscopy. Reversible cryo-arrest allows the precise determination of molecular patterns while conserving the dynamic capabilities of living cells. PMID:27400419

  3. 4-Formylaminooxyvinylglycine, an Herbicidal Germination-Arrest Factor (GAF) from Pseudomonas Rhizosphere Bacteria

    Science.gov (United States)

    A new oxyvinylglycine has been identified as a naturally occurring herbicide that irreversibly arrests germination of the seeds of grassy weeds; such as annual bluegrass (Poa annua), without significantly affecting the growth of established grass seedlings and mature plants, or germination of the se...

  4. Arrested coalescence of viscoelastic droplets: polydisperse doublets.

    Science.gov (United States)

    Dahiya, Prerna; Caggioni, Marco; Spicer, Patrick T

    2016-07-28

    Arrested droplet coalescence produces stable anisotropic shapes and is a key mechanism for microstructure development in foods, petroleum and pharmaceutical formulations. Past work has examined the dynamic elastic arrest of coalescing monodisperse droplet doublets and developed a simple model of doublet strain as a function of physical variables. Although the work describes experimental data well, it is limited to describing same-size droplets. A new model incorporating a generalized description of doublet shape is developed to describe polydisperse doublet formation in more realistic emulsion systems. Polydisperse doublets are shown to arrest at lower strains than monodisperse doublets as a result of the smaller contribution of surface area in a given pair. Larger droplet size ratios have lower relative degrees of strain because coalescence is arrested at an earlier stage than in more monodisperse cases. Experimental observations of polydisperse doublet formation indicate that the model under-predicts arrest strains at low solid levels and small droplet sizes. The discrepancy is hypothesized to be the result of nonlinear elastic deformation at high strains.This article is part of the themed issue 'Soft interfacial materials: from fundamentals to formulation'. PMID:27298435

  5. Cell cycle arrest and cell survival induce reverse trends of cardiolipin remodeling.

    Directory of Open Access Journals (Sweden)

    Yu-Jen Chao

    Full Text Available Cell survival from the arrested state can be a cause of the cancer recurrence. Transition from the arrest state to the growth state is highly regulated by mitochondrial activity, which is related to the lipid compositions of the mitochondrial membrane. Cardiolipin is a critical phospholipid for the mitochondrial integrity and functions. We examined the changes of cardiolipin species by LC-MS in the transition between cell cycle arrest and cell reviving in HT1080 fibrosarcoma cells. We have identified 41 cardiolipin species by MS/MS and semi-quantitated them to analyze the detailed changes of cardiolipin species. The mass spectra of cardiolipin with the same carbon number form an envelope, and the C64, C66, C68, C70 C72 and C74 envelopes in HT1080 cells show a normal distribution in the full scan mass spectrum. The cardiolipin quantity in a cell decreases while entering the cell cycle arrest, but maintains at a similar level through cell survival. While cells awakening from the arrested state and preparing itself for replication, the groups with short acyl chains, such as C64, C66 and C68 show a decrease of cardiolipin percentage, but the groups with long acyl chains, such as C70 and C72 display an increase of cardiolipin percentage. Interestingly, the trends of the cardiolipin species changes during the arresting state are completely opposite to cell growing state. Our results indicate that the cardiolipin species shift from the short chain to long chain cardiolipin during the transition from cell cycle arrest to cell progression.

  6. Renoprotective Effect of Lactoferrin against Chromium-Induced Acute Kidney Injury in Rats: Involvement of IL-18 and IGF-1 Inhibition.

    Directory of Open Access Journals (Sweden)

    Rehab Hegazy

    Full Text Available Hexavalent chromium (CrVI is a heavy metal widely used in more than 50 industries. Nephrotoxicity is a major adverse effect of chromium poisoning. The present study investigated the potential renoprotective effect of lactoferrin (Lf against potassium dichromate (PDC-induced acute kidney injury (AKI in rats. Beside, because previous studies suggest that interlukin-18 (IL-18 and insulin-like growth factor-1 (IGF-1 play important roles in promoting kidney damage, the present work aimed to evaluate the involvement of these two cytokines in PDC model of AKI and in the potential renoprotective effect of lactoferrin. Adult male albino Wistar rats were pretreated with Lf (200 mg/kg/day, p.o. or (300 mg/kg/day, p.o.; the doses that are usually used in the experiment studies, for 14 days followed by a single dose of PDC (15 mg/kg, s.c.. PDC caused significant increase in serum urea, creatinine, and total protein levels. This was accompanied with decreased renal glutathione content, and increased renal malondialdehyde, IL-18, IL-4, nuclear factor kappa B (NFκB, IGF-1, and the phosphorylated form of forkhead box protein O1 (FoxO1 levels. Moreover, normal expression IFN-γ mRNA and enhanced expression of TNF-α mRNA was demonstrated in renal tissues. Histopathological investigations provoked deleterious changes in the renal tissues. Tubular epithelial hyperplasia and apoptosis were demonstrated immunohistochemically by positive proliferating cell nuclear antigen (PCNA, Bax, and Caspase-3 expression, respectively. Pretreatment of rats with Lf in both doses significantly corrected all previously mentioned PDC-induced changes with no significant difference between both doses. In conclusion, the findings of the present study demonstrated the involvement of oxidative stress, inflammatory reactions, tubular hyperplasia and apoptosis in PDC-induced AKI. It suggested a role of IL-18 through stimulation of IL-4-induced inflammatory pathway, and IGF-1 through

  7. Cell cycle arrest by a gradient of Dpp signaling during Drosophila eye development

    Directory of Open Access Journals (Sweden)

    Bhattacharya Abhishek

    2010-03-01

    Full Text Available Abstract Background The secreted morphogen Dpp plays important roles in spatial regulation of gene expression and cell cycle progression in the developing Drosophila eye. Dpp signaling is required for timely cell cycle arrest ahead of the morphogenetic furrow as a prelude to differentiation, and is also important for eye disc growth. The dpp gene is expressed at multiple locations in the eye imaginal disc, including the morphogenetic furrow that sweeps across the eye disc as differentiation initiates. Results Studies of Brinker and Dad expression, and of Mad phosphorylation, establish that there is a gradient of Dpp signaling in the eye imaginal disc anterior to the morphogenetic furrow, predominantly in the anterior-posterior axis, and also Dpp signaling at the margins of the disc epithelium and in the dorsal peripodial membrane. Almost all signaling activity seems to spread through the plane of the epithelia, although peripodial epithelium cells can also respond to underlying disc cells. There is a graded requirement for Dpp signaling components for G1 arrest in the eye disc, with more stringent requirements further anteriorly where signaling is lower. The signaling level defines the cell cycle response, because elevated signaling through expression of an activated Thickveins receptor molecule arrested cells at more anterior locations. Very anterior regions of the eye disc were not arrested in response to activated receptor, however, and evidence is presented that expression of the Homothorax protein may contribute to this protection. By contrast to activated Thickveins, ectopic expression of processed Dpp leads to very high levels of Mad phosphorylation which appear to have non-physiological consequences. Conclusions G1 arrest occurs at a threshold level of Dpp signaling within a morphogen gradient in the anterior eye. G1 arrest is specific for one competent domain in the eye disc, allowing Dpp signaling to promote growth at earlier

  8. Juvenile Arrests, 2007. Juvenile Justice Bulletin

    Science.gov (United States)

    Puzzanchera, Charles

    2009-01-01

    This Bulletin summarizes 2007 juvenile crime and arrest data reported by local law enforcement agencies across the country and cited in the FBI report, "Crime in the United States 2007." The Bulletin describes the extent and nature of juvenile crime that comes to the attention of the justice system. It serves as a baseline for comparison for…

  9. Acute kidney injury after cardiac arrest

    OpenAIRE

    Tujjar, Omar; Mineo, Giulia; Dell’Anna, Antonio; Poyatos-Robles, Belen; Donadello, Katia; Scolletta, Sabino; Vincent, Jean-Louis; Taccone, Fabio Silvio

    2015-01-01

    Introduction The aim of this study was to evaluate the incidence and determinants of AKI in a large cohort of cardiac arrest patients. Methods We reviewed all patients admitted, for at least 48 hours, to our Dept. of Intensive Care after CA between January 2008 and October 2012. AKI was defined as oligo-anuria (daily urine output

  10. The Organizational Determinants of Police Arrest Decisions

    Science.gov (United States)

    Chappell, Allison T.; MacDonald, John M.; Manz, Patrick W.

    2006-01-01

    A limited amount of research has examined the relationship between characteristics of police organizations and policing styles. In particular, few studies have examined the link between organizational structures and police officer arrest decisions. Wilson's (1968) pioneering case study of police organizations suggested that individual police…

  11. Maternal Cardiac Arrest: A Practical and Comprehensive Review

    Directory of Open Access Journals (Sweden)

    Farida M. Jeejeebhoy

    2013-01-01

    Full Text Available Cardiac arrest during pregnancy is a dedicated chapter in the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care; however, a robust maternal cardiac arrest knowledge translation strategy and emergency response plan is not usually the focus of institutional emergency preparedness programs. Although maternal cardiac arrest is rare, the emergency department is a high-risk area for receiving pregnant women in either prearrest or full cardiac arrest. It is imperative that institutions review and update emergency response plans for a maternal arrest. This review highlights the most recent science, guidelines, and recommended implementation strategies related to a maternal arrest. The aim of this paper is to increase the understanding of the important physiological differences of, and management strategies for, a maternal cardiac arrest, as well as provide institutions with the most up-to-date literature on which they can build emergency preparedness programs for a maternal arrest.

  12. Myocardial stunning after resuscitation from cardiac arrest following spinal anaesthesia

    OpenAIRE

    Pranjali Madhav Kurhekar; VSG Yachendra; Simi P Babu; Raghavelu Govindasamy

    2014-01-01

    Cardiac arrest associated with spinal anaesthesia has been well researched. Myocardial stunning after successful resuscitation from cardiac arrest is seen in up to 2/3 rd of in-hospital cardiac arrests. Myocardial stunning after resuscitation from cardiac arrest associated with spinal anaesthesia has probably not been reported earlier. Our case, an ASA physical status I lady, posted for tubal reanastomosis surgery developed bradycardia followed by asystole, approximately 5 minutes after givin...

  13. Piperine causes G1 phase cell cycle arrest and apoptosis in melanoma cells through checkpoint kinase-1 activation.

    Directory of Open Access Journals (Sweden)

    Neel M Fofaria

    Full Text Available In this study, we determined the cytotoxic effects of piperine, a major constituent of black and long pepper in melanoma cells. Piperine treatment inhibited the growth of SK MEL 28 and B16 F0 cells in a dose and time-dependent manner. The growth inhibitory effects of piperine were mediated by cell cycle arrest of both the cell lines in G1 phase. The G1 arrest by piperine correlated with the down-regulation of cyclin D1 and induction of p21. Furthermore, this growth arrest by piperine treatment was associated with DNA damage as indicated by phosphorylation of H2AX at Ser139, activation of ataxia telangiectasia and rad3-related protein (ATR and checkpoint kinase 1 (Chk1. Pretreatment with AZD 7762, a Chk1 inhibitor not only abrogated the activation of Chk1 but also piperine mediated G1 arrest. Similarly, transfection of cells with Chk1 siRNA completely protected the cells from G1 arrest induced by piperine. Piperine treatment caused down-regulation of E2F1 and phosphorylation of retinoblastoma protein (Rb. Apoptosis induced by piperine was associated with down-regulation of XIAP, Bid (full length and cleavage of Caspase-3 and PARP. Furthermore, our results showed that piperine treatment generated ROS in melanoma cells. Blocking ROS by tiron protected the cells from piperine mediated cell cycle arrest and apoptosis. These results suggest that piperine mediated ROS played a critical role in inducing DNA damage and activation of Chk1 leading to G1 cell cycle arrest and apoptosis.

  14. Pediatric Cardiac Arrest Due to Trauma.

    Science.gov (United States)

    Kjellemo, Hugo; Hansen, Andreas E; Øines, Dennis A; Nilsen, Thor O; Wik, Lars

    2016-01-01

    Survival from pediatric cardiac arrest due to trauma has been reported to be 0.0%-8.8%. Some argue that resuscitation efforts in the case of trauma-related cardiac arrests are futile. We describe a successful outcome in the case of a child who suffered cardiac arrest caused by external traumatic airway obstruction. Our case illustrates how to deal with pediatric traumatic cardiac arrests in an out-of-hospital environment. It also illustrates how good clinical treatment in these situations may be supported by correct treatment after hospital admission when it is impossible to ventilate the patient to provide sufficient oxygen delivery to vital organs. This case relates to a lifeless child of 3-5 years, blue, and trapped by an electrically operated garage door. The first ambulance arrived to find several men trying to bend the frame and the door apart in order to extricate the child, who was hanging in the air with head and neck squeezed between the horizontally-moving garage door and the vertical door frame. One paramedic found a car jack and used it to push the door and the frame apart, allowing the lifeless child to be extricated. Basic life support was then initiated. Intubation was performed by the anesthesiologist without drugs. With FiO2 1.0 the first documented SaO2 was <50%. Restoration of Spontaneous Circulation was achieved after thirty minutes, and she was transported to the hospital. After a few hours she was put on venous-arterial ECMO for 5.5 days and discharged home after two months. Outpatient examinations during the rest of 2013 were positive, and the child found not to be suffering from any injuries, either physical or mental. The last follow-up in October 2014 demonstrated she had made a 100% recovery and she started school in August 2014. PMID:26930137

  15. Nuclear reactor melt arrest and coolability device

    Energy Technology Data Exchange (ETDEWEB)

    Theofanous, Theo G.; Dinh, Nam Truc; Wachowiak, Richard M.

    2016-06-14

    Example embodiments provide a Basemat-Internal Melt Arrest and Coolability device (BiMAC) that offers improved spatial and mechanical characteristics for use in damage prevention and risk mitigation in accident scenarios. Example embodiments may include a BiMAC having an inclination of less than 10-degrees from the basemat floor and/or coolant channels of less than 4 inches in diameter, while maintaining minimum safety margins required by the Nuclear Regulatory Commission.

  16. Hypothermia improves outcome from cardiac arrest.

    Science.gov (United States)

    Bernard, S A

    2005-12-01

    Out-of-hospital cardiac arrest is common and patients who are initially resuscitated by ambulance officers and transported to hospital are usually admitted to the intensive care unit (ICU). In the past, the treatment in the ICU consisted of supportive care only, and most patients remained unconscious due to the severe anoxic neurological injury. It was this neurological injury rather than cardiac complications that caused the high rate of morbidity and mortality. However, in the early 1990's, a series of animal experiments demonstrated convincingly that mild hypothermia induced after return of spontaneous circulation and maintained for several hours dramatically reduced the severity of the anoxic neurological injury. In the mid-1990's, preliminary human studies suggested that mild hypothermia could be induced and maintained in post-cardiac arrest patients without an increase in the rate of cardiac or other complications. In the late 1990's, two prospective, randomised, controlled trials were conducted and the results confirmed the animal data that mild hypothermia induced after resuscitation and maintained for 12 - 24 hours dramatically improved neurological and overall outcomes. On the basis of these studies, mild hypothermia was endorsed in 2003 by the International Liaison Committee on Resuscitation as a recommended treatment for comatose patients with an initial cardiac rhythm of ventricular fibrillation. However, the application of this therapy into routine clinical critical care practice has been slow. The reasons for this are uncertain, but may relate to the relative complexity of the treatment, unfamiliarity with the pathophysiology of hypothermia, lack of clear protocols and/or uncertainty of benefit in particular patients. Therefore, recent research in this area has focused on the development of feasible, inexpensive techniques for the early, rapid induction of mild hypothermia after cardiac arrest. Currently, the most promising strategy is a rapid

  17. Berberine induces p53-dependent cell cycle arrest and apoptosis of human osteosarcoma cells by inflicting DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Liu Zhaojian; Liu Qiao; Xu Bing; Wu Jingjing [Key Laboratory of Experimental Teratology of Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Guo Chun; Zhu Faliang [Institute of Immunology, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Yang Qiaozi [Department of Genetics, Rutgers University, Piscataway, NJ 08854 (United States); Gao Guimin [Key Laboratory of Experimental Teratology of Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Gong Yaoqin [Key Laboratory of Experimental Teratology of Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China)], E-mail: yxg8@sdu.edu.cn; Shao Changshun [Key Laboratory of Experimental Teratology of Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Department of Genetics, Rutgers University, Piscataway, NJ 08854 (United States)], E-mail: shao@biology.rutgers.edu

    2009-03-09

    Alkaloid berberine is widely used for the treatment of diarrhea and other diseases. Many laboratory studies showed that it exhibits anti-proliferative activity against a wide spectrum of cancer cells in culture. In this report we studied the mechanisms underlying the inhibitory effects of berberine on human osteosarcoma cells and on normal osteoblasts. The inhibition was largely attributed to cell cycle arrest at G1 and G2/M, and to a less extent, to apoptosis. The G1 arrest was dependent on p53, as G1 arrest was abolished in p53-deficient osteosarcoma cells. The induction of G1 arrest and apoptosis was accompanied by a p53-dependent up-regulation of p21 and pro-apoptotic genes. However, the G2/M arrest could be induced by berberine regardless of the status of p53. Interestingly, DNA double-strand breaks, as measured by the phosphorylation of H2AX, were remarkably accumulated in berberine-treated cells in a dose-dependent manner. Thus, one major mechanism by which berberine exerts its growth-inhibitory effect is to inflict genomic lesions on cells, which in turn trigger the activation of p53 and the p53-dependent cellular responses including cell cycle arrest and apoptosis.

  18. Apoptosis and cell-cycle arrest in human and murine tumor cells are initiated by isoprenoids.

    Science.gov (United States)

    Mo, H; Elson, C E

    1999-04-01

    Diverse classes of phytochemicals initiate biological responses that effectively lower cancer risk. One class of phytochemicals, broadly defined as pure and mixed isoprenoids, encompasses an estimated 22,000 individual components. A representative mixed isoprenoid, gamma-tocotrienol, suppresses the growth of murine B16(F10) melanoma cells, and with greater potency, the growth of human breast adenocarcinoma (MCF-7) and human leukemic (HL-60) cells. beta-Ionone, a pure isoprenoid, suppresses the growth of B16 cells and with greater potency, the growth of MCF-7, HL-60 and human colon adenocarcinoma (Caco-2) cells. Results obtained with diverse cell lines differing in ras and p53 status showed that the isoprenoid-mediated suppression of growth is independent of mutated ras and p53 functions. beta-Ionone suppressed the growth of human colon fibroblasts (CCD-18Co) but only when present at three-fold the concentration required to suppress the growth of Caco-2 cells. The isoprenoids initiated apoptosis and, concomitantly arrested cells in the G1 phase of the cell cycle. Both suppress 3-hydroxy-3-methylglutaryl CoA reductase activity. beta-Ionone and lovastatin interfered with the posttranslational processing of lamin B, an activity essential to assembly of daughter nuclei. This interference, we postulate, renders neosynthesized DNA available to the endonuclease activities leading to apoptotic cell death. Lovastatin-imposed mevalonate starvation suppressed the glycosylation and translocation of growth factor receptors to the cell surface. As a consequence, cells were arrested in the G1 phase of the cell cycle. This rationale may apply to the isoprenoid-mediated G1-phase arrest of tumor cells. The additive and potentially synergistic actions of these isoprenoids in the suppression of tumor cell proliferation and initiation of apoptosis coupled with the mass action of the diverse isoprenoid constituents of plant products may explain, in part, the impact of fruit, vegetable

  19. Sudden cardiac arrest following ventricular fibrillation attributed to anabolic steroid use in an adolescent.

    Science.gov (United States)

    Lichtenfeld, Jana; Deal, Barbara J; Crawford, Susan

    2016-06-01

    Anabolic androgenic steroids are synthetic derivatives of testosterone that promote the growth of skeletal muscles and have many recognised cardiovascular effects. We report the clinical presentation and pathological findings of an adolescent male whose sudden cardiac arrest following ventricular fibrillation was attributed to anabolic androgenic steroid use. The age of our patient reflects the usage of anabolic androgenic steroids among younger athletes and highlights the need for increased awareness among practitioners. PMID:26980272

  20. Global arrest of translation during invertebrate quiescence.

    Science.gov (United States)

    Hofmann, G E; Hand, S C

    1994-08-30

    Comparing the translational capacities of cell-free systems from aerobically developing embryos of the brine shrimp Artemia franciscana vs. quiescent embryos has revealed a global arrest of protein synthesis. Incorporation rates of [3H]leucine by lysates from 4-h anoxic embryos were 8% of those from aerobic (control) embryos, when assayed at the respective pH values measured for each treatment in vivo. Exposure of embryos to 4 h of aerobic acidosis (elevated CO2 in the presence of oxygen) suppressed protein synthesis to 3% of control values. These latter two experimental treatments promote developmental arrest of Artemia embryos and, concomitantly, cause acute declines in intracellular pH. When lysates from each treatment were assayed over a range of physiologically relevant pH values (pH 6.4-8.0), amino acid incorporation rates in lysates from quiescent embryos were consistently lower than values for the aerobic controls. Acute reversal of pH to alkaline values during the 6-min assays was not sufficient to return the incorporation rates of quiescent lysates to control values. Thus, a stable alteration in translational capacity of quiescent lysates is indicated. Addition of exogenous mRNA did not rescue the suppressed protein synthesis in quiescent lysates, which suggests that the acute blockage of amino acid incorporation is apparently not due to limitation in message. Thus, the results support a role for intracellular pH as an initial signaling event in translational control during quiescence yet, at the same time, indicate that a direct proton effect on the translational machinery is not the sole proximal agent for biosynthetic arrest in this primitive crustacean. PMID:8078909

  1. Abulia following an episode of cardiac arrest.

    Science.gov (United States)

    Naik, Vismay Dinesh

    2015-01-01

    The word 'abulia' means a lack of will, initiative or drive. The symptoms of abulia include lack of spontaneous action and speech, reduced emotional responsiveness and social interaction, poor attention and easy distractibility. These symptoms are independent of reduced levels of consciousness or cognitive impairment. We describe a case of a socially active 72-year-old female patient who presented with symptoms of abulia which may have occurred due to damage of the frontosubcortical circuits following an episode of cardiac arrest. The patient's symptoms improved dramatically following treatment with bromocriptine. PMID:26135487

  2. Global arrest of translation during invertebrate quiescence.

    OpenAIRE

    Hofmann, G E; Hand, S C

    1994-01-01

    Comparing the translational capacities of cell-free systems from aerobically developing embryos of the brine shrimp Artemia franciscana vs. quiescent embryos has revealed a global arrest of protein synthesis. Incorporation rates of [3H]leucine by lysates from 4-h anoxic embryos were 8% of those from aerobic (control) embryos, when assayed at the respective pH values measured for each treatment in vivo. Exposure of embryos to 4 h of aerobic acidosis (elevated CO2 in the presence of oxygen) sup...

  3. Sublingual Microcirculation is Impaired in Post-cardiac Arrest Patients

    DEFF Research Database (Denmark)

    G. Omar, Yasser; Massey, Michael; Wiuff Andersen, Lars; A. Giberson, Tyler; Berg, Katherine; N. Cocchi, Michael; I. Shapiro, Nathan; W. Donnino, Michael

    2013-01-01

    markers in the post-cardiac arrest state. METHODS: We prospectively evaluated the sublingual microcirculation in post-cardiac arrest patients, severe sepsis/septic shock patients, and healthy control patients using Sidestream Darkfield microscopy. Microcirculatory flow was assessed using the...... microcirculation flow index (MFI) at 6 and 24h in the cardiac arrest patients, and within 6h of emergency department admission in the sepsis and control patients. RESULTS: We evaluated 30 post-cardiac arrest patients, 16 severe sepsis/septic shock patients, and 9 healthy control patients. Sublingual...... microcirculatory blood flow was significantly impaired in post-cardiac arrest patients at 6h (MFI 2.6 [IQR: 2-2.9]) and 24h (2.7 [IQR: 2.3-2.9]) compared to controls (3.0 [IQR: 2.9-3.0]; p<0.01 and 0.02, respectively). After adjustment for initial APACHE II score, post-cardiac arrest patients had significantly...

  4. A case of thyroid storm with cardiac arrest

    Directory of Open Access Journals (Sweden)

    Nakashima Y

    2014-05-01

    Full Text Available Yutaka Nakashima,1 Tsuneaki Kenzaka,2 Masanobu Okayama,3 Eiji Kajii31Department for Support of Rural Medicine, Yamaguchi Grand Medical Center, 2Division of General Medicine, Center for Community Medicine, Jichi Medical University School of Medicine, Shimotsuke, Japan; 3Division of Community and Family Medicine, Center for Community Medicine, Jichi Medical University School of Medicine, Shimotsuke, JapanAbstract: A 23-year-old man became unconscious while jogging. He immediately received basic life support from a bystander and was transported to our hospital. On arrival, his spontaneous circulation had returned from a state of ventricular fibrillation and pulseless electrical activity. Following admission, hyperthyroidism led to a suspicion of thyroid storm, which was then diagnosed as a possible cause of the cardiac arrest. Although hyperthyroidism-induced cardiac arrest including ventricular fibrillation is rare, it should be considered when diagnosing the cause of treatable cardiac arrest.Keywords: hyperthyroidism, ventricular fibrillation, treatable cardiac arrest, cardiac arrest, cardiopulmonary arrest

  5. Myocardial stunning after resuscitation from cardiac arrest following spinal anaesthesia

    Directory of Open Access Journals (Sweden)

    Pranjali Madhav Kurhekar

    2014-01-01

    Full Text Available Cardiac arrest associated with spinal anaesthesia has been well researched. Myocardial stunning after successful resuscitation from cardiac arrest is seen in up to 2/3 rd of in-hospital cardiac arrests. Myocardial stunning after resuscitation from cardiac arrest associated with spinal anaesthesia has probably not been reported earlier. Our case, an ASA physical status I lady, posted for tubal reanastomosis surgery developed bradycardia followed by asystole, approximately 5 minutes after giving subarachnoid block. Return of spontaneous circulation (ROSC was achieved within 2 minutes with cardiopulmonary resuscitation (CPR and defibrillation for pulseless ventricular tachycardia. Patient developed delayed pulmonary oedema, which was probably due to myocardial stunning. In the present case, inadequate preloading could have precipitated bradycardia progressing to cardiac arrest which, after resuscitation led to reversible myocardial dysfunction. We conclude that early vasopressor infusion, titrated fluids and echocardiography should be considered in immediate post cardiac arrest phase following spinal anaesthesia.

  6. Postoperative cardiac arrest due to cardiac surgery complications

    International Nuclear Information System (INIS)

    To examine the role of anesthetists in the management of cardiac arrest occurring in association with cardiac anesthesia. In this retrospective study we studied the potential performances for each of the relevant incidents among 712 patients undergoing cardiac operations at Golestan and Naft Hospitals Ahwaz between November 2006 and July 2008. Out of total 712 patients undergoing cardiac surgery, cardiac arrest occurred in 28 cases (3.9%) due to different postoperative complications. This included massive bleeding (50% of cardiac arrest cases, 1.9% of patients); pulseless supra ventricular tachycardia (28.5% of cardiac arrest cases, 1.1% of patients); Heart Failure (7% of cardiac arrest cases, 0.2% of patients); Aorta Arc Rapture (3.5% of cardiac arrest cases, 0.1% of patients); Tamponade due to pericardial effusion (3.5% of cardiac arrest cases, 0.1% of total patients); Right Atrium Rupture (3.5% of cardiac arrest cases, 0.1% of patients) were detected after cardiac surgery. Out of 28 cases 7 deaths occurred (25% of cardiac arrest cases, 0.1% of patients). The most prevalent reason for cardiac arrest during post operative phase was massive bleeding (50%) followed by pulseless supra ventricular tachycardia (28.5%). Six patients had some morbidity and the remaining 15 patients recovered. There are often multiple contributing factors to a cardiac arrest under cardiac anesthesia, as much a complete systematic assessment of the patient, equipment, and drugs should be completed. We also found that the diagnosis and management of cardiac arrest in association with cardiac anesthesia differs considerably from that encountered elsewhere. (author)

  7. Hospital Variation in Survival After In‐hospital Cardiac Arrest

    OpenAIRE

    Merchant, Raina M.; Berg, Robert A.; Yang, Lin; Becker, Lance B.; Groeneveld, Peter W.; Chan, Paul S.; ,

    2014-01-01

    Background In‐hospital cardiac arrest (IHCA) is common and often fatal. However, the extent to which hospitals vary in survival outcomes and the degree to which this variation is explained by patient and hospital factors is unknown. Methods and Results Within Get with the Guidelines‐Resuscitation, we identified 135 896 index IHCA events at 468 hospitals. Using hierarchical models, we adjusted for demographics comorbidities and arrest characteristics (eg, initial rhythm, etiology, arrest locat...

  8. SPARC expression induces cell cycle arrest via STAT3 signaling pathway in medulloblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Chetty, Chandramu [Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL-61605 (United States); Dontula, Ranadheer [Section of Hematology/Oncology, Department of Medicine, University of Illinois College of Medicine at Chicago, 840 South Wood Street, Suite 820-E, Chicago, IL-60612 (United States); Ganji, Purnachandra Nagaraju [Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL-61605 (United States); Gujrati, Meena [Department of Pathology, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL-61605 (United States); Lakka, Sajani S., E-mail: slakka@uic.edu [Section of Hematology/Oncology, Department of Medicine, University of Illinois College of Medicine at Chicago, 840 South Wood Street, Suite 820-E, Chicago, IL-60612 (United States)

    2012-01-13

    Highlights: Black-Right-Pointing-Pointer Ectopic expression of SPARC impaired cell proliferation in medulloblastoma cells. Black-Right-Pointing-Pointer SPARC expression induces STAT3 mediated cell cycle arrest in medulloblastoma cells. Black-Right-Pointing-Pointer SPARC expression significantly inhibited pre-established tumor growth in nude-mice. -- Abstract: Dynamic cell interaction with ECM components has profound influence in cancer progression. SPARC is a component of the ECM, impairs the proliferation of different cell types and modulates tumor cell aggressive features. We previously reported that SPARC expression significantly impairs medulloblastoma tumor growth in vivo. In this study, we demonstrate that expression of SPARC inhibits medulloblastoma cell proliferation. MTT assay indicated a dose-dependent reduction in tumor cell proliferation in adenoviral mediated expression of SPARC full length cDNA (Ad-DsRed-SP) in D425 and UW228 cells. Flow cytometric analysis showed that Ad-DsRed-SP-infected cells accumulate in the G2/M phase of cell cycle. Further, immunoblot and immunoprecipitation analyses revealed that SPARC induced G2/M cell cycle arrest was mediated through inhibition of the Cyclin-B-regulated signaling pathway involving p21 and Cdc2 expression. Additionally, expression of SPARC decreased STAT3 phosphorylation at Tyr-705; constitutively active STAT3 expression reversed SPARC induced G2/M arrest. Ad-DsRed-SP significantly inhibited the pre-established orthotopic tumor growth and tumor volume in nude-mice. Immunohistochemical analysis of tumor sections from mice treated with Ad-DsRed-SP showed decreased immunoreactivity for pSTAT3 and increased immunoreactivity for p21 compared to tumor section from mice treated with mock and Ad-DsRed. Taken together our studies further reveal that STAT3 plays a key role in SPARC induced G2/M arrest in medulloblastoma cells. These new findings provide a molecular basis for the mechanistic understanding of the

  9. Resuscitation, prolonged cardiac arrest, and an automated chest compression device

    DEFF Research Database (Denmark)

    Risom, Martin; Jørgensen, Henrik; Rasmussen, Lars S;

    2010-01-01

    The European Resuscitation Council's 2005 guidelines for cardiopulmonary resuscitation (CPR) emphasize the delivery of uninterrupted chest compressions of adequate depth during cardiac arrest.......The European Resuscitation Council's 2005 guidelines for cardiopulmonary resuscitation (CPR) emphasize the delivery of uninterrupted chest compressions of adequate depth during cardiac arrest....

  10. Buoyant currents arrested by convective dissolution

    Science.gov (United States)

    MacMinn, Christopher W.; Juanes, Ruben

    2013-05-01

    When carbon dioxide (CO2) dissolves into water, the density of water increases. This seemingly insubstantial phenomenon has profound implications for geologic carbon sequestration. Here we show, by means of laboratory experiments with analog fluids, that the up-slope migration of a buoyant current of CO2 is arrested by the convective dissolution that ensues from a fingering instability at the moving CO2-groundwater interface. We consider the effectiveness of convective dissolution as a large-scale trapping mechanism in sloping aquifers, and we show that a small amount of slope is beneficial compared to the horizontal case. We study the development and coarsening of the fingering instability along the migrating current and predict the maximum migration distance of the current with a simple sharp-interface model. We show that convective dissolution exerts a powerful control on CO2 plume dynamics and, as a result, on the potential of geologic carbon sequestration.

  11. Maturation arrest of human oocytes at germinal vesicle stage

    Directory of Open Access Journals (Sweden)

    Zhi Qin Chen

    2010-01-01

    Full Text Available Maturation arrest of human oocytes may occur at various stages of the cell cycle. A total failure of human oocytes to complete meiosis is rarely observed during assisted conception cycles. We describe here a case of infertile couples for whom all oocytes repeatedly failed to mature at germinal vesicle (GV stage during in vitro fertilization/Intra cytoplasmic sperm injection (IVF/ICSI. The patient underwent controlled ovarian stimulation followed by oocyte retrieval and IVF/ICSI. The oocytes were stripped off cumulus cells prior to the ICSI procedure and their maturity status was defined. The oocyte maturation was repeatedly arrested at the GV. Oocyte maturation arrest may be the cause of infertility in this couple. The recognition of oocyte maturation arrest as a specific medical condition may contribute to the characterization of the currently known as "oocyte factor." The cellular and genetic mechanisms causing oocyte maturation arrest should be the subject for further investigation.

  12. Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells

    Directory of Open Access Journals (Sweden)

    Morris Robert

    2010-03-01

    Full Text Available Abstract Background Sulforaphane (SFN, an isothiocyanate phytochemical present predominantly in cruciferous vegetables such as brussels sprout and broccoli, is considered a promising chemo-preventive agent against cancer. In-vitro exposure to SFN appears to result in the induction of apoptosis and cell-cycle arrest in a variety of tumor types. However, the molecular mechanisms leading to the inhibition of cell cycle progression by SFN are poorly understood in epithelial ovarian cancer cells (EOC. The aim of this study is to understand the signaling mechanisms through which SFN influences the cell growth and proliferation in EOC. Results SFN at concentrations of 5 - 20 μM induced a dose-dependent suppression of growth in cell lines MDAH 2774 and SkOV-3 with an IC50 of ~8 μM after a 3 day exposure. Combination treatment with chemotherapeutic agent, paclitaxel, resulted in additive growth suppression. SFN at ~8 μM decreased growth by 40% and 20% on day 1 in MDAH 2774 and SkOV-3, respectively. Cells treated with cytotoxic concentrations of SFN have reduced cell migration and increased apoptotic cell death via an increase in Bak/Bcl-2 ratio and cleavage of procaspase-9 and poly (ADP-ribose-polymerase (PARP. Gene expression profile analysis of cell cycle regulated proteins demonstrated increased levels of tumor suppressor retinoblastoma protein (RB and decreased levels of E2F-1 transcription factor. SFN treatment resulted in G1 cell cycle arrest through down modulation of RB phosphorylation and by protecting the RB-E2F-1 complex. Conclusions SFN induces growth arrest and apoptosis in EOC cells. Inhibition of retinoblastoma (RB phosphorylation and reduction in levels of free E2F-1 appear to play an important role in EOC growth arrest.

  13. Evolution of the dragonfly head-arresting system

    OpenAIRE

    Gorb, S. N.

    1999-01-01

    The arrester or fixation system of the head in adult Odonata is unique among arthropods. This system involves the organs of two body segments: the head and the neck. It consists of a skeleton–muscle apparatus that sets the arrester parts in motion. The parts comprise formations covered with complicated microstructures: fields of microtrichia on the rear surface of the head and post-cervical sclerites of the neck. The arrester immobilizes the head during feeding or when the dragonfly is in tan...

  14. Induction and mechanism of growth arrest DNA damage-inducible gene 45 β in human hepatoma HepG2 cells by Triapine%Triapine对肝癌细胞株HepG2中GADD45β表达影响及其可能机制

    Institute of Scientific and Technical Information of China (English)

    王佳玉; 彭承宏; 邱伟华; 杨卫平; 林大伟; 衣琳; 李军; 汪洋; 覃胜灵; 施敏敏; 沈柏用

    2011-01-01

    目的:DNA损伤修复相关基因 GADD45β的特异性表达缺失与肝癌的恶性程度密切相关,本研究初步明确肝癌细胞中GADD45β近端启动子序列,探索3-氨基吡啶-2-甲醛硫代缩氨基脲(Triapine)对人肝癌细胞株HepG2的GADD45β表达影响及其可能机制.方法:体外合成GADD45β近端启动子序列(-618至-314),构建荧光素表达质粒,转染HepG2,根据启动子活性强度结合数据库分析存在的转录调节因子结合位点;以实时荧光定量PCR比较Triapine作用前后HepG2细胞GADD45β表达;进一步比较Triapine对GADD45β启动子活性的调控作用,分析Triapine对HepG2的抑制效应;并通过Caspase-8、Caspase-9和Caspase-3的表达变化测定凋亡的发生和发展.结果:GADD45β近端启动子中含有3个NF-κB (-602/-593、-581/-572、-537/-528)和1个E2F-1 (-470/-436)转录调节因子与启动子结合位点;2.5μmol/L和5μmol/L的Triapine作用后,GA DD45β/GA PDH分别为0.029 3和0.073 9,呈现剂量-诱导效应正相关,同时NF-KB和E2F-1启动子活性分别增强了1.5和0.8倍;高剂量Triapine对HepG2的DNA合成能力和细胞克隆形成能力的抑制率分别为75.25%和60.54%,呈现剂量-抑制效应正相关;Triapine作用后6h即出现HepG2凋亡高峰.结论:Triapine能通过增强转录调节因子的活性,诱导肝癌细胞中特异性缺失的GA DD45β基因表达;进而抑制肝癌细胞的增殖并启动凋亡途径.%Objective To identify the proximal promoter of down-expression of growth arrest DNA damage-inducible gene 45 B (GA DD45f$) and to evaluate the influence of Triapine to HCC cell lines. Methods The proximal promoter fragments (-618/-314) were synthesized in vitro and cloned into pGL3 basic luciferase expression plasmid, then transfected into the HepG2 cell line by electroporation. The promoter regions were identified in reference to TRANSFAC database. Following Triapine administration, quantitative real-time PC Ft was employed to

  15. Extracorporeal membrane oxygenation for pediatric cardiac arrest.

    Science.gov (United States)

    Ryan, Jennie

    2015-02-01

    Extracorporeal cardiopulmonary resuscitation (ECPR) remains a promising treatment for pediatric patients in cardiac arrest unresponsive to traditional cardiopulmonary resuscitation. With venoarterial extracorporeal support, blood is drained from the right atrium, oxygenated through the extracorporeal circuit, and transfused back to the body, bypassing the heart and lungs. The use of artificial oxygenation and perfusion thus provides the body a period of hemodynamic stability, while allowing resolution of underlying disease processes. Survival rates for ECPR patients are higher than those for traditional cardiopulmonary resuscitation (CPR), although neurological outcomes require further investigation. The impact of duration of CPR and length of treatment with extracorporeal membrane oxygenation vary in published reports. Furthermore, current guidelines for the initiation and use of ECPR are limited and may lead to confusion about appropriate use of this support. Many ethical concerns arise with this advanced form of life support. More often than not, the dilemma is not whether to withhold ECPR, but rather when to withdraw it. Although clinicians must decide if ECPR is appropriate and when further intervention is futile, the ultimate burden of choice is left to the patient's caregivers. Offering support and guidance to the patient's family as well as the patient is essential. PMID:25639578

  16. Crack-arrest behavior in SEN wide plates of low-upper-shelf base metal tested under nonisothermal conditions: WP-2 series

    International Nuclear Information System (INIS)

    The Heavy-Section Steel Technology (HSST) Program at the Oak Ridge National Laboratory under the sponsorship of the Nuclear Regulatory Commission is conducting analytical and experimental studies aimed at understanding the circumstances that would initiate the growth of an existing crack in a reactor pressure vessel (RPV) and the conditions leading to arrest of a propagating crack. Objectives of these studies are to determine (1) if the material will exhibit crack-arrest behavior when the driving force on a crack exceeds the ASME limit, (2) the relationship between KIa and temperature, and (3) the interaction of fracture modes (arrest, stable crack growth, unstable crack growth, and tensile instability) when arrest occurs at high temperatures. In meeting these objectives, crack-arrest data are being developed over an expanded temperature range through tests involving large thermally shocked cylinders, pressurized thermally shocked vessels, and wide-plate specimens. The wide-plate specimens provide the opportunity for a significant number of data points to be obtained at relatively affordable costs. These tests are designed to provide fracture-toughness measurements approaching or above the onset of the Charpy upper-shelf regime in a rising toughness region and with an increasing driving force. This document discusses test methodology and results. 23 refs., 92 figs., 25 tabs

  17. Radiation-induced apoptosis, necrosis and G2 arrest in Fadu and Hep2 cells

    International Nuclear Information System (INIS)

    Radiation damage is produced and viable cell number is reduced. We need to know the type of cell death by the ionizing radiation and the amount and duration of cell cycle arrest. In this study, we want to identified the main cause of the cellular damage in the oral cancer cells and normal keratinocytes with clinical useful radiation dosage. Human gingival tissue specimens obtained from healthy volunteers were used for primary culture of the normal human oral keratinocytes (NHOK). Primary NHOK were prepared from separated epithelial tissue and maintained in keratinocyte growth medium containing 0.15 mM calcium and a supplementary growth factor bullet kit as described previously. Fadu and Hep-2 cell lines were obtained from KCLB. Cells were irradiated in a (137) Cs gamma-irradiator at the dose of 10 Gy. The dose rate was 5.38 Gy/min. The necrotic cell death was examined with Lactate Dehydrogenase (LDH) activity in the culture medium. Every 4 day after irradiation, LDH activities were read and compared control group. Cell cycle phase distribution and preG1-incidence after radiation was analyzed by flow cytometry using Propidium Iodine (PI) staining. Cell cycle analysis were carried out with a FAC Star plus flowcytometry (FACS, Becton Dickinson, USA) and DNA histograms were processed with CELLFIT software (Becton Dickinson, USA). LDH activity increased in all of the experimental cells by the times. This pattern could be seen in the non-irradiated cells, and there was no difference between the non-irradiated cells and irradiated cells. We detected an induction of apoptosis after irradiation with a single dose of 10 Gy. The maximal rate of apoptosis ranged from 4.0% to 8.0% 4 days after irradiation. In all experimental cells, we detected G2/M arrest after irradiation with a single dose of 10 Gy. Yet there were differences in the number of G2/M arrested cells. The maximal rate of the G2/M ranges from 60.0% to 80.0% 24h after irradiation. There is no significant changes on

  18. Emergency Neurological Life Support: Resuscitation Following Cardiac Arrest.

    Science.gov (United States)

    Rittenberger, Jon C; Friess, Stuart; Polderman, Kees H

    2015-12-01

    Cardiac arrest is the most common cause of death in North America. Neurocritical care interventions, including targeted temperature management (TTM), have significantly improved neurological outcomes in patients successfully resuscitated from cardiac arrest. Therefore, resuscitation following cardiac arrest was chosen as an emergency neurological life support protocol. Patients remaining comatose following resuscitation from cardiac arrest should be considered for TTM. This protocol will review induction, maintenance, and re-warming phases of TTM, along with management of TTM side effects. Aggressive shivering suppression is necessary with this treatment to ensure the maintenance of a target temperature. Ancillary testing, including electrocardiography, computed tomography and/or magnetic resonance imaging of the brain, continuous electroencephalography monitoring, and correction of electrolyte, blood gas, and hematocrit changes, are also necessary to optimize outcomes. PMID:26438463

  19. [Effect of phenibut on the respiratory arrest caused by serotonin].

    Science.gov (United States)

    Tarakanov, I A; Tarasova, N N; Belova, E A; Safonov, V A

    2006-01-01

    The role of the GABAergic system in mechanisms of the respiratory arrest caused by serotonin administration was studied in anaesthetized rats. Under normal conditions, the systemic administration of serotonin (20-60 mg/kg, i.v.) resulted in drastic changes of the respiratory pattern, whereby the initial phase of increased respiratory rate was followed by the respiratory arrest. The preliminary injection of phenibut (400 mg/kg, i.p.) abolished or sharply reduced the duration of the respiratory arrest phase induced by serotonin. Bilateral vagotomy following the phenibut injection potentiated the anti-apnoesic effect of phenibut, which was evidence of the additive action of vagotomy and phenibut administration. The mechanism of apnea caused by serotonin administration is suggested to include a central GABAergic element, which is activated by phenibut so as to counteract the respiratory arrest. PMID:16579056

  20. Diacetylmorphine (heroin) body packer presenting with respiratory arrest.

    Science.gov (United States)

    Naseem, Arshad; Abbas, Shahid

    2009-04-01

    Intracorporeal concealment of illicit drugs known as 'body packing' is uncommonly reported. A body packer with swallowed capsules containing Diacetylmorphine (heroin) for smuggling purposes presented with respiratory arrest and recovered after ventilatory support and nalaxone infusion. PMID:19356347

  1. Human papillomavirus 16E6 and NFX1-123 potentiate notch signaling and differentiation without activating cellular arrest

    International Nuclear Information System (INIS)

    High-risk human papillomavirus (HR HPV) oncoproteins bind host cell proteins to dysregulate and uncouple apoptosis, senescence, differentiation, and growth. These pathways are important for both the viral life cycle and cancer development. HR HPV16 E6 (16E6) interacts with the cellular protein NFX1-123, and they collaboratively increase the growth and differentiation master regulator, Notch1. In 16E6 expressing keratinocytes (16E6 HFKs), the Notch canonical pathway genes Hes1 and Hes5 were increased with overexpression of NFX1-123, and their expression was directly linked to the activation or blockade of the Notch1 receptor. Keratinocyte differentiation genes Keratin 1 and Keratin 10 were also increased, but in contrast their upregulation was only indirectly associated with Notch1 receptor stimulation and was fully unlinked to growth arrest, increased p21Waf1/CIP1, or decreased proliferative factor Ki67. This leads to a model of 16E6, NFX1-123, and Notch1 differently regulating canonical and differentiation pathways and entirely uncoupling cellular arrest from increased differentiation. - Highlights: • 16E6 and NFX1-123 increased the Notch canonical pathway through Notch1. • 16E6 and NFX1-123 increased the differentiation pathway indirectly through Notch1. • 16E6 and NFX1-123 increased differentiation gene expression without growth arrest. • Increased NFX1-123 with 16E6 may create an ideal cellular phenotype for HPV

  2. Human papillomavirus 16E6 and NFX1-123 potentiate notch signaling and differentiation without activating cellular arrest

    Energy Technology Data Exchange (ETDEWEB)

    Vliet-Gregg, Portia A.; Hamilton, Jennifer R. [Center for Global Infectious Disease Research, Seattle Children' s Research Institute, 1900 Ninth Ave., Seattle, WA 98101 (United States); Katzenellenbogen, Rachel A., E-mail: rkatzen@uw.edu [Center for Global Infectious Disease Research, Seattle Children' s Research Institute, 1900 Ninth Ave., Seattle, WA 98101 (United States); Department of Pediatrics, Division of Adolescent Medicine, University of Washington, Seattle WA (United States)

    2015-04-15

    High-risk human papillomavirus (HR HPV) oncoproteins bind host cell proteins to dysregulate and uncouple apoptosis, senescence, differentiation, and growth. These pathways are important for both the viral life cycle and cancer development. HR HPV16 E6 (16E6) interacts with the cellular protein NFX1-123, and they collaboratively increase the growth and differentiation master regulator, Notch1. In 16E6 expressing keratinocytes (16E6 HFKs), the Notch canonical pathway genes Hes1 and Hes5 were increased with overexpression of NFX1-123, and their expression was directly linked to the activation or blockade of the Notch1 receptor. Keratinocyte differentiation genes Keratin 1 and Keratin 10 were also increased, but in contrast their upregulation was only indirectly associated with Notch1 receptor stimulation and was fully unlinked to growth arrest, increased p21{sup Waf1/CIP1}, or decreased proliferative factor Ki67. This leads to a model of 16E6, NFX1-123, and Notch1 differently regulating canonical and differentiation pathways and entirely uncoupling cellular arrest from increased differentiation. - Highlights: • 16E6 and NFX1-123 increased the Notch canonical pathway through Notch1. • 16E6 and NFX1-123 increased the differentiation pathway indirectly through Notch1. • 16E6 and NFX1-123 increased differentiation gene expression without growth arrest. • Increased NFX1-123 with 16E6 may create an ideal cellular phenotype for HPV.

