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Sample records for radio-induced death modulation

  1. Modules in Death Education.

    ERIC Educational Resources Information Center

    McCartney, K. Ann; And Others

    Designed for use with accompanying videotapes as single presentations or as a series for professionals or laypeople, or as supplementary modules in academic courses in psychology, marriage and family, health occupations, etc., these four learning modules focus on common phases of dying and grief as part of the normal cycle of living. The modules…

  2. Regulation of VDAC trafficking modulates cell death

    PubMed Central

    Dubey, Ashvini K; Godbole, Ashwini; Mathew, M K

    2016-01-01

    The voltage-dependent anion channel (VDAC) and mitochondria-associated hexokinase (HxK) have crucial roles in both cell survival and death. Both the individual abundances and their ratio seem to influence the balance of survival and death and are thus critical in scenarios, such as neurodegeneration and cancer. Elevated levels of both VDAC and HxK have been reported in cancerous cells. Physical interaction is surmised and specific residues or regions involved have been identified, but details of the interaction and the mechanism by which it modulates survival are yet to be elucidated. We and others have shown that heterologous expression of VDAC can induce cell death, which can be mitigated by concomitant overexpression of HxK. We have also observed that upon overexpression, fluorescently tagged VDAC is distributed between the cytosol and mitochondria. In this study, we show that cell death ensues only when the protein, which is synthesized on cytoplasmic ribosomes, migrates to the mitochondrion. Further, coexpression of rat HxK II (rHxKII) can delay the translocation of human VDAC1 (hVDAC1) protein to mitochondria and thereby inhibit VDAC-induced cell death. Variation in the level of HxK protein as seen endogenously in different cell lines, or as experimentally manipulated by silencing and overexpression, can lead to differential VDAC translocation kinetics and related cell death. The N-terminal region of HxK and the Glu73 residue of hVDAC1, which have previously been implicated in a physical interaction, are required for cytosolic retention of VDAC. Finally, we show that, in otherwise unperturbed cells in culture, there is a small but significant amount of soluble VDAC in the cytosol present in a complex with HxK. This complex could well determine how a cell is poised with respect to incoming thanatopic signals, thereby tilting the survival/death balance in pharmacologically interesting situations, such as neurodegeneration and cancer. PMID:28028442

  3. The Celebration of Death: Two Folk Tales about DEath. Mini-Module.

    ERIC Educational Resources Information Center

    African-American Inst., New York, NY. School Services Div.

    This module contains two African folk tales about death, two descriptions of African funerals, a lesson plan with 11 questions exploring the finality of and customs surrounding death, and a bibliography of five books which deal with African religious beliefs. The folk tales present concepts of death and immortality of the soul. The descriptions of…

  4. Correlation between radio-induced lymphocyte apoptosis measurements obtained from two French centres.

    PubMed

    Mirjolet, C; Merlin, J L; Dalban, C; Maingon, P; Azria, D

    2016-07-01

    In the era of modern treatment delivery, increasing the dose delivered to the target to improve local control might be modulated by the patient's intrinsic radio-sensitivity. A predictive assay based on radio-induced lymphocyte apoptosis quantification highlighted the significant correlation between CD4 and CD8 T-lymphocyte apoptosis and grade 2 or 3 radiation-induced late toxicities. By conducting this assay at several technical platforms, the aim of this study was to demonstrate that radio-induced lymphocyte apoptosis values obtained from two different platforms were comparable. For 25 patients included in the PARATOXOR trial running in Dijon the radio-induced lymphocyte apoptosis results obtained from the laboratory of Montpellier (IRCM, Inserm U1194, France), considered as the reference (referred to as Lab 1), were compared with those from the laboratory located at the Institut de cancérologie de Lorraine (ICL, France), referred to as Lab 2. Different statistical methods were used to measure the agreement between the radio-induced lymphocyte apoptosis data from the two laboratories (quantitative data). The Bland-Altman plot was used to identify potential bias. All statistical tests demonstrated good agreement between radio-induced lymphocyte apoptosis values obtained from both sites and no major bias was identified. Since radio-induced lymphocyte apoptosis values, which predict tolerance to radiotherapy, could be assessed by two laboratories and showed a high level of robustness and consistency, we can suggest that this assay be extended to any laboratories that use the same technique. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  5. Arabidopsis ACCELERATED CELL DEATH2 Modulates Programmed Cell DeathW⃞

    PubMed Central

    Yao, Nan; Greenberg, Jean T.

    2006-01-01

    The Arabidopsis thaliana chloroplast protein ACCELERATED CELL DEATH2 (ACD2) modulates the amount of programmed cell death (PCD) triggered by Pseudomonas syringae and protoporphyrin IX (PPIX) treatment. In vitro, ACD2 can reduce red chlorophyll catabolite, a chlorophyll derivative. We find that ACD2 shields root protoplasts that lack chlorophyll from light- and PPIX-induced PCD. Thus, chlorophyll catabolism is not obligatory for ACD2 anti-PCD function. Upon P. syringae infection, ACD2 levels and localization change in cells undergoing PCD and in their close neighbors. Thus, ACD2 shifts from being largely in chloroplasts to partitioning to chloroplasts, mitochondria, and, to a small extent, cytosol. ACD2 protects cells from PCD that requires the early mitochondrial oxidative burst. Later, the chloroplasts of dying cells generate NO, which only slightly affects cell viability. Finally, the mitochondria in dying cells have dramatically altered movements and cellular distribution. Overproduction of both ACD2 (localized to mitochondria and chloroplasts) and ascorbate peroxidase (localized to chloroplasts) greatly reduces P. syringae–induced PCD, suggesting a pro-PCD role for mitochondrial and chloroplast events. During infection, ACD2 may bind to and/or reduce PCD-inducing porphyrin-related molecules in mitochondria and possibly chloroplasts that generate reactive oxygen species, cause altered organelle behavior, and activate a cascade of PCD-inducing events. PMID:16387834

  6. Death-associated protein kinase-mediated cell death modulated by interaction with DANGER.

    PubMed

    Kang, Bingnan N; Ahmad, Abdullah S; Saleem, Sofiyan; Patterson, Randen L; Hester, Lynda; Doré, Sylvain; Snyder, Solomon H

    2010-01-06

    Death-associated protein kinase (DAPK) is a key player in multiple cell death signaling pathways. We report that DAPK is regulated by DANGER, a partial MAB-21 domain-containing protein. DANGER binds directly to DAPK and inhibits DAPK catalytic activity. DANGER-deficient mouse embryonic fibroblasts and neurons exhibit greater DAPK activity and increased sensitivity to cell death stimuli than do wild-type control cells. In addition, DANGER-deficient mice manifest more severe brain damage after acute excitotoxicity and transient cerebral ischemia than do control mice. Accordingly, DANGER may physiologically regulate the viability of neurons and represent a potential therapeutic target for stroke and neurodegenerative diseases.

  7. Jasmonic acid signaling modulates ozone-induced hypersensitive cell death.

    PubMed

    Rao, M V; Lee, H; Creelman, R A; Mullet, J E; Davis, K R

    2000-09-01

    Recent studies suggest that cross-talk between salicylic acid (SA)-, jasmonic acid (JA)-, and ethylene-dependent signaling pathways regulates plant responses to both abiotic and biotic stress factors. Earlier studies demonstrated that ozone (O(3)) exposure activates a hypersensitive response (HR)-like cell death pathway in the Arabidopsis ecotype Cvi-0. We now have confirmed the role of SA and JA signaling in influencing O(3)-induced cell death. Expression of salicylate hydroxylase (NahG) in Cvi-0 reduced O(3)-induced cell death. Methyl jasmonate (Me-JA) pretreatment of Cvi-0 decreased O(3)-induced H(2)O(2) content and SA concentrations and completely abolished O(3)-induced cell death. Cvi-0 synthesized as much JA as did Col-0 in response to O(3) exposure but exhibited much less sensitivity to exogenous Me-JA. Analyses of the responses to O(3) of the JA-signaling mutants jar1 and fad3/7/8 also demonstrated an antagonistic relationship between JA- and SA-signaling pathways in controlling the magnitude of O(3)-induced HR-like cell death.

  8. Ethylene insensitivity modulates ozone-induced cell death in birch.

    PubMed

    Vahala, Jorma; Ruonala, Raili; Keinänen, Markku; Tuominen, Hannele; Kangasjärvi, Jaakko

    2003-05-01

    We have used genotypic variation in birch (Betula pendula Roth) to investigate the roles of ozone (O(3))-induced ethylene (ET), jasmonic acid, and salicylic acid in the regulation of tissue tolerance to O(3). Of these hormones, ET evolution correlated best with O(3)-induced cell death. Disruption of ET perception by transformation of birch with the dominant negative mutant allele etr1-1 of the Arabidopsis ET receptor gene ETR1 or blocking of ET perception with 1-methylcyclopropene reduced but did not completely prevent the O(3)-induced cell death, when inhibition of ET biosynthesis with aminooxyacetic acid completely abolished O(3) lesion formation. This suggests the presence of an ET-signaling-independent but ET biosynthesis-dependent component in the ET-mediated stimulation of cell death in O(3)-exposed birch. Functional ET signaling was required for the O(3) induction of the gene encoding beta-cyanoalanine synthase, which catalyzes detoxification of the cyanide formed during ET biosynthesis. The results suggest that functional ET signaling is required to protect birch from the O(3)-induced cell death and that a decrease in ET sensitivity together with a simultaneous, high ET biosynthesis can potentially cause cell death through a deficient detoxification of cyanide.

  9. [Transient brain ischemia: NMDA receptor modulation and delayed neuronal death].

    PubMed

    Benquet, Pascal; Gee, Christine E; Gerber, Urs

    2008-02-01

    Transient global ischemia induces delayed neuronal death in certain cell types and brain regions while sparing cells in other areas. A key process through which oxygen-glucose deprivation triggers cell death is the excessive accumulation of the neurotransmitter glutamate leading to over excitation of neurons. In certain neurons this increase in glutamate will potentiate the NMDA type of glutamate receptor, which can then initiate cell death. This review provides an update of the neurophysiological, cellular and molecular mechanisms inducing post-ischemic plasticity of NMDA receptors, focusing on the sensitive CA1 pyramidal neurons in the hippocampus as compared to the relatively resistant neighboring CA3 neurons. Both a change in the equilibrium between protein tyrosine kinases/phosphatases and an increased density of surface NMDA receptors in response to ischemia may explain the selective vulnerability of specific cell types. Implications for the treatment of stroke and reasons for the failures of human clinical trials utilizing NMDA receptor antagonists are also discussed.

  10. Toll pathway modulates TNF-induced JNK-dependent cell death in Drosophila

    PubMed Central

    Wu, Chenxi; Chen, Changyan; Dai, Jianli; Zhang, Fan; Chen, Yujun; Li, Wenzhe; Pastor-Pareja, José Carlos; Xue, Lei

    2015-01-01

    Signalling networks that control the life or death of a cell are of central interest in modern biology. While the defined roles of the c-Jun N-terminal kinase (JNK) pathway in regulating cell death have been well-established, additional factors that modulate JNK-mediated cell death have yet to be fully elucidated. To identify novel regulators of JNK-dependent cell death, we performed a dominant-modifier screen in Drosophila and found that the Toll pathway participates in JNK-mediated cell death. Loss of Toll signalling suppresses ectopically and physiologically activated JNK signalling-induced cell death. Our epistasis analysis suggests that the Toll pathway acts as a downstream modulator for JNK-dependent cell death. In addition, gain of JNK signalling results in Toll pathway activation, revealed by stimulated transcription of Drosomycin (Drs) and increased cytoplasm-to-nucleus translocation of Dorsal. Furthermore, the Spätzle (Spz) family ligands for the Toll receptor are transcriptionally upregulated by activated JNK signalling in a non-cell-autonomous manner, providing a molecular mechanism for JNK-induced Toll pathway activation. Finally, gain of Toll signalling exacerbates JNK-mediated cell death and promotes cell death independent of caspases. Thus, we have identified another important function for the evolutionarily conserved Toll pathway, in addition to its well-studied roles in embryonic dorso-ventral patterning and innate immunity. PMID:26202785

  11. Toll pathway modulates TNF-induced JNK-dependent cell death in Drosophila.

    PubMed

    Wu, Chenxi; Chen, Changyan; Dai, Jianli; Zhang, Fan; Chen, Yujun; Li, Wenzhe; Pastor-Pareja, José Carlos; Xue, Lei

    2015-07-01

    Signalling networks that control the life or death of a cell are of central interest in modern biology. While the defined roles of the c-Jun N-terminal kinase (JNK) pathway in regulating cell death have been well-established, additional factors that modulate JNK-mediated cell death have yet to be fully elucidated. To identify novel regulators of JNK-dependent cell death, we performed a dominant-modifier screen in Drosophila and found that the Toll pathway participates in JNK-mediated cell death. Loss of Toll signalling suppresses ectopically and physiologically activated JNK signalling-induced cell death. Our epistasis analysis suggests that the Toll pathway acts as a downstream modulator for JNK-dependent cell death. In addition, gain of JNK signalling results in Toll pathway activation, revealed by stimulated transcription of Drosomycin (Drs) and increased cytoplasm-to-nucleus translocation of Dorsal. Furthermore, the Spätzle (Spz) family ligands for the Toll receptor are transcriptionally upregulated by activated JNK signalling in a non-cell-autonomous manner, providing a molecular mechanism for JNK-induced Toll pathway activation. Finally, gain of Toll signalling exacerbates JNK-mediated cell death and promotes cell death independent of caspases. Thus, we have identified another important function for the evolutionarily conserved Toll pathway, in addition to its well-studied roles in embryonic dorso-ventral patterning and innate immunity.

  12. A Central Role for Carbon-Overflow Pathways in the Modulation of Bacterial Cell Death

    PubMed Central

    Thomas, Vinai Chittezham; Sadykov, Marat R.; Chaudhari, Sujata S.; Jones, Joselyn; Endres, Jennifer L.; Widhelm, Todd J.; Ahn, Jong-Sam; Jawa, Randeep S.; Zimmerman, Matthew C.; Bayles, Kenneth W.

    2014-01-01

    Similar to developmental programs in eukaryotes, the death of a subpopulation of cells is thought to benefit bacterial biofilm development. However mechanisms that mediate a tight control over cell death are not clearly understood at the population level. Here we reveal that CidR dependent pyruvate oxidase (CidC) and α-acetolactate synthase/decarboxylase (AlsSD) overflow metabolic pathways, which are active during staphylococcal biofilm development, modulate cell death to achieve optimal biofilm biomass. Whereas acetate derived from CidC activity potentiates cell death in cells by a mechanism dependent on intracellular acidification and respiratory inhibition, AlsSD activity effectively counters CidC action by diverting carbon flux towards neutral rather than acidic byproducts and consuming intracellular protons in the process. Furthermore, the physiological features that accompany metabolic activation of cell death bears remarkable similarities to hallmarks of eukaryotic programmed cell death, including the generation of reactive oxygen species and DNA damage. Finally, we demonstrate that the metabolic modulation of cell death not only affects biofilm development but also biofilm-dependent disease outcomes. Given the ubiquity of such carbon overflow pathways in diverse bacterial species, we propose that the metabolic control of cell death may be a fundamental feature of prokaryotic development. PMID:24945831

  13. A module on death and dying to develop empathy in student pharmacists.

    PubMed

    Manolakis, Michael L; Olin, Jacqueline L; Thornton, Phillip L; Dolder, Christian R; Hanrahan, Conor

    2011-05-10

    To implement an integrated module on death and dying into a 15-week bioethics course and determine whether it increased student pharmacists' empathy. Students participated in a 5-week death and dying module that included presentation of the film Wit, an interactive lecture on hospice, and a lecture on the ethics of pain management. Fifty-six students completed the 30-item Balanced Emotional Empathy Scale (BEES) before and after completing the module and wrote a reflective essay. Students demonstrated an appreciation of patient-specific values in their essay. Quantitative data collected via BEES scores demonstrated significant improvement in measured empathy. A 5-week instructional model on death and dying significantly increased student empathy.

  14. Identification of modules related to programmed cell death in CHD based on EHEN.

    PubMed

    Jia, Xu; Li, Wan; Miao, Zhengqiang; Feng, Chenchen; Liu, Zhe; He, Yuehan; Lv, Junjie; Du, Youwen; Hou, Min; He, Weiming; Li, Danbin; Chen, Lina

    2014-01-01

    The formation and death of macrophages and foam cells are one of the major factors that cause coronary heart disease (CHD). In our study, based on the Edinburgh Human Metabolic Network (EHMN) metabolic network, we built an enzyme network which was constructed by enzymes (nodes) and reactions (edges) called the Edinburgh Human Enzyme Network (EHEN). By integrating the subcellular location information for the reactions and refining the protein-reaction relationships based on the location information, we proposed a computational approach to select modules related to programmed cell death. The identified module was in the EHEN-mitochondria (EHEN-M) and was confirmed to be related to programmed cell death, CHD pathogenesis, and lipid metabolism in the literature. We expected this method could analyze CHD better and more comprehensively from the point of programmed cell death in subnetworks.

  15. Hop/STI1 modulates retinal proliferation and cell death independent of PrPC.

    PubMed

    Arruda-Carvalho, Maithe; Njaine, Brian; Silveira, Mariana S; Linden, Rafael; Chiarini, Luciana B

    2007-09-21

    Hop/STI1 is a co-chaperone adaptor protein for Hsp70/Hsp90 complexes. Hop/STI1 is found extracellularly and modulates cell death and differentiation through interaction with the prion protein (PrP(C)). Here, we investigated the expression of hop/STI1 and its role upon cell proliferation and cell death in the developing retina. Hop/STI1 is more expressed in developing rat retina than in the mature tissue. Hop/STI1 blocks retinal cell death in the neuroblastic layer (NBL) in a PrP(C) dependent manner, but failed to protect ganglion cells against axotomy-induced cell death. An antibody raised against hop/STI1 (alpha-STI1) blocked both ganglion cell and NBL cell death independent of PrP(C). cAMP/PKA, ERK, PI3K and PKC signaling pathways were not involved in these effects. Hop/STI1 treatment reduced proliferation, while alpha-STI1 increased proliferation in the developing retina, both independent of PrP(C). We conclude that hop/STI1 can modulate both proliferation and cell death in the developing retina independent of PrP(C).

  16. Proteinase 3-dependent caspase-3 cleavage modulates neutrophil death and inflammation.

    PubMed

    Loison, Fabien; Zhu, Haiyan; Karatepe, Kutay; Kasorn, Anongnard; Liu, Peng; Ye, Keqiang; Zhou, Jiaxi; Cao, Shannan; Gong, Haiyan; Jenne, Dieter E; Remold-O'Donnell, Eileen; Xu, Yuanfu; Luo, Hongbo R

    2014-10-01

    Caspase-3-mediated spontaneous death in neutrophils is a prototype of programmed cell death and is critical for modulating physiopathological inflammatory responses; however, the underlying regulatory pathways remain ill defined. Here we determined that in aging neutrophils, the cleavage and activation of caspase-3 is independent of the canonical caspase-8- or caspase-9-mediated pathway. Instead, caspase-3 activation was mediated by serine protease proteinase 3 (PR3), which is present in the cytosol of aging neutrophils. Specifically, PR3 cleaved procaspase-3 at a site upstream of the canonical caspase-9 cleavage site. In mature neutrophils, PR3 was sequestered in granules and released during aging via lysosomal membrane permeabilization (LMP), leading to procaspase-3 cleavage and apoptosis. Pharmacological inhibition or knockdown of PR3 delayed neutrophil death in vitro and consistently delayed neutrophil death and augmented neutrophil accumulation at sites of inflammation in a murine model of peritonitis. Adoptive transfer of both WT and PR3-deficient neutrophils revealed that the delayed death of neutrophils lacking PR3 is due to an altered intrinsic apoptosis/survival pathway, rather than the inflammatory microenvironment. The presence of the suicide protease inhibitor SERPINB1 counterbalanced the protease activity of PR3 in aging neutrophils, and deletion of Serpinb1 accelerated neutrophil death. Taken together, our results reveal that PR3-mediated caspase-3 activation controls neutrophil spontaneous death.

  17. Proteinase 3–dependent caspase-3 cleavage modulates neutrophil death and inflammation

    PubMed Central

    Loison, Fabien; Zhu, Haiyan; Karatepe, Kutay; Kasorn, Anongnard; Liu, Peng; Ye, Keqiang; Zhou, Jiaxi; Cao, Shannan; Gong, Haiyan; Jenne, Dieter E.; Remold-O’Donnell, Eileen; Xu, Yuanfu; Luo, Hongbo R.

    2014-01-01

    Caspase-3–mediated spontaneous death in neutrophils is a prototype of programmed cell death and is critical for modulating physiopathological inflammatory responses; however, the underlying regulatory pathways remain ill defined. Here we determined that in aging neutrophils, the cleavage and activation of caspase-3 is independent of the canonical caspase-8– or caspase-9–mediated pathway. Instead, caspase-3 activation was mediated by serine protease proteinase 3 (PR3), which is present in the cytosol of aging neutrophils. Specifically, PR3 cleaved procaspase-3 at a site upstream of the canonical caspase-9 cleavage site. In mature neutrophils, PR3 was sequestered in granules and released during aging via lysosomal membrane permeabilization (LMP), leading to procaspase-3 cleavage and apoptosis. Pharmacological inhibition or knockdown of PR3 delayed neutrophil death in vitro and consistently delayed neutrophil death and augmented neutrophil accumulation at sites of inflammation in a murine model of peritonitis. Adoptive transfer of both WT and PR3-deficient neutrophils revealed that the delayed death of neutrophils lacking PR3 is due to an altered intrinsic apoptosis/survival pathway, rather than the inflammatory microenvironment. The presence of the suicide protease inhibitor SERPINB1 counterbalanced the protease activity of PR3 in aging neutrophils, and deletion of Serpinb1 accelerated neutrophil death. Taken together, our results reveal that PR3-mediated caspase-3 activation controls neutrophil spontaneous death. PMID:25180606

  18. Aspirin induces cell death by directly modulating mitochondrial voltage-dependent anion channel (VDAC)

    PubMed Central

    Tewari, Debanjan; Majumdar, Dhriti; Vallabhaneni, Sirisha; Bera, Amal Kanti

    2017-01-01

    Aspirin induces apoptotic cell death in various cancer cell lines. Here we showed that silencing of VDAC1 protected HeLa cells from aspirin-induced cell death. Compared to the wild type cells, VDAC1 knocked down cells showed lesser change of mitochondrial membrane potential (Δψm), upon aspirin treatment. Aspirin augmented ATP and ionomycin-induced mitochondrial Ca2+ uptake which was abolished in VDAC1 knocked down cells. Aspirin dissociated bound hexokinase II (HK-II) from mitochondria. Further, aspirin promoted the closure of recombinant human VDAC1, reconstituted in planar lipid bilayer. Taken together, these results imply that VDAC1 serves as a novel target for aspirin. Modulation of VDAC1 is possibly associated with the cell death and anticancer effects of aspirin. PMID:28327594

  19. Pelle Modulates dFoxO-Mediated Cell Death in Drosophila

    PubMed Central

    Chen, Changyan; Zhang, Shiping; Li, Chaojie; Li, Wenzhe; Wu, Shian; Xue, Lei

    2015-01-01

    Interleukin-1 receptor-associated kinases (IRAKs) are crucial mediators of the IL-1R/TLR signaling pathways that regulate the immune and inflammation response in mammals. Recent studies also suggest a critical role of IRAKs in tumor development, though the underlying mechanism remains elusive. Pelle is the sole Drosophila IRAK homolog implicated in the conserved Toll pathway that regulates Dorsal/Ventral patterning, innate immune response, muscle development and axon guidance. Here we report a novel function of pll in modulating apoptotic cell death, which is independent of the Toll pathway. We found that loss of pll results in reduced size in wing tissue, which is caused by a reduction in cell number but not cell size. Depletion of pll up-regulates the transcription of pro-apoptotic genes, and triggers caspase activation and cell death. The transcription factor dFoxO is required for loss-of-pll induced cell death. Furthermore, loss of pll activates dFoxO, promotes its translocation from cytoplasm to nucleus, and up-regulates the transcription of its target gene Thor/4E-BP. Finally, Pll physically interacts with dFoxO and phosphorylates dFoxO directly. This study not only identifies a previously unknown physiological function of pll in cell death, but also shed light on the mechanism of IRAKs in cell survival/death during tumorigenesis. PMID:26474173

  20. Protein Kinase Cβ Modulates Ligand-induced Cell Surface Death Receptor Accumulation

    PubMed Central

    Meng, Xue Wei; Heldebrant, Michael P.; Flatten, Karen S.; Loegering, David A.; Dai, Haiming; Schneider, Paula A.; Gomez, Timothy S.; Peterson, Kevin L.; Trushin, Sergey A.; Hess, Allan D.; Smith, B. Douglas; Karp, Judith E.; Billadeau, Daniel D.; Kaufmann, Scott H.

    2010-01-01

    Although treatment with the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) is known to protect a subset of cells from induction of apoptosis by death ligands such as Fas ligand and tumor necrosis factor-α-related apoptosis-inducing ligand, the mechanism of this protection is unknown. This study demonstrated that protection in short term apoptosis assays and long term proliferation assays was maximal when Jurkat or HL-60 human leukemia cells were treated with 2–5 nm PMA. Immunoblotting demonstrated that multiple PKC isoforms, including PKCα, PKCβ, PKCϵ, and PKCθ, translocated from the cytosol to a membrane-bound fraction at these PMA concentrations. When the ability of short hairpin RNA (shRNA) constructs that specifically down-regulated each of these isoforms was examined, PKCβ shRNA uniquely reversed PMA-induced protection against cell death. The PKCβ-selective small molecule inhibitor enzastaurin had a similar effect. Although mass spectrometry suggested that Fas is phosphorylated on a number of serines and threonines, mutation of these sites individually or collectively had no effect on Fas-mediated death signaling or PMA protection. Further experiments demonstrated that PMA diminished ligand-induced cell surface accumulation of Fas and DR5, and PKCβ shRNA or enzastaurin reversed this effect. Moreover, enzastaurin sensitized a variety of human tumor cell lines and clinical acute myelogenous leukemia isolates, which express abundant PKCβ, to tumor necrosis factor-α related apoptosis-inducing ligand-induced death in the absence of PMA. Collectively, these results identify a specific PKC isoform that modulates death receptor-mediated cytotoxicity as well as a small molecule inhibitor that mitigates the inhibitory effects of PKC activation on ligand-induced death receptor trafficking and cell death. PMID:19887445

  1. KUS121, a VCP modulator, attenuates ischemic retinal cell death via suppressing endoplasmic reticulum stress

    PubMed Central

    Hata, Masayuki; Ikeda, Hanako O.; Kikkawa, Chinami; Iwai, Sachiko; Muraoka, Yuki; Hasegawa, Tomoko; Kakizuka, Akira; Yoshimura, Nagahisa

    2017-01-01

    Ischemic neural damages cause several devastating diseases, including brain stroke and ischemic retinopathies, and endoplasmic reticulum (ER) stress has been proposed to be the underlying mechanism of the neuronal cell death of these conditions. We previously synthesized Kyoto University substances (KUSs) as modulators of valosin-containing protein (VCP); KUSs inhibit VCP ATPase activity and protect cells from different cell death-inducing insults. Here, we examined the efficacy of KUS121 in a rat model of retinal ischemic injury. Systemic administration of KUS121 to rats with ischemic retinal injury significantly suppressed inner retinal thinning and death of retinal ganglion and amacrine cells, with a significant functional maintenance of visual functions, as judged by electroretinography. Furthermore, intravitreal injection of KUS121, which is the clinically preferred route of drug administration for retinal diseases, appeared to show an equal or better neuroprotective efficacy in the ischemic retina compared with systemic administration. Indeed, induction of the ER stress marker C/EBP homologous protein (CHOP) after the ischemic insult was significantly suppressed by KUS121 administration. Our study suggests VCP modulation by KUS as a promising novel therapeutic strategy for ischemic neuronal diseases. PMID:28317920

  2. Identification of Genetic and Chemical Modulators of Zebrafish Mechanosensory Hair Cell Death

    PubMed Central

    Roberts, Brock; Linbo, Tor; Coffin, Allison B.; Knisely, Anna J.; Simon, Julian A.; Rubel, Edwin W.; Raible, David W.

    2008-01-01

    Inner ear sensory hair cell death is observed in the majority of hearing and balance disorders, affecting the health of more than 600 million people worldwide. While normal aging is the single greatest contributor, exposure to environmental toxins and therapeutic drugs such as aminoglycoside antibiotics and antineoplastic agents are significant contributors. Genetic variation contributes markedly to differences in normal disease progression during aging and in susceptibility to ototoxic agents. Using the lateral line system of larval zebrafish, we developed an in vivo drug toxicity interaction screen to uncover genetic modulators of antibiotic-induced hair cell death and to identify compounds that confer protection. We have identified 5 mutations that modulate aminoglycoside susceptibility. Further characterization and identification of one protective mutant, sentinel (snl), revealed a novel conserved vertebrate gene. A similar screen identified a new class of drug-like small molecules, benzothiophene carboxamides, that prevent aminoglycoside-induced hair cell death in zebrafish and in mammals. Testing for interaction with the sentinel mutation suggests that the gene and compounds may operate in different pathways. The combination of chemical screening with traditional genetic approaches is a new strategy for identifying drugs and drug targets to attenuate hearing and balance disorders. PMID:18454195

  3. Magnetic Zenith Enhancement of HF Radio-Induced Airglow Production at HAARP

    DTIC Science & Technology

    2003-02-22

    Magnetic zenith enhancement of HF radio-induced airglow production at HAARP T. R. Pedersen,1 M. McCarrick,2 E. Gerken,3 C. Selcher,4 D. Sentman,5 H ...E. Gerken, C. Selcher, D. Sentman, H . C. Carlson, and A. Gurevich, Magnetic zenith enhancement of HF radio- induced airglow production at HAARP...Unambiguous evidence of HF pump-enhanced airglow at auroral latitudes, Geophys. Res. Lett., 26(23), 2561–3564, 1999. Gurevich, A., H . Carlson, M. Kelley, T

  4. The Effect of an Instructional Module on Death and Dying on the Death Anxiety of Emergency Medical Technician Trainees.

    ERIC Educational Resources Information Center

    Coleman, Ted

    1993-01-01

    Examined whether instructional unit on death and dying during emergency medical technician course reduced death anxiety in trainees. Found no significant differences between treatment group (n=28) that received unit and control group (n=25) that did not on pre-, post-, or delayed-tests. Death education apparently had no more influence on death…

  5. Carbon monoxide and mitochondria—modulation of cell metabolism, redox response and cell death

    PubMed Central

    Almeida, Ana S.; Figueiredo-Pereira, Cláudia; Vieira, Helena L. A.

    2015-01-01

    Carbon monoxide (CO) is an endogenously produced gasotransmitter, which is associated with cytoprotection and cellular homeostasis in several distinct cell types and tissues. CO mainly targets mitochondria because: (i) mitochondrial heme-proteins are the main potential candidates for CO to bind, (ii) many CO's biological actions are dependent on mitochondrial ROS signaling and (iii) heme is generated in the mitochondrial compartment. Mitochondria are the key cell energy factory, producing ATP through oxidative phosphorylation and regulating cell metabolism. These organelles are also implicated in many cell signaling pathways and the production of reactive oxygen species (ROS). Finally, mitochondria contain several factors activating programmed cell death pathways, which are released from the mitochondrial inter-membrane space upon mitochondrial membrane permeabilization. Therefore, disclosing CO mode of action at mitochondria opens avenues for deeper understanding CO's biological properties. Herein, it is discussed how CO affects the three main aspects of mitochondrial modulation of cell function: metabolism, redox response and cell death. PMID:25709582

  6. Modulating cell-to-cell variability and sensitivity to death ligands by co-drugging

    NASA Astrophysics Data System (ADS)

    Flusberg, Deborah A.; Sorger, Peter K.

    2013-06-01

    TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) holds promise as an anti-cancer therapeutic but efficiently induces apoptosis in only a subset of tumor cell lines. Moreover, even in clonal populations of responsive lines, only a fraction of cells dies in response to TRAIL and individual cells exhibit cell-to-cell variability in the timing of cell death. Fractional killing in these cell populations appears to arise not from genetic differences among cells but rather from differences in gene expression states, fluctuations in protein levels and the extent to which TRAIL-induced death or survival pathways become activated. In this study, we ask how cell-to-cell variability manifests in cell types with different sensitivities to TRAIL, as well as how it changes when cells are exposed to combinations of drugs. We show that individual cells that survive treatment with TRAIL can regenerate the sensitivity and death-time distribution of the parental population, demonstrating that fractional killing is a stable property of cell populations. We also show that cell-to-cell variability in the timing and probability of apoptosis in response to treatment can be tuned using combinations of drugs that together increase apoptotic sensitivity compared to treatment with one drug alone. In the case of TRAIL, modulation of cell-to-cell variability by co-drugging appears to involve a reduction in the threshold for mitochondrial outer membrane permeabilization.

  7. Azadirachta indica modulates electrical properties and type of cell death in NDEA-induced hepatic tumors.

    PubMed

    Bharati, Sanjay; Rishi, Praveen; Koul, Ashwani

    2014-09-01

    Tissue electrical conductivity is an important indicator of tissue structure and composition. Present study demonstrates modulatory effect of Azadirachta indica on the electrical conductivity and cell death in hepatic tumors. Hepatic tumors were generated by intraperitoneal injection of N-nitrosodiethylamine (cumulative dose: 200 μg/g body mass) to male BALB/c mice. Aqueous A. indica leaf extract (AAILE) was administered orally at a dosage of 100 μg/g body mass till the termination of experiment. At the end of experiment, electrical conductivity of hepatic tumors was measured with four-pin electrode method. Tissues and tumors were then processed for TUNEL assay and DNA fragmentation analysis. The levels of TNF-α were also determined in the normal hepatic and tumor tissue. Hepatic tumors had higher electrical conductivity compared to normal liver tissue. An increased necrotic cell percentage along with elevated TNF-α was also observed. Although, AAILE co-treatment resulted in tumors with higher electrical conductivity compared to normal animals. However, the electrical conductivity was decreased significantly compared to untreated tumors. A significant increase in apoptotic cell percentage and concomitant decrease in necrotic cell percentage along with the increased TNF-α level was observed in these tumors. The results suggest that A. indica modulated mode of cell death in tumors and type of cell death had significant contribution in determining hepatic tumor electrical conductivity.

  8. Cell wall dynamics modulate acetic acid-induced apoptotic cell death of Saccharomyces cerevisiae

    PubMed Central

    Rego, António; Duarte, Ana M.; Azevedo, Flávio; Sousa, Maria J.; Côrte-Real, Manuela; Chaves, Susana R.

    2014-01-01

    Acetic acid triggers apoptotic cell death in Saccharomyces cerevisiae, similar to mammalian apoptosis. To uncover novel regulators of this process, we analyzed whether impairing MAPK signaling affected acetic acid-induced apoptosis and found the mating-pheromone response and, especially, the cell wall integrity pathways were the major mediators, especially the latter, which we characterized further. Screening downstream effectors of this pathway, namely targets of the transcription factor Rlm1p, highlighted decreased cell wall remodeling as particularly important for acetic acid resistance. Modulation of cell surface dynamics therefore emerges as a powerful strategy to increase acetic acid resistance, with potential application in industrial fermentations using yeast, and in biomedicine to exploit the higher sensitivity of colorectal carcinoma cells to apoptosis induced by acetate produced by intestinal propionibacteria. PMID:28357256

  9. MITA modulated autophagy flux promotes cell death in breast cancer cells.

    PubMed

    Bhatelia, Khyati; Singh, Kritarth; Prajapati, Paresh; Sripada, Lakshmi; Roy, Milton; Singh, Rajesh

    2017-03-31

    The crosstalk between inflammation and autophagy is an emerging phenomenon observed during tumorigenesis. Activation of NF-κB and IRF3 plays a key role in the regulation of cytokines that are involved in tumor growth and progression. The genes of innate immunity are known to regulate the master transcription factors like NF-κB and IRF3. Innate immunity pathways at the same time regulate the genes of the autophagy pathway which are essential for tumor cell metabolism. In the current study, we studied the role of MITA (Mediator of IRF3 Activation), a regulator of innate immunity, in the regulation of autophagy and its implication in cell death of breast cancer cells. Here, we report that MITA inhibits the fusion of autophagosome with lysosome as evident from different autophagy flux assays. The expression of MITA induces the translocation of p62 and NDP52 to mitochondria which further recruits LC3 for autophagosome formation. The expression of MITA decreased mitochondrial number and enhances mitochondrial ROS by increasing complex-I activity. The enhancement of autophagy flux with rapamycin or TFEB expression normalized MITA induced cell death. The evidences clearly show that MITA regulates autophagy flux and modulates mitochondrial turnover through mitophagy.

  10. Extracellular divalent cations modulate aminoglycoside-induced hair cell death in the zebrafish lateral line

    PubMed Central

    Coffin, Allison B.; Reinhart, Katherine E.; Owens, Kelly N.; Raible, David W.; Rubel, Edwin W

    2016-01-01

    Aminoglycoside antibiotics cause death of sensory hair cells. Research over the past decade has identified several key players in the intracellular cascade. However, the role of the extracellular environment in aminoglycoside ototoxicity has received comparatively little attention. The present study uses the zebrafish lateral line to demonstrate that extracellular calcium and magnesium ions modulate hair cell death from neomycin and gentamicin in vivo, with high levels of either divalent cation providing significant protection. Imaging experiments with fluorescently tagged gentamicin show that drug uptake is reduced under high calcium conditions. Treating fish with the hair cell transduction blocker amiloride also reduces aminoglycoside uptake, preventing the toxicity, and experiments with variable calcium and amiloride concentrations suggest complementary effects between the two protectants. Elevated magnesium, in contrast, does not appear to significantly attenuate drug uptake, suggesting that the two divalent cations may protect hair cells from aminoglycoside damage through different mechanisms. These results provide additional evidence for calcium- and transduction-dependent aminoglycoside uptake. Divalent cations provided differential protection from neomycin and gentamicin, with high cation concentrations almost completely protecting hair cells from neomycin and acute gentamicin toxicity, but offering reduced protection from continuous (6 hr) gentamicin exposure. These experiments lend further support to the hypothesis that aminoglycoside toxicity occurs via multiple pathways in a both a drug and time course-specific manner. PMID:19285547

  11. Innate immune response during Yersinia infection: critical modulation of cell death mechanisms through phagocyte activation.

    PubMed

    Bergsbaken, Tessa; Cookson, Brad T

    2009-11-01

    Yersinia pestis, the etiological agent of plague, is one of the most deadly pathogens on our planet. This organism shares important attributes with its ancestral progenitor, Yersinia pseudotuberculosis, including a 70-kb virulence plasmid, lymphotropism during growth in the mammalian host, and killing of host macrophages. Infections with both organisms are biphasic, where bacterial replication occurs initially with little inflammation, followed by phagocyte influx, inflammatory cytokine production, and tissue necrosis. During infection, plasmid-encoded attributes facilitate bacterial-induced macrophage death, which results from two distinct processes and corresponds to the inflammatory crescendo observed in vivo: Naïve cells die by apoptosis (noninflammatory), and later in infection, activated macrophages die by pyroptosis (inflammatory). The significance of this redirected cell death for the host is underscored by the importance of phagocyte activation for immunity to Yersinia and the protective role of pyroptosis during host responses to anthrax lethal toxin and infections with Francisella, Legionella, Pseudomonas, and Salmonella. The similarities of Y. pestis and Y. pseudotuberculosis, including conserved, plasmid-encoded functions inducing at least two distinct mechanisms of cell death, indicate that comparative studies are revealing about their critical pathogenic mechanism(s) and host innate immune responses during infection. Validation of this idea and evidence of similar interactions with the host immune system are provided by Y. pseudotuberculosis-priming, cross-protective immunity against Y. pestis. Despite these insights, additional studies indicate much remains to be understood concerning effective host responses against Yersinia, including chromosomally encoded attributes that also contribute to bacterial evasion and modulation of innate and adaptive immune responses.

  12. Hodgkin’s lymphoma emerging radiation treatment techniques: trade-offs between late radio-induced toxicities and secondary malignant neoplasms

    PubMed Central

    2013-01-01

    Background Purpose of this study is to explore the trade-offs between radio-induced toxicities and second malignant neoplasm (SMN) induction risk of different emerging radiotherapy techniques for Hodgkin’s lymphoma (HL) through a comprehensive dosimetric analysis on a representative clinical model. Methods Three different planning target volume (PTVi) scenarios of a female patient with supradiaphragmatic HL were used as models for the purpose of this study. Five treatment radiation techniques were simulated: an anterior-posterior parallel-opposed (AP-PA), a forward intensity modulated (FIMRT), an inverse intensity modulated (IMRT), a Tomotherapy (TOMO), a proton (PRO) technique. A radiation dose of 30 Gy or CGE was prescribed. Dose-volume histograms of PTVs and organs-at-risk (OARs) were calculated and related to available dose-volume constraints. SMN risk for breasts, thyroid, and lungs was estimated through the Organ Equivalent Dose model considering cell repopulation and inhomogeneous organ doses. Results With similar level of PTVi coverage, IMRT, TOMO and PRO plans generally reduced the OARs’ dose and accordingly the related radio-induced toxicities. However, only TOMO and PRO plans were compliant with all constraints in all scenarios. For the IMRT and TOMO plans an increased risk of development of breast, and lung SMN compared with AP-PA and FIMRT techniques was estimated. Only PRO plans seemed to reduce the risk of predicted SMN compared with AP-PA technique. Conclusions Our model–based study supports the use of advanced RT techniques to successfully spare OARs and to reduce the risk of radio-induced toxicities in HL patients. However, the estimated increase of SMNs’ risk inherent to TOMO and IMRT techniques should be carefully considered in the evaluation of a risk-adapted therapeutic strategy. PMID:23360559

  13. Microglia modulate brainstem serotonergic expression following neonatal sustained hypoxia exposure: implications for sudden infant death syndrome.

    PubMed

    MacFarlane, P M; Mayer, C A; Litvin, D G

    2016-06-01

    Neonatal sustained hypoxia exposure modifies brainstem microglia and serotonin expression. The altered brainstem neurochemistry is associated with impaired ventilatory responses to acute hypoxia and mortality. The deleterious effects of sustained hypoxia exposure can be prevented by an inhibitor of activated microglia. These observations demonstrate a potential cause of the brainstem serotonin abnormalities thought to be involved in sudden infant death syndrome. We showed previously that the end of the second postnatal week (days P11-15) represents a period of development during which the respiratory neural control system exhibits a heightened vulnerability to sustained hypoxia (SH, 11% O2 , 5 days) exposure. In the current study, we investigated whether the vulnerability to SH during the same developmental time period is associated with changes in brainstem serotonin (5-HT) expression and whether it can be prevented by the microglia inhibitor minocycline. Using whole-body plethysmography, SH attenuated the acute (5 min) hypoxic ventilatory response (HVR) and caused a high incidence of mortality compared to normoxia rats. SH also increased microglia cell numbers and decreased 5-HT immunoreactivity in the nucleus of the solitary tract (nTS) and dorsal motor nucleus of the vagus (DMNV). The attenuated HVR, mortality, and changes in nTS and DMNV immunoreactivity was prevented by minocycline (25 mg kg(-1) /2 days during SH). These data demonstrate that the 5-HT abnormalities in distinct respiratory neural control regions can be initiated by prolonged hypoxia exposure and may be modulated by microglia activity. These observations share several commonalities with the risk factors thought to underlie the aetiology of sudden infant death syndrome, including: (1) a vulnerable neonate; (2) a critical period of development; (3) evidence of hypoxia; (4) brainstem gliosis (particularly the nTS and DMNV); and (5) 5-HT abnormalities. © 2015 The Authors. The Journal of

  14. Receptor-interacting protein kinases modulate noise-induced sensory hair cell death

    PubMed Central

    Zheng, H-W; Chen, J; Sha, S-H

    2014-01-01

    Receptor-interacting protein (RIP) kinases promote the induction of necrotic cell death pathways. Here we investigated signaling pathways in outer hair cells (OHCs) of adult male CBA/J mice exposed to noise that causes permanent threshold shifts, with a particular focus on RIP kinase-regulated necroptosis. One hour after noise exposure, nuclei of OHCs in the basal region of the cochlea displayed both apoptotic and necrotic features. RIP1 and RIP3 protein levels increased and caspase-8 was activated. Treatment with pan-caspase inhibitor ZVAD blocked the activation of caspase-8 and reduced the number of apoptotic nuclei, while increasing levels of RIP1, RIP3, and necrotic OHCs. Conversely, treatment with necrosis inhibitor necrostatin-1 (Nec-1) or RIP3 siRNA (siRIP3) diminished noise-induced increases in RIP1 and RIP3, and decreased necrotic OHC nuclei. This treatment also increased the number of apoptotic nuclei without increasing activation of caspase-8. Consistent with the elevation of levels of RIP1 and RIP3, noise-induced active AMPKα levels increased with ZVAD treatment, but decreased with Nec-1 and siRIP3 treatment. Furthermore, treatment with siRIP3 did not alter the activation of caspase-8, but instead increased activation of caspase-9 and promoted endonuclease G translocation into OHC nuclei. Finally, auditory brainstem response functional measurements and morphological assessment of OHCs showed that ZVAD treatment reduces noise-induced deficits. This protective function is potentiated when combined with siRIP3 treatment. In conclusion, noise-induced OHC apoptosis and necrosis are modulated by caspases and RIP kinases, respectively. Inhibition of either pathway shifts the prevalence of OHC death to the alternative pathway. PMID:24874734

  15. Resistance to Cell Death and Its Modulation in Cancer Stem Cells

    PubMed Central

    Safa, Ahmad R.

    2017-01-01

    Accumulating evidence has demonstrated that human cancers arise from various tissues of origin that initiate from cancer stem cells (CSCs) or cancer-initiating cells. The extrinsic and intrinsic apoptotic pathways are dysregulated in CSCs, and these cells play crucial roles in tumor initiation, progression, cell death resistance, chemo- and radiotherapy resistance, and tumor recurrence. Understanding CSC-specific signaling proteins and pathways is necessary to identify specific therapeutic targets that may lead to the development of more efficient therapies selectively targeting CSCs. Several signaling pathways—including the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), maternal embryonic leucine zipper kinase (MELK), NOTCH1, and Wnt/β-catenin—and expression of the CSC markers CD133, CD24, CD44, Oct4, Sox2, Nanog, and ALDH1A1 maintain CSC properties. Studying such pathways may help to understand CSC biology and lead to the development of potential therapeutic interventions to render CSCs more sensitive to cell death triggered by chemotherapy and radiation therapy. Moreover, recent demonstrations of dedifferentiation of differentiated cancer cells into CSC-like cells have created significant complexity in the CSCs hypothesis. Therefore, any successful therapeutic agent or combination of drugs for cancer therapy must eliminate not only CSCs but differentiated cancer cells and the entire bulk of tumor cells. This review article expands on the CSC hypothesis and paradigm with respect to major signaling pathways and effectors that regulate CSC apoptosis resistance. Moreover, selective CSC apoptotic modulators and their therapeutic potential for making tumors more responsive to therapy are discussed. The use of novel therapies, including small-molecule inhibitors of specific proteins in signaling pathways that regulate stemness, proliferation and migration of CSCs, immunotherapy, and noncoding microRNAs may provide better means of

  16. Hop/STI1 modulates retinal proliferation and cell death independent of PrP{sup C}

    SciTech Connect

    Arruda-Carvalho, Maithe; Njaine, Brian; Silveira, Mariana S.; Linden, Rafael; Chiarini, Luciana B. . E-mail: chiarini@biof.ufrj.br

    2007-09-21

    Hop/STI1 is a co-chaperone adaptor protein for Hsp70/Hsp90 complexes. Hop/STI1 is found extracellularly and modulates cell death and differentiation through interaction with the prion protein (PrP{sup C}). Here, we investigated the expression of hop/STI1 and its role upon cell proliferation and cell death in the developing retina. Hop/STI1 is more expressed in developing rat retina than in the mature tissue. Hop/STI1 blocks retinal cell death in the neuroblastic layer (NBL) in a PrP{sup C} dependent manner, but failed to protect ganglion cells against axotomy-induced cell death. An antibody raised against hop/STI1 ({alpha}-STI1) blocked both ganglion cell and NBL cell death independent of PrP{sup C}. cAMP/PKA, ERK, PI3K and PKC signaling pathways were not involved in these effects. Hop/STI1 treatment reduced proliferation, while {alpha}-STI1 increased proliferation in the developing retina, both independent of PrP{sup C}. We conclude that hop/STI1 can modulate both proliferation and cell death in the developing retina independent of PrP{sup C}.

  17. Discussing Death, Dying, and End-of-Life Goals of Care: A Communication Skills Training Module for Oncology Nurses.

    PubMed

    Coyle, Nessa; Manna, Ruth; Shen, Megan; Banerjee, Smita C; Penn, Stacey; Pehrson, Cassandra; Krueger, Carol A; Maloney, Erin K; Zaider, Talia; Bylund, Carma L

    2015-12-01

    Effective communication, particularly at the end of life, is an essential skill for oncology nurses, but few receive formal training in this area. The aim of this article is to adapt an end-of-life care communication skills training (CST) module, originally developed for oncologists, for oncology nurses and to evaluate participants' confidence in using the communication skills learned and their satisfaction with the module. The adapted end-of-life care module consisted of a 45-minute didactic, exemplary video and 90 minutes of small group interaction and experiential role play with a simulated patient. Using a five-point Likert-type scale, 247 inpatient oncology nurses completed pre-/post-workshop surveys rating their confidence in discussing death, dying, and end-of-life goals of care with patients, as well as overall satisfaction with the module. Nurses' confidence in discussing death, dying, and end-of-life goals of care increased significantly after attending the workshop. Nurse participants indicated satisfaction with the module by agreeing or strongly agreeing to all six items assessing satisfaction 90%-98% of the time. Nurses' CST in discussing death, dying, and end-of-life care showed feasibility, acceptability, and potential benefit at improving confidence in having end-of-life care discussions.

  18. Localization of Barley yellow dwarf virus Movement Protein Modulating Programmed Cell Death in Nicotiana benthamiana

    PubMed Central

    Ju, Jiwon; Kim, Kangmin; Lee, Kui-Jae; Lee, Wang Hu; Ju, Ho-Jong

    2017-01-01

    Barley yellow dwarf virus (BYDV) belongs to Luteovirus and is limited only at phloem related tissues. An open reading frame (ORF) 4 of BYDV codes for the movement protein (MP) of BYDV gating plasmodesmata (PD) to facilitate virus movement. Like other Luteoviruses, ORF 4 of BYDV is embedded in the ORF3 but expressed from the different reading frame in leaky scanning manner. Although MP is a very important protein for systemic infection of BYDV, there was a little information. In this study, MP was characterized in terms of subcellular localization and programmed cell death (PCD). Gene of MP or its mutant (ΔMP) was expressed by Agroinfiltration method. MP was clearly localized at the nucleus and the PD, but ΔMP which was deleted distal N-terminus of MP showed no localization to PD exhibited the different target with original MP. In addition to PD localization, MP appeared associated with small granules in cytoplasm whereas ΔMP did not. MP associated with PD and small granules induced PCD, but ΔMP showed no association with PD and small granules did not exhibit PCD. Based on this study, the distal N-terminal region within MP is seemingly responsible for the localization of PD and the induction small granules and PCD induction. These results suggest that subcellular localization of BYDV MP may modulate the PCD in Nicotiana benthamiana. PMID:28167888

  19. Oleuropein Prevents Neuronal Death, Mitigates Mitochondrial Superoxide Production and Modulates Autophagy in a Dopaminergic Cellular Model.

    PubMed

    Achour, Imène; Arel-Dubeau, Anne-Marie; Renaud, Justine; Legrand, Manon; Attard, Everaldo; Germain, Marc; Martinoli, Maria-Grazia

    2016-08-09

    Parkinson's disease (PD) is a progressive neurodegenerative disorder, primarily affecting dopaminergic neurons in the substantia nigra. There is currently no cure for PD and present medications aim to alleviate clinical symptoms, thus prevention remains the ideal strategy to reduce the prevalence of this disease. The goal of this study was to investigate whether oleuropein (OLE), the major phenolic compound in olive derivatives, may prevent neuronal degeneration in a cellular dopaminergic model of PD, differentiated PC12 cells exposed to the potent parkinsonian toxin 6-hydroxydopamine (6-OHDA). We also investigated OLE's ability to mitigate mitochondrial oxidative stress and modulate the autophagic flux. Our results obtained by measuring cytotoxicity and apoptotic events demonstrate that OLE significantly decreases neuronal death. OLE could also reduce mitochondrial production of reactive oxygen species resulting from blocking superoxide dismutase activity. Moreover, quantification of autophagic and acidic vesicles in the cytoplasm alongside expression of specific autophagic markers uncovered a regulatory role for OLE against autophagic flux impairment induced by bafilomycin A1. Altogether, our results define OLE as a neuroprotective, anti-oxidative and autophagy-regulating molecule, in a neuronal dopaminergic cellular model.

  20. Deoxycholic acid modulates cell death signaling through changes in mitochondrial membrane properties[S

    PubMed Central

    Sousa, Tânia; Castro, Rui E.; Pinto, Sandra N.; Coutinho, Ana; Lucas, Susana D.; Moreira, Rui; Rodrigues, Cecília M. P.; Prieto, Manuel; Fernandes, Fábio

    2015-01-01

    Cytotoxic bile acids, such as deoxycholic acid (DCA), are responsible for hepatocyte cell death during intrahepatic cholestasis. The mechanisms responsible for this effect are unclear, and recent studies conflict, pointing to either a modulation of plasma membrane structure or mitochondrial-mediated toxicity through perturbation of mitochondrial outer membrane (MOM) properties. We conducted a comprehensive comparative study of the impact of cytotoxic and cytoprotective bile acids on the membrane structure of different cellular compartments. We show that DCA increases the plasma membrane fluidity of hepatocytes to a minor extent, and that this effect is not correlated with the incidence of apoptosis. Additionally, plasma membrane fluidity recovers to normal values over time suggesting the presence of cellular compensatory mechanisms for this perturbation. Colocalization experiments in living cells confirmed the presence of bile acids within mitochondrial membranes. Experiments with active isolated mitochondria revealed that physiologically active concentrations of DCA change MOM order in a concentration- and time-dependent manner, and that these changes preceded the mitochondrial permeability transition. Importantly, these effects are not observed on liposomes mimicking MOM lipid composition, suggesting that DCA apoptotic activity depends on features of mitochondrial membranes that are absent in protein-free mimetic liposomes, such as the double-membrane structure, lipid asymmetry, or mitochondrial protein environment. In contrast, the mechanism of action of cytoprotective bile acids is likely not associated with changes in cellular membrane structure. PMID:26351365

  1. Oleuropein Prevents Neuronal Death, Mitigates Mitochondrial Superoxide Production and Modulates Autophagy in a Dopaminergic Cellular Model

    PubMed Central

    Achour, Imène; Arel-Dubeau, Anne-Marie; Renaud, Justine; Legrand, Manon; Attard, Everaldo; Germain, Marc; Martinoli, Maria-Grazia

    2016-01-01

    Parkinson’s disease (PD) is a progressive neurodegenerative disorder, primarily affecting dopaminergic neurons in the substantia nigra. There is currently no cure for PD and present medications aim to alleviate clinical symptoms, thus prevention remains the ideal strategy to reduce the prevalence of this disease. The goal of this study was to investigate whether oleuropein (OLE), the major phenolic compound in olive derivatives, may prevent neuronal degeneration in a cellular dopaminergic model of PD, differentiated PC12 cells exposed to the potent parkinsonian toxin 6-hydroxydopamine (6-OHDA). We also investigated OLE’s ability to mitigate mitochondrial oxidative stress and modulate the autophagic flux. Our results obtained by measuring cytotoxicity and apoptotic events demonstrate that OLE significantly decreases neuronal death. OLE could also reduce mitochondrial production of reactive oxygen species resulting from blocking superoxide dismutase activity. Moreover, quantification of autophagic and acidic vesicles in the cytoplasm alongside expression of specific autophagic markers uncovered a regulatory role for OLE against autophagic flux impairment induced by bafilomycin A1. Altogether, our results define OLE as a neuroprotective, anti-oxidative and autophagy-regulating molecule, in a neuronal dopaminergic cellular model. PMID:27517912

  2. Localization of Barley yellow dwarf virus Movement Protein Modulating Programmed Cell Death in Nicotiana benthamiana.

    PubMed

    Ju, Jiwon; Kim, Kangmin; Lee, Kui-Jae; Lee, Wang Hu; Ju, Ho-Jong

    2017-02-01

    Barley yellow dwarf virus (BYDV) belongs to Luteovirus and is limited only at phloem related tissues. An open reading frame (ORF) 4 of BYDV codes for the movement protein (MP) of BYDV gating plasmodesmata (PD) to facilitate virus movement. Like other Luteoviruses, ORF 4 of BYDV is embedded in the ORF3 but expressed from the different reading frame in leaky scanning manner. Although MP is a very important protein for systemic infection of BYDV, there was a little information. In this study, MP was characterized in terms of subcellular localization and programmed cell death (PCD). Gene of MP or its mutant (ΔMP) was expressed by Agroinfiltration method. MP was clearly localized at the nucleus and the PD, but ΔMP which was deleted distal N-terminus of MP showed no localization to PD exhibited the different target with original MP. In addition to PD localization, MP appeared associated with small granules in cytoplasm whereas ΔMP did not. MP associated with PD and small granules induced PCD, but ΔMP showed no association with PD and small granules did not exhibit PCD. Based on this study, the distal N-terminal region within MP is seemingly responsible for the localization of PD and the induction small granules and PCD induction. These results suggest that subcellular localization of BYDV MP may modulate the PCD in Nicotiana benthamiana.

  3. Neisseria gonorrhoeae Modulates Cell Death in Human Endocervical Epithelial Cells through Export of Exosome-Associated cIAP2

    PubMed Central

    Massari, Paola

    2015-01-01

    Several bacterial pathogens persist and survive in the host by modulating host cell death pathways. We previously demonstrated that Neisseria gonorrhoeae, a Gram-negative pathogen responsible for the sexually transmitted infection gonorrhea, protects against exogenous induction of apoptosis in human cervical epithelial cells. However, induction of cell death by N. gonorrhoeae has also been reported in other cell types. The mechanisms by which N. gonorrhoeae modulates cell death are not clear, although a role for the inhibitor of apoptosis-2 (cIAP2) has been proposed. In this study, we confirmed that N. gonorrhoeae induces production of cIAP2 in human cervical epithelial cells. High levels of intracellular cIAP2 were detected early after N. gonorrhoeae stimulation, which was followed by a marked decrease at 24 h. At this time point, we observed increased levels of extracellular cIAP2 associated with exosomes and an overall increase in production of exosomes. Inhibition of cIAP2 in N. gonorrhoeae-stimulated epithelial cells resulted in increased cell death and interleukin-1β (IL-1β) production. Collectively these results indicate that N. gonorrhoeae stimulation of human endocervical epithelial cells induces the release of cIAP2, an essential regulator of cell death and immune signaling. PMID:26077759

  4. Neisseria gonorrhoeae Modulates Cell Death in Human Endocervical Epithelial Cells through Export of Exosome-Associated cIAP2.

    PubMed

    Nudel, Kathleen; Massari, Paola; Genco, Caroline A

    2015-09-01

    Several bacterial pathogens persist and survive in the host by modulating host cell death pathways. We previously demonstrated that Neisseria gonorrhoeae, a Gram-negative pathogen responsible for the sexually transmitted infection gonorrhea, protects against exogenous induction of apoptosis in human cervical epithelial cells. However, induction of cell death by N. gonorrhoeae has also been reported in other cell types. The mechanisms by which N. gonorrhoeae modulates cell death are not clear, although a role for the inhibitor of apoptosis-2 (cIAP2) has been proposed. In this study, we confirmed that N. gonorrhoeae induces production of cIAP2 in human cervical epithelial cells. High levels of intracellular cIAP2 were detected early after N. gonorrhoeae stimulation, which was followed by a marked decrease at 24 h. At this time point, we observed increased levels of extracellular cIAP2 associated with exosomes and an overall increase in production of exosomes. Inhibition of cIAP2 in N. gonorrhoeae-stimulated epithelial cells resulted in increased cell death and interleukin-1β (IL-1β) production. Collectively these results indicate that N. gonorrhoeae stimulation of human endocervical epithelial cells induces the release of cIAP2, an essential regulator of cell death and immune signaling.

  5. Using radio-induced fluorescence to determine the horizontal structure of ion layers in the mesosphere and lower thermosphere

    NASA Astrophysics Data System (ADS)

    Bernhardt, Paul A.; Gondarenko, Natalia A.; Guzdar, Parvez N.; Huba, Joseph D.; Ossakow, S. L.; Djuth, Frank T.; Tepley, C. A.; Sulzer, Michael P.; Kagan, Ludmila; Kelley, M. C.

    2002-01-01

    Two-dimensional images of Sporadic-E layers have been produced using a new technique called radio induced fluorescence (RIF). This technique makes the ion layers glow when being stimulated by high power radio waves. Normally the ion-layers do not radiate visible emissions. Experiments on January 1998 at Arecibo Observatory in Puerto Rico have shown that the layers can be made to glow at 557.7 nm and other wavelengths by illuminating them with radio waves at 3.175 MHz with effective radiated powers of 80 megawatts. The regions of the sporadic-E layers that have electron densities greater than the critical density for reflection of the radio waves emit electrons that collide with and excite atmospheric atomic oxygen and molecular nitrogen. A charge-coupled-device (CCD) imager located on the ground is used to capture images of the glowing E-region structures. The camera exposure times were in the range of 15 to 45 seconds. The images obtained using this technique show a wide variety of structures in the sporadic-E layers. Some layers cover the 15 x 30 km region illuminated by the radio wave beam. Other layers show strong modulation of the E-region by neutral wind instabilities. Two-dimensional computer simulations of the coupling between neutral wind turbulence and the ion layers simulate the structure in the images.

  6. SrrAB Modulates Staphylococcus aureus Cell Death through Regulation of cidABC Transcription

    PubMed Central

    Windham, Ian H.; Chaudhari, Sujata S.; Bose, Jeffrey L.; Thomas, Vinai C.

    2016-01-01

    ABSTRACT The death and lysis of a subpopulation in Staphylococcus aureus biofilm cells are thought to benefit the surviving population by releasing extracellular DNA, a critical component of the biofilm extracellular matrix. Although the means by which S. aureus controls cell death and lysis is not understood, studies implicate the role of the cidABC and lrgAB operons in this process. Recently, disruption of the srrAB regulatory locus was found to cause increased cell death during biofilm development, likely as a result of the sensitivity of this mutant to hypoxic growth. In the current study, we extended these findings by demonstrating that cell death in the ΔsrrAB mutant is dependent on expression of the cidABC operon. The effect of cidABC expression resulted in the generation of increased reactive oxygen species (ROS) accumulation and was independent of acetate production. Interestingly, consistently with previous studies, cidC-encoded pyruvate oxidase was found to be important for the generation of acetic acid, which initiates the cell death process. However, these studies also revealed for the first time an important role of the cidB gene in cell death, as disruption of cidB in the ΔsrrAB mutant background decreased ROS generation and cell death in a cidC-independent manner. The cidB mutation also caused decreased sensitivity to hydrogen peroxide, which suggests a complex role for this system in ROS metabolism. Overall, the results of this study provide further insight into the function of the cidABC operon in cell death and reveal its contribution to the oxidative stress response. IMPORTANCE The manuscript focuses on cell death mechanisms in Staphylococcus aureus and provides important new insights into the genes involved in this ill-defined process. By exploring the cause of increased stationary-phase death in an S. aureus ΔsrrAB regulatory mutant, we found that the decreased viability of this mutant was a consequence of the overexpression of the cid

  7. The canonical Wg signaling modulates Bsk-mediated cell death in Drosophila

    PubMed Central

    Zhang, S; Chen, C; Wu, C; Yang, Y; Li, W; Xue, L

    2015-01-01

    Cell death is an essential regulatory mechanism for removing unneeded cells in animal development and tissue homeostasis. The c-Jun N-terminal kinase (JNK) pathway has pivotal roles in the regulation of cell death in response to various intrinsic and extrinsic stress signals. The canonical Wingless (Wg) signaling has been implicated in cell proliferation and cell fate decisions, whereas its role in cell death remains largely elusive. Here, we report that activated Bsk (the Drosophila JNK homolog) induced cell death is mediated by the canonical Wg signaling. First, loss of Wg signaling abrogates Bsk-mediated caspase-independent cell death. Second, activation of Wg signaling promotes cell death in a caspase-independent manner. Third, activation of Bsk signaling results in upregulated transcription of wingless (wg) gene. Finally, Wg pathway participates in the physiological function of Bsk signaling in development. These findings not only reveal a previously undiscovered role of Wg signaling in Bsk-mediated cell death, but also provide a novel mechanism for the interplay between the two important signaling pathways in development. PMID:25855961

  8. Arecoline-induced death of human leukemia K562 cells is associated with surface up-modulation of TNFR2.

    PubMed

    Chen, Ying-Jung; Chang, Long-Sen

    2012-05-01

    The goal of the present study is to explore the contribution of tumor necrosis factor-α (TNFα)-related pathway to the cytotoxicity of arecoline on human leukemia K562 cells. Arecoline treatment induced death of K562 cells and increased surface expression of TNFα, TNFR1, and TNFR2. Unlike that of TNFR1 mRNA, transcriptional levels of TNFα and TNFR2 mRNA increased in arecoline-treated cells. Moreover, arecoline-induced down-regulation of ADAM17 maturation was involved in surface up-modulation of TNFR1, TNFR2, and TNFα. Arecoline-elicited increase in intracellular Ca(2+) concentration was responsible for JNK/c-Jun pathway activation and ERK inactivation. Abolition of JNK/c-Jun pathway suppressed arecoline-induced increase in transcriptional level of TNFα and TNFR2 mRNA. TNFα and TNFR2 promoter luciferase activity and chromatin immunoprecipitating analyses revealed that c-Jun increasingly bound with TNFα and TNFR2 promoter upon arecoline treatment. Over-expression of constitutively active MEK1 abolished the effect of arecoline on suppressing ADAM17 maturation. Pretreatment with TNFR2 antibody abrogated arecoline-induced increased susceptibility of K562 cells for the cytotoxicity of TNFα and arecoline-induced cell death. Taken together, our data suggest that up-modulation of TNFR2 surface expression is associated with arecoline-induced death of K562 cells. Copyright © 2011 Wiley Periodicals, Inc.

  9. Transcriptomic comparison between Brassica oleracea and rice (Oryza sativa) reveals diverse modulations on cell death in response to Sclerotinia sclerotiorum.

    PubMed

    Mei, Jiaqin; Ding, Yijuan; Li, Yuehua; Tong, Chaobo; Du, Hai; Yu, Yang; Wan, Huafan; Xiong, Qing; Yu, Jingyin; Liu, Shengyi; Li, Jiana; Qian, Wei

    2016-09-20

    Sclerotinia stem rot caused by Sclerotinia sclerotiorum is a devastating disease of Brassica crops, but not in rice. The leaves of a rice line, a partial resistant (R) and a susceptible (S) Brassica oleracea pool that bulked from a resistance-segregating F2 population were employed for transcriptome sequencing before and after inoculation by S. sclerotiorum for 6 and 12 h. Distinct transcriptome profiles were revealed between B. oleracea and rice in response to S. sclerotiorum. Enrichment analyses of GO and KEGG indicated an enhancement of antioxidant activity in the R B. oleracea and rice, and histochemical staining exhibited obvious lighter reactive oxygen species (ROS) accumulation and cell death in rice and the R B. oleracea as compared to that in the S B. oleracea. Significant enhancement of Ca(2+) signalling, a positive regulator of ROS and cell death, were detected in S B. oleracea after inoculation, while it was significantly repressed in the R B. oleracea group. Obvious difference was detected between two B. oleracea groups for WRKY transcription factors, particularly for those regulating cell death. These findings suggest diverse modulations on cell death in host in response to S. sclerotiorum. Our study provides useful insight into the resistant mechanism to S. sclerotiorum.

  10. Transcriptomic comparison between Brassica oleracea and rice (Oryza sativa) reveals diverse modulations on cell death in response to Sclerotinia sclerotiorum

    PubMed Central

    Mei, Jiaqin; Ding, Yijuan; Li, Yuehua; Tong, Chaobo; Du, Hai; Yu, Yang; Wan, Huafan; Xiong, Qing; Yu, Jingyin; Liu, Shengyi; Li, Jiana; Qian, Wei

    2016-01-01

    Sclerotinia stem rot caused by Sclerotinia sclerotiorum is a devastating disease of Brassica crops, but not in rice. The leaves of a rice line, a partial resistant (R) and a susceptible (S) Brassica oleracea pool that bulked from a resistance-segregating F2 population were employed for transcriptome sequencing before and after inoculation by S. sclerotiorum for 6 and 12 h. Distinct transcriptome profiles were revealed between B. oleracea and rice in response to S. sclerotiorum. Enrichment analyses of GO and KEGG indicated an enhancement of antioxidant activity in the R B. oleracea and rice, and histochemical staining exhibited obvious lighter reactive oxygen species (ROS) accumulation and cell death in rice and the R B. oleracea as compared to that in the S B. oleracea. Significant enhancement of Ca2+ signalling, a positive regulator of ROS and cell death, were detected in S B. oleracea after inoculation, while it was significantly repressed in the R B. oleracea group. Obvious difference was detected between two B. oleracea groups for WRKY transcription factors, particularly for those regulating cell death. These findings suggest diverse modulations on cell death in host in response to S. sclerotiorum. Our study provides useful insight into the resistant mechanism to S. sclerotiorum. PMID:27647523

  11. Ethylene Insensitivity Modulates Ozone-Induced Cell Death in Birch1

    PubMed Central

    Vahala, Jorma; Ruonala, Raili; Keinänen, Markku; Tuominen, Hannele; Kangasjärvi, Jaakko

    2003-01-01

    We have used genotypic variation in birch (Betula pendula Roth) to investigate the roles of ozone (O3)-induced ethylene (ET), jasmonic acid, and salicylic acid in the regulation of tissue tolerance to O3. Of these hormones, ET evolution correlated best with O3-induced cell death. Disruption of ET perception by transformation of birch with the dominant negative mutant allele etr1-1 of the Arabidopsis ET receptor gene ETR1 or blocking of ET perception with 1-methylcyclopropene reduced but did not completely prevent the O3-induced cell death, when inhibition of ET biosynthesis with aminooxyacetic acid completely abolished O3 lesion formation. This suggests the presence of an ET-signaling-independent but ET biosynthesis-dependent component in the ET-mediated stimulation of cell death in O3-exposed birch. Functional ET signaling was required for the O3 induction of the gene encoding β-cyanoalanine synthase, which catalyzes detoxification of the cyanide formed during ET biosynthesis. The results suggest that functional ET signaling is required to protect birch from the O3-induced cell death and that a decrease in ET sensitivity together with a simultaneous, high ET biosynthesis can potentially cause cell death through a deficient detoxification of cyanide. PMID:12746524

  12. Oncogene-Selective Sensitivity to Synchronous Cell Death following Modulation of the Amino Acid Nutrient Cystine.

    PubMed

    Poursaitidis, Ioannis; Wang, Xiaomeng; Crighton, Thomas; Labuschagne, Christiaan; Mason, David; Cramer, Shira L; Triplett, Kendra; Roy, Rajat; Pardo, Olivier E; Seckl, Michael J; Rowlinson, Scott W; Stone, Everett; Lamb, Richard F

    2017-03-14

    Cancer cells reprogram their metabolism, altering both uptake and utilization of extracellular nutrients. We individually depleted amino acid nutrients from isogenic cells expressing commonly activated oncogenes to identify correspondences between nutrient supply and viability. In HME (human mammary epithelial) cells, deprivation of cystine led to increased cell death in cells expressing an activated epidermal growth factor receptor (EGFR) mutant. Cell death occurred via synchronous ferroptosis, with generation of reactive oxygen species (ROS). Hydrogen peroxide promoted cell death, as both catalase and inhibition of NADPH oxidase 4 (NOX4) blocked ferroptosis. Blockade of EGFR or mitogen-activated protein kinase (MAPK) signaling similarly protected cells from ferroptosis, whereas treatment of xenografts derived from EGFR mutant non-small-cell lung cancer (NSCLC) with a cystine-depleting enzyme inhibited tumor growth in mice. Collectively, our results identify a potentially exploitable sensitization of some EGFR/MAPK-driven tumors to ferroptosis following cystine depletion.

  13. New aspects of 24(S)-hydroxycholesterol in modulating neuronal cell death.

    PubMed

    Noguchi, Noriko; Urano, Yasuomi; Takabe, Wakako; Saito, Yoshiro

    2015-10-01

    24(S)-Hydroxycholesterol (24S-OHC), which is enzymatically produced in the brain, has been known to play an important role in maintaining cholesterol homeostasis in the brain and has been proposed as a possible biomarker of neurodegenerative disease. Recent studies have revealed diverse functions of 24S-OHC and gained increased attention. For example, 24S-OHC at sublethal concentrations has been found to induce an adaptive response via activation of the liver X receptor signaling pathway, thereby protecting neuronal cells against subsequent oxidative stress. It has also been found that physiological concentrations of 24S-OHC suppress amyloid-β production via downregulation of amyloid precursor protein trafficking in neuronal cells. On the other hand, high concentrations of 24S-OHC have been found to induce a type of nonapoptotic programmed cell death in neuronal cells expressing little caspase-8. Because neuronal cell death induced by 24S-OHC has been found to proceed by a unique mechanism, which is different from but in some ways similar to necroptosis-necroptosis being a type of programmed necrosis induced by tumor necrosis factor α-neuronal cell death induced by 24S-OHC has been called "necroptosis-like" cell death. 24S-OHC-induced cell death is dependent on the formation of 24S-OHC esters but not on oxidative stress. This review article discusses newly reported aspects of 24S-OHC in neuronal cell death and sheds light on the possible importance of controlling 24S-OHC levels in the brain for preventing neurodegenerative disease.

  14. Melatonin ameliorates oxidative stress, modulates death receptor pathway proteins, and protects the rat cerebrum against bisphenol-A-induced apoptosis.

    PubMed

    El-Missiry, Mohamed A; Othman, Azza I; Al-Abdan, Monera A; El-Sayed, Aml A

    2014-12-15

    Epidemiological reports have indicated a correlation between the increasing of bisphenol-A (BPA) levels in the environment and the incidence of neurodegenerative diseases. In the present study, the protective effect of melatonin on oxidative stress and the death receptor apoptotic proteins in the cerebrum of the bisphenol-A-treated rats were examined. Adult male rats were orally administered melatonin (10mg/kg bw) concurrently with BPA (50mg/kg bw) 3 days a week for 6 weeks. BPA exposure resulted in significant elevations of oxidative stress, as evidenced by the increased malondialdehyde level and the decreased glutathione level and superoxide dismutase activity in the cerebrum. BPA caused an upregulation of p53 and CD95-Fas and activation of capsases-3 and 8, resulting in cerebral cell apoptosis. Melatonin significantly attenuated the BPA-evoked brain oxidative stress, modulated apoptotic-regulating proteins and protected against apoptosis. These data suggest that melatonin modulated important steps in the death receptor apoptotic pathway which likely related to its redox control properties. Melatonin is a promising pharmacological agent for preventing the potential neurotoxicity of BPA following occupational or environmental exposures.

  15. NR2B-NMDA receptor mediated modulation of the tyrosine phosphatase STEP regulates glutamate induced neuronal cell death

    PubMed Central

    Poddar, Ranjana; Deb, Ishani; Mukherjee, Saibal; Paul, Surojit

    2011-01-01

    The present study examines the role of a neuron-specific tyrosine phosphatase (STEP) in excitotoxic cell death. Our findings demonstrate that p38 MAPK, a stress-activated kinase that is known to play a role in the etiology of excitotoxic cell death is a substrate of STEP. Glutamate-mediated NMDA receptor stimulation leads to rapid but transient activation of p38 MAPK, which is primarily dependent on NR2A-NMDA receptor activation. Conversely, activation of NR2B-NMDA receptors leads to dephosphorylation and subsequent activation of STEP, which in turn leads to inactivation of p38 MAPK. Thus during transient NMDA receptor stimulation, increases in STEP activity appears to limit the duration of activation of p38 MAPK and improves neuronal survival. However, if NR2B-NMDA receptor stimulation is sustained, protective effects of STEP activation are lost, as these stimuli cause significant degradation of active STEP, leading to secondary activation of p38 MAP kinase. Consistent with this observation, a cell transducible TAT-STEP peptide that constitutively binds to p38 MAPK attenuated neuronal cell death caused by sustained NMDA receptor stimulation. The findings imply that the activation and levels of STEP are dependent on the duration and magnitude of NR2B-NMDA receptor stimulation and STEP serves as a modulator of NMDA receptor dependent neuronal injury, through its regulation of p38 MAPK. PMID:21029094

  16. Ferroxitosis: A cell death from modulation of oxidative phosphorylation and PKM2-dependent glycolysis in melanoma

    PubMed Central

    Lakhter, Alexander J.; Hamilton, James; Dagher, Pierre C.; Mukkamala, Suresh; Hato, Takashi; Dong, X. Charlie; Mayo, Lindsey D.; Harris, Robert A.; Shekhar, Anantha; Ivan, Mircea; Brustovetsky, Nickolay; Naidu, Samisubbu R.

    2014-01-01

    Reliance on glycolysis is a characteristic of malignancy, yet the development of resistance to BRAF inhibitors in melanoma is associated with gain of mitochondrial function. Concurrent attenuation of oxidative phosphorylation and HIF-1α/PKM2-dependent glycolysis promotes a non-apoptotic, iron- and oxygen-dependent cell death that we term ferroxitosis. The redox cycling agent menadione causes a robust increase in oxygen consumption, accompanied by significant loss of intracellular ATP and rapid cell death. Conversely, either hypoxic adaptation or iron chelation prevents menadione-induced ferroxitosis. Ectopic expression of K213Q HIF-1α mutant blunts the effects of menadione. However, knockdown of HIF-1α or PKM2 restores menadione-induced cytotoxicity in hypoxia. Similarly, exposure of melanoma cells to shikonin, a menadione analog and a potential PKM2 inhibitor, is sufficient to induce ferroxitosis under hypoxic conditions. Collectively, our findings reveal that ferroxitosis curtails metabolic plasticity in melanoma. PMID:25587028

  17. Lipopolysaccharide downregulates macrophage-derived IL-22 to modulate alcohol-induced hepatocyte cell death.

    PubMed

    Liu, Yaming; Verma, Vikas K; Malhi, Harmeet; Gores, Greg J; Kamath, Patrick S; Sanyal, Arun; Chalasani, Naga; Gao, Bin; Shah, Vijay H

    2017-09-01

    Interleukin-22 (IL-22) is a Th17 cell hepatoprotective cytokine that is undergoing clinical trials to treat patients with alcoholic hepatitis (AH). Lipopolysaccharide (LPS) activation of macrophage is implicated in hepatocyte cell death and pathogenesis of AH. The role of IL-22 production from macrophage, its regulation by LPS, and effects on alcohol-induced hepatocyte cell death are unexplored and were examined in this study. Low levels of IL-22 mRNA/protein were detected in macrophage but were significantly upregulated by 6.5-fold in response to the tissue reparative cytokine IL-10. Conversely, LPS significantly decreased IL-22 mRNA levels in a temporal and concentration-dependent manner with a maximum reduction of 5-fold. LPS downregulation of IL-22 mRNA levels was rescued in the presence of a pharmacological inhibitor of c-Jun NH2-terminal kinase (JNK) and by JNK knockdown. Next, we explored whether macrophage-derived IL-22 regulated ethanol-induced hepatocyte death. Conditioned media from IL-10-stimulated macrophages attenuated ethanol-induced hepatocyte caspase-3/7 activity, and apoptosis as assessed by fluorometric assay and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. This effect was diminished in conditioned media from macrophages with IL-22 knockdown. Cytokine analysis in sera samples of patients with AH revealed that IL-22 levels were significantly elevated compared with healthy controls and heavy-drinking controls, implying a state of IL-22 resistance in human AH. Macrophage-derived IL-22 protects hepatocytes from ethanol-induced cell death. IL-22 downregulation is a new regulatory target of LPS in the pathogenesis of AH.

  18. Palmitoylation of human FasL modulates its cell death-inducing function

    PubMed Central

    Guardiola-Serrano, F; Rossin, A; Cahuzac, N; Lückerath, K; Melzer, I; Mailfert, S; Marguet, D; Zörnig, M; Hueber, A-O

    2010-01-01

    Fas ligand (FasL) is a transmembrane protein that regulates cell death in Fas-bearing cells. FasL-mediated cell death is essential for immune system homeostasis and the elimination of viral or transformed cells. Because of its potent cytotoxic activity, FasL expression at the cell surface is tightly regulated, for example, via processing by ADAM10 and SPPL2a generating soluble FasL and the intracellular fragments APL (ADAM10-processed FasL form) and SPA (SPPL2a-processed APL). In this study, we report that FasL processing by ADAM10 counteracts Fas-mediated cell death and is strictly regulated by membrane localization, interactions and modifications of FasL. According to our observations, FasL processing occurs preferentially within cholesterol and sphingolipid-rich nanodomains (rafts) where efficient Fas–FasL contact occurs, Fas receptor and FasL interaction is also required for efficient FasL processing, and FasL palmitoylation, which occurs within its transmembrane domain, is critical for efficient FasL-mediated killing and FasL processing. PMID:21368861

  19. Modulating Both Tumor Cell Death and Innate Immunity Is Essential for Improving Radiation Therapy Effectiveness.

    PubMed

    Wu, Qiuji; Allouch, Awatef; Martins, Isabelle; Brenner, Catherine; Modjtahedi, Nazanine; Deutsch, Eric; Perfettini, Jean-Luc

    2017-01-01

    Radiation therapy is one of the cornerstones of cancer treatment. In tumor cells, exposure to ionizing radiation (IR) provokes DNA damages that trigger various forms of cell death such as apoptosis, necrosis, autophagic cell death, and mitotic catastrophe. IR can also induce cellular senescence that could serve as an additional antitumor barrier in a context-dependent manner. Moreover, accumulating evidence has demonstrated that IR interacts profoundly with tumor-infiltrating immune cells, which cooperatively drive treatment outcomes. Recent preclinical and clinical successes due to the combination of radiation therapy and immune checkpoint blockade have underscored the need for a better understanding of the interplay between radiation therapy and the immune system. In this review, we will present an overview of cell death modalities induced by IR, summarize the immunogenic properties of irradiated cancer cells, and discuss the biological consequences of IR on innate immune cell functions, with a particular attention on dendritic cells, macrophages, and NK cells. Finally, we will discuss their potential applications in cancer treatment.

  20. Molecules involved in the modulation of rapid cell death in Xanthomonas.

    PubMed

    Raju, K K; Gautam, Satyendra; Sharma, Arun

    2006-08-01

    In earlier studies from this laboratory, Xanthomonas campestris pv. glycines was found to exhibit a nutrition stress-related postexponential rapid cell death (RCD). The RCD was exhibited in protein-rich media but not in starch or other minimal media. This RCD in X. campestris pv. glycines was found to display features similar to those of the programmed cell death (PCD) of eukaryotes. Results of the present study showed that the observed RCD in this organism is both positively and negatively regulated by small molecules. The amino acids glycine and l-alanine as well as the D isomers of valine, methionine, and threonine were found to induce the synthesis of an active caspase-3-like protein that was associated with the onset of RCD. Addition of pyruvate and citrate to the culture medium induced both the synthesis of active caspase-3-like protein and RCD. Higher levels of intracellular accumulation of pyruvate and citrate were also observed under conditions favoring RCD. On the other hand, dextrin and maltose, the hydrolytic products of starch, inhibited the synthesis of the caspase-3-like protein. Addition of glucose and cyclic AMP (cAMP) to the RCD-favoring medium prevented RCD. Glucose, cAMP, caffeine (a known inhibitor of a phosphodiesterase that breaks down cAMP), and forskolin (from the herb Coleus forskholii, known to activate the enzyme adenylate cyclase that forms cAMP) inhibited the caspase enzyme activity in vivo and consequently the RCD process. The addition of glucose and other inhibitors of RCD enhanced intracellular cAMP accumulation. This is the first report demonstrating the involvement of small molecules in the regulation of nutrition stress-related stationary-phase rapid cell death in X. campestris pv. glycines, which is programmed.