  3. Early myoclonic status and outcome after cardiorespiratory arrest

    OpenAIRE

    Morris, H; Howard, R; Brown, P.

    1998-01-01

    It has been suggested that early myoclonic status after cardiorespiratory arrest is an agonal event.1 Here we describe three cases who developed early myoclonic status during a coma after cardiorespiratory arrest due to acute asthma. As consciousness improved, each patient developed Lance-Adams type multifocal myoclonus, but the eventual outcome was satisfactory. Only one patient needed assistance to walk, and all three were self caring. One patient had persistent dyscalc...

  4. Crack arrest saturation model under combined electrical and mechanical loadings

    OpenAIRE

    R.R. Bhargava; A. Setia

    2009-01-01

    Purpose: The investigation aims at proposing a model for cracked piezoelectric strip which is capable to arrest the crack.Design/methodology/approach: Under the combined effect of electrical and mechanical loadings applied at the edges of the strip, the developed saturation zone is produced at each tip of the crack. To arrest further opening of the crack, the rims of the developed saturation zones are subjected to in-plane cohesive, normal uniform constant saturation point electrical displace...

  5. Al-Qaeda arrest casts shadow over the LHC

    CERN Multimedia

    Dacey, James

    2010-01-01

    "Cern remains on course for the imminent switch-on of the Large Hadron Collider (LHC) despite the media frenzy following the recent arrest of a physicist who had been working at the facility. The researcher in question is a 32-year-old man of Algerian descent who is expected to face trail in France - the country in which he was arrested" (0.5 page)

  6. The psychosocial outcome of anoxic brain injury following cardiac arrest

    OpenAIRE

    Wilson, Michelle

    2012-01-01

    Aim of the study The psychosocial outcome of anoxic brain injury following cardiac arrest is a relatively under researched, but clinically important area. The aim of the current study was to add to the limited existing literature exploring the psychosocial outcome for cardiac arrest survivors, but specifically explore if there is a greater impact on psychosocial outcome in individuals experiencing anoxic brain injury as a result. Methods A range of self report measures were used to c...

  7. Cardiopulmonary arrest in pregnancy with schizophrenia: a case report

    OpenAIRE

    Kudo, Takako; Kaga, Akimune; Akagi, Kozo; Iwahashi, Hideki; Makino, Hiromitsu; WATANABE, YOKO; Kawamura, Takae; Sato, Taiju; Shinozaki, Tsuyoshi; Miwa, Shinya; Okazaki, Nobuo; Kure, Shigeo; Nakae, Shingi

    2014-01-01

    Background Cardiopulmonary arrest in pregnancy has a very high maternal and fetal mortality rate. We report a case of successful maternal and neonatal survival in association with emergency cesarean section of a schizophrenic pregnant patient. To our knowledge, this is the first reported case of cardiopulmonary arrest in a pregnant woman with schizophrenia. Case presentation The parents were Japanese. The mother was 39 years old and had no history of prior pregnancy. Her admission to our hosp...

  8. Usage of Lightning Arrester Line to Feed Light Electrical Loads

    Directory of Open Access Journals (Sweden)

    Hani B. Odeh

    2009-01-01

    Full Text Available In remote areas, light loads (tens of kilowatts are scattered and situated in the field of high voltage lines (66KV and above. These loads are very far from the main feeders/sub-stations (33KV-0.380KV. Feeding such loads in the traditional ways like provision of Diesel-Powered Stations, installation of new distribution lines from the Feeding Centers, or building new Sub-Stations are not practical ways from the economical point of view, because it requires huge additional expenses and will increase electrical power losses. These expenses are not worthy for such loads and therefore, it is necessary to search for other methods to supply them. One of these methods is to use the lightning arrester line as capacitive divider to supply the light loads. In this research, the induced voltage of the lightning arrester line was calculated when it is isolated from the earth. We found the capacitance between lightning arrester line versus the phases and lightning arrester. It was also found the selective power out of the lightning arrester line and the required length which is to be isolated from the earth keeping the main function of the lightning arrester line. When economically comparing between supplying the light electrical loads by traditional ways and the method of lightning arrester, it was found the advantage of using lightning arresters to supply such loads. Also, by using the traditional methods, it was noted that there is a power loss in the power transmission lines by a percentage of 1.8%.

  9. Dynamic propagation and cleavage crack arrest in bainitic steel

    International Nuclear Information System (INIS)

    In complement of the studies of harmfulness of defects, generally realized in term of initiation, the concept of crack arrest could be used as complementary analyses to the studies of safety. The stop occurs when the stress intensity factor becomes lower than crack arrest toughness (KIa) calculated in elasto-statics (KI ≤ KIa). The aim of this thesis is to understand and predict the stop of a crack propagating at high speed in a 18MND5 steel used in the pressure water reactor (PWR). The test chosen to study crack arrest is the disc thermal shock test. The observations under the scanning electron microscope of the fracture surface showed that the crack arrest always occurs in cleavage mode and that the critical microstructural entity with respect to the propagation and crack arrest corresponds to at least the size of the prior austenitic grain. The numerical analyses in elasto-statics confirm the conservatism of the codified curve of the RCC-M with respect to the values of KIa. The dynamic numerical analyses show that the deceleration of the crack measured at the end of the propagation is related to the global dynamic of the structure (vibrations). The transferability to components of crack arrest toughness obtained from tests analysed in static is thus not assured. The disc thermal shock tests were also modelled by considering a criterion of propagation and arrest of the type 'RKR' characterized by a critical stress sc which depends on the temperature. The results obtained account well for the crack jump measured in experiments as well as the shape of the crack arrest front. (author)

  10. TRICHOSTATIN A INHIBITS PROLIFERATION, INDUCES APOPTOSIS AND CELL CYCLE ARREST IN HELA CELLS

    Institute of Scientific and Technical Information of China (English)

    XU Zhou-min; WANG Yi-qun; MEI Qi; CHEN Jian; DU Jia; WEI Yan; XU Ying-chun

    2006-01-01

    Objective: The histone deacetylase inhibitors (HDACIS) have been shown to inhibit cancer cell proliferation, stimulate apoptosis, an induce cell cycle arrest. Our purpose was to investigate the antiproliferative effects of a HDACI, trichostatin A (TSA), against human cervical cancer cells (HeLa). Methods: HeLa cells were treated in vitro with various concentrations of TSA. The inhibitory effect of TSA on the growth of HeLa cells was measured by MTT assay. To detect the characteristic of apoptosis chromatin condensation, HeLa cells were stained with Hoechst 33258 in the presence of TSA. Induction of cell cycle arrest was studied by flow cytometry. Changes in gene expression of p53, p21Waf1 and p27Kip1 were studied by semiquantitative RT-PCR. Results: TSA inhibited cell growth in a time- and dose-dependent manner. Hoechst 33258 staining assay showed that TSA induced apoptosis. Cell cycle analysis indicated that treatment with TSA decreased the proportion of cells in S phase and increased the proportion of cells in G0/G1 and/or G2/M phases of the cell cycle. This was concomitant with overexpression of genes related to malignant phenotype, including an increase in p53, p21Waf1 and p27Kip1. Conclusion: These results suggest that TSA is effective in inhibiting growth of HeLa cells in vitro. The findings raise the possibility that TSA may prove particularly effective in treatment of cervical cancers.

  11. The primary cilium is a sensory organelle that regulates growth control and tissue homeostasis

    DEFF Research Database (Denmark)

    Christensen, Søren Tvorup; Schneider, Linda; Clement, Christian Alexandro;

    2006-01-01

    The growth-arrest specific receptor tyrosine kinase, PDGFRa, is up-regulated and targeted to the primary cilium during growth arrest in NIH3T3 cells and primary cultures of mouse embryonic fibroblasts (MEFs), and PDGF-AA-stimulated fibroblast cycle entrance is regulated through activation of cili...

  12. Situational ambiguity and gendered patterns of arrest for intimate partner violence.

    Science.gov (United States)

    Durfee, Alesha

    2012-01-01

    Using data from the 2005 National Incident-Based Reporting System (NIBRS), this analysis focuses on the impacts that domestic violence mandatory arrest policies have on arrest outcomes in "situationally ambiguous" cases: cases where both the female and male partners have been identified by police as both a victim and an offender. Results indicate that although officers arrest male partners more frequently than female partners, after controlling for incident and individual factors, mandatory arrest policies disproportionately affect women. Furthermore, correlates of arrest differ for male-only arrests versus female-only arrests. These findings are discussed in the context of changing legal responses to domestic violence. PMID:22411299

  13. Epidermal growth factor as a biologic switch in hair growth cycle

    OpenAIRE

    Mak, KKL; Chan, SY

    2003-01-01

    The hair growth cycle consists of three stages known as the anagen (growing), catagen (involution), and telogen (resting) phases. This cyclical growth of hair is regulated by a diversity of growth factors. Although normal expression of both epidermal growth factor and its receptor (EGFR) in the outer root sheath is down-regulated with the completion of follicular growth, here we show that continuous expression of epidermal growth factor in hair follicles of transgenic mice arrested follicular...

  14. Role of the retinoblastoma protein in cell cycle arrest mediated by a novel cell surface proliferation inhibitor

    Science.gov (United States)

    Enebo, D. J.; Fattaey, H. K.; Moos, P. J.; Johnson, T. C.; Spooner, B. S. (Principal Investigator)

    1994-01-01

    A novel cell regulatory sialoglycopeptide (CeReS-18), purified from the cell surface of bovine cerebral cortex cells has been shown to be a potent and reversible inhibitor of proliferation of a wide array of fibroblasts as well as epithelial-like cells and nontransformed and transformed cells. To investigate the possible mechanisms by which CeReS-18 exerts its inhibitory action, the effect of the inhibitor on the posttranslational regulation of the retinoblastoma susceptibility gene product (RB), a tumor suppressor gene, has been examined. It is shown that CeReS-18 mediated cell cycle arrest of both human diploid fibroblasts (HSBP) and mouse fibroblasts (Swiss 3T3) results in the maintenance of the RB protein in the hypophosphorylated state, consistent with a late G1 arrest site. Although their normal nontransformed counterparts are sensitive to cell cycle arrest mediated by CeReS-18, cell lines lacking a functional RB protein, through either genetic mutation or DNA tumor virus oncoprotein interaction, are less sensitive. The refractory nature of these cells is shown to be independent of specific surface receptors for the inhibitor, and another tumor suppressor gene (p53) does not appear to be involved in the CeReS-18 inhibition of cell proliferation. The requirement for a functional RB protein product, in order for CeReS-18 to mediate cell cycle arrest, is discussed in light of regulatory events associated with density-dependent growth inhibition.

  15. Nursing students’ knowledge about arrest rhythms and their treatment

    Directory of Open Access Journals (Sweden)

    Aikaterini Kyrgianidou

    2014-04-01

    Full Text Available Cardiovascular diseases are one of the leading causes of death worldwide. Knowledge of health professionals for the arrest rhythms, is considered particularly important for the early recognition and proper treatment. Aim: The purpose of the present study was to assess the knowledge of nursing students on arrest rhythms and how to treat them. Material and Methods: The sample studied included 151 students from the Department of Nursing A' (n = 60, 40% and B' (n = 91, 60%, TEI of Athens, of whom 83% (n=125 were women and 17% (n=26 were men with a mean age of 23 years. Data collection was performed with specially designed questionnaire, that apart from demographics and students’ education level, it included ten questions about arrest rhythms’ knowledge and also self-assessment questions of their level of knowledge. The data were analyzed with the SPSS package v.19, using the criteria t-Test and χ2. Results: Of all the participants in the research, 95% (n = 144 did not answer correctly more than 6 questions from a total of 10. The students of the Department of Nursing A’ recognized with greater accuracy the arrest rhythms (p = 0.003. Those studying in lower semester acknowledged best the arrest rhythms (p = 0.002. Students who had recently attended course in basic or advanced resuscitation recognized best the arrest rhythms (p = 0.006. Older students knew better right treatment of the arrest rhythms (p = 0.037. Also, students who had attended the course of cardiac nursing in the last year, knew better the right treatment (p <0.001. Finally, the level of self-assessment was in line with the actual level of knowledge of students (p = 0.05. Conclusions: Continuous attendance of courses, education on certified programs and refresh courses help to maintain a good level of knowledge for longer periods.

  16. Changing the guard: Polymer replaces porcelain for surge arresters

    Energy Technology Data Exchange (ETDEWEB)

    Skytt, T.; Gleimar, H. E. G.

    2002-07-01

    Surge arresters are safety devices which quickly and effectively limit the over voltages that can arise in transmission networks following lightning, switching and other transient events. The earliest forms of overvoltage protection, a simple air gap between electrodes, have long since been replaced by a new generation of gapless arresters with series-connected, non-linear zinc oxide varistors contained in a porcelain housing. Now these porcelain type surge arresters are being replaced by a new type, called PEXLIM (Polymeric EXcellent LIMiter), which uses the same block of zinc oxide as the porcelain type, but its housing is made of silicon rubber, a polymer. The new lightweight insulation material shows a number of properties superior to the porcelain, such as enhanced product safety and ease of handling. It is also more durable, resilient, yet solid and compact, water-repellent, lightweight, resistant to aging or light or ultra-violet radiation, as well as fire, has good electrical properties, and is environmentally friendly since it does not contain any substances harmful to the environment. These properties make this new type of surge arrester highly suitable for use in earthquake-prone areas; it can also replace more expensive and maintenance-intensive equipment. Having successfully broken into the lower voltage systems, these new type of surge arresters are now rapidly gaining ground at the higher voltage levels. ABB, the developer of PEXLIM, has already supplied these arresters to North America for use in an 800-kV grid. As further proof of its growing popularity, last year PEXLIM made up over half of the surge arrester production for applications up to and including 245 kV. 1 tab., 6 figs.

  17. Visualizing Vpr-induced G2 arrest and apoptosis.

    Directory of Open Access Journals (Sweden)

    Tomoyuki Murakami

    Full Text Available Vpr is an accessory protein of human immunodeficiency virus type 1 (HIV-1 with multiple functions. The induction of G2 arrest by Vpr plays a particularly important role in efficient viral replication because the transcriptional activity of the HIV-1 long terminal repeat is most active in G2 phase. The regulation of apoptosis by Vpr is also important for immune suppression and pathogenesis during HIV infection. However, it is not known whether Vpr-induced apoptosis depends on the ability of Vpr to induce G2 arrest, and the dynamics of Vpr-induced G2 arrest and apoptosis have not been visualized. We performed time-lapse imaging to examine the temporal relationship between Vpr-induced G2 arrest and apoptosis using HeLa cells containing the fluorescent ubiquitination-based cell cycle indicator2 (Fucci2. The dynamics of G2 arrest and subsequent long-term mitotic cell rounding in cells transfected with the Vpr-expression vector were visualized. These cells underwent nuclear mis-segregation after prolonged mitotic processes and then entered G1 phase. Some cells subsequently displayed evidence of apoptosis after prolonged mitotic processes and nuclear mis-segregation. Interestingly, Vpr-induced apoptosis was seldom observed in S or G2 phase. Likewise, visualization of synchronized HeLa/Fucci2 cells infected with an adenoviral vector expressing Vpr clearly showed that Vpr arrests the cell cycle at G2 phase, but does not induce apoptosis at S or G2 phase. Furthermore, time-lapse imaging of HeLa/Fucci2 cells expressing SCAT3.1, a caspase-3-sensitive fusion protein, clearly demonstrated that Vpr induces caspase-3-dependent apoptosis. Finally, to examine whether the effects of Vpr on G2 arrest and apoptosis were reversible, we performed live-cell imaging of a destabilizing domain fusion Vpr, which enabled rapid stabilization and destabilization by Shield1. The effects of Vpr on G2 arrest and subsequent apoptosis were reversible. This study is the first to

  18. Nucleation and Arrest of Dynamic Fault Rupture on a Pressurized Fault

    Science.gov (United States)

    Garagash, D.; Germanovich, L. N.

    2010-12-01

    Locally elevated pore pressure is a viable mechanism for reduction of fault strength and earthquake triggering. Possible sources of elevated pressure near faults that are associated with induced or triggered seismicity include (1) deep fluid injection into the crust (e.g., Healy et al, Science 1968); (2) fault-valve systems (inter-seismically impermeable fault transecting the suprahydrostatic pressure gradient, Sibson, Tectonophysics 1992); (3) metamorphic dehydration in thrust and normal fault systems. Although the mechanics of fault reactivation due to the pore pressure perturbation is generally well understood, there is a considerable lack of understanding of (1) the condition(s) under which the reactivation of fault slip leads to the nucleation of dynamic (earthquake) rupture; and (2) what is the extent of the dynamic rupture propagation before it is arrested (what separates micro-seismic events from earthquakes)? We address these questions by analyzing nucleation and possible arrest of the dynamic slip on a pressurized fault in the otherwise uniform background stress field. Evolving, locally-peaked pore pressure profile is generated by along-the-fault diffusion from a fluid source characterized by either a constant overpressure or constant flow rate. As a result, frictional strength of the fault, given by the product of the local normal effective stress and slip-weakening friction coefficient, reduces below the background stress within the pressurized region, which is expanding with time. This causes a shear crack, which growth is initially moderated by the pressure diffusion and, thus, quasi-static. The slip-weakening nature of friction suggests that the quasi-static growth may become eventually unstable, for example, leading to the nucleation of dynamic rupture. We extend the approach of Uenishi and Rice (JGR, 2003) to develop a solution for the extent of the nucleation patch and the time to the nucleation. A similar approach has been independently used by

  19. Current Pharmacological Advances in the Treatment of Cardiac Arrest

    Directory of Open Access Journals (Sweden)

    Andry Papastylianou

    2012-01-01

    Full Text Available Cardiac arrest is defined as the sudden cessation of spontaneous ventilation and circulation. Within 15 seconds of cardiac arrest, the patient loses consciousness, electroencephalogram becomes flat after 30 seconds, pupils dilate fully after 60 seconds, and cerebral damage takes place within 90–300 seconds. It is essential to act immediately as irreversible damage can occur in a short time. Cardiopulmonary resuscitation (CPR is an attempt to restore spontaneous circulation through a broad range of interventions which are early defibrillation, high-quality and uninterrupted chest compressions, advanced airway interventions, and pharmacological interventions. Drugs should be considered only after initial shocks have been delivered (when indicated and chest compressions and ventilation have been started. During cardiopulmonary resuscitation, no specific drug therapy has been shown to improve survival to hospital discharge after cardiac arrest, and only few drugs have a proven benefit for short-term survival. This paper reviews current pharmacological treatment of cardiac arrest. There are three groups of drugs relevant to the management of cardiac arrest: vasopressors, antiarrhythmics, and other drugs such as sodium bicarbonate, calcium, magnesium, atropine, fibrinolytic drugs, and corticosteroids.

  20. Sculpting Pickering Emulsion Droplets by Arrest and Jamming

    Science.gov (United States)

    Burke, Christopher; Wei, Zengyi; Caggioni, Marco; Spicer, Patrick; Atherton, Tim

    Pickering emulsion droplets can be arrested into non-spherical shapes--useful for applications such as active delivery--through a general mechanism of deformation followed by absorption of additional colloidal particles onto the interface, relaxation of the droplet caused by surface tension and arrest at some point due to crowding of the particles. We perform simulations of the arrest process to clarify the relative importance of diffusive rearrangement of particles and collective forcing due to surface evolution. Experiment and theory are compared, giving insight into the stability of the resulting capsules and the robustness of the production process for higher-throughput production in, for example, microfluidic systems. We adapt theoretical tools from the jamming literature to better understand the arrested configurations and long timescale evolution of the system: using linear programming and a penalty function approach, we identify unjamming motions in kinetically arrested states. We propose a paradigm of ``metric jamming'' to describe the limiting behavior of this class of system: a structure is metric-jammed if it is stable with respect to collective motion of the particles as well as evolution of the hypersurface on which the packing is embedded. Supported by a Cottrell Award from the Research Corporation for Science Advancement.

  1. Capecitabine-induced ventricular fibrillation arrest: Possible Kounis syndrome.

    Science.gov (United States)

    Kido, Kazuhiko; Adams, Val R; Morehead, Richard S; Flannery, Alexander H

    2016-04-01

    We report the case of capecitabine-induced ventricular fibrillation arrest, possibly secondary to type I Kounis syndrome. A 47-year-old man with a history of T3N1 moderately differentiated adenocarcinoma of the colon, status-post sigmoid resection, was started on adjuvant capecitabine approximately five months prior to presentation of cardiac arrest secondary to ventricular fibrillation. An electrocardiogram (EKG) revealed ST segment elevation on the lateral leads and the patient was taken emergently to the cardiac catheterization laboratory. The catheterization revealed no angiographically significant stenosis and coronary artery disease was ruled out. After ruling out other causes of cardiac arrest, the working diagnosis was capecitabine-induced ventricular fibrillation arrest. As such, an inflammatory work up was sent to evaluate for the possibility of a capecitabine hypersensitivity, or Kounis syndrome, and is the first documented report in the literature to do so when evaluating Kounis syndrome. Immunoglobulin E (IgE), tryptase, and C-reactive protein were normal but histamine, interleukin (IL)-6, and IL-10 were elevated. Histamine elevation supports the suspicion that our patient had type I Kounis syndrome. Naranjo adverse drug reaction probability scale indicates a probable adverse effect due to capecitabine with seven points. A case of capecitabine-induced ventricular fibrillation arrest is reported, with a potential for type 1 Kounis syndrome as an underlying pathology supported by immunologic work up. PMID:25870182

  2. Salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Xiaolan, E-mail: huxiaolan1998@yahoo.com.cn [Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou (China); Zhang, Xianqi [The 2nd Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou (China); Qiu, Shuifeng [Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou (China); Yu, Daihua; Lin, Shuxin [Fourth Military Medical University, Xi' an (China)

    2010-07-16

    Research highlights: {yields} Salidroside inhibits the growth of human breast cancer cells. {yields} Salidroside induces cell-cycle arrest of human breast cancer cells. {yields} Salidroside induces apoptosis of human breast cancer cell lines. -- Abstract: Recently, salidroside (p-hydroxyphenethyl-{beta}-D-glucoside) has been identified as one of the most potent compounds isolated from plants of the Rhodiola genus used widely in traditional Chinese medicine, but pharmacokinetic data on the compound are unavailable. We were the first to report the cytotoxic effects of salidroside on cancer cell lines derived from different tissues, and we found that human breast cancer MDA-MB-231 cells (estrogen receptor negative) were sensitive to the inhibitory action of low-concentration salidroside. To further investigate the cytotoxic effects of salidroside on breast cancer cells and reveal possible ER-related differences in response to salidroside, we used MDA-MB-231 cells and MCF-7 cells (estrogen receptor-positive) as models to study possible molecular mechanisms; we evaluated the effects of salidroside on cell growth characteristics, such as proliferation, cell cycle duration, and apoptosis, and on the expression of apoptosis-related molecules. Our results demonstrated for the first time that salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells and may be a promising candidate for breast cancer treatment.

  3. Cardiac arrest following ventilator fire: A rare cause

    Directory of Open Access Journals (Sweden)

    K Nazeer Ahmed

    2012-01-01

    Full Text Available Operating room fires are rare events, but when occur they result in serious and sometimes fatal consequences. Anaesthesia ventilator fire leading to cardiac arrest is a rare incident and has not been reported. We report a near catastrophic ventilator fire leading to cardiac arrest in a patient undergoing subtotal thyroidectomy. In the present case sparks due to friction or electrical short circuit within the ventilator might have acted as source of ignition leading to fire and explosion in the oxygen rich environment. The patient was successfully resuscitated and revived with uneventful recovery and no adverse sequelae. The cardiac arrest was possibly due to severe hypoxia resulting from inhalation of smoke containing high concentrations of carbon monoxide and other noxious gases.

  4. Investigating Different ZnO Arresters Models against Transient Waves

    Directory of Open Access Journals (Sweden)

    A. Babaee

    2011-12-01

    Full Text Available Metal oxide surge arresters have dynamic characteristics that are significant for over voltage coordination studies involving fast front surges. Several models with acceptable accuracy have been proposed to simulate this frequency-dependent behavior. In this paper, various electrical models are presented for surge arrester performance simulation against lightning impulse. The desirable model is obtained by using simulation results of the existing models and experimental tests. The IEEE proposed model is a proportional model can give satisfactory results for discharge currents within a range of time to crest for 0.5 to 45 :s but due to no existing residual voltage resulting switching current on the manufacture's datasheets decrease its performance generally. In this study the maximum residual voltage due to current impulse is analyzed too. In additional, the amount of discharged energy by surge arrester is focused.

  5. Oridonin induces apoptosis and cell cycle arrest of gallbladder cancer cells via the mitochondrial pathway

    International Nuclear Information System (INIS)

    Gallbladder cancer is the most frequent malignancy of the bile duct with high aggressive and extremely poor prognosis. The main objective of the paper was to investigate the inhibitory effects of oridonin, a diterpenoid isolated from Rabdosia rubescens, on gallbladder cancer both in vitro and in vivo and to explore the mechanisms underlying oridonin-induced apoptosis and cell cycle arrest. The anti-tumor activity of oridonin on SGC996 and NOZ cells was assessed by the MTT and colony forming assays. Cell cycle changes were detected by flow cytometric analysis. Apoptosis was detected by annexin V/PI double-staining and Hoechst 33342 staining assays. Loss of mitochondrial membrane potential was observed by Rhodamine 123 staining. The in vivo efficacy of oridonin was evaluated using a NOZ xenograft model in athymic nude mice. The expression of cell cycle- and apoptosis-related proteins in vitro and in vivo was analyzed by western blot analysis. Activation of caspases (caspase-3, -8 and -9) was measured by caspases activity assay. Oridonin induced potent growth inhibition, S-phase arrest, apoptosis, and colony-forming inhibition in SGC996 and NOZ cells in a dose-dependent manner. Intraperitoneal injection of oridonin (5, 10, or 15 mg/kg) for 3 weeks significantly inhibited the growth of NOZ xenografts in athymic nude mice. We demonstrated that oridonin regulated cell cycle-related proteins in response to S-phase arrest by western blot analysis. In contrast, we observed inhibition of NF-κB nuclear translocation and an increase Bax/Bcl-2 ratio accompanied by activated caspase-3, caspase-9 and PARP-1 cleavage after treatment with oridonin, which indicate that the mitochondrial pathway is involved in oridonin-mediated apoptosis. Oridonin possesses potent anti-gallbladder cancer activities that correlate with regulation of the mitochondrial pathway, which is critical for apoptosis and S-phase arrest. Therefore, oridonin has potential as a novel anti-tumor therapy for the

  6. Piperlongumine Suppresses Proliferation of Human Oral Squamous Cell Carcinoma through Cell Cycle Arrest, Apoptosis and Senescence.

    Science.gov (United States)

    Chen, San-Yuan; Liu, Geng-Hung; Chao, Wen-Ying; Shi, Chung-Sheng; Lin, Ching-Yen; Lim, Yun-Ping; Lu, Chieh-Hsiang; Lai, Peng-Yeh; Chen, Hau-Ren; Lee, Ying-Ray

    2016-01-01

    Oral squamous cell carcinoma (OSCC), an aggressive cancer originating in the oral cavity, is one of the leading causes of cancer deaths in males worldwide. This study investigated the antitumor activity and mechanisms of piperlongumine (PL), a natural compound isolated from Piper longum L., in human OSCC cells. The effects of PL on cell proliferation, the cell cycle, apoptosis, senescence and reactive oxygen species (ROS) levels in human OSCC cells were investigated. PL effectively inhibited cell growth, caused cell cycle arrest and induced apoptosis and senescence in OSCC cells. Moreover, PL-mediated anti-human OSCC behavior was inhibited by an ROS scavenger N-acetyl-l-cysteine (NAC) treatment, suggesting that regulation of ROS was involved in the mechanism of the anticancer activity of PL. These findings suggest that PL suppresses tumor growth by regulating the cell cycle and inducing apoptosis and senescence and is a potential chemotherapy agent for human OSCC cells. PMID:27120594

  7. Piperlongumine Suppresses Proliferation of Human Oral Squamous Cell Carcinoma through Cell Cycle Arrest, Apoptosis and Senescence

    Directory of Open Access Journals (Sweden)

    San-Yuan Chen

    2016-04-01

    Full Text Available Oral squamous cell carcinoma (OSCC, an aggressive cancer originating in the oral cavity, is one of the leading causes of cancer deaths in males worldwide. This study investigated the antitumor activity and mechanisms of piperlongumine (PL, a natural compound isolated from Piper longum L., in human OSCC cells. The effects of PL on cell proliferation, the cell cycle, apoptosis, senescence and reactive oxygen species (ROS levels in human OSCC cells were investigated. PL effectively inhibited cell growth, caused cell cycle arrest and induced apoptosis and senescence in OSCC cells. Moreover, PL-mediated anti-human OSCC behavior was inhibited by an ROS scavenger N-acetyl-l-cysteine (NAC treatment, suggesting that regulation of ROS was involved in the mechanism of the anticancer activity of PL. These findings suggest that PL suppresses tumor growth by regulating the cell cycle and inducing apoptosis and senescence and is a potential chemotherapy agent for human OSCC cells.

  8. Drug therapy in cardiac arrest: a review of the literature.

    Science.gov (United States)

    Lundin, Andreas; Djärv, Therese; Engdahl, Johan; Hollenberg, Jacob; Nordberg, Per; Ravn-Fischer, Annika; Ringh, Mattias; Rysz, Susanne; Svensson, Leif; Herlitz, Johan; Lundgren, Peter

    2016-01-01

    The aim of this study was to review the literature on human studies of drug therapy in cardiac arrest during the last 25 years. In May 2015, a systematic literature search was performed in PubMed, Embase, the Cochrane Library, and CRD databases. Prospective interventional and observational studies evaluating a specified drug therapy in human cardiac arrest reporting a clinical endpoint [i.e. return of spontaneous circulation (ROSC) or survival] and published in English 1990 or later were included, whereas animal studies, case series and reports, studies of drug administration, drug pharmacology, non-specified drug therapies, preventive drug therapy, drug administration after ROSC, studies with primarily physiological endpoints, and studies of traumatic cardiac arrest were excluded. The literature search identified a total of 8936 articles. Eighty-eight articles met our inclusion criteria and were included in the review. We identified no human study in which drug therapy, compared with placebo, improved long-term survival. Regarding adrenaline and amiodarone, the drugs currently recommended in cardiac arrest, two prospective randomized placebo-controlled trials, were identified for adrenaline, and one for amiodarone, but they were all underpowered to detect differences in survival to hospital discharge. Of all reviewed studies, only one recent prospective study demonstrated improved neurological outcome with one therapy over another using a combination of vasopressin, steroids, and adrenaline as the intervention compared with standard adrenaline administration. The evidence base for drug therapy in cardiac arrest is scarce. However, many human studies on drug therapy in cardiac arrest have not been powered to identify differences in important clinical outcomes such as survival to hospital discharge and favourable neurological outcome. Efforts are needed to initiate large multicentre prospective randomized clinical trials to evaluate both currently recommended and

  9. Swedish ambulance nurses' experiences of nursing patients suffering cardiac arrest.

    Science.gov (United States)

    Larsson, Ricard; Engström, Åsa

    2013-04-01

    Effective pre-hospital treatment of a person suffering cardiac arrest is a challenging task for the ambulance nurses. The aim of this study was to describe ambulance nurses' experiences of nursing patients suffering cardiac arrest. Qualitative personal interviews were conducted during 2011 in Sweden with seven ambulance nurses with experience of nursing patients suffering cardiac arrests. The interview texts were analyzed using qualitative thematic content analysis, which resulted in the formulation of one theme with six categories. Mutual preparation, regular training and education were important factors in the nursing of patients suffering cardiac arrest. Ambulance nurses are placed in ethically demanding situations regarding if and for how long they should continue cardio-pulmonary resuscitation (CPR) to accord with pre-hospital cardiac guidelines and patients' wishes. When a cardiac arrest patient is nursed their relatives also need the attention of ambulance nurses. Reflection is one way for ambulance nurses to learn from, and talk about, their experiences. This study provides knowledge of ambulance nurses' experiences in the care of people with cardiac arrest. Better feedback about the care given by the ambulance nurses, and about the diagnosis and nursing care the patients received after they were admitted to the hospital are suggested as improvements that would allow ambulance nurses to learn more from their experience. Further development and research concerning the technical equipment might improve the situation for both the ambulance nurses and the patients. Ambulance nurses need regularly training and education to be prepared for saving people's lives and also to be able to make the right decisions. PMID:23577977

  10. Hypernegative Supercoiling Inhibits Growth by Causing RNA Degradation▿

    OpenAIRE

    Baaklini, Imad; Usongo, Valentine; Nolent, Flora; Sanscartier, Patrick; Hraiky, Chadi; Drlica, Karl; Drolet, Marc

    2008-01-01

    Transcription-induced hypernegative supercoiling is a hallmark of Escherichia coli topoisomerase I (topA) mutants. However, its physiological significance has remained unclear. Temperature downshift of a mutant yielded transient growth arrest and a parallel increase in hypernegative supercoiling that was more severe with lower temperature. Both properties were alleviated by overexpression of RNase HI. While ribosomes in extracts showed normal activity when obtained during growth arrest, mRNA ...

  11. Out-of-Hospital Cardiac Arrest in Denmark

    DEFF Research Database (Denmark)

    Wissenberg Jørgensen, Mads

    years ago in Denmark. These findings led to several national initiatives to strengthen bystander resuscitation attempts and advance care. Despite these nationwide efforts, it was unknown prior to this project whether these efforts resulted in changes in resuscitation attempts by bystanders and changes...... in patient survival following out-of hospital cardiac arrest; utilizing the Danish nationwide registries, we sought to answer these questions. Moreover, in order to further improve understanding and target future national strategies for cardiac arrest management, we examined whether there were sex...

  12. Evolution Arrests Invasions of Cooperative Populations

    Science.gov (United States)

    Korolev, Kirill S.

    2015-11-01

    Population expansions trigger many biomedical and ecological transitions, from tumor growth to invasions of non-native species. Although population spreading often selects for more invasive phenotypes, we show that this outcome is far from inevitable. In cooperative populations, mutations reducing dispersal have a competitive advantage. Such mutations then steadily accumulate at the expansion front, bringing invasion to a halt. Our findings are a rare example of evolution driving the population into an unfavorable state, and they could lead to new strategies to combat unwelcome invaders.

  13. Induction of G2/M arrest by pseudolaric acid B is mediated by activation of the ATM signaling pathway

    Institute of Scientific and Technical Information of China (English)

    Ai-guo MENG; Ling-lingJIANG

    2009-01-01

    Aim: The aim of this study was to investigate the mechanism of pseudolaric acid B (PLAB)-induced cell cycle arrest in human melanoma SK-28 cells. Methods: Cell growth inhibition was detected by MTT assay, the cell cycle was analyzed by flow cytometry, and protein expression was examined by Western blot analysis.Results: PLAB inhibited the growth of human melanoma ceils and induced G2/M arrest in SK-28 cells, accompanied by an up-regulation of Cdc2 phosphorylation and a subsequent down-regulation of Cdc2 expression. Furthermore, PLAB decreased the expression of Cdc25C phosphatase and increased the expression of Wee1 kinase. Meanwhile, a reduction in Cdc2 activity was party due to induction of the expression of p21wsaf1/cip1 in a p53-dependent manner. In addition, PLAB activated the checkpoint kinase, Chk2, and increased the expression of p53, two major targets of ATM kinase. These effects were inhibited by caffeine, an ATM kinase inhibitor. We also found that PLAB significantly enhanced ATM kinase activity. Conclusion: Taken together, these results suggest that PLAB induced G2/M arrest in human melanoma cells via a mechanism involving the activation of ATM, and the effect of PLAB on Cdc2 activity was mediated via interactions with the Chk2-Cdc25C and p53 signalling pathways, two distinct downstream pathways of ATM. PLAB may be a promising chemopreventive agent for treating human melanoma.

  14. Crack arrest model for a piezoelectric strip subjected to Model loadings

    Directory of Open Access Journals (Sweden)

    R.R. Bhargava

    2007-06-01

    Full Text Available Purpose: The present paper aims at proposing a crack arrest model for an infinitely long narrow, poled ceramic strip weakened by a finite hairline straight crack when the edges of the strip are subjected to combined mechanical and electrical loads.Design/methodology/approach: (Model As a consequence of loads the rims of crack open forming a yield zone ahead of each tip of the crack. To arrest the crack from further opening the rims of the yield zones are subjected to normal cohesive quadratically varying yield point stress. Two cases are presented when edges of the strip are subjected to: Case-I~in-plane stresses and electrical displacement or Case-II~in-plane stresses and in-plane electric field. Problems are solved using Fourier integral transform method.Findings: The stress intensity factor, yield zone length, crack opening displacement, crack growth rate have been calculated. Their variation with respect to affecting parameters viz. yield zone length, width of the strip, material constant, electrical and mechanical loads has been depicted graphically.Research limitations/implications: The material of the strip is assumed mechanically brittle and electrically ductile consequently mechanically singularity is encountered first. The investigations in this paper are carried at this level. Also the crack yielding under the loads is considered small scale hence the yield zone is assumed to be lying on the line segment ahead of the crack.Practical implications: Piezoelectric ceramics are widely used as sensors and actuators, this necessity prompts the fracture study on such ceramics under different loading conditions.Originality/value: The paper gives an assessment of the quadratically varying load required to be prescribed on yield zones so as to arrest the opening of the crack. The investigations are useful to smart material design technology where sensors and actuators are manufactured.

  15. Crack arrest model for a piezoelectric strip subjected to Mode-I loadings

    Directory of Open Access Journals (Sweden)

    R.R. Bhargava

    2007-01-01

    Full Text Available Purpose: The present paper aims at proposing a crack arrest model for an infinitely long narrow, poledceramic strip weakened by a finite hairline straight crack when the edges of the strip are subjected to combinedmechanical and electrical loads.Design/methodology/approach: (Model As a consequence of loads the rims of crack open forming a yieldzone ahead of each tip of the crack. To arrest the crack from further opening the rims of the yield zones aresubjected to normal cohesive quadratically varying yield point stress. Two cases are presented when edges ofthe strip are subjected to: Case-I~in-plane stresses and electrical displacement or Case-II~in-plane stresses andin-plane electric field. Problems are solved using Fourier integral transform method.Findings: The stress intensity factor, yield zone length, crack opening displacement, crack growth rate havebeen calculated. Their variation with respect to affecting parameters viz. yield zone length, width of the strip,material constant, electrical and mechanical loads has been depicted graphically.Research limitations/implications: The material of the strip is assumed mechanically brittle and electricallyductile consequently mechanically singularity is encountered first. The investigations in this paper are carried atthis level. Also the crack yielding under the loads is considered small scale hence the yield zone is assumed tobe lying on the line segment ahead of the crack.Practical implications: Piezoelectric ceramics are widely used as sensors and actuators, this necessity promptsthe fracture study on such ceramics under different loading conditions.Originality/value: The paper gives an assessment of the quadratically varying load required to be prescribedon yield zones so as to arrest the opening of the crack. The investigations are useful to smart material designtechnology where sensors and actuators are manufactured.

  16. Lysophosphatidate induces chemo-resistance by releasing breast cancer cells from taxol-induced mitotic arrest.

    Directory of Open Access Journals (Sweden)

    Nasser Samadi

    Full Text Available BACKGROUND: Taxol is a microtubule stabilizing agent that arrests cells in mitosis leading to cell death. Taxol is widely used to treat breast cancer, but resistance occurs in 25-69% of patients and it is vital to understand how Taxol resistance develops to improve chemotherapy. The effects of chemotherapeutic agents are overcome by survival signals that cancer cells receive. We focused our studies on autotaxin, which is a secreted protein that increases tumor growth, aggressiveness, angiogenesis and metastasis. We discovered that autotaxin strongly antagonizes the Taxol-induced killing of breast cancer and melanoma cells by converting the abundant extra-cellular lipid, lysophosphatidylcholine, into lysophosphatidate. This lipid stimulates specific G-protein coupled receptors that activate survival signals. METHODOLOGY/PRINCIPAL FINDINGS: In this study we determined the basis of these antagonistic actions of lysophosphatidate towards Taxol-induced G2/M arrest and cell death using cultured breast cancer cells. Lysophosphatidate does not antagonize Taxol action in MCF-7 cells by increasing Taxol metabolism or its expulsion through multi-drug resistance transporters. Lysophosphatidate does not lower the percentage of cells accumulating in G2/M by decreasing exit from S-phase or selective stimulation of cell death in G2/M. Instead, LPA had an unexpected and remarkable action in enabling MCF-7 and MDA-MB-468 cells, which had been arrested in G2/M by Taxol, to normalize spindle structure and divide, thus avoiding cell death. This action involves displacement of Taxol from the tubulin polymer fraction, which based on inhibitor studies, depends on activation of LPA receptors and phosphatidylinositol 3-kinase. CONCLUSIONS/SIGNIFICANCE: This work demonstrates a previously unknown consequence of lysophosphatidate action that explains why autotaxin and lysophosphatidate protect against Taxol-induced cell death and promote resistance to the action of this

  17. Radioprotection and Cell Cycle Arrest of Intestinal Epithelial Cells by Darinaparsin, a Tumor Radiosensitizer

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Junqiang; Doi, Hiroshi [Department of Radiation Oncology, School of Medicine, Stanford University, Stanford, California (United States); Saar, Matthias; Santos, Jennifer [Department of Urology, School of Medicine, Stanford University, Stanford, California (United States); Li, Xuejun; Peehl, Donna M. [Department of Radiation Oncology, School of Medicine, Stanford University, Stanford, California (United States); Knox, Susan J., E-mail: sknox@stanford.edu [Department of Radiation Oncology, School of Medicine, Stanford University, Stanford, California (United States)

    2013-12-01

    Purpose: It was recently reported that the organic arsenic compound darinaparsin (DPS) is a cytotoxin and radiosensitizer of tumor cells in vitro and in subcutaneous xenograft tumors. Surprisingly, it was also found that DPS protects normal intestinal crypt epithelial cells (CECs) from clonogenic death after ionizing radiation (IR). Here we tested the DPS radiosensitizing effect in a clinically relevant model of prostate cancer and explored the radioprotective effect and mechanism of DPS on CECs. Methods and Materials: The radiation modification effect of DPS was tested in a mouse model of orthotopic xenograft prostate cancer and of IR-induced acute gastrointestinal syndrome. The effect of DPS on CEC DNA damage and DNA damage responses was determined by immunohistochemistry. Results: In the mouse model of IR-induced gastrointestinal syndrome, DPS treatment before IR accelerated recovery from body weight loss and increased animal survival. DPS decreased post-IR DNA damage and cell death, suggesting that the radioprotective effect was mediated by enhanced DNA damage repair. Shortly after DPS injection, significant cell cycle arrest was observed in CECs at both G1/S and G2/M checkpoints, which was accompanied by the activation of cell cycle inhibitors p21 and growth arrest and DNA-damage-inducible protein 45 alpha (GADD45A). Further investigation revealed that DPS activated ataxia telangiectasia mutated (ATM), an important inducer of DNA damage repair and cell cycle arrest. Conclusions: DPS selectively radioprotected normal intestinal CECs and sensitized prostate cancer cells in a clinically relevant model. This effect may be, at least in part, mediated by DNA damage response activation and has the potential to significantly increase the therapeutic index of radiation therapy.

  18. Radioprotection and Cell Cycle Arrest of Intestinal Epithelial Cells by Darinaparsin, a Tumor Radiosensitizer

    International Nuclear Information System (INIS)

    Purpose: It was recently reported that the organic arsenic compound darinaparsin (DPS) is a cytotoxin and radiosensitizer of tumor cells in vitro and in subcutaneous xenograft tumors. Surprisingly, it was also found that DPS protects normal intestinal crypt epithelial cells (CECs) from clonogenic death after ionizing radiation (IR). Here we tested the DPS radiosensitizing effect in a clinically relevant model of prostate cancer and explored the radioprotective effect and mechanism of DPS on CECs. Methods and Materials: The radiation modification effect of DPS was tested in a mouse model of orthotopic xenograft prostate cancer and of IR-induced acute gastrointestinal syndrome. The effect of DPS on CEC DNA damage and DNA damage responses was determined by immunohistochemistry. Results: In the mouse model of IR-induced gastrointestinal syndrome, DPS treatment before IR accelerated recovery from body weight loss and increased animal survival. DPS decreased post-IR DNA damage and cell death, suggesting that the radioprotective effect was mediated by enhanced DNA damage repair. Shortly after DPS injection, significant cell cycle arrest was observed in CECs at both G1/S and G2/M checkpoints, which was accompanied by the activation of cell cycle inhibitors p21 and growth arrest and DNA-damage-inducible protein 45 alpha (GADD45A). Further investigation revealed that DPS activated ataxia telangiectasia mutated (ATM), an important inducer of DNA damage repair and cell cycle arrest. Conclusions: DPS selectively radioprotected normal intestinal CECs and sensitized prostate cancer cells in a clinically relevant model. This effect may be, at least in part, mediated by DNA damage response activation and has the potential to significantly increase the therapeutic index of radiation therapy

  19. Proteotoxic stress induces a cell-cycle arrest by stimulating Lon to degrade the replication initiator DnaA.

    Science.gov (United States)

    Jonas, Kristina; Liu, Jing; Chien, Peter; Laub, Michael T

    2013-08-01

    The decision to initiate DNA replication is a critical step in the cell cycle of all organisms. Cells often delay replication in the face of stressful conditions, but the underlying mechanisms remain incompletely defined. Here, we demonstrate in Caulobacter crescentus that proteotoxic stress induces a cell-cycle arrest by triggering the degradation of DnaA, the conserved replication initiator. A depletion of available Hsp70 chaperone, DnaK, either through genetic manipulation or heat shock, induces synthesis of the Lon protease, which can directly degrade DnaA. Unexpectedly, we find that unfolded proteins, which accumulate following a loss of DnaK, also allosterically activate Lon to degrade DnaA, thereby ensuring a cell-cycle arrest. Our work reveals a mechanism for regulating DNA replication under adverse growth conditions. Additionally, our data indicate that unfolded proteins can actively and directly alter substrate recognition by cellular proteases. PMID:23911325

  20. Police Management Training Factors Influencing DWI Arrests. Final Report.

    Science.gov (United States)

    Bishop, Edward W.

    The development of training material for police management personnel concerning command and supervisory actions appropriate for more effective driving-while-intoxicated (DWI) enforcement is desired. The training is based on two research studies that identified environmental and attitudinal factors influencing a patrolman's arrest decision. These…

  1. Cdc20 control of cell fate during prolonged mitotic arrest

    DEFF Research Database (Denmark)

    Nilsson, Jakob

    2011-01-01

    The fate of cells arrested in mitosis by antimitotic compounds is complex but is influenced by competition between pathways promoting cell death and pathways promoting mitotic exit. As components of both of these pathways are regulated by Cdc20-dependent degradation, I hypothesize that variations...

  2. Hemodynamics and vasopressor support in therapeutic hypothermia after cardiac arrest

    DEFF Research Database (Denmark)

    Bro-Jeppesen, John; Kjaergaard, Jesper; Søholm, Helle;

    2014-01-01

    AIM: Inducing therapeutic hypothermia (TH) in Out-of-Hospital Cardiac Arrest (OHCA) can be challenging due to its impact on central hemodynamics and vasopressors are frequently used to maintain adequate organ perfusion. The aim of this study was to assess the association between level of vasopres...

  3. Heart Attack or Sudden Cardiac Arrest: How Are They Different?

    Science.gov (United States)

    ... for Heart360 Cardiovascular Conditions • Conditions Home • Arrhythmia and Atrial Fibrillation • Cardiac Arrest • Cardiac Rehab • Cardiomyopathy • Cardiovascular Conditions of Childhood • Cholesterol • Congenital Heart Defects • Diabetes • Heart Attack • Heart Failure (HF) • Heart Valve Problems and Disease • High Blood ...

  4. Bad Behavior : Delinquency, Arrest and Early School Leaving

    NARCIS (Netherlands)

    Ward, Shannon; Williams, J.; van Ours, Jan

    2015-01-01

    In this paper we investigate the effects of delinquency and arrest on school leaving using information on males from the National Longitudinal Survey of Youth 1997. We use a multivariate mixed proportional hazard framework in order to account for common unobserved confounders and reverse causality.

  5. Parenting and Women Arrested for Intimate Partner Violence

    Science.gov (United States)

    Simmons, Catherine A.; Lehmann, Peter; Dia, David A.

    2010-01-01

    Exploring the relationship between parenting and women's use of violence the current study surveyed 106 mothers arrested for intimate partner violence (IPV) related crimes on parenting styles and attitudes toward when using violence against their partner is justified. Findings indicate parenting styles indicative of low belief in using physical…

  6. Ventilation and gas exchange management after cardiac arrest.

    Science.gov (United States)

    Sutherasan, Yuda; Raimondo, Pasquale; Pelosi, Paolo

    2015-12-01

    For several decades, physicians had integrated several interventions aiming to improve the outcomes in post-cardiac arrest patients. However, the mortality rate after cardiac arrest is still as high as 50%. Post-cardiac arrest syndrome is associated with high morbidity and mortality due to not only poor neurological outcome and cardiovascular failure but also respiratory dysfunction. To minimize ventilator-associated lung injury, protective mechanical ventilation by using low tidal volume ventilation and driving pressure may decrease pulmonary complications and improve survival. Low level of positive end-expiratory pressure (PEEP) can be initiated and titrated with careful cardiac output and respiratory mechanics monitoring. Furthermore, optimizing gas exchange by avoiding hypoxia and hyperoxia as well as maintaining normocarbia may improve neurological and survival outcome. Early multidisciplinary cardiac rehabilitation intervention is recommended. Minimally invasive monitoring techniques, that is, echocardiography, transpulmonary thermodilution method measuring extravascular lung water, as well as transcranial Doppler ultrasound, might be useful to improve appropriate management of post-cardiac arrest patients. PMID:26670813

  7. 19 CFR 162.63 - Arrests and seizures.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Arrests and seizures. 162.63 Section 162.63 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) INSPECTION, SEARCH, AND SEIZURE Controlled Substances, Narcotics, and Marihuana §...

  8. Description of a collaborative community approach to impacting juvenile arrests.

    Science.gov (United States)

    Barrett, James G; Janopaul-Naylor, Elizabeth

    2016-05-01

    Although the burden of mental health disorders among youth involved with the juvenile justice system is high, few communities have effectively integrated mental health resources with law enforcement (Myers & Farrell, 2008). The city of Cambridge, Massachusetts has developed the Safety Net Collaborative, which is a multiagency integrated model of preventive services for at-risk youth involving mental health providers, police officers, schools, and the department of youth and families. There are 6,000 youth in the city's public schools under the local police jurisdiction. Youth are referred to this program by schools, courts, and parents. There are approximately 30 active cases each year. Initial outcome measures were tracked, including number of arrests, diversions, and mental health referrals. Rate of decline in arrests was compared pre and post implementation. Community arrests have decreased by more than 50% since implementing this model. Contracting with mental health services has led to an average 94 outpatient mental health provider referral per year. The results show positive trends in arrest rates after implementation of this collaborative model of preventive services. These findings support greater research and utilization of integrated, preventive service models for at-risk youth. (PsycINFO Database Record PMID:27148947

  9. Mechanisms of immunosuppression by organotins : apoptosis vs. proliferative arrest

    NARCIS (Netherlands)

    Gennari, Alessandra

    2001-01-01

    Mechanisms of immunosuppression by organotins-apoptosis vs. proliferative arrest. The organotin compounds di-n-butyltin dichloride (DBTC) and trin-butyltin chloride (TBTC), used as stabilizers and biocides respectively, induce thymus atrophy inhibiting immature thymocyte proliferation. The aim of

  10. Anaphylactic shock and cardiac arrest caused by thiamine infusion

    DEFF Research Database (Denmark)

    Juel, Jacob; Pareek, Manan; Langfrits, Christian Sigvald;

    2013-01-01

    intoxication and developed cardiac arrest due to anaphylactic shock following intravenous thiamine infusion. The patient was successfully resuscitated after 15 min and repeated epinephrine administrations. He was discharged in good health after 14 days. This case report emphasises both the importance...

  11. Mechanisms involved in ceramide-induced cell cycle arrest in human hepatocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Jing Wang; Xiao-Wen Lv; Jie-Ping Shi; Xiao-Song Hu

    2007-01-01

    AIM:To investigate the effect of ceramide on the cell cycle in human hepatocarcinoma Bel7402 cells.Possible molecular mechanisms were explored.METHODS:[3-(4,5)-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide(MTT)assay,plasmid transfection,reporter assay,FACS and Western blotting analyses were employed to investigate the effect and the related molecular mechanisms of C2-ceramide on the cell cycle of Bel7402 cells.RESULTS:C2-ceramide was found to inhibit the growth of Bel7402 cells by inducing cell cycle arrest.During the process,the expression of p21 protein increased,while that of cyclinD1,phospho-ERK1/2 and c-myc decreased.Furthermore,the level of CDK7 was downregulated,while the transcriptional activity of PPARγ was upregulated.Addition of GW9662,which is a PPARγ specific antagonist,could reserve the modulation action on CDK7.CONCLUSION:Our results support the hypothesis that cell cycle arrest induced by C2-ceramide may be mediated via accumulation of p21 and reduction of cyclinD1 and CDK7,at least partly,through PPARγ activation.The ERK signaling pathway was involved in this process.

  12. Tea pigments induce cell-cycle arrest and apoptosis in HepG2 cells

    Institute of Scientific and Technical Information of China (English)

    Xu-Dong Jia; Chi Han; Jun-Shi Chen

    2005-01-01

    AIM: To investigate the molecular mechanisms by which tea pigments exert preventive effects on liver carcinogenesis.METHODS: HepG2 cells were seeded at a density of 5×105/well in six-well culture dishes and incubated overnight. The cells then were treated with various concentrations of tea pigments over 3 d, harvested by trypsinization, and counted using a hemocytometer. Flow cytometric analysis was performed by a flow cytometer after propidium iodide labeling. Bcl-2 and p21WAF1 proteins were determined by Western blotting. In addition, DNA laddering assay was performed on treated and untreated cultured HepG2 cells.RESULTS: Tea pigments inhibited the growth of HepG2 cells in a dose-dependent manner. Flow-cytometric analysis showed that tea pigments arrested cell cycle progression at G1 phase. DNA laddering was used to investigate apoptotic cell death, and the result showed that 100 mg/L of tea pigments caused typical DNA laddering. Our study also showed that tea pigments induced upregulation of p21WAF1 protein and downregulation of Bcl-2 protein.CONCLUSION: Tea pigments induce cell-cycle arrest and apoptosis. Tea pigments may be used as an ideal chemopreventive agent.

  13. X-ray-induced G 2 arrest in ataxia telangiectasia lymphoblastoid cells

    International Nuclear Information System (INIS)

    Sensitivity to X-ray-induced G-2 arrest was compared between ataxia telangiectasia (AT) lymphoblastoid cells and normal human cells. Flow cytometrical analysis of cells following X-ray irradiation revealed that the fraction of cells with 4n DNA content was greater in AT cells than in normal cells as previously reported by other investigators. However, the other parameterss for cell-cycle progression kinetics including mitotic indices, cumulative mitotic indices and cumulative labelled mitotic indices indicated that X-ray-induced G-2 arrest as a function of dose in AT cells was indistinguishable from that in normal cells. Moreover, no significant difference in cell viability was noted between AT and normal cells until 48 h following X-irradiation up to 2.6 Gy, although X-irradiated At cells, compared to normal cells, showed a significantly decrease survival in terms of cell multiplication in growth medium and colony formation in soft agar. These data collectively suggest that the greater accumulation of AT cells with 4n DNA content in flow cytometry cannot be attributed to more stringent irreversible blockage of cell-cycle progression at the G-2 phase and eventual cell death there. The possible reasons for this greater accumulation are discussed. (Author). 19 refs.; 5 figs.; 2 tabs

  14. Nucleostemin Depletion Induces Post-G1 Arrest Apoptosis in Chronic Myelogenous Leukemia K562 Cells

    Directory of Open Access Journals (Sweden)

    Negin Seyed-Gogani

    2013-12-01

    Full Text Available Purpose: Despite significant improvements in treatment of chronic myelogenous leukemia (CML, the emergence of leukemic stem cell (LSC concept questioned efficacy of current therapeutical protocols. Remaining issue on CML includes finding and targeting of the key genes responsible for self-renewal and proliferation of LSCs. Nucleostemin (NS is a new protein localized in the nucleolus of most stem cells and tumor cells which regulates their self-renewal and cell cycle progression. The aim of this study was to investigate effects of NS knocking down in K562 cell line as an in vitro model of CML. Methods: NS gene silencing was performed using a specific small interfering RNA (NS-siRNA. The gene expression level of NS was evaluated by RT-PCR. The viability and growth rate of K562 cells were determined by trypan blue exclusion test. Cell cycle distribution of the cells was analyzed by flow cytometry. Results: Our results showed that NS knocking down inhibited proliferation and viability of K562 cells in a time-dependent manner. Cell cycle studies revealed that NS depletion resulted in G1 cell cycle arrest at short times of transfection (24 h followed with apoptosis at longer times (48 and 72 h, suggest that post-G1 arrest apoptosis is occurred in K562 cells. Conclusion: Overall, these results point to essential role of NS in K562 cells, thus, this gene might be considered as a promising target for treatment of CML.

  15. Explaining Discrepancies in Arrest Rates Between Black and White Male Juveniles

    OpenAIRE

    Fite, Paula J.; Wynn, Porche’; Pardini, Dustin A.

    2009-01-01

    The authors investigated discrepancies in arrest rates between Black and White male juveniles by examining the role of early risk factors for arrest. Two hypotheses were evaluated: (a) Disproportionate minority arrest is due to increased exposure to early risk factors, and (b) a differential sensitivity to early risk factors contributes to disproportionate minority arrest. The study included 481 Black and White boys who were followed from childhood to early adulthood. A higher incidence of ea...

  16. Survival of Phenotypic Information during Cellular Growth Transitions.

    Science.gov (United States)

    Ray, J Christian J

    2016-08-19

    Phenotypic memory can predispose cells to physiological outcomes, contribute to heterogeneity in cellular populations, and allow computation of environmental features, such as nutrient gradients. In bacteria and synthetic circuits in general, memory can often be set by protein concentrations: because of the relative stability of proteins, the degradation rate is often dominated by the growth rate, and inheritance is a significant factor. Cells can then be primed to respond to events that recur with frequencies faster than the time to eliminate proteins. Protein memory can be extended if cells reach extremely low growth rates or no growth. Here we characterize the necessary time scales for different quantities of protein memory, measured as relative entropy (Kullback-Leibler divergence), for a variety of cellular growth arrest transition dynamics. We identify a critical manifold in relative protein degradation/growth arrest time scales where information is, in principle, preserved indefinitely because proteins are trapped at a concentration determined by the competing time scales as long as nongrowth-mediated protein degradation is negligible. We next asked what characteristics of growth arrest dynamics and initial protein distributions best preserve or eliminate information about previous environments. We identified that sharp growth arrest transitions with skewed initial protein distributions optimize flexibility, with information preservation and minimal cost of residual protein. As a result, a nearly memoryless regime, corresponding to a form of bet-hedging, may be an optimal strategy for storage of information by protein concentrations in growth-arrested cells. PMID:26910476

  17. Gender and Relational-Distance Effects in Arrests for Domestic Violence

    Science.gov (United States)

    Lally, William; DeMaris, Alfred

    2012-01-01

    This study tests two hypotheses regarding factors affecting arrest of the perpetrator in domestic violence incidents. Black's relational-distance thesis is that the probability of arrest increases with increasing relational distance between perpetrator and victim. Klinger's leniency principle suggests that the probability of arrest is lower for…

  18. U.S. Juvenile Arrests: Gang Membership, Social Class, and Labeling Effects

    Science.gov (United States)

    Tapia, Mike

    2011-01-01

    This study addresses the link between gang membership and arrest frequency, exploring the Gang x Socioeconomic status interaction on those arrests. Notoriously poor, delinquent, and often well-known to police, America's gang youth should have very high odds of arrest. Yet it is unclear whether mere membership in a gang increases the risk of arrest…

  19. Pediatric defibrillation after cardiac arrest: initial response and outcome

    Science.gov (United States)

    Rodríguez-Núñez, Antonio; López-Herce, Jesús; García, Cristina; Domínguez, Pedro; Carrillo, Angel; Bellón, Jose María

    2006-01-01

    Introduction Shockable rhythms are rare in pediatric cardiac arrest and the results of defibrillation are uncertain. The objective of this study was to analyze the results of cardiopulmonary resuscitation that included defibrillation in children. Methods Forty-four out of 241 children (18.2%) who were resuscitated from inhospital or out-of-hospital cardiac arrest had been treated with manual defibrillation. Data were recorded according to the Utstein style. Outcome variables were a sustained return of spontaneous circulation (ROSC) and one-year survival. Characteristics of patients and of resuscitation were evaluated. Results Cardiac disease was the major cause of arrest in this group. Ventricular fibrillation (VF) or pulseless ventricular tachycardia (PVT) was the first documented electrocardiogram rhythm in 19 patients (43.2%). A shockable rhythm developed during resuscitation in 25 patients (56.8%). The first shock (dose, 2 J/kg) terminated VF or PVT in eight patients (18.1%). Seventeen children (38.6%) needed more than three shocks to solve VF or PVT. ROSC was achieved in 28 cases (63.6%) and it was sustained in 19 patients (43.2%). Only three patients (6.8%), however, survived at 1-year follow-up. Children with VF or PVT as the first documented rhythm had better ROSC, better initial survival and better final survival than children with subsequent VF or PVT. Children who survived were older than the finally dead patients. No significant differences in response rate were observed when first and second shocks were compared. The survival rate was higher in patients treated with a second shock dose of 2 J/kg than in those who received higher doses. Outcome was not related to the cause or the location of arrest. The survival rate was inversely related to the duration of cardiopulmonary resuscitation. Conclusion Defibrillation is necessary in 18% of children who suffer cardiac arrest. Termination of VF or PVT after the first defibrillation dose is achieved in a low

  20. The use of COD and plastic instability in crack propagation and arrest in shells

    Science.gov (United States)

    Erdogan, F.; Ratwani, M.

    1974-01-01

    The initiation, growth, and possible arrest of fracture in cylindrical shells containing initial defects are dealt with. For those defects which may be approximated by a part-through semi-elliptic surface crack which is sufficiently shallow so that part of the net ligament in the plane of the crack is still elastic, the existing flat plate solution is modified to take into account the shell curvature effect as well as the effect of the thickness and the small scale plastic deformations. The problem of large defects is then considered under the assumptions that the defect may be approximated by a relatively deep meridional part-through surface crack and the net ligament through the shell wall is fully yielded. The results given are based on an 8th order bending theory of shallow shells using a conventional plastic strip model to account for the plastic deformations around the crack border.

  1. Arrest of rapid crack propagation in polymer pipes

    Energy Technology Data Exchange (ETDEWEB)

    Flueler, P.; Farshad, M. [EMPA, Duebendorf (Switzerland)

    1995-12-31

    The design of rapid crack arresters for polymer pipes was studied. Mechanisms that would inhibit a running crack and strengthen existing pipes against dynamic fracture and to enhance their degree of safety were examined. The crack arresters examined were based on the principle that rapid crack propagation (RCP) could not occur in pipe walls that were less than a `critical thickness`. Sections of pipe whose walls were thinned were reinforced with a reinforcing ring. Another variation was to produce a pipe with partially adhered multilayer walls. A third variation tried was a multi-layer pipe segment with a damping element and reinforcing rings. Experiments were successful in reducing RCP, but these preliminary results were considered exploratory and would require further confirmation. 2 figs., 8 refs.

  2. Increased risk of sudden cardiac arrest in obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Warnier, Miriam Jacoba; Blom, Marieke Tabo; Bardai, Abdennasser;

    2013-01-01

    BACKGROUND: We aimed to determine whether (1) patients with obstructive pulmonary disease (OPD) have an increased risk of sudden cardiac arrest (SCA) due to ventricular tachycardia or fibrillation (VT/VF), and (2) the SCA risk is mediated by cardiovascular risk-profile and/or respiratory drug use....... METHODS: A community-based case-control study was performed, with 1310 cases of SCA of the ARREST study and 5793 age, sex and SCA-date matched non-SCA controls from the PHARMO database. Only incident SCA cases, age older than 40 years, that resulted from unequivocal cardiac causes...... with electrocardiographic documentation of VT/VF were included. Conditional logistic regression analysis was used to assess the association between SCA and OPD. Pre-specified subgroup analyses were performed regarding age, sex, cardiovascular risk-profile, disease severity, and current use of respiratory drugs. RESULTS...

  3. Cell cycle control after DNA damage: arrest, recovery and adaptation

    International Nuclear Information System (INIS)

    DNA damage triggers surveillance mechanisms, the DNA checkpoints, that control the genome integrity. The DNA checkpoints induce several responses, either cellular or transcriptional, that favor DNA repair. In particular, activation of the DNA checkpoints inhibits cell cycle progression in all phases, depending on the stage when lesions occur. These arrests are generally transient and cells ultimately reenter the cell division cycle whether lesions have been repaired (this process is termed 'recovery') or have proved un-repairable (this option is called 'adaptation'). The mechanisms controlling cell cycle arrests, recovery and adaptation are largely conserved among eukaryotes, and much information is now available for the yeast Saccharomyces cerevisiae, that is used as a model organism in these studies. (author)

  4. Characteristics of in-hospital cardiac arrest and cardiopulmonary resuscitation

    Directory of Open Access Journals (Sweden)

    Josip Ivić

    2009-02-01

    Full Text Available Aim We have studied epidemiology of in-hospital cardiac arrest, characteristics of organizing a reanimationand its,procedures as well as its documenting.Methods We analyzed all resuscitation procedure data where anesthesiology reanimation teams (RT providedcardiopulmonary resuscitation (CPR during one-year period. We included resuscitation attemptsthat were initiated outside the Department of Anesthesiology, excluding incidents in operation rooms andIntensive Care Unit (ICU. Data on every cardiac arrest and CPR were entered in a special form.Results During one-year period 87 CPR were performed. Victims of cardiac arrest were principallyelderly patients (age 60 – 80, mostly male (60%. Most frequent victims were neurological patients(42%, surgical patients (21% and neurosurgical patients (10%. The leading cause of cardiac arrestwas primary heart disease, following neurological diseases and respiration disorders of severe etiology.In over 90% cases CPR was initiated by medical personnel in their respective departments, RT arrivedwithin 5 minutes in 73,56% cases. Initially survival was 32%, but full recovery was accomplished in 4patients out of 87 (4,6%.Conclusion Victims of cardiac arrest are patients whose primary disease contributes to occurrence ofcardiorespiratory complications. High mortality and low percentage of full recovery can be explainedby characteristics of patients (old age, nature and seriousness of primary disease which significantly affectthe outcome of CPR. In some cases a question is raised whether to initiate the CPR at all. We wouldlike to point out that continous monitoring of potentially critical patients may prevent cardiorespiratoryincidents whereas the quality and success of CPR may be improved by training of staff and better technicalequipment on the relevant locations in the in the hospital where such incidents usually occur.

  5. Nontrapping arrest of Langmuir wave damping near the threshold amplitude

    OpenAIRE

    Ivanov, A.V.; Cairns, Iver H.

    2005-01-01

    Evolution of a Langmuir wave is studied numerically for finite amplitudes slightly above the threshold which separates damping from nondamping cases. Arrest of linear damping is found to be a second-order effect due to ballistic evolution of perturbations, resonant power transfer between field and particles, and organization of phase space into a positive slope for the average distribution function $f_{av}$ around the resonant wave phase speed $v_\\phi$. Near the threshold trapping in the wave...

  6. Anaphylactic shock and cardiac arrest caused by thiamine infusion

    OpenAIRE

    Juel, Jacob; Pareek, Manan; Langfrits, Christian Sigvald; Jensen, Svend Eggert

    2013-01-01

    Parenteral thiamine has a very high safety profile. The most common adverse effect is local irritation; however, anaphylactic or anaphylactoid reactions may occur, mostly related to intravenous administration. We describe a 44-year-old man, a chronic alcoholic, who was admitted with alcohol intoxication and developed cardiac arrest due to anaphylactic shock following intravenous thiamine infusion. The patient was successfully resuscitated after 15 min and repeated epinephrine administrations....

  7. Electrocardiogram characteristics prior to in-hospital cardiac arrest

    OpenAIRE

    Attin, Mina; Feld, Gregory; Lemus, Hector; Najarian, Kayvan; Shandilya, Sharad; Wang, Lu; Sabouriazad, Pouya; Lin, Chii-Dean

    2014-01-01

    Survival after in-hospital cardiac arrest (I-HCA) remains < 30 %. There is very limited literature exploring the electrocardiogram changes prior to I-HCA. The purpose of the study was to determine demographics and electrocardiographic predictors prior to I-HCA. A retrospective study was conducted among 39 cardiovascular subjects who had cardiopulmonary resuscitation from I-HCA with initial rhythms of pulseless electrical activity (PEA) and asystole. Demographics including medical history, eje...

  8. Luminescence from Tube-Arrest Bubbles in Pure Glycerin

    Institute of Scientific and Technical Information of China (English)

    陈岐岱; 王龙

    2004-01-01

    Single transient cavitation bubble with luminescence has been generated in pure glycerin by using the ‘tube arrest'method. The analyses of high-speed photograph and light emission data suggest that the light emission would be a single bubble sonoluminescence. The luminescence pulse width is observed to wry from sub-nanosecond to about 30 ns. The width and intensity of luminescence pulses increases with the height of the liquid column height and decreases with the liquid temperature.

  9. Hyperoxia toxicity after cardiac arrest: What is the evidence?

    OpenAIRE

    Llitjos, Jean-François; Mira, Jean-Paul; Duranteau, Jacques; Cariou, Alain

    2016-01-01

    This review gives an overview of current knowledge on hyperoxia pathophysiology and examines experimental and human evidence of hyperoxia effects after cardiac arrest. Oxygen plays a pivotal role in critical care management as a lifesaving therapy through the compensation of the imbalance between oxygen requirements and supply. However, growing evidence sustains the hypothesis of reactive oxygen species overproduction-mediated toxicity during hyperoxia, thus exacerbating organ failure by vari...

  10. Arresting Strategy Based on Dynamic Criminal Networks Changing over Time

    Directory of Open Access Journals (Sweden)

    Junqing Yuan

    2013-01-01

    Full Text Available We investigate a sequence of dynamic criminal networks on a time series based on the dynamic network analysis (DNA. According to the change of networks’ structure, networks’ variation trend is analyzed to forecast its future structure. Finally, an optimal arresting time and priority list are designed based on our analysis. Better results can be expected than that based on social network analysis (SNA.

  11. Oral Phenytoin Toxicity Causing Sinus Arrest: A Case Report

    Science.gov (United States)

    Thimmisetty, Ravi K.; Gorthi, Janardhana Rao

    2014-01-01

    We present a case of sinus node arrest leading to symptomatic junctional bradycardia from oral phenytoin toxicity, which is a rare presentation. Our patient had no prior cardiac history and was on phenytoin therapy for seizure disorder. Although bradycardia is more commonly associated with intravenous phenytoin and there were few case reports of bradycardia with oral phenytoin reported, the literature is limited. In this case report, we also reviewed the pathophysiology of phenytoin-induced cardiac toxicity. PMID:25343048

  12. Patients with polycystic ovary syndrome have successful embryo arrest

    OpenAIRE

    Yin, Baoli; Hao, Haoying; Wei, Duo; Song, Xiaobing; Xie, Juanke; Zhang, Cuilian

    2015-01-01

    In this retrospective study, we investigate the relationship between embryo arrest and polycystic ovary syndrome (PCOS) during in vitro fertilization-embryo transfer (IVF-ET). In this study, 667 subjects were enrolled, including 330 patients with PCOS and 337 subjects without PCOS. The subjects underwent in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) cycles at the Reproductive Medical Centre of Henan Provincial Hospital from January 2009 to December ...

  13. ADULTHOOD ANIMAL ABUSE AMONG MEN ARRESTED FOR DOMESTIC VIOLENCE

    OpenAIRE

    Febres, Jeniimarie; Brasfield, Hope; Shorey, Ryan C.; Elmquist, Joanna; Ninnemann, Andrew; Schonbrun, Yael C.; Temple, Jeff R.; Recupero, Patricia R.; Stuart, Gregory L.

    2014-01-01

    Learning more about intimate partner violence (IPV) perpetrators could aid the development of more effective treatments. The prevalence of adulthood animal abuse (AAA) perpetration and its association with IPV perpetration, antisociality, and alcohol use in 307 men arrested for domestic violence was examined. 41% (n = 125) of the men committed at least one act of animal abuse since the age of 18, in contrast to the 3.0% prevalence rate reported by men in the general population. Controlling fo...

  14. Advances in crack-arrest technology for reactor pressure vessels

    Energy Technology Data Exchange (ETDEWEB)

    Bass, B.R.; Pugh, C.E.

    1988-01-01

    The Heavy-Section Steel Technology (HSST) Program at the Oak Ridge National Laboratory (ORNL) under the sponsorship of the US Nuclear Regulatory Commission is continuing to improve the understanding of conditions that govern the initiation, rapid propagation, arrest, and ductile tearing of cracks in reactor pressure vessel (RPV) steels. This paper describes recent advances in a coordinated effort being conducted under the HSST Program by ORNL and several subcontracting groups to develop the crack-arrest data base and the analytical tools required to construct inelastic dynamic fracture models for RPV steels. Large-scale tests are being carried out to generate crack-arrest toughness data at temperatures approaching and above the onset of Charpy upper-shelf behavior. Small- and intermediate-size specimens subjected to static and dynamic loading are being developed and tested to provide additional fracture data for RPV steels. Viscoplastic effects are being included in dynamic fracture models and computer programs and their utility validated through analyses of data from carefully controlled experiments. Recent studies are described that examine convergence problems associated with energy-based fracture parameters in viscoplastic-dynamic fracture applications. Alternative techniques that have potential for achieving convergent solutions for fracture parameters in the context of viscoplastic-dynamic models are discussed. 46 refs., 15 figs., 3 tabs.

  15. Hyperoxia toxicity after cardiac arrest: What is the evidence?

    Science.gov (United States)

    Llitjos, Jean-François; Mira, Jean-Paul; Duranteau, Jacques; Cariou, Alain

    2016-12-01

    This review gives an overview of current knowledge on hyperoxia pathophysiology and examines experimental and human evidence of hyperoxia effects after cardiac arrest. Oxygen plays a pivotal role in critical care management as a lifesaving therapy through the compensation of the imbalance between oxygen requirements and supply. However, growing evidence sustains the hypothesis of reactive oxygen species overproduction-mediated toxicity during hyperoxia, thus exacerbating organ failure by various oxidative cellular injuries. In the cardiac arrest context, evidence of hyperoxia effects on outcome is fairly conflicting. Although prospective data are lacking, retrospective studies and meta-analysis suggest that hyperoxia could be associated with an increased mortality. However, data originate from retrospective, heterogeneous and inconsistent studies presenting various biases that are detailed in this review. Therefore, after an original and detailed analysis of all experimental and clinical studies, we herein provide new ideas and concepts that could participate to improve knowledge on oxygen toxicity and help in developing further prospective controlled randomized trials on this topic. Up to now, the strategy recommended by international guidelines on cardiac arrest (i.e., targeting an oxyhemoglobin saturation of 94-98 %) should be applied in order to avoid deleterious hypoxia and potent hyperoxia. PMID:27003426

  16. An analysis of mandatory arrest policy on domestic violence

    Directory of Open Access Journals (Sweden)

    Ahmet Çelik

    2013-05-01

    Full Text Available Women are more likely to be beaten, raped, or killed because of domestic violence. Men have beaten their wives and partners for centuries with no payback from the criminal justice system. Recent decades domestic violence cases became an important focal point for criminal justice system. Despite increased public awareness, domestic violence remains a serious public policy issue in all around the world. Domestic violence was historically an area of policing where officers were reluctant to interfere because of its sensitive nature vary from one culture to another. Governments started to face with increased liability for police inaction. Therefore law makers passed laws requiring the warrantless arrests of individuals for misdemeanor assault of an intimate partner. This article tries to explain background information over domestic violence from public policy perspective at first. Then tries to explain mandatory arrest policies with its goals and effects. After evaluation and implications of mandatory arrest policies on domestic violence this article concludes by recommending various policy recommendation at the end.

  17. Molecular interplay between cdk4 and p21 dictates G0/G1 cell cycle arrest in prostate cancer cells

    OpenAIRE

    Gulappa, Thippeswamy; Reddy, Ramadevi Subramani; Suman, Suman; Nyakeriga, Alice M; Damodaran, Chendil

    2013-01-01

    This study examined the effect of 3, 9-dihydroxy-2-prenylcoumestan (pso), a furanocoumarin, on PC-3 and C4-2B castration-resistant prostate cancer (CRPC) cell lines. Pso caused significant G0/G1 cell cycle arrest and inhibition of cell growth. Molecular analysis of cyclin (D1, D2, D3, and E), cyclin-dependent kinase (cdk) (cdks 2, 4, and 6), and cdk inhibitor (p21 and p27) expression suggested transcriptional regulation of the cdk inhibitors and more significant downregulation of cdk4 than of...

  18. Descriptive Analysis of Medication Administration During Inpatient Cardiopulmonary Arrest Resuscitation (from the Mayo Registry for Telemetry Efficacy in Arrest Study).

    Science.gov (United States)

    Snipelisky, David; Ray, Jordan; Matcha, Gautam; Roy, Archana; Dumitrascu, Adrian; Harris, Dana; Bosworth, Veronica; Clark, Brooke; Thomas, Colleen S; Heckman, Michael G; Vadeboncoeur, Tyler; Kusumoto, Fred; Burton, M Caroline

    2016-05-15

    Advanced cardiovascular life support guidelines exist, yet there are variations in clinical practice. Our study aims to describe the utilization of medications during resuscitation from in-hospital cardiopulmonary arrest. A retrospective review of patients who suffered a cardiopulmonary arrest from May 2008 to June 2014 was performed. Clinical and resuscitation data, including timing and dose of medications used, were extracted from the electronic medical record and comparisons made. A total of 94 patients were included in the study. Patients were divided into different groups based on the medication combination used during resuscitation: (1) epinephrine; (2) epinephrine and bicarbonate; (3) epinephrine, bicarbonate, and calcium; (4) epinephrine, bicarbonate, and epinephrine drip; and (5) epinephrine, bicarbonate, calcium, and epinephrine drip. No difference in baseline demographics or clinical data was present, apart from history of dementia and the use of calcium channel blockers. The number of medications given was correlated with resuscitation duration (Spearman's rank correlation = 0.50, p <0.001). The proportion of patients who died during the arrest was 12.5% in those who received epinephrine alone, 30.0% in those who received only epinephrine and bicarbonate, and 46.7% to 57.9% in the remaining groups. Patients receiving only epinephrine had shorter resuscitation durations compared to that of the other groups (p <0.001) and improved survival (p = 0.003). In conclusion, providers frequently use nonguideline medications in resuscitation efforts for in-hospital cardiopulmonary arrests. Increased duration and mortality rates were found in those resuscitations compared with epinephrine alone, likely due to the longer resuscitation duration in the former groups. PMID:27015887

  19. Joints and Mineral Veins in Limestone-Marl Alternations: Arrest and Fracture Frequencies

    Science.gov (United States)

    Philipp, S. L.; Reyer, D.

    2009-05-01

    materials science. Some fractures may also be arrested by slip at contacts. For fractures to propagate, the stress field along their potential pathways must be favorable and essentially homogeneous so that the probability of fracture arrest is minimized. The field observations show that most joints, and many mineral veins, become arrested, primarily at layer contacts. Fractures that are restricted to single layers are referred to as stratabound, whereas for non- stratabound fractures, layering does not affect fracture growth. Different types of fractures react differently to host-rock layering. Fractures formed at great depths are generally less likely to become stratabound, but different fractures also seem to "feel" the rock layers and contacts differently. For example, mineral veins are much more often non-stratabound than joints. In our study areas there is also a clear inverse correlation between layer thicknesses and joint frequencies, particularly for layering on a decimeter-scale. The calcite veins, however, are not related to layer thickness. The results have important implications for the permeability of fluid reservoirs, such as for petroleum, gas, geothermal or ground water. Whereas correlations with layer thicknesses may be used for joint frequencies in the subsurface and thus reservoir permeabilities, it is more difficult to predict how many reservoir fractures are likely to be stratabound. A reservoir where most fractures are stratabound is less likely to develop interconnected fracture systems than a reservoir with non-stratabound fractures. Thus, a reservoir with mostly stratabound fractures may not reach the percolation threshold needed for significant permeability.

  20. The cancer-germline antigen SSX2 causes cell cycle arrest and DNA damage in cancer cells

    DEFF Research Database (Denmark)

    Greve, Katrine Buch Vidén; Lindgreen, Jonas; Terp, Mikkel Green;

    2011-01-01

    increase in the number of gamma-H2AX ‘DNA damage foci’, indicating replicative stress, which may lead to genomic instability. As the p53 tumor suppressor is an inducer of G1 arrest after DNA damage and often deregulated in cancer cells, we investigated if the growth reduction due to SSX2 expression was p53...... dependent. The growth reduction was similar in isogenic colon cancer cells with and without p53, indicating that SSX2 is able to inhibit the growth of cancer cells, even in absence of functional p53. Our results show that SSX2 acts as an inhibitor of cancer cell proliferation, possibly through replicative......The SSX family of cancer and germline antigens is mainly expressed in the germ cells of healthy individuals as well as wide range of cancers and is therefore potential targets for immunotherapy. However, little is known about the role of SSX proteins in tumorigenesis and normal cell function. Here...

  1. Pravastatin induces cell cycle arrest and decreased production of VEGF and bFGF in multiple myeloma cell line.

    Science.gov (United States)

    Trojan, P J J; Bohatch-Junior, M S; Otuki, M F; Souza-Fonseca-Guimarães, F; Svidnicki, P V; Nogaroto, V; Fernandes, D; Krum, E A; Favero, G M

    2016-02-01

    Multiple myeloma (MM) is a B cell bone marrow neoplasia characterized by inflammation with an intense secretion of growth factors that promote tumor growth, cell survival, migration and invasion. The aim of this study was to evaluate the effects of pravastatin, a drug used to reduce cholesterol, in a MM cell line.Cell cycle and viability were determinate by Trypan Blue and Propidium Iodide. IL6, VEGF, bFGF and TGFβ were quantified by ELISA and qRT-PCR including here de HMG CoA reductase. It was observed reduction of cell viability, increase of cells in G0/G1 phase of the cell cycle and reducing the factors VEGF and bFGF without influence on 3-Methyl-Glutaryl Coenzyme A reductase expression.The results demonstrated that pravastatin induces cell cycle arrest in G0/G1 and decreased production of growth factors in Multiple Myeloma cell line. PMID:26909624

  2. Hexavalent chromium induces chromosome instability in human urothelial cells.

    Science.gov (United States)

    Wise, Sandra S; Holmes, Amie L; Liou, Louis; Adam, Rosalyn M; Wise, John Pierce

    2016-04-01

    Numerous metals are well-known human bladder carcinogens. Despite the significant occupational and public health concern of metals and bladder cancer, the carcinogenic mechanisms remain largely unknown. Chromium, in particular, is a metal of concern as incidences of bladder cancer have been found elevated in chromate workers, and there is an increasing concern for patients with metal hip implants. However, the impact of hexavalent chromium (Cr(VI)) on bladder cells has not been studied. We compared chromate toxicity in two bladder cell lines; primary human urothelial cells and hTERT-immortalized human urothelial cells. Cr(VI) induced a concentration- and time-dependent increase in chromosome damage in both cell lines, with the hTERT-immortalized cells exhibiting more chromosome damage than the primary cells. Chronic exposure to Cr(VI) also induced a concentration-dependent increase in aneuploid metaphases in both cell lines which was not observed after a 24h exposure. Aneuploidy induction was higher in the hTERT-immortalized cells. When we correct for uptake, Cr(VI) induces a similar amount of chromosome damage and aneuploidy suggesting that the differences in Cr(VI) sensitivity between the two cells lines were due to differences in uptake. The increase in chromosome instability after chronic chromate treatment suggests this may be a mechanism for chromate-induced bladder cancer, specifically, and may be a mechanism for metal-induced bladder cancer, in general. PMID:26908176

  3. Hospital Variation in Survival After In‐hospital Cardiac Arrest

    Science.gov (United States)

    Merchant, Raina M.; Berg, Robert A.; Yang, Lin; Becker, Lance B.; Groeneveld, Peter W.; Chan, Paul S.

    2014-01-01

    Background In‐hospital cardiac arrest (IHCA) is common and often fatal. However, the extent to which hospitals vary in survival outcomes and the degree to which this variation is explained by patient and hospital factors is unknown. Methods and Results Within Get with the Guidelines‐Resuscitation, we identified 135 896 index IHCA events at 468 hospitals. Using hierarchical models, we adjusted for demographics comorbidities and arrest characteristics (eg, initial rhythm, etiology, arrest location) to generate risk‐adjusted rates of in‐hospital survival. To quantify the extent of hospital‐level variation in risk‐adjusted rates, we calculated the median odds ratio (OR). Among study hospitals, there was significant variation in unadjusted survival rates. The median unadjusted rate for the bottom decile was 8.3% (range: 0% to 10.7%) and for the top decile was 31.4% (28.6% to 51.7%). After adjusting for 36 predictors of in‐hospital survival, there remained substantial variation in rates of in‐hospital survival across sites: bottom decile (median rate, 12.4% [0% to 15.6%]) versus top decile (median rate, 22.7% [21.0% to 36.2%]). The median OR for risk‐adjusted survival was 1.42 (95% CI: 1.37 to 1.46), which suggests a substantial 42% difference in the odds of survival for patients with similar case‐mix at similar hospitals. Further, significant variation persisted within hospital subgroups (eg, bed size, academic). Conclusion Significant variability in IHCA survival exists across hospitals, and this variation persists despite adjustment for measured patient factors and within hospital subgroups. These findings suggest that other hospital factors may account for the observed site‐level variations in IHCA survival. PMID:24487717

  4. Berberine induces cell cycle arrest and apoptosis in human gastric carcinoma SNU-5 cell line

    Institute of Scientific and Technical Information of China (English)

    Jing-Pin Lin; Jai-Sing Yang; Jau-Hong Lee; Wen-Tsong Hsieh; Jing-Gung Chung

    2006-01-01

    AIM: To investigate the relationship between the inhibited growth (cytotoxic activity) of berberine and apoptotic pathway with its molecular mechanism of action.METHODS: The in vitro cytotoxic techniques were complemented by cell cycle analysis and determination of sub-G1 for apoptosis in human gastric carcinoma SNU-5 cells. Percentage of viable cells, cell cycle, and sub-G1 group (apoptosis) were examined and determined by the flow cytometric methods. The associated proteins for cell cycle arrest and apoptosis were examined by Western blotting.RESULTS: For SNU-5 cell line, the IC (50) was found to be 48 μmol/L of berberine. In SNU-5 cells treated with 25-200 μmol/L berberine, G2/M cell cycle arrest was observed which was associated with a marked increment of the expression of p53, Wee1 and CDk1 proteins and decreased cyclin B. A concentration-dependent decrease of cells in G0/G1 phase and an increase in G2/M phase were detected. In addition, apoptosis detected as sub-G0 cell population in cell cycle measurement was proved in 25-200 μmol/L berberine-treated cells by monitoring the apoptotic pathway. Apoptosis was identified by sub-G0 cell population, and upregulation of Bax, downregulation of Bcl-2, release of Ca2+, decreased the mitochondrial membrane potential and then led to the release of mitochondrial cytochrome C into the cytoplasm and caused the activation of caspase-3, and finally led to the occurrence of apoptosis.CONCLUSION: Berberine induces p53 expression and leads to the decrease of the mitochondrial membrane potential, Cytochrome C release and activation of caspase-3 for the induction of apoptosis.

  5. Cardiac arrest caused by multiple recurrent pulmonary embolism

    DEFF Research Database (Denmark)

    Hannig, Kjartan Eskjaer; Husted, Steen Elkjaer; Grove, Erik Lerkevang

    2011-01-01

    Pulmonary embolism is a common condition with a high mortality. We describe a previously healthy 68-year-old male who suffered three pulmonary embolisms during a short period of time, including two embolisms while on anticoagulant treatment. This paper illustrates three important points. (1) The...... importance of optimal anticoagulant treatment in the prevention of pulmonary embolism reoccurrence. (2) The benefit of immediate accessibility to echocardiography in the handling of haemodynamically unstable patients with an unknown underlying cause. (3) Thrombolytic treatment should always be considered and...... may be life-saving in patients with cardiac arrest suspected to be caused by pulmonary embolism....

  6. Axial crack propagation and arrest in pressurized fuselage

    Science.gov (United States)

    Kosai, M.; Shimamoto, A.; Yu, C.-T.; Walker, S. I.; Kobayashi, A. S.; Tan, P.

    1994-01-01

    The crack arrest capability of a tear strap in a pressurized precracked fuselage was studied through instrumented axial rupture tests of small scale models of an idealized fuselage. Upon pressurization, rapid crack propagation initiated at an axial through crack along the stringer and immediately kinked due to the mixed modes 1 and 2 state caused by the one-sided opening of the crack flap. The diagonally running crack further turned at the tear straps. Dynamic finite element analysis of the rupturing cylinder showed that the crack kinked and also ran straight in the presence of a mixed mode state according to a modified two-parameter crack kinking criterion.

  7. Bleeding following deep hypothermia and circulatory arrest in children.

    Science.gov (United States)

    Mossad, Emad B; Machado, Sandra; Apostolakis, John

    2007-03-01

    Deep hypothermic circulatory arrest (DHCA) is a technique of extracorporeal circulation commonly used in children with complex congenital heart defects undergoing surgical repairs. The use of profound cooling (20 degrees C) and complete cessation of circulation allow adequate exposure and correction of these complex lesions, with enhanced cerebral protection. However, the profound physiologic state of DHCA results in significant derangement of the coagulation system and a high incidence of postoperative bleeding. This review examines the impact of DHCA on bleeding and transfusion requirements in children and the pathophysiology of DHCA-induced platelet dysfunction. It also focuses on possible pharmacologic interventions to decrease bleeding following DHCA in children. PMID:17484172

  8. Cerebral blood flow in humans following resuscitation from cardiac arrest

    International Nuclear Information System (INIS)

    Cerebral blood flow was measured by xenon-133 washout in 13 patients 6-46 hours after being resuscitated from cardiac arrest. Patients regaining consciousness had relatively normal cerebral blood flow before regaining consciousness, but all patients who died without regaining consciousness had increased cerebral blood flow that appeared within 24 hours after resuscitation (except in one patient in whom the first measurement was delayed until 28 hours after resuscitation, by which time cerebral blood flow was increased). The cause of the delayed-onset increase in cerebral blood flow is not known, but the increase may have adverse effects on brain function and may indicate the onset of irreversible brain damage

  9. Venoarterial Extracorporeal Membrane Oxygenation in Adults With Cardiac Arrest.

    Science.gov (United States)

    Patel, Jignesh K; Schoenfeld, Elinor; Parnia, Sam; Singer, Adam J; Edelman, Norman

    2016-07-01

    Cardiac arrest (CA) is a major cause of morbidity and mortality worldwide. Despite the use of conventional cardiopulmonary resuscitation (CPR), rates of return of spontaneous circulation and survival with minimal neurologic impairment remain low. Utilization of venoarterial extracorporeal membrane oxygenation (ECMO) for CA in adults is steadily increasing. Propensity-matched cohort studies have reported outcomes associated with ECMO use to be superior to that of conventional CPR alone in in-hospital patients with CA. In this review, we discuss the mechanism, indications, complications, and evidence for ECMO in CA in adults. PMID:25922385

  10. Development of New Type Gap Arrester for Earth Fault Protection in AC Feeding System

    Science.gov (United States)

    Ajiki, Kohji; Morimoto, Hiroaki; Hisamizu, Yasuzi; Kinoshita, Nobuo; Takai, Wataru; Sato, Ryogo

    A gap arrester is being used for ground fault protection in AC Feeding System. However there are faults in which a conventional gap arrester burns down in a normal state of circuit. We investigated the cause of the fault in which a gap arrester burns. Then, it was found out that the cause of the fault was the discharge of AC current from the surge voltage. Therefore, we developed a new type gap arrester which does not burn down. The new type gap arrester is composed of a discharge tube and a zinc oxide element which are connected in series. Unnecessary AC current discharge is prevented by this structure. The new type gap arrester is actually used at the railroad track.