  1. Cyclic dinucleotides modulate human T-cell response through monocyte cell death.

    PubMed

    Tosolini, Marie; Pont, Frédéric; Verhoeyen, Els; Fournié, Jean-Jacques

    2015-12-01

    Cyclic dinucleotides, a class of microbial messengers, have been recently identified in bacteria, but their activity in humans remains largely unknown. Here, we have studied the function of cyclic dinucleotides in humans. We found that c-di-AMP and cGAMP, two adenosine-based cyclic dinucleotides, activated T lymphocytes in an unusual manner through monocyte cell death. c-di-AMP and cGAMP induced the selective apoptosis of human monocytes, and T lymphocytes were activated by the direct contact with these dying monocytes. The ensuing T-cell response comprised cell-cycle exit, phenotypic maturation into effector memory cells and proliferation arrest, but not cell death. This quiescence was transient since T cells remained fully responsive to further restimulation. Together, our results depict a novel activation pattern for human T lymphocytes: a transient quiescence induced by c-di-AMP- or cGAMP-primed apoptotic monocytes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Hydroxychloroquine modulates metabolic activity and proliferation and induces autophagic cell death of human dermal fibroblasts.

    PubMed

    Ramser, Bettina; Kokot, Agatha; Metze, Dieter; Weiss, Nina; Luger, Thomas A; Böhm, Markus

    2009-10-01

    Hydroxychloroquine (HCQ) is a commonly used therapeutic agent in skin disorders. Some reports also suggest that HCQ can be useful in fibroblastic diseases of the skin. Here, we investigated the effects of HCQ in human dermal fibroblasts (HDFs). HCQ significantly reduced the metabolic activity and suppressed cell proliferation (IC(50) = approximately 30 microM) of HDFs. The antiproliferative effect of HCQ was associated with decreased activation of the extracellular signal-regulated kinases 1/2 but not with inhibition of the mammalian target of the rapamycin pathway or with dephosphorylation of Akt. HCQ induced a distinct type of cell death in HDFs, characterized by surface exposure of phosphatidylserine but a lack of morphological signs of apoptosis and absence of DNA fragmentation. The HCQ-treated HDFs instead showed autophagic vacuoles with double membranes and digested organelle content. These vacuoles showed light-chain 3 immunostaining, in accordance with increased protein amounts of this autophagy marker. Induction of autophagic cell death by HCQ was also paralleled by increased expression of Beclin-1, a key regulator of autophagy. Our findings indicate that HDFs are target cells of HCQ and form a rationale on the basis of which the in vivo effects of antimalarials can be studied in patients with aberrant fibroblast function.

  3. Marine Benthic Diatoms Contain Compounds Able to Induce Leukemia Cell Death and Modulate Blood Platelet Activity

    PubMed Central

    Prestegard, Siv Kristin; Oftedal, Linn; Coyne, Rosie Theresa; Nygaard, Gyrid; Skjærven, Kaja Helvik; Knutsen, Gjert; Døskeland, Stein Ove; Herfindal, Lars

    2009-01-01

    In spite of the high abundance and species diversity of diatoms, only a few bioactive compounds from them have been described. The present study reveals a high number of mammalian cell death inducing substances in biofilm-associated diatoms sampled from the intertidal zone. Extracts from the genera Melosira, Amphora, Phaeodactylum and Nitzschia were all found to induce leukemia cell death, with either classical apoptotic or autophagic features. Several extracts also contained inhibitors of thrombin-induced blood platelet activation. Some of this activity was caused by a high content of adenosine in the diatoms, ranging from 0.07 to 0.31 μg/mg dry weight. However, most of the bioactivity was adenosine deaminase-resistant. An adenosine deaminase-resistant active fraction from one of the extracts was partially purified and shown to induce apoptosis with a distinct phenotype. The results show that benthic diatoms typically found in the intertidal zone may represent a richer source of interesting bioactive compounds than hitherto recognized. PMID:20098602

  4. Porphyromonas gingivalis Differentially Modulates Cell Death Profile in Ox-LDL and TNF-α Pre-Treated Endothelial Cells

    PubMed Central

    Bugueno, Isaac Maximiliano; Khelif, Yacine; Seelam, Narendra; Morand, David-Nicolas; Tenenbaum, Henri; Davideau, Jean-Luc; Huck, Olivier

    2016-01-01

    Objective Clinical studies demonstrated a potential link between atherosclerosis and periodontitis. Porphyromonas gingivalis (Pg), one of the main periodontal pathogen, has been associated to atheromatous plaque worsening. However, synergism between infection and other endothelial stressors such as oxidized-LDL or TNF-α especially on endothelial cell (EC) death has not been investigated. This study aims to assess the role of Pg on EC death in an inflammatory context and to determine potential molecular pathways involved. Methods Human umbilical vein ECs (HUVECs) were infected with Pg (MOI 100) or stimulated by its lipopolysaccharide (Pg-LPS) (1μg/ml) for 24 to 48 hours. Cell viability was measured with AlamarBlue test, type of cell death induced was assessed using Annexin V/propidium iodide staining. mRNA expression regarding caspase-1, -3, -9, Bcl-2, Bax-1 and Apaf-1 has been evaluated with RT-qPCR. Caspases enzymatic activity and concentration of APAF-1 protein were evaluated to confirm mRNA results. Results Pg infection and Pg-LPS stimulation induced EC death. A cumulative effect has been observed in Ox-LDL pre-treated ECs infected or stimulated. This effect was not observed in TNF-α pre-treated cells. Pg infection promotes EC necrosis, however, in infected Ox-LDL pre-treated ECs, apoptosis was promoted. This effect was not observed in TNF-α pre-treated cells highlighting specificity of molecular pathways activated. Regarding mRNA expression, Pg increased expression of pro-apoptotic genes including caspases-1,-3,-9, Bax-1 and decreased expression of anti-apoptotic Bcl-2. In Ox-LDL pre-treated ECs, Pg increased significantly the expression of Apaf-1. These results were confirmed at the protein level. Conclusion This study contributes to demonstrate that Pg and its Pg-LPS could exacerbate Ox-LDL and TNF-α induced endothelial injury through increase of EC death. Interestingly, molecular pathways are differentially modulated by the infection in function of the

  5. Porphyromonas gingivalis Differentially Modulates Cell Death Profile in Ox-LDL and TNF-α Pre-Treated Endothelial Cells.

    PubMed

    Bugueno, Isaac Maximiliano; Khelif, Yacine; Seelam, Narendra; Morand, David-Nicolas; Tenenbaum, Henri; Davideau, Jean-Luc; Huck, Olivier

    2016-01-01

    Clinical studies demonstrated a potential link between atherosclerosis and periodontitis. Porphyromonas gingivalis (Pg), one of the main periodontal pathogen, has been associated to atheromatous plaque worsening. However, synergism between infection and other endothelial stressors such as oxidized-LDL or TNF-α especially on endothelial cell (EC) death has not been investigated. This study aims to assess the role of Pg on EC death in an inflammatory context and to determine potential molecular pathways involved. Human umbilical vein ECs (HUVECs) were infected with Pg (MOI 100) or stimulated by its lipopolysaccharide (Pg-LPS) (1μg/ml) for 24 to 48 hours. Cell viability was measured with AlamarBlue test, type of cell death induced was assessed using Annexin V/propidium iodide staining. mRNA expression regarding caspase-1, -3, -9, Bcl-2, Bax-1 and Apaf-1 has been evaluated with RT-qPCR. Caspases enzymatic activity and concentration of APAF-1 protein were evaluated to confirm mRNA results. Pg infection and Pg-LPS stimulation induced EC death. A cumulative effect has been observed in Ox-LDL pre-treated ECs infected or stimulated. This effect was not observed in TNF-α pre-treated cells. Pg infection promotes EC necrosis, however, in infected Ox-LDL pre-treated ECs, apoptosis was promoted. This effect was not observed in TNF-α pre-treated cells highlighting specificity of molecular pathways activated. Regarding mRNA expression, Pg increased expression of pro-apoptotic genes including caspases-1,-3,-9, Bax-1 and decreased expression of anti-apoptotic Bcl-2. In Ox-LDL pre-treated ECs, Pg increased significantly the expression of Apaf-1. These results were confirmed at the protein level. This study contributes to demonstrate that Pg and its Pg-LPS could exacerbate Ox-LDL and TNF-α induced endothelial injury through increase of EC death. Interestingly, molecular pathways are differentially modulated by the infection in function of the pre-stimulation.

  6. Biotransformed soybean extract induces cell death of estrogen-dependent breast cancer cells by modulation of apoptotic proteins.

    PubMed

    Stocco, Bianca; Toledo, Karina A; Fumagalli, Helen F; Bianchini, Francine J; Fortes, Vanessa S; Fonseca, Maria José V; Toloi, Maria Regina T

    2015-01-01

    The process of soybean biotransformation increases the quantity of isoflavones (daidzein and genistein), which besides being considered an alternative to estroprogestive hormone replacement therapy (HRT), are able of hindering the growth and development of tumor cells. We investigated the effects of soybean extract biotransformed by fungus on estrogen-dependent (MCF-7) and nondependent (SK-BR-3) breast cell lines. Cells were treated with different concentrations of biotransformed (BSE) and nonbiotransformed soybean extract (SE), or daidzein (D) and genistein (G) patterns isolated and in combination (D + G). Afterwards, we analyzed cell viability by MTT assay, phosphatidylserine exposure and cell permeability by flow cytometry; expression of apoptotic proteins by Western blotting. BSE promoted reduction in cell viability and increase in DNA degradation in both cell lines. In addition, we verified increase in cell permeability and in the expression of phosphatidylserine, as well as modulation in the expression of apoptotic proteins in MCF-7 cells. The cells did not show any signs of cell death when incubated with the controls (D, G, and D + G). Unknown components found in the BSE induce cell death by apoptosis and necrosis, mainly in MCF-7 cells. These processes depend on the activation of caspase-3 and involve an increase in the expression of proapoptotic molecules.

  7. Killing Two Cells with One Stone: Pharmacologic BCL-2 Family Targeting for Cancer Cell Death and Immune Modulation.

    PubMed

    Ludwig, Lindsey M; Nassin, Michele L; Hadji, Abbas; LaBelle, James L

    2016-01-01

    A crucial component of regulating organismal homeostasis is maintaining proper cell number and eliminating damaged or potentially malignant cells. Apoptosis, or programed cell death, is the mechanism responsible for this equilibrium. The intrinsic apoptotic pathway is also especially important in the development and maintenance of the immune system. Apoptosis is essential for proper positive and negative selection during B- and T-cell development and for efficient contraction of expanded lymphocytes following an immune response. Tight regulation of the apoptotic pathway is critical, as excessive cell death can lead to immunodeficiency while apoptotic resistance can lead to aberrant lymphoproliferation and autoimmune disease. Dysregulation of cell death is implicated in a wide range of hematological malignancies, and targeting various components of the apoptotic machinery in these cases is an attractive chemotherapeutic strategy. A wide array of compounds has been developed with the purpose of reactivating the intrinsic apoptotic pathway. These compounds, termed BH3 mimetics are garnering considerable attention as they gain greater clinical oncologic significance. As their use expands, it will be imperative to understand the effects these compounds have on immune homeostasis. Uncovering their potential immunomodulatory activity may allow for administration of BH3 mimetics for direct tumor cell killing as well as novel therapies for a wide range of immune-based directives. This review will summarize the major proteins involved in the intrinsic apoptotic pathway and define their roles in normal immune development and disease. Clinical and preclinical BH3 mimetics are described within the context of what is currently known about their ability to affect immune function. Prospects for future antitumor immune amplification and immune modulation are then proposed.

  8. Killing Two Cells with One Stone: Pharmacologic BCL-2 Family Targeting for Cancer Cell Death and Immune Modulation

    PubMed Central

    Ludwig, Lindsey M.; Nassin, Michele L.; Hadji, Abbas; LaBelle, James L.

    2016-01-01

    A crucial component of regulating organismal homeostasis is maintaining proper cell number and eliminating damaged or potentially malignant cells. Apoptosis, or programed cell death, is the mechanism responsible for this equilibrium. The intrinsic apoptotic pathway is also especially important in the development and maintenance of the immune system. Apoptosis is essential for proper positive and negative selection during B- and T-cell development and for efficient contraction of expanded lymphocytes following an immune response. Tight regulation of the apoptotic pathway is critical, as excessive cell death can lead to immunodeficiency while apoptotic resistance can lead to aberrant lymphoproliferation and autoimmune disease. Dysregulation of cell death is implicated in a wide range of hematological malignancies, and targeting various components of the apoptotic machinery in these cases is an attractive chemotherapeutic strategy. A wide array of compounds has been developed with the purpose of reactivating the intrinsic apoptotic pathway. These compounds, termed BH3 mimetics are garnering considerable attention as they gain greater clinical oncologic significance. As their use expands, it will be imperative to understand the effects these compounds have on immune homeostasis. Uncovering their potential immunomodulatory activity may allow for administration of BH3 mimetics for direct tumor cell killing as well as novel therapies for a wide range of immune-based directives. This review will summarize the major proteins involved in the intrinsic apoptotic pathway and define their roles in normal immune development and disease. Clinical and preclinical BH3 mimetics are described within the context of what is currently known about their ability to affect immune function. Prospects for future antitumor immune amplification and immune modulation are then proposed. PMID:28066751

  9. Extracellular calcium triggers unique transcriptional programs and modulates staurosporine-induced cell death in Neurospora crassa

    PubMed Central

    Gonçalves, A. P.; Monteiro, João; Lucchi, Chiara; Kowbel, David J.; Cordeiro, J. M.; Correia-de-Sá, Paulo; Rigden, Daniel J.; Glass, N. L.; Videira, Arnaldo

    2014-01-01

    Alterations in the intracellular levels of calcium are a common response to cell death stimuli in animals and fungi and, particularly, in the Neurospora crassa response to staurosporine. We highlight the importance of the extracellular availability of Ca2+ for this response. Limitation of the ion in the culture medium further sensitizes cells to the drug and results in increased accumulation of reactive oxygen species (ROS). Conversely, an approximately 30-fold excess of external Ca2+ leads to increased drug tolerance and lower ROS generation. In line with this, distinct staurosporine-induced cytosolic Ca2+ signaling profiles were observed in the absence or presence of excessive external Ca2+. High-throughput RNA sequencing revealed that different concentrations of extracellular Ca2+ define distinct transcriptional programs. Our transcriptional profiling also pointed to two putative novel Ca2+-binding proteins, encoded by the NCU08524 and NCU06607 genes, and provides a reference dataset for future investigations on the role of Ca2+ in fungal biology. PMID:28357255

  10. Epigenetic status of argininosuccinate synthetase and argininosuccinate lyase modulates autophagy and cell death in glioblastoma.

    PubMed

    Syed, N; Langer, J; Janczar, K; Singh, P; Lo Nigro, C; Lattanzio, L; Coley, H M; Hatzimichael, E; Bomalaski, J; Szlosarek, P; Awad, M; O'Neil, K; Roncaroli, F; Crook, T

    2013-01-17

    Arginine deprivation, either by nutritional starvation or exposure to ADI-PEG20, induces adaptive transcriptional upregulation of ASS1 and ASL in glioblastoma multiforme ex vivo cultures and cell lines. This adaptive transcriptional upregulation is blocked by neoplasia-specific CpG island methylation in either gene, causing arginine auxotrophy and cell death. In cells with methylated ASS1 or ASL CpG islands, ADI-PEG20 initially induces a protective autophagic response, but abrogation of this by chloroquine accelerates and potentiates cytotoxicity. Concomitant methylation in the CpG islands of both ASS1 and ASL, observed in a subset of cases, confers hypersensitivity to ADI-PEG20. Cancer stem cells positive for CD133 and methylation in the ASL CpG island retain sensitivity to ADI-PEG20. Our results show for the first time that epigenetic changes occur in both of the two key genes of arginine biosynthesis in human cancer and confer sensitivity to therapeutic arginine deprivation. We demonstrate that methylation status of the CpG islands, rather than expression levels per se of the genes, predicts sensitivity to arginine deprivation. Our results suggest a novel therapeutic strategy for this invariably fatal central nervous system neoplasm for which we have identified robust biomarkers and which overcomes the limitations to conventional chemotherapy imposed by the blood/brain barrier.

  11. Epigenetic status of argininosuccinate synthetase and argininosuccinate lyase modulates autophagy and cell death in glioblastoma

    PubMed Central

    Syed, N; Langer, J; Janczar, K; Singh, P; Lo Nigro, C; Lattanzio, L; Coley, H M; Hatzimichael, E; Bomalaski, J; Szlosarek, P; Awad, M; O'Neil, K; Roncaroli, F; Crook, T

    2013-01-01

    Arginine deprivation, either by nutritional starvation or exposure to ADI-PEG20, induces adaptive transcriptional upregulation of ASS1 and ASL in glioblastoma multiforme ex vivo cultures and cell lines. This adaptive transcriptional upregulation is blocked by neoplasia-specific CpG island methylation in either gene, causing arginine auxotrophy and cell death. In cells with methylated ASS1 or ASL CpG islands, ADI-PEG20 initially induces a protective autophagic response, but abrogation of this by chloroquine accelerates and potentiates cytotoxicity. Concomitant methylation in the CpG islands of both ASS1 and ASL, observed in a subset of cases, confers hypersensitivity to ADI-PEG20. Cancer stem cells positive for CD133 and methylation in the ASL CpG island retain sensitivity to ADI-PEG20. Our results show for the first time that epigenetic changes occur in both of the two key genes of arginine biosynthesis in human cancer and confer sensitivity to therapeutic arginine deprivation. We demonstrate that methylation status of the CpG islands, rather than expression levels per se of the genes, predicts sensitivity to arginine deprivation. Our results suggest a novel therapeutic strategy for this invariably fatal central nervous system neoplasm for which we have identified robust biomarkers and which overcomes the limitations to conventional chemotherapy imposed by the blood/brain barrier. PMID:23328665

  12. A novel ligand of calcitonin receptor reveals a potential new sensor that modulates programmed cell death

    PubMed Central

    Furness, SGB; Hare, DL; Kourakis, A; Turnley, AM; Wookey, PJ

    2016-01-01

    We have discovered that the accumulation of an anti-calcitonin receptor (anti-CTR) antibody conjugated to a fluorophore (mAb2C4:AF568) provides a robust signal for cells undergoing apoptotic programmed cell death (PCD). PCD is an absolute requirement for normal development of metazoan organisms. PCD is a hallmark of common diseases such as cardiovascular disease and tissue rejection in graft versus host pathologies, and chemotherapeutics work by increasing PCD. This robust signal or high fluorescent events were verified by confocal microscopy and flow cytometry in several cell lines and a primary culture in which PCD had been induced. In Jurkat cells, GBM-L2 and MG63 cells, the percentage undergoing PCD that were positive for both mAb2C4:AF568 and annexin V ranged between 70 and >90%. In MG63 cells induced for the preapoptotic cell stress response (PACSR), the normal expression of α-tubulin, a key structural component of the cytoskeleton, and accumulation of mAb2C4:AF568 were mutually exclusive. Our data support a model in which CTR is upregulated during PACSR and recycles to the plasma membrane with apoptosis. In cells committed to apoptosis (α-tubulin negative), there is accumulation of the CTR-ligand mAb2C4:AF568 generating a high fluorescent event. The reagent mAb2C4:AF568 effectively identifies a novel event linked to apoptosis. PMID:27777788

  13. Calreticulin Release at an Early Stage of Death Modulates the Clearance by Macrophages of Apoptotic Cells

    PubMed Central

    Osman, Rim; Tacnet-Delorme, Pascale; Kleman, Jean-Philippe; Millet, Arnaud; Frachet, Philippe

    2017-01-01

    Calreticulin (CRT) is a well-known “eat-me” signal harbored by dying cells participating in their recognition by phagocytes. CRT is also recognized to deeply impact the immune response to altered self-cells. In this study, we focus on the role of the newly exposed CRT following cell death induction. We show that if CRT increases at the outer face of the plasma membrane and is well recognized by C1q even when phosphatidylserine is not yet detected, CRT is also released in the surrounding milieu and is able to interact with phagocytes. We observed that exogenous CRT is endocytosed by THP1 macrophages through macropinocytosis and that internalization is associated with a particular phenotype characterized by an increase of cell spreading and migration, an upregulation of CD14, an increase of interleukin-8 release, and a decrease of early apoptotic cell uptake. Importantly, CRT-induced pro-inflammatory phenotype was confirmed on human monocytes-derived macrophages by the overexpression of CD40 and CD274, and we found that monocyte-derived macrophages exposed to CRT display a peculiar polarization notably associated with a downregulation of the histocompatibility complex of class II molecules hampering its description through the classical M1/M2 dichotomy. Altogether our results highlight the role of soluble CRT with strong possible consequences on the macrophage-mediated immune response to dying cell. PMID:28878781

  14. Apoptotic cell death during Drosophila oogenesis is differentially increased by electromagnetic radiation depending on modulation, intensity and duration of exposure.

    PubMed

    Sagioglou, Niki E; Manta, Areti K; Giannarakis, Ioannis K; Skouroliakou, Aikaterini S; Margaritis, Lukas H

    2016-01-01

    Present generations are being repeatedly exposed to different types and doses of non-ionizing radiation (NIR) from wireless technologies (FM radio, TETRA and TV stations, GSM and UMTS phones/base stations, Wi-Fi networks, DECT phones). Although there is controversy on the published data regarding the non-thermal effects of NIR, studies have convincingly demonstrated bioeffects. Their results indicate that modulation, intensity, exposure duration and model system are important factors determining the biological response to irradiation. Attempting to address the dependence of NIR bioeffectiveness on these factors, apoptosis in the model biological system Drosophila melanogaster was studied under different exposure protocols. A signal generator was used operating alternatively under Continuous Wave (CW) or Frequency Modulation (FM) emission modes, at three power output values (10 dB, 0, -10 dB), under four carrier frequencies (100, 395, 682, 900 MHz). Newly emerged flies were exposed either acutely (6 min or 60 min on the 6th day), or repeatedly (6 min or 60 min daily for the first 6 days of their life). All exposure protocols resulted in an increase of apoptotic cell death (ACD) observed in egg chambers, even at very low electric field strengths. FM waves seem to have a stronger effect in ACD than continuous waves. Regarding intensity and temporal exposure pattern, EMF-biological tissue interaction is not linear in response. Intensity threshold for the induction of biological effects depends on frequency, modulation and temporal exposure pattern with unknown so far mechanisms. Given this complexity, translating such experimental data into possible human exposure guidelines is yet arbitrary.

  15. A sphingosine 1-phosphate 1 receptor agonist modulates brain death-induced neurogenic pulmonary injury.

    PubMed

    Sammani, Saad; Park, Ki-Sung; Zaidi, Syed R; Mathew, Biji; Wang, Ting; Huang, Yong; Zhou, Tong; Lussier, Yves A; Husain, Aliya N; Moreno-Vinasco, Liliana; Vigneswaran, Wickii T; Garcia, Joe G N

    2011-11-01

    Lung transplantation remains the only viable therapy for patients with end-stage lung disease. However, the full utilization of this strategy is severely compromised by a lack of donor lung availability. The vast majority of donor lungs available for transplantation are from individuals after brain death (BD). Unfortunately, the early autonomic storm that accompanies BD often results in neurogenic pulmonary edema (NPE), producing varying degrees of lung injury or leading to primary graft dysfunction after transplantation. We demonstrated that sphingosine 1-phosphate (S1P)/analogues, which are major barrier-enhancing agents, reduce vascular permeability via the S1P1 receptor, S1PR1. Because primary lung graft dysfunction is induced by lung vascular endothelial cell barrier dysfunction, we hypothesized that the S1PR1 agonist, SEW-2871, may attenuate NPE when administered to the donor shortly after BD. Significant lung injury was observed after BD, with increases of approximately 60% in bronchoalveolar lavage (BAL) total protein, cell counts, and lung tissue wet/dry (W/D) weight ratios. In contrast, rats receiving SEW-2871 (0.1 mg/kg) 15 minutes after BD and assessed after 4 hours exhibited significant lung protection (∼ 50% reduction, P = 0.01), as reflected by reduced BAL protein/albumin, cytokines, cellularity, and lung tissue wet/dry weight ratio. Microarray analysis at 4 hours revealed a global impact of both BD and SEW on lung gene expression, with a differential gene expression of enriched immune-response/inflammation pathways across all groups. Overall, SEW served to attenuate the BD-mediated up-regulation of gene expression. Two potential biomarkers, TNF and chemokine CC motif receptor-like 2, exhibited gene array dysregulation. We conclude that SEW-2871 significantly attenuates BD-induced lung injury, and may serve as a potential candidate to improve human donor availability.

  16. Nicotine-mediated signals modulate cell death and survival of T lymphocytes

    SciTech Connect

    Oloris, Silvia C.S.; Frazer-Abel, Ashley A.; Jubala, Cristan M.; Fosmire, Susan P.; Helm, Karen M.; Robinson, Sally R.; Korpela, Derek M.; Duckett, Megan M.; Baksh, Shairaz; Modiano, Jaime F.

    2010-02-01

    The capacity of nicotine to affect the behavior of non-neuronal cells through neuronal nicotinic acetylcholine receptors (nAChRs) has been the subject of considerable recent attention. Previously, we showed that exposure to nicotine activates the nuclear factor of activated T cells (NFAT) transcription factor in lymphocytes and endothelial cells, leading to alterations in cellular growth and vascular endothelial growth factor production. Here, we extend these studies to document effects of nicotine on lymphocyte survival. The data show that nicotine induces paradoxical effects that might alternatively enforce survival or trigger apoptosis, suggesting that depending on timing and context, nicotine might act both as a survival factor or as an inducer of apoptosis in normal or transformed lymphocytes, and possibly other non-neuronal cells. In addition, our results show that, while having overlapping functions, low and high affinity nAChRs also transmit signals that promote distinct outcomes in lymphocytes. The sum of our data suggests that selective modulation of nAChRs might be useful to regulate lymphocyte activation and survival in health and disease.

  17. S-nitrosylation-mediated redox transcriptional switch modulates neurogenesis and neuronal cell death.

    PubMed

    Okamoto, Shu-Ichi; Nakamura, Tomohiro; Cieplak, Piotr; Chan, Shing Fai; Kalashnikova, Evgenia; Liao, Lujian; Saleem, Sofiyan; Han, Xuemei; Clemente, Arjay; Nutter, Anthony; Sances, Sam; Brechtel, Christopher; Haus, Daniel; Haun, Florian; Sanz-Blasco, Sara; Huang, Xiayu; Li, Hao; Zaremba, Jeffrey D; Cui, Jiankun; Gu, Zezong; Nikzad, Rana; Harrop, Anne; McKercher, Scott R; Godzik, Adam; Yates, John R; Lipton, Stuart A

    2014-07-10

    Redox-mediated posttranslational modifications represent a molecular switch that controls major mechanisms of cell function. Nitric oxide (NO) can mediate redox reactions via S-nitrosylation, representing transfer of an NO group to a critical protein thiol. NO is known to modulate neurogenesis and neuronal survival in various brain regions in disparate neurodegenerative conditions. However, a unifying molecular mechanism linking these phenomena remains unknown. Here, we report that S-nitrosylation of myocyte enhancer factor 2 (MEF2) transcription factors acts as a redox switch to inhibit both neurogenesis and neuronal survival. Structure-based analysis reveals that MEF2 dimerization creates a pocket, facilitating S-nitrosylation at an evolutionally conserved cysteine residue in the DNA binding domain. S-Nitrosylation disrupts MEF2-DNA binding and transcriptional activity, leading to impaired neurogenesis and survival in vitro and in vivo. Our data define a molecular switch whereby redox-mediated posttranslational modification controls both neurogenesis and neurodegeneration via a single transcriptional signaling cascade. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  18. S-Nitrosylation—Mediated Redox Transcriptional Switch Modulates Neurogenesis and Neuronal Cell Death

    PubMed Central

    Okamoto, Shu-ichi; Nakamura, Tomohiro; Cieplak, Piotr; Chan, Shing Fai; Kalashnikova, Evgenia; Liao, Lujian; Saleem, Sofiyan; Han, Xuemei; Clemente, Arjay; Nutter, Anthony; Sances, Sam; Brechtel, Christopher; Haus, Daniel; Haun, Florian; Sanz-Blasco, Sara; Huang, Xiayu; Li, Hao; Zaremba, Jeffrey D.; Cui, Jiankun; Gu, Zezong; Nikzad, Rana; Harrop, Anne; McKercher, Scott R.; Godzik, Adam; Yates, John R.; Lipton, Stuart A.

    2014-01-01

    SUMMARY Redox-mediated posttranslational modifications represent a molecular switch that controls major mechanisms of cell function. Nitric oxide (NO) can mediate redox reactions via S-nitrosylation, representing transfer of an NO group to a critical protein thiol. NO is known to modulate neurogenesis and neuronal survival in various brain regions in disparate neurodegenerative conditions. However, a unifying molecular mechanism linking these phenomena remains unknown. Here we report that S-nitrosylation of myocyte enhancer factor 2 (MEF2) transcription factors acts as a redox switch to inhibit both neurogenesis and neuronal survival. Structure-based analysis reveals that MEF2 dimerization creates a pocket, facilitating S-nitrosylation at an evolutionally conserved cysteine residue in the DNA binding domain. S-Nitrosylation disrupts MEF2-DNA binding and transcriptional activity, leading to impaired neurogenesis and survival in vitro and in vivo. Our data define a novel molecular switch whereby redox-mediated posttranslational modification controls both neurogenesis and neurodegeneration via a single transcriptional signaling cascade. PMID:25001280

  19. Smac mimetics induce inflammation and necrotic tumour cell death by modulating macrophage activity

    PubMed Central

    Lecis, D; De Cesare, M; Perego, P; Conti, A; Corna, E; Drago, C; Seneci, P; Walczak, H; Colombo, M P; Delia, D; Sangaletti, S

    2013-01-01

    Smac mimetics (SMs) comprise a class of small molecules that target members of the inhibitor of apoptosis family of pro-survival proteins, whose expression in cancer cells hinders the action of conventional chemotherapeutics. Herein, we describe the activity of SM83, a newly synthesised dimeric SM, in two cancer ascites models: athymic nude mice injected intraperitoneally with IGROV-1 human ovarian carcinoma cells and immunocompetent BALB/c mice injected with murine Meth A sarcoma cells. SM83 rapidly killed ascitic IGROV-1 and Meth A cells in vivo (prolonging mouse survival), but was ineffective against the same cells in vitro. IGROV-1 cells in nude mice were killed within the ascites by a non-apoptotic, tumour necrosis factor (TNF)-dependent mechanism. SM83 administration triggered a rapid inflammatory event characterised by host secretion of TNF, interleukin-1β and interferon-γ. This inflammatory response was associated with the reversion of the phenotype of tumour-associated macrophages from a pro-tumoural M2- to a pro-inflammatory M1-like state. SM83 treatment was also associated with a massive recruitment of neutrophils that, however, was not essential for the antitumoural activity of this compound. In BALB/c mice bearing Meth A ascites, SM83 treatment was in some cases curative, and these mice became resistant to a second injection of cancer cells, suggesting that they had developed an adaptive immune response. Altogether, these results indicate that, in vivo, SM83 modulates the immune system within the tumour microenvironment and, through its pro-inflammatory action, leads cancer cells to die by necrosis with the release of high-mobility group box-1. In conclusion, our work provides evidence that SMs could be more therapeutically active than expected by stimulating the immune system. PMID:24232096

  20. Prediction of clinical toxicity in locally advanced head and neck cancer patients by radio-induced apoptosis in peripheral blood lymphocytes (PBLs)

    PubMed Central

    2010-01-01

    Head and neck cancer is treated mainly by surgery and radiotherapy. Normal tissue toxicity due to x-ray exposure is a limiting factor for treatment success. Many efforts have been employed to develop predictive tests applied to clinical practice. Determination of lymphocyte radio-sensitivity by radio-induced apoptosis arises as a possible method to predict tissue toxicity due to radiotherapy. The aim of the present study was to analyze radio-induced apoptosis of peripheral blood lymphocytes in head and neck cancer patients and to explore their role in predicting radiation induced toxicity. Seventy nine consecutive patients suffering from head and neck cancer, diagnosed and treated in our institution, were included in the study. Toxicity was evaluated using the Radiation Therapy Oncology Group scale. Peripheral blood lymphocytes were isolated and irradiated at 0, 1, 2 and 8 Gy during 24 hours. Apoptosis was measured by flow cytometry using annexin V/propidium iodide. Lymphocytes were marked with CD45 APC-conjugated monoclonal antibody. Radiation-induced apoptosis increased in order to radiation dose and fitted to a semi logarithmic model defined by two constants: α and β. α, as the origin of the curve in the Y axis determining the percentage of spontaneous cell death, and β, as the slope of the curve determining the percentage of cell death induced at a determined radiation dose, were obtained. β value was statistically associated to normal tissue toxicity in terms of severe xerostomia, as higher levels of apoptosis were observed in patients with low toxicity (p = 0.035; Exp(B) 0.224, I.C.95% (0.060-0.904)). These data agree with our previous results and suggest that it is possible to estimate the radiosensitivity of peripheral blood lymphocytes from patients determining the radiation induced apoptosis with annexin V/propidium iodide staining. β values observed define an individual radiosensitivity profile that could predict late toxicity due to radiotherapy

  1. Studying p53 family proteins in yeast: Induction of autophagic cell death and modulation by interactors and small molecules

    SciTech Connect

    Leão, Mariana; Gomes, Sara; Bessa, Cláudia; Soares, Joana; Raimundo, Liliana; Monti, Paola; Fronza, Gilberto; Pereira, Clara; Saraiva, Lucília

    2015-01-01

    In this work, the yeast Saccharomyces cerevisiae was used to individually study human p53, p63 (full length and truncated forms) and p73. Using this cell system, the effect of these proteins on cell proliferation and death, and the influence of MDM2 and MDMX on their activities were analyzed. When expressed in yeast, wild-type p53, TAp63, ΔNp63 and TAp73 induced growth inhibition associated with S-phase cell cycle arrest. This growth inhibition was accompanied by reactive oxygen species production and autophagic cell death. Furthermore, they stimulated rapamycin-induced autophagy. On the contrary, none of the tested p53 family members induced apoptosis either per se or after apoptotic stimuli. As previously reported for p53, also TAp63, ΔNp63 and TAp73 increased actin expression levels and its depolarization, suggesting that ACT1 is also a p63 and p73 putative yeast target gene. Additionally, MDM2 and MDMX inhibited the activity of all tested p53 family members in yeast, although the effect was weaker on TAp63. Moreover, Nutlin-3a and SJ-172550 were identified as potential inhibitors of the p73 interaction with MDM2 and MDMX, respectively. Altogether, the yeast-based assays herein developed can be envisaged as a simplified cell system to study the involvement of p53 family members in autophagy, the modulation of their activities by specific interactors (MDM2 and MDMX), and the potential of new small molecules to modulate these interactions. - Highlights: • p53, p63 and p73 are individually studied in the yeast S. cerevisiae. • p53 family members induce ROS production, cell cycle arrest and autophagy in yeast. • p53 family members increase actin depolarization and expression levels in yeast. • MDM2 and MDMX inhibit the activity of p53 family members in yeast. • Yeast can be a useful tool to study the biology and drugability of p53, p63 and p73.

  2. Chromium (VI)-induced oxidative stress, apoptotic cell death and modulation of p53 tumor suppressor gene.

    PubMed

    Bagchi, D; Bagchi, M; Stohs, S J

    2001-06-01

    Chromium (VI) is a widely used industrial chemical, extensively used in paints, metal finishes, steel including stainless steel manufacturing, alloy cast irons, chrome, and wood treatment. On the contrary, chromium (III) salts such as chromium polynicotinate, chromium chloride and chromium picolinate, are used as micronutrients and nutritional supplements, and have been demonstrated to exhibit a significant number of health benefits in rodents and humans. However, the cause for the hexavalent chromium to induce cytotoxicity is not entirely understood. A series of in vitro and in vivo studies have demonstrated that chromium (VI) induces an oxidative stress through enhanced production of reactive oxygen species (ROS) leading to genomic DNA damage and oxidative deterioration of lipids and proteins. A cascade of cellular events occur following chromium (VI)-induced oxidative stress including enhanced production of superoxide anion and hydroxyl radicals, increased lipid peroxidation and genomic DNA fragmentation, modulation of intracellular oxidized states, activation of protein kinase C, apoptotic cell death and altered gene expression. In this paper, we have demonstrated concentration- and time-dependent effects of sodium dichromate (chromium (VI) or Cr (VI)) on enhanced production of superoxide anion and hydroxyl radicals, changes in intracellular oxidized states as determined by laser scanning confocal microscopy, DNA fragmentation and apoptotic cell death (by flow cytometry) in human peripheral blood mononuclear cells. These results were compared with the concentration-dependent effects of chromium (VI) on chronic myelogenous leukemic K562 cells and J774A.1 murine macrophage cells. Chromium (VI)-induced enhanced production of ROS, as well as oxidative tissue and DNA damage were observed in these cells. More pronounced effect was observed on chronic myelogenous leukemic K562 cells and J774A.1 murine macrophage cells. Furthermore, we have assessed the effect of a

  3. Radio Induced Fluorescence (RIF) Imaging Of E-region Quasi-periodic Structures

    NASA Astrophysics Data System (ADS)

    Bernhardt, P. A.

    The horizontal structure of sporadic-E layers has been imaged using artificial airglow excited by high power radio waves. In January 1998, the HF facility at Arecibo, Puerto Rico beamed a 80 MW signal upward at 3.175 MHz. The beam reflected in the E- region near 120 km altitude to excite green-line emissions at 557.7 nm. Ground based images showed quasi-periodic structures with periods near 2 and 10 km. These struc- tures been interpreted as being produced by Kelvin-Helmholtz (K-H) instabilities in the neutral atmosphere. The excitation of radio induced fluorescence (RIF) emissions has been studied with both one-dimensional and two-dimensional computer simulations of the conversion of electromagnetic waves into electron plasma waves. The steep gradients on the bottomside of the E-layer provide conditions for efficient mode conversion. The re- sulting Langmuir waves accelerate electrons to energies between 2 and 10 eV. These suprathermal electrons collide with oxygen atoms to produce green-line emissions. The optical glow only occurs in the parts of the E-region where the plamsa is dense enough to reflect the 3.175 MHz radio waves. Results of the E-layer observations using the RIF technique have shown horizontal stuctures that are most likely produced by the K-H instability. A numerical model has been generated to demonstrate the effects of neutral wind shears on the E-region structures. The model includes the effects of both speed-shear and turning shear dy- namics. The results of the numerical model are used to suggest future research using high-power radio wave to study the ion dynamics of the lower thermosphere.

  4. Identification of an anabolic selective androgen receptor modulator that actively induces death of androgen-independent prostate cancer cells.

    PubMed

    Schmidt, Azriel; Meissner, Robert S; Gentile, Michael A; Chisamore, Michael J; Opas, Evan E; Scafonas, Angela; Cusick, Tara E; Gambone, Carlo; Pennypacker, Brenda; Hodor, Paul; Perkins, James J; Bai, Chang; Ferraro, Damien; Bettoun, David J; Wilkinson, Hilary A; Alves, Stephen E; Flores, Osvaldo; Ray, William J

    2014-09-01

    Prostate cancer (PCa) initially responds to inhibition of androgen receptor (AR) signaling, but inevitably progresses to hormone ablation-resistant disease. Much effort is focused on optimizing this androgen deprivation strategy by improving hormone depletion and AR antagonism. However we found that bicalutamide, a clinically used antiandrogen, actually resembles a selective AR modulator (SARM), as it partially regulates 24% of endogenously 5α-dihydrotestosterone (DHT)-responsive genes in AR(+) MDA-MB-453 breast cancer cells. These data suggested that passive blocking of all AR functions is not required for PCa therapy. Hence, we adopted an active strategy that calls for the development of novel SARMs, which induce a unique gene expression profile that is intolerable to PCa cells. Therefore, we screened 3000 SARMs for the ability to arrest the androgen-independent growth of AR(+) 22Rv1 and LNCaP PCa cells but not AR(-) PC3 or DU145 cells. We identified only one such compound; the 4-aza-steroid, MK-4541, a potent and selective SARM. MK-4541 induces caspase-3 activity and cell death in both androgen-independent, AR(+) PCa cell lines but spares AR(-) cells or AR(+) non-PCa cells. This activity correlates with its promoter context- and cell-type dependent transcriptional effects. In rats, MK-4541 inhibits the trophic effects of DHT on the prostate, but not the levator ani muscle, and triggers an anabolic response in the periosteal compartment of bone. Therefore, MK-4541 has the potential to effectively manage prostatic hypertrophic diseases owing to its antitumor SARM-like mechanism, while simultaneously maintaining the anabolic benefits of natural androgens.

  5. Nitric oxide modulates cadmium influx during cadmium-induced programmed cell death in tobacco BY-2 cells.

    PubMed

    Ma, Wenwen; Xu, Wenzhong; Xu, Hua; Chen, Yanshan; He, Zhenyan; Ma, Mi

    2010-07-01

    Nitric oxide (NO) is a bioactive gas and functions as a signaling molecule in plants exposed to diverse biotic and abiotic stresses including cadmium (Cd(2+)). Cd(2+) is a non-essential and toxic heavy metal, which has been reported to induce programmed cell death (PCD) in plants. Here, we investigated the role of NO in Cd(2+)-induced PCD in tobacco BY-2 cells (Nicotiana tabacum L. cv. Bright Yellow 2). In this work, BY-2 cells exposed to 150 microM CdCl(2) underwent PCD with TUNEL-positive nuclei, significant chromatin condensation and the increasing expression of a PCD-related gene Hsr203J. Accompanied with the occurring of PCD, the production of NO increased significantly. The supplement of NO by sodium nitroprusside (SNP) had accelerated the PCD, whereas the NO synthase inhibitor Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME) and NO-specific scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) alleviated this toxicity. To investigate the mechanism by which NO exerted its function, Cd(2+) concentration was measured subsequently. SNP led more Cd(2+) content than Cd(2+) treatment alone. By contrast, the prevention of NO by L-NAME decreased Cd(2+) accumulation. Using the scanning ion-selective electrode technique, we analyzed the pattern and rate of Cd(2+) fluxes. This analysis revealed the promotion of Cd(2+) influxes into cells by application of SNP, while L-NAME and cPTIO reduced the rate of Cd(2+) uptake or even resulted in net Cd(2+) efflux. Based on these founding, we concluded that NO played a positive role in CdCl(2)-induced PCD by modulating Cd(2+) uptake and thus promoting Cd(2+) accumulation in BY-2 cells.