  11. Overexpression of cyclin L2 induces apoptosis and cell-cycle arrest in human lung cancer cells

    Institute of Scientific and Technical Information of China (English)

    LI Hong-li; WANG Tong-shan; LI Xiao-yu; LI Nan; HUANG Ding-zhi; CHEN Qi; BA Yi

    2007-01-01

    Background Uncontrolled cell division is one of the hallmarks of tumor growth. Researches have been focused on numerous molecules involved in this process. Cyclins are critical regulatory proteins of cell cycle progression and/or transcription. The present study aimed to investigate the anti-proliferative effect of cyclin L2, and to define its growth regulatory mechanisms using human lung adenocarcinoma cell line A549.Methods Human cyclin L2 was transfected into human lung adenocarcinoma cells (A549 cell), and was expressed in a mammalian expression vector pcDNA3.1. The effects and mechanisms of the cyclin L2 in cell growth, cell cycle analysis and apoptosis were studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry or Western blot, respectively.Results Overexpression of cyclin L2 inhibited the growth of A549 cells. Cell cycle analysis in cells transfected with pCCNL2 revealed an increment in proportion in G0/G1 phase ((68.07 ± 4.2)%) in contrast to (60.39 ± 2.82)% of the cells transfected with mock vector. Apoptosis occurred in (7.25 ± 0.98)% cells transfected with pCCNL2, as compared with (1.25 ± 0.21)% of the mock vector control group. Cyclin L2-induced-G0/G1 arrest and apoptosis involved upregulation of caspase-3 and downregulation of Bcl-2 and survivin.Conclusion The results indicate that overexpression of cyclin L2 protein may promote efficient growth inhibition of human lung adenocarcinoma cells by inducing G0/G1 cell cycle arrest and apoptosis.

  12. Developmentally arrested structures preceding cerebellar tumors in von Hippel–Lindau disease

    OpenAIRE

    Shively, Sharon B; Falke, Eric A; Li, Jie; Tran, Maxine G B; Thompson, Eli R; Maxwell, Patrick H; Roessler, Erich; Oldfield, Edward H; Lonser, Russell R.; Vortmeyer, Alexander O

    2011-01-01

    There is increasing evidence that suggests that knockout of tumor-suppressor gene function causes developmental arrest and protraction of cellular differentiation. In the peripheral nervous system of patients with the tumor-suppressor gene disorder, von Hippel–Lindau disease, we have demonstrated developmentally arrested structural elements composed of hemangioblast progenitor cells. Some developmentally arrested structural elements progress to a frank tumor, hemangioblastoma. However, in von...

  13. Brazilian production development of class 2 polymeric surge arresters for transmission line application

    Energy Technology Data Exchange (ETDEWEB)

    Dellallibera, Adriano A. [Industria Eletromecanica Balestro, Mogi Mirim, SP (Brazil)], E-mail: adrianoad@balestro.com; Andrade, Antonio Donizetti de; Bezerra, Ana Cristina Guara; Duarte, Jose Vicente Pereira; Gois, Paulo Marcio Batista; Markiewicz, Rubens Leopoldo [Companhia Energetica de Minas Gerais (CEMIG), Belo Horizonte, MG (Brazil)], Emails: andonize@cemig.com.br, anacris@cemig.com.br, vicente@cemig.com.br, pgois@cemig.com.br, rlmark@cemig.com.br

    2007-07-01

    This paper shows the steeps of Brazilian class 2 ZnO lightning surge arrester development and production, aiming to attend the goal of CEMIG transmission lines performance improvement against lightning discharges action. The description of CEMIG transmission lines performance, before and after the ZnO lightning arresters installation, the necessity of use of ZnO lightning surge arrester, the prototypes manufacture, tests, problems and solutions are presented. (author)

  14. Using force in arrests against those who are not resisting can mean more violent prisoners.

    OpenAIRE

    Klahm, Charles; Steiner, Benjamin; Meade, Benjamin

    2015-01-01

    Recent events have seen a re-evaluation of the relationship between the police and citizens, with increased concern about the use of force during arrests. In new research, Charles Klahm, Benjamin Steiner, and Benjamin Meade find another consequence of police using violent force during arrests: once in prison, inmates who did not resist their arrests were more likely to be involved in rule violations, including acts of violence. They argue that these inmates’ beliefs that their treatment was u...

  15. IARS2 silencing induces non-small cell lung cancer cells proliferation inhibition, cell cycle arrest and promotes cell apoptosis.

    Science.gov (United States)

    Yin, J; Liu, W; Li, R; Liu, J; Zhang, Y; Tang, W; Wang, K

    2016-01-01

    The purpose of this study was to investigate the potential role of Ileucyl-tRNA synthetase (IARS2) silencing in non-small cell lung cancer (NSCLC). The silencing of IARS2 in H1299 cells and A549 cells were performed by lentivirus encoding shRNAs. The efficiency of IARS2 silencing was detected by quantitative real time PCR and western blot. The effects of IARS2 silencing on cell growth, cell apoptosis, cell cycle and cell colony formation ability were assessed by cells counting, MTT assay, flow cytometer analysis and soft agar colony formation assay, respectively. Compared with negative control group, IARS2 was significantly knockdown by transfection with lentivirus encoding shRNA of IARS2. The IARS2 silencing significantly inhibited the cells proliferation and cells colony formation ability, induced cell cycle arrest at G1/S phase and promoted cell apoptosis. IARS2 silencing induced NSCLC cells growth inhibition, cell cycle arrest and promoted cell apoptosis. These results suggest that IARS2 may be a novel target for the treatment of NSCLC. PMID:26639235

  16. Focused Cardiac Ultrasound Diagnosis of Cor Triatriatum Sinistrum in Pediatric Cardiac Arrest

    Directory of Open Access Journals (Sweden)

    Thompson Kehrl,

    2015-10-01

    Full Text Available Cardiac arrest in the adolescent population secondary to congenital heart disease (CHD is rare. Focused cardiac ultrasound (FoCUS in the emergency department (ED can yield important clinical information, aid in resuscitative efforts during cardiac arrest and is commonly integrated into the evaluation of patients with pulseless electrical activity (PEA. We report a case of pediatric cardiac arrest in which FoCUS was used to diagnose a critical CHD known as cor triatriatum sinistrum as the likely cause for PEA cardiac arrest and help direct ED resuscitation.

  17. Altered brain energetics induces mitochondrial fission arrest in Alzheimer's Disease.

    Science.gov (United States)

    Zhang, Liang; Trushin, Sergey; Christensen, Trace A; Bachmeier, Benjamin V; Gateno, Benjamin; Schroeder, Andreas; Yao, Jia; Itoh, Kie; Sesaki, Hiromi; Poon, Wayne W; Gylys, Karen H; Patterson, Emily R; Parisi, Joseph E; Diaz Brinton, Roberta; Salisbury, Jeffrey L; Trushina, Eugenia

    2016-01-01

    Altered brain metabolism is associated with progression of Alzheimer's Disease (AD). Mitochondria respond to bioenergetic changes by continuous fission and fusion. To account for three dimensional architecture of the brain tissue and organelles, we applied 3-dimensional electron microscopy (3D EM) reconstruction to visualize mitochondrial structure in the brain tissue from patients and mouse models of AD. We identified a previously unknown mitochondrial fission arrest phenotype that results in elongated interconnected organelles, "mitochondria-on-a-string" (MOAS). Our data suggest that MOAS formation may occur at the final stages of fission process and was not associated with altered translocation of activated dynamin related protein 1 (Drp1) to mitochondria but with reduced GTPase activity. Since MOAS formation was also observed in the brain tissue of wild-type mice in response to hypoxia or during chronological aging, fission arrest may represent fundamental compensatory adaptation to bioenergetic stress providing protection against mitophagy that may preserve residual mitochondrial function. The discovery of novel mitochondrial phenotype that occurs in the brain tissue in response to energetic stress accurately detected only using 3D EM reconstruction argues for a major role of mitochondrial dynamics in regulating neuronal survival. PMID:26729583

  18. Student perceptions of sudden cardiac arrest: a qualitative inquiry.

    Science.gov (United States)

    McDonough, Annette; Callan, Krista; Egizio, Katelyn; Kenney, Kaye; Gray, Gillian; Mundry, Gillian; Re, Gillian

    Sudden cardiac arrest (SCA) is the number one cause of death in young athletes in high school and university settings. Survival and outcomes of SCA is dependent on appropriate recognition of symptoms and immediate cardiopulmonary resuscitation (CPR), along with a shock from an automatic external defibrillator (AED). The three aims of the authors' study presented in this article were: to describe university students' perceptions and beliefs about sudden cardiac arrest, to describe university students' understanding of an AED and their level of preparedness to recognize and respond to a life threatening emergency event, and to identify university students' experiences of responding to handling life-threatening emergency events. Qualitative methodology was employed using semi-structured interviews and thematic analysis. Three major themes emerged from data analysis: confusion, uncertainty, and fear/uncomfortableness. These themes characterised participant's perceptions about SCA. The authors concluded that a lack of understanding of what SCA is and participants' inability to respond to an emergency event was evident. PMID:22585265

  19. Variation in Out-of-Hospital Cardiac Arrest Management

    Directory of Open Access Journals (Sweden)

    Jason M. Jones

    2016-01-01

    Full Text Available Objective. To evaluate variation in airway management strategies in one suburban emergency medical services system treating patients experiencing out-of-hospital cardiac arrest (OHCA. Method. Retrospective chart review of all adult OHCA resuscitation during a 13-month period, specifically comparing airway management decisions. Results. Paramedics demonstrated considerable variation in their approaches to airway management. Approximately half of all OHCA patients received more than one airway management attempt (38/77 [49%], and one-quarter underwent three or more attempts (25/77 [25%]. One-third of patients arrived at the emergency department with a different airway device than initially selected (25/77 [32%]. Conclusion. This study confirmed our hypothesis that paramedics’ selection of ventilation strategies in cardiac arrest varies considerably. This observation raises concern because airway management diverts time and energy from interventions known to improve outcomes in OHCA management, such as cardiopulmonary resuscitation and defibrillation. More research is needed to identify more focused airway management strategies for prehospital care providers.

  20. Experience with bretylium tosylate by a hospital cardiac arrest team.

    Science.gov (United States)

    Holder, D A; Sniderman, A D; Fraser, G; Fallen, E L

    1977-03-01

    The effect of bretylium tosylate (BT) was determined in 27 consecutive cases of resistant ventricular fibrillation (VF) encountered by a hospital cardiac arrest team. The VF was sustained and completely resistant to multiple injections of lidocaine, sequential DC shocks at 400 watt-sec and one or a combination of intravenous propranolol, diphenylhydantoin or procainamide. Following 30 min of sustained cardiac massage, BT (5 mg/kg i.v.) was administered. In 20 patients, VF was terminated within 9-12 min after DC shock. Eight of these patients failed to recover while 12 (44%) of all patients resuscitated survived to be discharged from hospital. Eleven out of 20 (55%) of all patients who had a cardiac arrest outside the CCU were survivors; only one out of seven in the CCU were successfully resuscitated. While receiving maintanance BT post-resuscitation (5 mg/kg i.m. q 8-12 hrs x 48 hrs), half the patients developed hypotension and three required vasopressors and/or fluid replacement. The data indicate that BT is a useful agent in patients with sustained VF refractory to repeated lidocaine injections, some other antiarrhythmic agents, and multiple DC shocks. PMID:837490

  1. Non-equilibrium theory of arrested spinodal decomposition

    Energy Technology Data Exchange (ETDEWEB)

    Olais-Govea, José Manuel; López-Flores, Leticia; Medina-Noyola, Magdaleno [Instituto de Física “Manuel Sandoval Vallarta,” Universidad Autónoma de San Luis Potosí, Álvaro Obregón 64, 78000 San Luis Potosí, SLP (Mexico)

    2015-11-07

    The non-equilibrium self-consistent generalized Langevin equation theory of irreversible relaxation [P. E. Ramŕez-González and M. Medina-Noyola, Phys. Rev. E 82, 061503 (2010); 82, 061504 (2010)] is applied to the description of the non-equilibrium processes involved in the spinodal decomposition of suddenly and deeply quenched simple liquids. For model liquids with hard-sphere plus attractive (Yukawa or square well) pair potential, the theory predicts that the spinodal curve, besides being the threshold of the thermodynamic stability of homogeneous states, is also the borderline between the regions of ergodic and non-ergodic homogeneous states. It also predicts that the high-density liquid-glass transition line, whose high-temperature limit corresponds to the well-known hard-sphere glass transition, at lower temperature intersects the spinodal curve and continues inside the spinodal region as a glass-glass transition line. Within the region bounded from below by this low-temperature glass-glass transition and from above by the spinodal dynamic arrest line, we can recognize two distinct domains with qualitatively different temperature dependence of various physical properties. We interpret these two domains as corresponding to full gas-liquid phase separation conditions and to the formation of physical gels by arrested spinodal decomposition. The resulting theoretical scenario is consistent with the corresponding experimental observations in a specific colloidal model system.

  2. Imaging Bone Morphogenetic Protein 7 Induced Cell Cycle Arrest in Experimental Gliomas

    Directory of Open Access Journals (Sweden)

    Anke Klose

    2011-03-01

    Full Text Available Bone morphogenetic protein 7 (BMP-7 belongs to the superfamily of transforming growth factor β-like cytokines, which can act either as tumor suppressors or as tumor promoters depending on cell type and differentiation. Our investigations focused on analyzing the effects of BMP-7 during glioma cell proliferation in vitro and in vivo. BMP-7 treatment decreased the proliferation of Gli36ΔEGFR-LITG glioma cells up to 50%through a cell cycle arrest in the G1 phase but not by induction of apoptosis. This effect was mediated by the modulation of the expression and phosphorylation of cyclin-dependent kinase 2, cyclin-dependent kinase inhibitor p21, and downstream retinoblastoma protein. Furthermore, in vivo optical imaging of luciferase activity of Gli36ΔEGFR-LITG cells implanted intracranially into nude mice in the presence or absence of BMP-7 treatment corroborated the antiproliferative effects of this cytokine. This report clearly underlines the tumor-suppressive role of BMP-7 in glioma-derived cells. Taken together, our results indicate that manipulating the BMP/transforming growth factor β signaling cascade may serve as a new strategy for imaging-guided molecular-targeted therapy of malignant gliomas.

  3. Wogonin induced G1 cell cycle arrest by regulating Wnt/β-catenin signaling pathway and inactivating CDK8 in human colorectal cancer carcinoma cells

    International Nuclear Information System (INIS)

    Highlights: • Wogonin inhibited HCT116 cells growth and arrested at G1 phase of the cell cycle. • Wogonin down-regulated the canonical Wnt/β-catenin signaling pathway. • Wogonin interfered in the combination of β-catenin and TCF/Lef. • Wogonin limited the kinase activity of CDK8. - Abstract: Wogonin, a naturally occurring mono-flavonoid, has been reported to have tumor therapeutic potential and good selectivity both in vitro and in vivo. Herein, we investigated the anti-proliferation effects and associated mechanisms of wogonin in human colorectal cancer in vitro. The flow-cytometric analysis showed that wogonin induced a G1 phase cell cycle arrest in HCT116 cells in a concentration- and time-dependent manner. Meanwhile, the cell cycle-related proteins, such as cyclin A, E, D1, and CDK2, 4 were down-regulated in wogonin-induced G1 cell cycle arrest. Furthermore, we showed that the anti-proliferation and G1 arrest effect of wogonin on HCT116 cells was associated with deregulation of Wnt/β-catenin signaling pathway. Wogonin-treated cells showed decreased intracellular levels of Wnt proteins, and activated degradation complex to phosphorylated and targeted β-catenin for proteasomal degradation. Wogonin inhibited β-catenin-mediated transcription by interfering in the transcriptional activity of TCF/Lef, and repressing the kinase activity of CDK8 which has been considered as an oncogene involving in the development of colorectal cancers. Moreover, CDK8 siRNA-transfected HCT116 cells showed similar results to wogonin treated cells. Thus, our data suggested that wogonin induced anti-proliferation and G1 arrest via Wnt/β-catenin signaling pathway and it can be developed as a therapeutic agent against human colorectal cancer

  4. Overexpression of USF Increases TGF-β1 Protein Levels, But G1 Phase Arrest was not Induced in FRTL-5 Cells

    OpenAIRE

    Kim, Keun-Sook; Jung, Hye Seung; Chung, Yun Jae; Jung, Tae Sik; Jang, Hye Won; Lee, Myung-Shik; Kim, Kwang-Won; Chung, Jae Hoon

    2008-01-01

    Transforming growth factor-β1 (TGF-β1) is a potent inhibitor of cellular growth and proliferation by G1 phase arrest or apoptosis. We investigated the association of TGF-β1 with the anti-proliferative effect of upstream stimulatory factor (USF) in Fischer rat thyroid cell line (FRTL-5) cells. [Methyl-3H] thymidine uptake was measured after treatment of FRTL-5 cells with TGF-β1 to identify its anti-proliferative effect. USF-1 and USF-2 proteins were in vitro translated, and an electrophoretic ...

  5. Effects of allitridi on cell cycle arrest of human gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Min-Wen Ha; Rui Ma; Li-Ping Shun; Yue-Hua Gong; Yuan Yuan

    2005-01-01

    AIM: To determine the effect of allitridi on cell cycle of human gastric cancer (HGC) cell lines MGC803 and SGC7901 and its possible mechanism.METHODS: Trypan blue dye exclusion was used to evaluate the proliferation, inhibition of cells and damages of these cells were detected with electron microscope.Flow cytometry and cell mitotic index were used to analyze the change of cell cycle, immunohistochemistry, and RT-PCR was used to examine expression of the p21WAF1 gene.RESULTS: MGC803 cell growth was inhibited by allitridi with 24 h IC50 being 6.4 μg/mL. SGC7901 cell growth was also inhibited by allitridi with 24 h IC50 being 7.3 μg/mL.After being treated with allitridi at the concentration of 12 μg/mL for 24 h, cells were found to have direct cytotoxic effects, including broken cellular membrane, swollen and vesiculated mitochondria and rough endoplasmic reticula,and mass lipid droplet. When cells were treated with allitridi at the concentration of 3, 6, and 9 μg/mL for 24 h, the percentage of G0/G1 phase cells was decreased and that of G2/M phase cells was significantly increased (P = 0.002)compared with those in the group. When cells were treated with allitridi at the concentration of 6 μg/mL, cell mitotic index was much higher (P = 0.003) than that of control group, indicating that allitridi could cause gastric cancer cell arrest in M phase. Besides, the expression levels of p21WAF1 gene of MGC803 cells and p21WAF1 gene of SGC7901 cells were remarkably upregulated after treatment.CONCLUSION: Allitridi can cause gastric cancer cell arrest in M phase, and this may be one of the mechanisms for inhibiting cell proliferation. Effect of allitridi on cells in M phas e may be associated with the upregulation of p21WAF1 genes. This study provides experimental data for clinical use of allitridi in the treatment of gastric carcinoma.

  6. Characterization of microsporidia-induced developmental arrest and a transmembrane leucine-rich repeat protein in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Robert J Luallen

    Full Text Available Microsporidia comprise a highly diverged phylum of intracellular, eukaryotic pathogens, with some species able to cause life-threatening illnesses in immunocompromised patients. To better understand microsporidian infection in animals, we study infection of the genetic model organism Caenorhabditis elegans and a species of microsporidia, Nematocida parisii, which infects Caenorhabditis nematodes in the wild. We conducted a targeted RNAi screen for host C. elegans genes important for infection and growth of N. parisii, using nematode larval arrest as an assay for infection. Here, we present the results of this RNAi screen, and our analyses on one of the RNAi hits from the screen that was ultimately not corroborated by loss of function mutants. This hit was an RNAi clone against F56A8.3, a conserved gene that encodes a transmembrane protein containing leucine-rich repeats (LRRs, a domain found in numerous pathogen receptors from other systems. This RNAi clone caused C. elegans to be resistant to infection by N. parisii, leading to reduced larval arrest and lower pathogen load. Characterization of the endogenous F56A8.3 protein revealed that it is expressed in the intestine, localized to the membrane around lysosome-related organelles (LROs, and exists in two different protein isoforms in C. elegans. We used the CRISPR-Cas9 system to edit the F56A8.3 locus and created both a frameshift mutant resulting in a truncated protein and a complete knockout mutant. Neither of these mutants was able to recapitulate the infection phenotypes of the RNAi clone, indicating that the RNAi-mediated phenotypes are due to an off-target effect of the RNAi clone. Nevertheless, this study describes microsporidia-induced developmental arrest in C. elegans, presents results from an RNAi screen for host genes important for microsporidian infection, and characterizes aspects of the conserved F56A8.3 gene and its protein product.

  7. Characterization of microsporidia-induced developmental arrest and a transmembrane leucine-rich repeat protein in Caenorhabditis elegans.

    Science.gov (United States)

    Luallen, Robert J; Bakowski, Malina A; Troemel, Emily R

    2015-01-01

    Microsporidia comprise a highly diverged phylum of intracellular, eukaryotic pathogens, with some species able to cause life-threatening illnesses in immunocompromised patients. To better understand microsporidian infection in animals, we study infection of the genetic model organism Caenorhabditis elegans and a species of microsporidia, Nematocida parisii, which infects Caenorhabditis nematodes in the wild. We conducted a targeted RNAi screen for host C. elegans genes important for infection and growth of N. parisii, using nematode larval arrest as an assay for infection. Here, we present the results of this RNAi screen, and our analyses on one of the RNAi hits from the screen that was ultimately not corroborated by loss of function mutants. This hit was an RNAi clone against F56A8.3, a conserved gene that encodes a transmembrane protein containing leucine-rich repeats (LRRs), a domain found in numerous pathogen receptors from other systems. This RNAi clone caused C. elegans to be resistant to infection by N. parisii, leading to reduced larval arrest and lower pathogen load. Characterization of the endogenous F56A8.3 protein revealed that it is expressed in the intestine, localized to the membrane around lysosome-related organelles (LROs), and exists in two different protein isoforms in C. elegans. We used the CRISPR-Cas9 system to edit the F56A8.3 locus and created both a frameshift mutant resulting in a truncated protein and a complete knockout mutant. Neither of these mutants was able to recapitulate the infection phenotypes of the RNAi clone, indicating that the RNAi-mediated phenotypes are due to an off-target effect of the RNAi clone. Nevertheless, this study describes microsporidia-induced developmental arrest in C. elegans, presents results from an RNAi screen for host genes important for microsporidian infection, and characterizes aspects of the conserved F56A8.3 gene and its protein product. PMID:25874557

  8. Hellebrigenin induces cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells through inhibition of Akt.

    Science.gov (United States)

    Deng, Li-Juan; Hu, Li-Ping; Peng, Qun-Long; Yang, Xiao-Lin; Bai, Liang-Liang; Yiu, Anita; Li, Yong; Tian, Hai-Yan; Ye, Wen-Cai; Zhang, Dong-Mei

    2014-08-01

    Hellebrigenin, one of bufadienolides belonging to cardioactive steroids, was found in skin secretions of toads and plants of Helleborus and Kalanchoe genera. In searching for natural constituents with anti-hepatoma activities, we found that hellebrigenin, isolated from traditional Chinese medicine Venenum Bufonis, potently reduced the viability and colony formation of human hepatocellular carcinoma cells HepG2, and went on to explore the underlying molecular mechanisms. Our results demonstrated that hellebrigenin triggered DNA damage through DNA double-stranded breaks and subsequently induced cell cycle G2/M arrest associated with up-regulation of p-ATM (Ser(1981)), p-Chk2 (Tyr(68)), p-CDK1 (Tyr(15)) and Cyclin B1, and down-regulation of p-CDC25C (Ser(216)). It was also found that hellebrigenin induced mitochondrial apoptosis, characterized by Bax translocation to mitochondria, disruption of mitochondrial membrane potential, release of cytochrome c into cytosol and sequential activation of caspases and PARP. In addition, Akt expression and phosphorylation were inhibited by hellebrigenin, whereas Akt silencing with siRNA significantly blocked cell cycle arrest but enhanced apoptosis induced by hellebrigenin. Activation of Akt by human insulin-like growth factor I (hIGF-I) could obviously attenuate hellebrigenin-induced cell death. In summary, our study is the first to report the efficacy of hellebrigenin against HepG2 and elucidated its molecular mechanisms including DNA damage, mitochondria collapse, cell cycle arrest and apoptosis, which will contribute to the development of hellebrigenin into a chemotherapeutic agent in the treatment of liver cancer. PMID:24954031

  9. 33 CFR Appendix A to Part 154 - Guidelines for Detonation Flame Arresters

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Guidelines for Detonation Flame... Appendix A to Part 154—Guidelines for Detonation Flame Arresters This appendix contains the draft ASTM standard for detonation flame arresters. Devices meeting this standard will be accepted by the...

  10. 38 CFR 3.375 - Determination of inactivity (complete arrest) in tuberculosis.

    Science.gov (United States)

    2010-07-01

    ... inactivity (complete arrest) in tuberculosis. 3.375 Section 3.375 Pensions, Bonuses, and Veterans' Relief...) in tuberculosis. (a) Pulmonary tuberculosis. A veteran shown to have had pulmonary tuberculosis will...) Nonpulmonary disease. Determination of complete arrest of nonpulmonary tuberculosis requires absence...

  11. Program Completion and Re-Arrest in a Batterer Intervention System

    Science.gov (United States)

    Bennett, Larry W.; Stoops, Charles; Call, Christine; Flett, Heather

    2007-01-01

    Objective: The authors examine the effects of batterer intervention program (BIP) completion on domestic violence re-arrest in an urban system of 30 BIPs with a common set of state standards, common program completion criteria, and centralized criminal justice supervision. Method: 899 men arrested for domestic violence were assessed and completed…

  12. 46 CFR 30.10-63 - Spark arrester-TB/ALL.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Spark arrester-TB/ALL. 30.10-63 Section 30.10-63...-63 Spark arrester—TB/ALL. The term spark arrester means any device, assembly, or method of a... sparks in exhaust pipes from internal combustion engines....

  13. Mutations in the Kv1.5 channel gene KCNA5 in cardiac arrest patients

    DEFF Research Database (Denmark)

    Nielsen, Nathalie H; Winkel, Bo G; Kanters, Jørgen K; Schmitt, Nicole; Hofman-Bang, Jacob; Jensen, Henrik S; Bentzen, Bo H; Sigurd, Bjarne; Larsen, Lars Allan; Andersen, Paal S; Kjeldsen, Keld; Grunnet, Morten; Christiansen, Michael; Olesen, Søren-Peter; Haunsø, Stig

    2007-01-01

    Mutations in one of the ion channels shaping the cardiac action potential can lead to action potential prolongation. However, only in a minority of cardiac arrest cases mutations in the known arrhythmia-related genes can be identified. In two patients with arrhythmia and cardiac arrest, we identi...

  14. Same-Sex and Race-Based Disparities in Statutory Rape Arrests.

    Science.gov (United States)

    Chaffin, Mark; Chenoweth, Stephanie; Letourneau, Elizabeth J

    2016-01-01

    This study tests a liberation hypothesis for statutory rape incidents, specifically that there may be same-sex and race/ethnicity arrest disparities among statutory rape incidents and that these will be greater among statutory rape than among forcible sex crime incidents. 26,726 reported incidents of statutory rape as defined under state statutes and 96,474 forcible sex crime incidents were extracted from National Incident-Based Reporting System data sets. Arrest outcomes were tested using multilevel modeling. Same-sex statutory rape pairings were rare but had much higher arrest odds. A victim-offender romantic relationship amplified arrest odds for same-sex pairings, but damped arrest odds for male-on-female pairings. Same-sex disparities were larger among statutory than among forcible incidents. Female-on-male incidents had uniformly lower arrest odds. Race/ethnicity effects were smaller than gender effects and more complexly patterned. The findings support the liberation hypothesis for same-sex statutory rape arrest disparities, particularly among same-sex romantic pairings. Support for race/ethnicity-based arrest disparities was limited and mixed. PMID:25416040

  15. A Summary and Analysis of Warrantless Arrest Statutes for Domestic Violence in the United States

    Science.gov (United States)

    Zeoli, April M.; Norris, Alexis; Brenner, Hannah

    2011-01-01

    In the United States, all 50 states and the District of Columbia have enacted statutes that allow police officers to make warrantless arrests for domestic violence given probable cause; however, state laws differ from one another in multiple, important ways. Research on domestic violence warrantless arrest laws rarely describe them as anything…

  16. [Thoracic lavage and open cardiac massage as treatment of hypothermic cardiac arrest--case report].

    Science.gov (United States)

    Koponen, Timo; Vänni, Ville; Kettunen, Minna; Reinikainen, Matti; Hakala, Tapio

    2016-01-01

    Cardiopulmonary bypass is the treatment of choice for a severely hypothermic patient with cardiac arrest. However, the treatment is not always available. We describe a successful three-and-a-half hour resuscitation of a hypothermic cardiac arrest patient with manual chest compressions followed by open cardiac massage and rewarming with thoracic lavage. PMID:27188092

  17. [Cardiopulmonary resuscitation and post-cardiac arrest brain injury].

    Science.gov (United States)

    Sakurai, Atsushi

    2016-02-01

    One of the most important topics in the field of resuscitation at present is the drafting of the 2015 version of the Consensus on Science and Treatment Recommendation (CoSTR) by the International Liaison Committee on Resuscitation. The Japan Resuscitation Council is preparing its 2015 Guideline based on this CoSTR and plans to release it in October 2015. A critical change in the upcoming CoSTR is the adoption of the GRADE system. The new Guideline incorporating the GRADE system will surely be more scientific than the previous Guideline issued in 2010. Meanwhile, an important finding appeared in a report from Nielsen et al.: hypothermia at a targeted temperature of 33 degrees C did not confer a benefit versus 36 degrees in unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause. PMID:26915250

  18. A Unique Case of Cardiac Arrest following K2 Abuse

    Directory of Open Access Journals (Sweden)

    Saif Ibrahim

    2014-01-01

    Full Text Available Sudden cardiac death (SCD accounts for up to 450,000 deaths every year in the United States (Zipes et al. (2006. Most cases of sudden cardiac death occur in subjects with no prior history of heart disease (Myerburg et al. (1998. The incidence of sudden death in a general population has been shown to increase contemporaneously with substance abuse (Phillips et al. (1999. The causative association of sudden death with cocaine, methadone, and volatile agents is well established (Adgey et al. (1995 and Isner et al. (1986. We describe a case of out-of-hospital cardiac arrest temporally related to abuse of the synthetic cannabinoid street drug known as K2. To our knowledge, there are no previously documented cases of sudden cardiac death associated with synthetic cannabinoids although they have been linked to myocardial infarction in teenagers despite normal coronary angiography (Mir et al. (2011.

  19. Dynamical Arrest, Structural Disorder, and Optimization of Organic Photovoltaic Devices

    Energy Technology Data Exchange (ETDEWEB)

    Gould, Ian; Dmitry, Matyushov

    2014-09-11

    This project describes fundamental experimental and theoretical work that relates to charge separation and migration in the solid, heterogeneous or aggregated state. Marcus theory assumes a system in equilibrium with all possible solvent (dipolar) configurations, with rapid interconversion among these on the ET timescale. This project has addressed the more general situation where the medium is at least partially frozen on the ET timescale, i.e. under conditions of dynamical arrest. The approach combined theory and experiment and includes: (1) Computer simulations of model systems, (2) Development of analytical procedures consistent with computer experiment and (3) Experimental studies and testing of the formal theories on this data. Electron transfer processes are unique as a consequence of the close connection between kinetics, spectroscopy and theory, which is an essential component of this work.

  20. Anaphylactic shock and cardiac arrest caused by thiamine infusion.

    Science.gov (United States)

    Juel, Jacob; Pareek, Manan; Langfrits, Christian Sigvald; Jensen, Svend Eggert

    2013-01-01

    Parenteral thiamine has a very high safety profile. The most common adverse effect is local irritation; however, anaphylactic or anaphylactoid reactions may occur, mostly related to intravenous administration. We describe a 44-year-old man, a chronic alcoholic, who was admitted with alcohol intoxication and developed cardiac arrest due to anaphylactic shock following intravenous thiamine infusion. The patient was successfully resuscitated after 15 min and repeated epinephrine administrations. He was discharged in good health after 14 days. This case report emphasises both the importance of recognising the symptoms of anaphylaxis and the fact that facilities for treating anaphylaxis and cardiopulmonary resuscitation should be available when thiamine or for that matter, any drug is given in-hospital. PMID:23853017

  1. Cardiopulmonary arrest induced by anaphylactoid reaction with contrast media.

    Science.gov (United States)

    Nakamura, Iwao; Hori, Shingo; Funabiki, Tomohiro; Sekine, Kazuhiko; Kimura, Hiroyuki; Fujishima, Seitaro; Aoki, Katsunori; Kuribayashi, Sachio; Aikawa, Naoki

    2002-05-01

    Anaphylactoid reactions to iodinated contrast media can cause life-threatening events and even death. A 44-year-old woman presented with cardiopulmonary arrest (CPA) immediately following the administration of nonionic iodinated contrast media for an intravenous pyelography. Her cardiac rhythm during CPA was asystole. She was successfully resuscitated by the radiologists supported by paged emergency physicians using the prompt intravenous administration of 1 mg of epinephrine. Neither laryngeal edema nor bronchial spasm was observed during the course of treatment, and she was discharged on the 4th day without any complications. The patient did not have a history of allergy, but had experienced a myocardial infarction and aortitis. She had undergone 11 angiographies and had been taking a beta-adrenergic receptor antagonist. Planned emergency medical backup is advisable to ensure resuscitation in the event of an anaphylactoid reaction to the use of contrast media in-hospital settings. PMID:12009227

  2. Cardiac arrest due to airway obstruction in hereditary angioedema.

    Science.gov (United States)

    Fuse, Takashi; Nakada, Taka-aki; Taniguchi, Masashi; Mizushima, Yasuaki; Matsuoka, Tetsuya

    2015-12-01

    Hereditary angioedema (HAE) is a rare genetic disease caused by a deficiency of functional C1 esterase inhibitor that causes swelling attacks in various body tissues. We hereby report a case of out-of-hospital cardiac arrest due to airway obstruction in HAE. Cutaneous swelling and abdominal pain attacks caused by gastrointestinal wall swelling are common symptoms in HAE, whereas laryngeal swelling is rare. Emergency physicians may have few chances to experience cases of life-threatening laryngeal edema resulting in a delay from symptom onset to the diagnosis of HAE. Hereditary angioedema is diagnosed by performing complement blood tests. Because safe and effective treatment options are available for the life-threatening swellings in HAE, the diagnosis potentially reduces the risk of asphyxiation in patients and their blood relatives. PMID:25913082

  3. Opiate Withdrawal Complicated by Tetany and Cardiac Arrest

    Directory of Open Access Journals (Sweden)

    Irfanali R. Kugasia

    2014-01-01

    Full Text Available Patients with symptoms of opiate withdrawal, after the administration of opiate antagonist by paramedics, are a common presentation in the emergency department of hospitals. Though most of opiate withdrawal symptoms are benign, rarely they can become life threatening. This case highlights how a benign opiate withdrawal symptom of hyperventilation led to severe respiratory alkalosis that degenerated into tetany and cardiac arrest. Though this patient was successfully resuscitated, it is imperative that severe withdrawal symptoms are timely identified and immediate steps are taken to prevent catastrophes. An easier way to reverse the severe opiate withdrawal symptom would be with either low dose methadone or partial opiate agonists like buprenorphine. However, if severe acid-base disorder is identified, it would be safer to electively intubate these patients for better control of their respiratory and acid-base status.

  4. Making Food Protein Gels via an Arrested Spinodal Decomposition.

    Science.gov (United States)

    Mahmoudi, Najet; Stradner, Anna

    2015-12-17

    We report an investigation of the structural and dynamic properties of mixtures of food colloid casein micelles and low molecular weight poly(ethylene oxide). A combination of visual observations, confocal laser scanning microscopy, diffusing wave spectroscopy, and oscillatory shear rheometry is used to characterize the state diagram of the mixtures and describe the structural and dynamic properties of the resulting fluid and solid-like structures. We demonstrate the formation of gel-like structures through an arrested spinodal decomposition mechanism. We discuss our observations in view of previous experimental and theoretical studies with synthetic and food colloids, and comment on the potential of such a route toward gels for food processing. PMID:26595592

  5. Electronic registration of out-of-hospital cardiac arrests

    DEFF Research Database (Denmark)

    Nielsen, Niels Dalsgaard; Dahl, Michael; Gade, John;

    2007-01-01

    patients according to whether they received first aid, the identity of the first aid provider and the initial cardiac rhythm as diagnosed by the patient monitor.   Results: 18,666 patients where in contact with an emergency ambulance in the study period. Of those 296 (89/100,000/year) met the definition of...... cardiac arrest. 83 of those (28 %) received first aid. The first aid was provided by layman (68 %), physicians (11 %), nurses (11 %) and first-aiders (4 %). In 6 % the identity of the first aid provider was unknown. The majority of the patients (n = 177 (58 %)) had asystole upon ambulance arrival. 37 (12...... considerably higher incidence rate for OHCA, than documented by the analogue nationwide registry. Further we discovered a high rate of first aid to OHCA-patients. Finally our data showed a high occurence of asystolia in patients who met the official criteria for OHCA....

  6. Standardized EEG interpretation accurately predicts prognosis after cardiac arrest

    DEFF Research Database (Denmark)

    Westhall, Erik; Rossetti, Andrea O; van Rootselaar, Anne-Fleur; Wesenberg Kjaer, Troels; Horn, Janneke; Ullén, Susann; Friberg, Hans; Nielsen, Niklas; Rosén, Ingmar; Åneman, Anders; Erlinge, David; Gasche, Yvan; Hassager, Christian; Hovdenes, Jan; Kjaergaard, Jesper; Kuiper, Michael; Pellis, Tommaso; Stammet, Pascal; Wanscher, Michael; Wetterslev, Jørn; Wise, Matt P; Cronberg, Tobias

    2016-01-01

    OBJECTIVE: To identify reliable predictors of outcome in comatose patients after cardiac arrest using a single routine EEG and standardized interpretation according to the terminology proposed by the American Clinical Neurophysiology Society. METHODS: In this cohort study, 4 EEG specialists......, blinded to outcome, evaluated prospectively recorded EEGs in the Target Temperature Management trial (TTM trial) that randomized patients to 33°C vs 36°C. Routine EEG was performed in patients still comatose after rewarming. EEGs were classified into highly malignant (suppression, suppression with...... periodic discharges, burst-suppression), malignant (periodic or rhythmic patterns, pathological or nonreactive background), and benign EEG (absence of malignant features). Poor outcome was defined as best Cerebral Performance Category score 3-5 until 180 days. RESULTS: Eight TTM sites randomized 202...

  7. Deficiency of G1 regulators P53, P21Cip1 and/or pRb decreases hepatocyte sensitivity to TGFβ cell cycle arrest

    International Nuclear Information System (INIS)

    TGFβ is critical to control hepatocyte proliferation by inducing G1-growth arrest through multiple pathways leading to inhibition of E2F transcription activity. The retinoblastoma protein pRb is a key controller of E2F activity and G1/S transition which can be inhibited in viral hepatitis. It is not known whether the impairment of pRb would alter the growth inhibitory potential of TGFβ in disease. We asked how Rb-deficiency would affect responses to TGFβ-induced cell cycle arrest. Primary hepatocytes isolated from Rb-floxed mice were infected with an adenovirus expressing CRE-recombinase to delete the Rb gene. In control cells treatment with TGFβ prevented cells to enter S phase via decreased cMYC activity, activation of P16INK4A and P21Cip and reduction of E2F activity. In Rb-null hepatocytes, cMYC activity decreased slightly but P16INK4A was not activated and the great majority of cells continued cycling. Rb is therefore central to TGFβ-induced cell cycle arrest in hepatocytes. However some Rb-null hepatocytes remained sensitive to TGFβ-induced cell cycle arrest. As these hepatocytes expressed very high levels of P21Cip1 and P53 we investigated whether these proteins regulate pRb-independent signaling to cell cycle arrest by evaluating the consequences of disruption of p53 and p21Cip1. Hepatocytes deficient in p53 or p21Cip1 showed diminished growth inhibition by TGFβ. Double deficiency had a similar impact showing that in cells containing functional pRb; P21Cip and P53 work through the same pathway to regulate G1/S in response to TGFβ. In Rb-deficient cells however, p53 but not p21Cip deficiency had an additive effect highlighting a pRb-independent-P53-dependent effector pathway of inhibition of E2F activity. The present results show that otherwise genetically normal hepatocytes with disabled p53, p21Cip1 or Rb genes respond less well to the antiproliferative effects of TGFβ. As the function of these critical cellular proteins can be impaired by common

  8. Deficiency of G1 regulators P53, P21Cip1 and/or pRb decreases hepatocyte sensitivity to TGFβ cell cycle arrest

    Directory of Open Access Journals (Sweden)

    Harrison David J

    2007-11-01

    Full Text Available Abstract Background TGFβ is critical to control hepatocyte proliferation by inducing G1-growth arrest through multiple pathways leading to inhibition of E2F transcription activity. The retinoblastoma protein pRb is a key controller of E2F activity and G1/S transition which can be inhibited in viral hepatitis. It is not known whether the impairment of pRb would alter the growth inhibitory potential of TGFβ in disease. We asked how Rb-deficiency would affect responses to TGFβ-induced cell cycle arrest. Results Primary hepatocytes isolated from Rb-floxed mice were infected with an adenovirus expressing CRE-recombinase to delete the Rb gene. In control cells treatment with TGFβ prevented cells to enter S phase via decreased cMYC activity, activation of P16INK4A and P21Cip and reduction of E2F activity. In Rb-null hepatocytes, cMYC activity decreased slightly but P16INK4A was not activated and the great majority of cells continued cycling. Rb is therefore central to TGFβ-induced cell cycle arrest in hepatocytes. However some Rb-null hepatocytes remained sensitive to TGFβ-induced cell cycle arrest. As these hepatocytes expressed very high levels of P21Cip1 and P53 we investigated whether these proteins regulate pRb-independent signaling to cell cycle arrest by evaluating the consequences of disruption of p53 and p21Cip1. Hepatocytes deficient in p53 or p21Cip1 showed diminished growth inhibition by TGFβ. Double deficiency had a similar impact showing that in cells containing functional pRb; P21Cip and P53 work through the same pathway to regulate G1/S in response to TGFβ. In Rb-deficient cells however, p53 but not p21Cip deficiency had an additive effect highlighting a pRb-independent-P53-dependent effector pathway of inhibition of E2F activity. Conclusion The present results show that otherwise genetically normal hepatocytes with disabled p53, p21Cip1 or Rb genes respond less well to the antiproliferative effects of TGFβ. As the function of

  9. Standardized EEG interpretation accurately predicts prognosis after cardiac arrest

    Science.gov (United States)

    Rossetti, Andrea O.; van Rootselaar, Anne-Fleur; Wesenberg Kjaer, Troels; Horn, Janneke; Ullén, Susann; Friberg, Hans; Nielsen, Niklas; Rosén, Ingmar; Åneman, Anders; Erlinge, David; Gasche, Yvan; Hassager, Christian; Hovdenes, Jan; Kjaergaard, Jesper; Kuiper, Michael; Pellis, Tommaso; Stammet, Pascal; Wanscher, Michael; Wetterslev, Jørn; Wise, Matt P.; Cronberg, Tobias

    2016-01-01

    Objective: To identify reliable predictors of outcome in comatose patients after cardiac arrest using a single routine EEG and standardized interpretation according to the terminology proposed by the American Clinical Neurophysiology Society. Methods: In this cohort study, 4 EEG specialists, blinded to outcome, evaluated prospectively recorded EEGs in the Target Temperature Management trial (TTM trial) that randomized patients to 33°C vs 36°C. Routine EEG was performed in patients still comatose after rewarming. EEGs were classified into highly malignant (suppression, suppression with periodic discharges, burst-suppression), malignant (periodic or rhythmic patterns, pathological or nonreactive background), and benign EEG (absence of malignant features). Poor outcome was defined as best Cerebral Performance Category score 3–5 until 180 days. Results: Eight TTM sites randomized 202 patients. EEGs were recorded in 103 patients at a median 77 hours after cardiac arrest; 37% had a highly malignant EEG and all had a poor outcome (specificity 100%, sensitivity 50%). Any malignant EEG feature had a low specificity to predict poor prognosis (48%) but if 2 malignant EEG features were present specificity increased to 96% (p < 0.001). Specificity and sensitivity were not significantly affected by targeted temperature or sedation. A benign EEG was found in 1% of the patients with a poor outcome. Conclusions: Highly malignant EEG after rewarming reliably predicted poor outcome in half of patients without false predictions. An isolated finding of a single malignant feature did not predict poor outcome whereas a benign EEG was highly predictive of a good outcome. PMID:26865516

  10. Arrest as a General Property of the Supercooled Liquid State.

    Science.gov (United States)

    Sluyters, Jan H; Sluyters-Rehbach, Margaretha

    2016-04-21

    Owing to the universal presence of intermolecular interactions, it has to be expected that at some well-defined lower temperature a liquid loses its dynamic properties like fluidity and self-diffusion. As a sequel to two earlier papers on the discovery of such an arrest temperature T0 for supercooled water at 243 K, where also the coexisting vapor pressure was found to become zero, in this paper a further study is undertaken of the behavior of a selection of other liquids. At first, two simple equations of state (van der Waals and virial) are shown in principle to predict a zero vapor pressure at a finite temperature. The interaction parameters B (second virial coefficient) and μJT (Joule-Thomson coefficient) of the vapor are found to become virtually infinite at a temperature T0,B, with a value equal or close to the T0 derived from the liquid properties. Just as earlier found for water, the latter is obtained by extrapolation of several available dynamic and equilibrium data, which should produce an intersection with the temperature axis at the same T0 value. With the exception of molten salts and liquid pure metals, this condition appears to be fulfilled quite accurately. Thus, the temperature of arrest is a general phenomenon for supercooled liquids. As an illustration, it is shown how the PVT diagram of carbon dioxide can be extended into the supercooled temperature region. It is argued that T0 is the temperature below which the Boltzmann energy, kT, is lower than the minimal energy needed for a molecule to break the interactions with its surrounding molecules. We propose to name this minimal energy, kT0, the multimolecular potential of the liquid object. The relationship of the liquid multimolecular potential with the pair potential, ε, of the molecular species is established for various examples and appears to be a proportionality with ε ≈ 2kT0. PMID:27070201

  11. Cardiac arrest during gamete release in chum salmon regulated by the parasympathetic nerve system.

    Directory of Open Access Journals (Sweden)

    Yuya Makiguchi

    Full Text Available Cardiac arrest caused by startling stimuli, such as visual and vibration stimuli, has been reported in some animals and could be considered as an extraordinary case of bradycardia and defined as reversible missed heart beats. Variability of the heart rate is established as a balance between an autonomic system, namely cholinergic vagus inhibition, and excitatory adrenergic stimulation of neural and hormonal action in teleost. However, the cardiac arrest and its regulating nervous mechanism remain poorly understood. We show, by using electrocardiogram (ECG data loggers, that cardiac arrest occurs in chum salmon (Oncorhynchus keta at the moment of gamete release for 7.39+/-1.61 s in females and for 5.20+/-0.97 s in males. The increase in heart rate during spawning behavior relative to the background rate during the resting period suggests that cardiac arrest is a characteristic physiological phenomenon of the extraordinarily high heart rate during spawning behavior. The ECG morphological analysis showed a peaked and tall T-wave adjacent to the cardiac arrest, indicating an increase in potassium permeability in cardiac muscle cells, which would function to retard the cardiac action potential. Pharmacological studies showed that the cardiac arrest was abolished by injection of atropine, a muscarinic receptor antagonist, revealing that the cardiac arrest is a reflex response of the parasympathetic nerve system, although injection of sotalol, a beta-adrenergic antagonist, did not affect the cardiac arrest. We conclude that cardiac arrest during gamete release in spawning release in spawning chum salmon is a physiological reflex response controlled by the parasympathetic nervous system. This cardiac arrest represents a response to the gaping behavior that occurs at the moment of gamete release.