  6. Mitochondrial peroxiredoxin-5 as potential modulator of mitochondria-ER crosstalk in MPP+-induced cell death.

    PubMed

    De Simoni, Stéphanie; Linard, Dominique; Hermans, Emmanuel; Knoops, Bernard; Goemaere, Julie

    2013-05-01

    Peroxiredoxin-5 (PRDX5) is an antioxidant enzyme which differs from the other peroxiredoxins with regards to its enzymatic mechanism, its high affinity for organic peroxides and peroxynitrite and its wide subcellular distribution. In particular, the mitochondrial isoform of PRDX5 confers a remarkable cytoprotection toward oxidative stress to mammalian cells. Mitochondrial dysfunction and disruption of Ca²⁺ homeostasis are implicated in neurodegeneration. Growing evidence supports that endoplasmic reticulum (ER) could operate in tandem with mitochondria to regulate intracellular Ca²⁺ fluxes in neurodegenerative processes. Here, we overexpressed mitochondrial PRDX5 in SH-SY5Y cells to dissect the role of this enzyme in 1-methyl-4-phenylpyridinium (MPP)⁺-induced cell death. Our data show that mitochondria-dependent apoptosis triggered by MPP⁺, assessed by the measurement of caspase-9 activation and mitochondrial DNA damage, is prevented by mitochondrial PRDX5 overexpression. Moreover, PRDX5 overexpression blocks the increase in intracellular Ca²⁺, Ca²⁺-dependent activation of calpains and Bax cleavage. Finally, using Ca²⁺ channel inhibitors (Nimodipine, Dantrolene and 2-APB), we show that Ca²⁺ release arises essentially from ER stores through 1,4,5-inositol-trisphosphate receptors (IP3 R). Altogether, our results suggest that the MPP⁺ mitochondrial pathway of apoptosis is regulated by mitochondrial PRDX5 in a process that could involve redox modulation of Ca²⁺ transporters via a crosstalk between mitochondria and ER.

  7. Activation and modulation of cardiac poly-adenosine diphosphate ribose polymerase activity in a rat model of brain death.

    PubMed

    Brain, John G; Rostron, Anthony J; Dark, John H; Kirby, John A

    2008-05-15

    DNA damage during transplantation can activate poly-adenosine diphosphate ribose polymerase (PARP) resulting in the generation of polymers of adenosine diphosphate-ribose (PAR). Excessive linkage of PAR to nuclear proteins can induce cell death, thereby limiting the function of transplanted organs. This study uses a rat model of brain death to determine the profile of PARP activation and whether mechanisms that lead to cell death can be ameliorated by appropriate donor resuscitation. The expression of PAR-linked nuclear proteins within cardiac myocytes was greatly increased after the induction of donor brain death. Importantly, infusion of noradrenaline or vasopressin to normalize the chronic hypotension produced by brain death reduced the expression of PAR to a level below baseline. These data suggest that chronic hypotension after donor brain death has the potential to limit cardiac function through the activation of PARP; however, this early cause of graft damage can be mitigated by appropriate donor resuscitation.

  8. Radio-induced alteration in cordierite - Implications for petrology, gemmology and materials science

    NASA Astrophysics Data System (ADS)

    Krickl, R.; Nasdala, L.; Grambole, D.; Kaindl, R.

    2009-04-01

    Cordierite is a common metamorphic and magmatic mineral, which is used as petrologic tool for reconstructing the history of its host rock. Further applications include cordierite gemstones and the use of synthetic analogs in ceramics. Cordierite is stable over a wide temperature and pressure range and relatively resistant to chemical alteration; however, its properties can be significantly changed upon the impact of external irradiation. In the course of a comprehensive study, natural radiohaloes in cordierite (a widespread feature caused by the impact of alpha-particles originating from radioactive inclusions) as well as artificial analogs produced by implantation of 8.8 MeV He2+ ions were investigated using modern micro-techniques. Additional irradiation experiments were performed using O6+ ions, electrons and gamma-rays. Ion irradiation causes yellow colouration that is strongly pleochroic, and fades at higher doses. The possibility of radiation-treatment for enhancing the quality of gem-cordierite is discussed. While samples remain crystalline up to doses of 1016 He2+/cm2, the same material is fully amorphised when irradiated with the same dose of 30 MeV O6+ ions. These different observations may help to estimate the performance assessment of cordierite-ceramics in radiated environments. A very important result concerning the petrological use of cordierite is the radio-induced transformation of channel constituents: Inside the irradiated areas the vibrational bands of CO2 decrease in intensity, whereas two new bands appear at 2135 cm-1 (both IR- and Raman-active; cf. Nasdala et al., 2006) and 1550 cm-1 (only Raman-activ). They are assigned to stretching vibrations of carbon monoxide and molecular oxygen, respectively, thus indicating a radio-chemical transformation 2CO2 → 2CO + O2 in alpha-irradiated cordierite. This study yields the first spectroscopic evidence for the irradiation-induced formation of molecular oxygen in cordierite. Polarised vibrational

  9. Muscarinic M1 receptor partially modulates higher sensitivity to cadmium-induced cell death in primary basal forebrain cholinergic neurons: A cholinesterase variants dependent mechanism.

    PubMed

    Del Pino, Javier; Zeballos, Gabriela; Anadon, María José; Díaz, María Jesús; Moyano, Paula; Díaz, Gloria Gómez; García, Jimena; Lobo, Margarita; Frejo, María Teresa

    2016-06-15

    Cadmium is a toxic compound reported to produce cognitive dysfunctions, though the mechanisms involved are unknown. In a previous work we described how cadmium blocks cholinergic transmission and induces greater cell death in primary cholinergic neurons from the basal forebrain. It also induces cell death in SN56 cholinergic neurons from the basal forebrain through M1R blockage, alterations in the expression of AChE variants and GSK-3β, and an increase in Aβ and total and phosphorylated Tau protein levels. It was observed that the silencing or blockage of M1R altered ChAT activity, GSK-3β, AChE splice variants gene expression, and Aβ and Tau protein formation. Furthermore, AChE-S variants were associated with the same actions modulated by M1R. Accordingly, we hypothesized that cholinergic transmission blockage and higher sensitivity to cadmium-induced cell death of primary basal forebrain cholinergic neurons is mediated by M1R blockage, which triggers this effect through alteration of the expression of AChE variants. To prove this hypothesis, we evaluated, in primary culture from the basal forebrain region, whether M1R silencing induces greater cell death in cholinergic neurons than cadmium does, and whether in SN56 cells M1R mediates the mechanisms described so as to play a part in the cadmium induction of cholinergic transmission blockage and cell death in this cell line through alteration of the expression of AChE variants. Our results prove that M1R silencing by cadmium partially mediates the greater cell death observed on basal forebrain cholinergic neurons. Moreover, all previously described mechanisms for blocking cholinergic transmission and inducing cell death on SN56 cells after cadmium exposure are partially mediated by M1R through the alteration of AChE expression. Thus, our results may explain cognitive dysfunctions observed in cadmium toxicity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Modulation of cell death in human colorectal and breast cancer cells through a manganese chelate by involving GSH with intracellular p53 status.

    PubMed

    Banerjee, Kaushik; Das, Satyajit; Majumder, Saikat; Majumdar, Subrata; Biswas, Jaydip; Choudhuri, Soumitra Kumar

    2017-03-01

    Chemotherapy is central to current treatment modality especially for advanced and metastatic colorectal and breast cancers. Targeting the key molecular events of the neoplastic cells may open a possibility to treat cancer. Although some improvements in understanding of colorectal and breast cancer treatment have been recorded, the involvement of glutathione (GSH) and dependency of p53 status on the modulation of GSH-mediated treatment efficacy have been largely overlooked. Herein, we tried to decipher the underlying mechanism of the action of Mn-N-(2-hydroxyacetophenone) glycinate (MnNG) against differential p53 status bearing Hct116, MCF-7, and MDA-MB-468 cells on the backdrop of intracellular GSH level and reveal the role of p53 status in modulating GSH-dependant abrogation of MnNG-induced apoptosis in these cancer cells. Present study discloses that MnNG targets specifically wild-type-p53 expressing Hct116 and MCF-7 cells by significantly depleting both cytosolic, mitochondrial GSH, and modulating nuclear GSH through Glutathione reductase and Glutamate-cysteine ligase depletion that may in turn induce p53-mediated intrinsic apoptosis in them. Thus GSH addition abrogates p53-mediated apoptosis in wild-type-p53 expressing cells. GSH addition also overrides MnNG-induced modulation of phase II detoxifying parameters in them. However, GSH addition partially replenishes the down-regulated or modulated GSH pool in cytosol, mitochondria, and nucleus, and relatively abrogates MnNG-induced intrinsic apoptosis in p53-mutated MDA-MB-468 cells. On the contrary, although MnNG induces significant cell death in p53-null Hct116 cells, GSH addition fails to negate MnNG-induced cell death. Thus p53 status with intracellular GSH is critical for the modulation of MnNG-induced apoptosis.

  11. Autophagy protein p62/SQSTM1 is involved in HAMLET-induced cell death by modulating apotosis in U87MG cells.

    PubMed

    Zhang, Y-B; Gong, J-L; Xing, T-Y; Zheng, S-P; Ding, W

    2013-03-21

    HAMLET is a complex of oleic acids and decalcified α-lactalbumin that was discovered to selectively kill tumor cells both in vitro and in vivo. Autophagy is an important cellular process involved in drug-induced cell death of glioma cells. We treated U87MG human glioma cells with HAMLET and found that the cell viability was significantly decreased and accompanied with the activation of autophagy. Interestingly, we observed an increase in p62/SQSTM1, an important substrate of autophagosome enzymes, at the protein level upon HAMLET treatment for short periods. To better understand the functionality of autophagy and p62/SQSTM1 in HAMLET-induced cell death, we modulated the level of autophagy or p62/SQSTM1 with biochemical or genetic methods. The results showed that inhibition of autophagy aggravated HAMLET-induced cell death, whereas activation of authophagy attenuated this process. Meanwhile, we found that overexpression of wild-type p62/SQSTM1 was able to activate caspase-8, and then promote HAMLET-induced apoptosis, whereas knockdown of p62/SQSTM1 manifested the opposite effect. We further demonstrated that the function of p62/SQSTM1 following HAMLET treatment required its C-terminus UBA domain. Our results indicated that in addition to being a marker of autophagy activation in HAMLET-treated glioma cells, p62/SQSTM1 could also function as an important mediator for the activation of caspase-8-dependent cell death.

  12. Autophagy protein p62/SQSTM1 is involved in HAMLET-induced cell death by modulating apotosis in U87MG cells

    PubMed Central

    Zhang, Y-B; Gong, J-L; Xing, T-Y; Zheng, S-P; Ding, W

    2013-01-01

    HAMLET is a complex of oleic acids and decalcified α-lactalbumin that was discovered to selectively kill tumor cells both in vitro and in vivo. Autophagy is an important cellular process involved in drug-induced cell death of glioma cells. We treated U87MG human glioma cells with HAMLET and found that the cell viability was significantly decreased and accompanied with the activation of autophagy. Interestingly, we observed an increase in p62/SQSTM1, an important substrate of autophagosome enzymes, at the protein level upon HAMLET treatment for short periods. To better understand the functionality of autophagy and p62/SQSTM1 in HAMLET-induced cell death, we modulated the level of autophagy or p62/SQSTM1 with biochemical or genetic methods. The results showed that inhibition of autophagy aggravated HAMLET-induced cell death, whereas activation of authophagy attenuated this process. Meanwhile, we found that overexpression of wild-type p62/SQSTM1 was able to activate caspase-8, and then promote HAMLET-induced apoptosis, whereas knockdown of p62/SQSTM1 manifested the opposite effect. We further demonstrated that the function of p62/SQSTM1 following HAMLET treatment required its C-terminus UBA domain. Our results indicated that in addition to being a marker of autophagy activation in HAMLET-treated glioma cells, p62/SQSTM1 could also function as an important mediator for the activation of caspase-8-dependent cell death. PMID:23519119

  13. HSP70 and EndoG modulate cell death by heat in human skin keratinocytes in vitro.

    PubMed

    Chinnathambi, Sathivel; Tomanek-Chalkley, Ann; Bickenbach, Jackie R

    2008-01-01

    We examined how young and old keratinocytes died from heat stress in vitro. We found that keratinocyte cell death was not due to oxidative stress as neither Mn-SOD nor Cu-Zn-SOD was produced in either young or old heated keratinocytes. Instead, analysis of the anti-apoptotic factors, Bcl2 and HSP70, and the pro-apoptotic factors, caspase 3, caspase 8, Apaf-1, cytochrome c, AIF, and EndoG, indicated that keratinocyte cell death occurred via the caspase-independent EndoG apoptotic pathway. We found that both young and old keratinocytes died via the same pathway, and that we could specifically reduce both young and old keratinocyte death by addition of the EndoG inhibitor NEM. Further analysis suggested that the difference between young and old keratinocyte death was due to the synthesis of HSP70 protein, with the increase in response to heat more pronounced in young keratinocytes than in old keratinocytes. When we inhibited HSP70 by adding quercetin, death was increased in both young and old keratinocytes, but more so in old keratinocytes. These data suggest that old keratinocytes may die more readily than young keratinocytes when heated because they synthesize HSP70 at a lower efficiency. Such findings suggest that HSP70 production may be age-dependent.

  14. Resting heart rate and risk of sudden cardiac death in the general population: influence of left ventricular systolic dysfunction and heart rate-modulating drugs.

    PubMed

    Teodorescu, Carmen; Reinier, Kyndaron; Uy-Evanado, Audrey; Gunson, Karen; Jui, Jonathan; Chugh, Sumeet S

    2013-08-01

    Higher levels of resting heart rate (HR) have been associated with sudden cardiac death (SCD) but mechanisms are poorly understood. We hypothesized that severe left ventricular systolic dysfunction (LVSD) and HR-modulating drugs explain the HR-SCD relationship. To evaluate the relationship between HR, severe LVSD, HR-modulating drugs, and SCD in the community by using a case-control approach. From the ongoing Oregon Sudden Unexpected Death Study, SCD cases (n = 378) aged ≥35 years and with electrocardiogram-documented resting HR were compared to 378 age- and gender-matched control subjects with coronary artery disease (mean age 68 ± 13 years; 69% man). Associations with SCD were assessed by using multivariable logistic regression. Mean resting HR was significantly higher among SCD cases compared to controls (7.5 beats/min difference; P < .0001). HR was a significant determinant of SCD after adjustment for significant comorbidities and medications (odds ratio for 10 beats/min increase 1.26; 95% confidence interval 1.14-1.38; P < .0001). After considering LVSD, resting HR was slightly attenuated but remained significantly associated with SCD (P = .005). In addition to diabetes and digoxin as well as pulmonary and renal disease, LVSD was also independently associated with SCD (odds ratio 1.79; 95% confidence interval 1.11-2.87; P = .02). Contrary to expectations, the significant relationship between increased resting HR and SCD persisted even after adjustment for LVSD and HR-modulating drugs. These findings suggest a potential role for additional novel interventions/therapies that modulate autonomic tone. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  15. METACASPASE9 modulates autophagy to confine cell death to the target cells during Arabidopsis vascular xylem differentiation

    PubMed Central

    Escamez, Sacha; André, Domenique; Zhang, Bo; Bollhöner, Benjamin; Pesquet, Edouard; Tuominen, Hannele

    2016-01-01

    ABSTRACT We uncovered that the level of autophagy in plant cells undergoing programmed cell death determines the fate of the surrounding cells. Our approach consisted of using Arabidopsis thaliana cell cultures capable of differentiating into two different cell types: vascular tracheary elements (TEs) that undergo programmed cell death (PCD) and protoplast autolysis, and parenchymatic non-TEs that remain alive. The TE cell type displayed higher levels of autophagy when expression of the TE-specific METACASPASE9 (MC9) was reduced using RNAi (MC9-RNAi). Misregulation of autophagy in the MC9-RNAi TEs coincided with ectopic death of the non-TEs, implying the existence of an autophagy-dependent intercellular signalling from within the TEs towards the non-TEs. Viability of the non-TEs was restored when AUTOPHAGY2 (ATG2) was downregulated specifically in MC9-RNAi TEs, demonstrating the importance of autophagy in the spatial confinement of cell death. Our results suggest that other eukaryotic cells undergoing PCD might also need to tightly regulate their level of autophagy to avoid detrimental consequences for the surrounding cells. PMID:26740571

  16. Functional characterization of NAC55 transcription factor from oilseed rape (Brassica napus L.) as a novel transcriptional activator modulating reactive oxygen species accumulation and cell death.

    PubMed

    Niu, Fangfang; Wang, Chen; Yan, Jingli; Guo, Xiaohua; Wu, Feifei; Yang, Bo; Deyholos, Michael K; Jiang, Yuan-Qing

    2016-09-01

    NAC transcription factors (TFs) are plant-specific and play important roles in development, responses to biotic and abiotic cues and hormone signaling. So far, only a few NAC genes have been reported to regulate cell death. In this study, we identified and characterized a NAC55 gene isolated from oilseed rape (Brassica napus L.). BnaNAC55 responds to multiple stresses, including cold, heat, abscisic acid (ABA), jasmonic acid (JA) and a necrotrophic fungal pathogen Sclerotinia sclerotiorum. BnaNAC55 has transactivation activity and is located in the nucleus. BnaNAC55 is able to form homodimers in planta. Unlike ANAC055, full-length BnaNAC55, but not either the N-terminal NAC domain or C-terminal regulatory domain, induces ROS accumulation and hypersensitive response (HR)-like cell death when expressed both in oilseed rape protoplasts and Nicotiana benthamiana. Furthermore, BnaNAC55 expression causes obvious nuclear DNA fragmentation. Moreover, quantitative reverse transcription PCR (qRT-PCR) analysis identified that the expression levels of multiple genes regulating ROS production and scavenging, defense response as well as senescence are significantly induced. Using a dual luciferase reporter assay, we further confirm that BnaNAC55 could activate the expression of a few ROS and defense-related gene expression. Taken together, our work has identified a novel NAC TF from oilseed rape that modulates ROS accumulation and cell death.

  17. Activation of the intrinsic cell death pathway, increased apoptosis and modulation of astrocytes in the cerebellum of diabetic rats.

    PubMed

    Lechuga-Sancho, Alfonso M; Arroba, Ana I; Frago, Laura M; Pañeda, Covadonga; García-Cáceres, Cristina; Delgado Rubín de Célix, Arancha; Argente, Jesús; Chowen, Julie A

    2006-08-01

    Poorly controlled diabetes mellitus results in structural and functional changes in many brain regions. We demonstrate that in streptozotocin-induced diabetic rats cell death is increased and proliferation decreased in the cerebellum, indicating overall cell loss. Levels of both the proform and cleaved forms of caspases 3, 6 and 9 are increased, with no change in caspases 7, 8 or 12. Colocalization of glial fibrillary acidic protein (GFAP) and cleaved caspase 3 and GFAP in TUNEL-positive cells increased in diabetic rats. Changes in GFAP levels paralleled modifications in proliferating cell nuclear antigen (PCNA), increasing at 1 week of diabetes and decreasing thereafter, and proliferating GFAP-positive cells were decreased in the cerebellum of diabetic rats. These results suggest that astrocytes are dramatically affected in the cerebellum, including an increase in cell death and a decrease in proliferation, and this could play a role in the structural and functional changes in this brain area in diabetes.

  18. Novel histone deacetylase inhibitor CG200745 induces clonogenic cell death by modulating acetylation of p53 in cancer cells.

    PubMed

    Oh, Eun-Taex; Park, Moon-Taek; Choi, Bo-Hwa; Ro, Seonggu; Choi, Eun-Kyung; Jeong, Seong-Yun; Park, Heon Joo

    2012-04-01

    Histone deacetylase (HDAC) plays an important role in cancer onset and progression. Therefore, inhibition of HDAC offers potential as an effective cancer treatment regimen. CG200745, (E)-N(1)-(3-(dimethylamino)propyl)-N(8)-hydroxy-2-((naphthalene-1-loxy)methyl)oct-2-enediamide, is a novel HDAC inhibitor presently undergoing a phase I clinical trial. Enhancement of p53 acetylation by HDAC inhibitors induces cell cycle arrest, differentiation, and apoptosis in cancer cells. The purpose of the present study was to investigate the role of p53 acetylation in the cancer cell death caused by CG200745. CG200745-induced clonogenic cell death was 2-fold greater in RKO cells expressing wild-type p53 than in p53-deficient RC10.1 cells. CG200745 treatment was also cytotoxic to PC-3 human prostate cancer cells, which express wild-type p53. CG200745 increased acetylation of p53 lysine residues K320, K373, and K382. CG200745 induced the accumulation of p53, promoted p53-dependent transactivation, and enhanced the expression of MDM2 and p21(Waf1/Cip1) proteins, which are encoded by p53 target genes. An examination of CG200745 effects on p53 acetylation using cells transfected with various p53 mutants showed that cells expressing p53 K382R mutants were significantly resistant to CG200745-induced clonogenic cell death compared with wild-type p53 cells. Moreover, p53 transactivation in response to CG200745 was suppressed in all cells carrying mutant forms of p53, especially K382R. Taken together, these results suggest that acetylation of p53 at K382 plays an important role in CG200745-induced p53 transactivation and clonogenic cell death.

  19. Metacaspase-8 modulates programmed cell death induced by ultraviolet light and H2O2 in Arabidopsis.

    PubMed

    He, Rui; Drury, Georgina E; Rotari, Vitalie I; Gordon, Anna; Willer, Martin; Farzaneh, Tabasum; Woltering, Ernst J; Gallois, Patrick

    2008-01-11

    Programmed cell death (PCD) is a genetically controlled cell death that is regulated during development and activated in response to environmental stresses or pathogen infection. The degree of conservation of PCD across kingdoms and phylum is not yet clear; however, whereas caspases are proteases that act as key components of animal apoptosis, plants have no orthologous caspase sequences in their genomes. The discovery of plant and fungi metacaspases as proteases most closely related to animal caspases led to the hypothesis that metacaspases are the functional homologues of animal caspases in these organisms. Arabidopsis thaliana has nine metacaspase genes, and so far it is unknown which members of the family if any are involved in the regulation of PCD. We show here that metacaspase-8 (AtMC8) is a member of the gene family strongly up-regulated by oxidative stresses caused by UVC, H(2)O(2), or methyl viologen. This up-regulation was dependent of RCD1, a mediator of the oxidative stress response. Recombinant metacaspase-8 cleaved after arginine, had a pH optimum of 8, and complemented the H(2)O(2) no-death phenotype of a yeast metacaspase knock-out. Overexpressing AtMC8 up-regulated PCD induced by UVC or H(2)O(2), and knocking out AtMC8 reduced cell death triggered by UVC and H(2)O(2) in protoplasts. Knock-out seeds and seedlings had an increased tolerance to the herbicide methyl viologen. We suggest that metacaspase-8 is part of an evolutionary conserved PCD pathway activated by oxidative stress.

  20. Chemotherapy-induced immunogenic modulation of tumor cells enhances killing by cytotoxic T lymphocytes and is distinct from immunogenic cell death.

    PubMed

    Hodge, James W; Garnett, Charlie T; Farsaci, Benedetto; Palena, Claudia; Tsang, Kwong-Yok; Ferrone, Soldano; Gameiro, Sofia R

    2013-08-01

    Certain chemotherapeutic regimens trigger cancer cell death while inducing dendritic cell maturation and subsequent immune responses. However, chemotherapy-induced immunogenic cell death (ICD) has thus far been restricted to select agents. In contrast, several chemotherapeutic drugs modulate antitumor immune responses, despite not inducing classic ICD. In addition, in many cases tumor cells do not die after treatment. Here, using docetaxel, one of the most widely used cancer chemotherapeutic agents, as a model, we examined phenotypic and functional consequences of tumor cells that do not die from ICD. Docetaxel treatment of tumor cells did not induce ATP or high-mobility group box 1 (HMGB1) secretion, or cell death. However, calreticulin (CRT) exposure was observed in all cell lines examined after chemotherapy treatment. Killing by carcinoembryonic antigen (CEA), MUC-1, or PSA-specific CD8(+) CTLs was significantly enhanced after docetaxel treatment. This killing was associated with increases in components of antigen-processing machinery, and mediated largely by CRT membrane translocation, as determined by functional knockdown of CRT, PERK, or CRT-blocking peptide. A docetaxel-resistant cell line was selected (MDR-1(+), CD133(+)) by continuous exposure to docetaxel. These cells, while resistant to direct cytostatic effects of docetaxel, were not resistant to the chemomodulatory effects that resulted in enhancement of CTL killing. Here, we provide an operational definition of "immunogenic modulation," where exposure of tumor cells to nonlethal/sublethal doses of chemotherapy alters tumor phenotype to render the tumor more sensitive to CTL killing. These observations are distinct and complementary to ICD and highlight a mechanism whereby chemotherapy can be used in combination with immunotherapy. Copyright © 2013 UICC.

  1. Quercetin modulates NF-kappa B and AP-1/JNK pathways to induce cell death in human hepatoma cells.

    PubMed

    Granado-Serrano, Ana Belén; Martín, María Angeles; Bravo, Laura; Goya, Luis; Ramos, Sonia

    2010-01-01

    Quercetin, a dietary flavonoid, has been shown to possess anticarcinogenic properties, but the precise molecular mechanisms of action are not thoroughly elucidated. The aim of this study was to investigate the regulatory effect of quercetin (50 microM) on two main transcription factors (NF-kappa B and AP-1) related to survival/proliferation pathways in a human hepatoma cell line (HepG2) over time. Quercetin induced a significant time-dependent inactivation of the NF-kappa B pathway consistent with a downregulation of the NF-kappa B binding activity (from 15 min onward). These features were in concert with a time-dependent activation (starting at 15 min and maintained up to 18 h) of the AP-1/JNK pathway, which played an important role in the control of the cell death induced by the flavonoid and contributed to the regulation of survival/proliferation (AKT, ERK) and death (caspase-3, p38, unbalance of Bcl-2 proapoptotic and antiapoptotic proteins) signals. These data suggest that NF-kappa B and AP-1 play a main role in the tight regulation of survival/proliferation pathways exerted by quercetin and that the sustained JNK/AP-1 activation and inhibition of NF-kappa B provoked by the flavonoid induced HepG2 death.

  2. Overexpression of alpha-synuclein at non-toxic levels increases dopaminergic cell death induced by copper exposure via modulation of protein degradation pathways.

    PubMed

    Anandhan, Annadurai; Rodriguez-Rocha, Humberto; Bohovych, Iryna; Griggs, Amy M; Zavala-Flores, Laura; Reyes-Reyes, Elsa M; Seravalli, Javier; Stanciu, Lia A; Lee, Jaekwon; Rochet, Jean-Christophe; Khalimonchuk, Oleh; Franco, Rodrigo

    2015-09-01

    Gene multiplications or point mutations in alpha (α)-synuclein are associated with familial and sporadic Parkinson's disease (PD). An increase in copper (Cu) levels has been reported in the cerebrospinal fluid and blood of PD patients, while occupational exposure to Cu has been suggested to augment the risk to develop PD. We aimed to elucidate the mechanisms by which α-synuclein and Cu regulate dopaminergic cell death. Short-term overexpression of wild type (WT) or mutant A53T α-synuclein had no toxic effect in human dopaminergic cells and primary midbrain cultures, but it exerted a synergistic effect on Cu-induced cell death. Cell death induced by Cu was potentiated by overexpression of the Cu transporter protein 1 (Ctr1) and depletion of intracellular glutathione (GSH) indicating that the toxic effects of Cu are linked to alterations in its intracellular homeostasis. Using the redox sensor roGFP, we demonstrated that Cu-induced oxidative stress was primarily localized in the cytosol and not in the mitochondria. However, α-synuclein overexpression had no effect on Cu-induced oxidative stress. WT or A53T α-synuclein overexpression exacerbated Cu toxicity in dopaminergic and yeast cells in the absence of α-synuclein aggregation. Cu increased autophagic flux and protein ubiquitination. Impairment of autophagy by overexpression of a dominant negative Atg5 form or inhibition of the ubiquitin/proteasome system (UPS) with MG132 enhanced Cu-induced cell death. However, only inhibition of the UPS stimulated the synergistic toxic effects of Cu and α-synuclein overexpression. Our results demonstrate that α-synuclein stimulates Cu toxicity in dopaminergic cells independent from its aggregation via modulation of protein degradation pathways.

  3. Overexpression of alpha-synuclein at non-toxic levels increases dopaminergic cell death induced by copper exposure via modulation of protein degradation pathways

    PubMed Central

    Anandhan, Annadurai; Rodriguez-Rocha, Humberto; Bohovych, Iryna; Griggs, Amy M.; Zavala-Flores, Laura; Reyes-Reyes, Elsa M.; Seravalli, Javier; Stanciu, Lia A.; Lee, Jaekwon; Rochet, Jean-Christophe; Khalimonchuk, Oleh; Franco, Rodrigo

    2014-01-01

    Gene multiplications or point mutations in alpha (α)-synuclein are associated with familial and sporadic Parkinson’s disease (PD). An increase in copper (Cu) levels has been reported in the cerebrospinal fluid and blood of PD patients, while occupational exposure to Cu has been suggested to augment the risk to develop PD. We aimed to elucidate the mechanisms by which α-synuclein and Cu regulate dopaminergic cell death. Short-term overexpression of WT or A53T α-synuclein had no toxic effect in human dopaminergic cells and primary midbrain cultures, but it exerted a synergistic effect on Cu-induced cell death. Cell death induced by Cu was potentiated by overexpression of the Cu transporter protein 1 (Ctr1) and depletion of intracellular glutathione (GSH) indicating that the toxic effects of Cu are linked to alterations in its intracellular homeostasis. Using the redox sensor roGFP, we demonstrated that Cu-induced oxidative stress was primarily localized in the cytosol and not in the mitochondria. However, α-synuclein overexpression had no effect on Cu-induced oxidative stress. WT or A53T α-synuclein overexpression exacerbated Cu toxicity in dopaminergic cells and yeast in the absence of α-synuclein aggregation. Cu increased autophagic flux and protein ubiquitination. Impairment of autophagy by overexpression of a dominant negative Atg5 form or inhibition of the ubiquitin/proteasome system (UPS) with MG132 enhanced Cu-induced cell death. However, only inhibition of the UPS stimulated the synergistic toxic effects of Cu and α-synuclein overexpression. Our results demonstrate that α-synuclein stimulates Cu toxicity in dopaminergic cells independent from its aggregation via modulation of protein degradation pathways. PMID:25497688

  4. Polyamines modulate the roscovitine-induced cell death switch decision autophagy vs. apoptosis in MCF-7 and MDA-MB-231 breast cancer cells.

    PubMed

    Arisan, Elif Damla; Akkoç, Yunus; Akyüz, Kaan Gencer; Kerman, Ezgi Melek; Obakan, Pinar; Çoker-Gürkan, Ajda; Palavan Ünsal, Narçin

    2015-06-01

    Current clinical strategies against breast cancer mainly involve the use of anti‑hormonal agents to decrease estrogen production; however, development of resistance is a major problem. The resistance phenotype depends on the modulation of cell‑cycle regulatory proteins, cyclins and cyclin‑dependent kinases. Roscovitine, a selective inhibitor of cyclin‑dependent kinases, shows high therapeutic potential by causing cell‑cycle arrest in various cancer types. Autophagy is a type of cell death characterized by the enzymatic degradation of macromolecules and organelles in double‑ or multi‑membrane autophagic vesicles. This process has important physiological functions, including the degradation of misfolded proteins and organelle turnover. Recently, the switch between autophagy and apoptosis has been proposed to constitute an important regulator of cell death in response to chemotherapeutic drugs. The process is regulated by several proteins, such as the proteins of the Atg family, essential for the initial formation of the autophagosome, and PI3K, important at the early stages of autophagic vesicle formation. Polyamines (PAs) are small aliphatic amines that play major roles in a number of eukaryotic processes, including cell proliferation. The PA levels are regulated by ornithine decarboxylase (ODC), the rate‑limiting enzyme in PA biosynthesis. In this study, we aimed to investigate the role of PAs in roscovitine‑induced autophagic/apoptotic cell death in estrogen receptor‑positive MCF‑7 and estrogen receptor‑negative MDA‑MB‑231 breast cancer cells. We show that MDA‑MB‑231 cells are more resistant to roscovitine than MCF‑7 cells. This difference was related to the regulation of autophagic key molecules in MDA‑MB‑231 cells. In addition, we found that exogenous PAs have a role in the cell death decision between roscovitine‑induced apoptosis or autophagy in MCF‑7 and MDA‑MB‑231 breast cancer cells.

  5. Proanthocyanidin exposure to B6C3F1 mice significantly attenuates dimethylnitrosamine-induced liver tumor induction and mortality by differentially modulating programmed and unprogrammed cell deaths.

    PubMed

    Ray, Sidhartha D; Parikh, Hemal; Bagchi, Debasis

    2005-11-11

    Proanthocyanidins are of current interest as chemopreventive agents. The potential of the pre-, post- and co-exposure of proanthocyanidin-rich grape seed extract (GSPE) in preventing, reducing and/or delaying dimethylnitrosamine (N-nitrosodimethylamine, DMN)-induced liver tumorigenesis, carcinogenesis and mortality in male B6C3F1 mice was determined. Animals were divided into six groups: I-control, II-GSPE alone, III-DMN alone, IV-GSPE+DMN, V-DMN exposure (3 months) followed by GSPE diet (9 months) and VI-GSPE diet (3 months)+DMN (3 months)+control diet (6 months). DMN exposure (0-8 weeks: 5mg/kg; 8-12 weeks: 10mg/kg, i.p.) was limited to a total period of 3 months. GSPE was incorporated in laboratory chow (ADI: 100mg/kg b.w.). Animals were sacrificed at 3 month intervals, and serum chemistry, liver histopathology, integrity of hepatic genomic DNA, antioxidant status, and rates of apoptotic and necrotic cell deaths were determined. DMN-induced liver tumor formation (85%) and animal lethality (38%) were powerfully antagonized by co-administration of GSPE+DMN (tumor positive: 45%; death: 11%). More than 75% of the DMN-treated animals had numerous tumors (five or more), which were significantly reduced in the GSPE+DMN group (35%). GSPE also negatively influenced other protocols specifically designed to test initiation and progression phases. Thus, GSPE was instrumental in modulating metabolic cascades and regulated orchestration of cell death processes involved during the multistage tumorigenic process. These results unraveled that long-term exposure to proanthocyanidin-rich grape seed extract may serve as a potent barrier to all three stages of DMN-induced liver carcinogenesis and tumorigenesis by selectively altering oxidative stress, genomic integrity and cell death patterns in vivo.

  6. The biphosphinic paladacycle complex induces melanoma cell death through lysosomal-mitochondrial axis modulation and impaired autophagy.

    PubMed

    Gigli, Rafael; Pereira, Gustavo J S; Antunes, Fernanda; Bechara, Alexandre; Garcia, Daniel M; Spindola, Daniel G; Jasiulionis, Mirian G; Caires, Antonio C F; Smaili, Soraya S; Bincoletto, Claudia

    2016-01-01

    Recently, palladium complexes have been extensively studied as cyclization of these complexes by cyclometallation reactions increased their stability making them promising antitumor compounds. In this study, we have investigated apoptosis induced by the Biphosphinic Paladacycle Complex (BPC11) and possible cross talk between apoptosis and autophagy in cell line models of metastatic (Tm5) and non-metastatic (4C11-) melanoma. The BPC11-induced cell death in melanoma involved the lysosomal-mitochondrial axis, which is characterized by LMP, CatB activation and increased Bax protein levels following its translocation to mitochondria. Mitochondrial hyperpolarization, followed by membrane potential dissipation and cleavage of caspase-3, also resulted in cell death after 24 h of incubation. We also found that BPC11-mediated LC3II formation and increased p62 protein levels, suggesting blocked autophagy, probably due to LMP. Interestingly, the treatment of Tm5 and 4C11(-) cells with 3-methyladenine (3-MA), an inhibitor of the initial stage of autophagy, potentiated the effects of BPC11. We conclude that BPC11 is an anti-melanoma agent and that autophagy may be acting as a mechanism of melanoma cells resistance. Also, these data highlight the importance of studies involving autophagy and apoptosis during pre-clinical studies of new drugs with anticancer properties.

  7. Curcumin attenuates paraquat-induced cell death in human neuroblastoma cells through modulating oxidative stress and autophagy.

    PubMed

    Jaroonwitchawan, Thiranut; Chaicharoenaudomrung, Nipha; Namkaew, Jirapat; Noisa, Parinya

    2017-01-01

    Paraquat is a neurotoxic agent, and oxidative stress plays an important role in neuronal cell death after paraquat exposure. In this study, we assessed the neuroprotective effect of curcumin against paraquat and explored the underlying mechanisms of curcumin in vitro. Curcumin treatment prevented paraquat-induced reactive oxygen species (ROS) and apoptotic cell death. Curcumin also exerted a neuroprotective effect by increasing the expression of anti-apoptotic and antioxidant genes. The pretreatment of curcumin significantly decreased gene expression and protein production of amyloid precursor protein. The activation of autophagy process was found defective in paraquat-induced cells, indicated by the accumulation and reduction of LC3I/II. Noteworthy, curcumin restored LC3I/II expression after the pretreatment. Collectively, curcumin demonstrated as a prominent suppressor of ROS, and could reverse autophagy induction in SH-SY5Y cells. The consequences of this were the reduction of APP production and prevention of SH-SY5Y cells from apoptosis. Altogether, curcumin potentially serves as a therapeutic agent of neurodegenerative diseases, associated with ROS overproduction and autophagy dysfunction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Silymarin modulates doxorubicin-induced oxidative stress, Bcl-xL and p53 expression while preventing apoptotic and necrotic cell death in the liver

    SciTech Connect

    Patel, Nirav; Joseph, Cecil; Corcoran, George B.; Ray, Sidhartha D.

    2010-06-01

    The emergence of silymarin (SMN) as a natural remedy for liver diseases, coupled with its entry into NIH clinical trial, signifies its hepatoprotective potential. SMN is noted for its ability to interfere with apoptotic signaling while acting as an antioxidant. This in vivo study was designed to explore the hepatotoxic potential of Doxorubicin (Dox), the well-known cardiotoxin, and in particular whether pre-exposures to SMN can prevent hepatotoxicity by reducing Dox-induced free radical mediated oxidative stress, by modulating expression of apoptotic signaling proteins like Bcl-xL, and by minimizing liver cell death occurring by apoptosis or necrosis. Groups of male ICR mice included Control, Dox alone, SMN alone, and Dox with SMN pre/co-treatment. Control and Dox groups received saline i.p. for 14 days. SMN was administered p.o. for 14 days at 16 mg/kg/day. An approximate LD{sub 50} dose of Dox, 60 mg/kg, was administered i.p. on day 12 to animals receiving saline or SMN. Animals were euthanized 48 h later. Dox alone induced frank liver injury (> 50-fold increase in serum ALT) and oxidative stress (> 20-fold increase in malondialdehyde [MDA]), as well as direct damage to DNA (> 15-fold increase in DNA fragmentation). Coincident genomic damage and oxidative stress influenced genomic stability, reflected in increased PARP activity and p53 expression. Decreases in Bcl-xL protein coupled with enhanced accumulation of cytochrome c in the cytosol accompanied elevated indexes of apoptotic and necrotic cell death. Significantly, SMN exposure reduced Dox hepatotoxicity and associated apoptotic and necrotic cell death. The effects of SMN on Dox were broad, including the ability to modulate changes in both Bcl-xL and p53 expression. In animals treated with SMN, tissue Bcl-xL expression exceeded control values after Dox treatment. Taken together, these results demonstrated that SMN (i) reduced, delayed onset, or prevented toxic effects of Dox which are typically associated

  9. Ubiquitinated Sirtuin 1 (SIRT1) Function Is Modulated during DNA Damage-induced Cell Death and Survival*

    PubMed Central

    Peng, Lirong; Yuan, Zhigang; Li, Yixuan; Ling, Hongbo; Izumi, Victoria; Fang, Bin; Fukasawa, Kenji; Koomen, John; Chen, Jiandong; Seto, Edward

    2015-01-01

    Downstream signaling of physiological and pathological cell responses depends on post-translational modification such as ubiquitination. The mechanisms regulating downstream DNA damage response (DDR) signaling are not completely elucidated. Sirtuin 1 (SIRT1), the founding member of Class III histone deacetylases, regulates multiple steps in DDR and is closely associated with many physiological and pathological processes. However, the role of post-translational modification or ubiquitination of SIRT1 during DDR is unclear. We show that SIRT1 is dynamically and distinctly ubiquitinated in response to DNA damage. SIRT1 was ubiquitinated by the MDM2 E3 ligase in vitro and in vivo. SIRT1 ubiquitination under normal conditions had no effect on its enzymatic activity or rate of degradation; hypo-ubiquitination, however, reduced SIRT1 nuclear localization. Ubiquitination of SIRT1 affected its function in cell death and survival in response to DNA damage. Our results suggest that ubiquitination is required for SIRT1 function during DDR. PMID:25670865

  10. Ubiquitinated sirtuin 1 (SIRT1) function is modulated during DNA damage-induced cell death and survival.

    PubMed

    Peng, Lirong; Yuan, Zhigang; Li, Yixuan; Ling, Hongbo; Izumi, Victoria; Fang, Bin; Fukasawa, Kenji; Koomen, John; Chen, Jiandong; Seto, Edward

    2015-04-03

    Downstream signaling of physiological and pathological cell responses depends on post-translational modification such as ubiquitination. The mechanisms regulating downstream DNA damage response (DDR) signaling are not completely elucidated. Sirtuin 1 (SIRT1), the founding member of Class III histone deacetylases, regulates multiple steps in DDR and is closely associated with many physiological and pathological processes. However, the role of post-translational modification or ubiquitination of SIRT1 during DDR is unclear. We show that SIRT1 is dynamically and distinctly ubiquitinated in response to DNA damage. SIRT1 was ubiquitinated by the MDM2 E3 ligase in vitro and in vivo. SIRT1 ubiquitination under normal conditions had no effect on its enzymatic activity or rate of degradation; hypo-ubiquitination, however, reduced SIRT1 nuclear localization. Ubiquitination of SIRT1 affected its function in cell death and survival in response to DNA damage. Our results suggest that ubiquitination is required for SIRT1 function during DDR.

  11. NQDI 1, an inhibitor of ASK1 attenuates acute ischemic renal injury by modulating oxidative stress and cell death.

    PubMed

    El Eter, Eman

    2013-09-01

    Apoptosis signal-regulating kinase 1 (ASK1) is among the signaling events that lead to postischemic cell death. Inhibition of ASK1 pathway protected hearts from ischemic damage. The present study evaluated the renal protective effects of NQDI 1, an inhibitor of ASK1, in an animal model of acute ischemic renal failure. Male Wistar rats were subjected to right nephrectomy and clamping of left renal pedicle for 45 min, or sham operation. The administration of NQDI 1 attenuated renal dysfunction and histological changes characteristic for renal ischemia/reperfusion injury (IRI). Apoptosis of renal tissues, as detected by TUNEL staining, was also reduced together with p53 protein expression, and renal levels of MDA and SOD with NQDI 1 administration and BCL2 was up regulated. In conclusion, inhibition of ASK1 is of therapeutic potential against acute ischemic renal injury. Its protective effects are mediated via inhibition of apoptosis and oxidative stress.

  12. Rapamycin protects against neuronal death and improves neurological function with modulation of microglia after experimental intracerebral hemorrhage in rats.

    PubMed

    Li, D; Liu, F; Yang, T; Jin, T; Zhang, H; Luo, X; Wang, M

    2016-09-30

    Intracerebral hemorrhage (ICH) results in a devastating brain disorder with high mortality and poor prognosis and effective therapeutic intervention for the disease remains a challenge at present. The present study investigated the neuroprotective effects of rapamycin on ICH-induced brain damage and the possible involvement of activated microglia. ICH was induced in rats by injection of type IV collagenase into striatum. Different dose of rapamycin was systemically administrated by intraperitoneal injection beginning at 1 h after ICH induction. Western blot analysis showed that ICH led to a long-lasting increase of phosphorylated mTOR and this hyperactivation of mTOR was reduced by systemic administration of rapamycin. Rapamycin treatment significantly improved the sensorimotor deficits induced by ICH, and attenuated ICH-induced brain edema formation as well as lesion volume. Nissl and Fluoro-Jade C staining demonstrated that administration with rapamycin remarkably decreased neuronal death surrounding the hematoma at 7 d after ICH insult. ELISA and real-time quantitative PCR demonstrated that rapamycin inhibited ICH-induced excessive expression of TNF-α and IL-1β in ipsilateral hemisphere. Furthermore, activation of microglia induced by ICH was significantly suppressed by rapamycin administration. These data indicated that treatment of rapamycin following ICH decreased the brain injuries and neuronal death at the peri-hematoma striatum, and increased neurological function, which associated with reduced the levels of proinflammatory cytokines and activated microglia. The results provide novel insight into the neuroprotective therapeutic strategy of rapamycin for ICH insult, which possibly involving the regulation of microglial activation.

  13. Hijacking of the jasmonate pathway by the mycotoxin fumonisin B1 (FB1) to initiate programmed cell death in Arabidopsis is modulated by RGLG3 and RGLG4.

    PubMed

    Zhang, Xu; Wu, Qian; Cui, Shao; Ren, Jiao; Qian, Wanqiang; Yang, Yang; He, Shanping; Chu, Jinfang; Sun, Xiaohong; Yan, Cunyu; Yu, Xiangchun; An, Chengcai

    2015-05-01

    The mycotoxin fumonisin B1 (FB1) is a strong inducer of programmed cell death (PCD) in plants, but its underlying mechanism remains unclear. Here, we describe two ubiquitin ligases, RING DOMAIN LIGASE3 (RGLG3) and RGLG4, which control FB1-triggered PCD by modulating the jasmonate (JA) signalling pathway in Arabidopsis thaliana. RGLG3 and RGLG4 transcription was sensitive to FB1. Arabidopsis FB1 sensitivity was suppressed by loss of function of RGLG3 and RGLG4 and was increased by their overexpression. Thus RGLG3 and RGLG4 have coordinated and positive roles in FB1-elicited PCD. Mutated JA perception by coi1 disrupted the RGLG3- and RGLG4-related response to FB1 and interfered with their roles in cell death. Although FB1 induced JA-responsive defence genes, it repressed growth-related, as well as JA biosynthesis-related, genes. Consistently, FB1 application reduced JA content in wild-type plants. Furthermore, exogenously applied salicylic acid additively suppressed JA signalling with FB1 treatment, suggesting that FB1-induced salicylic acid inhibits the JA pathway during this process. All of these effects were attenuated in rglg3 rglg4 plants. Altogether, these data suggest that the JA pathway is hijacked by the toxin FB1 to elicit PCD, which is coordinated by Arabidopsis RGLG3 and RGLG4. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  14. Immunological effects of sublingual immunotherapy: clinical efficacy is associated with modulation of programmed cell death ligand 1, IL-10, and IgG4.

    PubMed

    Piconi, Stefania; Trabattoni, Daria; Rainone, Veronica; Borgonovo, Linda; Passerini, Simone; Rizzardini, Giuliano; Frati, Franco; Iemoli, Enrico; Clerici, Mario

    2010-12-15

    Sublingual immunotherapy (SLIT) is an alternate route of administration of allergen-specific immunotherapy with an improved safety profile; to clarify the immune mechanisms elicited by this therapy, we analyzed the clinical and immunologic effects of SLIT in patients with a clinical history of ragweed sensitization. To analyze possible difference among immunotherapeutic protocols, we also compared patients receiving preseasonal, seasonal, or prolonged sublingual therapy (≥ 3 y); patients receiving symptomatic therapy alone were enrolled as well in the study. Clinical and immunological parameters were measured twice in and out of the pollination period. Clinical benefits, as measured by the visual analog scale for symptoms and for use of drugs, were evident in all three groups of individuals receiving immunotherapy, but were significantly better in patients undergoing prolonged SLIT. Immunologically, SLIT resulted in increased IL-10 production, programmed cell death ligand 1 expression, and concentration of allergen-specific IgG4, as well as in the reduction of CD80 and CD86 expression and IL-4 production. SLIT, thus, is associated with modulation of programmed cell death ligand 1 expression and IL-10 synthesis and favors the production of allergen-specific IgG4. These effects are evident from the first pollen season, independently from therapeutic regimen (preseasonal or seasonal) even if a prolonged treatment is necessary to obtain full clinical efficacy. A more detailed understanding of the interaction of allergen and APCs within the oral mucosa will allow improved targeting of allergy vaccine.

  15. In vivo siRNA delivery of Keap1 modulates death and survival signaling pathways and attenuates concanavalin-A-induced acute liver injury in mice

    PubMed Central

    González-Rodríguez, Águeda; Reibert, Bjorn; Amann, Thomas; Constien, Rainier; Rondinone, Cristina M.; Valverde, Ángela M.

    2014-01-01

    Oxidative stress contributes to the progression of acute liver failure (ALF). Transcription factor nuclear factor-erythroid 2-related factor (Nrf2) serves as an endogenous regulator by which cells combat oxidative stress. We have investigated liver damage and the balance between death and survival signaling pathways in concanavalin A (ConA)-mediated ALF using in vivo siRNA delivery targeting Keap1 in hepatocytes. For that goal, mice were injected with Keap1- or luciferase-siRNA-containing liposomes via the tail vein. After 48 hours, ALF was induced by ConA. Liver histology, pro-inflammatory mediators, antioxidant responses, cellular death, and stress and survival signaling were assessed. Keap1 mRNA and protein levels significantly decreased in livers of Keap1-siRNA-injected mice. In these animals, histological liver damage was less evident than in control mice when challenged with ConA. Likewise, markers of cellular death (FasL and caspases 8, 3 and 1) decreased at 4 and 8 hours post-injection. Nuclear Nrf2 and its target, hemoxygenase 1 (HO1), were elevated in Keap1-siRNA-injected mice compared with control animals, resulting in reduced oxidative stress in the liver. Similarly, mRNA levels of pro-inflammatory cytokines were reduced in livers from Keap1-siRNA-injected mice. At the molecular level, activation of c-jun (NH2) terminal kinase (JNK) was ameliorated, whereas the insulin-like growth factor I receptor (IGFIR) survival pathway was maintained upon ConA injection in Keap1-siRNA-treated mice. In conclusion, our results have revealed a potential therapeutic use of in vivo siRNA technology targeted to Keap1 to combat oxidative stress by modulating Nrf2-mediated antioxidant responses and IGFIR survival signaling during the progression of ALF. PMID:24997191

  16. Subtype-Specific Radiation Response and Therapeutic Effect of FAS Death Receptor Modulation in Human Breast Cancer.

    PubMed

    Lee, Chen-Ting; Zhou, Yingchun; Roy-Choudhury, Kingshuk; Siamakpour-Reihani, Sharareh; Young, Kenneth; Hoang, Peter; Kirkpatrick, John P; Chi, Jen-Tsan A; Dewhirst, Mark W; Horton, Janet K

    2017-08-01

    Breast cancer is the most common malignancy diagnosed among women and represents a heterogeneous group of subtypes. Radiation therapy is a critical component of treatment for breast cancer patients. However, little is known about radiation response among these intrinsic subtypes. In previous studies, we identified a significant induction of FAS after irradiation in biologically favorable breast cancer patients and breast cancer cell lines. Here, we expanded our study and investigated radiation response in a mouse model of breast cancer. MCF7 (luminal), HCC1954 (HER2(+)) or SUM159 (basal) cells were implanted orthotopically into the dorsal mammary fat pad of nude mice. These mice were then treated with different doses of radiation to assess tumor growth control. We further investigated the therapeutic effect of FAS modulation by silencing FAS in radiation-responsive tumors and injecting FAS agonist antibody into radiation-resistant tumors. Exposure to radiation inhibited MCF7, and to a lesser extent HCC1954 tumor growth in a dose-dependent manner. In contrast, SUM159 tumors were resistant to radiation. The estimated TCD50 values were 19.3 Gy for MCF7 and 44.9 Gy for SUM159. Radiation induced FAS expression in MCF7 tumors, but not SUM159 tumors. We found that silencing of FAS did not negatively impact radiation response in MCF7 tumors, possibly due to compensation by other apoptotic pathways. On the other hand, FAS activating antibody in combination with radiation treatment delayed SUM159 and HCC1954 tumor growth. However, it did not reach statistical significance compared to radiation treatment alone. Our results suggest that there is intrinsic variation in radiation response among breast cancer subtypes. FAS activation concurrent with radiation slows tumor growth in the radiation-resistant subtypes, but the effect was not significant. Alternative subtype-specific modulators of radiation response are under investigation.

  17. Bifurcation analysis and potential landscapes of the p53-Mdm2 module regulated by the co-activator programmed cell death 5.

    PubMed

    Bi, Yuanhong; Yang, Zhuoqin; Zhuge, Changjing; Lei, Jinzhi

    2015-11-01

    The dynamics of p53 play important roles in the regulation of cell fate decisions in response to various stresses, and programmed cell death 5 (PDCD5) functions as a co-activator of p53 that modulates p53 dynamics. In the present paper, we investigated how p53 dynamics are modulated by PDCD5 during the deoxyribose nucleic acid damage response using methods of bifurcation analysis and potential landscape. Our results revealed that p53 activities display rich dynamics under different PDCD5 levels, including monostability, bistability with two stable steady states, oscillations, and the coexistence of a stable steady state (or two states) and an oscillatory state. The physical properties of the p53 oscillations were further demonstrated by the potential landscape in which the potential force attracts the system state to the limit cycle attractor, and the curl flux force drives coherent oscillation along the cyclic trajectory. We also investigated the efficiency with which PDCD5 induced p53 oscillations. We show that Hopf bifurcation can be induced by increasing the PDCD5 efficiency and that the system dynamics exhibited clear transition features in both barrier height and energy dissipation when the efficiency was close to the bifurcation point.

  18. Bifurcation analysis and potential landscapes of the p53-Mdm2 module regulated by the co-activator programmed cell death 5

    NASA Astrophysics Data System (ADS)

    Bi, Yuanhong; Yang, Zhuoqin; Zhuge, Changjing; Lei, Jinzhi

    2015-11-01

    The dynamics of p53 play important roles in the regulation of cell fate decisions in response to various stresses, and programmed cell death 5 (PDCD5) functions as a co-activator of p53 that modulates p53 dynamics. In the present paper, we investigated how p53 dynamics are modulated by PDCD5 during the deoxyribose nucleic acid damage response using methods of bifurcation analysis and potential landscape. Our results revealed that p53 activities display rich dynamics under different PDCD5 levels, including monostability, bistability with two stable steady states, oscillations, and the coexistence of a stable steady state (or two states) and an oscillatory state. The physical properties of the p53 oscillations were further demonstrated by the potential landscape in which the potential force attracts the system state to the limit cycle attractor, and the curl flux force drives coherent oscillation along the cyclic trajectory. We also investigated the efficiency with which PDCD5 induced p53 oscillations. We show that Hopf bifurcation can be induced by increasing the PDCD5 efficiency and that the system dynamics exhibited clear transition features in both barrier height and energy dissipation when the efficiency was close to the bifurcation point.

  19. miR-125b promotes cell death by targeting spindle assembly checkpoint gene MAD1 and modulating mitotic progression

    PubMed Central

    Bhattacharjya, S; Nath, S; Ghose, J; Maiti, G P; Biswas, N; Bandyopadhyay, S; Panda, C K; Bhattacharyya, N P; Roychoudhury, S

    2013-01-01

    The spindle assembly checkpoint (SAC) is a ‘wait-anaphase' mechanism that has evolved in eukaryotic cells in response to the stochastic nature of chromosome–spindle attachments. In the recent past, different aspects of the SAC regulation have been described. However, the role of microRNAs in the SAC is vaguely understood. We report here that Mad1, a core SAC protein, is repressed by human miR-125b. Mad1 serves as an adaptor protein for Mad2 – which functions to inhibit anaphase entry till the chromosomal defects in metaphase are corrected. We show that exogenous expression of miR-125b, through downregulation of Mad1, delays cells at metaphase. As a result of this delay, cells proceed towards apoptotic death, which follows from elevated chromosomal abnormalities upon ectopic expression of miR-125b. Moreover, expressions of Mad1 and miR-125b are inversely correlated in a variety of cancer cell lines, as well as in primary head and neck tumour tissues. We conclude that increased expression of miR-125b inhibits cell proliferation by suppressing Mad1 and activating the SAC transiently. We hypothesize an optimum Mad1 level and thus, a properly scheduled SAC is maintained partly by miR-125b. PMID:23099851

  20. Quercetin derivative induces cell death in glioma cells by modulating NF-κB nuclear translocation and caspase-3 activation.

    PubMed

    Kiekow, Cíntia J; Figueiró, Fabrício; Dietrich, Fabrícia; Vechia, Luciana Dalla; Pires, Elisa N S; Jandrey, Elisa H F; Gnoatto, Simone C B; Salbego, Christianne G; Battastini, Ana Maria O; Gosmann, Grace

    2016-03-10

    Treated glioblastoma multiforme (GBM) patients only survive 6 to 14months after diagnosis; therefore, the development of novel therapeutic strategies to treat gliomas remains critically necessary. Considering that phenolic compounds, like quercetin, have the potential to be used in the chemotreatment of gliomas and that some flavonoids exhibit the ability to cross the BBB, in the present study, we investigated the antitumor effect of flavonoids (including chalcones, flavones, flavanones and flavonols). Initially their activities were tested in C6 glioma cells screened using the MTT method, resulting in the selection of chalcone 2 whose feasibility was confirmed by a Trypan Blue exclusion assay in the low μM range on C6 glioma cells. Cell cycle and apoptotic death analyses on C6 glioma cells were also performed, and chalcone 2 increased the apoptosis of the cells but did not alter the cell cycle progression. In addition, treatments with these two compounds were not cytotoxic to hippocampal organotypic cultures, a model of healthy neural cells. Furthermore, the results indicated that 2 induced apoptosis by inhibition of NF-κB and activation of active caspase-3 in glioma cells, suggesting that it is a potential prototype to develop new treatments for GBM in the future. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. The regulation of p53 up-regulated modulator of apoptosis by JNK/c-Jun pathway in β-amyloid-induced neuron death.

    PubMed

    Akhter, Rumana; Sanphui, Priyankar; Das, Hrishita; Saha, Pampa; Biswas, Subhas Chandra

    2015-09-01

    Neuronal loss in selective areas of brain underlies the pathology of Alzheimer's disease (AD). Recent evidences place oligomeric β-amyloid (Aβ) central to the disease. However, mechanism of neuron death in response to Aβ remains elusive. Activation of the c-Jun N-terminal kinase (JNK) pathway and induction of the AP-1 transcription factor c-Jun are reported in AD. However, targets of JNK/c-Jun in Aβ-induced neuron death are mostly unknown. Our study shows that pro-apoptotic proteins, Bim (Bcl-2 interacting mediator of cell death) and Puma (p53 up-regulated modulator of apoptosis) are targets of c-Jun in Aβ-treated neurons. We demonstrate that the JNK/c-Jun pathway is activated, in cultures of cortical neurons following treatment with oligomeric Aβ and in AD transgenic mice, and that inhibition of this pathway by selective inhibitor blocks induction of Puma by Aβ. We also find that both JNK and p53 pathways co-operatively regulate Puma expression in Aβ-treated neurons. Moreover, we identified a novel AP1-binding site on rat puma gene which is necessary for direct binding of c-Jun with Puma promoter. Finally, we find that knocking down of c-Jun by siRNA provides significant protection from Aβ toxicity and that induction of Bim and Puma by Aβ in neurons requires c-Jun. Taken together, our results suggest that both Bim and Puma are target of c-Jun and elucidate the intricate regulation of Puma expression by JNK/c-Jun and p53 pathways in neurons upon Aβ toxicity. JNK/c-Jun pathway is shown to be activated in neurons of the Alzheimer's disease (AD) brain and plays a vital role in neuron death in AD models. However, downstream targets of c-Jun in this disease have not been thoroughly elucidated. Our study shows that two important pro-apoptotic proteins, Bim (Bcl-2 interacting mediator of cell death) and Puma (p53 up-regulated modulator of apoptosis) are targets of c-Jun in Aβ-treated neurons. We demonstrate that the JNK/c-jun pathway is activated, in cultures

  2. Podophyllotoxin and Rutin Modulates Ionizing Radiation-Induced Oxidative Stress and Apoptotic Cell Death in Mice Bone Marrow and Spleen

    PubMed Central

    Singh, Abhinav; Yashavarddhan, M. H.; Kalita, Bhargab; Ranjan, Rajiv; Bajaj, Sania; Prakash, Hridayesh; Gupta, Manju Lata

    2017-01-01

    The present study is aimed to investigate the radioprotective efficacy of G-003M (combination of podophyllotoxin and rutin) against gamma radiation-induced oxidative stress and subsequent cell death in mice bone marrow and spleen. Prophylactic administration of G-003M (−1 h) rendered more than 85% survival in mice exposed to 9 Gy (lethal dose) with dose reduction factor of 1.26. G-003M pretreated mice demonstrated significantly reduced level of reactive oxygen species, membrane lipid peroxidation, and retained glutathione level. In the same group, we obtained increased expression of master redox regulator, nuclear factor erythroid-derived like-2 factor (Nrf-2), and its downstream targets (heme oxygenase-1, Nqo-1, glutathione S-transferase, and thioredoxin reductase-1). In addition, G-003M preadministration has also shown a significant reduction in Keap-1 level (Nrf-2 inhibitor). Radiation-induced lethality was significantly amended in combination-treated (G-003M) mice as demonstrated by reduced 8-OHdG, annexin V FITC+ cells, and restored mitochondrial membrane potential. Expression of antiapoptotic protein Bcl-2 and Bcl-xL was restored in G-003M pretreated group. However, proapoptotic proteins (Puma, Bax, Bak, Caspase-3, and Caspase-7) were significantly declined in this group. Further analysis of immune cells revealed G-003M-mediated restoration of CD3 and CD19 receptor, which was found decreased to significant level following irradiation. Similarly, Gr-1, a marker of granulocytes, was also retained by G-003M administration prior to radiation. Modulatory potential of this formulation (G-003M) can be exploited as a safe and effective countermeasure against radiation-induced lymphohemopoietic injury. PMID:28289414

  3. Podophyllotoxin and Rutin Modulates Ionizing Radiation-Induced Oxidative Stress and Apoptotic Cell Death in Mice Bone Marrow and Spleen.

    PubMed

    Singh, Abhinav; Yashavarddhan, M H; Kalita, Bhargab; Ranjan, Rajiv; Bajaj, Sania; Prakash, Hridayesh; Gupta, Manju Lata

    2017-01-01

    The present study is aimed to investigate the radioprotective efficacy of G-003M (combination of podophyllotoxin and rutin) against gamma radiation-induced oxidative stress and subsequent cell death in mice bone marrow and spleen. Prophylactic administration of G-003M (-1 h) rendered more than 85% survival in mice exposed to 9 Gy (lethal dose) with dose reduction factor of 1.26. G-003M pretreated mice demonstrated significantly reduced level of reactive oxygen species, membrane lipid peroxidation, and retained glutathione level. In the same group, we obtained increased expression of master redox regulator, nuclear factor erythroid-derived like-2 factor (Nrf-2), and its downstream targets (heme oxygenase-1, Nqo-1, glutathione S-transferase, and thioredoxin reductase-1). In addition, G-003M preadministration has also shown a significant reduction in Keap-1 level (Nrf-2 inhibitor). Radiation-induced lethality was significantly amended in combination-treated (G-003M) mice as demonstrated by reduced 8-OHdG, annexin V FITC(+) cells, and restored mitochondrial membrane potential. Expression of antiapoptotic protein Bcl-2 and Bcl-xL was restored in G-003M pretreated group. However, proapoptotic proteins (Puma, Bax, Bak, Caspase-3, and Caspase-7) were significantly declined in this group. Further analysis of immune cells revealed G-003M-mediated restoration of CD3 and CD19 receptor, which was found decreased to significant level following irradiation. Similarly, Gr-1, a marker of granulocytes, was also retained by G-003M administration prior to radiation. Modulatory potential of this formulation (G-003M) can be exploited as a safe and effective countermeasure against radiation-induced lymphohemopoietic injury.

  4. Bursicon Functions within the Drosophila Central Nervous System to Modulate Wing Expansion Behavior, Hormone Secretion, and Cell Death

    PubMed Central

    Peabody, Nathan C.; Diao, Fengqiu; Luan, Haojiang; Wang, Howard; Dewey, Elizabeth M.; Honegger, Hans-Willi; White, Benjamin H.

    2009-01-01

    Hormones are often responsible for synchronizing somatic physiological changes with changes in behavior. Ecdysis (i.e. the shedding of the exoskeleton) in insects has served as a useful model for elucidating the molecular and cellular mechanisms of this synchronization, and has provided numerous insights into the hormonal coordination of body and behavior. An example in which the mechanisms have remained enigmatic is the neurohormone bursicon, which after the final molt, coordinates the plasticization and tanning of the initially folded wings with behaviors that drive wing expansion. The somatic effects of the hormone are governed by bursicon that is released into the blood from neurons in the abdominal ganglion (the BAG), which die after wing expansion. How bursicon induces the behavioral programs required for wing expansion, however, has remained unknown. Here we show by targeted suppression of excitability that a pair of bursicon-immunoreactive neurons distinct from the BAG and located within the subesophageal ganglion in Drosophila (the BSEG) is involved in controlling wing expansion behaviors. Unlike the BAG, the BSEG arborize widely in the nervous system, including within the abdominal neuromeres, suggesting that, in addition to governing behavior, they also may modulate the BAG. Indeed, we show that animals lacking bursicon receptor function have deficits both in the humoral release of bursicon and in post-eclosion apoptosis of the BAG. Our results reveal novel neuromodulatory functions for bursicon and support the hypothesis that the BSEG are essential for orchestrating both the behavioral and somatic processes underlying wing expansion. PMID:19118171

  5. Death Imagery and Death Anxiety.

    ERIC Educational Resources Information Center

    McDonald, Rita T.; Hilgendorf, William A.

    1986-01-01

    Investigated the relationship between death imagery and death anxiety among 179 undergraduate students. Results reveal subjects with low death anxiety scores had more positive death images. Subjects who imagined death to be young had a more positive image of death. Death was seen as male by majority of respondents. (Author/BL)

  6. α-Tocopherol at Nanomolar Concentration Protects PC12 Cells from Hydrogen Peroxide-Induced Death and Modulates Protein Kinase Activities

    PubMed Central

    Zakharova, Irina O.; Sokolova, Tatyana V.; Bayunova, Liubov V.; Vlasova, Yulia A.; Rychkova, Maria P.; Avrova, Natalia F.

    2012-01-01

    The aim of this work was to compare protective and anti-apoptotic effects of α-tocopherol at nanomolar and micromolar concentrations against 0.2 mM H2O2-induced toxicity in the PC12 neuronal cell line and to reveal protein kinases that contribute to α-tocopherol protective action. The protection by 100 nM α-tocopherol against H2O2-induced PC12 cell death was pronounced if the time of pre-incubation with α-tocopherol was 3–18 h. For the first time, the protective effect of α-tocopherol was shown to depend on its concentration in the nanomolar range (1 nM < 10 nM < 100 nM), if the pre-incubation time was 18 h. Nanomolar and micromolar α-tocopherol decreased the number of PC12 cells in late apoptosis induced by H2O2 to the same extent if pre-incubation time was 18 h. Immunoblotting data showed that α-tocopherol markedly diminished the time of maximal activation of extracellular signal-regulated kinase 1/2 (ERK 1/2) and protein kinase B (Akt)-induced in PC12 cells by H2O2. Inhibitors of MEK 1/2, PI 3-kinase and protein kinase C (PKC) diminished the protective effect of α-tocopherol against H2O2-initiated toxicity if the pre-incubation time was long. The modulation of ERK 1/2, Akt and PKC activities appears to participate in the protection by α-tocopherol against H2O2-induced death of PC12 cells. The data obtained suggest that inhibition by α-tocopherol in late stage ERK 1/2 and Akt activation induced by H2O2 in PC12 cells makes contribution to its protective effect, while total inhibition of these enzymes is not protective. PMID:23109870

  7. Newly synthesized quinazolinone HMJ-38 suppresses angiogenetic responses and triggers human umbilical vein endothelial cell apoptosis through p53-modulated Fas/death receptor signaling

    SciTech Connect

    Chiang, Jo-Hua; Yang, Jai-Sing; Lu, Chi-Cheng; Hour, Mann-Jen; Chang, Shu-Jen; Lee, Tsung-Han; Chung, Jing-Gung

    2013-06-01

    The current study aims to investigate the antiangiogenic responses and apoptotic death of human umbilical vein endothelial cells (HUVECs) by a newly synthesized compound named 2-(3′-methoxyphenyl)-6-pyrrolidinyl-4-quinazolinone (HMJ-38). This work attempted to not only explore the effects of angiogenesis on in vivo and ex vivo studies but also hypothesize the implications for HUVECs (an ideal cell model for angiogenesis in vitro) and further undermined apoptotic experiments to verify the underlying molecular signaling by HMJ-38. Our results demonstrated that HMJ-38 significantly inhibited blood vessel growth and microvessel formation by the mouse Matrigel plug assay of angiogenesis, and the suppression of microsprouting from the rat aortic ring assay was observed after HMJ-38 exposure. In addition, HMJ-38 disrupted the tube formation and blocked the ability of HUVECs to migrate in response to VEGF. We also found that HMJ-38 triggered cell apoptosis of HUVECs in vitro. HMJ-38 concentration-dependently suppressed viability and induced apoptotic damage in HUVECs. HMJ-38-influenced HUVECs were performed by determining the oxidative stress (ROS production) and ATM/p53-modulated Fas and DR4/DR5 signals that were examined by flow cytometry, Western blotting, siRNA and real-time RT-PCR analyses, respectively. Our findings demonstrate that p53-regulated extrinsic pathway might fully contribute to HMJ-38-provoked apoptotic death in HUVECs. In view of these observations, we conclude that HMJ-38 reduces angiogenesis in vivo and ex vivo as well as induces apoptosis of HUVECs in vitro. Overall, HMJ-38 has a potent anti-neovascularization effect and could warrant being a vascular targeting agent in the future. - Highlights: • HMJ-38 suppresses angiogenic actions in vivo and ex vivo. • Inhibitions of blood vessel and microvessel formation by HMJ-38 are acted. • Cytotoxic effects of HUVECs occur by HMJ-38 challenge. • p53-modulated extrinsic pathway contributes to HMJ-38

  8. Mechanisms of drug sensitization to TRA-8, an agonistic death receptor 5 antibody, involve modulation of the intrinsic apoptotic pathway in human breast cancer cells.

    PubMed

    Amm, Hope M; Zhou, Tong; Steg, Adam D; Kuo, Huichien; Li, Yufeng; Buchsbaum, Donald J

    2011-04-01

    TRA-8, a monoclonal antibody to death receptor 5 induces apoptosis in various cancer cells; however, the degree of sensitivity varies from highly sensitive to resistant. We have previously shown that resistance to TRA-8 can be reversed by using chemotherapeutic agents, but the mechanism underlying this sensitization was not fully understood. Here, we examined the combination of TRA-8 with doxorubicin or bortezomib in breast cancer cells. In TRA-8-resistant BT-474 and T47D cells, both chemotherapy agents synergistically sensitized cells to TRA-8 cytotoxicity with enhanced activation of apoptosis shown by cleavage of caspases and PARP, reduced Bid, increased proapoptotic Bcl-2 proteins, and increased mitochondrial membrane depolarization. Doxorubicin or bortezomib combined with TRA-8 also reduced Bcl-XL and X-linked inhibitors of apoptosis (XIAP) in treated cells. Furthermore, targeting these proteins with pharmacologic modulators, AT-101, BH3I-2' and AT-406, produced sensitization to TRA-8. TRA-8 combined with AT-101 or BH3I-2', inhibitors of antiapoptotic Bcl-2 proteins, produced synergistic cytotoxicity against ZR-75-1, BT-474, and T47D cells. The IAP-targeting compound, AT-406, was synergistic with TRA-8 in BT-474 cells, and to a lesser extent T47D cells. Activation of the intrinsic apoptotic pathway was a common mechanism associated with sensitization of TRA-8-resistant breast cancer cell lines. Collectively, these studies show that the Bcl-2 and IAP families of proteins are involved in TRA-8 and chemotherapy resistance via their modulation of the intrinsic apoptotic pathway. Targeting these proteins with novel agents sensitized TRA-8-resistant breast cancer cells, suggesting this approach may represent a potent therapeutic strategy in the treatment of breast cancer. ©2011 AACR.

  9. Mechanisms of drug sensitization to TRA-8, an agonistic death receptor 5 antibody, involve modulation of the intrinsic apoptotic pathway in human breast cancer cells

    PubMed Central

    Amm, Hope M.; Zhou, Tong; Steg, Adam D.; Kuo, Huichien; Li, Yufeng; Buchsbaum, Donald J.

    2011-01-01

    TRA-8, a monoclonal antibody to death receptor 5 induces apoptosis in various cancer cells; however the degree of sensitivity varies from highly sensitive to resistant. We have previously shown resistance to TRA-8 can be reversed using chemotherapeutic agents, but the mechanism underlying this sensitization was not fully understood. Here, we examined the combination of TRA-8 with doxorubicin or bortezomib in breast cancer cells. In TRA-8 resistant BT-474 and T47D cells, both chemotherapy agents synergistically sensitized cells to TRA-8 cytotoxicity with enhanced activation of apoptosis demonstrated by cleavage of caspases and PARP, reduced Bid, increased pro-apoptotic Bcl-2 proteins, and increased mitochondrial membrane depolarization. Doxorubicin or bortezomib combined with TRA-8 also reduced Bcl-XL and XIAP in treated cells. Furthermore, targeting these proteins with pharmacological modulators, AT-101, BH3I-2′ and AT-406, produced sensitization to TRA-8. TRA-8 combined with AT-101 or BH3I-2′, inhibitors of anti-apoptotic Bcl-2 proteins, produced synergistic cytotoxicity against ZR-75-1, BT-474, and T47D cells. The IAP targeting compound, AT-406, was synergistic with TRA-8 in BT-474 cells and to a lesser extent T47D cells. Activation of the intrinsic apoptotic pathway was a common mechanism associated with sensitization of TRA-8 resistant breast cancer cell lines. Collectively, these studies show that the Bcl-2 and IAP families of proteins are involved in TRA-8 and chemotherapy resistance via their modulation of the intrinsic apoptotic pathway. Targeting these proteins with novel agents sensitized TRA-8 resistant breast cancer cells, suggesting this approach may represent a potent therapeutic strategy in the treatment of breast cancer. PMID:21357440

  10. Jerantinine A induces tumor-specific cell death through modulation of splicing factor 3b subunit 1 (SF3B1)

    PubMed Central

    Chung, Felicia Fei-Lei; Tan, Perry Faith Tze Ming; Raja, Vijay Joseph; Tan, Boon-Shing; Lim, Kuan-Hon; Kam, Toh-Seok; Hii, Ling-Wei; Tan, Si Hoey; See, Sze-Jia; Tan, Yuen-Fen; Wong, Li-Zhe; Yam, Wai Keat; Mai, Chun Wai; Bradshaw, Tracey D.; Leong, Chee-Onn

    2017-01-01

    Precursor mRNA (pre-mRNA) splicing is catalyzed by a large ribonucleoprotein complex known as the spliceosome. Numerous studies have indicated that aberrant splicing patterns or mutations in spliceosome components, including the splicing factor 3b subunit 1 (SF3B1), are associated with hallmark cancer phenotypes. This has led to the identification and development of small molecules with spliceosome-modulating activity as potential anticancer agents. Jerantinine A (JA) is a novel indole alkaloid which displays potent anti-proliferative activities against human cancer cell lines by inhibiting tubulin polymerization and inducing G2/M cell cycle arrest. Using a combined pooled-genome wide shRNA library screen and global proteomic profiling, we showed that JA targets the spliceosome by up-regulating SF3B1 and SF3B3 protein in breast cancer cells. Notably, JA induced significant tumor-specific cell death and a significant increase in unspliced pre-mRNAs. In contrast, depletion of endogenous SF3B1 abrogated the apoptotic effects, but not the G2/M cell cycle arrest induced by JA. Further analyses showed that JA stabilizes endogenous SF3B1 protein in breast cancer cells and induced dissociation of the protein from the nucleosome complex. Together, these results demonstrate that JA exerts its antitumor activity by targeting SF3B1 and SF3B3 in addition to its reported targeting of tubulin polymerization. PMID:28198434

  11. Genistein inhibition of OGD-induced brain neuron death correlates with its modulation of apoptosis, voltage-gated potassium and sodium currents and glutamate signal pathway.

    PubMed

    Ma, Xue-Ling; Zhang, Feng; Wang, Yu-Xiang; He, Cong-Cong; Tian, Kun; Wang, Hong-Gang; An, Di; Heng, Bin; Liu, Yan-Qiang

    2016-07-25

    In the present study, we established an in vitro model of hypoxic-ischemia via exposing primary neurons of newborn rats to oxygen-glucose deprivation (OGD) and observing the effects of genistein, a soybean isoflavone, on hypoxic-ischemic neuron viability, apoptosis, voltage-activated potassium (Kv) and sodium (Nav) currents, and glutamate receptor subunits. The results indicated that OGD exposure reduced the viability and increased the apoptosis of brain neurons. Meanwhile, OGD exposure caused changes in the current-voltage curves and current amplitude values of voltage-activated potassium and sodium currents; OGD exposure also decreased GluR2 expression and increased NR2 expression. However, genistein at least partially reversed the effects caused by OGD. The results suggest that hypoxic-ischemia-caused neuronal apoptosis/death is related to an increase in K(+) efflux, a decrease in Na(+) influx, a down-regulation of GluR2, and an up-regulation of NR2. Genistein may exert some neuroprotective effects via the modulation of Kv and Nav currents and the glutamate signal pathway, mediated by GluR2 and NR2. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Modulation of P2X4/P2X7/Pannexin-1 sensitivity to extracellular ATP via Ivermectin induces a non-apoptotic and inflammatory form of cancer cell death

    PubMed Central

    Draganov, Dobrin; Gopalakrishna-Pillai, Sailesh; Chen, Yun-Ru; Zuckerman, Neta; Moeller, Sara; Wang, Carrie; Ann, David; Lee, Peter P.

    2015-01-01

    Overexpression of P2X7 receptors correlates with tumor growth and metastasis. Yet, release of ATP is associated with immunogenic cancer cell death as well as inflammatory responses caused by necrotic cell death at sites of trauma or ischemia-reperfusion injury. Using an FDA-approved anti-parasitic agent Ivermectin as a prototype agent to allosterically modulate P2X4 receptors, we can switch the balance between the dual pro-survival and cytotoxic functions of purinergic signaling in breast cancer cells. This is mediated through augmented opening of the P2X4/P2X7-gated Pannexin-1 channels that drives a mixed apoptotic and necrotic mode of cell death associated with activation of caspase-1 and is consistent with pyroptosis. We show that cancer cell death is dependent on ATP release and death signals downstream of P2X7 receptors that can be reversed by inhibition of NADPH oxidases-generated ROS, Ca2+/Calmodulin-dependent protein kinase II (CaMKII) or mitochondrial permeability transition pore (MPTP). Ivermectin induces autophagy and release of ATP and HMGB1, key mediators of inflammation. Potentiated P2X4/P2X7 signaling can be further linked to the ATP rich tumor microenvironment providing a mechanistic explanation for the tumor selectivity of purinergic receptors modulation and its potential to be used as a platform for integrated cancer immunotherapy. PMID:26552848

  13. The Influence of an Educational Intervention Module on Death and Dying on Death Anxiety, Life Satisfaction and Locus of Control Among Middle Aged and Older Adults in North Carolina. Summary and Workshop Guide.

    ERIC Educational Resources Information Center

    Trent, Curtis; And Others

    The research findings of many thanatologists have brought an awareness to the general public that the study of death and dying is an appropriate and instructional need for many people. The attitudes of middle aged and older adults regarding death anxiety, life satisfaction, and locus of control were examined to determine whether adults would…

  14. Death Cafe.

    PubMed

    Miles, Lizzy; Corr, Charles A

    2017-06-01

    This article explains the meaning of the phrase Death Cafe and describes what typically occurs at a Death Cafe gathering. The article traces the history of the Death Cafe movement, explores some reasons why people take part in a Death Cafe gathering, and gives examples of what individuals think they might derive from their participation. In addition, this article notes similarities between the Death Cafe movement and three other developments in the field of death, dying, and bereavement. Finally, this article identifies two provisional lessons that can be drawn from Death Cafe gatherings and the Death Cafe movement itself.

  15. Hydrogen sulfide delays GA-triggered programmed cell death in wheat aleurone layers by the modulation of glutathione homeostasis and heme oxygenase-1 expression.

    PubMed

    Xie, Yanjie; Zhang, Chen; Lai, Diwen; Sun, Ya; Samma, Muhammad Kaleem; Zhang, Jing; Shen, Wenbiao

    2014-01-15

    Hydrogen sulfide (H2S) is considered as a cellular signaling intermediate in higher plants, but corresponding molecular mechanisms and signal transduction pathways in plant biology are still limited. In the present study, a combination of pharmacological and biochemical approaches was used to study the effect of H2S on the alleviation of GA-induced programmed cell death (PCD) in wheat aleurone cells. The results showed that in contrast with the responses of ABA, GA brought about a gradual decrease of l-cysteine desulfhydrase (LCD) activity and H2S production, and thereafter PCD occurred. Exogenous H2S donor sodium hydrosulfide (NaHS) not only effectively blocked the decrease of endogenous H2S release, but also alleviated GA-triggered PCD in wheat aleurone cells. These responses were sensitive to hypotaurine (HT), a H2S scavenger, suggesting that this effect of NaHS was in an H2S-dependent fashion. Further experiment confirmed that H2S, rather than other sodium- or sulphur-containing compounds derived from the decomposing of NaHS, was attributed to the rescuing response. Importantly, the reversing effect was associated with glutathione (GSH) because the NaHS triggered increases of endogenous GSH content and the ratio of GSH/oxidized GSH (GSSG) in GA-treated layers, and the NaHS-mediated alleviation of PCD was markedly eliminated by l-buthionine-sulfoximine (BSO, a selective inhibitor of GSH biosynthesis). The inducible effect of NaHS was also ascribed to the modulation of heme oxygenase-1 (HO-1), because the specific inhibitor of HO-1 zinc protoporphyrin IX (ZnPP) significantly suppressed the NaHS-related responses. By contrast, the above inhibitory effects were reversed partially when carbon monoxide (CO) aqueous solution or bilirubin (BR), two of the by-products of HO-1, was added, respectively. NaHS-triggered HO-1 gene expression in GA-treated layers was also confirmed. Together, the above results clearly suggested that the H2S-delayed PCD in GA-treated wheat

  16. Centella asiatica modulates cancer cachexia associated inflammatory cytokines and cell death in leukaemic THP-1 cells and peripheral blood mononuclear cells (PBMC's).