  12. Pfaffosidic Fraction from Hebanthe paniculata Induces Cell Cycle Arrest and Caspase-3-Induced Apoptosis in HepG2 Cells

    Directory of Open Access Journals (Sweden)

    Tereza Cristina da Silva

    2015-01-01

    Full Text Available Hebanthe paniculata roots (formerly Pfaffia paniculata and popularly known as Brazilian ginseng show antineoplastic, chemopreventive, and antiproliferative properties. Functional properties of these roots and their extracts are usually attributed to the pfaffosidic fraction, which is composed mainly by pfaffosides A–F. However, the therapeutic potential of this fraction in cancer cells is not yet entirely understood. This study aimed to analyze the antitumoral effects of the purified pfaffosidic fraction or saponinic fraction on the human hepatocellular carcinoma HepG2 cell line. Cellular viability, proliferation, and apoptosis were evaluated, respectively, by MTT assay, BrdU incorporation, activated caspase-3 immunocytochemistry, and DNA fragmentation assay. Cell cycle was analyzed by flow cytometry and the cell cycle-related proteins were analyzed by quantitative PCR and Western blot. The cells exposed to pfaffosidic fraction had reduced viability and cellular growth, induced G2/M at 48 h or S at 72 h arrest, and increased sub-G1 cell population via cyclin E downregulation, p27KIP1 overexpression, and caspase-3-induced apoptosis, without affecting the DNA integrity. Antitumoral effects of pfaffosidic fraction from H. paniculata in HepG2 cells originated by multimechanisms of action might be associated with cell cycle arrest in the S phase, by CDK2 and cyclin E downregulation and p27KIP1 overexpression, besides induction of apoptosis through caspase-3 activation.

  13. Histone Modification Is Involved in Okadaic Acid (OA Induced DNA Damage Response and G2-M Transition Arrest in Maize.

    Directory of Open Access Journals (Sweden)

    Hao Zhang

    Full Text Available Histone modifications are involved in regulation of chromatin structure. To investigate the relationship between chromatin modification and cell cycle regulation during plant cell proliferation, Okadaic acid (OA, a specific inhibitor of serine/threonine protein phosphatase, was applied in this study. The results showed that OA caused the cell cycle arrest at preprophase, leading to seedling growth inhibition. Western blotting assay revealed that the spatial distribution of phosphorylation of Ser10 histone H3 tails (H3S10ph signals was altered under OA treatment. Reactive oxygen species (ROS was found to be at higher levels and TdT-mediated dUTP nick end labeling (TUNEL assay displayed DNA breaks happened at the chromatin after treatment with OA, companied with an increase in the acetylation of histone H4 at lysine 5 (H4K5ac level. From these observations, we speculated that the alteration of the spatial distribution of H3S10ph and the level of H4K5ac was involved in the procedure that OA induced DNA breaks and G2-M arrested by the accumulation of ROS, and that the histone H3S10ph and H4K5ac might facilitate DNA repair by their association with the chromatin decondensation.

  14. Antiproliferative effect of rapamycin on human T-cell leukemia cell line Jurkat by cell cycle arrest and telomerase inhibition

    Institute of Scientific and Technical Information of China (English)

    Yan-min ZHAO; Qian ZHOU; Yun XU; Xiao-yu LAI; He HUANG

    2008-01-01

    Aim:To examine the ability of rapamycin to suppress growth and regulate telomerase activity in the human T-cell leukemia cell line Jurkat. Methods:Cell proliferation was assessed after exposure to rapamycin by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle progression and apoptosis were determined by flow cytometry. The proteins important for cell cycle progres-sion and Akt/mammalian target of rapamycin signaling cascade were assessed by Western blotting. Telomerase activity was quantified by telomeric repeat amplication protocol assay. The human telomerase reverse transcriptase (hTERT) mRNA levels were determined by semi-quantitative RT-PCR. Results:Rapamycin inhibited the proliferation of Jurkat, induced G1 phase arrest, unregulated the pro-tein level of p21 as well as p27, and downregulated cyclinD3, phospho-p70s6k, and phospho-s6, but had no effect on apoptosis. Treatment with rapamycin reduced telomerase activity, and reduced hTERT mRNA and protein expression. Conclusion:Rapamycin displayed a potent antileukemic effect in the human T-cell leukemia cell line by inhibition of cell proliferation through G1 cell cycle arrest and also through the suppression of telomerase activity, suggesting that rapamycin may have potential clinical implications in the treatment of some leukemias.

  15. Phytoestrogen bakuchiol exhibits in vitro and in vivo anti-breast cancer effects by inducing S phase arrest and apoptosis

    Directory of Open Access Journals (Sweden)

    Li eLi

    2016-05-01

    Full Text Available Phytoestrogen has been proposed as an alternative to hormone replacement therapy, which has been demonstrated to promote a high risk of breast cancer. However, the effect of phytoestrogen on breast cancer development has not been fully understood. Bakuchiol is an active ingredient of a traditional Chinese herbal medicine Fructus Psoraleae, the dried ripe fruit of Psoralea corylifolia L. (Fabaceae. The in vitro and in vivo estrogenic activities and anti-breast cancer effects of bakuchiol have not been well studied. We found that bakuchiol induced the GFP expression in transgenic medaka (Oryzias melastigma, Tg, Chg:GFP dose-dependently (0-1 µg/ml, demonstrating its in vivo estrogenic activity. Low dose of bakuchiol (1 µg/ml induced the cell proliferation and ERα expression in MCF-7 cells, which could be blocked by the antiestrogen ICI 182780, suggesting the in vitro estrogenic activity of bakuchiol. Our data indicated that high doses of bakuchiol (>2 µg/ml inhibited breast cancer cell growth, with a stronger antiproliferative effect than resveratrol, a widely studied analogue of bakuchiol. High doses of bakuchiol (4 µg/ml, 7 µg/ml and 10 µg/ml were used for the further in vitro anti-breast cancer studies. Bakuchiol induced ERβ expression and suppressed ERα expression in MCF-7 cells. It also induced S phase arrest in both MCF-7 and MDA-MB-231 cells, which could be rescued by caffeine. Knock-down of p21 also marginally rescued S phase arrest in MCF-7 cells. The S phase arrest was accompanied by the upregulation of ATM, P-Cdc2 (Tyr15, Myt1, P-Wee1 (Ser642, p21 and Cyclin B1, suggesting that blocking of Cdc2 activation may play an important role in bakuchiol-induced S phase arrest. Furthermore, bakuchiol induced cell apoptosis and disturbed mitochondrial membrane potential in MCF-7 cells. The bakuchiol-induced apoptosis was associated with increased expression of Caspase family and Bcl-2 family proteins, suggesting that bakuchiol may induce

  16. Phytoestrogen Bakuchiol Exhibits In Vitro and In Vivo Anti-breast Cancer Effects by Inducing S Phase Arrest and Apoptosis.

    Science.gov (United States)

    Li, Li; Chen, Xueping; Liu, Chi C; Lee, Lai S; Man, Cornelia; Cheng, Shuk H

    2016-01-01

    Phytoestrogen has been proposed as an alternative to hormone replacement therapy, which has been demonstrated to promote a high risk of breast cancer. However, the effect of phytoestrogen on breast cancer development has not been fully understood. Bakuchiol is an active ingredient of a traditional Chinese herbal medicine Fructus Psoraleae, the dried ripe fruit of Psoralea corylifolia L. (Fabaceae). The in vitro and in vivo estrogenic activities and anti-breast cancer effects of bakuchiol have not been well-studied. We found that bakuchiol induced the GFP expression in transgenic medaka (Oryzias melastigma, Tg, Chg:GFP) dose-dependently (0-1 μg/ml), demonstrating its in vivo estrogenic activity. Low dose of bakuchiol (1 μg/ml) induced the cell proliferation and ERα expression in MCF-7 cells, which could be blocked by the anti-estrogen ICI 182780, suggesting the in vitro estrogenic activity of bakuchiol. Our data indicated that high doses of bakuchiol (>2 μg/ml) inhibited breast cancer cell growth, with a stronger anti-proliferative effect than resveratrol, a widely studied analog of bakuchiol. High doses of bakuchiol (4, 7, and 10 μg/ml) were used for the further in vitro anti-breast cancer studies. Bakuchiol induced ERβ expression and suppressed ERα expression in MCF-7 cells. It also induced S phase arrest in both MCF-7 and MDA-MB-231 cells, which could be rescued by caffeine. Knock-down of p21 also marginally rescued S phase arrest in MCF-7 cells. The S phase arrest was accompanied by the upregulation of ATM, P-Cdc2 (Tyr15), Myt1, P-Wee1 (Ser642), p21 and Cyclin B1, suggesting that blocking of Cdc2 activation may play an important role in bakuchiol-induced S phase arrest. Furthermore, bakuchiol induced cell apoptosis and disturbed mitochondrial membrane potential in MCF-7 cells. The bakuchiol-induced apoptosis was associated with increased expression of Caspase family and Bcl-2 family proteins, suggesting that bakuchiol may induce apoptosis via intrinsic

  17. Ionic and Wigner Glasses, Superionic Conductors, and Spinodal Electrostatic Gels: Dynamically Arrested Phases of the Primitive Model

    International Nuclear Information System (INIS)

    Based on the recently proposed self-consistent generalized Langevin equation theory of dynamic arrest, in this letter we show that the ergodic-nonergodic phase diagram of a classical mixture of charged hard spheres (the so-called 'primitive model' of ionic solutions and molten salts) includes arrested phases corresponding to nonconducting ionic glasses, partially arrested states that represent solid electrolytes (or 'superionic' conductors), low-density colloidal Wigner glasses, and low-density electrostatic gels associated with arrested spinodal decomposition.

  18. Induction of autophagy by proteasome inhibitor is associated with proliferative arrest in colon cancer cells

    International Nuclear Information System (INIS)

    The ubiquitin-proteasome system (UPS) and lysosome-dependent macroautophagy (autophagy) are two major intracellular pathways for protein degradation. Blockade of UPS by proteasome inhibitors has been shown to activate autophagy. Recent evidence also suggests that proteasome inhibitors may inhibit cancer growth. In this study, the effect of a proteasome inhibitor MG-132 on the proliferation and autophagy of cultured colon cancer cells (HT-29) was elucidated. Results showed that MG-132 inhibited HT-29 cell proliferation and induced G2/M cell cycle arrest which was associated with the formation of LC3+ autophagic vacuoles and the accumulation of acidic vesicular organelles. MG-132 also increased the protein expression of LC3-I and -II in a time-dependent manner. In this connection, 3-methyladenine, a Class III phosphoinositide 3-kinase inhibitor, significantly abolished the formation of LC3+ autophagic vacuoles and the expression of LC3-II but not LC3-I induced by MG-132. Taken together, this study demonstrates that inhibition of proteasome in colon cancer cells lowers cell proliferation and activates autophagy. This discovery may shed a new light on the novel function of proteasome in the regulation of autophagy and proliferation in colon cancer cells

  19. Cordycepin Induces S Phase Arrest and Apoptosis in Human Gallbladder Cancer Cells

    Directory of Open Access Journals (Sweden)

    Xu-An Wang

    2014-07-01

    Full Text Available Gallbladder cancer is the most common malignant tumor of the biliary tract, and this condition has a rather dismal prognosis, with an extremely low five-year survival rate. To improve the outcome of unresectable and recurrent gallbladder cancer, it is necessary to develop new effective treatments and drugs. The purpose of the present study was to evaluate the effects of cordycepin on human gallbladder cells and uncover the molecular mechanisms responsible for these effects. The Cell Counting Kit-8 (CCK-8 and colony formation assays revealed that cordycepin affected the viability and proliferation of human gallbladder cancer cells in a dose- and time-dependent manner. Flow cytometric analysis showed that cordycepin induced S phase arrest in human gallbladder cancer cell lines(NOZ and GBC-SD cells. Cordycepin-induced apoptosis was observed using an Annexin V/propidium iodide (PI double-staining assay, and the mitochondrial membrane potential (ΔΨm decreased in a dose-dependent manner. Additionally, western blot analysis revealed the upregulation of cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP and Bax and the downregulation of Bcl-2, cyclin A and Cdk-2 in cordycepin-treated cells. Moreover, cordycepin inhibited tumor growth in nude mice bearing NOZ tumors. Our results indicate that this drug may represent an effective treatment for gallbladder carcinoma.

  20. "On-The-Spot" Arresting of Chondroitin Sulphate Proteoglycans: Implications for Ovarian Adenocarcinoma Recognition and Intervention.

    Science.gov (United States)

    Pradeep, Priyamvada; Choonara, Yahya E; Kumar, Pradeep; Pillay, Viness

    2016-01-01

    Ovarian Cancer (OC) is one of the leading causes of cancer-associated death among women. The underlying biochemical cause of OC proliferation is usually attributed to the over-expression of Chondroitin Sulphate Proteoglycans (CSPGs) wherein the CS-E subgroup plays a major role in tumor cell proliferation by over-expressing vascular endothelial growth factor (VEGF). We hereby hypothesize that by targeting the OC extracellular matrix using a CS-E-specific antibody, GD3G7, we could provide spatial delivery of crosslinkers and anti-VEGF agents to firstly induce in vivo crosslinking and complexation (arresting) of CS-E into a "biogel mass" for efficient and effective detection, detachment and reduction of tumorous tissue, and secondly inhibit angiogenesis in OC. It is further proposed that the antibody-assisted targeted delivery of CS-E crosslinkers can bind to highly anionic CS-E to form a polyelectrolyte complex to inhibit the formation of ovarian tumor spheroids that are responsible for spheroid-induced mesothelial clearance and progression of OC. The hypothesis also describes the potential in vivo "On-The-Spot" CSPG crosslinkers such as sodium trimetaphosphate (physical crosslinker), 1,12-diaminododecane (chemical crosslinker), poly(ethylene glycol) diglycidyl ether (synthetic polymer), and chitosan (natural polyelectrolyte-forming agent). In conclusion, this hypothesis proposes in vivo spatial crosslinking of CSPGs as a potential theranostic intervention strategy for OC-a first in the field of cancer research. PMID:27438831

  1. Inactivation of nucleolin leads to nucleolar disruption, cell cycle arrest and defects in centrosome duplication

    Directory of Open Access Journals (Sweden)

    Thiry Marc

    2007-08-01

    Full Text Available Abstract Background Nucleolin is a major component of the nucleolus, but is also found in other cell compartments. This protein is involved in various aspects of ribosome biogenesis from transcription regulation to the assembly of pre-ribosomal particles; however, many reports suggest that it could also play an important role in non nucleolar functions. To explore nucleolin function in cell proliferation and cell cycle regulation we used siRNA to down regulate the expression of nucleolin. Results We found that, in addition to the expected effects on pre-ribosomal RNA accumulation and nucleolar structure, the absence of nucleolin results in a cell growth arrest, accumulation in G2, and an increase of apoptosis. Numerous nuclear alterations, including the presence of micronuclei, multiple nuclei or large nuclei are also observed. In addition, a large number of mitotic cells showed a defect in the control of centrosome duplication, as indicated by the presence of more than 2 centrosomes per cell associated with a multipolar spindle structure in the absence of nucleolin. This phenotype is very similar to that obtained with the inactivation of another nucleolar protein, B23. Conclusion Our findings uncovered a new role for nucleolin in cell division, and highlight the importance of nucleolar proteins for centrosome duplication.

  2. Two-dimensional Turbulence in Symmetric Binary-Fluid Mixtures: Coarsening Arrest by the Inverse Cascade

    CERN Document Server

    Perlekar, Prasad; Pandit, Rahul

    2015-01-01

    We study two-dimensional (2D) binary-fluid turbulence by carrying out an extensive direct numerical simulation (DNS) of the forced, statistically steady turbulence in the coupled Cahn-Hilliard and Navier-Stokes equations. In the absence of any coupling, we choose parameters that lead (a) to spinodal decomposition and domain growth, which is characterized by the spatiotemporal evolution of the Cahn-Hilliard order parameter $\\phi$, and (b) the formation of an inverse-energy-cascade regime in the energy spectrum $E(k)$, in which energy cascades towards wave numbers $k$ that are smaller than the energy-injection scale $k_{inj}$ in the turbulent fluid. We show that the Cahn-Hilliard-Navier-Stokes coupling leads to an arrest of phase separation at a length scale $L_c$, which we evaluate from $S(k)$, the spectrum of the fluctuations of $\\phi$. We demonstrate that (a) $L_c \\sim L_H$, the Hinze scale that follows from balancing inertial and interfacial-tension forces, and (b) $L_c$ is independent, within error bars, o...

  3. 2-Methoxyestradiol induces cell cycle arrest and apoptosis of nasopharyngeal carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Ning-ning ZHOU; Xiao-feng ZHU; Jun-ming ZHOU; Man-zhi LI; Xiao-shi ZHANG; Peng HUANG; Wen-qi JIANG

    2004-01-01

    AIM: To investigate 2-methoxyestradiol induced apoptosis and its mechanism of action in CNE2 cell lines.METHODS: CNE2 cells were cultured in RPMI-1640 medium and treated with 2-methoxyestradiol in different concentrations. MTT assay was used to detect growth inhibition. Flow cytometry and DNA ladders were used to detect apoptosis. Western blotting was used to observe the expression of p53, p21WAF1, Bax, and Bcl-2 protein.RESULTS: 2-methoxyestradiol inhibited proliferation of nasopharyngeal carcinoma CNE2 cells with IC50 value of2.82 μrnol/L. The results of flow cytometry showed an accumulation of CNE2 cells in G2/M phase in response to2-methoxyestradiol. Treatment of CNE2 cells with 2-methoxyestradiol resulted in DNA fragmentation. The expression levels of protein p53 and Bcl-2 decreased following 2-methoxyestradiol treatment in CNE2 cells, whereas Bax and p21WAF1 protein expression were unaffected after treatment with 2-methoxyestradiol. CONCLUSION:These results suggest that 2-methoxyestradiol induced cell cycle arrest at G2/M phase and apoptosis of CNE2 cells which was associated to Bcl-2 down-regulation.

  4. Arrest Decisions as Precludes To? An Evaluation of Policy Related Research. Volume I: Administrative Summary and Training Script.

    Science.gov (United States)

    Neithercutt, M. G.; And Others

    The document is the first part of a study conducted to evaluate policy-related research on police arrest discretion as an alternative solution to arrest. It presents the administrative summary of the Arrest Decisions as Preludes To? (ADAPT) project and contains scripts intended for use by police departments as a staff training device. The…

  5. Sorafenib induces growth arrest and apoptosis of human glioblastoma cells via dephosphorylation of STAT3

    OpenAIRE

    Yang, Fan; Brown, Christine; Buettner, Ralf; HEDVAT, MICHAEL; Starr, Renate; Scuto, Anna; Schroeder, Anne; Jensen, Michael; Jove, Richard

    2010-01-01

    Glioblastoma is the most common type of primary brain tumor and is rapidly progressive with few treatment options. Here, we report that sorafenib (≤ 10 μM) inhibited cell proliferation and induced apoptosis in two established cell lines (U87, U251) and two primary cultures (PBT015, PBT022) from human glioblastomas. Effects of sorafenib on these tumor cells were associated with inhibiting phosphorylated STAT3 (Tyr705). Expression of a constitutively activated STAT3 mutant partially blocked the...

  6. Involucrin and envelope competence in human keratinocytes: Modulation by hydrocortisone, retinyl acetate and growth arrest

    OpenAIRE

    Rice, Rh; Cline, PR

    1983-01-01

    Involucrin accumulation and ionophore-assisted envelope for mation, markers of keratinocyte differentiation, were found to be highly dependent on culture conditions in the malignant epidermal keratinocyte line, SCC-13, derived from a human squamous cell carcinoma. In confluent cultures, approximately one-half of the cells were competent to form envelopes when grown in medium without hydrocortisone or retinyl acetate supplementation. Ad dition of hydrocortisone to the medi...

  7. Arrest of endotoxin-induced hypotension by transforming growth factor beta1.

    OpenAIRE

    Perrella, M A; Hsieh, C. M.; W. S. Lee; Shieh, S; Tsai, J C; Patterson, C.; Lowenstein, C. J.; Long, N C; Haber, E; Shore, S.; Lee, M E

    1996-01-01

    Septic shock is a cytokine-mediated process typically caused by a severe underlying infection. Toxins generated by the infecting organism trigger a cascade of events leading to hypotension, to multiple organ system failure, and frequently to death. Beyond supportive care, no effective therapy is available for the treatment of septic shock. Nitric oxide (NO) is a potent vasodilator generated late in the sepsis pathway leading to hypotension; therefore, NO represents a potential target for ther...

  8. Vernonia amygdalina—Induced Growth Arrest and Apoptosis of Breast Cancer (MCF-7) Cells

    OpenAIRE

    Yedjou, Clement G.; Izevbigie, Ernest B.; Tchounwou, Paul B.

    2013-01-01

    Breast cancer is the second leading cause of cancer-related deaths of women in the United States. Fortunately, the mortality rate from breast cancer has decreased in recent years due to an increased emphasis on early detection and more effective treatments. Although great advancements have been made in the treatment and control of cancer progression, significant deficiencies and room for improvement remain. The central objective of this research was to further determine the in vitro mechanism...

  9. Tumor-targeting Salmonella typhimurium A1-R arrests growth of breast-cancer brain metastasis

    OpenAIRE

    Zhang, Yong; Miwa, Shinji; Zhang, Nan; Hoffman, Robert M.; Zhao, Ming

    2014-01-01

    Brain metastasis is a morbid, treatment-resistant, end-stage frequent occurrence in breast cancer patients. The aim of this study was to evaluate the efficacy of tumor-targeting Salmonella typhimurium A1-R on breast cancer brain metastases. High brain-metastatic variants of murine 4T1 breast cancer cells expressing red fluorescent protein (RFP) were injected orthotopically in the mammary fat pad in non-transgenic nude mice or in the left ventricle of non-transgenic nude mice and transgenic nu...

  10. Aureobasidin A arrests growth of yeast cells through both ceramide intoxication and deprivation of essential inositolphosphorylceramides

    DEFF Research Database (Denmark)

    Cerantola, Vanessa; Guillas, Isabelle; Roubaty, Carole;

    2009-01-01

    All mature Saccharomyces cerevisiae sphingolipids comprise inositolphosphorylceramides containing C26:0 or C24:0 fatty acids and either phytosphingosine or dihydrosphingosine. Here we analysed the lipid profile of lag1Delta lac1Delta mutants lacking acyl-CoA-dependent ceramide synthesis, which re...

  11. Dichotomy of AML1-ETO Functions: Growth Arrest versus Block of Differentiation†

    OpenAIRE

    Burel, Sebastien A.; Harakawa, Nari; Zhou, Liming; Pabst, Thomas; Tenen, Daniel G.; Zhang, Dong-Er

    2001-01-01

    The fusion gene AML1-ETO is the product of t(8;21)(q22;q22), one of the most common chromosomal translocations associated with acute myeloid leukemia. To investigate the impact of AML1-ETO on hematopoiesis, tetracycline-inducible AML1-ETO-expressing cell lines were generated using myeloid cells. AML1-ETO is tightly and strongly induced upon tetracycline withdrawal. The proliferation of AML1-ETO+ cells was markedly reduced, and most of the cells eventually underwent apoptosis. RNase protection...

  12. Nanoparticle growth. Facet development during platinum nanocube growth.

    Science.gov (United States)

    Liao, Hong-Gang; Zherebetskyy, Danylo; Xin, Huolin; Czarnik, Cory; Ercius, Peter; Elmlund, Hans; Pan, Ming; Wang, Lin-Wang; Zheng, Haimei

    2014-08-22

    An understanding of how facets of a nanocrystal develop is critical for controlling nanocrystal shape and designing novel functional materials. However, the atomic pathways of nanocrystal facet development are mostly unknown because of the lack of direct observation. We report the imaging of platinum nanocube growth in a liquid cell using transmission electron microscopy with high spatial and temporal resolution. The growth rates of all low index facets are similar until the {100} facets stop growth. The continuous growth of the rest facets leads to a nanocube. Our calculation shows that the much lower ligand mobility on the {100} facets is responsible for the arresting of {100} growing facets. These findings shed light on nanocrystal shape-control mechanisms and future design of nanomaterials. PMID:25146287

  13. Use of forces from instrumented Charpy V-notch testing to determine crack-arrest toughness

    International Nuclear Information System (INIS)

    The objective of this investigation is an estimation of the crack-arrest toughness, particularly of irradiated materials, from voltage versus time output of an instrumented setup during a test on a Charpy V-notch (CVN) specimen. This voltage versus time trace (which can be converted to force versus displacement) displays events during fracture of the specimen. Various stages of the fracture process can be identified on the trace, including an arrest point indicating arrest of brittle fracture. The force at arrest, Fa, versus test temperature, T, relationship is examined to explore possible relationships to other experimental measures of crack-arrest toughness such as the drop-weight nil-ductility temperature (NDT), or crack-arrest toughness, Ka. For a wide range of weld and plate materials, the temperature at which Fa = 2.45 kN correlates with NDT with a standard deviation, sigma, of about 11 K. Excluding the so-called low upper-shelf energy (USE) welds from the analysis resulted in Fa = 4.12 kN and σ = 6.6 K. The estimates of the correlation of the temperature for Fa = 7.4 kN with the temperature at 100-MPa√m level for a mean American Society of Mechanical Engineers (ASME) type KIa curve through crack-arrest toughness values show that prediction of conservative values of Ka are possible

  14. Experimental study and local approach of cleavage crack arrest in a bainitic steel

    International Nuclear Information System (INIS)

    EDF wants to complete the assessment of reactor pressure vessels, usually based on crack initiation concept, by crack arrest concept. The work aims at improving the knowledge of cleavage crack arrest in a reactor pressure vessel steel. For that purpose, isothermal crack arrest experiments were performed for temperatures ranging from - 150 C up to - 50 C on compact tensile specimens and on pre-cracked rings submitted to compressive loading. Fractographic observations revealed that the whole crack propagation and arrest occurs by cleavage even if ductile tearing occurs before initiation of the unstable crack propagation. A local cleavage crack arrest criterion is applied in finite element computations carried out in elasto-visco-plasticity and in full dynamics: the crack propagates since the largest principal stress reaches a critical stress. The application of this criterion on the experiments leads to a good prediction of the crack speed and of the crack length and shows that the critical stress increases with the temperature in relation with dissipation features observed on the fracture surfaces. Dependence to the geometry is observed; it can be due to the assumption used for the 2D computations. The study of the structural dynamic shows that the crack arrest phenomenon is very linked to the global dynamics of the structure: crack arrest and crack closure occur approximately at the same time. (author)

  15. Performance analysis of surge arrester on high voltage systems using ATP

    Energy Technology Data Exchange (ETDEWEB)

    Nallagownden, P.; Magumane, A.H. [Univ. Teknologi Petronas, Perak (Malaysia); Kanth, K.S.R. [Tenaga National Berhad (Malaysia)

    2008-07-01

    Lightning strikes are among the major factors that cause failures in electrical power systems. Phase to ground arresters are commonly installed at power transformer terminals to offer some lightning protection. However, it is important to understand the performance of metal oxide arresters under very fast transient overvoltages in order to determine the protection zone of the arrester and to achieve economical benefits. This study investigated lightning overvoltage protection in a complete three-phase scheme of a 500 KV substation. Overvoltages originated from direct lightning stroke on a phase of a real overhead line (OHL) model. The effect of the separation distance of the arrester from the transformer connected at the open end of the substations was investigated as well as the performance of the arrester for different substation configurations. In the first scenario, the connection of the arrester and transformer was done with a direct connection of an overhead line. In the second scenario, the connection of these devices was done through a cable. Both the overhead line and cable lengths were varied and the maximum overvoltages coming to the transformer were recorded. The results showed that there is a direct proportionality between overvoltages and length of the overhead line or cable. As long the length of the line or cable between the arrester and the transformer was increased, the vulnerability of the transformer to receive high overvoltages also increased. Surge overvoltages were found to be very sensitive to impedance of the line or cable. The direct connections of overhead lines between the arrester and transformer make it necessary to add some protective device. It was suggested that surge arresters should be installed every 200 meters along the overhead lines in order to ensure the safety of equipment. 12 refs., 4 tabs., 8 figs.

  16. Hypothermic cardiac arrest: an 11 year review of ED management and outcome.

    Science.gov (United States)

    Brunette, D D; McVaney, K

    2000-07-01

    The purpose of this study was to examine the emergency department (ED) management of hypothermic cardiac arrest and its outcome. The medical records of all patients with hypothermic cardiac arrest treated in the ED from January 1, 1988 to January 31, 1999 were retrospectively reviewed. Data collected included initial body temperature, serum potassium, methods of rewarming, return of perfusing rhythm, and morbidity and mortality. Data were analyzed by descriptive methods. Eleven patients were treated in the ED resuscitation room for hypothermic cardiac arrest. Six patients were found in cardiac arrest in the field, one patient arrested during transport, and four patients arrested after ED arrival. The average initial temperature was 79.1 degrees F (range 69.0 degrees F to 86.7 degrees F). Seven patients received an ED thoracotomy with internal cardiac massage and warm mediastinal irrigation. Four patients had airway management in the ED and then direct transport to the operating room for cardiac bypass rewarming. Three of the seven patients who received an ED thoracotomy subsequently went to intraoperative cardiac bypass rewarming. Five of the seven (71.4%) patients who received an ED thoracotomy survived, versus none of the four patients (0%) who went directly to intraoperative cardiac bypass. A direct comparison of immediate ED thoracotomy versus intraoperative cardiac bypass without ED thoracotomy is cautiously made as this was an unmatched and nonrandomized study. Three of the surviving patients underwent intraoperative cardiac bypass rewarming after receiving an ED thoracotomy. In two of these patients a perfusing rhythm had been established after thoracotomy in the ED and before transport to the operating room for cardiac bypass. Only one of seven (14.3%) patients who arrested prehospital survived versus four of four (100%) who arrested in the ED. ED thoracotomy with internal cardiac massage and mediastinal irrigation rewarming is effective in the management

  17. The chick somitogenesis oscillator is arrested before all paraxial mesoderm is segmented into somites

    Directory of Open Access Journals (Sweden)

    McGrew Michael J

    2010-02-01

    Full Text Available Abstract Background Somitogenesis is the earliest sign of segmentation in the developing vertebrate embryo. This process starts very early, soon after gastrulation has initiated and proceeds in an anterior-to-posterior direction during body axis elongation. It is widely accepted that somitogenesis is controlled by a molecular oscillator with the same periodicity as somite formation. This periodic mechanism is repeated a specific number of times until the embryo acquires a defined specie-specific final number of somites at the end of the process of axis elongation. This final number of somites varies widely between vertebrate species. How termination of the process of somitogenesis is determined is still unknown. Results Here we show that during development there is an imbalance between the speed of somite formation and growth of the presomitic mesoderm (PSM/tail bud. This decrease in the PSM size of the chick embryo is not due to an acceleration of the speed of somite formation because it remains constant until the last stages of somitogenesis, when it slows down. When the chick embryo reaches its final number of somites at stage HH 24-25 there is still some remaining unsegmented PSM in which expression of components of the somitogenesis oscillator is no longer dynamic. Finally, we identify a change in expression of retinoic acid regulating factors in the tail bud at late stages of somitogenesis, such that in the chick embryo there is a pronounced onset of Raldh2 expression while in the mouse embryo the expression of the RA inhibitor Cyp26A1 is downregulated. Conclusions Our results show that the chick somitogenesis oscillator is arrested before all paraxial mesoderm is segmented into somites. In addition, endogenous retinoic acid is probably also involved in the termination of the process of segmentation, and in tail growth in general.

  18. Studies on the effect of cell cycle arrest on central metabolism in the diatom Phaeodactylum tricornutum, using physiological and systems biology approaches

    Science.gov (United States)

    Kim, Joomi

    Diatoms (Bacillarophyceae) are photosynthetic unicellular microalgae that have risen to ecological prominence in the modern oceans over the past 30 million years. They are excellent candidates for biodiesel feedstocks. Global climate change has led to an interest in algal triacylglycerols (TAGs) as feedstocks for sustainable biodiesel, and diatoms are attractive candidates for TAG production as one of the most productive and environmentally flexible algae in the contemporary oceans. For Chapter 2, a genome-scale metabolic model was constructed to calculate intracellular fluxes of a diatom under different growth conditions. The model identified enzymes that may be relevant to increasing lipid synthesis, explored how transporters affect flux outputs, and explored unusual features of diatoms, including the Entner-Douderoff and phosphoketolase pathways, and glycolytic enzymes in their mitochondria. Chapter 3 discusses how cell cycle arrest via cyclin-dependent kinase (Cdk) inhibition, can increase accumulation of TAGs, and shift metabolism away from protein synthesis. For Chapter 4, transcriptome analysis of cells under cell cycle arrest was performed to show that the pattern of gene expression was fundamentally different from nitrogen stress. Most of the genes related to fatty acid and TAG synthesis were up-regulated. The gene expression pattern for light harvesting complexes was similar to cells stressed by high light, suggesting that arrested cells have smaller sinks for photosynthetically generated electrons.

  19. Sudden Cardiac Death and Post Cardiac Arrest Syndrome. An Overview

    Directory of Open Access Journals (Sweden)

    Zima Endre

    2015-10-01

    Full Text Available A satisfactory neurologic outcome is the key factor for survival in patients with sudden cardiac death (SCD, however this is highly dependent on the haemodynamic status. Short term cardiopulmonary resuscitation and regained consciousness on the return of spontaneous circulation (ROSC is indicative of a better prognosis. The evaluation and treatment of SCD triggering factors and of underlying acute and chronic diseases will facilitate prevention and lower the risk of cardiac arrest. Long term CPR and a prolonged unconscious status after ROSC, in the Intensive Care Units or Coronary Care Units, indicates the need for specific treatment and supportive therapy including efforts to prevent hyperthermia. The prognosis of these patients is unpredictable within the first seventy two hours, due to unknown responses to therapeutic management and the lack of specific prognostic factors. Patients in these circumstances require the highest level of intensive care and aetiology driven treatment without any delay, independently of their coma state. Current guidelines sugest the use of multiple procedures in arriving at a diagnosis and prognosis of these critical cases.

  20. Dexmedetomidine Related Bradycardia Leading to Cardiac Arrest in a Dog

    Directory of Open Access Journals (Sweden)

    C. Y. Chen2, K-S. Chen1,2, K. M. Chang2, W. M. Lee1,2, S. C. Chang1,2 and H. C. Wang1,2

    2012-10-01

    Full Text Available A 2-year-old, mixed breed female dog (16 kg underwent an exploratory laparotomy following ultrasonographic diagnosis of foreign body and a segment of small intestine intussusceptions. The patient was classified as an ASA II. Ketamine (1mg/kg, IV, and dexmedetomidine (2.5 µg/kg, IV, and morphine (0.6 mg/kg, SC were given as anesthetic premedication. Propofol (0.1 mg/kg, IV titrated to a total amount of 4 ml (2.5 mg/ kg was given for intubation. Asystole was occurred. Cardiac resuscitation was then conducted immediately. Atipamezole (0.1 ml was injected, but showed no response on ECG. Atropine (0.02 mg/kg was then injected, and a second dosage was given. Two-three mins later, the heart rate at 84 beats/min. The NIBP showed 203/132 with MAP 153 mmHg, and the SpO2 showed 95% after the cardiac function was regained. Dexmedetomidine related bradycardia leading to cardiac arrest has been suggested in this case.

  1. A conservative approach to esthetically treat stained arrested caries lesions.

    Science.gov (United States)

    Al-Angari, Sarah S; Hara, Anderson T

    2016-01-01

    Esthetic treatment of stained arrested caries lesions (ACLs) has mostly been done using invasive restorative techniques. The aim of this paper was to propose and report the efficacy of a conservative approach based on dental bleaching to esthetically treat these lesions, both experimentally (extracted teeth) and clinically. In a laboratory experiment, ten extracted human teeth with stained ACLs in either pit and fissure or smooth surface were selected and treated with 15% carbamide peroxide gel, 4 h per day, for a total of 6 days. The second part of the paper reports a clinical case of pit and fissure-stained ACLs in four posterior teeth, which were treated with 40% hydrogen peroxide in-office bleaching. Digital photographs were taken in both parts to document the efficacy of the treatment. The lesions showed noticeable increase in color lightness indicating the efficacy and suitability of the proposed approach. By using the conservative clinical technique presented, the esthetics of most stained ACLs could be improved, eliminating the need for invasive restorative treatments. PMID:27092359

  2. Nitisinone Arrests but Does Not Reverse Ochronosis in Alkaptonuric Mice.

    Science.gov (United States)

    Keenan, Craig M; Preston, Andrew J; Sutherland, Hazel; Wilson, Peter J; Psarelli, Eftychia E; Cox, Trevor F; Ranganath, Lakshminarayan R; Jarvis, Jonathan C; Gallagher, James A

    2015-01-01

    Alkaptonuria (AKU) is an ultrarare autosomal recessive disorder resulting from a deficiency of homogentisate 1,2 dioxygenase (HGD), an enzyme involved in the catabolism of phenylalanine and tyrosine. Loss of HGD function prevents metabolism of homogentisic acid (HGA), leading to increased levels of plasma HGA and urinary excretion. Excess HGA becomes deposited in collagenous tissues and subsequently undergoes polymerisation, principally in the cartilages of loaded joints, in a process known as ochronosis. This results in an early-onset, devastating osteoarthropathy for which there is currently no effective treatment. We recently described the natural history of ochronosis in a murine model of AKU, demonstrating that deposition of ochronotic pigment begins very early in life and accumulates with age. Using this model, we were able to show that lifetime treatment with nitisinone, a potential therapy for AKU, was able to completely prevent deposition of ochronotic pigment. However, although nitisinone has been shown to inhibit ochronotic deposition, whether it can also facilitate removal of existing pigment has not yet been examined. We describe here that midlife administration of nitisinone to AKU mice arrests further deposition of ochronotic pigment in the tibiofemoral joint, but does not result in the clearance of existing pigment. We also demonstrate the dose-dependent response of plasma HGA to nitisinone, highlighting its efficacy for personalised medicine, where dosage can be tailored to the individual AKU patient. PMID:25940034

  3. Efficiency of Super-Eddington Magnetically-Arrested Accretion

    CERN Document Server

    McKinney, Jonathan C; Avara, Mark

    2015-01-01

    The radiative efficiency of super-Eddington accreting black holes (BHs) is explored for magnetically-arrested disks (MADs), where magnetic flux builds-up to saturation near the BH. Our three-dimensional general relativistic radiation magnetohydrodynamic (GRRMHD) simulation of a spinning BH (spin $a/M=0.8$) accreting at $\\sim 50$ times Eddington shows a total efficiency $\\sim 50\\%$ when time-averaged and total efficiency $\\gtrsim 100\\%$ in moments. Magnetic compression by the magnetic flux near the rotating BH leads to a thin disk, whose radiation escapes via advection by a magnetized wind and via transport through a low-density channel created by a Blandford-Znajek (BZ) jet. The BZ efficiency is sub-optimal due to inertial loading of field lines by optically thick radiation, leading to BZ efficiency $\\sim 40\\%$ on the horizon and BZ efficiency $\\sim 5\\%$ by $r\\sim 400r_g$ (gravitational radii) via absorption by the wind. Importantly, radiation escapes at $r\\sim 400r_g$ with efficiency $\\eta\\approx 15\\%$ (lumi...

  4. Efficiency of Thin Magnetically-Arrested Disks Around Black Holes

    CERN Document Server

    Avara, Mark J; Reynolds, Chris S

    2015-01-01

    The radiative and jet efficiencies of thin magnetized accretion disks around black holes (BHs) are affected by BH spin and the presence of a magnetic field that, when strong, could lead to large deviations from Novikov-Thorne (NT) thin disk theory. To seek the maximum deviations, we perform general relativistic magnetohydrodynamic (GRMHD) simulations of radiatively efficient thin (half-height $H$ to radius $R$ of $H/R\\approx 0.10$) disks around moderately rotating BHs with $a/M=0.5$. First, our simulations, evolved for $108,000r_g/c$ (gravitational radius $r_g$ and speed of light $c$), show that large-scale magnetic field readily accretes inward even through our thin disk and builds-up to the magnetically-arrested disk (MAD) state. Second, our simulations of thin MADs show the disk achieves a radiative efficiency of $\\eta_{\\rm r}\\approx 15\\%$ (after estimating photon capture), which is about twice the NT value of $\\eta_{\\rm r}\\sim 8\\%$ for $a/M=0.5$ and gives the same luminosity as a NT disk with $a/M\\approx ...

  5. The perception of children of elementary education about cardiorespiratory arrest

    Directory of Open Access Journals (Sweden)

    Mariélli Terassi

    2015-03-01

    Full Text Available Cardiorespiratory arrest (CRA is a serious situation that occurs frequently in public environments, which makes assistance training of the general population of great importance. The objective was to understand the perception of children on CRA. Qualitative research conducted with children 8-10 years old enrolled in a private elementary school with a constructive proposal. Data collection occurred between the months of October and November 2013 in a recorded collective interview. As a criterion for inclusion students should be enrolled in the institution and accept to participate in the research with the consent of a guardian. Thirty children participated in the study. The students were divided into four groups: 5th year, 4th year, 3rd year A and 3rd year B, with an average of 08 students per group. The interviews were analyzed using the Bardin content analysis methodology. From the speeches, two categories emerged: Child's prior knowledge on CRA and how to act on the event of a CRA. Children associate the event of sudden CRA to a condition in which the heart and/or lungs suddenly stop acting. Seeking emergency assistance was reported as one of the main actions to be taken if a person is unconscious. It was observed that the 5th graders had best prior knowledge about the topic CRA when compared to students in the 3rd year. The thematic approach of CRA in schools contributes to the exchange of experiences, awareness of children and building new knowledge-oriented health education.

  6. Intravenous ranitidine: Rapid bolus can lead to cardiac arrest

    Directory of Open Access Journals (Sweden)

    Kamlesh J Upadhyay

    2015-01-01

    Full Text Available This is a rare case report of a 30-year-old male, who was admitted to the Maxillofacial Surgery Department of the Dental College for a malunited fracture of the mandible and zygomatic bones. He was given oral medications namely, cefixime, metronidazole, ondansetron, and ranitidine for three days prior to the operation with complete normal preoperative workup. He had no significant past medical or family history. On the day of the operation, he was given injectable dexamethasone, cefotaxime, ondansetron, ranitidine, and metronidazole half-an-hour prior to the operation. In less than five minutes of giving a bolus ranitidine injection, the patient developed a cardiac arrest and was resuscitated by the anesthetist team on duty. He was transferred to the Intensive Care Unit (ICU on a ventilator, which was soon removed and the patient was off vasopressors, with stable vitals for 24 hours after the event. He was then transferred to the general ward of Medicine Department and observed for a further two days during which the patient remained uneventful and was finally transferred back to the Dental Department.