    PubMed

    Naidoo, Dhaneshree Bestinee; Chuturgoon, Anil Amichund; Phulukdaree, Alisa; Guruprasad, Kanive Parashiva; Satyamoorthy, Kapaettu; Sewram, Vikash

    2017-08-01

    Cancer cachexia is associated with increased pro-inflammatory cytokine levels. Centella asiatica (C. asiatica) possesses antioxidant, anti-inflammatory and anti-tumour potential. We investigated the modulation of antioxidants, cytokines and cell death by C. asiatica ethanolic leaf extract (CLE) in leukaemic THP-1 cells and normal peripheral blood mononuclear cells (PBMC's). Cytotoxcity of CLE was determined at 24 and 72 h (h). Oxidant scavenging activity of CLE was evaluated using the 2, 2-diphenyl-1 picrylhydrazyl (DPPH) assay. Glutathione (GSH) levels, caspase (-8, -9, -3/7) activities and adenosine triphosphate (ATP) levels (Luminometry) were then assayed. The levels of tumour necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β and IL-10 were also assessed using enzyme-linked immunosorbant assay. CLE decreased PBMC viability between 33.25-74.55% (24 h: 0.2-0.8 mg/ml CLE and 72 h: 0.4-0.8 mg/ml CLE) and THP-1 viability by 28.404% (72 h: 0.8 mg/ml CLE) (p < 0.0001). Oxidant scavenging activity was increased by CLE (0.05-0.8 mg/ml) (p < 0.0001). PBMC TNF-α and IL-10 levels were decreased by CLE (0.05-0.8 mg/ml) (p < 0.0001). However, PBMC IL-6 and IL-1β concentrations were increased at 0.05-0.2 mg/ml CLE but decreased at 0.4 mg/ml CLE (p < 0.0001). In THP-1 cells, CLE (0.2-0.8 mg/ml) decreased IL-1β and IL-6 whereas increased IL-10 levels (p < 0.0001). In both cell lines, CLE (0.05-0.2 mg/ml, 24 and 72 h) increased GSH concentrations (p < 0.0001). At 24 h, caspase (-9, -3/7) activities was increased by CLE (0.05-0.8 mg/ml) in PBMC's whereas decreased by CLE (0.2-0.4 mg/ml) in THP-1 cells (p < 0.0001). At 72 h, CLE (0.05-0.8 mg/ml) decreased caspase (-9, -3/7) activities and ATP levels in both cell lines (p < 0.0001). In PBMC's and THP-1 cells, CLE proved to effectively modulate antioxidant activity, inflammatory cytokines and cell death. In THP-1 cells, CLE decreased pro-inflammatory cytokine levels whereas it increased

  17. Voodoo death.

    PubMed

    Lester, David

    2009-01-01

    Scholarly writing on voodoo death is reviewed. Criticisms that voodoo deaths in indigenous societies have never been well documented are refuted with cases medically documented in developed nations. The work of Cannon and Richter on sudden death in animals is reviewed and dismissed as irrelevant for understanding voodoo death. The role of starvation and dehydration is discussed, and it is suggested that the given-up/giving-up hypothesis best fits the phenomenon of voodoo death. Hypotheses for future research are suggested.

  18. Cot Deaths.

    ERIC Educational Resources Information Center

    Tyrrell, Shelagh

    1985-01-01

    Addresses the tragedy of crib deaths, giving particular attention to causes, prevention, and medical research on Sudden Infant Death Syndrome (SIDS). Gives anecdotal accounts of coping strategies used by parents and families of SIDS infants. (DT)

  19. Cot Deaths.

    ERIC Educational Resources Information Center

    Tyrrell, Shelagh

    1985-01-01

    Addresses the tragedy of crib deaths, giving particular attention to causes, prevention, and medical research on Sudden Infant Death Syndrome (SIDS). Gives anecdotal accounts of coping strategies used by parents and families of SIDS infants. (DT)

  20. The effect of MAPK inhibitors and ROS modulators on cell growth and death of H₂O₂-treated HeLa cells.

    PubMed

    Park, Woo Hyun

    2013-08-01

    Reactive oxygen species (ROS) influence the signaling of mitogen‑activated protein kinases (MAPKs) involved in cell survival and death. In the present study, the toxicological effect of hydrogen peroxide (H2O2) on HeLa cervical cancer cells was evaluated following treatment with MAPK inhibitors [MAP kinase or ERK kinase (MEK), c‑Jun N‑terminal kinase (JNK) or p38], N‑acetyl cysteine (NAC) and propyl gallate (PG) (well‑known antioxidants), or L‑buthionine sulfoximine [BSO; an inhibitor of glutathione (GSH) synthesis]. Treatment with 100 µM H2O2 inhibited the growth of HeLa cells and induced cell death, which was accompanied by loss of the mitochondrial membrane potential (MMP; ΔΨm). H2O2 did not induce any specific phase arrests of the cell cycle. ROS levels increased, while GSH levels decreased in H2O2‑treated HeLa cells after 1 and 24 h of treatment. The MAPK inhibitors enhanced H2O2‑induced HeLa cell death, while only p38 inhibitor increased ROS levels. Both NAC and PG attenuated H2O2‑induced HeLa cell growth inhibition and death together with the suppression of ROS levels. BSO increased ROS levels in H2O2‑treated HeLa cells without increasing cell death. The levels of MMP (ΔΨm) loss and GSH depletion were not closely associated with the levels of apoptosis in HeLa cells treated with the MAPK inhibitors, NAC, PG or BSO, in the presence of H2O2. In conclusion, H2O2 induced HeLa cell growth inhibition and death. MAPK inhibitors generally enhanced H2O2‑induced HeLa cell death. In particular, p38 inhibitor increased ROS levels in H2O2‑treated HeLa cells, while NAC and PG attenuated H2O2‑induced HeLa cell death by suppressing ROS levels.

  1. Ectopic expression of H2AX protein promotes TrkA-induced cell death via modulation of TrkA tyrosine-490 phosphorylation and JNK activity upon DNA damage

    SciTech Connect

    Jung, Eun Joo; Kim, Deok Ryong

    2011-01-21

    Research highlights: {yields} We established TrkA-inducible U2OS cells stably expressing GFP-H2AX proteins. {yields} GFP-H2AX was colocalized with TrkA in the cytoplasm. {yields} {gamma}H2AX production was significantly increased upon activation of TrkA and suppressed by TrkA inhibitor or JNK inhibitor. {yields} Ectopic expression of H2AX promoted TrkA-mediated cell death through the modulation of TrkA tyrosine-490 phosphorylation and JNK activity upon DNA damage. -- Abstract: We previously reported that TrkA overexpression causes accumulation of {gamma}H2AX proteins in the cytoplasm, subsequently leading to massive cell death in U2OS cells. To further investigate how cytoplasmic H2AX is associated with TrkA-induced cell death, we established TrkA-inducible cells stably expressing GFP-tagged H2AX. We found that TrkA co-localizes with ectopically expressed GFP-H2AX proteins in the cytoplasm, especially at the juxta-nuclear membranes, which supports our previous results about a functional connection between TrkA and {gamma}H2AX in TrkA-induced cell death. {gamma}H2AX production from GFP-H2AX proteins was significantly increased when TrkA was overexpressed. Moreover, ectopic expression of H2AX activated TrkA-mediated signal pathways via up-regulation of TrkA tyrosine-490 phosphorylation. In addition, suppression of TrkA tyrosine-490 phosphorylation under a certain condition was removed by ectopic expression of H2AX, indicating a functional role of H2AX in the maintenance of TrkA activity. Indeed, TrkA-induced cell death was highly elevated by ectopic H2AX expression, and it was further accelerated by DNA damage via JNK activation. These all results suggest that cytoplasmic H2AX could play an important role in TrkA-mediated cell death by modulating TrkA upon DNA damage.

  2. Steroidal Saponin Diosgenin from Dioscorea bulbifera Protects Cardiac Cells from Hypoxia-reoxygenation Injury Through Modulation of Pro-survival and Pro-death Molecules

    PubMed Central

    Jayachandran, Karuppiah Shanmugasundarapandian; Vasanthi, A. Hannah Rachel; Gurusamy, Narasimman

    2016-01-01

    Background: Diosgenin, a steroidal saponin from plants, exhibits many biological potentials. Herein, the cardioprotective role of diosgenin is studied. Materials and Methods: The effect of diosgenin, isolated from Dioscorea bulbifera, was studied on hypoxia-reoxygenation (HR) in H9c2 cardiomyoblast cells. The amount of diosgenin in the plant extract was analyzed by high-performance thin layer chromatography using a solvent system comprising of chloroform:methanol:acetic acid:formic acid (13:4.5:1.5:1). Cardioprotection was checked by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Further, the release of lactate dehydrogenase, an enzyme released during cell death was checked. The proteins responsible for cell death (Bax) and cell survival (Bcl-2, hemeoxygenase-1 and Akt) were analyzed using Western blot to check the cardioprotective role of diosgenin. Conclusion: Supplementation of diosgenin mitigates HR injury, thereby exhibiting cardioprotective potential. SUMMARY The cardioprotective effect of Diosgenin was evidenced from the improved cell survival after hypoxia-reoxygenation injury demonstrated through MTT cell survival assay.The release of lactate dehydrogenase, an enzyme released during cell death was decreased by Diosgenin.Diosgenin upregulated the pro-survival molecules like B-cell lymphoma 2 (Bcl-2), heme oxygenase-1 and the phosphorylation of ATK (at serine 473); and at the same time pro-.death molecules like Bax was downregulated.Thus, Diosgenin as a plant based steroidal saponin is confirmed to mitigate ischemic reperfusion injury. Figure PMID:27041852

  3. GOLPH3 Mediated Golgi Stress Response in Modulating N2A Cell Death upon Oxygen-Glucose Deprivation and Reoxygenation Injury.

    PubMed

    Li, Ting; You, Hong; Mo, Xiaoye; He, Wenfang; Tang, Xiangqi; Jiang, Zheng; Chen, Shiyu; Chen, Yang; Zhang, Jie; Hu, Zhiping

    2016-03-01

    Increasing evidence implicating that the organelle-dependent initiation of cell death merits further research. The evidence also implicates Golgi as a sensor and common downstream-effector of stress signals in cell death pathways, and it undergoes disassembly and fragmentation during apoptosis in several neurological disorders. It has also been reported that during apoptotic cell death, there is a cross talk between ER, mitochondria, and Golgi. Thus, we hypothesized that Golgi might trigger death signals during oxidative stress through its own machinery. The current study found that GOLPH3, an outer membrane protein of the Golgi complex, was significantly upregulated in N2A cells upon oxygen-glucose deprivation and reoxygenation (OGD/R), positioning from the compact perinuclear ribbon to dispersed vesicle-like structures throughout the cytoplasm. Additionally, elevated GOLPH3 promoted a stress-induced conversion of the LC3 subunit I to II and reactive oxygen species (ROS) production in long-term OGD/R groups. The collective data indicated that GOLPH3 not only acted as a sensor of Golgi stress for its prompt upregulation during oxidative stress but also as an initiator that triggered and propagated specific Golgi stress signals to downstream effectors. This affected ROS production and stress-related autophagy and finally controlled the entry into apoptosis. The data also supported the hypothesis that the Golgi apparatus could be an ideal target for stroke, neurodegenerative diseases, or cancer therapy through its own functional proteins.

  4. Modulation of Glutathione Hemostasis by Inhibition of 12/15-Lipoxygenase Prevents ROS-Mediated Cell Death after Hepatic Ischemia and Reperfusion

    PubMed Central

    Thomas, Michael N.; Guba, Markus; Angele, Martin K.; Werner, Jens; Conrad, Marcus; Steib, Christian J.; Holdt, Lesca M.; Andrassy, Joachim; Khandoga, Andrej; Rentsch, Markus

    2017-01-01

    Background Reactive oxygen species- (ROS-) mediated ischemia-reperfusion injury (IRI) detrimentally impacts liver transplantation and resection. 12/15-Lipoxygenase (12/15-LOX), an antagonistic protein of the glutathione peroxidase 4 (GPX4) signaling cascade, was proven to mediate cell death in postischemic cerebral and myocardial tissue. The aim of this study was to investigate the impact of 12/15-LOX inhibition on hepatic IRI. Methods Livers of C57BL/6 mice were exposed to 60 minutes of partial warm ischemia and 90 minutes of reperfusion after previous Baicalein administration, an inhibitor of 12/15-LOX. Tissue samples were analyzed by TUNEL assay, Western blot, and spectral photometry. Results TUNEL labeling showed a significant reduction of hepatic cell death following baicalein pretreatment. Western Blot analysis revealed a significant downregulation of Jun-amino-terminal-kinase (JNK), caspase-3, and poly-ADP-ribose-polymerase (PARP), besides considerably lowered p44/42-MAP-kinase (ERK1/2) expression after Baicalein administration. A significant elevation of glutathione oxidation was measured in Baicalein pretreated livers. Conclusion Our data show that inhibition of 12/15-lipoxygenase causes significant cell death reduction after hepatic ischemia and reperfusion by enhancing glutathione metabolism. We conclude that GPX4-dependent cell death signaling cascade might play a major role in development of hepatic IRI, in which the investigated proteins JNK, caspase-3, ERK1/2, and PARP might contribute to tissue damage. PMID:28811867

  5. Activation of apoptosis signal-regulating kinase 1 is a key factor in paraquat-induced cell death: modulation by the Nrf2/Trx axis.

    PubMed

    Niso-Santano, Mireia; González-Polo, Rosa A; Bravo-San Pedro, José M; Gómez-Sánchez, Rubén; Lastres-Becker, Isabel; Ortiz-Ortiz, Miguel A; Soler, Germán; Morán, José M; Cuadrado, Antonio; Fuentes, José M

    2010-05-15

    Although oxidative stress is fundamental to the etiopathology of Parkinson disease, the signaling molecules involved in transduction after oxidant exposure to cell death are ill-defined, thus making it difficult to identify molecular targets of therapeutic relevance. We have addressed this question in human dopaminergic neuroblastoma SH-SY5Y cells exposed to the parkinsonian toxin paraquat (PQ). This toxin elicited a dose-dependent increase in reactive oxygen species and cell death that correlated with activation of ASK1 and the stress kinases p38 and JNK. The relevance of these kinases in channeling PQ neurotoxicity was demonstrated with the use of interference RNA for ASK1 and two well-established pharmaceutical inhibitors for JNK and p38. The toxic effect of PQ was substantially attenuated by preincubation with vitamin E, blocking ASK1 pathways and preventing oxidative stress and cell death. In a search for a physiological pathway that might counterbalance PQ-induced ASK1 activation, we analyzed the role of the transcription factor Nrf2, master regulator of redox homeostasis, and its target thioredoxin (Trx), which binds and inhibits ASK1. Trx levels were undetectable in Nrf2-deficient mouse embryo fibroblasts (MEFs), whereas they were constitutively high in Keap1-deficient MEFs as well as in SH-SY5Y cells treated with sulforaphane (SFN). Consistent with these data, Nrf2-deficient MEFs were more sensitive and Keap1-deficient MEFs and SH-SY5Y cells incubated with SFN were more resistant to PQ-induced cell death. This study identifies ASK1/JNK and ASK1/p38 as two critical pathways involved in the activation of cell death under oxidative stress conditions and identifies the Nrf2/Trx axis as a new target to block these pathways and protect from oxidant exposure such as that found in Parkinson and other neurodegenerative diseases. Copyright 2010 Elsevier Inc. All rights reserved.

  6. Natural death.

    PubMed

    Oehmichen, M; Meissner, C

    2000-01-01

    The increasing age of every human being is the beginning of the end of life, an obviously natural process, but any attempt to define the term 'natural death' soon encounters difficulties in defining what is meant by 'natural'. In the industrialized countries of the West, for example 'natural death' is thought of as the opposite of non-natural types of death such as accidental death, suicide, and homicide. The aim of our present survey is to discuss the meaning of the term 'natural death' under a clinical, a forensic and a scientific point of view with regard to recent developments especially in molecular biology. If there are 'external' physical influences, a medical-technical manipulation, a therapeutic or molecular biological intervention cannot be definitely ruled out as the cause of death, then use of the term 'natural death' in general is open to question. It will only remain meaningful if it can be applied with a specific meaning in definite practical situations. Current research and medical technology, however, do not allow use of the term 'natural death' in its conventional sense: it can thus be stricken from the medical vocabulary. Copyright 2000 S. Karger AG, Basel

  7. Invariant death.

    PubMed

    Frank, Steven A

    2016-01-01

    In nematodes, environmental or physiological perturbations alter death's scaling of time. In human cancer, genetic perturbations alter death's curvature of time. Those changes in scale and curvature follow the constraining contours of death's invariant geometry. I show that the constraints arise from a fundamental extension to the theories of randomness, invariance and scale. A generalized Gompertz law follows. The constraints imposed by the invariant Gompertz geometry explain the tendency of perturbations to stretch or bend death's scaling of time. Variability in death rate arises from a combination of constraining universal laws and particular biological processes.

  8. The essential role of p53-up-regulated modulator of apoptosis (Puma) and its regulation by FoxO3a transcription factor in β-amyloid-induced neuron death.

    PubMed

    Akhter, Rumana; Sanphui, Priyankar; Biswas, Subhas Chandra

    2014-04-11

    Neurodegeneration underlies the pathology of Alzheimer disease (AD). The molecules responsible for such neurodegeneration in AD brain are mostly unknown. Recent findings indicate that the BH3-only proteins of the Bcl-2 family play an essential role in various cell death paradigms, including neurodegeneration. Here we report that Puma (p53-up-regulated modulator of apoptosis), an important member of the BH3-only protein family, is up-regulated in neurons upon toxic β-amyloid 1-42 (Aβ(1-42)) exposure both in vitro and in vivo. Down-regulation of Puma by specific siRNA provides significant protection against neuron death induced by Aβ(1-42). We further demonstrate that the activation of p53 and inhibition of PI3K/Akt pathways induce Puma. The transcription factor FoxO3a, which is activated when PI3K/Akt signaling is inhibited, directly binds with the Puma gene and induces its expression upon exposure of neurons to oligomeric Aβ(1-42). Moreover, Puma cooperates with another BH3-only protein, Bim, which is already implicated in AD. Our results thus suggest that Puma is activated by both p53 and PI3K/Akt/FoxO3a pathways and cooperates with Bim to induce neuron death in response to Aβ(1-42).

  9. 6-Shogaol Inhibits Breast Cancer Cells and Stem Cell-Like Spheroids by Modulation of Notch Signaling Pathway and Induction of Autophagic Cell Death.

    PubMed

    Ray, Anasuya; Vasudevan, Smreti; Sengupta, Suparna

    2015-01-01

    Cancer stem cells (CSCs) pose a serious obstacle to cancer therapy as they can be responsible for poor prognosis and tumour relapse. In this study, we have investigated inhibitory activity of the ginger-derived compound 6-shogaol against breast cancer cells both in monolayer and in cancer-stem cell-like spheroid culture. The spheroids were generated from adherent breast cancer cells. 6-shogaol was effective in killing both breast cancer monolayer cells and spheroids at doses that were not toxic to noncancerous cells. The percentages of CD44+CD24-/low cells and the secondary sphere content were reduced drastically upon treatment with 6-shogaol confirming its action on CSCs. Treatment with 6-shogaol caused cytoplasmic vacuole formation and cleavage of microtubule associated protein Light Chain3 (LC3) in both monolayer and spheroid culture indicating that it induced autophagy. Kinetic analysis of the LC3 expression and a combination treatment with chloroquine revealed that the autophagic flux instigated cell death in 6-shogaol treated breast cancer cells in contrast to the autophagy inhibitor chloroquine. Furthermore, 6-shogaol-induced cell death got suppressed in the presence of chloroquine and a very low level of apoptosis was exhibited even after prolonged treatment of the compound, suggesting that autophagy is the major mode of cell death induced by 6-shogaol in breast cancer cells. 6-shogaol reduced the expression levels of Cleaved Notch1 and its target proteins Hes1 and Cyclin D1 in spheroids, and the reduction was further pronounced in the presence of a γ-secretase inhibitor. Secondary sphere formation in the presence of the inhibitor was also further reduced by 6-shogaol. Together, these results indicate that the inhibitory action of 6-shogaol on spheroid growth and sustainability is conferred through γ-secretase mediated down-regulation of Notch signaling. The efficacy of 6-shogaol in monolayer and cancer stem cell-like spheroids raise hope for its

  10. Flavonoid baicalein modulates H2O2-induced mitogen-activated protein kinases activation and cell death in SK-N-MC cells.

    PubMed

    Moslehi, Maryam; Meshkini, Azadeh; Yazdanparast, Razieh

    2012-05-01

    It is believed that ROS-induced oxidative stress triggers numerous signaling pathways which are involved in neurodegenerative diseases, including Alzheimer's disease. To find the effective drugs for neurodegenerative diseases, the deep delve into molecular mechanisms underlie these diseases is necessary. In the current study, we investigated the effects of flavonoid baicalein on H(2)O(2)-induced oxidative stress and cell death in SK-N-MC cells. Our results revealed that the treatment of SK-N-MC cells with H(2)O(2) led to a decrease in cell viability through phosphorylation and activation of extracellular signal-regulated kinases (ERKs) and c-Jun N-terminal kinases (JNKs) pathways followed by increase in Bax/Bcl2 ratio and initiation of caspase-dependent apoptotic pathways. In addition, our results showed that the exposure of SK-N-MC cells to H(2)O(2) ended up in reduction of glutathione (GSH) levels of SK-N-MC cells via JNK/ERK-mediated down-regulation of γ-glutamyl-cysteine synthetase (γ-GCS) expression. Our results demonstrated that flavonoid baicalein protected against H(2)O(2)-induced cell death by inhibition of JNK/ERK pathways activation and other key molecules in apoptotic pathways, including blockage of Bax and caspase-9 activation, induction of Bcl-2 expression and prevention of cell death. Baicalein supported intracellular defense mechanisms through maintaining GSH levels in SK-N-MC cells by the removal of inhibition effects of JNK/ERK pathways from γ-GCS expression. In addition, baicalein attenuated lipid and protein peroxidation and intracellular reactive oxygen species in SK-N-MC cells. In accordance with these observations, baicalein can be a promising candidate in antioxidant therapy and designing of natural-based drug for ROS-induced neurodegenerative disorders.

  11. Modulation of notch signaling pathway to prevent H2O2/menadione-induced SK-N-MC cells death by EUK134.

    PubMed

    Kamarehei, Maryam; Yazdanparast, Razieh

    2014-10-01

    The brain in Alzheimer's disease is under increased oxidative stress, and this may have a role in the pathogenesis and neural death in this disorder. It has been verified that numerous signaling pathways involved in neurodegenerative disorders are activated in response to reactive oxygen species (ROS). EUK134, a synthetic salen-manganese antioxidant complex, has been found to possess many interesting pharmacological activities awaiting exploration. The present study is to characterize the role of Notch signaling in apoptotic cell death of SK-N-MC cells. The cells were treated with hydrogen peroxide (H2O2) or menadione to induce oxidative stress. The free-radical scavenging capabilities of EUK134 were studied through the MTT assay, glutathione peroxidase (GPx) enzyme activity assay, and glutathione (GSH) Levels. The extents of lipid peroxidation, protein carbonyl formation, and intracellular ROS levels, as markers of oxidative stress, were also studied. Our results showed that H2O2/menadione reduced GSH levels and GPx activity. However, EUK134 protected cells against ROS-induced cell death by down-regulation of lipid peroxidation and protein carbonyl formation as well as restoration of antioxidant enzymes activity. ROS induced apoptosis and increased NICD and HES1 expression. Inhibition of NICD production proved that Notch signaling is involved in apoptosis through p53 activation. Moreover, H2O2/menadione led to Numb protein down-regulation which upon EUK134 pretreatment, its level increased and subsequently prevented Notch pathway activation. We indicated that EUK134 can be a promising candidate in designing natural-based drugs for ROS-induced neurodegenerative diseases. Collectively, ROS activated Notch signaling in SK-N-MC cells leading to cell apoptosis.

  12. 6-Shogaol Inhibits Breast Cancer Cells and Stem Cell-Like Spheroids by Modulation of Notch Signaling Pathway and Induction of Autophagic Cell Death

    PubMed Central

    Ray, Anasuya; Vasudevan, Smreti; Sengupta, Suparna

    2015-01-01

    Cancer stem cells (CSCs) pose a serious obstacle to cancer therapy as they can be responsible for poor prognosis and tumour relapse. In this study, we have investigated inhibitory activity of the ginger-derived compound 6-shogaol against breast cancer cells both in monolayer and in cancer-stem cell-like spheroid culture. The spheroids were generated from adherent breast cancer cells. 6-shogaol was effective in killing both breast cancer monolayer cells and spheroids at doses that were not toxic to noncancerous cells. The percentages of CD44+CD24-/low cells and the secondary sphere content were reduced drastically upon treatment with 6-shogaol confirming its action on CSCs. Treatment with 6-shogaol caused cytoplasmic vacuole formation and cleavage of microtubule associated protein Light Chain3 (LC3) in both monolayer and spheroid culture indicating that it induced autophagy. Kinetic analysis of the LC3 expression and a combination treatment with chloroquine revealed that the autophagic flux instigated cell death in 6-shogaol treated breast cancer cells in contrast to the autophagy inhibitor chloroquine. Furthermore, 6-shogaol-induced cell death got suppressed in the presence of chloroquine and a very low level of apoptosis was exhibited even after prolonged treatment of the compound, suggesting that autophagy is the major mode of cell death induced by 6-shogaol in breast cancer cells. 6-shogaol reduced the expression levels of Cleaved Notch1 and its target proteins Hes1 and Cyclin D1 in spheroids, and the reduction was further pronounced in the presence of a γ-secretase inhibitor. Secondary sphere formation in the presence of the inhibitor was also further reduced by 6-shogaol. Together, these results indicate that the inhibitory action of 6-shogaol on spheroid growth and sustainability is conferred through γ-secretase mediated down-regulation of Notch signaling. The efficacy of 6-shogaol in monolayer and cancer stem cell-like spheroids raise hope for its

  13. Sudden cardiac death and obesity.

    PubMed

    Plourde, Benoit; Sarrazin, Jean-François; Nault, Isabelle; Poirier, Paul

    2014-09-01

    For individuals and the society as a whole, the increased risk of sudden cardiac death in obese patients is becoming a major challenge, especially since obesity prevalence has been increasing steadily around the globe. Traditional risk factors and obesity often coexist. Hypertension, diabetes, obstructive sleep apnea and metabolic syndrome are well-known risk factors for CV disease and are often present in the obese patient. Although the bulk of evidence is circumstantial, sudden cardiac death and obesity share common traditional CV risk factors. Structural, functional and metabolic factors modulate and influence the risk of sudden cardiac death in the obese population. Other risk factors such as left ventricular hypertrophy, increased number of premature ventricular complexes, altered QT interval and reduced heart rate variability are all documented in both obese and sudden cardiac death populations. The present review focuses on out-of-hospital sudden cardiac death and potential mechanisms leading to sudden cardiac death in this population.

  14. Direct modulation of the outer mitochondrial membrane channel, voltage-dependent anion channel 1 (VDAC1) by cannabidiol: a novel mechanism for cannabinoid-induced cell death

    PubMed Central

    Rimmerman, N; Ben-Hail, D; Porat, Z; Juknat, A; Kozela, E; Daniels, M P; Connelly, P S; Leishman, E; Bradshaw, H B; Shoshan-Barmatz, V; Vogel, Z

    2013-01-01

    Cannabidiol (CBD) is a non-psychoactive plant cannabinoid that inhibits cell proliferation and induces cell death of cancer cells and activated immune cells. It is not an agonist of the classical CB1/CB2 cannabinoid receptors and the mechanism by which it functions is unknown. Here, we studied the effects of CBD on various mitochondrial functions in BV-2 microglial cells. Our findings indicate that CBD treatment leads to a biphasic increase in intracellular calcium levels and to changes in mitochondrial function and morphology leading to cell death. Density gradient fractionation analysis by mass spectrometry and western blotting showed colocalization of CBD with protein markers of mitochondria. Single-channel recordings of the outer-mitochondrial membrane protein, the voltage-dependent anion channel 1 (VDAC1) functioning in cell energy, metabolic homeostasis and apoptosis revealed that CBD markedly decreases channel conductance. Finally, using microscale thermophoresis, we showed a direct interaction between purified fluorescently labeled VDAC1 and CBD. Thus, VDAC1 seems to serve as a novel mitochondrial target for CBD. The inhibition of VDAC1 by CBD may be responsible for the immunosuppressive and anticancer effects of CBD. PMID:24309936

  15. Direct modulation of the outer mitochondrial membrane channel, voltage-dependent anion channel 1 (VDAC1) by cannabidiol: a novel mechanism for cannabinoid-induced cell death.

    PubMed

    Rimmerman, N; Ben-Hail, D; Porat, Z; Juknat, A; Kozela, E; Daniels, M P; Connelly, P S; Leishman, E; Bradshaw, H B; Shoshan-Barmatz, V; Vogel, Z

    2013-12-05

    Cannabidiol (CBD) is a non-psychoactive plant cannabinoid that inhibits cell proliferation and induces cell death of cancer cells and activated immune cells. It is not an agonist of the classical CB1/CB2 cannabinoid receptors and the mechanism by which it functions is unknown. Here, we studied the effects of CBD on various mitochondrial functions in BV-2 microglial cells. Our findings indicate that CBD treatment leads to a biphasic increase in intracellular calcium levels and to changes in mitochondrial function and morphology leading to cell death. Density gradient fractionation analysis by mass spectrometry and western blotting showed colocalization of CBD with protein markers of mitochondria. Single-channel recordings of the outer-mitochondrial membrane protein, the voltage-dependent anion channel 1 (VDAC1) functioning in cell energy, metabolic homeostasis and apoptosis revealed that CBD markedly decreases channel conductance. Finally, using microscale thermophoresis, we showed a direct interaction between purified fluorescently labeled VDAC1 and CBD. Thus, VDAC1 seems to serve as a novel mitochondrial target for CBD. The inhibition of VDAC1 by CBD may be responsible for the immunosuppressive and anticancer effects of CBD.

  16. Modulation of the Unfolded Protein Response by Tauroursodeoxycholic Acid Counteracts Apoptotic Cell Death and Fibrosis in a Mouse Model for Secondary Biliary Liver Fibrosis.

    PubMed

    Paridaens, Annelies; Raevens, Sarah; Devisscher, Lindsey; Bogaerts, Eliene; Verhelst, Xavier; Hoorens, Anne; Van Vlierberghe, Hans; van Grunsven, Leo A; Geerts, Anja; Colle, Isabelle

    2017-01-20

    The role of endoplasmic reticulum stress and the unfolded protein response (UPR) in cholestatic liver disease and fibrosis is not fully unraveled. Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, has been shown to reduce endoplasmic reticulum (ER) stress and counteract apoptosis in different pathologies. We aimed to investigate the therapeutic potential of TUDCA in experimental secondary biliary liver fibrosis in mice, induced by common bile duct ligation. The kinetics of the hepatic UPR and apoptosis during the development of biliary fibrosis was studied by measuring markers at six different timepoints post-surgery by qPCR and Western blot. Next, we investigated the therapeutic potential of TUDCA, 10 mg/kg/day in drinking water, on liver damage (AST/ALT levels) and fibrosis (Sirius red-staining), in both a preventive and therapeutic setting. Common bile duct ligation resulted in the increased protein expression of CCAAT/enhancer-binding protein homologous protein (CHOP) at all timepoints, along with upregulation of pro-apoptotic caspase 3 and 12, tumor necrosis factor receptor superfamily, member 1A (TNFRsf1a) and Fas-Associated protein with Death Domain (FADD) expression. Treatment with TUDCA led to a significant reduction of liver fibrosis, accompanied by a slight reduction of liver damage, decreased hepatic protein expression of CHOP and reduced gene and protein expression of pro-apoptotic markers. These data indicate that TUDCA exerts a beneficial effect on liver fibrosis in a model of cholestatic liver disease, and suggest that this effect might, at least in part, be attributed to decreased hepatic UPR signaling and apoptotic cell death.

  17. A novel quinone-based derivative (DTNQ-Pro) induces apoptotic death via modulation of heat shock protein expression in Caco-2 cells

    PubMed Central

    Gomez-Monterrey, Isabel; Campiglia, Pietro; Bertamino, Alessia; Aquino, Claudio; Sala, Marina; Grieco, Paolo; Dicitore, Alessandra; Vanacore, Daniela; Porta, Amalia; Maresca, Bruno; Novellino, Ettore; Stiuso, Paola

    2010-01-01

    Background and purpose: The resistance of human colon adenocarcinoma cells to antineoplastic agents may be related to the high endogenous expression of stress proteins, including the family of heat shock proteins (HSPs). Recently, a quinone-based pentacyclic derivative, DTNQ-Pro, showed high cytotoxic activity in human colon carcinoma cell lines. The aim of the present study was to determine the precise cellular mechanisms of this cytotoxic action of DTNQ-Pro. Experimental approach: Using human colorectal carcinoma-derived Caco-2 cells as a model, we studied the effects of DTNQ-Pro on cellular viability and oxidative stress; HSP70 and HSP27 accumulation; and cell cycle, differentiation and apoptosis. Key results: Incubation of Caco-2 cells with DTNQ-Pro reduced cell growth and increased the levels of reactive oxygen species in mitochondria. After 48 h of treatment, cells surviving showed an increased expression of Mn-superoxide dismutase (SOD), nitric oxide production and membrane lipid peroxidation. Treatment with DTNQ-Pro decreased HSP70 expression, and redistributed HSP27 and vimentin within the cell. DTNQ-Pro down-regulated the expression of A and B cyclins with arrest of the cell cycle in S phase and increased cellular differentiation. A second treatment of Caco-2 cells with DTNQ-Pro induced cellular death by activation of the apoptotic pathway. Conclusions and implications: DTNQ-Pro causes Caco-2 cell death by induction of apoptosis via inhibition of HSP70 accumulation and the intracellular redistribution of HSP27. These findings suggest the potential use of DTNQ-Pro in combination chemotherapy for colon cancer. PMID:20590589

  18. Modulation of the Unfolded Protein Response by Tauroursodeoxycholic Acid Counteracts Apoptotic Cell Death and Fibrosis in a Mouse Model for Secondary Biliary Liver Fibrosis

    PubMed Central

    Paridaens, Annelies; Raevens, Sarah; Devisscher, Lindsey; Bogaerts, Eliene; Verhelst, Xavier; Hoorens, Anne; van Vlierberghe, Hans; Van Grunsven, Leo A.; Geerts, Anja; Colle, Isabelle

    2017-01-01

    The role of endoplasmic reticulum stress and the unfolded protein response (UPR) in cholestatic liver disease and fibrosis is not fully unraveled. Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, has been shown to reduce endoplasmic reticulum (ER) stress and counteract apoptosis in different pathologies. We aimed to investigate the therapeutic potential of TUDCA in experimental secondary biliary liver fibrosis in mice, induced by common bile duct ligation. The kinetics of the hepatic UPR and apoptosis during the development of biliary fibrosis was studied by measuring markers at six different timepoints post-surgery by qPCR and Western blot. Next, we investigated the therapeutic potential of TUDCA, 10 mg/kg/day in drinking water, on liver damage (AST/ALT levels) and fibrosis (Sirius red-staining), in both a preventive and therapeutic setting. Common bile duct ligation resulted in the increased protein expression of CCAAT/enhancer-binding protein homologous protein (CHOP) at all timepoints, along with upregulation of pro-apoptotic caspase 3 and 12, tumor necrosis factor receptor superfamily, member 1A (TNFRsf1a) and Fas-Associated protein with Death Domain (FADD) expression. Treatment with TUDCA led to a significant reduction of liver fibrosis, accompanied by a slight reduction of liver damage, decreased hepatic protein expression of CHOP and reduced gene and protein expression of pro-apoptotic markers. These data indicate that TUDCA exerts a beneficial effect on liver fibrosis in a model of cholestatic liver disease, and suggest that this effect might, at least in part, be attributed to decreased hepatic UPR signaling and apoptotic cell death. PMID:28117681

  19. Death foretold.

    PubMed

    Biderman, A; Herman, J

    2000-01-01

    We briefly trace the history of a belief in the possibility that a person in apparent good health may accurately predict his or her own demise. The phenomenon is referred to as death foretold and we present presumed examples of it from the Bible, world literature, medical writings and newspaper reports without pretending to completeness. In two widely quoted scientific papers, death foretold is subsumed under the wider heading of decease due to psychic stress. We speculate on a possible link between the two, taking into consideration the fact that most people who prophesy their end are of an advanced age.

  20. Regulation of death induction and chemosensitizing action of 3-bromopyruvate in myeloid leukemia cells: energy depletion, oxidative stress, and protein kinase activity modulation.

    PubMed

    Calviño, Eva; Estañ, María Cristina; Sánchez-Martín, Carlos; Brea, Rocío; de Blas, Elena; Boyano-Adánez, María del Carmen; Rial, Eduardo; Aller, Patricio

    2014-02-01

    3-Bromopyruvate (3-BrP) is an alkylating, energy-depleting drug that is of interest in antitumor therapies, although the mechanisms underlying its cytotoxicity are ill-defined. We show here that 3-BrP causes concentration-dependent cell death of HL60 and other human myeloid leukemia cells, inducing both apoptosis and necrosis at 20-30 μM and a pure necrotic response at 60 μM. Low concentrations of 3-BrP (10-20 μM) brought about a rapid inhibition of glycolysis, which at higher concentrations was followed by the inhibition of mitochondrial respiration. The combination of these effects causes concentration-dependent ATP depletion, although this cannot explain the lethality at intermediate 3-BrP concentrations (20-30 μM). The oxidative stress caused by exposure to 3-BrP was evident as a moderate overproduction of reactive oxygen species and a concentration-dependent depletion of glutathione, which was an important determinant of 3-BrP toxicity. In addition, 3-BrP caused glutathione-dependent stimulation of p38 mitogen-activated protein kinase (MAPK), mitogen-induced extracellular kinase (MEK)/extracellular signal-regulated kinase (ERK), and protein kinase B (Akt)/mammalian target of rapamycin/p70S6K phosphorylation or activation, as well as rapid LKB-1/AMP kinase (AMPK) activation, which was later followed by Akt-mediated inactivation. Experiments with pharmacological inhibitors revealed that p38 MAPK activation enhances 3-BrP toxicity, which is conversely restrained by ERK and Akt activity. Finally, 3-BrP was seen to cooperate with antitumor agents like arsenic trioxide and curcumin in causing cell death, a response apparently mediated by both the generation of oxidative stress induced by 3-BrP and the attenuation of Akt and ERK activation by curcumin. In summary, 3-BrP cytotoxicity is the result of several combined regulatory mechanisms that might represent important targets to improve therapeutic efficacy.

  1. Design and Synthesis of Antitumor Heck-Coupled Sclareol Analogues: Modulation of BH3 Family Members by SS-12 in Autophagy and Apoptotic Cell Death.

    PubMed

    Shakeel-u-Rehman; Rah, Bilal; Lone, Shabir H; Rasool, Reyaz Ur; Farooq, Saleem; Nayak, Debasis; Chikan, Naveed Anjum; Chakraborty, Souneek; Behl, Akanksha; Mondhe, Dilip Manikaro; Goswami, Anindya; Bhat, Khursheed Ahmad

    2015-04-23

    Sclareol, a promising anticancer labdane diterpene, was isolated from Salvia sclarea. Keeping the basic stereochemistry-rich framework of the molecule intact, a method for the synthesis of novel sclareol analogues was designed using palladium(II)-catalyzed oxidative Heck coupling reaction in order to study their structure-activity relationship. Both sclareol and its derivatives showed an interesting cytotoxicity profile, with 15-(4-fluorophenyl)sclareol (SS-12) as the most potent analogue, having IC50 = 0.082 μM against PC-3 cells. It was found that SS-12 commonly interacts with Bcl-2 and Beclin 1 BH3 domain proteins and enhances autophagic flux by modulating autophagy-related proteins. Moreover, inhibition of autophagy by autophagy inhibitors protected against SS-12-induced apoptosis. Finally, SS-12 effectively suppressed tumor growth in vivo in Ehrlich's ascitic and solid Sarcoma-180 mouse models.

  2. Pathogen-mediated proteolysis of the cell death regulator RIPK1 and the host defense modulator RIPK2 in human aortic endothelial cells.

    PubMed

    Madrigal, Andrés G; Barth, Kenneth; Papadopoulos, George; Genco, Caroline Attardo

    2012-01-01

    Porphyromonas gingivalis is the primary etiologic agent of periodontal disease that is associated with other human chronic inflammatory diseases, including atherosclerosis. The ability of P. gingivalis to invade and persist within human aortic endothelial cells (HAEC) has been postulated to contribute to a low to moderate chronic state of inflammation, although how this is specifically achieved has not been well defined. In this study, we demonstrate that P. gingivalis infection of HAEC resulted in the rapid cleavage of receptor interacting protein 1 (RIPK1), a mediator of tumor necrosis factor (TNF) receptor-1 (TNF-R1)-induced cell activation or death, and RIPK2, a key mediator of both innate immune signaling and adaptive immunity. The cleavage of RIPK1 or RIPK2 was not observed in cells treated with apoptotic stimuli, or cells stimulated with agonists to TNF-R1, nucleotide oligomerization domain receptor 1(NOD1), NOD2, Toll-like receptor 2 (TLR2) or TLR4. P. gingivalis-induced cleavage of RIPK1 and RIPK2 was inhibited in the presence of a lysine-specific gingipain (Kgp) inhibitor. RIPK1 and RIPK2 cleavage was not observed in HAEC treated with an isogenic mutant deficient in the lysine-specific gingipain, confirming a role for Kgp in the cleavage of RIPK1 and RIPK2. Similar proteolysis of poly (ADP-ribose) polymerase (PARP) was observed. We also demonstrated direct proteolysis of RIPK2 by P. gingivalis in a cell-free system which was abrogated in the presence of a Kgp-specific protease inhibitor. Our studies thus reveal an important role for pathogen-mediated modification of cellular kinases as a potential strategy for bacterial persistence within target host cells, which is associated with low-grade chronic inflammation, a hallmark of pathogen-mediated chronic inflammatory disorders.

  3. Programmed Death 1 Regulates Memory Phenotype CD4 T Cell Accumulation, Inhibits Expansion of the Effector Memory Phenotype Subset and Modulates Production of Effector Cytokines

    PubMed Central

    Charlton, Joanna J.; Tsoukatou, Debbie; Mamalaki, Clio; Chatzidakis, Ioannis

    2015-01-01

    Memory phenotype CD4 T cells are found in normal mice and arise through response to environmental antigens or homeostatic mechanisms. The factors that regulate the homeostasis of memory phenotype CD4 cells are not clear. In the present study we demonstrate that there is a marked accumulation of memory phenotype CD4 cells, specifically of the effector memory (TEM) phenotype, in lymphoid organs and tissues of mice deficient for the negative co-stimulatory receptor programmed death 1 (PD-1). This can be correlated with decreased apoptosis but not with enhanced homeostatic turnover potential of these cells. PD-1 ablation increased the frequency of memory phenotype CD4 IFN-γ producers but decreased the respective frequency of IL-17A-producing cells. In particular, IFN-γ producers were more abundant but IL-17A producing cells were more scarce among PD-1 KO TEM-phenotype cells relative to WT. Transfer of peripheral naïve CD4 T cells suggested that accumulated PD-1 KO TEM-phenotype cells are of peripheral and not of thymic origin. This accumulation effect was mediated by CD4 cell-intrinsic mechanisms as shown by mixed bone marrow chimera experiments. Naïve PD-1 KO CD4 T cells gave rise to higher numbers of TEM-phenotype lymphopenia-induced proliferation memory cells. In conclusion, we provide evidence that PD-1 has an important role in determining the composition and functional aspects of memory phenotype CD4 T cell pool. PMID:25803808

  4. Mlo, a modulator of plant defense and cell death, is a novel calmodulin-binding protein. Isolation and characterization of a rice Mlo homologue.

    PubMed

    Kim, Min Chul; Lee, Sang Hyoung; Kim, Jong Kyong; Chun, Hyun Jin; Choi, Man Soo; Chung, Woo Sik; Moon, Byeong Cheol; Kang, Chang Ho; Park, Chan Young; Yoo, Jae Hyuk; Kang, Yun Hwan; Koo, Seong Cheol; Koo, Yoon Duck; Jung, Jae Cheol; Kim, Sun Tae; Schulze-Lefert, Paul; Lee, Sang Yeol; Cho, Moo Je

    2002-05-31

    Transient influx of Ca(2+) constitutes an early event in the signaling cascades that trigger plant defense responses. However, the downstream components of defense-associated Ca(2+) signaling are largely unknown. Because Ca(2+) signals are mediated by Ca(2+)-binding proteins, including calmodulin (CaM), identification and characterization of CaM-binding proteins elicited by pathogens should provide insights into the mechanism by which Ca(2+) regulates defense responses. In this study, we isolated a gene encoding rice Mlo (Oryza sativa Mlo; OsMlo) using a protein-protein interaction-based screening of a cDNA expression library constructed from pathogen-elicited rice suspension cells. OsMlo has a molecular mass of 62 kDa and shares 65% sequence identity and scaffold topology with barley Mlo, a heptahelical transmembrane protein known to function as a negative regulator of broad spectrum disease resistance and leaf cell death. By using gel overlay assays, we showed that OsMlo produced in Escherichia coli binds to soybean CaM isoform-1 (SCaM-1) in a Ca(2+)-dependent manner. We located a 20-amino acid CaM-binding domain (CaMBD) in the OsMlo C-terminal cytoplasmic tail that is necessary and sufficient for Ca(2+)-dependent CaM complex formation. Specific binding of the conserved CaMBD to CaM was corroborated by site-directed mutagenesis, a gel mobility shift assay, and a competition assay with a Ca(2+)/CaM-dependent enzyme. Expression of OsMlo was strongly induced by a fungal pathogen and by plant defense signaling molecules. We propose that binding of Ca(2+)-loaded CaM to the C-terminal tail may be a common feature of Mlo proteins.

  5. The crude extract of Corni Fructus induces apoptotic cell death through reactive oxygen species-modulated pathways in U-2 OS human osteosarcoma cells.

    PubMed

    Liao, Ching-Lung; Hsu, Shu-Chun; Yu, Chien-Chih; Yang, Jai-Sing; Tang, Nou-Ying; Wood, Wellington Gibson; Lin, Jaung-Geng; Chung, Jing-Gung

    2014-09-01

    Crude extract of Corni Fructus (CECF) has been used in Traditional Chinese medicine for the treatment of different diseases for hundreds of years. The purpose of this study was to investigate the cytotoxic effects of CECF on U-2 OS human osteosarcoma cells. Flow cytometry was used for measuring the percentage of viable cells, cell-cycle distribution, apoptotic cells in sub-G1 phase, reactive oxygen species (ROS), Ca(2+) levels, and mitochondrial membrane potential (ΔΨm ). Comet assay and 4'-6-diamidino-2-phenylindole staining were used for examining DNA damage and condensation. Western blotting was used to examine apoptosis-associated protein levels in U-2 OS cells after exposed to CECF. Immunostaining and confocal laser system microscope were used to examine protein translocation after CECF incubation. CECF decreased the percentage of viability, induced DNA damage and DNA condensation, G₀/G₁ arrest, and apoptosis in U-2 OS cells. CECF-stimulated activities of caspase-8, caspase-9, and caspase-3, ROS, and Ca(2+) production, decreased ΔΨm levels of in U-2 OS cells. CECF increased protein levels of caspase-3, caspase-9, Bax, cytochrome c, GRP78, AIF, ATF-6α, Fas, TRAIL, p21, p27, and p16 which were associated with cell-cycle arrest and apoptosis. These findings suggest that CECF triggers apoptosis in U-2 OS cells via ROS-modulated caspase-dependent and -independent pathways. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

  6. Brain death.

    PubMed

    Wijdicks, Eelco F M

    2013-01-01

    The diagnosis of brain death should be based on a simple premise. If every possible confounder has been excluded and all possible treatments have been tried or considered, irreversible loss of brain function is clinically recognized as the absence of brainstem reflexes, verified apnea, loss of vascular tone, invariant heart rate, and, eventually, cardiac standstill. This condition cannot be reversed - not even partly - by medical or surgical intervention, and thus is final. Many countries in the world have introduced laws that acknowledge that a patient can be declared brain-dead by neurologic standards. The U.S. law differs substantially from all other brain death legislation in the world because the U.S. law does not spell out details of the neurologic examination. Evidence-based practice guidelines serve as a standard. In this chapter, I discuss the history of development of the criteria, the current clinical examination, and some of the ethical and legal issues that have emerged. Generally, the concept of brain death has been accepted by all major religions. But patients' families may have different ideas and are mostly influenced by cultural attitudes, traditional customs, and personal beliefs. Suggestions are offered to support these families.

  7. Inhibition of microRNA-21 via locked nucleic acid-anti-miR suppressed metastatic features of colorectal cancer cells through modulation of programmed cell death 4.

    PubMed

    Nedaeinia, Reza; Sharifi, Mohammadreza; Avan, Amir; Kazemi, Mohammad; Nabinejad, Abdolreza; Ferns, Gordon A; Ghayour-Mobarhan, Majid; Salehi, Rasoul

    2017-03-01

    Colorectal cancer is among the most lethal of malignancies, due to its propensity to metastatic spread and multifactorial-chemoresistance. The latter property supports the need to identify novel therapeutic approaches for the treatment of colorectal cancer. MicroRNAs are endogenous non-coding small RNA molecules that function as post-transcriptional regulators of gene expression. Recently, programmed cell death 4 has been identified as a protein that increases during apoptosis. This gene is among the potential targets of miR-21 (OncomiR). Locked nucleic acid-modified oligonucleotides have recently emerged as a potential therapeutic option for targeting microRNAs. The aim of this study was to explore the functional role of locked nucleic acid-anti-miR-21 in the LS174T cell line in vitro and in vivo models. LS174T cells were treated with locked nucleic acid-anti-miR-21 for 24, 48, and 72 h in vitro. The expression of miR-21 and PDCD4 at messenger RNA (mRNA) level was evaluated by quantitative real-time polymerase chain reaction, while the protein level of PDCD4 was determined by Western blotting. Cell migratory behavior and the cluster-forming ability of cells were assessed before and after therapy. The disseminated tumor cells were assessed in the chick chorioallantoic membrane model by Alu quantitative polymerase chain reaction. Locked nucleic acid-anti-miR-21 was transfected successfully into the LS174T cells and inhibited the expression of miR-21. Locked nucleic acid-anti-miR-21 inhibited the migration and the number of cells forming clusters. Moreover, we found that locked nucleic acid-anti-miR-21 transfection was associated with a significant reduction in metastatic properties as assessed by the in ovo model. Our findings demonstrated the novel therapeutic potential of locked nucleic acid-anti-miR-21 in colon adenocarcinoma with high miR-21 expression.

  8. Is It Time to Tailor the Prediction of Radio-Induced Toxicity in Prostate Cancer Patients? Building the First Set of Nomograms for Late Rectal Syndrome

    SciTech Connect

    Valdagni, Riccardo; Kattan, Michael W.; Rancati, Tiziana; Yu Changhong; Vavassori, Vittorio; Fellin, Giovanni; Cagna, Elena; Gabriele, Pietro; Mauro, Flora Anna; Baccolini, Micaela; Bianchi, Carla; Menegotti, Loris; Monti, Angelo F.; Stasi, Michele; Giganti, Maria Olga; and others

    2012-04-01

    Purpose: Development of user-friendly tools for the prediction of single-patient probability of late rectal toxicity after conformal radiotherapy for prostate cancer. Methods and Materials: This multicenter protocol was characterized by the prospective evaluation of rectal toxicity through self-assessed questionnaires (minimum follow-up, 36 months) by 718 adult men in the AIROPROS 0102 trial. Doses were between 70 and 80 Gy. Nomograms were created based on multivariable logistic regression analysis. Three endpoints were considered: G2 to G3 late rectal bleeding (52/718 events), G3 late rectal bleeding (24/718 events), and G2 to G3 late fecal incontinence (LINC, 19/718 events). Results: Inputs for the nomogram for G2 to G3 late rectal bleeding estimation were as follows: presence of abdominal surgery before RT, percentage volume of rectum receiving >75 Gy (V75Gy), and nomogram-based estimation of the probability of G2 to G3 acute gastrointestinal toxicity (continuous variable, which was estimated using a previously published nomogram). G3 late rectal bleeding estimation was based on abdominal surgery before RT, V75Gy, and NOMACU. Prediction of G2 to G3 late fecal incontinence was based on abdominal surgery before RT, presence of hemorrhoids, use of antihypertensive medications (protective factor), and percentage volume of rectum receiving >40 Gy. Conclusions: We developed and internally validated the first set of nomograms available in the literature for the prediction of radio-induced toxicity in prostate cancer patients. Calculations included dosimetric as well as clinical variables to help radiation oncologists predict late rectal morbidity, thus introducing the possibility of RT plan corrections to better tailor treatment to the patient's characteristics, to avoid unnecessary worsening of quality of life, and to provide support to the patient in selecting the best therapeutic approach.

  9. [Expression of the radio-inducible TK suicide gene controlled by Egr-1 promoter in pancreatic cancer cells: an in vitro experiment].

    PubMed

    Liu, Jin-long; Liu, Xun-liang; Qian, Qing; Du, Qing; Guo, Shi-ying; Li, Chao-jun; Miao, Yi

    2008-07-22

    To investigate the expression of radio-inducible herpes simplex virus thymidine kinase (TK) suicide gene controlled by early growth response-1 (Egr-1) promoter in pancreatic cancer cells. Adenoviral vector pAdEgr-1-TK containing green fluorescent protein (GFP) was constructed. Human pancreatic cancer cells of the line PC-3 were cultured, transfected with pAdEgr-1-TK, and then exposed to 60Co source gamma-radiation at the doses of 0, 5, 7.5, 10, 15, and 20 Gy respectively for 24 hours. RT-PCR and Western blotting were used to detect the TK mRNA and protein expression in the PC3 cells. The TK mRNA expression levels of the PC3 cells exposed to y-radiation at the doses of 0, 5, 7.5, 10, 15, and 20 Gy respectively were (67.3 +/- 2.1)%, (89.3 +/- 1.0)%, (114.7 +/- 5.7)%, (140.5 +/- 3.1)%, (134.5 +/- 4.0)%, and (117.4 +/- 3.4)% respectively. The TK mRNA expression level was markedly increased after exposure to gamma-radiation, especially that t the dose of 10 Gy (all P < 0.01). The TK protein expression levels of the PC3 cells exposed to y-radiation at the doses of 0, 5, 7.5, 10, 15, and 20 Gy were (5.4 +/- 0.7)%, (7.6 +/- 0.9)%, (21.5 +/- 1.5)%, (35.7 +/- l1.4)%, (32.1 +/- 1.2)%, and (28.8 +/- 1.5)% respectively. The Egr-1 promoter causes high expression of TK suicide gene in cancer cells after exposure to 60Co-gamma-radiation. These data provide an experimental basis for gene therapy.

  10. [Accompany death].

    PubMed

    Salvador Borrell, Montserrat

    2010-11-01

    One of the roles of nursing is to take care of the patients in terminal situation. The time, the experience, the formation, and the personal and professional attitudes that the nurse has will propitiate that taking care of moribund patients might turn into one of the more rewarding human experiences in life. There for, it is indispensable that nurses assume death as a natural and inevitable reality to achieve. The principal aim of the study is to evaluate the competence of confrontation and the autoefficiency of the welfare among nurses who work with adult patients at the end of the life. Descriptive study realized in the units of Oncology, Hametology and Palliative Care of the following centers: La Fe, Clínico, Dr. Peset, H. General, Arnau de Vilanova and Dr. Moliner de Portacoelli in Valencia (Spain). The following instruments were used: the Bugen Scale of confrontation of the Death (1980-1981) and the Robbins Scale of Autoefficiency (1992). Data suggests that major coping gives major autoeffciency and vice versa. The realized study opens numerous questions, specially related with training and the burden of preparation along the whole professional career, in order to achieve competence for coping and autoefficiency.

  11. Invariant death

    PubMed Central

    Frank, Steven A.

    2016-01-01

    In nematodes, environmental or physiological perturbations alter death’s scaling of time. In human cancer, genetic perturbations alter death’s curvature of time. Those changes in scale and curvature follow the constraining contours of death’s invariant geometry. I show that the constraints arise from a fundamental extension to the theories of randomness, invariance and scale. A generalized Gompertz law follows. The constraints imposed by the invariant Gompertz geometry explain the tendency of perturbations to stretch or bend death’s scaling of time. Variability in death rate arises from a combination of constraining universal laws and particular biological processes. PMID:27785361

  12. Identification, cloning and characterization of R2R3-MYB gene family in canola (Brassica napus L.) identify a novel member modulating ROS accumulation and hypersensitive-like cell death.

    PubMed

    Chen, Bisi; Niu, Fangfang; Liu, Wu-Zhen; Yang, Bo; Zhang, Jingxiao; Ma, Jieyu; Cheng, Hao; Han, Feng; Jiang, Yuan-Qing

    2016-04-01

    The R2R3-MYB proteins comprise one of the largest families of transcription factors in plants. Although genome-wide analysis of this family has been carried out in some plant species, little is known about R2R3-MYB genes in canola (Brassica napus L.). In this study, we have identified 76 R2R3-MYB genes in the canola genome through mining of expressed sequence tags (ESTs). The cDNA sequences of 44 MYB genes were successfully cloned. The transcriptional activities of BnaMYB proteins encoded by these genes were assayed in yeast. The subcellular localizations of representative R2R3-MYB proteins were investigated through GFP fusion. Besides, the transcript abundance level analysis during abiotic conditions and ABA treatment identified a group of R2R3-MYB genes that responded to one or more treatments. Furthermore, we identified a previously functionally unknown MYB gene-BnaMYB78, which modulates reactive oxygen species (ROS)-dependent cell death in Nicotiana benthamiana, through regulating the transcription of a few ROS- and defence-related genes. Taken together, this study has provided a solid foundation for understanding the roles and regulatory mechanism of canola R2R3-MYB genes. © The Author 2016. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

  13. Identification, cloning and characterization of R2R3-MYB gene family in canola (Brassica napus L.) identify a novel member modulating ROS accumulation and hypersensitive-like cell death

    PubMed Central

    Chen, Bisi; Niu, Fangfang; Liu, Wu-Zhen; Yang, Bo; Zhang, Jingxiao; Ma, Jieyu; Cheng, Hao; Han, Feng; Jiang, Yuan-Qing

    2016-01-01

    The R2R3-MYB proteins comprise one of the largest families of transcription factors in plants. Although genome-wide analysis of this family has been carried out in some plant species, little is known about R2R3-MYB genes in canola (Brassica napus L.). In this study, we have identified 76 R2R3-MYB genes in the canola genome through mining of expressed sequence tags (ESTs). The cDNA sequences of 44 MYB genes were successfully cloned. The transcriptional activities of BnaMYB proteins encoded by these genes were assayed in yeast. The subcellular localizations of representative R2R3-MYB proteins were investigated through GFP fusion. Besides, the transcript abundance level analysis during abiotic conditions and ABA treatment identified a group of R2R3-MYB genes that responded to one or more treatments. Furthermore, we identified a previously functionally unknown MYB gene-BnaMYB78, which modulates reactive oxygen species (ROS)-dependent cell death in Nicotiana benthamiana, through regulating the transcription of a few ROS- and defence-related genes. Taken together, this study has provided a solid foundation for understanding the roles and regulatory mechanism of canola R2R3-MYB genes. PMID:26800702

  14. Glutathione Efflux and Cell Death

    PubMed Central

    2012-01-01

    Abstract Significance: Glutathione (GSH) depletion is a central signaling event that regulates the activation of cell death pathways. GSH depletion is often taken as a marker of oxidative stress and thus, as a consequence of its antioxidant properties scavenging reactive species of both oxygen and nitrogen (ROS/RNS). Recent Advances: There is increasing evidence demonstrating that GSH loss is an active phenomenon regulating the redox signaling events modulating cell death activation and progression. Critical Issues: In this work, we review the role of GSH depletion by its efflux, as an important event regulating alterations in the cellular redox balance during cell death independent from oxidative stress and ROS/RNS formation. We discuss the mechanisms involved in GSH efflux during cell death progression and the redox signaling events by which GSH depletion regulates the activation of the cell death machinery. Future Directions: The evidence summarized here clearly places GSH transport as a central mechanism mediating redox signaling during cell death progression. Future studies should be directed toward identifying the molecular identity of GSH transporters mediating GSH extrusion during cell death, and addressing the lack of sensitive approaches to quantify GSH efflux. Antioxid. Redox Signal. 17, 1694–1713. PMID:22656858

  15. Encountering Death: Structured Activities for Death Awareness.

    ERIC Educational Resources Information Center

    Welch, Ira David; And Others

    This book is intended to be used as a supplement to standard textbooks on death and dying for college students. Chapter 1 "Encountering Death in the Self" builds the foundation for increased self-awareness for the study of death and dying. Chapter 2 "Encountering Death in the Family" provides activities which are appropriate for a wide variety of…

  16. Death and dignity through fresh eyes.

    PubMed

    Phillips, Matthew; Pilkington, Ruth; Patterson, Aileen; Hennessy, Martina

    2011-12-01

    Trinity College Dublin remains one of the Medical Schools that uses traditional dissection to teach anatomy, exposing students from the first week of entry to cadavers. This early exposure makes it imperative that issues surrounding death and donor remains are explored early on within the main structure of the curriculum. The School of Medicine began a programme of Medical Humanities student-selected modules (SSMs) in 2010, and the opportunity to offer a module on medical ethics regarding death and dignity was taken. A course was devised that touched only lightly on subjects such as palliative care and the concept of a good death. The course focused much more strongly on the reality of death as part of cultural and societal identity and placement. This was facilitated by field trips to settings where discussions regarding death, dying and dignity were commonplace and authentic experiences, rather than classroom discussions based on theoretical circumstances that may not yet have been experienced by the student. The module ran very well, with students feeling that they had had a chance to think critically about the role of death as an event with significance within society and culture, rather than purely in a medico-legal framework. Options to extend the module to the compulsory element of the course, to be built upon in later years looking at more technical aspects surrounding death, are being explored. © Blackwell Publishing Ltd 2011.

  17. Death Education and Death Fear Reduction

    ERIC Educational Resources Information Center

    Mueller, Mary Louise

    1976-01-01

    The study examined the possibility of reducing the fear of death in early adolescents through a 12-lesson unit designed to assist the student to achieve an attitude of integration toward life and death. (NQ)

  18. Aging and Death Education.

    ERIC Educational Resources Information Center

    Pinder, Margaret M.; Hayslip, Bert, Jr.

    1980-01-01

    The elderly death rate is somewhat higher than the death rate in general. Numbers of schools with gerontological curricula and frequency of death education courses are positively related to elderly death rates. The contention that elderly deaths have less social impact is not supported. (JAC)

  19. Death: 'nothing' gives insight.

    PubMed

    Ettema, Eric J

    2013-08-01

    According to a widely accepted belief, we cannot know our own death--death means 'nothing' to us. At first sight, the meaning of 'nothing' just implies the negation or absence of 'something'. Death then simply refers to the negation or absence of life. As a consequence, however, death has no meaning of itself. This leads to an ontological paradox in which death is both acknowledged and denied: death is … nothing. In this article, I investigate whether insight into the ontological paradox of the nothingness of death can contribute to a good end-of-life. By analysing Aquinas', Heidegger's and Derrida's understanding of death as nothingness, I explore how giving meaning to death on different ontological levels connects to, and at the same time provides resistance against, the harsh reality of death. By doing so, I intend to demonstrate that insight into the nothingness of death can count as a framework for a meaningful dealing with death.

  20. [Unobserved death of an infant: cot death?].

    PubMed

    van Wouwe, J P; Dandachli, T H; Huber, J

    1999-10-02

    Three children, two girls aged 8 and 12 months and one boy aged 7 weeks, were found dead unexpectedly. Autopsy revealed pneumonia in two children, following which the diagnosis of 'natural, explained death' was made; one child showed no abnormalities and the diagnosis read 'natural, unexplained death' (cot death). Autopsy may currently only be performed with parental permission or, in case of doubt about unnatural cause of death, by order of the public prosecutor. The authors propose routine performance of a protocolled autopsy by GP, pediatrician, pathologist and medical examiner in order to avoid subsequent and possibly incorrect doubt about the cause of death.

  1. Programmed cell death receptor ligand 1 modulates the regulatory T cells' capacity to repress shock/sepsis-induced indirect acute lung injury by recruiting phosphatase SRC homology region 2 domain-containing phosphatase 1.

    PubMed

    Tang, Lunxian; Bai, Jianwen; Chung, Chun-Shiang; Lomas-Neira, Joanne; Chen, Yaping; Huang, Xin; Ayala, Alfred

    2015-01-01

    We recently reported that adoptively transferred (AT) exogenous CD4+ CD25+ regulatory T cells (Tregs) to wild-type (WT) mice can directly act to repress shock/sepsis-induced experimental indirect acute lung injury (iALI), and this is mediated in part by programmed cell death receptor 1 (PD-1). In this study, we further determine whether recipient mouse lacking PD-L1, one of the primary ligands for PD-1, contributes to the manipulation of the Tregs' capacity to repress lung injury. To do this, Tregs isolated from the spleen of WT mice were AT into PD-L1 mice subjected to hemorrhagic shock and subsequent to cecal ligation and puncture to induce iALI. Samples were collected for analyses 24 h after cecal ligation and puncture. We found that in PD-L1-recipient mice, AT WT-Tregs lost the ability to reverse the development of iALI seen in WT recipient mice (i.e., no reduction of lung injury indices assessed by histology and vascular leakage, failure to decrease the lung neutrophil influx [myeloperoxidase activity], or the rise in lung apoptosis [caspase 3 activity]). Also, a significant increase in interleukin 1β (IL-1β) and keratinocyte-derived chemokine, but no changes in IL-6, IL-10, and IL-17A levels in lung tissues were seen in these mice compared with iALI mice without AT of Tregs. Furthermore, we noted that the lung tissue tyrosine phosphatase Src homology region 2 domain-containing phosphatase 1 (SHP-1), but not SHP-2, was activated with the AT of Tregs in PD-L1(-/-) iALI mice. Finally, through local depletion of CD4+ T cells or CD25+ (Tregs) in the lung, prior to inducing iALI, we found that SHP-1 activation was associated with the loss of Tregs' protective effects in vivo. Collectively, our data reveal that PD-L1 is a critical modulator of Tregs' ability to suppress iALI, and this appears to involve SHP-1 activation.

  2. Role of programmed cell death in development.

    PubMed

    Ranganath, R M; Nagashree, N R

    2001-01-01

    Programmed cell death (PCD) is an integral part of both animal and plant development. In animals, model systems such as Caenorhabditis elegans, Drosophila melanogaster, and mice have shown a general cell death profile of induction, caspase mediation, cell death, and phagocytosis. Tremendous strides have been made in cell death research in animals in the past decade. The ordering of the C. elegans genes Ced-3, 4 and 9, identification of caspase-activated DNase that degrades nuclear DNA during PCD, identification of signal transduction modules involving caspases as well as the caspase-independent pathway, and the involvement of mitochondria are some of the findings of immense value in understanding animal PCDs. Similarly, the caspase inactivation mechanisms of infecting viruses to stall host cell death give a new dimension to the viral infection process. However, plant cell death profiles provide an entirely different scenario. The presence of a cell wall that cannot be phagocytosed, absence of the hallmarks of animal PCDs such as DNA laddering, formation of apoptotic bodies, a cell-death-specific nuclease, a biochemical machinery of killer enzymes such as caspases all point to novel ways of cell elimination. Large gaps in our understanding of plant cell death have prompted speculative inferences and comparisons with animal cell death mechanisms. This paper deals with both animals and plants for a holistic view on cell death in eukaryotes.

  3. Children and Death.

    ERIC Educational Resources Information Center

    Brennan, Andrew J. J.

    Health professionals and educators should develop their abilities to educate about death and to comfort the bereaved. Due to lower death rates, the lack of philosophical religious views, and distorted perceptions of death contributed by television, death has become a mystery instead of a segment of the common experience. Particularly when a child…

  4. Brain Death Determination.

    PubMed

    Spinello, Irene M

    2015-09-01

    In the United States, each year 1% to 2% of deaths are brain deaths. Considerable variation in the practice of determining brain death still remains, despite the publication of practice parameters in 1995 and an evidence-based guideline update in 2010. This review is intended to give bedside clinicians an overview of definition, the causes and pitfalls of misdiagnosing brain death, and a focus on the specifics of the brain death determination process.

  5. Using National Inpatient Death Rates as a Benchmark to Identify Hospitals with Inaccurate Cause of Death Reporting - Missouri, 2009-2012.

    PubMed

    Lloyd, Jennifer; Jahanpour, Ehsan; Angell, Brian; Ward, Craig; Hunter, Andy; Baysinger, Cherri; Turabelidze, George

    2017-01-13

    Reporting causes of death accurately is essential to public health and hospital-based programs; however, some U.S. studies have identified substantial inaccuracies in cause of death reporting. Using CDC's national inpatient hospital death rates as a benchmark, the Missouri Department of Health and Senior Services (DHSS) analyzed inpatient death rates reported by hospitals with high inpatient death rates in St. Louis and Kansas City metro areas. Among the selected hospitals with high inpatient death rates, 45.8% of death certificates indicated an underlying cause of death that was inconsistent with CDC's Guidelines for Death Certificate completion. Selected hospitals with high inpatient death rates were more likely to overreport heart disease and renal disease, and underreport cancer as an underlying cause of death. Based on these findings, the Missouri DHSS initiated a new web-based training module for death certificate completion based on the CDC guidelines in an effort to improve accuracy in cause of death reporting.

  6. Death Education and Death-Related Attitudes.

    ERIC Educational Resources Information Center

    Hoelter, Jon W.; Epley, Rita J.

    1979-01-01

    Assessed the impact of a death and dying course. Results showed no significant pre-test/post-test differences for the experimental or the control group, but indicated initial differences between the two groups, suggesting that students enrolling in a death and dying course have more favorable attitudes toward both suicide and abortion. (Author)

  7. Whither brain death?

    PubMed

    Bernat, James L

    2014-01-01

    The publicity surrounding the recent McMath and Muñoz cases has rekindled public interest in brain death: the familiar term for human death determination by showing the irreversible cessation of clinical brain functions. The concept of brain death was developed decades ago to permit withdrawal of therapy in hopeless cases and to permit organ donation. It has become widely established medical practice, and laws permit it in all U.S. jurisdictions. Brain death has a biophilosophical justification as a standard for determining human death but remains poorly understood by the public and by health professionals. The current controversies over brain death are largely restricted to the academy, but some practitioners express ambivalence over whether brain death is equivalent to human death. Brain death remains an accepted and sound concept, but more work is necessary to establish its biophilosophical justification and to educate health professionals and the public.

  8. Physician-assisted death

    PubMed Central

    Abrahao, Agessandro; Downar, James; Pinto, Hanika; Dupré, Nicolas; Izenberg, Aaron; Kingston, William; Korngut, Lawrence; O'Connell, Colleen; Petrescu, Nicolae; Shoesmith, Christen; Tandon, Anu; Vargas-Santos, Ana Beatriz

    2016-01-01

    Objective: To survey amyotrophic lateral sclerosis (ALS) health care providers to determine attitudes regarding physician-assisted death (PAD) after the Supreme Court of Canada (SCC) invalidated the Criminal Code provisions that prohibit PAD in February 2015. Methods: We conducted a Canada-wide survey of physicians and allied health professionals (AHP) involved in the care of patients with ALS on their opinions regarding (1) the SCC ruling, (2) their willingness to participate in PAD, and (3) the PAD implementation process for patients with ALS. Results: We received 231 responses from ALS health care providers representing all 15 academic ALS centers in Canada, with an overall response rate for invited participants of 74%. The majority of physicians and AHP agreed with the SCC ruling and believed that patients with moderate and severe stage ALS should have access to PAD; however, most physicians would not provide a lethal prescription or injection to an eligible patient. They preferred the patient obtain a second opinion to confirm eligibility, have a psychiatric assessment, and then be referred to a third party to administer PAD. The majority of respondents felt unprepared for the initiation of this program and favored the development of PAD training modules and guidelines. Conclusions: ALS health care providers support the SCC decision and the majority believe PAD should be available to patients with moderate to severe ALS with physical or emotional suffering. However, few clinicians are willing to directly provide PAD and additional training and guidelines are required before implementation in Canada. PMID:27178703

  9. Death by fraternity hazing.

    PubMed

    Boglioli, L R; Taff, M L

    1995-03-01

    Fraternity hazing can cause a variety of injuries and deaths. We recently had the opportunity to investigate a heat-related death that occurred during a college fraternity event. The original death investigation did not consider the circumstances of death, environmental conditions, or the subtle autopsy findings related to heat stroke. This case is intended to alert health care professionals that deaths on college campuses may be related to fraternity hazing and may require in-depth investigations. An analysis of the death and a discussion of heat-related injuries are presented.

  10. [Mechanisms of gamma-inducible death of Jurkat cells line].

    PubMed

    Gamkrelidze, M M; Bezhitashvili, N D; Pavliashvili, A T; Mchedlishvili, T V; Sanikidze, T V

    2008-06-01

    Mechanisms of radio-inducible death of Jurkat cells were investigated. Human lymphoblastoid T-cell line Jurkat is widely established model for studying apoptosis mechanisms. The cell was radiated by "Teragam" (Czech Republic) by dose 2 g during 1 minute. After radiation cells were incubated at standard conditions during 24 hours. After gamma radiation in cell population amount of cells in gaplois (apoptotic G 0) stage was increased 8,2 folds, in diplois (G 0/G1) stage - by 17%, in synthetic (S) stage decreased by 35% and tetraploid (G2/M) stage by 73% in comparison to control group. It was revealed intensive production of free radicals of oxygen and nitric oxide and decreasing activity of antioxidant enzymes (superoxidismutasa, catalasa and glutathione peroxidase). Revealed dependence between intensification of apoptosis and radiation-induced arrest of cell cycle G2/M phase may be determined by excess amount of free oxygen and nitrogen radicals generated in Jurkat cells as a result of nondirect effects of low doses of gamma radiation.

  11. Death and Grief

    MedlinePlus

    ... A Week of Healthy Breakfasts Shyness Death and Grief KidsHealth > For Teens > Death and Grief Print A ... Yourself en español Muerte y duelo What Is Grief? Grief is the reaction we have in response ...

  12. Children's Experience with Death.

    ERIC Educational Resources Information Center

    Zeligs, Rose

    Children's concepts of death grow with their age and development The three-year-old begins to notice that living things move and make sounds. The five-year-old thinks that life and death are reversable, but the six-year-old knows that death is final and brings sorrow. Children from eight through ten are interested in the causes of death and what…

  13. Are Death Anxiety and Death Depression Distinct Entities?

    ERIC Educational Resources Information Center

    Alvarado, Katherine A.; And Others

    1993-01-01

    Administered Death Anxiety Scale and Death Depression Scale to 200 individuals. Two scales correlated 0.55. Factor analysis of combined 32 items revealed factors: "death anxiety" having highest factor loadings with Death Anxiety Scale, "death depression" having highest factor loadings with Death Depression Scale, "death of…

  14. Are Death Anxiety and Death Depression Distinct Entities?

    ERIC Educational Resources Information Center

    Alvarado, Katherine A.; And Others

    1993-01-01

    Administered Death Anxiety Scale and Death Depression Scale to 200 individuals. Two scales correlated 0.55. Factor analysis of combined 32 items revealed factors: "death anxiety" having highest factor loadings with Death Anxiety Scale, "death depression" having highest factor loadings with Death Depression Scale, "death of…

  15. Identity and Death Anxiety.

    ERIC Educational Resources Information Center

    Sterling, Christopher M.; Van Horn, K. Roger

    1989-01-01

    Examined relationships between death anxiety and Erikson's concept of ego identity in White male undergraduates (N=63). Found involvement in identity crisis or decision-making period appeared to have increased death anxiety. Recommends further research between death anxiety and ego identity development. (Author/ABL)

  16. Death Anxiety and Politics.

    ERIC Educational Resources Information Center

    Peterson, Steven A.

    1986-01-01

    Explores the relationship between death anxiety and sociopolitical attitudes and political behavior. Data from a sample of 209 undergraduate students indicate that death anxiety is modestly related to attitudes reflecting a turning away from the social and political world. Death anxiety does not seem related to political behavior. (Author)

  17. Separation, Part I: Death.

    ERIC Educational Resources Information Center

    Jordan, Anne Devereaux

    1997-01-01

    Contends literature is the one place where death still abides, where grief is felt and consolation can be sought. States that young readers can gain a recognition in books that death is natural. Discusses death in folk and fairy tales, in 17th-century didactic children's books and in modern and contemporary literature. Outlines characteristics of…

  18. Infant death scene investigation.

    PubMed

    Tabor, Pamela D; Ragan, Krista

    2015-01-01

    The sudden unexpected death of an infant is a tragedy to the family, a concern to the community, and an indicator of national health. To accurately determine the cause and manner of the infant's death, a thorough and accurate death scene investigation by properly trained personnel is key. Funding and resources are directed based on autopsy reports, which are only as accurate as the scene investigation. The investigation should include a standardized format, body diagrams, and a photographed or videotaped scene recreation utilizing doll reenactment. Forensic nurses, with their basic nursing knowledge and additional forensic skills and abilities, are optimally suited to conduct infant death scene investigations as well as train others to properly conduct death scene investigations. Currently, 49 states have child death review teams, which is an idea avenue for a forensic nurse to become involved in death scene investigations.

  19. [The diagnosis of death].

    PubMed

    Echeverría, Carlos; Goic, Alejandro; Lavados, Manuel; Quintana, Carlos; Rojas, Alberto; Serani, Alejandro; Vacarezza, Ricardo

    2004-01-01

    This paper undertakes an analysis of the scientific criteria used in the diagnosis of death and underscores the importance of intellectual rigor in the definition of medical concepts, particularly regarding such a critical issue as the diagnosis of death. Under the cardiorespiratory criterion, death is defined as "the irreversible cessation of the functioning of an organism as a whole", and the tests used to confirm this criterion (negative life-signs) are sensitive and specific. In this case, cadaverous phenomena appear immediately following the diagnosis of death. On the other hand, doubts have arisen concerning the theoretical and the inner consistency of the criterion of brain death, since it does not satisfy the definition of "the irreversible cessation of the functioning of an organism as a whole", nor the requirement of "total and irreversible cessation of all functions of the entire brain, including the brain stem". There is evidence to the effect that the tests used to confirm this criterion are not specific enough. It is clear that brain death marks the beginning of a process that eventually ends in death, though death does not occur at that moment. From an ethical point of view, the conflict arises between the need to provide an unequivocal diagnosis of death and the possibility of saving a life through organ transplantation. The sensitive issue of brain death calls for a more thorough and in-depth discussion among physicians and the community at large.

  20. Programmed cell death: Superman meets Dr Death.

    PubMed

    Meier, Pascal; Silke, John

    2003-12-01

    This year's Cold Spring Harbor meeting on programmed cell death (September 17-21, 2003), organised by Craig Thompson and Junying Yuan, was proof that the 'golden age' of research in this field is far from over. There was a flurry of fascinating insights into the regulation of diverse apoptotic pathways and unexpected non-apoptotic roles for some of the key apoptotic regulators and effectors. In addition to their role in cell death, components of the apoptotic molecular machinery are now known to also function in a variety of essential cellular processes, such as regulating glucose homeostasis, lipid metabolism, cell proliferation and differentiation.

  1. Deaths during recreational activity.

    PubMed

    Copeland, A R

    1984-06-01

    This study of recreational deaths in the "land of sun and fun" has pointed out several useful factors. Firstly, accidental deaths are more common than naturals. Secondly, the most common accidental death is drowning while swimming. The latter is not usually at public facilities, but rather at unsupervised uninstitutionalized surroundings. Finally, a younger population is involved with a frequent number of them with alcohol detected and/or drugs.

  2. A good death.

    PubMed

    2011-10-26

    Definitions of a good death often include being at home. Dying at home may be optimal for the patient but could place a significant burden on families and leave them with traumatic memories. Death in hospital should not mean that it is a 'bad death'. How someone dies is more important than where they die and nurses should be taught to provide good end of life care in all settings.

  3. [The extraordinary death].

    PubMed

    Plattner, Thomas; Zollinger, Ulrich

    2008-07-01

    The examination of a deceased person is an important duty for physicians. It comprises the certification of death, the certification of the identity of the deceased, a thorough examination of the body, an estimation of the moment of death and ends with the decision, if death was caused by a certain or possible violent cause in which case it must be reported to the authorities. Problems and pitfalls are discussed on the basis of practical case presentations.

  4. The Effects of Death Education.

    ERIC Educational Resources Information Center

    Freitag, Carl B.; Hassler, Shawn David

    Although fear of death is recorded in the writings of the oldest major religions, the study of death and the fear of death have only occurred for the last few decades. Death education courses have grown in number since the early 1970's. College students participated in an investigation of the effects of death education on death anxiety by…

  5. The Effects of Death Education.

    ERIC Educational Resources Information Center

    Freitag, Carl B.; Hassler, Shawn David

    Although fear of death is recorded in the writings of the oldest major religions, the study of death and the fear of death have only occurred for the last few decades. Death education courses have grown in number since the early 1970's. College students participated in an investigation of the effects of death education on death anxiety by…

  6. Mozart's illnesses and death.

    PubMed Central

    Davies, P J

    1983-01-01

    Throughout his life Mozart suffered frequent attacks of tonsillitis. In 1784 he developed post-streptococcal Schönlein-Henoch syndrome which caused chronic glomerular nephritis and chronic renal failure. His fatal illness was due to Schönlein-Henoch purpura, with death from cerebral haemorrhage and bronchopneumonia. Venesection(s) may have contributed to his death. PMID:6352940

  7. Death Obsession in Palestinians

    ERIC Educational Resources Information Center

    Abdel-Khalek, Ahmed M.; Al-Arja, Nahida S.; Abdalla, Taysir

    2006-01-01

    The authors explored death obsession level and correlates among a sample (N=601) of Palestinians living in the city of Beit Jala, the village of Al-Khader, and the Aida refugee camp in the Bethlehem area. They live in war conditions; the houses of half of them have been demolished. The Death Obsession Scale (DOS) was administered. Its alpha…

  8. Programmed cell death

    SciTech Connect

    1995-12-31

    The purpose of this conference to provide a multidisciplinary forum for exchange of state-of-the-art information on the role programmed cell death plays in normal development and homeostasis of many organisms. This volume contains abstracts of papers in the following areas: invertebrate development; immunology/neurology; bcl-2 family; biochemistry; programmed cell death in viruses; oncogenesis; vertebrate development; and diseases.

  9. The Psychology of Death

    ERIC Educational Resources Information Center

    Fields, B. Celestine

    1976-01-01

    Forty-eight black men and women living and/or attending school in the St. Louis and Washington, D.C. areas responded to questionnaires concerning feelings, attitudes, emotions, etc. towards death and dying. It is concluded that blacks see death as a very significant happening; and that although in some areas blacks have become Americanized in…

  10. Death with dignity.

    PubMed

    Mathiews, Ann Kimberlin

    2010-01-01

    The concept of death with dignity evolves over a nurse's career. A new nurse focuses on the patient as a person. As the nurse gains experience, she facilitates family grieving. As a seasoned professional, the nurse emphasizes the dignity that, through effective nursing, can be restored to dying. Preservation of dignity is found in the way we honor death.

  11. Death Writ Large

    ERIC Educational Resources Information Center

    Kastenbaum, Robert

    2004-01-01

    Mainstream thanatology has devoted its efforts to improving the understanding, care, and social integration of people who are confronted with life-threatening illness or bereavement. This article suggests that it might now be time to expand the scope and mission to include large-scale death and death that occurs through complex and multi-domain…

  12. Facing Up to Death

    ERIC Educational Resources Information Center

    Ross, Elizabeth Kubler

    1972-01-01

    Doctor urges that Americans accept death as a part of life and suggests ways of helping dying patients and their families face reality calmly, with peace. Dying children and their siblings, as well as children's feelings about relatives' deaths, are also discussed. (PD)

  13. The Sociology of Death

    ERIC Educational Resources Information Center

    Fulton, Robert

    1977-01-01

    When we start to look at the issues associated with dying and death, we must do so in terms of the broadest parameters imaginable. Presented at the Conference on Death and Dying: Education, Counseling, and Care, December 1-3, 1976, Orlando, Florida. (Author)

  14. Facing Up to Death

    ERIC Educational Resources Information Center

    Ross, Elizabeth Kubler

    1972-01-01

    Doctor urges that Americans accept death as a part of life and suggests ways of helping dying patients and their families face reality calmly, with peace. Dying children and their siblings, as well as children's feelings about relatives' deaths, are also discussed. (PD)

  15. The Sociology of Death

    ERIC Educational Resources Information Center

    Fulton, Robert

    1977-01-01

    When we start to look at the issues associated with dying and death, we must do so in terms of the broadest parameters imaginable. Presented at the Conference on Death and Dying: Education, Counseling, and Care, December 1-3, 1976, Orlando, Florida. (Author)

  16. Education for Death

    ERIC Educational Resources Information Center

    Puolimatka, Tapio; Solasaari, Ulla

    2006-01-01

    Death is an unavoidable fact of human life, which cannot be totally ignored in education. Children reflect on death and raise questions that deserve serious answers. If an educator completely evades the issue, children will seek other conversation partners. It is possible to find arguments both from secular and religious sources, which alleviate…

  17. Death in Literature.

    ERIC Educational Resources Information Center

    Perkins, Lola A.

    "Death in Literature," a nine-week elective course for high school juniors and seniors, was added to the English curriculum at a Kansas City high school in 1976. It has proved very popular with students and is being expanded to 18 weeks. The explicit objectives of the course are to help students to explore the theme of death in various types of…

  18. Death, Children, and Books.

    ERIC Educational Resources Information Center

    Carr, Robin L.