  7. Intravenous ranitidine: Rapid bolus can lead to cardiac arrest.

    Science.gov (United States)

    Upadhyay, Kamlesh J; Parmar, Sarita J; Parikh, Rohan Pravinbhai; Gauswami, Prashant K; Dadhaniya, Nikunj; Surela, Abhilash

    2015-01-01

    This is a rare case report of a 30-year-old male, who was admitted to the Maxillofacial Surgery Department of the Dental College for a malunited fracture of the mandible and zygomatic bones. He was given oral medications namely, cefixime, metronidazole, ondansetron, and ranitidine for three days prior to the operation with complete normal preoperative workup. He had no significant past medical or family history. On the day of the operation, he was given injectable dexamethasone, cefotaxime, ondansetron, ranitidine, and metronidazole half-an-hour prior to the operation. In less than five minutes of giving a bolus ranitidine injection, the patient developed a cardiac arrest and was resuscitated by the anesthetist team on duty. He was transferred to the Intensive Care Unit (ICU) on a ventilator, which was soon removed and the patient was off vasopressors, with stable vitals for 24 hours after the event. He was then transferred to the general ward of Medicine Department and observed for a further two days during which the patient remained uneventful and was finally transferred back to the Dental Department. PMID:25969659

  8. A Literature Review Revisiting Phenytoin-Induced Sinus Arrest.

    Science.gov (United States)

    Parsai, Shireen; Hariri, Imad; Taleb, Mohammad; Yoon, Youngsook

    2016-01-01

    Classically, phenytoin (PTN) infusion for the treatment of status epilepticus has been proven to be associated with cardiovascular toxicity, including dysrhythmias, hypotension, and cardiovascular collapse. Subsequently, fosphenytoin (FOS) was introduced on the market in 1997 with claims of having less cardiac toxicity. However, since then, many accounts of cardiac events have been reported undermining these claims. FOS gained popularity due to its water solubility, which allows 3 times faster infusion in comparison with PTN with less venous irritation and local toxicity. FOS is the phosphate ester prodrug of PTN and is rapidly converted to PTN independent of the dose and rate of administration. Intravenous FOS and PTN are bioequivalent. Adverse cardiac effects of both intravenous FOS and PTN have been correlated to the rate of infusion, concentration of the agent, known risk factors, or pre-existing hypersensitivity, and most cases have been identified after infusing a loading dose of these medications. This case report is unique, in that, the patient developed sinus arrest while concurrently receiving oral PTN and intravenous FOS. Clinicians should be more cognizant of the association of FOS and PTN with adverse cardiac events. Baseline electrocardiogram should be obtained on all patients prescribed FOS or PTN to identify underlying cardiac problems that may place the patient in a higher risk category. Telemetry should be performed on all patients receiving PTN in an inpatient setting. PMID:25549077

  9. Cadmium and zinc reversibly arrest development of Artemia larvae

    Energy Technology Data Exchange (ETDEWEB)

    Bagshaw, J.C.; Rafiee, P.; Matthews, C.O.; MacRae, T.H.

    1986-08-01

    Despite the widespread distribution of heavy metals such as cadmium and zinc in the environment and their well-known cytotoxicity and embryotoxicity in mammals, comparatively little is known about their effect on aquatic organisms, particularly invertebrates. Post-gastrula and early larval development of the brine shrimp, Artemia, present some useful advantages for studies of developmental aspects of environmental toxicology. Dormant encysted gastrulae, erroneously called brine shrimp eggs, can be obtained commercially and raised in the laboratory under completely defined conditions. Following a period of post-gastrula development within the cyst, pre-nauplius larvae emerge through a crack in the cyst shell. A few hours later, free-swimming nauplius larvae hatch. Cadmium is acutely toxic to both adults and nauplius larvae of Artemia, but the reported LC50s are as high as 10 mM, depending on larval age. In this paper the authors show that pre-nauplius larvae prior to hatching are much more sensitive to cadmium than are hatched nauplius larvae. At 0.1 ..mu..m, cadmium retards development and hatching of larvae; higher concentrations block hatching almost completely and thus are lethal. However, the larvae arrested at the emergence stage survive for 24 hours or more before succumbing to the effects of cadmium, and during this period the potentially lethal effect is reversible if the larvae are placed in cadmium-free medium. The effects of zinc parallel those of cadmium, although zinc is somewhat less toxic than cadmium at equal concentrations.

  10. Intravenous ranitidine: Rapid bolus can lead to cardiac arrest

    Science.gov (United States)

    Upadhyay, Kamlesh J; Parmar, Sarita J; Parikh, Rohan Pravinbhai; Gauswami, Prashant K; Dadhaniya, Nikunj; Surela, Abhilash

    2015-01-01

    This is a rare case report of a 30-year-old male, who was admitted to the Maxillofacial Surgery Department of the Dental College for a malunited fracture of the mandible and zygomatic bones. He was given oral medications namely, cefixime, metronidazole, ondansetron, and ranitidine for three days prior to the operation with complete normal preoperative workup. He had no significant past medical or family history. On the day of the operation, he was given injectable dexamethasone, cefotaxime, ondansetron, ranitidine, and metronidazole half-an-hour prior to the operation. In less than five minutes of giving a bolus ranitidine injection, the patient developed a cardiac arrest and was resuscitated by the anesthetist team on duty. He was transferred to the Intensive Care Unit (ICU) on a ventilator, which was soon removed and the patient was off vasopressors, with stable vitals for 24 hours after the event. He was then transferred to the general ward of Medicine Department and observed for a further two days during which the patient remained uneventful and was finally transferred back to the Dental Department. PMID:25969659

  11. Sequential steps for developmental arrest in Arabidopsis seeds

    NARCIS (Netherlands)

    Raz, V.; Bergervoet, J.H.W.; Koornneef, M.

    2001-01-01

    The continuous growth of the plant embryo is interrupted during the seed maturation processes which results in a dormant seed. The embryo continues development after germination when it grows into a seedling. The embryo growth phase starts after morphogenesis and ends when the embryo fills the seed

  12. Omega-3 Polyunsaturated Fatty Acids Trigger Cell Cycle Arrest and Induce Apoptosis in Human Neuroblastoma LA-N-1 Cells

    Directory of Open Access Journals (Sweden)

    Wai Wing So

    2015-08-01

    Full Text Available Omega-3 (n-3 fatty acids are dietary long-chain fatty acids with an array of health benefits. Previous research has demonstrated the growth-inhibitory effect of n-3 fatty acids on different cancer cell lines in vitro, yet their anti-tumor effects and underlying action mechanisms on human neuroblastoma LA-N-1 cells have not yet been reported. In this study, we showed that docosahexaenoic acid (DHA and eicosapentaenoic acid (EPA exhibited time- and concentration-dependent anti-proliferative effect on the human neuroblastoma LA-N-1 cells, but had minimal cytotoxicity on the normal or non-tumorigenic cells, as measured by MTT reduction assay. Mechanistic studies indicated that DHA and EPA triggered G0/G1 cell cycle arrest in LA-N-1 cells, as detected by flow cytometry, which was accompanied by a decrease in the expression of CDK2 and cyclin E proteins. Moreover, DHA and EPA could also induce apoptosis in LA-N-1 cells as revealed by an increase in DNA fragmentation, phosphatidylserine externalization and mitochondrial membrane depolarization. Up-regulation of Bax, activated caspase-3 and caspase-9 proteins, and down-regulation of Bcl-XL protein, might account for the occurrence of apoptotic events. Collectively, our results suggest that the growth-inhibitory effect of DHA and EPA on LA-N-1 cells might be mediated, at least in part, via triggering of cell cycle arrest and apoptosis. Therefore, DHA and EPA are potential anti-cancer agents which might be used for the adjuvant therapy or combination therapy with the conventional anti-cancer drugs for the treatment of some forms of human neuroblastoma with minimal toxicity.

  13. Eriocalyxin B induces apoptosis and cell cycle arrest in pancreatic adenocarcinoma cells through caspase- and p53-dependent pathways

    International Nuclear Information System (INIS)

    Pancreatic cancer is difficult to detect early and responds poorly to chemotherapy. A breakthrough in the development of new therapeutic agents is urgently needed. Eriocalyxin B (EriB), isolated from the Isodon eriocalyx plant, is an ent-kaurane diterpenoid with promise as a broad-spectrum anti-cancer agent. The anti-leukemic activity of EriB, including the underlying mechanisms involved, has been particularly well documented. In this study, we demonstrated for the first time EriB's potent cytotoxicity against four pancreatic adenocarcinoma cell lines, namely PANC-1, SW1990, CAPAN-1, and CAPAN-2. The effects were comparable to that of the chemotherapeutic camptothecin (CAM), but with much lower toxicity against normal human liver WRL68 cells. EriB's cytoxicity against CAPAN-2 cells was found to involve caspase-dependent apoptosis and cell cycle arrest at the G2/M phase. Moreover, the p53 pathway was found to be activated by EriB in these cells. Furthermore, in vivo studies showed that EriB inhibited the growth of human pancreatic tumor xenografts in BALB/c nude mice without significant secondary adverse effects. These results suggest that EriB should be considered a candidate for pancreatic cancer treatment. -- Highlights: ► We study Eriocalyxin B (EriB)'s cytotoxic effects on pancreatic cancer cell lines. ► EriB inhibits cell proliferation via mediation of apoptosis and cell cycle arrest. ► The effects are involved in caspase-dependent apoptosis and p53 pathway. ► In vivo study also shows EriB inhibits the growth of human pancreatic tumor. ► EriB can be a good candidate for chemotherapy in pancreatic cancer.

  14. Eriocalyxin B induces apoptosis and cell cycle arrest in pancreatic adenocarcinoma cells through caspase- and p53-dependent pathways

    Energy Technology Data Exchange (ETDEWEB)

    Li, Lin [School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong (China); Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong (China); Yue, Grace G.L. [Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong (China); Lau, Clara B.S. [Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); Sun, Handong [State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, CAS, Yunnan (China); Fung, Kwok Pui [School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong (China); Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong (China); Leung, Ping Chung [Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong (China); Han, Quanbin, E-mail: simonhan@hkbu.edu.hk [Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong (China); School of Chinese Medicine, The Hong Kong Baptist University, Hong Kong (China); Leung, Po Sing, E-mail: psleung@cuhk.edu.hk [School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong (China)

    2012-07-01

    Pancreatic cancer is difficult to detect early and responds poorly to chemotherapy. A breakthrough in the development of new therapeutic agents is urgently needed. Eriocalyxin B (EriB), isolated from the Isodon eriocalyx plant, is an ent-kaurane diterpenoid with promise as a broad-spectrum anti-cancer agent. The anti-leukemic activity of EriB, including the underlying mechanisms involved, has been particularly well documented. In this study, we demonstrated for the first time EriB's potent cytotoxicity against four pancreatic adenocarcinoma cell lines, namely PANC-1, SW1990, CAPAN-1, and CAPAN-2. The effects were comparable to that of the chemotherapeutic camptothecin (CAM), but with much lower toxicity against normal human liver WRL68 cells. EriB's cytoxicity against CAPAN-2 cells was found to involve caspase-dependent apoptosis and cell cycle arrest at the G2/M phase. Moreover, the p53 pathway was found to be activated by EriB in these cells. Furthermore, in vivo studies showed that EriB inhibited the growth of human pancreatic tumor xenografts in BALB/c nude mice without significant secondary adverse effects. These results suggest that EriB should be considered a candidate for pancreatic cancer treatment. -- Highlights: ► We study Eriocalyxin B (EriB)'s cytotoxic effects on pancreatic cancer cell lines. ► EriB inhibits cell proliferation via mediation of apoptosis and cell cycle arrest. ► The effects are involved in caspase-dependent apoptosis and p53 pathway. ► In vivo study also shows EriB inhibits the growth of human pancreatic tumor. ► EriB can be a good candidate for chemotherapy in pancreatic cancer.

  15. Progestins reinitiate cell cycle progression in antiestrogen-arrested breast cancer cells through the B-isoform of progesterone receptor.

    Science.gov (United States)

    McGowan, Eileen M; Russell, Amanda J; Boonyaratanakornkit, Viroj; Saunders, Darren N; Lehrbach, Gillian M; Sergio, C Marcelo; Musgrove, Elizabeth A; Edwards, Dean P; Sutherland, Robert L

    2007-09-15

    Estrogen treatment of MCF-7 human breast cancer cells allows the reinitiation of synchronous cell cycle progression in antiestrogen-arrested cells. Here, we report that progestins also reinitiate cell cycle progression in this model. Using clonal cell lines derived from progesterone receptor (PR)-negative MCF-7M13 cells expressing wild-type or mutant forms of PRA and PRB, we show that this effect is mediated via PRB, not PRA. Cell cycle progression did not occur with a DNA-binding domain mutant of PRB but was unaffected by mutation in the NH(2)-terminal, SH3 domain interaction motif, which mediates rapid progestin activation of c-Src. Thus, the progestin-induced proliferative response in antiestrogen-inhibited cells is mediated primarily by the transcriptional activity of PRB. Analysis of selected cell cycle targets showed that progestin treatment induced levels of cyclin D1 expression and retinoblastoma protein (Rb) phosphorylation similar to those induced by estradiol. In contrast, progestin treatment resulted in only a 1.2-fold induction of c-Myc compared with a 10-fold induction by estradiol. These results support the conclusion that progestin, in a PRB-dependent manner, can overcome the growth-inhibitory effects of antiestrogens in estrogen receptor/PR-positive breast cancer cells by the induction of cyclin D1 expression. The mediation of this effect by PRB, but not PRA, further suggests a mechanism whereby abnormal regulation of the normal expression ratios of PR isoforms in breast cancer could lead to the attenuation of antiestrogen-mediated growth arrest. PMID:17875737

  16. Mechanisms of G1 cell cycle arrest and apoptosis in myeloma cells induced by hybrid-compound histone deacetylase inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Seiko [Division of Infections and Molecular Biology, Kyushu Dental University (Japan); Division of Maxillofacial Surgery, Kyushu Dental University (Japan); Okinaga, Toshinori; Ariyoshi, Wataru [Division of Infections and Molecular Biology, Kyushu Dental University (Japan); Oral Biology Research Center, Kyushu Dental University (Japan); Takahashi, Osamu; Iwanaga, Kenjiro [Division of Maxillofacial Surgery, Kyushu Dental University (Japan); Nishino, Norikazu [Oral Biology Research Center, Kyushu Dental University (Japan); Tominaga, Kazuhiro [Division of Maxillofacial Surgery, Kyushu Dental University (Japan); Nishihara, Tatsuji, E-mail: tatsujin@kyu-dent.ac.jp [Division of Infections and Molecular Biology, Kyushu Dental University (Japan); Oral Biology Research Center, Kyushu Dental University (Japan)

    2013-05-10

    Highlights: •Novel histone deacetylase inhibitor Ky-2, remarkably inhibits myeloma cell growth. •Ky-2 demonstrates no cytotoxicity against normal lymphocytic cells. •Ky-2 induces cell cycle arrest through the cell cycle-associated proteins. •Ky-2 induces Bcl-2-inhibitable apoptosis through a caspase-dependent cascade. -- Abstract: Objectives: Histone deacetylase (HDAC) inhibitors are new therapeutic agents, used to treat various types of malignant cancers. In the present study, we investigated the effects of Ky-2, a hybrid-compound HDAC inhibitor, on the growth of mouse myeloma cells. Materials and methods: Myeloma cells, HS-72, P3U1, and mouse normal cells were used in this study. Effect of HDAC inhibitors on cell viability was determined by WST-assay and trypan blue assay. Cell cycle was analyzed using flow cytometer. The expression of cell cycle regulatory and the apoptosis associated proteins were examined by Western blot analysis. Hoechst’s staining was used to detect apoptotic cells. Results: Our findings showed that Ky-2 decreased the levels of HDACs, while it enhanced acetylation of histone H3. Myeloma cell proliferation was inhibited by Ky-2 treatment. Interestingly, Ky-2 had no cytotoxic effects on mouse normal cells. Ky-2 treatment induced G1-phase cell cycle arrest and accumulation of a sub-G1 phase population, while Western blotting analysis revealed that expressions of the cell cycle-associated proteins were up-regulated. Also, Ky-2 enhanced the cleavage of caspase-9 and -3 in myeloma cells, followed by DNA fragmentation. In addition, Ky-2 was not found to induce apoptosis in bcl-2 overexpressing myeloma cells. Conclusion: These findings suggest that Ky-2 induces apoptosis via a caspase-dependent cascade and Bcl-2-inhibitable mechanism in myeloma cells.

  17. Mechanisms of G1 cell cycle arrest and apoptosis in myeloma cells induced by hybrid-compound histone deacetylase inhibitor

    International Nuclear Information System (INIS)

    Highlights: •Novel histone deacetylase inhibitor Ky-2, remarkably inhibits myeloma cell growth. •Ky-2 demonstrates no cytotoxicity against normal lymphocytic cells. •Ky-2 induces cell cycle arrest through the cell cycle-associated proteins. •Ky-2 induces Bcl-2-inhibitable apoptosis through a caspase-dependent cascade. -- Abstract: Objectives: Histone deacetylase (HDAC) inhibitors are new therapeutic agents, used to treat various types of malignant cancers. In the present study, we investigated the effects of Ky-2, a hybrid-compound HDAC inhibitor, on the growth of mouse myeloma cells. Materials and methods: Myeloma cells, HS-72, P3U1, and mouse normal cells were used in this study. Effect of HDAC inhibitors on cell viability was determined by WST-assay and trypan blue assay. Cell cycle was analyzed using flow cytometer. The expression of cell cycle regulatory and the apoptosis associated proteins were examined by Western blot analysis. Hoechst’s staining was used to detect apoptotic cells. Results: Our findings showed that Ky-2 decreased the levels of HDACs, while it enhanced acetylation of histone H3. Myeloma cell proliferation was inhibited by Ky-2 treatment. Interestingly, Ky-2 had no cytotoxic effects on mouse normal cells. Ky-2 treatment induced G1-phase cell cycle arrest and accumulation of a sub-G1 phase population, while Western blotting analysis revealed that expressions of the cell cycle-associated proteins were up-regulated. Also, Ky-2 enhanced the cleavage of caspase-9 and -3 in myeloma cells, followed by DNA fragmentation. In addition, Ky-2 was not found to induce apoptosis in bcl-2 overexpressing myeloma cells. Conclusion: These findings suggest that Ky-2 induces apoptosis via a caspase-dependent cascade and Bcl-2-inhibitable mechanism in myeloma cells

  18. Radical intermediate generation and cell cycle arrest by an aqueous extract of Thunbergia Laurifolia Linn. In human breast cancer cells.

    Science.gov (United States)

    Jetawattana, Suwimol; Boonsirichai, Kanokporn; Charoen, Savapong; Martin, Sean M

    2015-01-01

    Thunbergia Laurifolia Linn. (TL) is one of the most familiar plants in Thai traditional medicine that is used to treat various conditions, including cancer. However, the antitumor activity of TL or its constituents has never been reported at the molecular level to support the folklore claim. The present study was designed to investigate the antitumor effect of an aqueous extract of TL in human breast cancer cells and the possible mechanism(s) of action. An aqueous crude extract was prepared from dried leaves of TL. Folin-Ciocalteu colorimetric assays were used to determine the total phenolic content. Antiproliferative and cell cycle effects were evaluated in human breast adenocarcinoma MCF-7 cells by MTT reduction assay, cell growth inhibition, clonogenic cell survival, and flow cytometric analysis. Free radical generation by the extracts was detected using electron paramagnetic resonance spectroscopy. The exposure of human breast adenocarcinoma MCF-7 cells to a TL aqueous extract resulted in decreases in cell growth, clonogenic cell survival, and cell viability in a concentration-dependent manner with an IC50 value of 843 μg/ml. Treatments with extract for 24 h at 250 μg/ml or higher induced cell cycle arrest as indicated by a significant increase of cell population in the G1 phase and a significant decrease in the S phase of the cell cycle. The capability of the aqueous extract to generate radical intermediates was observed at both high pH and near-neutral pH conditions. The findings suggest the antitumor bioactivities of TL against selected breast cancer cells may be due to induction of a G1 cell cycle arrest. Cytotoxicity and cell cycle perturbation that are associated with a high concentration of the extract could be in part explained by the total phenolic contents in the extract and the capacity to generate radical intermediates to modulate cellular proliferative signals. PMID:26028099

  19. Evaluation of biomarkers of cell cycle arrest and inflammation in prediction of dialysis or recovery after kidney transplantation.

    Science.gov (United States)

    Pianta, Timothy J; Peake, Philip W; Pickering, John W; Kelleher, Michaela; Buckley, Nicholas A; Endre, Zoltan H

    2015-12-01

    Early prediction of delayed graft function (DGF) after kidney transplantation would facilitate patient management. Cell cycle arrest and inflammation are implicated in the pathogenesis of DGF. We assessed the utility of two novel acute kidney injury (AKI) biomarkers, urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), and five inflammatory markers to predict DGF following deceased-donor kidney transplantation. Serial urine concentrations of TIMP-2 and IGFBP7 were measured immediately after transplantation in 56 recipients along with vascular endothelial growth factor-A (VEGF-A), macrophage migration inhibitory factor (MIF), monocyte chemotactic protein-1 (MCP-1), trefoil factor 3 (TFF3) and chemokine (C-X-C) ligand 16 (CXCL16). Delayed graft function (DGF) was defined as requirement for dialysis within 7 days. Integrated discrimination improvement analysis was used to evaluate whether these biomarkers enhanced prediction of DGF independently of a validated clinical risk prediction model. DGF occurred in 22 patients (39%). At 4 h after kidney reperfusion, the area under the receiver operator characteristic curve (AUC) for VEGF-A was good (AUC > 0.80); for TIMP-2, IGFBP7 and [TIMP-2] × [IGFBP7] fair (AUCs 0.70-0.79); and for MIF, MCP-1, TFF3 and CXCL16 poor (AUC < 0.70). Only TIMP-2 and VEGF significantly enhanced the DGF prediction at 4 and 12 h. The cell cycle arrest marker urinary TIMP-2 and the inflammatory biomarker VEGF-A are potentially useful adjuncts to clinical data for early prediction of DGF. PMID:26174580

  20. The Effect of Irradiation and Epidermal Growth Factor on Cell Cycle and Apoptosis Induction in Human Epithelial Tumor Cell Lines

    International Nuclear Information System (INIS)

    This study was aimed to evaluate the cell cycle arrest and apoptosis induction after irradiation and epidermal growth factor (EGF) treatment in three human epithelial tumor cell lines (A431, Siha, KB). Single irradiation of 2, 5 and 10 Gy was done on three cell lines with 5.38 Gy/min dose rate using Cs-137 irradiator at room temperature. Also, EGF of 10 ng/ml was added immediately after 10 Gy irradiation. Cell growth was evaluated by counting the living cell number using a hemocytometer at 1 day, 2 days, 3 days, 4 days and 5 days after irradiation. Cell cycle arrest and apoptosis induction were assayed with the flow cytometry at 8 hours, 12 hours, 1 day, 2 days, 3 days, 4 days and 5 days after irradiation. Growth of irradiated three cell lines were inhibited in proportion to radiation dose. EGF treatment after irradiation showed various results according to cell lines. On all cell lines, G2 arrest was detected after 8 hours and maximized after 12 hours or 1 day. Amount of G2 arrest was positively dose dependent. But, EGF showed no significant change on G2 arrest. G2 arrest was recovered with time at 2 Gy and 5 Gy irradiation. But, at 10 Gy irradiation, G2 arrest was continued. Apoptosis was detected at 10 Gy irradiation. On EGF treated group after irradiation, A431 and Siha cell lines showed slightly increased apoptosis but there was no statistically significant difference. KB cell line showed no marked change of apoptosis induction. Irradiation effects cell cycle arrest and apoptosis induction in three human epithelial tumor cell lines but epidermal growth factor doesn't effect change of cell cycle arrest and apoptosis induction.

  1. Association of National Initiatives to Improve Cardiac Arrest Management With Rates of Bystander Intervention and Patient Survival After Out-of-Hospital Cardiac Arrest

    DEFF Research Database (Denmark)

    Wissenberg, Mads; Lippert, Freddy K; Folke, Fredrik;

    2013-01-01

    IMPORTANCE Out-of-hospital cardiac arrest is a major health problem associated with poor outcomes. Early recognition and intervention are critical for patient survival. Bystander cardiopulmonary resuscitation (CPR) is one factor among many associated with improved survival. OBJECTIVE To examine...... temporal changes in bystander resuscitation attempts and survival during a 10-year period in which several national initiatives were taken to increase rates of bystander resuscitation and improve advanced care. DESIGN, SETTING, AND PARTICIPANTS Patients with out-of-hospital cardiac arrest for which...

  2. Separation of craniopagus Siamese twins using cardiopulmonary bypass and hypothermic circulatory arrest.

    Science.gov (United States)

    Cameron, D E; Reitz, B A; Carson, B S; Long, D M; Dufresne, C R; Vander Kolk, C A; Maxwell, L G; Tilghman, D M; Nichols, D G; Wetzel, R C

    1989-11-01

    Occipitally joined craniopagus Siamese twins were separated with the use of cardiopulmonary bypass and hypothermic circulatory arrest. The 7-month-old infants shared a large sagittal venous sinus that precluded conventional neurosurgical approach because of risk of exsanguination and air embolism. After craniotomy and preliminary exposure of the sinus, each twin underwent sternotomy and total cardiopulmonary bypass with deep hypothermia. Hypothermic circulatory arrest allowed safe division and subsequent reconstruction of the sinus remnants. Several unusual problems were encountered, including transfusion of a large blood volume from one extracorporeal circuit to the other through the common venous sinus, deleterious warming of the exposed brain during circulatory arrest, and thrombosis of both pump oxygenators. Both infants survived, although recovery was complicated in each by neurologic injury, cranial wound infection, and hydrocephalus. This case demonstrates the valuable supportive role of cardiopulmonary bypass and hypothermic circulatory arrest in the management of complex surgical problems of otherwise inoperable patients. PMID:2682024

  3. Therapeutic Hypothermia and Out-of-Hospital Cardiac Arrest in a Child with Hypertrophic Obstructive Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Nancy Spurkeland

    2015-01-01

    Full Text Available Neurologic outcomes following pediatric cardiac arrest are consistently poor. Early initiation of cardiopulmonary resuscitation has been shown to have positive effects on both survival to hospital discharge, and improved neurological outcomes after cardiac arrest. Additionally, the use of therapeutic hypothermia may improve survival in pediatric cardiac arrest patients admitted to the intensive care unit. We report a child with congenital hypertrophic obstructive cardiomyopathy and an out-of-hospital cardiac arrest, in whom the early initiation of effective prolonged cardiopulmonary resuscitation and subsequent administration of therapeutic hypothermia contributed to a positive outcome with no gross neurologic sequelae. Continuing efforts should be made to promote and employ high-quality cardiopulmonary resuscitation, which likely contributed to the positive outcome of this case. Further research will be necessary to develop and solidify national guidelines for the implementation of therapeutic hypothermia in selected subpopulations of children with OHCA.

  4. EU Citizenship and European Arrest Warrant: The Same Rights for All?

    Directory of Open Access Journals (Sweden)

    Tony Marguery

    2011-06-01

    Full Text Available In the case Wolzenburg, the principle of non-discrimination of European Union citizens is applied to the European arrest warrant. The implementation of the European arrest warrant by the Member States cannot escape a control of proportional- ity made by the Court. Member States may impose a period of residence of five years to foreign Europeans citizens in order for them to rely on an optional ground for non-execution of a European arrest warrant (Article 4(6 of the Framework Deci- sion on the European arrest warrant. Home nationals are not obliged to comply with a residence requirement. It is possible for Member States to justify an exception to the principle of non-discrimination of European citizens with a legitimate inter- est. The chances of social reintegration of a person convicted constitute such an interest. The national measure resulting in a difference of treatment must be proportional to that interest.

  5. Biofilm Community Dynamics in Bench-Scale Annular Reactors Simulating Arrestment of Chloraminated Drinking Water Nitrification

    Science.gov (United States)

    Annular reactors (ARs) were used to study biofilm community succession and provide an ecological insight during nitrification arrestment through simultaneously increasing monochloramine (NH2Cl) and chlorine to nitrogen mass ratios, resulting in four operational periods (I to IV)....

  6. Arrest of metamorphosis induced by x rays in flesh fly, Sarcophaga peregrina

    International Nuclear Information System (INIS)

    Arrest of metamorphosis induced by x irradiation at prepupal stage was studied histologically, and age dependency of radiosensitivity with regard to this effect was examined. Prepupae did not cease their development soon after irradiation, but continued to develop and evaginated the head and the thorax. At this point, development came to a stop. In these animals, not only the histogenesis of imaginal tissues but also the histolysis of larval tissues was arrested. Since the arrest of development was not observed after irradiation at the pupal stage, the effect was considered to result from inhibition of initiation of postpupation development. A possible mechanism of the arrest of postpupation development in the irradiated animals was discussed in connection with the neuroendocrine control of insect development

  7. Temporal differences in out-of-hospital cardiac arrest incidence and survival

    DEFF Research Database (Denmark)

    Bagai, Akshay; McNally, Bryan F.; Al-Khatib, Sana M.;

    2013-01-01

    Understanding temporal differences in the incidence and outcomes of out-of-hospital cardiac arrest (OHCA) has important implications for developing preventative strategies and optimizing systems for OHCA care....

  8. Optimizing Neurologically Intact Survival from Sudden Cardiac Arrest: A Call to Action

    Directory of Open Access Journals (Sweden)

    Jeffrey M. Goodloe

    2014-11-01

    Full Text Available The U.S. national out-of-hospital and in-hospital cardiac arrest survival rates, although improving recently, have remained suboptimal despite the collective efforts of individuals, communities, and professional societies. Only until very recently, and still with inconsistency, has focus been placed specifically on survival with pre-arrest neurologic function. The reality of current approaches to sudden cardiac arrest is that they are often lacking an integrative, multi-disciplinary approach, and without deserved funding and outcome analysis. In this manuscript, a multidisciplinary group of authors propose practice, process, technology, and policy initiatives to improve cardiac arrest survival with a focus on neurologic function. [West J Emerg Med. 2014;15(7:-0.

  9. Hospital discharge diagnoses of ventricular arrhythmias and cardiac arrest were useful for epidemiologic research

    DEFF Research Database (Denmark)

    De Bruin, M L; van Hemel, N M; Leufkens, H G M;

    2005-01-01

    OBJECTIVE: We investigated the validity of hospital discharge diagnosis regarding ventricular arrhythmias and cardiac arrest. METHODS: We identified patients whose record in the PHARMO record linkage system database showed a code for ventricular or unspecified cardiac arrhythmias according to codes...

  10. Radiological analyses of France Telecom surge arresters. Study performed for the CGT FAPT Cantal

    International Nuclear Information System (INIS)

    This document reports the radiological characterization of various versions of surge arresters used in the past to protect telephone lines against over-voltages. These equipment, which use various radioactive materials, were assessed by gamma radiation flow measurements, alpha-beta-gamma count rate measurements, dose rate measurements, gamma spectrometry analyses, tritium emanation test, radon 222 emanation test, smearing. Recommendations are formulated to manage radioactive surge arresters which are still being operated

  11. Difference of cell cycle arrests induced by lidamycin in human breast cancer cells.

    Science.gov (United States)

    Liu, Xia; He, Hongwei; Feng, Yun; Zhang, Min; Ren, Kaihuan; Shao, Rongguang

    2006-02-01

    Lidamycin (LDM) is a member of the enediyne antibiotic family. It is undergoing phase I clinical trials in China as a potential chemotherapeutic agent. In the present study, we investigated the mechanism by which LDM induced cell cycle arrest in human breast cancer cells. The results showed that LDM induced G1 arrest in p53 wild-type MCF-7 cells at low concentrations, and caused both G1 and G2/M arrests at higher concentrations. In contrast, LDM induced only G2/M arrest in p53-mutant MCF-7/DOX cells. Western blotting analysis indicated that LDM-induced G1 and G2/M arrests in MCF-7 cells were associated with an increase of p53 and p21, and a decrease of phosphorylated retinoblastoma tumor suppressor protein, cyclin-dependent kinase (Cdk), Cdc2 and cyclin B1 protein levels. However, LDM-induced G2/M arrest in MCF-7/DOX cells was correlated with the reduction of cyclin B1 expression. Further study indicated that the downregulation of cyclin B1 by LDM in MCF-7 cells was associated with decreasing cyclin B1 mRNA levels and promoting protein degradation, whereas it was only due to inducing cyclin B1 protein degradation in MCF-7/DOX cells. In addition, activation of checkpoint kinases Chk1 or Chk2 maybe contributed to LDM-induced cell cycle arrest. Taken together, we provide the first evidence that LDM induces different cell cycle arrests in human breast cancer cells, which are dependent on drug concentration and p53 status. These findings are helpful in understanding the molecular anti-cancer mechanisms of LDM and support its clinical trials. PMID:16428935

  12. Crack arrest model for a piezoelectric strip subjected to Mode-I loadings

    OpenAIRE

    R.R. Bhargava; Amit Setia

    2007-01-01

    Purpose: The present paper aims at proposing a crack arrest model for an infinitely long narrow, poledceramic strip weakened by a finite hairline straight crack when the edges of the strip are subjected to combinedmechanical and electrical loads.Design/methodology/approach: (Model) As a consequence of loads the rims of crack open forming a yieldzone ahead of each tip of the crack. To arrest the crack from further opening the rims of the yield zones aresubjected to normal cohesive quadraticall...

  13. TGEV nucleocapsid protein induces cell cycle arrest and apoptosis through activation of p53 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Li [College of Veterinary Medicine, Northwest A and F University, Yangling, Shaanxi 712100 (China); College of Life Sciences, Hainan Normal University, Haikou, Hainan 571158 (China); Huang, Yong; Du, Qian; Dong, Feng; Zhao, Xiaomin; Zhang, Wenlong; Xu, Xingang [College of Veterinary Medicine, Northwest A and F University, Yangling, Shaanxi 712100 (China); Tong, Dewen, E-mail: dwtong@nwsuaf.edu.cn [College of Veterinary Medicine, Northwest A and F University, Yangling, Shaanxi 712100 (China)

    2014-03-07

    Highlights: • TGEV N protein reduces cell viability by inducing cell cycle arrest and apoptosis. • TGEV N protein induces cell cycle arrest and apoptosis by regulating p53 signaling. • TGEV N protein plays important roles in TGEV-induced cell cycle arrest and apoptosis. - Abstract: Our previous studies showed that TGEV infection could induce cell cycle arrest and apoptosis via activation of p53 signaling in cultured host cells. However, it is unclear which viral gene causes these effects. In this study, we investigated the effects of TGEV nucleocapsid (N) protein on PK-15 cells. We found that TGEV N protein suppressed cell proliferation by causing cell cycle arrest at the S and G2/M phases and apoptosis. Characterization of various cellular proteins that are involved in regulating cell cycle progression demonstrated that the expression of N gene resulted in an accumulation of p53 and p21, which suppressed cyclin B1, cdc2 and cdk2 expression. Moreover, the expression of TGEV N gene promoted translocation of Bax to mitochondria, which in turn caused the release of cytochrome c, followed by activation of caspase-3, resulting in cell apoptosis in the transfected PK-15 cells following cell cycle arrest. Further studies showed that p53 inhibitor attenuated TGEV N protein induced cell cycle arrest at S and G2/M phases and apoptosis through reversing the expression changes of cdc2, cdk2 and cyclin B1 and the translocation changes of Bax and cytochrome c induced by TGEV N protein. Taken together, these results demonstrated that TGEV N protein might play an important role in TGEV infection-induced p53 activation and cell cycle arrest at the S and G2/M phases and apoptosis occurrence.

  14. Why Do Increased Arrest Rates Appear to Reduce Crime: Deterrence, Incapacitation, or Measurement Error?

    OpenAIRE

    Steven D. Levitt

    1995-01-01

    A strong, negative empirical correlation exists between arrest rates and reported crime rates. While this relationship has often been interpreted as support for the deterrence hypothesis, it is equally consistent with incapacitation effects, and/or a spurious correlation that would be induced by measurement error in reported crime rates. This paper attempts to discriminate between deterrence, incapacitation, and measurement error as explanations for the empirical relationship between arrest r...

  15. Effect of four resuscitation methods on lung ventilation of pigs with respiratory arrest

    OpenAIRE

    Ya-hua LIU; Xiu-man LI; Li-xiang WANG

    2012-01-01

    Objective To observe the effects of four cardiopulmonary resuscitation (CPR) methods on lung ventilation of pigs with respiratory arrest. The four CPR methods included chest compression CPR (C-CPR), compression under the diaphragm CPR (D-CPR), abdominal compression CPR (A-CPR), and abdominal wall lifting and compression CPR (L-CPR). Methods  A total of 28 healthy domestic pigs were randomly divided into four groups. The pig respiratory arrest model was reproduced by intravenous injection of s...

  16. Establishing the Aus-ROC Australian and New Zealand out-of-hospital cardiac arrest Epistry

    OpenAIRE

    Beck, Ben; Bray, Janet; Smith, Karen; Walker, Tony; Grantham, Hugh; Hein, Cindy; Thorrowgood, Melanie; Smith, Anthony; Smith, Tony; Dicker, Bridget; Swain, Andy; Bailey, Mark; Bosley, Emma; Pemberton, Katherine; Cameron, Peter

    2016-01-01

    Introduction Out-of-hospital cardiac arrest (OHCA) is a global health problem with low survival. Regional variation in survival has heightened interest in combining cardiac arrest registries to understand and improve OHCA outcomes. While individual OHCA registries exist in Australian and New Zealand ambulance services, until recently these registries have not been combined. The aim of this protocol paper is to describe the rationale and methods of the Australian Resuscitation Outcomes Consort...

  17. Caries remineralisation and arresting effect in children by professionally applied fluoride treatment – a systematic review

    OpenAIRE

    Gao, Sherry Shiqian; Zhang, Shinan; Mei, May Lei; Lo, Edward Chin-Man; Chu, Chun-Hung

    2016-01-01

    Background As a low-cost and easily operated treatment, the use of professionally applied topical fluoride was approved for preventing dental caries and remineralising early enamel caries or white spot lesions. It is also used to arrest dentine caries. The aim of this study is to investigate the clinical efficacy of professional fluoride therapy in remineralising and arresting caries in children. Method A systematic search of publications from 1948 to 2014 was conducted using four databases: ...

  18. Effects of Abusive Parenting, Caretaker Arrests, and Deviant Behavior on Dating Violence among Homeless Young Adults

    OpenAIRE

    Tyler, Kimberly A.; Schmitz, Rachel M.

    2015-01-01

    Though dating violence is widespread among young adult homeless populations, its risk factors are poorly understood by scholars. To address this gap, the current study uses a social learning theory to examine the effects of abusive parenting and caretaker arrests on dating violence among 172 homeless young adults. Results from path analyses revealed that child physical abuse and caretaker arrests were positively associated with engaging in a greater number of school fights, which, in turn, wa...

  19. The Oxygen-Rich Postnatal Environment Induces Cardiomyocyte Cell-Cycle Arrest through DNA Damage Response

    OpenAIRE

    Bao\\xa0N. Puente; Wataru Kimura; Shalini\\xa0A. Muralidhar; Jesung Moon; James\\xa0F. Amatruda; Kate\\xa0L. Phelps; David Grinsfelder; Beverly\\xa0A. Rothermel; Rui Chen; Joseph\\xa0A. Garcia; Celio\\xa0X. Santos; SuWannee Thet; Eiichiro Mori; Michael\\xa0T. Kinter; Paul\\xa0M. Rindler

    2014-01-01

    The mammalian heart has a remarkable regenerative capacity for a short period of time after birth, after which the majority of cardiomyocytes permanently exit cell cycle. We sought to determine the primary post-natal event that results in cardiomyocyte cell-cycle arrest. We hypothesized that transition to the oxygen rich postnatal environment is the upstream signal that results in cell cycle arrest of cardiomyocytes. Here we show that reactive oxygen species (ROS), oxidative DNA damage, and D...

  20. A randomized clinical trial on arresting dentin caries in preschool children by topical fluorides

    OpenAIRE

    Duangthip, Duangporn

    2015-01-01

    Introduction: Silver diammine fluoride (SDF) has been found to be effective in preventing and arresting dental caries in children. The annual or semi-annual application of SDF may not be practical in migratory populations or effective high caries risk patients. So far, no data are available about the effectiveness of intensive fluoride treatment in arresting dental caries in primary teeth. Objectives: This study aimed to compare the effectiveness of three topical fluoride application prot...

  1. Local stresses, dyke arrest and surface deformation in volcanic edificesand rift zones

    Directory of Open Access Journals (Sweden)

    L. S. Brenner

    2004-06-01

    Full Text Available Field studies indicate that nearly all eruptions in volcanic edifices and rift zones are supplied with magma through fractures (dykes that are opened by magmatic overpressure. While (inferred dyke injections are frequent during unrest periods, volcanic eruptions are, in comparison, infrequent, suggesting that most dykes become arrested at certain depths in the crust, in agreement with field studies. The frequency of dyke arrest can be partly explained by the numerical models presented here which indicate that volcanic edifices and rift zones consisting of rocks of contrasting mechanical properties, such as soft pyroclastic layers and stiff lava flows, commonly develop local stress fields that encourage dyke arrest. During unrest, surface deformation studies are routinely used to infer the geometries of arrested dykes, and some models (using homogeneous, isotropic half-spaces infer large grabens to be induced by such dykes. Our results, however, show that the dyke-tip tensile stresses are normally much greater than the induced surface stresses, making it difficult to explain how a dyke can induce surface stresses in excess of the tensile (or shear strength while the same strength is not exceeded at the (arrested dyke tip. Also, arrested dyke tips in eroded or active rift zones are normally not associated with dyke-induced grabens or normal faults, and some dykes arrested within a few metres of the surface do not generate faults or grabens. The numerical models show that abrupt changes in Young's moduli(stiffnesses, layers with relatively high dyke-normal compressive stresses (stress barriers, and weak horizontal contacts may make the dyke-induced surface tensile stresses too small for significant fault or graben formation to occur in rift zones or volcanic edifices. Also, these small surface stresses may have no simple relation to the dyke geometry or the depth to its tip. Thus, for a layered crust with weak contacts, straightforward

  2. Double Bolus Thrombolysis for Suspected Massive Pulmonary Embolism during Cardiac Arrest

    OpenAIRE

    Gerard O’Connor; Gareth Fitzpatrick; Ayman El-Gammal; Peadar Gilligan

    2015-01-01

    More than 70% of cardiac arrest cases are caused by acute myocardial infarction (AMI) or pulmonary embolism (PE). Although thrombolytic therapy is a recognised therapy for both AMI and PE, its indiscriminate use is not routinely recommended during cardiopulmonary resuscitation (CPR). We present a case describing the successful use of double dose thrombolysis during cardiac arrest caused by pulmonary embolism. Notwithstanding the relative lack of high-level evidence, this case suggests a scena...

  3. miR-6734 Up-Regulates p21 Gene Expression and Induces Cell Cycle Arrest and Apoptosis in Colon Cancer Cells

    Science.gov (United States)

    Kang, Moo Rim; Park, Ki Hwan; Yang, Jeong-Ook; Lee, Chang Woo; Oh, Soo Jin; Yun, Jieun; Lee, Myeong Youl; Han, Sang-Bae; Kang, Jong Soon

    2016-01-01

    Recently, microRNAs have been implicated in the regulation of gene expression in terms of both gene silencing and gene activation. Here, we investigated the effects of miR-6734, which has a sequence homology with a specific region of p21WAF1/CIP1 (p21) promoter, on cancer cell growth and the mechanisms involved in this effect. miR-6734 up-regulated p21 expression at both mRNA and protein levels and chromatin immunoprecipitation analysis using biotin-labeled miR-6734 confirmed the association of miR-6734 with p21 promoter. Moreover, miR-6734 inhibited cancer cell growth and induced cell cycle arrest and apoptosis in HCT-116 cells, which was abolished by knockdown of p21. The phosphorylation of Rb and the cleavage of caspase 3 and PARP were suppressed by miR-6734 transfection in HCT-116 cells and these effects were also reversed by p21 knockdown. In addition, miR-6734 transfection caused prolonged induction of p21 gene and modification of histones in p21 promoter, which are typical aspects of a phenomenon referred to as RNA activation (RNAa). Collectively, our results demonstrated that miR-6734 inhibits the growth of colon cancer cells by up-regulating p21 gene expression and subsequent induction of cell cycle arrest and apoptosis, suggesting its role as an important endogenous regulator of cancer cell proliferation and survival. PMID:27509128

  4. Protein synthetic requirements for caffeine amelioration of radiation-induced G/sub 2/-arrest

    International Nuclear Information System (INIS)

    Irradiated cells are arrested in G/sub 2/ (transition point [TP] = 32 min before cell selection in mitosis). Irradiated cells do not recover from G/sub 2/ arrest in the presence of cycloheximide (CHM) indicating dependence of recovery on protein synthesis. Irradiated cells in the presence of caffeine progress to mitosis without arrest. The authors investigate whether irradiated cells in the presence of caffeine require protein synthesis to progress to mitosis. Mitotic cell selection was used to monitor the progression of irradiated CHO cells (150 rad) during exposure to 5 mM caffeine and/or 50 μg/ml CHM. Protein synthesis inhibition was confirmed using /sup 3/H-leucine incorporation. Cells exposed to CHM alone are arrested in G/sub 2/ (TP=49 min), thus cells beyond this point have synthesized all proteins necessary for entry into mitosis. In the presence of caffeine, unirradiated cells exposed to CHM are not arrested at all in G/sub 2/, instead arrest occurs near the S/G/sub 2/ boundary (TP=95 min) indicating that caffeine alleviates the dependence of G/sub 2/ cell progression on protein synthesis. However, irradiated cells exposed to both caffeine and CHM are only able to progress to mitosis if beyond the CHM-TP. Irradiated cells in the presence of caffeine thus behave as untreated cells and require protein synthesis for progression to mitosis when prior to the CHM-TP

  5. Sudden cardiac arrest in a patient with epilepsy induced by chronic inflammation on the cerebral surface

    Institute of Scientific and Technical Information of China (English)

    Yuxi Liu; Weicheng Hao; Xiaoming Yang; Yimin Wang; Yu Su

    2012-01-01

    The present study analyzed a patient with epilepsy due to chronic inflammation on the cerebral surface underwent sudden cardiac arrest. Paradoxical brain discharge, which occurred prior to epileptic seizures, induced a sudden cardiac arrest. However, when the focal brain pressure was relieved, cardiac arrest disappeared. A 27-year-old male patient underwent pre-surgical video-electroencephalogram monitoring for 160 hours. During monitoring, secondary tonic-clonic seizures occurred five times. A burst of paradoxical brain discharges occurred at 2-19 seconds (mean 8 seconds) prior to epileptic seizures. After 2-3 seconds, sudden cardiac arrest occurred and lasted for 12-22 seconds (average 16 seconds). The heart rate subsequently returned to a normal rate. Results revealed arachnoid pachymenia and adhesions, as well as mucus on the focal cerebral surface, combined with poor circulation and increased pressure. Intracranial electrodes were placed using surgical methods. Following removal of the arachnoid adhesions and mucus on the local cerebral surface, paradoxical brain discharge and epileptic seizures occurred three times, but sudden cardiac arrest was not recorded during 150-hour monitoring. Post-surgical histological examination indicated meningitis. Experimental findings suggested that paradoxical brain discharge led to cardiac arrest instead of epileptic seizures; the insult was associated with chronic inflammation on the cerebral surface, which subsequently led to hypertension and poor blood circulation in focal cerebral areas.

  6. Role of Surface to Volume Ratio of Zinc Oxide Arrester Blocks on the Energy Absorption Capability

    International Nuclear Information System (INIS)

    The functional life of a zinc oxide arrester block is largely dependent on its energy absorption capability. This capability is an important performance characteristic of a lighting arrester which leads to enhanced reliability of a surge protection system. An arrester block is usually cylindrical in shape with two flat surfaces. Injected energy of transient electrical surge into the arrester body is transformed into heat and dissipated through the surface of the disc body. This study has been conducted to observe whether the higher surface to volume (S/V) ratio of an arrester block enhances the capability of energy absorption or not. The round side or C-surface of the cylindrical disc was ground by diamond wheel to transform into hexagonal shape. By making the modification of the geometrical shape an increase of about 11% in S/V ratio was achieved. ZnO arrester blocks of both shapes were tested for energy. The average energy absorption capability for the hexagonal discs was found to be 483 J.cm−3 compared to that of 357 J.cm−3 for the discs having the cylindrical shape. Thus, about 35% increase in energy absorption capability is observed for the hexagonal discs. This knowledge can be useful in designing the geometry of the device for improved functional reliability of electrical system.

  7. Master curve based correlation between static initiation toughness KIC and crack arrest toughness KIa

    International Nuclear Information System (INIS)

    Historically the ASME reference curve concept assumes a constant relation between static fracture toughness initiation toughness and crack arrest toughness. In reality, this is not the case. Experimental results show that the difference between KIC and KIa is material specific. For some materials there is a big difference while for others they nearly coincide. So far, however, no systematic study regarding a possible correlation between the two parameters has been performed. The recent Master curve method, developed for brittle fracture initiation estimation, has enabled a consistent analysis of fracture initiation toughness data. The Master curve method has been modified to be able to describe also crack arrest toughness. Here, this modified 'crack arrest master curve' is further validated and used to develop a simple, but yet (for safety assessment purpose) adequately accurate correlation between the two fracture toughness parameters. The correlation enables the estimation of crack arrest toughness from small Charpy-sized static fracture toughness tests. The correlation is valid for low Nickel steels ≤ (1.2% Ni). If a more accurate description of the crack arrest toughness is required, it can either be measured experimentally or estimated from instrumented Charpy-V crack arrest load information. (orig.)

  8. Use of Sodium Bicarbonate in Cardiac Arrest: Current Guidelines and Literature Review.

    Science.gov (United States)

    Velissaris, Dimitrios; Karamouzos, Vassilios; Pierrakos, Charalampos; Koniari, Ioanna; Apostolopoulou, Christina; Karanikolas, Menelaos

    2016-04-01

    The aim of the review was to summarize the literature over the last 25 years regarding bicarbonate administration in out-of-hospital cardiac arrest. A PubMed search was conducted using the terms "bicarbonates" and "cardiac arrest", limited to human studies and reviews published in English (or at least with a meaningful abstract in English) in the last 25 years. Clinical and experimental data raised questions regarding the safety and effectiveness of sodium bicarbonate (SB) administration during cardiac arrest. Earlier advanced cardiac life support (ACLS) guidelines recommended routine bicarbonate administration as part of the ACLS algorithm, but recent guidelines no longer recommend its use. The debate in the literature is ongoing, but at the present time, SB administration is only recommended for cardiac arrest related to hypokalemia or overdose of tricyclic antidepressants. Several studies challenge the assumption that bicarbonate administration is beneficial for treatment of acidosis in cardiac arrest. At the present time, there is a trend against using bicarbonates in cardiac arrest, and this trend is supported by guidelines published by professional societies and organizations. PMID:26985247

  9. Incidence of out-of-hospital cardiac arrest.

    Science.gov (United States)

    Rea, Thomas D; Pearce, Rachel M; Raghunathan, Trivellore E; Lemaitre, Rozenn N; Sotoodehnia, Nona; Jouven, Xavier; Siscovick, David S

    2004-06-15

    Estimates of the incidence of out-of-hospital primary cardiac arrest (CA) have typically relied solely upon emergency medical service or death certificate records and have not investigated incidence in clinical subgroups. Overall and temporal patterns of CA incidence were investigated in clinically defined groups using systematic methods to ascertain CA. Estimates of incidence were derived from a population-based case-control study in a large health plan from 1986 to 1994. Subjects were enrollees aged 50 to 79 years who had had CA (n = 1,275). A stratified random sample of enrollees who had not had CA was used to estimate the population at risk with various clinical characteristics (n = 2,323). Poisson's regression was used to estimate incidence overall and for 3-year time periods (1986 to 1988, 1989 to 1991, and 1992 to 1994). The overall CA incidence was 1.89/1,000 subject-years and varied up to 30-fold across clinical subgroups. For example, incidence was 5.98/1,000 subject-years in subjects with any clinically recognized heart disease compared with 0.82/1,000 subject-years in subjects without heart disease. In subgroups with heart disease, incidence was 13.69/1,000 subject-years in subjects with prior myocardial infarction and 21.87/1,000 subject-years in subjects with heart failure. Risk decreased by 20% from the initial to the final time period, with a greater decrease observed in those with (25%) compared with those without (12%) clinical heart disease. Thus, CA incidence varied considerably across clinical groups. The results provide insights regarding absolute and population-attributable risk in clinically defined subgroups, information that may aid strategies aimed at reducing mortality from CA. PMID:15194012

  10. Mechanisms involved in alternariol-induced cell cycle arrest

    International Nuclear Information System (INIS)

    Alternariol (AOH), a mycotoxin produced by Alternaria sp, is often found as a contaminant in fruit and cereal products. Here we employed the murine macrophage cell line RAW 264.7 to test the hypothesis that AOH causes toxicity as a response to DNA damage. AOH at concentrations of 15–30 μM almost completely blocked cell proliferation. Within 30 min treatment, AOH (30 μM) significantly increased the level of reactive oxygen species (ROS). Furthermore, DNA base oxidations as well as DNA strand breaks and/or alkaline labile sites were detected by the comet assay after 2 h exposure of AOH. Cell death (mostly necrosis) was observed after prolonged exposure to the highest concentration of AOH (60 μM for 24 and 48 h) in our study. The DNA damage response involved phosphorylation (activation) of histone H2AX and check point kinase-1- and 2 (Chk-1/2). Moreover, AOH activated p53 and increased the expression of p21, Cyclin B, MDM2, and Sestrin 2; likewise the level of several miRNA was affected. AOH-induced Sestrin 2 expression was regulated by p53 and could at least partly be inhibited by antioxidants, suggesting a role of ROS in the response. Interestingly, the addition of antioxidants did not inhibit cell cycle arrest. Although the formation of ROS by itself was not directly linked cell proliferation, AOH-induced DNA damage and resulting transcriptional changes in p21, MDM2, and Cyclin B likely contribute to the reduced cell proliferation; while Sestrin 2 would contribute to the oxidant defense.

  11. Mechanisms involved in alternariol-induced cell cycle arrest

    Energy Technology Data Exchange (ETDEWEB)

    Solhaug, A., E-mail: Anita.Solhaug@vetinst.no [Norwegian Veterinary Institute, Oslo (Norway); Vines, L.L. [Michigan State University, Department of Food Science and Human Nutrition, East Lansing, MI (United States); Ivanova, L.; Spilsberg, B. [Norwegian Veterinary Institute, Oslo (Norway); Holme, J.A. [Norwegian Institute of Public Health, Division of Environmental Medicine, Oslo (Norway); Pestka, J. [Michigan State University, Department of Food Science and Human Nutrition, East Lansing, MI (United States); Collins, A. [University of Oslo, Department of Nutrition, Faculty of Medicine, Oslo (Norway); Eriksen, G.S. [Norwegian Veterinary Institute, Oslo (Norway)

    2012-10-15

    Alternariol (AOH), a mycotoxin produced by Alternaria sp, is often found as a contaminant in fruit and cereal products. Here we employed the murine macrophage cell line RAW 264.7 to test the hypothesis that AOH causes toxicity as a response to DNA damage. AOH at concentrations of 15-30 {mu}M almost completely blocked cell proliferation. Within 30 min treatment, AOH (30 {mu}M) significantly increased the level of reactive oxygen species (ROS). Furthermore, DNA base oxidations as well as DNA strand breaks and/or alkaline labile sites were detected by the comet assay after 2 h exposure of AOH. Cell death (mostly necrosis) was observed after prolonged exposure to the highest concentration of AOH (60 {mu}M for 24 and 48 h) in our study. The DNA damage response involved phosphorylation (activation) of histone H2AX and check point kinase-1- and 2 (Chk-1/2). Moreover, AOH activated p53 and increased the expression of p21, Cyclin B, MDM2, and Sestrin 2; likewise the level of several miRNA was affected. AOH-induced Sestrin 2 expression was regulated by p53 and could at least partly be inhibited by antioxidants, suggesting a role of ROS in the response. Interestingly, the addition of antioxidants did not inhibit cell cycle arrest. Although the formation of ROS by itself was not directly linked cell proliferation, AOH-induced DNA damage and resulting transcriptional changes in p21, MDM2, and Cyclin B likely contribute to the reduced cell proliferation; while Sestrin 2 would contribute to the oxidant defense.

  12. Snake constriction rapidly induces circulatory arrest in rats.

    Science.gov (United States)

    Boback, Scott M; McCann, Katelyn J; Wood, Kevin A; McNeal, Patrick M; Blankenship, Emmett L; Zwemer, Charles F

    2015-07-01

    As legless predators, snakes are unique in their ability to immobilize and kill their prey through the process of constriction, and yet how this pressure incapacitates and ultimately kills the prey remains unknown. In this study, we examined the cardiovascular function of anesthetized rats before, during and after being constricted by boas (Boa constrictor) to examine the effect of constriction on the prey's circulatory function. The results demonstrate that within 6 s of being constricted, peripheral arterial blood pressure (PBP) at the femoral artery dropped to 1/2 of baseline values while central venous pressure (CVP) increased 6-fold from baseline during the same time. Electrocardiographic recordings from the anesthetized rat's heart revealed profound bradycardia as heart rate (fH) dropped to nearly half of baseline within 60 s of being constricted, and QRS duration nearly doubled over the same time period. By the end of constriction (mean 6.5±1 min), rat PBP dropped 2.9-fold, fH dropped 3.9-fold, systemic perfusion pressure (SPP=PBP-CVP) dropped 5.7-fold, and 91% of rats (10 of 11) had evidence of cardiac electrical dysfunction. Blood drawn immediately after constriction revealed that, relative to baseline, rats were hyperkalemic (serum potassium levels nearly doubled) and acidotic (blood pH dropped from 7.4 to 7.0). These results are the first to document the physiological response of prey to constriction and support the hypothesis that snake constriction induces rapid prey death due to circulatory arrest. PMID:26202779

  13. The Arrested Black Men in Europe: Criminal or Victim?

    Directory of Open Access Journals (Sweden)

    Michael Platzer

    2007-12-01

    Full Text Available The Africans detained in Austria have been targeted by police by their skin color, often are arrested with violence, are poorly defended by assigned defense lawyers, given longer sentences than Austrian citizens and have less access to alternatives or bail.A modified form of the United Nations Crime Victim questionnaire was administered to all the African prisoners at the Vienna’s Central Detention Facility. It revealed that the Africans were not only victims of violence (sometimes even torture and crimes (assault-58%, burglary-32%, fraud-27%, bribery-33% in their home countries, but also 24 percent had experienced assault, 16% theft, and 13% had been defrauded in Austria-much higher rates than the EU citizen. On the other hand, the Africans are rarely charged with burglary, robbery, or violent crimes. They are primarily arrested for the possession or sale of narcotic drugs (83% and an additional four percent for resisting arrest. This is primarily the result of insufficient financial support provided to asylum seekers and the prohibition to work pending their determination of immigrant status. Because of the long appeal processes and the practical impossibility of deporting certain nationalities, a type of underground community is taking root where simple survival is the determining factor whether to commit a non-violent offence. Les Africains détenus en Autriche sont visés par la police à cause de la couleur de leur peau; ils sont souvent arrêtés avec violence, sont mal défendus par leurs avocats de défense, doivent passer de plus longues périodes en prison que des citoyens autrichiens ayant commis un crime pareil, et ils ont moins d'accès aux mesures extrajudiciaires et au système de liberté sous caution. Une forme modifiée du questionnaire de victimes de crime des Nations Unies fut administrée à tous les prisonniers africains au Service Central de la Détention de Vienne. Les résultats indiquèrent que les Africains furent

  14. Aspafilioside B induces G2/M cell cycle arrest and apoptosis by up-regulating H-Ras and N-Ras via ERK and p38 MAPK signaling pathways in human hepatoma HepG2 cells.

    Science.gov (United States)

    Liu, Wei; Ning, Rui; Chen, Rui-Ni; Huang, Xue-Feng; Dai, Qin-Sheng; Hu, Jin-Hua; Wang, Yu-Wen; Wu, Li-Li; Xiong, Jing; Hu, Gang; Guo, Qing-Long; Yang, Jian; Wang, Hao

    2016-05-01

    We recently establish that aspafilioside B, a steroidal saponin extracted from Asparagus filicinus, is an active cytotoxic component. However, its antitumor activity is till unknown. In this study, the anticancer effect of aspafilioside B against HCC cells and the underlying mechanisms were investigated. Our results showed that aspafilioside B inhibited the growth and proliferation of HCC cell lines. Further study revealed that aspafilioside B could significantly induce G2 phase cell cycle arrest and apoptosis, accompanying the accumulation of reactive oxygen species (ROS), but blocking ROS generation with N-acetyl-l-cysteine (NAC) could not prevent G2/M arrest and apoptosis. Additionally, treatment with aspafilioside B induced phosphorylation of extracellular signal-regulated kinase (ERK) and p38 MAP kinase. Moreover, both ERK inhibitor PD98059 and p38 inhibitor SB203580 almost abolished the G2/M phase arrest and apoptosis induced by aspafilioside B, and reversed the expression of cell cycle- and apoptosis-related proteins. We also found that aspafilioside B treatment increased both Ras and Raf activation, and transfection of cells with H-Ras and N-Ras shRNA almost attenuated aspafilioside B-induced G2 phase arrest and apoptosis as well as the ERK and p38 activation. Finally, in vivo, aspafilioside B suppressed tumor growth in mouse xenograft models, and the mechanism was the same as in vitro study. Collectively, these findings indicated that aspafilioside B may up-regulate H-Ras and N-Ras, causing c-Raf phosphorylation, and lead to ERK and p38 activation, which consequently induced the G2 phase arrest and apoptosis. This study provides the evidence that aspafilioside B is a promising therapeutic agent against HCC. PMID:25683703

  15. LRD-22, a novel dual dithiocarbamatic acid ester, inhibits Aurora-A kinase and induces apoptosis and cell cycle arrest in HepG2 cells

    International Nuclear Information System (INIS)

    In this study we investigated the antitumor activity of the novel dual dithiocarbamatic acid ester LRD-22 in vitro and in vivo. Several cancer cell lines were employed to determine the effect of LRD-22 on cell growth, and the MTT assay showed there was a significant decrease in viable tumor cell numbers in the presence of LRD-22, especially in the HepG2 cell line. Colony formation assay also showed LRD-22 strongly inhibits HepG2 cell growth. Evaluation of the mechanism involved showed that inhibitory effects of LRD-22 on cell growth are due to induction of apoptosis and G2/M arrest. LRD-22 inhibited Aurora-A phosphorylation at Thr288 and subsequently impaired p53 phosphorylation at Ser315 which was associated with the proteasome degradation pathway. Tumor suppressor protein p53 is stabilized by this mechanism and accumulates through inhibition of Aurora-A kinase activity via treatment with LRD-22. In vivo study of HepG2 xenograft in nude mice also shows LRD-22 suppresses tumor growth at a concentration of 5 mg/kg without animals suffering loss of body weight. In conclusion, our results demonstrate LRD-22 acts as an Aurora-A kinase inhibitor to induce apoptosis and inhibit proliferation in HepG2 cells, and should be considered as a promising targeting agent for HCC therapy. - Highlights: • LRD-22 significantly inhibits cancer cell growth, especially in the HepG2 cell line. • The inhibitory effect of LRD-22 is due to induction of apoptosis and cell cycle arrest. • LRD-22 inhibits Aurora-A phosphorylation which results in subsequent impairment of the p53 pathway. • LRD-22 suppresses tumor growth in xenograft mice without body weight loss

  16. LRD-22, a novel dual dithiocarbamatic acid ester, inhibits Aurora-A kinase and induces apoptosis and cell cycle arrest in HepG2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Huiling; Li, Ridong [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing (China); Li, Li [Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing (China); Ge, Zemei [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing (China); Zhou, Rouli, E-mail: rlzhou@bjmu.edu.cn [Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing (China); Li, Runtao, E-mail: lirt@bjmu.edu.cn [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing (China)

    2015-02-27

    In this study we investigated the antitumor activity of the novel dual dithiocarbamatic acid ester LRD-22 in vitro and in vivo. Several cancer cell lines were employed to determine the effect of LRD-22 on cell growth, and the MTT assay showed there was a significant decrease in viable tumor cell numbers in the presence of LRD-22, especially in the HepG2 cell line. Colony formation assay also showed LRD-22 strongly inhibits HepG2 cell growth. Evaluation of the mechanism involved showed that inhibitory effects of LRD-22 on cell growth are due to induction of apoptosis and G2/M arrest. LRD-22 inhibited Aurora-A phosphorylation at Thr{sub 288} and subsequently impaired p53 phosphorylation at Ser{sub 315} which was associated with the proteasome degradation pathway. Tumor suppressor protein p53 is stabilized by this mechanism and accumulates through inhibition of Aurora-A kinase activity via treatment with LRD-22. In vivo study of HepG2 xenograft in nude mice also shows LRD-22 suppresses tumor growth at a concentration of 5 mg/kg without animals suffering loss of body weight. In conclusion, our results demonstrate LRD-22 acts as an Aurora-A kinase inhibitor to induce apoptosis and inhibit proliferation in HepG2 cells, and should be considered as a promising targeting agent for HCC therapy. - Highlights: • LRD-22 significantly inhibits cancer cell growth, especially in the HepG2 cell line. • The inhibitory effect of LRD-22 is due to induction of apoptosis and cell cycle arrest. • LRD-22 inhibits Aurora-A phosphorylation which results in subsequent impairment of the p53 pathway. • LRD-22 suppresses tumor growth in xenograft mice without body weight loss.

  17. Clinical investigation: thyroid function test abnormalities in cardiac arrest associated with acute coronary syndrome

    Science.gov (United States)

    Iltumur, Kenan; Olmez, Gonul; Arıturk, Zuhal; Taskesen, Tuncay; Toprak, Nizamettin

    2005-01-01

    Introduction It is known that thyroid homeostasis is altered during the acute phase of cardiac arrest. However, it is not clear under what conditions, how and for how long these alterations occur. In the present study we examined thyroid function tests (TFTs) in the acute phase of cardiac arrest caused by acute coronary syndrome (ACS) and at the end of the first 2 months after the event. Method Fifty patients with cardiac arrest induced by ACS and 31 patients with acute myocardial infarction (AMI) who did not require cardioversion or cardiopulmonary resuscitation were enrolled in the study, as were 40 healthy volunteers. The patients were divided into three groups based on duration of cardiac arrest (10 min). Blood samples were collected for thyroid-stimulating hormone (TSH), tri-iodothyronine (T3), free T3, thyroxine (T4), free T4, troponin-I and creatine kinase-MB measurements. The blood samples for TFTs were taken at 72 hours and at 2 months after the acute event in the cardiac arrest and AMI groups, but only once in the control group. Results The T3 and free T3 levels at 72 hours in the cardiac arrest group were significantly lower than in both the AMI and control groups (P 0.05). At the 2-month evaluation, a dramatic improvement was observed in T3 and free T3 levels in the cardiac arrest group (P < 0.0001). In those patients whose cardiac arrest duration was in excess of 10 min, levels of T3, free T3, T4 and TSH were significantly lower than those in patients whose cardiac arrest duration was under 5 min (P < 0.001, P < 0.001, P < 0.005 and P < 0.05, respectively). Conclusion TFTs are significantly altered in cardiac arrest induced by ACS. Changes in TFTs are even more pronounced in patients with longer periods of resuscitation. The changes in the surviving patients were characterized by euthyroid sick syndrome, and this improved by 2 months in those patients who did not progress into a vegetative state. PMID:16137355

  18. Cell cycle arrest biomarkers in human lung cancer cells after treatment with selenium in culture.

    Science.gov (United States)

    Swede, Helen; Dong, Yan; Reid, Mary; Marshall, James; Ip, Clement

    2003-11-01

    In the planning of future intervention trials using chemopreventive agents against lung cancer, it is critical to evaluate the effect on biomarkers implicated specifically in lung carcinogenesis. With the use of the H520 and H522 human lung cancer cell lines, the present study showed that treatment with selenium (in the form of methylseleninic acid) inhibited cell growth, arrested cell cycle progression at G(1), and induced apoptosis as a late event. Because H520 cells were more sensitive to selenium than H522 cells (IC(50) of MSA was 2.5 or 10 micro M for H520 or H522 cells, respectively, at 24 h), a panel of nine cell cycle regulatory proteins known to be involved in G(1)-->S transition was assessed by Western analysis using whole cell lysate from H520 cells. These nine proteins (DP1, cdc25A, cyclin A, cyclin B(1), cyclin D(1), cdk1, cdk5, p21(WAF1), and GADD153) have been reported previously by our laboratory to be modulated by MSA in human breast and prostate cancer cells. Our data showed that only four (DP1, cdc25A, p21(WAF1), and GADD153) of nine biomarkers produced the expected changes after treatment of lung cancer cells with MSA. This finding raises the possibility that the molecular targets sensitive to selenium modulation may be tissue specific. Thus, the selection of selenium biomarkers for evaluation in an intervention trial must be based on empirical data derived from the cancer cell type of interest. PMID:14652289

  19. Absence of p53 in Clara cells favours multinucleation and loss of cell cycle arrest

    Directory of Open Access Journals (Sweden)

    Clarke Alan R

    2002-11-01

    Full Text Available Abstract Background The p53 oncosuppressor protein is a critical mediator of the response to injury in mammalian cells and is mutationally inactivated in the majority of lung malignancies. In this analysis, the effects of p53-deficiency were investigated in short-term primary cultures of murine bronchiolar Clara cells. Clara cells, isolated from gene-targeted p53-deficient mice, were compared to cells derived from wild type littermates. Results p53 null cultures displayed abnormal morphology; specifically, a high incidence of multinucleation, which increased with time in culture. Multinucleated cells were proficient in S phase DNA synthesis, as determined by BrdU incorporation. However, multinucleation did not reflect altered rates of S phase synthesis, which were similar between wild type and p53-/- cultures. Nucleation defects in p53-/- Clara cells associated with increased centrosome number, as determined by confocal microscopy of pericentrin-stained cultures, and may highlight a novel role of p53 in preserving genomic integrity in lung epithelial cells. Effects of p53-deficiency were also studied following exposure to DNA damage. A p53-dependent reduction in the BrdU index was observed in Clara cells following ionizing radiation. The reduction in BrdU index in wild type cells displayed serum-dependency, and occurred only in the absence of serum. Taken together, these findings demonstrate that in murine primary Clara cell culture, cell cycle arrest is a p53-mediated response to DNA damage, and that extracellular factors, such as serum, influence this response. Conclusion These findings highlight functions of wild type p53 protein in bipolar spindle formation, centrosome regulation, and growth control in bronchiolar Clara cells.

  20. The Principle of Proportionality and the European Arrest Warrant

    Directory of Open Access Journals (Sweden)

    Sarah Haggenmüller

    2013-01-01

    Full Text Available The European Arrest Warrant (EAW is a grossly coercive instrument that was designed for the persecution of serious cross-border crimes. In recent years, however, Member States have increasingly reported cases in which EAWs have not been issued for serious, but rather for harmless and minor offences. This article analyses the reasons behind the disproportionate use of the EAW and outlines measures to alleviate the problem. Thereby, it claims that in current debates different categories of disproportionate use of EAWs are often lumped together, and only concentrate on the introduction of a (binding proportionality test, failing to consider other alternative legislative solutions regarding minor crimes, such as the introduction of new comparable and effective alternative measures. These, however, are considered to be crucial for an alleviation of disproportionate warrants. La orden de detención europea (ODE es un instrumento extremadamente coercitivo que fue diseñado para la persecución de delitos transfronterizos graves. En años recientes, sin embargo, los Estados miembro han notificado cada vez más casos en los que la ODE no se debía a delitos serios, sino a casos menores e inofensivos.. En este artículo se analizan las razones que hay detrás del uso desproporcionado de la orden de detención europea y propone medidas para paliar el problema. De esta manera, se defiende que el debate actual, frecuentemente agrupan diferentes categorías de uso desproporcionado de la ODE, y sólo se concentran en la introducción de un test de proporcionalidad (vinculante, sin tener en cuenta otras soluciones legislativas alternativas, en lo que respecta a delitos menores, como la introducción de nuevas medidas alternativas, comparables y eficaces. Sin embargo, se considera que estas medidas son cruciales para reducir las órdenes de arresto desproporcionadas. DOWNLOAD THIS PAPER FROM SSRN: http://ssrn.com/abstract=2200874

  1. Classic swine fever virus NS2 protein leads to the induction of cell cycle arrest at S-phase and endoplasmic reticulum stress

    Directory of Open Access Journals (Sweden)

    He Lei

    2010-01-01

    Full Text Available Abstract Background Classical swine fever (CSF caused by virulent strains of Classical swine fever virus (CSFV is a haemorrhagic disease of pigs, characterized by disseminated intravascular coagulation, thrombocytopoenia and immunosuppression, and the swine endothelial vascular cell is one of the CSFV target cells. In this report, we investigated the previously unknown subcellular localization and function of CSFV NS2 protein by examining its effects on cell growth and cell cycle progression. Results Stable swine umbilical vein endothelial cell line (SUVEC expressing CSFV NS2 were established and showed that the protein localized to the endoplasmic reticulum (ER. Cellular analysis revealed that replication of NS2-expressing cell lines was inhibited by 20-30% due to cell cycle arrest at S-phase. The NS2 protein also induced ER stress and activated the nuclear transcription factor kappa B (NF-κB. A significant increase in cyclin A transcriptional levels was observed in NS2-expressing cells but was accompanied by a concomitant increase in the proteasomal degradation of cyclin A protein. Therefore, the induction of cell cycle arrest at S-phase by CSFV NS2 protein is associated with increased turnover of cyclin A protein rather than the down-regulation of cyclin A transcription. Conclusions All the data suggest that CSFV NS2 protein modulate the cellular growth and cell cycle progression through inducing the S-phase arrest and provide a cellular environment that is advantageous for viral replication. These findings provide novel information on the function of the poorly characterized CSFV NS2 protein.

  2. The Effects of Local Police Surges on Crime and Arrests in New York City.

    Science.gov (United States)

    MacDonald, John; Fagan, Jeffrey; Geller, Amanda

    2016-01-01

    The New York Police Department (NYPD) under Operation Impact deployed extra police officers to high crime areas designated as impact zones. Officers were encouraged to conduct investigative stops in these areas. City officials credited the program as one of the leading causes of New York City's low crime rate. We tested the effects of Operation Impact on reported crimes and arrests from 2004 to 2012 using a difference-in-differences approach. We used Poisson regression models to compare differences in crime and arrest counts before and after census block groups were designated as impact zones compared to census block groups in the same NYPD precincts but outside impact zones. Impact zones were significantly associated with reductions in total reported crimes, assaults, burglaries, drug violations, misdemeanor crimes, felony property crimes, robberies, and felony violent crimes. Impact zones were significantly associated with increases in total reported arrests, arrests for burglary, arrests for weapons, arrests for misdemeanor crimes, and arrests for property felony crimes. Impact zones were also significantly associated with increases in investigative stops for suspected crimes, but only the increase in stops made based on probable cause indicators of criminal behaviors were associated with crime reductions. The largest increase in investigative stops in impact zones was based on indicators of suspicious behavior that had no measurable effect on crime. The findings suggest that saturating high crime blocks with police helped reduce crime in New York City, but that the bulk of the investigative stops did not play an important role in the crime reductions. The findings indicate that crime reduction can be achieved with more focused investigative stops. PMID:27310252

  3. The Effects of Local Police Surges on Crime and Arrests in New York City.

    Directory of Open Access Journals (Sweden)

    John MacDonald

    Full Text Available The New York Police Department (NYPD under Operation Impact deployed extra police officers to high crime areas designated as impact zones. Officers were encouraged to conduct investigative stops in these areas. City officials credited the program as one of the leading causes of New York City's low crime rate. We tested the effects of Operation Impact on reported crimes and arrests from 2004 to 2012 using a difference-in-differences approach. We used Poisson regression models to compare differences in crime and arrest counts before and after census block groups were designated as impact zones compared to census block groups in the same NYPD precincts but outside impact zones. Impact zones were significantly associated with reductions in total reported crimes, assaults, burglaries, drug violations, misdemeanor crimes, felony property crimes, robberies, and felony violent crimes. Impact zones were significantly associated with increases in total reported arrests, arrests for burglary, arrests for weapons, arrests for misdemeanor crimes, and arrests for property felony crimes. Impact zones were also significantly associated with increases in investigative stops for suspected crimes, but only the increase in stops made based on probable cause indicators of criminal behaviors were associated with crime reductions. The largest increase in investigative stops in impact zones was based on indicators of suspicious behavior that had no measurable effect on crime. The findings suggest that saturating high crime blocks with police helped reduce crime in New York City, but that the bulk of the investigative stops did not play an important role in the crime reductions. The findings indicate that crime reduction can be achieved with more focused investigative stops.

  4. The Effects of Local Police Surges on Crime and Arrests in New York City

    Science.gov (United States)

    MacDonald, John; Fagan, Jeffrey; Geller, Amanda

    2016-01-01

    The New York Police Department (NYPD) under Operation Impact deployed extra police officers to high crime areas designated as impact zones. Officers were encouraged to conduct investigative stops in these areas. City officials credited the program as one of the leading causes of New York City’s low crime rate. We tested the effects of Operation Impact on reported crimes and arrests from 2004 to 2012 using a difference-in-differences approach. We used Poisson regression models to compare differences in crime and arrest counts before and after census block groups were designated as impact zones compared to census block groups in the same NYPD precincts but outside impact zones. Impact zones were significantly associated with reductions in total reported crimes, assaults, burglaries, drug violations, misdemeanor crimes, felony property crimes, robberies, and felony violent crimes. Impact zones were significantly associated with increases in total reported arrests, arrests for burglary, arrests for weapons, arrests for misdemeanor crimes, and arrests for property felony crimes. Impact zones were also significantly associated with increases in investigative stops for suspected crimes, but only the increase in stops made based on probable cause indicators of criminal behaviors were associated with crime reductions. The largest increase in investigative stops in impact zones was based on indicators of suspicious behavior that had no measurable effect on crime. The findings suggest that saturating high crime blocks with police helped reduce crime in New York City, but that the bulk of the investigative stops did not play an important role in the crime reductions. The findings indicate that crime reduction can be achieved with more focused investigative stops. PMID:27310252

  5. RBP-J-interacting and tubulin-associated protein induces apoptosis and cell cycle arrest in human hepatocellular carcinoma by activating the p53–Fbxw7 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Haihe [The Key Laboratory of Molecular Diagnosis in Laboratory Medicine, Department of Pathogenobiology, Daqing Branch of Harbin Medical University, Daqing 163319 (China); Yang, Zhanchun [Department of General Surgery of Fifth Clinical Hospital of Harbin Medical University, Daqing 163319 (China); Liu, Chunbo; Huang, Shishun; Wang, Hongzhi; Chen, Yingli [The Key Laboratory of Molecular Diagnosis in Laboratory Medicine, Department of Pathogenobiology, Daqing Branch of Harbin Medical University, Daqing 163319 (China); Chen, Guofu, E-mail: zhangyanjie3@aliyun.com [Department of General Surgery of Fifth Clinical Hospital of Harbin Medical University, Daqing 163319 (China)

    2014-11-07

    Highlights: • RITA overexpression increased protein expression of p53 and Fbxw7 and downregulated the expression of cyclin D1, cyclin E, CDK2, Hes-1 and NF-κB p65. • RITA can significantly inhibit the in vitro growth of SMMC7721 and HepG2 cells. • RITA exerts tumor-suppressive effects in hepatocarcinogenesis through induction of G0/G1 cell cycle arrest and apoptosis and suggest a therapeutic application of RITA in HCC. - Abstract: Aberrant Notch signaling is observed in human hepatocellular carcinoma (HCC) and has been associated with the modulation of cell growth. However, the role of Notch signaling in HCC and its underlying mechanism remain elusive. RBP-J-interacting and tubulin-associated (RITA) mediates the nuclear export of RBP-J to tubulin fibers and downregulates Notch-mediated transcription. In this study, we found that RITA overexpression increased protein expression of p53 and Fbxw7 and downregulated the expression of cyclin D1, cyclin E, CDK2, Hes-1 and NF-κB p65. These changes led to growth inhibition and induced G0/G1 cell cycle arrest and apoptosis in SMMC7721 and HepG2 cells. Our findings indicate that RITA exerts tumor-suppressive effects in hepatocarcinogenesis through induction of G0/G1 cell cycle arrest and apoptosis and suggest a therapeutic application of RITA in HCC.

  6. Growth Hormone

    Science.gov (United States)

    ... page: Was this page helpful? Also known as: GH; Human Growth Hormone; HGH; Somatotropin; Growth Hormone Stimulation Test; Growth Hormone ... I should know? How is it used? Growth hormone (GH) testing is primarily used to identify growth hormone ...

  7. Effect of Multiple Lightning Strikes on .the Performance of ZnOLightning Arrester Block%Effect of Multiple Lightning Strikes on .the Performance of ZnOLightning Arrester Block

    Institute of Scientific and Technical Information of China (English)

    Haryono T; Sirait K T; Tumiran; Hamzah Berahim

    2011-01-01

    A lightning arrester is used for electrical equipment protection against damage due to lightning strikes. One example of protected electrical equipment is electrical power transformer. If there is no lightning arrester installed to the transformer, when a lightning strike happens, it may receive a very high lightning overvoltage, which is certainly resulted in the transformer damage at its insulation. Usually, a lightning arrester specification data attached to a light- ning arrester contains the rating data of the lightning arrester current and voltage. In the use of lightning arrester, the possibility of receiving multiple lightning strikes is not taken into account sometimes. In fact, in some places, the number of multiple strikes in short duration is quiet high in number. This condition makes the lightning arrester being stroked by multiple lightning strikes. Therefore, it may change the lightning arrester's properties, and then the arrester may not be able to provide good electrical equipment protection against lightning strike anymore. This condition will result in great loss to electrical companies and electrical consumers. Therefore, this research studied the effect of applying multiple lightning strikes to ZnO lightning arrester block. Every time a group of lightning impulse current is applied to the ZnO lightning arrester block, it is followed by the measuring of its 50 Hz voltage and current characteristic. The changing in the ZnO lightning arrester block 50 Hz characteristic then can be analyzed. It was found that by applying more numbers of lightning strikes which made the arrester becoming worse, even though, actually, the lightning impulse peak current was still under the rating of the lightning arrester current. In this ease for a 5 kA, 24 kV lightning arrester, even though the lightning impulse peak current flowing through the ZnO lightning arrester block was still 2500 A, the lightning arrester ZnO block had already been damaged. Having been

  8. Potential for the G2/M arrest assay to predict patient susceptibility to severe reactions following radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Perez, A.; Grabenbauer, G.G.; Sauer, R.; Distel, L.V.R. [Dept. of Radiation Oncology, Friedrich Alexander Univ. Erlangen-Nuremberg (Germany); Sprung, C.N. [Div. of Research, Peter MacCallum Cancer Centre, and Dept. of Biochemistry and Molecular Biology, Melbourne Univ., VIC (Australia)

    2007-02-15

    Background and purpose: cell-cycle regulation and checkpoint activation are crucial factors for radiation-induced DNA damage processing. The G2/M phase arrest was assessed in lymphoblastoid cell lines and phytohemagglutinin-stimulated T-lymphocytes of different radiosensitivities to study the relationship of G2/M arrest to radiosensitivity. Material and methods: G2/M arrest was analyzed after in vitro irradiation by 2 and 5 Gy of ionizing radiation up to 6 days using 17 lymphoblastoid cell lines from healthy individuals, ataxia-telangiectasia (AT) patients, Nijmegen breakage syndrome (NBS) patients and cancer patients with clinically increased radiosensitivity. In a second approach, phytohemagglutinin-stimulated T-lymphocytes from 15 healthy individuals, twelve cancer patients, and five cancer patients hypersensitive to ionizing radiation were studied. Image cytometry was performed to analyze G2/M arrest. Results: two of the three AT cell lines showed markedly increased G2/M arrest compared to controls. NBS cells were comparable to controls up to day 3, but then demonstrated a slightly increased G2/M arrest. Two of the six radiosensitive lymphoblast cell lines and the five radiosensitive cancer patients' T-lymphocytes assayed showed a reduction in G2/M arrest, while healthy individuals showed no difference from cancer patients. Conclusion: the interrelation between G2/M arrest and radiosensitivity is not readily apparent since a variety of radiosensitive cells from patients with radiosensitive syndromes and patients identified as radiosensitive following radiation treatment showed inconsistent G2/M arrest dynamics. Secondary effects, like loss of clonogenicity, G1/S phase arrest and failure of G2/M arrest may contribute to variation of the G2/M arrest endpoint and obscure assessment of cellular radiosensitivity using this method. (orig.)

  9. Structural Characterization of RNA Polymerase II Complexes Arrested by a Cyclobutane Pyrimidine Dimer in the Transcribed Strand of Template DNA*

    OpenAIRE

    Tornaletti, Silvia; Reines, Daniel; Hanawalt, Philip C.

    1999-01-01

    We have characterized the properties of immunopurified transcription complexes arrested at a specifically located cyclobutane pyrimidine dimer (CPD) using enzymatic probes and an in vitro transcription system with purified RNA polymerase II (RNAP II) and initiation factors. To help understand how RNAP II distinguishes between a natural impediment and a lesion in the DNA to initiate a repair event, we have compared the conformation of RNAP II complexes arrested at a CPD with complexes arrested...

  10. The administration of dextrose during in-hospital cardiac arrest is associated with increased mortality and neurologic morbidity

    OpenAIRE

    Peng, Teng J; Andersen, Lars W.; Saindon, Brian Z.; Giberson, Tyler A; Kim, Won Young; Berg, Katherine; Novack, Victor; Donnino, Michael W; ,

    2015-01-01

    Introduction Dextrose may be used during cardiac arrest resuscitation to prevent or reverse hypoglycemia. However, the incidence of dextrose administration during cardiac arrest and the association of dextrose administration with survival and other outcomes are unknown. Methods We used the Get With The Guidelines®-Resuscitation national registry to identify adult patients with an in-hospital cardiac arrest between the years 2000 and 2010. To assess the adjusted effects of dextrose administrat...

  11. Gender differences in street economy and social network correlates of arrest among heroin injectors in Baltimore, Maryland

    OpenAIRE

    Curry, Aaron D.; Latkin, Carl A.

    2003-01-01

    In a sample of 761 heroin injectors in Baltimore, Maryland, correlates of arrest for drug-related and non-drug-related criminal offenses, by gender, were examined. This investigation examined gender differences in involvement in the drug economy and correlates of arrest. Correlates included roles in the street drug economy, social network attributes, and economic and demographic variables. Gender differences were found. Selling drugs was strongly associated with drug-related arrests for males...

  12. DNA damage-induced metaphase I arrest is mediated by the spindle assembly checkpoint and maternal age

    OpenAIRE

    Marangos, P; Stevense, M.; Niaka, K.; Lagoudaki, M.; Nabti, I.; Jessberger, R.; Carroll, J.

    2015-01-01

    In mammalian oocytes DNA damage can cause chromosomal abnormalities that potentially lead to infertility and developmental disorders. However, there is little known about the response of oocytes to DNA damage. Here we find that oocytes with DNA damage arrest at metaphase of the first meiosis (MI). The MI arrest is induced by the spindle assembly checkpoint (SAC) because inhibiting the SAC overrides the DNA damage-induced MI arrest. Furthermore, this MI checkpoint is compromised in oocytes fro...

  13. Smoking marijuana in public: the spatial and policy shift in New York City arrests, 1992–2003

    OpenAIRE

    Golub Andrew; Johnson Bruce D; Dunlap Eloise

    2006-01-01

    Abstract Background During the 1990s, the New York Police Department (NYPD) greatly expanded arrests for smoking marijuana in public view (MPV). By 2000, MPV accounted for 15% of all arrests. The NYPD's supporters report this arrest activity is just part of quality-of-life (QOL) policing, which seeks to promote order in public locations by aggressively patrolling for behaviors that offend the general population. The NYPD's critics contend the NYPD has disproportionately targeted poor, black a...

  14. A novel parameter estimation method for metal oxide surge arrester models

    Indian Academy of Sciences (India)

    Mehdi Nafar; Gevork B Gharehpetian; Taher Niknam

    2011-12-01

    Accurate modelling and exact determination of Metal Oxide (MO) surge arrester parameters are very important for arrester allocation, insulation coordination studies and systems reliability calculations. In this paper, a new technique, which is the combination of Adaptive Particle Swarm Optimization (APSO) and Ant Colony Optimization (ACO) algorithms and linking the MATLAB and EMTP, is proposed to estimate the parameters of MO surge arrester models. The proposed algorithm is named Modified Adaptive Particle Swarm Optimization (MAPSO). In the proposed algorithm, to overcome the drawback of the PSO algorithm (convergence to local optima), the inertia weight is tuned by using fuzzy rules and the cognitive and the social parameters are self-adaptively adjusted. Also, to improve the global search capability and prevent the convergence to local minima, ACO algorithm is combined to the proposed APSO algorithm. The transient models of MO surge arrester have been simulated by using ATP-EMTP. The results of simulations have been applied to the program, which is based on MAPSO algorithm and can determine the fitness and parameters of different models. The validity and the accuracy of estimated parameters of surge arrester models are assessed by comparing the predicted residual voltage with experimental results.

  15. The Practice of Therapeutic Hypothermia after Cardiac Arrest in France: A National Survey

    Science.gov (United States)

    Orban, Jean-Christophe; Cattet, Florian; Lefrant, Jean-Yves; Leone, Marc; Jaber, Samir; Constantin, Jean-Michel; Allaouchiche, Bernard; Ichai, Carole

    2012-01-01

    Aims Cardiac arrest is a major health concern worldwide accounting for 375,000 cases per year in Europe with a survival rate of <10%. Therapeutic hypothermia has been shown to improve patients’ neurological outcome and is recommended by scientific societies. Despite these guidelines, different surveys report a heterogeneous application of this treatment. The aim of the present study was to evaluate the clinical practice of therapeutic hypothermia in cardiac arrest patients. Methods This self-declarative web based survey was proposed to all registered French adult intensive care units (ICUs) (n = 357). Paediatrics and neurosurgery ICUs were excluded. The different questions addressed the structure, the practical modalities of therapeutic hypothermia and the use of prognostic factors in patients admitted after cardiac arrest. Results One hundred and thirty-two out of 357 ICUs (37%) answered the questionnaire. Adherence to recommendations regarding the targeted temperature and hypothermia duration were 98% and 94% respectively. Both guidelines were followed in 92% ICUs. During therapeutic hypothermia, sedative drugs were given in 99% ICUs, mostly midazolam (77%) and sufentanil (59%). Neuromuscular blocking agents (NMBA) were used in 97% ICUs, mainly cisatracurium (77%). Numerous prognostic factors were used after cardiac arrest such as clinical factors (95%), biomarkers (53%), electroencephalography (78%) and evoked potentials (35%). Conclusions In France, adherence to recommendations for therapeutic hypothermia after cardiac arrest is higher than those previously reported in other countries. Numerous prognostic factors are widely used even if their reliability remains controversial. PMID:23049783

  16. Main Complications of Mild Induced Hypothermia after Cardiac Arrest: A Review Article

    Directory of Open Access Journals (Sweden)

    Hassan Soleimanpour

    2014-03-01

    Full Text Available The aim of the present study is to assess the complications of mild induced hypothermia (MIH in patients with cardiac arrest. Presently, based on the guidelines of the American heart Association, MIH following successful cardiopulmonary resuscitation (CPR in unconscious adult patients due to ventricular fibrillation (VF with out-of-hospital cardiac arrest (OOHCA is essential and required. However, MIH could be associated with complications in Patients with cardiac arrest. Studies conducted on the precautions and care following cardiac arrest and MIH were included. Valid scientific data bases were used for data collection. The obtained results from different studies revealed that mild MIH could be associated with numerous complications and the knowledge and awareness of the medical staff from the complications is required to guarantee successful therapeutic approaches in MIH following cardiac arrest which is a novel medical facility with different styles and complications. Overall, further future studies are required to improve the quality of MIH, to increase survival and to decrease complications rates.

  17. Management of survivors of cardiac arrest - the importance of genetic investigation.

    Science.gov (United States)

    Schwartz, Peter J; Dagradi, Federica

    2016-09-01

    Management of survivors of cardiac arrest is largely based on a traditional approach. However, during the past decade, arrhythmias of genetic origin have increasingly been recognized as contributing to many more cases than previously appreciated. This realization is forcing physicians managing the survivors of cardiac arrest also to consider family members. In this Perspectives article, we examine the appropriate management approaches for survivors of cardiac arrests related to channelopathies, cardiomyopathies, or ischaemic heart disease, and for their families. Important implications for families of individuals who have experienced sudden cardiac death as part of sudden infant death syndrome or during sport activity are also discussed. Congenital long QT syndrome provides a paradigm of the logical sequence of the steps that should be performed. When a diagnosis of the cause of the cardiac arrest is certain or probable, every effort should be made to identify the genetic basis of disease, because this approach will enable the identification and early protection of similarly affected family members. Accordingly, the availability in hospitals of at least one cardiologist with cardiovascular genetics expertise would improve the management of survivors of cardiac arrest as well as of their families. PMID:27383078

  18. Dimensional study of the dynamical arrest in a random Lorentz gas.

    Science.gov (United States)

    Jin, Yuliang; Charbonneau, Patrick

    2015-04-01

    The random Lorentz gas (RLG) is a minimal model for transport in heterogeneous media. Upon increasing the obstacle density, it exhibits a growing subdiffusive transport regime and then a dynamical arrest. Here, we study the dimensional dependence of the dynamical arrest, which can be mapped onto the void percolation transition for Poisson-distributed point obstacles. We numerically determine the arrest in dimensions d=2-6. Comparison of the results with standard mode-coupling theory reveals that the dynamical theory prediction grows increasingly worse with d. In an effort to clarify the origin of this discrepancy, we relate the dynamical arrest in the RLG to the dynamic glass transition of the infinite-range Mari-Kurchan-model glass former. Through a mixed static and dynamical analysis, we then extract an improved dimensional scaling form as well as a geometrical upper bound for the arrest. The results suggest that understanding the asymptotic behavior of the random Lorentz gas may be key to surmounting fundamental difficulties with the mode-coupling theory of glasses. PMID:25974497

  19. STUDY ON SURGE ARRESTER PERFORMANCE DUE TO LIGHTNING STROKE IN 20 KV DISTRIBUTION LINES

    Directory of Open Access Journals (Sweden)

    Agung Warsito

    2012-02-01

    Full Text Available Electric energy has been transmiting from power station to end user with transmission and distribution lines.Lightning strokes are problems that occure in transmission and distribution lines and make them fault when theelectric energy were transmited. Surge Diverter or Lightning Arrester has been installing to reduce these faults.In this paper the simulation of lightning stroke and lightning arrester performance on distribution lines 20 kVwere done using EMTP (Electromagnetic Transient Program. Some parameters such us impuls voltage andincreasing voltage on distribution line was inverstigated. As case study in this simulation, Mojosongo 1 mainfeeder 20 kV three phase lines were used.The simulation results show that the lightning stroke 20 kA in By1-61-61E-84-9I on S phase at 0,1 ms, makevoltage on S phase was increased about 1,3054 MV. For R phase and T phase will increase of induced voltagewere 0.79539 MV and 0.80484 MV. We also show the performance of MOV Arrester (Metal Oxide Varistor inovercoming lightning stroke trouble, where arrester can decrease voltage up to 15.198 kV on S phase, while atR phase and T phase arrester can decrease voltage up to 11.375 kV and 13.616 kV.

  20. [Ability of typical greenery shrubs of Beijing to adsorb and arrest PM2.5 ].

    Science.gov (United States)

    Liang, Dan; Wang, Bin; Wang, Yun-qi; Zhang, Hui-lan; Yang, Song-nan; Li, Ang

    2014-09-01

    Four typical types of green shrubs of Beijing (Euonymus japonicus, Buxus microphylla, Berberis thunbergii cv. atropurpurea, Taxus cuspidate cv. nana) were selected to study their capacities in adsorbing and arresting PM2.5 using both field observations and air chamber simulations. Concurrently, in order to analyze the pollution characteristics of Beijing in winter and spring, the PM2.5 concentrations of December 2012 to May 2013 were collected. Experimental results showed that: From the gas chamber experiments, the ability to adsorb and arrest PM2.5 was in the order of Berberis thunbergii cv. atropurpurea > Buxus microphylla > Taxus cuspidate cv. nana > Euonymus japonicus, mainly due to the differences in leaf characteristics; Outside measurement results showed that the ability to adsorb and arrest PM2.5 was ranked as Buxus microphylla > Berberis thunbergii cv. atropurpurea > Taxus cuspidate cv. nana > Euonymus japonicus. Chamber simulation and outdoor observation showed that Buxus microphylla and Berberis thunbergii cv. atropurpurea had strong ability to adsorb and arrest PM2.5; Meanwhile, the slight differences between the chamber simulation and outdoor observation results might be related to plant structure. Compared to tree species, the planting condition of shrub species was loose, and it greened quickly; By analyzing the Beijing PM2.5 concentration values in winter and spring, it was found that the PM2.5 concentration was particularly high in the winter of Beijing, and evergreen shrubs maintained the ability to adsorb and arrest PM2.5. PMID:25518685

  1. A novel program focused on women survivors who were enrolled in a cardiac arrest pathway.

    Science.gov (United States)

    Herzog, Eyal; Tamis, Jacqueline; Aziz, Emad F; Shapiro, Janet M

    2013-03-01

    The number of cases of out-of-hospital cardiac arrest is estimated to be 300,000/year in the United States. Two landmark studies published in 2002 demonstrated that therapeutic hypothermia decreased mortality and improved neurological outcome after out-of-hospital cardiac arrest. Our institutional pathway for the management of survivors of cardiac arrest stresses teamwork involving multiple disciplines, including cardiology, critical care, nursing, neurology, infectious diseases, physical therapy, social work, and pastoral care. Involvement of the patients' families is critical in the understanding of the process and in the decision making and goals of care when neurological prognosis is poor. In a unique approach, we have included the survivors in the process. Our approach to quality improvement includes a yearly conference incorporating the voices of survivors and families. This conference serves as a means to review our experience, educate clinicians, involve all healthcare providers in the outcome, and provide a model of communication and professionalism to trainees. During review of our experience, we noted the small number of women undergoing therapeutic hypothermia, accounting for only 21% of all patients undergoing this therapy after cardiac arrest. This led to a conference that focused on cardiac disease and cardiac arrest in women. PMID:23411605

  2. Double Bolus Thrombolysis for Suspected Massive Pulmonary Embolism during Cardiac Arrest

    Directory of Open Access Journals (Sweden)

    Gerard O’Connor

    2015-01-01

    Full Text Available More than 70% of cardiac arrest cases are caused by acute myocardial infarction (AMI or pulmonary embolism (PE. Although thrombolytic therapy is a recognised therapy for both AMI and PE, its indiscriminate use is not routinely recommended during cardiopulmonary resuscitation (CPR. We present a case describing the successful use of double dose thrombolysis during cardiac arrest caused by pulmonary embolism. Notwithstanding the relative lack of high-level evidence, this case suggests a scenario in which recombinant tissue Plasminogen Activator (rtPA may be beneficial in cardiac arrest. In addition to the strong clinical suspicion of pulmonary embolism as the causative agent of the patient’s cardiac arrest, the extremely low end-tidal CO2 suggested a massive PE. The absence of dilatation of the right heart on subxiphoid ultrasound argued against the diagnosis of PE, but not conclusively so. In the context of the circulatory collapse induced by cardiac arrest, this aspect was relegated in terms of importance. The second dose of rtPA utilised in this case resulted in return of spontaneous circulation (ROSC and did not result in haemorrhage or an adverse effect.

  3. Double Bolus Thrombolysis for Suspected Massive Pulmonary Embolism during Cardiac Arrest.

    Science.gov (United States)

    O'Connor, Gerard; Fitzpatrick, Gareth; El-Gammal, Ayman; Gilligan, Peadar

    2015-01-01

    More than 70% of cardiac arrest cases are caused by acute myocardial infarction (AMI) or pulmonary embolism (PE). Although thrombolytic therapy is a recognised therapy for both AMI and PE, its indiscriminate use is not routinely recommended during cardiopulmonary resuscitation (CPR). We present a case describing the successful use of double dose thrombolysis during cardiac arrest caused by pulmonary embolism. Notwithstanding the relative lack of high-level evidence, this case suggests a scenario in which recombinant tissue Plasminogen Activator (rtPA) may be beneficial in cardiac arrest. In addition to the strong clinical suspicion of pulmonary embolism as the causative agent of the patient's cardiac arrest, the extremely low end-tidal CO2 suggested a massive PE. The absence of dilatation of the right heart on subxiphoid ultrasound argued against the diagnosis of PE, but not conclusively so. In the context of the circulatory collapse induced by cardiac arrest, this aspect was relegated in terms of importance. The second dose of rtPA utilised in this case resulted in return of spontaneous circulation (ROSC) and did not result in haemorrhage or an adverse effect. PMID:26664765

  4. Overexpression of p27KIP1 induced cell cycle arrest in G1 phase and subsequent apoptosis in HCC-9204 cell line

    Institute of Scientific and Technical Information of China (English)

    Jiang Li; Wen Liang Wang; Xin Ke Yang; Xin Xin Yu; Yun De Hou; Meng Liang Ge; Jie Zhang

    2000-01-01

    AIM We have previously reported that inducible over-expresaion of Bak may prolong cell cycle in G1 phase and lead to apoptosis in HCC-9204 cells. This study is to investigate whether p27KIP1 plays an important role in this process. MEHODS In order to elucidate the exact function of p27KIP1 in this process, a zinc inducible p27KIP1 stable transfectant and transient p27KIP1- GFP fusion transfectant were constructed. The effects of inducible p27KIP1 on cell growth, cell cycle arrest and apoptosis were examined in the mock, control pMD vector, and pMD-KIP1 transfected HCC-9204 cells. RESULTS This p27KIP1-GFP transfectant may transiently express the fusion gene. The cell growth was reduced by 35% at 48 h of p27KIP1 induction with zinc treatment as determined by trypan blue exclusion assay. These differences remained the same after 72 h of p27KIP1 expression, p27KIP1 caused cell cycle arrest after 24 h of induction, with 40% increase in G1 population. Prolonged p27KIP1 expression in this cell line induced apoptotic cell death reflected by TUNEL assay. Fourty-eight h and 72 h of p27KIP1 expression showed a characteristic DNA ladder on agarose gel electrophoresis.

  5. Cell division arrest by gamma-irradiation in photoautotrophic suspension culture of Euphorbia characias: maintenance of photosynthetic capacity and overaccumulation of sucrose

    International Nuclear Information System (INIS)

    Gamma-irradiation (250 Gy) applied to photoautotrophic cell suspensions of Euphorbia characias L. in the exponential growth phase led to the arrest of cell division and to a subsequent overaccumulation of sucrose and dry matter. From the fourth day of culture, the chlorophyll content and gross photosynthesis were not depressed by gamma-treatment nor by sugar accumulation. In both cultures, no difference was observed between oxygen uptake in the light at CO2 saturating concentration and in the dark, suggesting that no change in energy-dissipative reactions took place after irradiation. A slight increase in oxygen uptake in both light and dark was observed in irradiated cells during the first four days. However, in the absence of limiting factors, the photosynthetic capacities of the dividing and irradiated non-dividing photoautotrophic cells were identical but higher than that of the non-dividing cells in the stationary growth phase. This suggests that gamma-irradiation arrests cell division by a mechanism different to that occurring in stationary-phase cultures. This may be of value in investigating the metabolism of secondary products. (author)

  6. Acute right ventricular myocardial injury and sudden cardiac arrest in a patient with persistent spontaneous coronary vasospasm

    Institute of Scientific and Technical Information of China (English)

    Hung Ming-Yow; Li Ju-Chi; Hao Wen-Rui; Wu Cheng-Hsueh; Hung Ming-Jui

    2011-01-01

    Coronary vasospasm is a rare diagnosis resulting in sudden arrhythmic cardiac arrest. We report a case of a healthy,non-smoking elderly woman resuscitated from arrhythmic cardiac arrest. She had persistent spontaneous coronaxy vasospasm, leading to right ventricular myocardial injury and failure, and shock. She responded quickly to intravenous normal saline bolus infusion, but had irreversible neurological sequelae. Additionally, she had atrial fibrillation preceding ischemic ventricular fibrillation, a rare finding in coronary vasospasm-related cardiac arrest. We suggest immediate coronary angiography of patients in sudden arrhythmic cardiac arrest with acute right ventricular failure for a prompt,accurate diagnosis and appropriate management of the coronary vasospasm.

  7. 2-Methoxy-4-vinylphenol can induce cell cycle arrest by blocking the hyper-phosphorylation of retinoblastoma protein in benzo[a]pyrene-treated NIH3T3 cells

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jin Boo [Bioresource Sciences, Andong National University, Andong 760749 (Korea, Republic of); Jeong, Hyung Jin, E-mail: jhj@andong.ac.kr [Bioresource Sciences, Andong National University, Andong 760749 (Korea, Republic of)

    2010-10-01

    Research highlights: {yields} 2M4VP activated the expression of p21 and p15 protein, and down-regulated the expression of cyclin D1 and cyclin E. {yields} 2M4VP inhibited hyper-phosphorylation of Rb protein. {yields} 2M4VP induced cell cycle arrest from G1 to S. {yields} 2M4VP inhibited hyper-proliferation of the cells in BaP-treated cells. {yields} 2M4VP induces growth arrest of BaP-treated cells by blocking hyper-phosphorylation of Rb via regulating the expression of cell cycle-related proteins. -- Abstract: Benzo[a]pyrene (BaP) is an environment carcinogen that can enhance cell proliferation by disturbing the signal transduction pathways in cell cycle regulation. In this study, the effects of 2M4VP on cell proliferation, cell cycle and cell cycle regulatory proteins were studied in BaP-treated NIH 3T3 cells to establish the molecular mechanisms of 2M4VP as anti-proliferative agents. 2M4VP exerted a dose-dependent inhibitory effect on cell growth correlated with a G1 arrest. Analysis of G1 cell cycle regulators expression revealed 2M4VP increased expression of CDK inhibitor, p21Waf1/Cip1 and p15 INK4b, decreased expression of cyclin D1 and cyclin E, and inhibited kinase activities of CDK4 and CDK2. However, 2M4VP did not affect the expression of CDK4 and CDK2. Also, 2M4VP inhibited the hyper-phosphorylation of Rb induced by BaP. Our results suggest that 2M4VP induce growth arrest of BaP-treated NIH 3T3 cells by blocking the hyper-phosphorylation of Rb via regulating the expression of cell cycle-related proteins.

  8. Disturbances of sensation occasioned by experimental arrest of blood flow

    Directory of Open Access Journals (Sweden)

    Alfred Auersperg

    1949-12-01

    Full Text Available Disturbances of sensation in the hand were studied during and after experimental arrest of circulation to the arm. Blockage of circulation was performed as outlined by Lewis and Pochin, by putting the cuff of a sphygmomanometer on the upper arm and bringing the pressure rapidly up to 200 mm/Hg. The experiments listed below were intended to demonstrate the variability of a central reaction brought about by fairly definite disturbances of the ischaemic periphery. All experiments were made on the present writers and repeated on nine other subjects, none of whom had systolic pressure reaching 150 mm/Hg. I - Blockage of circulation in both arms led to symmetrical phenomena in both hands (thermal paresthesias, tingling and hyposthesia, both under symmetrical experimental circumstances, and under the following variations: So long as the cuff pressure on both arms was above the systolic blood pressure, differences as great as 300 mm/Hg in one cuff and 150 mm in the other did not alter the symmetry of the effects. Neither was symmetry and synchronism of paresthesias affected when compression on one side preceded equal compression on the other up to 20 seconds. II - When a punctate pressure is applied to the paresthetic field the paresthesias disappear around that point and the latter is clearly brought out from the indifferent background produced in the area of depressed skin. On the basis of Kugelberg's findings, it seems that this occurs because the impulses caused by pressure have a higher frequency and substitute the spontaneous abnormal discharges of the ischaemic nerve fibers. III - Repeated mechanical stimulation of a fingertip during the experiment failed to show any influence on sensory (touch thresholds, in contrast, therefore, to what would be expected on the basis of the physiologic experiments which show rapid fatigue of ischaemic structures. IV - In contrast to what might be expected from the intense changes undergone by receptors in the

  9. Sudden Cardiac Arrest due to Brugada Syndrome: a Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    R Soleimanirad

    2013-04-01

    Full Text Available Brugada Syndrome is a rare cause of sudden cardiac arrest and has a unique ECG pattern. In fact, with ST-segment elevation down sloping in the right precordial leads (v1-v3, RBBB pattern in lateral leads and J-point elevation is revealed. We must notice and avoid trigger factors of this syndrome during general anesthesia. Patient is a 39 old man who attended to emergency department with sudden cardiac arrest and resuscitate. He was transferred to ICU for management of hypoxic ischemic encephalopathy. Complementary studies concluded the diagnosis of Brugada syndrome. We must consider Brugada syndrome within patients with family history of sudden cardiac arrest. Moreover, we must avoid trigger factors of this syndrome such as fever, bradicardia and electrolyte abnormality (specialy Na, Ca abnormalities during general anesthesia and if they appear, we should treat them.

  10. Arrested pneumatization of the sphenoid sinus mimicking intraosseous lesions of the skull base

    International Nuclear Information System (INIS)

    Arrested pneumatization of the sphenoid sinus is a developmental variant that is not always well recognized and is often confused with other pathologies associated with the skull base. This report describes the case of a patient referred for cone-beam computed tomography (CBCT) imaging for dental implant therapy. CBCT demonstrated a well-defined incidental lesion in the left sphenoid sinus with soft tissue-like density and sclerotic borders with internal curvilinear opacifications. The differential diagnoses included intraosseous lipoma, arrested pneumatization of the sphenoid sinus, chondrosarcoma, chondroid chordoma, and ossifying fibroma. The radiographic diagnosis of arrested pneumatization was based on the location of the lesion, its well-defined nature, the presence of internal opacifications, and lack of expansion. Gray-scale CBCT imaging of the area demonstrated values similar to fatty tissue. This case highlighted the fact that benign developmental variants associated with the skull base share similar radiographic features with more serious pathological entities.

  11. Spontaneous subarachnoid hemorrhage as a differential diagnosis of pre-hospital cardiac arrest

    Directory of Open Access Journals (Sweden)

    Sohil Pothiawala

    2012-01-01

    Full Text Available Spontaneous subarachnoid hemorrhage is the most common neurological disorder leading to pre-hospital cardiac arrest. ECG changes in SAH may mimic myocardial infarction or ischemia, and thus lead to delayed treatment of the primary problem. Early identification of SAH-induced cardiac arrest with the use of computed tomography scan of the brain obtained immediately after resuscitation will aid emergency physicians make further decisions. The overall prognosis of patients who are resuscitated is extremely poor. But, prompt neurosurgical referral and multidisciplinary intensive care management can improve the survival rate and the functional outcome. Thus, physicians should consider SAH as a differential diagnosis in patients presenting with pre-hospital cardiac arrest.

  12. Effect of caffeine on radiation-induced mitotic delay: delayed expression of G2 arrest

    International Nuclear Information System (INIS)

    In the presence of 5 mM caffeine, irradiated (1.5 Gy) S and G2 cells progressed to mitosis in register and without arrest in G2. Caffeine (5 mM) markedly reduced mitotic delay even after radiation doses up to 20 Gy. When caffeine was removed from irradiated (1.5 Gy) and caffeine-treated cells, a period of G2 arrest followed, similar in length to that produced by radiation alone. The arrest expressed was independent of the duration of the caffeine treatment for exposures up to 3 hr. The similarity of the response to the cited effects of caffeine on S-phase delay suggests a common basis for delay induction in S and G2 phases

  13. Arrested pneumatization of the sphenoid sinus mimicking intraosseous lesions of the skull base

    Energy Technology Data Exchange (ETDEWEB)

    Jalali, Elnaz; Tadinada, Aditya [Dept. of Oral and Maxillofacial Radiology, University of Connecticut School of Dental Medicine, Farmington (United States)

    2015-03-15

    Arrested pneumatization of the sphenoid sinus is a developmental variant that is not always well recognized and is often confused with other pathologies associated with the skull base. This report describes the case of a patient referred for cone-beam computed tomography (CBCT) imaging for dental implant therapy. CBCT demonstrated a well-defined incidental lesion in the left sphenoid sinus with soft tissue-like density and sclerotic borders with internal curvilinear opacifications. The differential diagnoses included intraosseous lipoma, arrested pneumatization of the sphenoid sinus, chondrosarcoma, chondroid chordoma, and ossifying fibroma. The radiographic diagnosis of arrested pneumatization was based on the location of the lesion, its well-defined nature, the presence of internal opacifications, and lack of expansion. Gray-scale CBCT imaging of the area demonstrated values similar to fatty tissue. This case highlighted the fact that benign developmental variants associated with the skull base share similar radiographic features with more serious pathological entities.

  14. Assessment of risks for employees of France Telecom regarding overvoltage arresters containing radio-elements

    International Nuclear Information System (INIS)

    As a great number of overvoltage arresters used by France Telecom to protect its telecommunication network against disturbing voltages (notably lightning) contain radio-elements, this report aims at assessing dose levels and associated risks for employees exposed to radioactive overvoltage arrester when setting them up, exploiting installations containing such arresters, or when removing them. After a presentation of these devices, a modelling of activities and geometries is proposed, as well as computation tools. Different scenarios and exposure situations are considered. As far as risks are concerned, after a recall on cancers and ionizing radiation, and on the exposure of France Telecom employees, the report comments the knowledge on radio-induced cancers; notably breast cancer, skin cancer, and mouth and pharynx cancers

  15. Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest

    DEFF Research Database (Denmark)

    Nielsen, Niklas; Wetterslev, Jørn; Cronberg, Tobias;

    2013-01-01

    unknown. Our objective was to compare two target temperatures, both intended to prevent fever. Methods In an international trial, we randomly assigned 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33°C or 36°C. The......Background Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is...... (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar. Conclusions In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33°C did not confer a benefit as...

  16. Utilization of polymer enclosed intermediate class arresters to improve the performance of modern power systems

    International Nuclear Information System (INIS)

    This paper introduces the first commercially available polymer enclosed intermediate class metal oxide surge arrester. It describes the unique construction of the design, including reduced size, increased flexibility, a collared seal on the polymer housing and an open webbed fiberglass-epoxy module which houses the metal oxide disc elements. Performance advantages are discussed. These include improved short term contamination performance of the insulator-like polymer design when compared to multi-unit porcelain housed designs. Data will show that polymer housed open-webbed fiberglass module construction extends the pressure relief capability beyond that of typical porcelain enclosed designs. The capability of the polymer enclosed design to withstand repeated pressure relief tests, simulating system reclose on a failed arrester, is also discussed. This paper discusses the circumstances at one utility which has considered utilizing polymer enclosed intermediate class arresters to effectively upgrade their system protection capabilities

  17. Barriers to recognition of out-of-hospital cardiac arrest during emergency medical calls

    DEFF Research Database (Denmark)

    Alfsen, David; Møller, Thea Palsgaard; Egerod, Ingrid; Lippert, Freddy K

    2015-01-01

    inductive thematic analysis of recordings of out-of-hospital cardiac arrest emergency calls from December 2012. Participants were the callers (bystanders) and the emergency medical dispatchers. Data were analysed using a hermeneutic approach. RESULTS: Based on the concept of data saturation, 13 recordings...... influences the dispatchers' recognition of OHCA, focusing on the communication during the emergency call. The purpose of this study is to identify factors affecting medical dispatchers' recognition of OHCA during emergency calls in a qualitative analysis of calls. METHODS: An investigator triangulated...... of not recognised cardiac arrest and 8 recordings of recognised cardiac arrests were analysed. Three main themes, six subthemes and an embedded theme emerged from the analysis: caller's physical distance (caller near patient, caller not near patient), caller's emotional distance (keeping calm, losing...

  18. Characterization of the N-methoxyindole-3-carbinol (NI3C)–Induced Cell Cycle Arrest in Human Colon Cancer Cell Lines

    DEFF Research Database (Denmark)

    Neave, Antje S.; Sarup, Sussi; Seidelin, Michel; Duus, Fritz; Vang, Ole

    2005-01-01

    study was to show the effect of NI3C on cell growth of two human colon cancer cell lines, DLD-1 and HCT-116. For the first time it is shown that NI3C inhibits cellular growth of DLD-1 and HCT-116 and that NI3C is a more potent inhibitor of cell proliferation than I3C. In addition to the inhibition of...... cellular proliferation, NI3C caused an accumulation of HCT-116 cells in the G2/M phase, in contrast to I3C, which led to an accumulation of the colon cells in G0/G1 phase. Furthermore, NI3C delays the G1-S phase transition of synchronized HCT-116 cells. The indole-mediated cell-cycle arrest may be related...

  19. Surviving Sudden Cardiac Arrest: A Pilot Qualitative Survey Study of Survivors.

    Science.gov (United States)

    Sawyer, Kelly N; Brown, Frances; Christensen, Roxanne; Damino, Colleen; Newman, Mary M; Kurz, Michael C

    2016-06-01

    Research describing survivors of sudden cardiac arrest (SCA) has centered on quantifying functional ability, perceived quality of life, and neurocognitive assessment. Many gaps remain, however, regarding survivors' psychosocial perceptions of life in the aftermath of cardiac arrest. An important influence upon those perceptions is the presence of support and its role in a survivor's life. An Internet-based pilot survey study was conducted to gather data from SCA survivors and friends and/or family members (FFMs) representing their support system. The survey was distributed to members of the Sudden Cardiac Arrest Foundation (SCAF) via the Internet by SCAF leadership. Questions included both discrete multiple-choice and open-ended formats. Inductive thematic analyses were completed by three independent researchers trained in qualitative research methodology to identify primary themes consistent among study participants until thematic saturation was achieved. No statistical inferences were made. A total of 205 surveys were returned over the 5-month study period (July to November 2013); nine were received blank, leaving 196 surveys available for review. Major themes identified for survivors (N = 157) include the significance of and desire to share experiences with others; subculture identification (unique experience from those suffering a heart attack); and the need to seek a new normal, both personally and inter-personally. Major themes identified for FFMs (N = 39) include recognition of loved one's memory loss; a lack of information at discharge, including expectations after discharge; and concern for the patient experiencing another cardiac arrest. This pilot, qualitative survey study suggests several common themes important to survivors, and FFMs, of cardiac arrest. These themes may serve as a basis for future patient-centered focus groups and the development of patient-centered guidelines for patients and support persons of those surviving cardiac arrest

  20. Survival to admission after out-of-hospital cardiac arrest in Seoul, South Korea

    Directory of Open Access Journals (Sweden)

    Kim JH

    2014-09-01

    Full Text Available Jin-Hue Kim,1 Tai-Hwan Uhm2 1Department of Emergency Medical Technology, Sun Moon University, Asan-si, Chungnam, South Korea; 2Department of Emergency Medical Services, Eulji University, Seongnam-si, Gyeonggi-do, South Korea Purpose: Out-of-hospital cardiac arrest (OHCA data derived according to the Utstein Style guidelines was used to try to determine factors influencing survival to admission (STA and epidemiological rates of OHCA. Patients and methods: This was an observational study of all age groups based on data from prehospital care reports in Seoul, South Korea. The collected data were reported according to the Utstein Style template for OHCA and analyzed in order to compare STA with non-STA. Univariate analysis was conducted using a binomial logistic regression model to identify predictors associated with trauma patients. Results: Eighty-three (4.8% OHCA survivors were admitted to the emergency department with carotid pulse. The median time from arrest to emergency medical personnel defibrillation was statistically significantly shorter in STA cases (8.0 minutes than in non-STA cases (12.0 minutes; P<0.001. Factors independently associated with better prognosis in terms of trauma patients were female sex (odds ratio [OR]: 0.67; 95% confidence interval [95% CI]: 0.50–0.91; P=0.01, arrest at home (OR: 0.36; 95% CI: 0.27–0.49; P<0.001, and witnessed arrest (OR: 2.64; 95% CI: 1.94–3.39; P<0.001. Conclusion: Early basic life support, performed by either a layperson or emergency medical personnel, had a positive effect on STA. Male sex, arrest outside of the home, and witnessed arrest are significantly associated with trauma. Keywords: Utstein Style, prehospital, defibrillation, basic life support

  1. Modeling and Simulation of Arresting Gear System with Multibody Dynamic Approach

    OpenAIRE

    Wenhou Shen; Zhihua Zhao; Gexue Ren; Jiapeng Liu

    2013-01-01

    The arresting dynamics of the aircraft on the aircraft carrier involves both a transient wave propagation process in rope and a smooth decelerating of aircraft. This brings great challenge on simulating the whole process since the former one needs small time-step to guarantee the stability, while the later needs large time-step to reduce calculation time. To solve this problem, this paper proposes a full-scale multibody dynamics model of arresting gear system making use of variable time-step ...

  2. Crack arrest model for a piezoelectric strip subjected to Model loadings

    OpenAIRE

    R.R. Bhargava; A. Setia

    2007-01-01

    Purpose: The present paper aims at proposing a crack arrest model for an infinitely long narrow, poled ceramic strip weakened by a finite hairline straight crack when the edges of the strip are subjected to combined mechanical and electrical loads.Design/methodology/approach: (Model) As a consequence of loads the rims of crack open forming a yield zone ahead of each tip of the crack. To arrest the crack from further opening the rims of the yield zones are subjected to normal cohesive quadra...

  3. Cardiac arrest in intensive care unit: Case report and future recommendations

    Directory of Open Access Journals (Sweden)

    Mohammad A

    2010-01-01

    Full Text Available Initiation of hemofiltration in a patient in septic shock can cause hemodynamic compromise potentially leading to cardiac arrest. We propose that the standard ′4Hs and 4Ts′ approach to the differential diagnosis of a cardiac arrest should be supplemented in critically ill patients with anaphylaxis and human and technical errors involving drug administration (the 5 th H and T. To illustrate the point, we report a case where norepinephrine infused through a central venous catheter (CVC was being removed by the central venovenous hemofiltration (CVVH catheter causing the hemodynamic instability. CVVH has this potential of interfering with the systemic availability of drugs infused via a closely located CVC.

  4. The ATM signaling cascade promotes recombination-dependent pachytene arrest in mouse spermatocytes.

    Directory of Open Access Journals (Sweden)

    Sarai Pacheco

    2015-03-01

    Full Text Available Most mutations that compromise meiotic recombination or synapsis in mouse spermatocytes result in arrest and apoptosis at the pachytene stage of the first meiotic prophase. Two main mechanisms are thought to trigger arrest: one independent of the double-strand breaks (DSBs that initiate meiotic recombination, and another activated by persistent recombination intermediates. Mechanisms underlying the recombination-dependent arrest response are not well understood, so we sought to identify factors involved by examining mutants deficient for TRIP13, a conserved AAA+ ATPase required for the completion of meiotic DSB repair. We find that spermatocytes with a hypomorphic Trip13 mutation (Trip13mod/mod arrest with features characteristic of early pachynema in wild type, namely, fully synapsed chromosomes without incorporation of the histone variant H1t into chromatin. These cells then undergo apoptosis, possibly in response to the arrest or in response to a defect in sex body formation. However, TRIP13-deficient cells that additionally lack the DSB-responsive kinase ATM progress further, reaching an H1t-positive stage (i.e., similar to mid/late pachynema in wild type despite the presence of unrepaired DSBs. TRIP13-deficient spermatocytes also progress to an H1t-positive stage if ATM activity is attenuated by hypomorphic mutations in Mre11 or Nbs1 or by elimination of the ATM-effector kinase CHK2. These mutant backgrounds nonetheless experience an apoptotic block to further spermatogenic progression, most likely caused by failure to form a sex body. DSB numbers are elevated in Mre11 and Nbs1 hypomorphs but not Chk2 mutants, thus delineating genetic requirements for the ATM-dependent negative feedback loop that regulates DSB numbers. The findings demonstrate for the first time that ATM-dependent signaling enforces the normal pachytene response to persistent recombination intermediates. Our work supports the conclusion that recombination defects trigger

  5. Prehospital behaviour of patients admitted with acute coronary syndrome or witnessed cardiac arrest

    DEFF Research Database (Denmark)

    Ottesen, Michael Mundt; Dixen, Ulrik; Torp-Pedersen, Christian; Køber, Lars

    2003-01-01

    OBJECTIVE: To study prehospital behaviour of patients admitted with acute coronary syndrome or witnessed cardiac arrest. DESIGN: Structured interview of 250 consecutive patients with acute coronary syndrome and relatives of 48 patients with witnessed cardiac arrest. The following courses of action...... hundred and thirteen patients (45%) knew of thrombolytic therapy. Twenty-seven of 75 patients with knowledge of the benefit of prompt treatment with thrombolysis, acted in accordance with this awareness. CONCLUSION: Patients misinterpret symptoms of acute coronary syndrome and are misguided when calling...

  6. Prehospital therapeutic hypothermia after cardiac arrest--from current concepts to a future standard.

    Science.gov (United States)

    Kämäräinen, Antti; Hoppu, Sanna; Silfvast, Tom; Virkkunen, Ilkka

    2009-01-01

    Therapeutic hypothermia has been shown to improve survival and neurological outcome after prehospital cardiac arrest. Existing experimental and clinical evidence supports the notion that delayed cooling results in lesser benefit compared to early induction of mild hypothermia soon after return of spontaneous circulation. Therefore a practical approach would be to initiate cooling already in the prehospital setting. The purpose of this review was to evaluate current clinical studies on prehospital induction of mild hypothermia after cardiac arrest. Most reported studies present data on cooling rates, safety and feasibility of different methods, but are inconclusive as regarding to outcome effects. PMID:19821967

  7. Prehospital therapeutic hypothermia after cardiac arrest - from current concepts to a future standard

    Directory of Open Access Journals (Sweden)

    Hoppu Sanna

    2009-10-01

    Full Text Available Abstract Therapeutic hypothermia has been shown to improve survival and neurological outcome after prehospital cardiac arrest. Existing experimental and clinical evidence supports the notion that delayed cooling results in lesser benefit compared to early induction of mild hypothermia soon after return of spontaneous circulation. Therefore a practical approach would be to initiate cooling already in the prehospital setting. The purpose of this review was to evaluate current clinical studies on prehospital induction of mild hypothermia after cardiac arrest. Most reported studies present data on cooling rates, safety and feasibility of different methods, but are inconclusive as regarding to outcome effects.

  8. Prehospital therapeutic hypothermia after cardiac arrest - from current concepts to a future standard

    Science.gov (United States)

    Kämäräinen, Antti; Hoppu, Sanna; Silfvast, Tom; Virkkunen, Ilkka

    2009-01-01

    Therapeutic hypothermia has been shown to improve survival and neurological outcome after prehospital cardiac arrest. Existing experimental and clinical evidence supports the notion that delayed cooling results in lesser benefit compared to early induction of mild hypothermia soon after return of spontaneous circulation. Therefore a practical approach would be to initiate cooling already in the prehospital setting. The purpose of this review was to evaluate current clinical studies on prehospital induction of mild hypothermia after cardiac arrest. Most reported studies present data on cooling rates, safety and feasibility of different methods, but are inconclusive as regarding to outcome effects. PMID:19821967

  9. The G2-arrest in the BALB/c embryo: relationship with transcription

    International Nuclear Information System (INIS)

    One-cell embryos of the BALB/c strain are extremely sensitive to the radiation-induced G2-arrest. Earlier studies suggested that the period of sensitivity to this effect is restricted to the S phase. This point was now studied more in details, using very synchronous embryonic populations and a higher dose of X-rays. The sensitivity towards radiation-induced G2-arrest was also investigated at the two immediately following stages of preimplantation development, i.e. the two-cell and the four-cell stages. (authors)

  10. Technology-facilitated Organized Abuse: An Examination of Law Enforcement Arrest Cases

    Directory of Open Access Journals (Sweden)

    Janis Wolak

    2015-07-01

    Full Text Available This paper looks at cases of organized abuse (that is, two or more offenders working in concert and having two or more victims, not solely familial reported by law enforcement respondents during the three waves of the National Juvenile Online Victimization (NJOV Study (n=29. The NJOV Study collected data from a national US sample of law enforcement agencies about technology-facilitated crimes ending in arrest at three time points: mid-2000 to mid-2001, 2005 and 2009. The paper reports on the prevalence of technology-facilitated organized abuse ending in arrest, contexts of cases and characteristics of offenders and victims. 

  11. Achieving Control of Lesion Growth in CNS with Minimal Damage

    CERN Document Server

    Raja, Mathankumar

    2012-01-01

    Lesions in central nervous system (CNS) and their growth leads to debilitating diseases like Multiple Sclerosis (MS), Alzheimer's etc. We developed a model earlier which shows how the lesion growth can be arrested through a beneficial auto-immune mechanism. The success of the approach depends on a set of control parameters and their phase space was shown to have a smooth manifold separating the uncontrolled lesion growth region from the controlled. Here we show that an optimal set of parameter values exist which minimizes system damage while achieving control of lesion growth.

  12. Induction of S-Phase Arrest in Human Glioma Cells by Selenocysteine, a Natural Selenium-Containing Agent Via Triggering Reactive Oxygen Species-Mediated DNA Damage and Modulating MAPKs and AKT Pathways.

    Science.gov (United States)

    Wang, Kun; Fu, Xiao-Ting; Li, Yuan; Hou, Ya-Jun; Yang, Ming-Feng; Sun, Jing-Yi; Yi, Shu-Ying; Fan, Cun-Dong; Fu, Xiao-Yan; Zhai, Jing; Sun, Bao-Liang

    2016-06-01

    Selenocysteine (SeC) a natural available selenoamino acid exhibits novel anticancer activities against human cancer cell lines. However, the growth inhibitory effect and mechanism of SeC in human glioma cells remain unclear. The present study reveals that SeC time- and dose-dependently inhibited U251 and U87 human glioma cells growth by induction of S-phase cell cycle arrest, followed by the marked decrease of cyclin A. SeC-induced S-phase arrest was achieved by inducing DNA damage through triggering generation of reactive oxygen species (ROS) and superoxide anion, with concomitant increase of TUNEL-positive cells and induction of p21waf1/Cip1 and p53. SeC treatment also caused the activation of p38MAPK, JNK and ERK, and inactivation of AKT. Four inhibitors of MAPKs and AKT pathways further confirmed their roles in SeC-induced S-phase arrest in human glioma cells. Our findings advance the understanding on the molecular mechanisms of SeC in human glioma management. PMID:26846141

  13. Arecoline decreases interleukin-6 production and induces apoptosis and cell cycle arrest in human basal cell carcinoma cells

    International Nuclear Information System (INIS)

    Arecoline, the most abundant areca alkaloid, has been reported to decrease interleukin-6 (IL-6) levels in epithelial cancer cells. Since IL-6 overexpression contributes to the tumorigenic potency of basal cell carcinoma (BCC), this study was designed to investigate whether arecoline altered IL-6 expression and its downstream regulation of apoptosis and the cell cycle in cultured BCC-1/KMC cells. BCC-1/KMC cells and a human keratinocyte cell line, HaCaT, were treated with arecoline at concentrations ranging from 10 to 100 μg/ml, then IL-6 production and expression of apoptosis- and cell cycle progress-related factors were examined. After 24 h exposure, arecoline inhibited BCC-1/KMC cell growth and decreased IL-6 production in terms of mRNA expression and protein secretion, but had no effect on HaCaT cells. Analysis of DNA fragmentation and chromatin condensation showed that arecoline induced apoptosis of BCC-1/KMC cells in a dose-dependent manner, activated caspase-3, and decreased expression of the anti-apoptotic protein Bcl-2. In addition, arecoline induced progressive and sustained accumulation of BCC-1/KMC cells in G2/M phase as a result of reducing checkpoint Cdc2 activity by decreasing Cdc25C phosphatase levels and increasing p53 levels. Furthermore, subcutaneous injection of arecoline led to decreased BCC-1/KMC tumor growth in BALB/c mice by inducing apoptosis. This study demonstrates that arecoline has potential for preventing BCC tumorigenesis by reducing levels of the tumor cell survival factor IL-6, increasing levels of the tumor suppressor factor p53, and eliciting cell cycle arrest, followed by apoptosis. Highlights: ► Arecoline has potential to prevent against basal cell carcinoma tumorigenesis. ► It has more effectiveness on BCC as compared with a human keratinocyte cell line. ► Mechanisms involved including reducing tumor cells’ survival factor IL-6, ► Decreasing Cdc25C phosphatase, enhancing tumor suppressor factor p53, ► Eliciting G2/M

  14. Arecoline decreases interleukin-6 production and induces apoptosis and cell cycle arrest in human basal cell carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Li-Wen [Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Hsieh, Bau-Shan; Cheng, Hsiao-Ling [Department of Biochemistry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Hu, Yu-Chen [Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Chang, Wen-Tsan [Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Division of Hepatobiliarypancreatic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan (China); Chang, Kee-Lung, E-mail: Chang.KeeLung@msa.hinet.net [Department of Biochemistry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China)

    2012-01-15

    Arecoline, the most abundant areca alkaloid, has been reported to decrease interleukin-6 (IL-6) levels in epithelial cancer cells. Since IL-6 overexpression contributes to the tumorigenic potency of basal cell carcinoma (BCC), this study was designed to investigate whether arecoline altered IL-6 expression and its downstream regulation of apoptosis and the cell cycle in cultured BCC-1/KMC cells. BCC-1/KMC cells and a human keratinocyte cell line, HaCaT, were treated with arecoline at concentrations ranging from 10 to 100 μg/ml, then IL-6 production and expression of apoptosis- and cell cycle progress-related factors were examined. After 24 h exposure, arecoline inhibited BCC-1/KMC cell growth and decreased IL-6 production in terms of mRNA expression and protein secretion, but had no effect on HaCaT cells. Analysis of DNA fragmentation and chromatin condensation showed that arecoline induced apoptosis of BCC-1/KMC cells in a dose-dependent manner, activated caspase-3, and decreased expression of the anti-apoptotic protein Bcl-2. In addition, arecoline induced progressive and sustained accumulation of BCC-1/KMC cells in G2/M phase as a result of reducing checkpoint Cdc2 activity by decreasing Cdc25C phosphatase levels and increasing p53 levels. Furthermore, subcutaneous injection of arecoline led to decreased BCC-1/KMC tumor growth in BALB/c mice by inducing apoptosis. This study demonstrates that arecoline has potential for preventing BCC tumorigenesis by reducing levels of the tumor cell survival factor IL-6, increasing levels of the tumor suppressor factor p53, and eliciting cell cycle arrest, followed by apoptosis. Highlights: ► Arecoline has potential to prevent against basal cell carcinoma tumorigenesis. ► It has more effectiveness on BCC as compared with a human keratinocyte cell line. ► Mechanisms involved including reducing tumor cells’ survival factor IL-6, ► Decreasing Cdc25C phosphatase, enhancing tumor suppressor factor p53, ► Eliciting G2/M

  15. The ethanol extract of Scutellaria baicalensis and the active compounds induce cell cycle arrest and apoptosis including upregulation of p53 and Bax in human lung cancer cells

    International Nuclear Information System (INIS)

    Despite a lack of scientific authentication, Scutellaria baicalensis is clinically used in Chinese medicine as a traditional adjuvant to chemotherapy of lung cancer. In this study, cytotoxicity assays demonstrated that crude ethanolic extracts of S. baicalensis were selectively toxic to human lung cancer cell lines A549, SK-LU-1 and SK-MES-1 compared with normal human lung fibroblasts. The active compounds baicalin, baicalein and wogonin did not exhibit such selectivity. Following exposure to the crude extracts, cellular protein expression in the cancer cell lines was assessed using 2D gel electrophoresis coupled with MALDI-TOF-MS/Protein Fingerprinting. The altered protein expression indicated that cell growth arrest and apoptosis were potential mechanisms of cytotoxicity. These observations were supported by PI staining cell cycle analysis using flow cytometry and Annexin-V apoptotic analysis by fluorescence microscopy of cancer cells treated with the crude extract and pure active compounds. Moreover, specific immunoblotting identification showed the decreased expression of cyclin A results in the S phase arrest of A549 whereas the G0/G1 phase arrest in SK-MES-1 cells results from the decreased expression of cyclin D1. Following treatment, increased expression in the cancer cells of key proteins related to the enhancement of apoptosis was observed for p53 and Bax. These results provide further insight into the molecular mechanisms underlying the clinical use of this herb as an adjuvant to lung cancer therapy. - Research highlights: → Scutellaria baicalensis is a clinical adjuvant to lung cancer chemotherapy in China. → Scutellaria ethanol extracts selectively toxic to A549, SK-LU-1 and SK-MES-1. → Baicalin, baicalein and wogonin were toxic to all lung cancer cell lines. → Proteomics identified increased p53 and BAX in response to Scutellaria extracts.

  16. Anti-Tumor Effect of Rutin on Human Neuroblastoma Cell Lines through Inducing G2/M Cell Cycle Arrest and Promoting Apoptosis

    Directory of Open Access Journals (Sweden)

    Hongyan Chen

    2013-01-01

    Full Text Available Aims. To further investigate the antineuroblastoma effect of rutin which is a type of flavonoid. Methods. The antiproliferation of rutin in human neuroblastoma cells LAN-5 were detected by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. Chemotaxis of LAN-5 cells was assessed using transwell migration chambers and scratch wound migration assay. The cell cycle arrest and apoptosis in a dose-dependent manner was measured by flow cytometric and fluorescent microscopy analyses. The apoptosis-related proteins BAX and BCL2 as well as MYCN mRNA express were determined by RT-PCR analysis. Secreted TNF-α level were determined using specific enzyme-linked immunosorbent assay kits. Results. Rutin significantly inhibited the growth of LAN-5 cells and chemotactic ability. Flow cytometric analysis revealed that rutin induced G2/M arrest in the cell cycle progression and induced cell apoptosis. The RT-PCR showed that rutin could decrease BCL2 expression and BCL2/BAX ratio. In the meantime, the MYCN mRNA level and the secretion of TNF-α were inhibited. Conclusion. These results suggest that rutin produces obvious antineuroblastoma effects via induced G2/M arrest in the cell cycle progression and induced cell apoptosis as well as regulating the expression of gene related to apoptosis and so on. It supports the viability of developing rutin as a novel therapeutic prodrug for neuroblastoma treatment, as well as providing a new path on anticancer effect of Chinese traditional drug.

  17. The Influence of Electrode Material on Gas-Filled Surge Arresters Response Time in gamma and X radiation field

    International Nuclear Information System (INIS)

    The aim of this paper is to investigate the influence of electrode material on the gas filled surge arrester' model pulse shape characteristic in gamma and X radiation field. We found that both radiations have increased gas filled surge arresters response time. The obtained results show that the optimal solution for GFSA model is with Al electrodes. (author)

  18. Distinct Initiation and Maintenance Mechanisms Cooperate to Induce G1 Cell Cycle Arrest in Response to DNA Damage

    NARCIS (Netherlands)

    Agami, R.; Bernards, R.A.

    2000-01-01

    DNA damage causes stabilization of p53, leading to G1 arrest through induction of p21cip1. As this process requires transcription, several hours are needed to exert this response. We show that DNA damage causes an immediate and p53-independent G1 arrest, caused by rapid proteolysis of cyclin D1. Deg

  19. Gender differences in street economy and social network correlates of arrest among heroin injectors in Baltimore, Maryland.

    Science.gov (United States)

    Curry, Aaron D; Latkin, Carl A

    2003-09-01

    In a sample of 761 heroin injectors in Baltimore, Maryland, correlates of arrest for drug-related and non-drug-related criminal offenses, by gender, were examined. This investigation examined gender differences in involvement in the drug economy and correlates of arrest. Correlates included roles in the street drug economy, social network attributes, and economic and demographic variables. Gender differences were found. Selling drugs was strongly associated with drug-related arrests for males. Steering (i.e., publicizing drug brands) was highly associated with drug-related arrests for females. Level of heroin addiction was associated with drug-related arrests for males, but not for females. The associations of social network variables with arrests also differed by gender. For females but not males, a higher number of females in one's network was associated with a lower frequency of arrests. For males, having at least one heroin injector in the personal network was associated with a decreased frequency of arrest, while for females the direction of the association was reversed. These findings suggest the importance of modeling drug behaviors by gender. PMID:12930885

  20. Complex Systems Analysis of Arrested Neural Cell Differentiation during Development and Analogous Cell Cycling Models in Carcinogenesis

    OpenAIRE

    Baianu, Professor I.C.; Prisecaru, M.S. V

    2004-01-01

    A new approach to the modular, complex systems analysis of nonlinear dynamics of arrested neural cell Differentiation--induced cell proliferation during organismic development and the analogous cell cycling network transformations involved in carcinogenesis is proposed. Neural tissue arrested differentiation that induces cell proliferation during perturbed development and Carcinogenesis are complex processes that involve dynamically inter-connected biomolecules in the intercellular, membrane...