    The books listed in this annotated bibliography are intended to help children understand the reality of death and deal with the mystery and emotions that accompany it. Each entry indicates the genre and reading level of the book and provides a brief description of the attitude toward death that it conveys. The selections include fables, fantasy,…

  19. Death Acceptance through Ritual

    ERIC Educational Resources Information Center

    Reeves, Nancy C.

    2011-01-01

    This article summarizes the author's original research, which sought to discover the elements necessary for using death-related ritual as a psychotherapeutic technique for grieving people who experience their grief as "stuck," "unending," "maladaptive," and so on. A "death-related ritual" is defined as a ceremony, directly involving at least 1…

  20. Conflicting Thoughts about Death

    ERIC Educational Resources Information Center

    Harris, Paul L.

    2011-01-01

    Most research on children's conception of death has probed their understanding of its biological aspects: its inevitability, irreversibility and terminal impact. Yet many adults subscribe to a religious conception implying that death marks the beginning of a new life. Two recent empirical studies confirm that in the course of development, children…

  1. Death Writ Large

    ERIC Educational Resources Information Center

    Kastenbaum, Robert

    2004-01-01

    Mainstream thanatology has devoted its efforts to improving the understanding, care, and social integration of people who are confronted with life-threatening illness or bereavement. This article suggests that it might now be time to expand the scope and mission to include large-scale death and death that occurs through complex and multi-domain…

  2. Near-death experiences.

    PubMed Central

    Blackmore, S J

    1996-01-01

    Reactions to claims of near-death experiences (NDE) range from the popular view that this must be evidence for life after death, to outright rejection of the experiences as, at best, drug induced hallucinations or, at worse, pure invention. Twenty years, and much research, later, it is clear that neither extreme is correct. PMID:8683504

  3. Death Acceptance through Ritual

    ERIC Educational Resources Information Center

    Reeves, Nancy C.

    2011-01-01

    This article summarizes the author's original research, which sought to discover the elements necessary for using death-related ritual as a psychotherapeutic technique for grieving people who experience their grief as "stuck," "unending," "maladaptive," and so on. A "death-related ritual" is defined as a ceremony, directly involving at least 1…

  4. Conflicting Thoughts about Death

    ERIC Educational Resources Information Center

    Harris, Paul L.

    2011-01-01

    Most research on children's conception of death has probed their understanding of its biological aspects: its inevitability, irreversibility and terminal impact. Yet many adults subscribe to a religious conception implying that death marks the beginning of a new life. Two recent empirical studies confirm that in the course of development, children…

  5. Dyadic Death: A Typology.

    ERIC Educational Resources Information Center

    Berman, Alan L.

    1996-01-01

    Describes and illustrates distinct types of dyadic death (where a second victim acts in consort with or is killed by a person who then commits suicide). Suggests an organizing dynamic of dyadic death and claims that levels of dominance, dependence-enmeshment, and the presence or absence of hostility influence the proposed typology. (RJM)

  6. Physician-assisted death.

    PubMed Central

    1995-01-01

    Physician-assisted death includes both euthanasia and assistance in suicide. The CMA urges its members to adhere to the principles of palliative care. It does not support euthanasia and assisted suicide. The following policy summary includes definitions of euthanasia and assisted suicide, background information, basic ethical principles and physician concerns about legalization of physician-assisted death. PMID:7632208

  7. Brain Death and Islam

    PubMed Central

    Ziad-Miller, Amna; Elamin, Elamin M.

    2014-01-01

    How one defines death may vary. It is important for clinicians to recognize those aspects of a patient’s religious beliefs that may directly influence medical care and how such practices may interface with local laws governing the determination of death. Debate continues about the validity and certainty of brain death criteria within Islamic traditions. A search of PubMed, Scopus, EMBASE, Web of Science, PsycNet, Sociological Abstracts, DIALOGUE ProQuest, Lexus Nexus, Google, and applicable religious texts was conducted to address the question of whether brain death is accepted as true death among Islamic scholars and clinicians and to discuss how divergent opinions may affect clinical care. The results of the literature review inform this discussion. Brain death has been acknowledged as representing true death by many Muslim scholars and medical organizations, including the Islamic Fiqh Academies of the Organization of the Islamic Conference and the Muslim World League, the Islamic Medical Association of North America, and other faith-based medical organizations as well as legal rulings by multiple Islamic nations. However, consensus in the Muslim world is not unanimous, and a sizable minority accepts death by cardiopulmonary criteria only. PMID:25287999

  8. Death, Children, and Books.

    ERIC Educational Resources Information Center

    Carr, Robin L.

    The books listed in this annotated bibliography are intended to help children understand the reality of death and deal with the mystery and emotions that accompany it. Each entry indicates the genre and reading level of the book and provides a brief description of the attitude toward death that it conveys. The selections include fables, fantasy,…

  9. Death Obsession in Palestinians

    ERIC Educational Resources Information Center

    Abdel-Khalek, Ahmed M.; Al-Arja, Nahida S.; Abdalla, Taysir

    2006-01-01

    The authors explored death obsession level and correlates among a sample (N=601) of Palestinians living in the city of Beit Jala, the village of Al-Khader, and the Aida refugee camp in the Bethlehem area. They live in war conditions; the houses of half of them have been demolished. The Death Obsession Scale (DOS) was administered. Its alpha…

  10. Death with dignity

    PubMed Central

    Allmark, P.

    2002-01-01

    The purpose of this article is to develop a conception of death with dignity and to examine whether it is vulnerable to the sort of criticisms that have been made of other conceptions. In this conception "death" is taken to apply to the process of dying; "dignity" is taken to be something that attaches to people because of their personal qualities. In particular, someone lives with dignity if they live well (in accordance with reason, as Aristotle would see it). It follows that health care professionals cannot confer on patients either dignity or death with dignity. They can, however, attempt to ensure that the patient dies without indignity. Indignities are affronts to human dignity, and include such things as serious pain and the exclusion of patients from involvement in decisions about their lives and deaths. This fairly modest conception of death with dignity avoids the traps of being overly subjective or of viewing the sick and helpless as "undignified". PMID:12161582

  11. Death with dignity.

    PubMed

    Allmark, Peter

    2002-08-01

    The purpose of this article is to develop a conception of death with dignity and to examine whether it is vulnerable to the sort of criticisms that have been made of other conceptions. In this conception "death" is taken to apply to the process of dying; "dignity" is taken to be something that attaches to people because of their personal qualities. In particular, someone lives with dignity if they live well (in accordance with reason, as Aristotle would see it). It follows that health care professionals cannot confer on patients either dignity or death with dignity. They can, however, attempt to ensure that the patient dies without indignity. Indignities are affronts to human dignity, and include such things as serious pain and the exclusion of patients from involvement in decisions about their lives and deaths. This fairly modest conception of death with dignity avoids the traps of being overly subjective or of viewing the sick and helpless as "undignified".

  12. Death in Denmark.

    PubMed Central

    Evans, M

    1990-01-01

    Does it matter that the hearts of 'brainstem dead' patients may persist in beating spontaneously? Hostile reactions, to the Danish inclusion of cardiac criteria in the determination of death, betray reductionist views of human life at the core of 'brainstem' conceptions of death. Such views (whether centred on neurological function or on abstractions concerning 'personhood') supplant the richness of human life and death with the poverty of essentialism: and mask the lethal nature of beating-heart organ retrieval. The affirmation of cardiac criteria for death is not an alternative form of essentialism as some critics suppose, but part of an understanding of human life and death which rejects essentialism altogether. The spontaneously persistent heartbeat does not constitute human life, but most certainly counts for it. PMID:2287015

  13. Death Cafés: Death Doulas and Family Communication

    PubMed Central

    Baldwin, Paula K.

    2017-01-01

    The Death Café is part of the Death Positive movement, and as such, is uniquely positioned to bring the dialogue about death and dying to the public. Participants in a Death Café typically have two different perspectives. Some participants have not experienced death in their family and friends’ circle and wish to converse with others about their beliefs on death and dying. Others are those who have experienced death somewhere in their circle of friends and families. One of goals of the Death Café facilitators is to help attendees reconcile their family narratives regarding death using the broader lens of the Death Café. Using the insights provided by interviews from 15 Death Café facilitators, this manuscript discusses the role of the Death Café facilitators as the death doulas of family communication. PMID:28445392

  14. Life and Death Decision Analysis.

    DTIC Science & Technology

    1979-12-01

    LIFE SMOKING: CANCER, EMPHYSEMA, SHORTENED LIFE BATHING: FALLING, ELECTROCUTION CONTRACEPTION: DEATH , ILLNESS PREGNANCY: DEATH , ILLNESS ABORTION ...economic effect is the one with the highest probability of causing my death . -13- EXPECTED NET SYSTEM DESIGN BENEFIT TO ME DEATH DEATH (r A(excluding death ...0-AO81 424 STANFORD UNIV CALIF DEPT OF ENGtNEERING-ECONOM!C SYSTEMS F/6 12/1 LIFE ANDI DEATH DECISION ANALYSIS.CU) DEC 79 R A HOWARD N0OOIN-79-C-0036

  15. [Death experience. Antidote against fear to death].

    PubMed

    Fericgla, Josep M

    2003-12-01

    Fortunately, anthropology has brought to our modern society a higher interest for mankind's cultural dimension and the values which each people employ in order to make sense out of the changes which occur during our lives. It is this cultural dimension which permits men to develop our innate capacities and to become humans. However, in order to achieve this, we need experiences which are codified and interpreted by a values system which each individual has made his/her own. Some of these experiences take place inside cultural mores constructed expressly so that they are useful for one's lifestyle; these are known as rites. A rite, therefore, is an experience which leaves an impression, which implies social and biographical changes, which provides meaning to human beings' universal interests. Nonetheless, since rites usually are organized by diverse religions, it is convenient, as we enter the 21st Century, to speak about Experiences which Activate Structures as means to approach, to come to grasp with, some of the great causes of anxiety in humans: death and insanity. These Experiences which Activate Structures allow us to subjectively experiment, to conquer our fears and to be more conscious of our here and our now. Workshops on the Living Integration of One's Own Death are included in this context as an appropriate forum through which to approach death with knowledge and serenity, inducing changes in our own lifestyle as well and helping us to overcome situations of existential blockage.

  16. Effects of Death Education on Conscious and Unconscious Death Anxiety.

    ERIC Educational Resources Information Center

    Hayslip, Bert, Jr.; And Others

    1994-01-01

    Adults (n=162) varying in extent of participation in didactic or experiential forms of death education versus those who had no such exposure to death and dying-related issues completed measures of conscious and unconscious death fears. Findings suggest that didactic death education was effective in altering death anxiety, although effects were…

  17. Brain death is not death: a critique of the concept, criterion, and tests of brain death.

    PubMed

    Joffe, Ari R

    2009-01-01

    This paper suggests that there are insurmountable problems for brain death as a criterion of death. The following are argued: (1) brain death does not meet an accepted concept of death, and is not the loss of integration of the organism as a whole; (2) brain death does not meet the criterion of brain death itself; brain death is not the irreversible loss of all critical functions of the entire brain; and (3) brain death may, however rarely, be reversible. I conclude that brain death, while a devastating neurological state with a dismal prognosis, is not death.

  18. Unusual sudden death.

    PubMed Central

    Warren, J. V.

    1985-01-01

    In contrast to usual sudden death seen in the course of coronary artery disease, individuals dying suddenly from other causes form a complex array of situations. In some the causes are readily identifiable. No simple pattern is available to identify the potential candidate, but on review of the many causes some moves by the physician may be helpful. For example, a more complete physical evaluation of young individuals participating in competitive athletics is in order. This is particularly true if the athlete reports an episode of unexplained syncope. This may well be the warning of a propensity towards sudden death under physical and emotional stress. Knowledge of the specific problems in underwater swimming and diving, in high altitude exposure and in various circumstances such as certain weight reduction diets and industrial exposures may lead to control of some types of unusual sudden death. Clearly, more studies are needed to give answers in so called crib death. As the incidence of usual sudden death falls, these unusual forms of sudden death will represent a more important fraction of sudden death in general. PMID:6537674

  19. Sudden cardiac death.

    PubMed

    Kuriachan, Vikas P; Sumner, Glen L; Mitchell, L Brent

    2015-04-01

    Sudden death accounts for 300,000-400,000 deaths annually in the United States. Most sudden deaths are cardiac, and most sudden cardiac deaths are related to arrhythmias secondary to structural heart disease or primary electrical abnormalities of the heart. The most common structural disease leading to sudden death is ischemic heart disease. Nonischemic cardiomyopathy and other structural abnormalities such as arrhythmogenic ventricular dysplasia and hypertrophic cardiomyopathy may also be causative. Patients without structural disease have a primary electrical abnormality, such as long-QT syndrome or Brugada syndrome. Severe left ventricular systolic dysfunction is the main marker for sudden death in patients with ischemic or nonischemic cardiomyopathy. In other conditions, other markers for structural heart disease and electrical abnormalities need to be considered. It is seen that β-blocker therapy is associated with a reduction in sudden cardiac death across a broad range of disorders. Nevertheless, the implantable cardioverter defibrillator remains the most effective treatment strategy in selected patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Suicide on Death Row.

    PubMed

    Tartaro, Christine; Lester, David

    2016-11-01

    Despite the level of supervision of inmates on death row, their suicide rate is higher than both the male prison population in the United States and the population of males over the age of 14 in free society. This study presents suicide data for death row inmates from 1978 through 2010. For the years 1978 through 2010, suicide rates on death row were higher than that for the general population of males over the age of 15 and for state prisons for all but 2 years.

  1. Byron on Death

    DTIC Science & Technology

    1991-01-01

    in "To Inez") may be found in the aptly titled poem " Euthanasia " (1812). Not only does the poem embody a clear conception of Death , more importantly...stanza of " Euthanasia " clearly hE is the oblivion of Death as something to be welcomed. This sentiment is echoed by the First Destiny in Manfred: The...dreaded. It would be something better still never to have been. The conception of and attitude toward Death clearly expressed in " Euthanasia " and evidenced

  2. An autologous in situ tumor vaccination approach for hepatocellular carcinoma. 2. Tumor-specific immunity and cure after radio-inducible suicide gene therapy and systemic CD40-ligand and Flt3-ligand gene therapy in an orthotopic tumor model.

    PubMed

    Kawashita, Yujo; Deb, Niloy J; Garg, Madhur K; Kabarriti, Rafi; Fan, Zuoheng; Alfieri, Alan A; Roy-Chowdhury, Jayanta; Guha, Chandan

    2014-08-01

    Diffuse hepatocellular carcinoma (HCC) is a lethal disease that radiation therapy (RT) currently has a limited role in treating because of the potential for developing fatal radiation-induced liver disease. However, recently diffuse HCC, "radio-inducible suicide gene therapy" has been shown to enhance local tumor control and residual microscopic disease within the liver for diffuse HCC, by using a combination of chemoactivation and molecular radiosensitization. We have demonstrated that the addition of recombinant adenovirus-expressing human Flt3 ligand (Adeno-Flt3L) after radio-inducible suicide gene therapy induced a Th1-biased, immune response and enhanced tumor control in an ectopic model of HCC. We hypothesized that sequential administration of recombinant adenovirus-expressing CD40L (Adeno-CD40L) could further potentiate the efficacy of our trimodal therapy with RT + HSV-TK + Adeno-Flt3L. We examined our hypothesis in an orthotopic model of diffuse HCC using BNL1ME A.7R.1 (BNL) cells in Balb/c mice. BNL murine hepatoma cells (5 × 10(4)) transfected with an expression vector of HSV-TK under the control of a radiation-inducible promoter were injected intraportally into BALB/cJ mice. Fourteen days after the HCC injection, mice were treated with a 25 Gy dose of radiation to the whole liver, followed by ganciclovir (GCV) treatment and systemic adenoviral cytokine gene therapy (Flt3L or CD40L or both). Untreated mice died in 27 ± 4 days. Radiation therapy alone had a marginal effect on survival (median = 35 ± 7 days) and the addition of HSV-TK/GCV gene therapy improved the median survival to 47 ± 6 days. However, the addition of Adeno-Flt3L to radiation therapy and HSV-TK/GCV therapy significantly (P = 0.0005) increased survival to a median of 63 ± 20 days with 44% (7/16) of the animals still alive 116 days after tumor implantation. The curative effect of Flt3L was completely abolished when using immunodeficient nude mice or mice depleted for CD4, CD8 and

  3. Children's Death Concepts and Ethnicity.

    ERIC Educational Resources Information Center

    Wass, Hannelore; Towry, Betty J.

    1980-01-01

    Relationships between death concepts of Black and White children and their racial status were examined. Lower-middle-class elementary children completed a four-item questionnaire on death. Most children defined death as the end of living and listed physical causes as the explanation of death. In general, children's death concepts were similar.…

  4. Lipids and cell death in yeast

    PubMed Central

    Eisenberg, Tobias; Büttner, Sabrina

    2014-01-01

    Understanding lipid-induced malfunction represents a major challenge of today's biomedical research. The connection of lipids to cellular and organ dysfunction, cell death, and disease (often referred to as lipotoxicity) is more complex than the sole lipotoxic effects of excess free fatty acids and requires genetically tractable model systems for mechanistic investigation. We herein summarize recent advances in the field of lipid-induced toxicity that employ the established model system for cell death and aging research of budding yeast Saccharomyces cerevisiae. Studies in yeast have shed light on various aspects of lipotoxicity, including free fatty acid toxicity, sphingolipid-modulated cell death as well as the involvement of cardiolipin and lipid peroxidation in the mitochondrial pathways of apoptosis. Regimens used range from exogenously applied lipids, genetic modulation of lipolysis and triacylglyceride synthesis, variations in sphingolipid/ceramide metabolism as well as changes in peroxisome function by either genetic or pharmacological means. In future, the yeast model of programmed cell death will further contribute to the clarification of crucial questions of lipid-associated malfunction. PMID:24119111

  5. Death Valley, California

    NASA Image and Video Library

    2009-06-29

    Death Valley, Calif., has the lowest point in North America, Badwater at 85.5 meters 282 feet below sea level. It is also the driest and hottest location in North America. This image is from NASA Terra spacecraft.

  6. Eighth Amendment & Death Penalty.

    ERIC Educational Resources Information Center

    Shortall, Joseph M.; Merrill, Denise W.

    1987-01-01

    Presents a lesson on capital punishment for juveniles based on three hypothetical cases. The goal of the lesson is to have students understand the complexities of decisions regarding the death penalty for juveniles. (JDH)

  7. Eighth Amendment & Death Penalty.

    ERIC Educational Resources Information Center

    Shortall, Joseph M.; Merrill, Denise W.

    1987-01-01

    Presents a lesson on capital punishment for juveniles based on three hypothetical cases. The goal of the lesson is to have students understand the complexities of decisions regarding the death penalty for juveniles. (JDH)

  8. Hitler's Death Camps.

    ERIC Educational Resources Information Center

    Wieser, Paul

    1995-01-01

    Presents a high school lesson on Hitler's death camps and the widespread policy of brutality and oppression against European Jews. Includes student objectives, instructional procedures, and a chart listing the value of used clothing taken from the Jews. (CFR)

  9. Another Death Star?

    NASA Image and Video Library

    2012-12-03

    Although Mimas holds the unofficial designation of Death Star moon, Tethys is seen here also vaguely resembling the space station from Star Wars. Apparently, Tethys doesnt want Mimas to have all the fun!

  10. Flying by the Death

    NASA Image and Video Library

    2010-03-29

    In this view captured by NASA Cassini spacecraft on its closest-ever flyby of Saturn moon Mimas, large Herschel Crater dominates Mimas, making the moon look like the Death Star in the movie Star Wars.

  11. Hitler's Death Camps.

    ERIC Educational Resources Information Center

    Wieser, Paul

    1995-01-01

    Presents a high school lesson on Hitler's death camps and the widespread policy of brutality and oppression against European Jews. Includes student objectives, instructional procedures, and a chart listing the value of used clothing taken from the Jews. (CFR)

  12. Coping with death.

    PubMed

    Linebarger, Jennifer S; Sahler, Olle Jane Z; Egan, Kelsey A

    2009-09-01

    Children's concept of death is influenced by experience, culture, and developmental stage. Dying children benefit from open communication about death, based on research findings and clinical experience (summarized in Hurwitz, 2004). Everyone in the family is affected by the loss of a loved one, even the youngest family members. Pediatricians can help families by listening and supporting them during the processes of loss and bereavement.

  13. A Good Death

    PubMed Central

    2007-01-01

    The Institute of Medicine defines a good death a “one that is free from avoidable death and suffering for patients, families and caregivers in general accordance with the patients’ and families’ wishes.”. The current system creates barriers to reducing the stress and suffering that accompany a patient’s end of life. Data and eHealth technology, if it were more accessible, could help patients, families, and caregivers to cope with end of life issues. PMID:17478415

  14. Preparation for Death

    PubMed Central

    Scott, J. F.

    1981-01-01

    Preparation for death is a physical, psychosocial and spiritual process needing the active participation of both patient and physician. Physicians' denial of death leads to unrelieved symptoms, inappropriate treatment, and poor communication in the care of the terminally ill. This paper discusses strategies to minimize the effect of denial describing a goal-setting approach to terminal care and the use of quality of life indices. Several principles are presented on how to tell bad news to patients. PMID:21289837

  15. Funerals against death

    PubMed Central

    Bailey, Tara; Walter, Tony

    2016-01-01

    While anthropological studies in non-Western societies show how funerals protect the community from the threat of death, sociological studies of British funerals have so far focused on meanings for the private family. The article reports on results from a Mass Observation directive – the first British study to focus specifically on the entire funeral congregation – and shows how attendees experience the contemporary life-centred funeral as a symbolic conquest of death. While the eulogy’s accuracy is important, even more so – at least for some – is its authenticity, namely that the speaker has personal knowledge of the deceased. Whereas Davies analyses the power of professionally delivered ritual words against death, our data reveals how admired is the courage exercised by non-professionals in speaking against death, however faltering their words. Further, the very presence of a congregation whose members have known the deceased in diverse ways embodies a configurational eulogy, which we term relationships against death. We thus argue that funerals symbolically conquer death not only through words delivered by ritual specialists, but also through those who knew the deceased congregating and speaking. PMID:27019605

  16. Classification of cell death

    PubMed Central

    Kroemer, G; Galluzzi, L; Vandenabeele, P; Abrams, J; Alnemri, ES; Baehrecke, EH; Blagosklonny, MV; El-Deiry, WS; Golstein, P; Green, DR; Hengartner, M; Knight, RA; Kumar, S; Lipton, SA; Malorni, W; Nuñez, G; Peter, ME; Tschopp, J; Yuan, J; Piacentini, M; Zhivotovsky, B; Melino, G

    2009-01-01

    Different types of cell death are often defined by morphological criteria, without a clear reference to precise biochemical mechanisms. The Nomenclature Committee on Cell Death (NCCD) proposes unified criteria for the definition of cell death and of its different morphologies, while formulating several caveats against the misuse of words and concepts that slow down progress in the area of cell death research. Authors, reviewers and editors of scientific periodicals are invited to abandon expressions like ‘percentage apoptosis’ and to replace them with more accurate descriptions of the biochemical and cellular parameters that are actually measured. Moreover, at the present stage, it should be accepted that caspase-independent mechanisms can cooperate with (or substitute for) caspases in the execution of lethal signaling pathways and that ‘autophagic cell death’ is a type of cell death occurring together with (but not necessarily by) autophagic vacuolization. This study details the 2009 recommendations of the NCCD on the use of cell death-related terminology including ‘entosis’, ‘mitotic catastrophe’, ‘necrosis’, ‘necroptosis’ and ‘pyroptosis’. PMID:18846107

  17. The death instinct.

    PubMed

    Lowental, U

    1983-01-01

    The death instinct has always been a controversial concept, insufficient to account for actual dying, and usually taken to be fused with aggression. After dislodging it from the shadow of aggression in order to evaluate its function, the instinct turns out to be one of the components that form the death motivation. Human beings develop a complex motivation for death, one that is more than biology (instincts) or physics (entropy). It includes (a) the death instinct, the primary analogue; (b) sequellae of the universal experience of object-loss, with identification and fantasies of a restorative reunion; (c) guilt over hostile attitudes toward the lost object, with depression, longings for atonement , and self-punishment; (d) compliance with reality, like that of old age or grave sickness. Examined in light of the complementary series of Freud's aetiological equation, the death instinct turns into a precondition of the composition motivation. Death motivation is a comprehensive concept, since patients express various of its aspects during their psychoanalyses , and it facilitates a metapsychological understanding and refines the accuracy of interpretation.

  18. Dictyostelium cell death

    PubMed Central

    Levraud, Jean-Pierre; Adam, Myriam; Luciani, Marie-Françoise; de Chastellier, Chantal; Blanton, Richard L.; Golstein, Pierre

    2003-01-01

    Cell death in the stalk of Dictyostelium discoideum, a prototypic vacuolar cell death, can be studied in vitro using cells differentiating as a monolayer. To identify early events, we examined potentially dying cells at a time when the classical signs of Dictyostelium cell death, such as heavy vacuolization and membrane lesions, were not yet apparent. We observed that most cells proceeded through a stereotyped series of differentiation stages, including the emergence of “paddle” cells showing high motility and strikingly marked subcellular compartmentalization with actin segregation. Paddle cell emergence and subsequent demise with paddle-to-round cell transition may be critical to the cell death process, as they were contemporary with irreversibility assessed through time-lapse videos and clonogenicity tests. Paddle cell demise was not related to formation of the cellulose shell because cells where the cellulose-synthase gene had been inactivated underwent death indistinguishable from that of parental cells. A major subcellular alteration at the paddle-to-round cell transition was the disappearance of F-actin. The Dictyostelium vacuolar cell death pathway thus does not require cellulose synthesis and includes early actin rearrangements (F-actin segregation, then depolymerization), contemporary with irreversibility, corresponding to the emergence and demise of highly polarized paddle cells. PMID:12654899

  19. Death obsession in Palestinians.

    PubMed

    Abdel-Khalek, Ahmed M; Al-Arja, Nahida S; Abdalla, Taysir

    2006-04-01

    The authors explored death obsession level and correlates among a sample (N = 601) of Palestinians living in the city of Beit Jala, the village of Al-Khader, and the Aida refugee camp in the Bethlehem area. They live in war conditions; the houses of half of them have been demolished. The Death Obsession Scale (DOS) was administered. Its alpha reliability was .92, denoting high internal consistency. Among women, it yielded 1 factor, (General Death Obsession), whereas among men it yielded 3 factors: Death Rumination, Death Dominance, and Death Idea Repetition. Palestinian men and women attained significantly lower DOS mean scores than participants from 4 Arab countries: Egypt, Kuwait, Syria, and Lebanon in 7 out of 8 comparisons. However, Palestinian women had significantly higher DOS mean score than their Spanish, American and British counterparts, whereas Palestinian men had significantly higher mean DOS score than Spanish peers. The low DOS scores of Palestinians, in proportion to other Arab samples, may reflect their adaptation to strife and violence.

  20. [Deaths in hotels].

    PubMed

    Risse, Manfred; Weilbächer, Nadine; Birngruber, Christoph; Verhoff, Marcel A

    2010-01-01

    There are no verified statistics about deaths occurring in hotels, and only a few cases have been described in the literature. A recent case induced us to conduct a systematic search for deaths in hotels in the autopsy reports of the Institute of Legal Medicine in Giessen for the period from 1968 to 2009. This search yielded 22 evaluable cases in which persons had been found dead or had died in hotels. Data evaluated in the study were sex and age of the deceased, reason for the stay in the hotel and cause of death. Among the deaths, 18 were males and 4 females and the average age was 41 and 40 years respectively. 6 of the male guests had died from a natural and 10 from a non-natural cause. In the remaining two cases, the cause of death could not be determined, but as there was no evidence that another party had been involved, the cases were not further investigated. Of the 4 female guests, 3 had died of a natural cause; in one case, the cause of death remained unclear even after morphological and toxicological investigations. Surprisingly, a third of the men were found to be temporarily living in hotels due to social circumstances. This was not true for any of the women. Our retrospective analysis is based on a comparatively small number of deaths in what were mostly hotels in small to medium-sized towns. Interestingly, the gender ratio of 18:4 for deceased men and women was significantly higher than the usual gender ratio of 2:1 found for forensic autopsies. To be able to draw further conclusions, a greater number of cases would have to be analysed, for example by recruiting additional case files from other institutes of legal medicine. This would also open up the option of investigating possible regional variations.

  1. Modulation techniques

    NASA Technical Reports Server (NTRS)

    Schilling, D. L.

    1982-01-01

    Bandwidth efficient digital modulation techniques, proposed for use on and/or applied to satellite channels, are reviewed. In a survey of recent works on digital modulation techniques, the performance of several schemes operating in various environments are compared. Topics covered include: (1) quadrature phase shift keying; (2) offset - QPSK and MSK; (3) combined modulation and coding; and (4) spectrally efficient modulation techniques.

  2. Apoptosis repressor with caspase recruitment domain modulates second mitochondrial-derived activator of caspases mimetic-induced cell death through BIRC2/MAP3K14 signalling in acute myeloid leukaemia.

    PubMed

    Mak, Po Y; Mak, Duncan H; Ruvolo, Vivian; Jacamo, Rodrigo; Kornblau, Steven M; Kantarjian, Hagop; Andreeff, Michael; Carter, Bing Z

    2014-11-01

    Overexpression of the apoptosis repressor with caspase recruitment domain (ARC, also termed NOL3) protein predicts adverse outcome in patients with acute myeloid leukaemia (AML) and confers drug resistance to AML cells. The second mitochondrial-derived activator of caspases (SMAC, also termed DIABLO) mimetic, birinapant, promotes extrinsic apoptosis in AML cells. SMAC mimetics induce cleavage of cellular inhibitor of apoptosis (cIAP) proteins, leading to stabilization of the nuclear factor-κB (NF-κB)-inducing kinase (MAP3K14, also termed NIK) and activation of non-canonical NF-κB signalling. To enhance the therapeutic potential of SMAC mimetics in AML, we investigated the regulation and role of ARC in birinapant-induced apoptosis. We showed that birinapant increases ARC in AML and bone marrow-derived mesenchymal stromal cells (MSCs). Downregulation of MAP3K14 by siRNA decreased ARC levels and suppressed birinapant-induced ARC increase. Reverse-phase protein array analysis of 511 samples from newly diagnosed AML patients showed that BIRC2 (also termed cIAP1) and ARC were inversely correlated. Knockdown of ARC sensitized, while overexpression attenuated, birinapant-induced apoptosis. Furthermore, ARC knockdown in MSCs sensitized co-cultured AML cells to birinapant-induced apoptosis. Our data demonstrate that ARC is regulated via BIRC2/MAP3K14 signalling and its overexpression in AML or MSCs can function as a resistant factor to birinapant-induced leukaemia cell death, suggesting that strategies to inhibit ARC will improve the therapeutic potential of SMAC mimetics. © 2014 John Wiley & Sons Ltd.

  3. Metabolism and epigenetics in the nervous system: Creating cellular fitness and resistance to neuronal death in neurological conditions via modulation of oxygen-, iron-, and 2-oxoglutarate-dependent dioxygenases

    PubMed Central

    Karuppagounder, Saravanan S.; Kumar, Amit; Shao, Diana S.; Zille, Marietta; Bourassa, Megan W.; Caulfield, Joseph T.; Alim, Ishraq; Ratan, Rajiv R.

    2015-01-01

    Modern definitions of epigenetics incorporate models for transient but biologically important changes in gene expression that are unrelated to DNA code but responsive to environmental changes such as injury-induced stress. In this scheme, changes in oxygen levels (hypoxia) and/or metabolic co-factors (iron deficiency or diminished 2-oxoglutarate levels) are transduced into broad genetic programs that return the cell and the organism to a homeostatic set point. Over the past two decades, exciting studies have identified a superfamily of iron-, oxygen-, and 2-oxoglutarate-dependent dioxygenases that sit in the nucleus as modulators of transcription factor stability, co-activator function, histone demethylases, and DNA demethylases. These studies have provided a concrete molecular scheme for how changes in metabolism observed in a host of neurological conditions, including stroke, traumatic brain injury, and Alzheimer’s disease, could be transduced into adaptive gene expression to protect the nervous system. We will discuss these enzymes in this short review, focusing primarily on the ten eleven translocation (TET) DNA demethylases, the jumonji (JmJc) histone demethylases, and the oxygen-sensing prolyl hydroxylase domain enzymes (HIF PHDs). PMID:26232572

  4. The Influenza Virus H5N1 Infection Can Induce ROS Production for Viral Replication and Host Cell Death in A549 Cells Modulated by Human Cu/Zn Superoxide Dismutase (SOD1) Overexpression.

    PubMed

    Lin, Xian; Wang, Ruifang; Zou, Wei; Sun, Xin; Liu, Xiaokun; Zhao, Lianzhong; Wang, Shengyu; Jin, Meilin

    2016-01-08

    Highly pathogenic H5N1 infections are often accompanied by excessive pro-inflammatory response, high viral titer, and apoptosis; as such, the efficient control of these infections poses a great challenge. The pathogenesis of influenza virus infection is also related to oxidative stress. However, the role of endogenic genes with antioxidant effect in the control of influenza viruses, especially H5N1 viruses, should be further investigated. In this study, the H5N1 infection in lung epithelial cells decreased Cu/Zn superoxide dismutase (SOD1) expression at mRNA and protein levels. Forced SOD1 expression significantly inhibited the H5N1-induced increase in reactive oxygen species, decreased pro-inflammatory response, prevented p65 and p38 phosphorylation, and impeded viral ribonucleoprotein nuclear export and viral replication. The SOD1 overexpression also rescued H5N1-induced cellular apoptosis and alleviated H5N1-caused mitochondrial dysfunction. Therefore, this study described the role of SOD1 in the replication of H5N1 influenza virus and emphasized the relevance of this enzyme in the control of H5N1 replication in epithelial cells. Pharmacological modulation or targeting SOD1 may open a new way to fight H5N1 influenza virus.

  5. Metabolism and epigenetics in the nervous system: Creating cellular fitness and resistance to neuronal death in neurological conditions via modulation of oxygen-, iron-, and 2-oxoglutarate-dependent dioxygenases.

    PubMed

    Karuppagounder, Saravanan S; Kumar, Amit; Shao, Diana S; Zille, Marietta; Bourassa, Megan W; Caulfield, Joseph T; Alim, Ishraq; Ratan, Rajiv R

    2015-12-02

    Modern definitions of epigenetics incorporate models for transient but biologically important changes in gene expression that are unrelated to DNA code but responsive to environmental changes such as injury-induced stress. In this scheme, changes in oxygen levels (hypoxia) and/or metabolic co-factors (iron deficiency or diminished 2-oxoglutarate levels) are transduced into broad genetic programs that return the cell and the organism to a homeostatic set point. Over the past two decades, exciting studies have identified a superfamily of iron-, oxygen-, and 2-oxoglutarate-dependent dioxygenases that sit in the nucleus as modulators of transcription factor stability, co-activator function, histone demethylases, and DNA demethylases. These studies have provided a concrete molecular scheme for how changes in metabolism observed in a host of neurological conditions, including stroke, traumatic brain injury, and Alzheimer's disease, could be transduced into adaptive gene expression to protect the nervous system. We will discuss these enzymes in this short review, focusing primarily on the ten eleven translocation (TET) DNA demethylases, the jumonji (JmJc) histone demethylases, and the oxygen-sensing prolyl hydroxylase domain enzymes (HIF PHDs). This article is part of a Special Issue entitled SI: Neuroprotection. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. [Brain death diagnosis].

    PubMed

    Escudero, Dolores

    2009-05-01

    Brain death has been recognized by the scientific community as the person's death, and accepted in the legislation of different countries. Brain death is defined as the irreversible ending of the functions of all the intracranial neurological structure in both the brain and brain stem. This clinical situation appears when intracranial pressure exceeds the patient's systolic blood pressure, leading to brain circulatory arrest. The most frequent are cerebral hemorrhage and cranioencephalic trauma. Clinical diagnostic must be done by doctors with expertise in neurocritical patient treatment. This diagnosis is based on a systematic, complete and extremely rigorous clinical examination that confirms a non-reactive coma, absence of brain stem reflex, and absence of spontaneous breathing. Instrumental tests may be obligatory in some cases, this depending on each country. Electroencephalogram and evoked potentials are the electrophysiological tests used. In patients treated with sedative drugs, cerebral blood flow evaluation tests, such as cerebral angiography, transcranial Doppler or 99Tc-HMPAO scintigraphy, will be used. More than 92% of the transplants performed in Spain are performed with brain death donor organs. Brain death confirmation is a high responsibility act, with medical, ethical and legal significance since it requires removal of all artificial support, or organs extraction for transplant. Extensive knowledge on its diagnostic and correct decision making avoid unnecessary use of resources and improves management of organs for transplant.

  7. Potentiality, irreversibility, and death.

    PubMed

    Lizza, John P

    2005-02-01

    There has been growing concern about whether individuals who satisfy neurological criteria for death or who become non-heart-beating organ donors are really dead. This concern has focused on the issue of the potential for recovery that these individuals may still have and whether their conditions are irreversible. In this article I examine the concepts of potentiality and irreversibility that have been invoked in the discussions of the definition of death and non-heart-beating organ donation. I initially focus on the recent challenge by D. Alan Shewmon to accepting any neurological criterion of death. I argue that Shewmon relies on a problematic and unrealistic concept of potentiality, and that a better, more realistic concept of potentiality is consistent with accepting a neurological criterion for death. I then turn to an analysis of how the concept of irreversibility has been used in discussion of non-heart-beating organ donation. Similarly, I argue that some participants in this discussion have invoked a problematic and unrealistic concept of irreversibility. I then propose an alternative, more realistic account of irreversibility that explains how "irreversibility" should be understood in the definition and criteria of death.

  8. Precisely Tracking Childhood Death.

    PubMed

    Farag, Tamer H; Koplan, Jeffrey P; Breiman, Robert F; Madhi, Shabir A; Heaton, Penny M; Mundel, Trevor; Ordi, Jaume; Bassat, Quique; Menendez, Clara; Dowell, Scott F

    2017-07-01

    Little is known about the specific causes of neonatal and under-five childhood death in high-mortality geographic regions due to a lack of primary data and dependence on inaccurate tools, such as verbal autopsy. To meet the ambitious new Sustainable Development Goal 3.2 to eliminate preventable child mortality in every country, better approaches are needed to precisely determine specific causes of death so that prevention and treatment interventions can be strengthened and focused. Minimally invasive tissue sampling (MITS) is a technique that uses needle-based postmortem sampling, followed by advanced histopathology and microbiology to definitely determine cause of death. The Bill & Melinda Gates Foundation is supporting a new surveillance system called the Child Health and Mortality Prevention Surveillance network, which will determine cause of death using MITS in combination with other information, and yield cause-specific population-based mortality rates, eventually in up to 12-15 sites in sub-Saharan Africa and south Asia. However, the Gates Foundation funding alone is not enough. We call on governments, other funders, and international stakeholders to expand the use of pathology-based cause of death determination to provide the information needed to end preventable childhood mortality.

  9. Programmed cell death.

    PubMed

    Samuilov, V D; Oleskin, A V; Lagunova, E M

    2000-08-01

    This paper reviews data on programmed cell death (apoptosis) in animals and plants. Necrosis is a pathological scenario of cell death, which entails an inflammatory response in animal tissues. Apoptosis results in the disintegration of animal/plant cells into membrane vesicles enclosing the intracellular content, which are thereupon engulfed by adjacent or specialized cells (phagocytes) in animals. Plants lack such specialized cells, and plant cell walls prevent phagocytosis. The paper considers the main molecular mechanisms of apoptosis in animals and the pathways of activation of caspases, evolutionarily conserved cysteine proteases. A self-contained section concerns itself with the process of programmed cell death (PCD) in microorganisms including: 1) cell death in the myxomycete Dictyostelium discoideum and the parasitic flagellate Trypanosoma cruzi; 2) PCD in genetically manipulated yeast expressing the proapoptotic Bax and Bak proteins; 3) the death of a part of a prokaryotic cell population upon the depletion of nutrient resources or under stress; 4) the elimination of cells after a loss of a plasmid encoding a stable cytotoxic agent in combination with an unstable antidote; and 5) PCD in phage-infected bacterial cells.

  10. Precisely Tracking Childhood Death

    PubMed Central

    Farag, Tamer H.; Koplan, Jeffrey P.; Breiman, Robert F.; Madhi, Shabir A.; Heaton, Penny M.; Mundel, Trevor; Ordi, Jaume; Bassat, Quique; Menendez, Clara; Dowell, Scott F.

    2017-01-01

    Abstract. Little is known about the specific causes of neonatal and under-five childhood death in high-mortality geographic regions due to a lack of primary data and dependence on inaccurate tools, such as verbal autopsy. To meet the ambitious new Sustainable Development Goal 3.2 to eliminate preventable child mortality in every country, better approaches are needed to precisely determine specific causes of death so that prevention and treatment interventions can be strengthened and focused. Minimally invasive tissue sampling (MITS) is a technique that uses needle-based postmortem sampling, followed by advanced histopathology and microbiology to definitely determine cause of death. The Bill & Melinda Gates Foundation is supporting a new surveillance system called the Child Health and Mortality Prevention Surveillance network, which will determine cause of death using MITS in combination with other information, and yield cause-specific population-based mortality rates, eventually in up to 12–15 sites in sub-Saharan Africa and south Asia. However, the Gates Foundation funding alone is not enough. We call on governments, other funders, and international stakeholders to expand the use of pathology-based cause of death determination to provide the information needed to end preventable childhood mortality. PMID:28719334

  11. Pediatric brain death determination.

    PubMed

    Mathur, Mudit; Ashwal, Stephen

    2015-04-01

    Clinical guidelines for the determination of brain death in children were first published in 1987. These guidelines were revised in 2011 under the auspices of the Society of Critical Care Medicine, the American Academy of Pediatrics, and the Child Neurology Society, and provide the minimum standards that must be satisfied before brain death can be declared in infants and children. After achieving physiologic stability and exclusion of confounders, two examinations including apnea testing separated by an observation period (24 hours for term newborns up to 30 days of age, and 12 hours for infants and children from 31 days up to 18 years) are required to establish brain death. Apnea testing should demonstrate a final arterial PaCO2 20 mm Hg above the baseline and ≥ 60 mm Hg with no respiratory effort during the testing period. Ancillary studies (electroencephalogram and radionuclide cerebral blood flow) are not required to establish brain death and are not a substitute for the neurologic examination. The committee concluded that ancillary studies may be used (1) when components of the examination or apnea testing cannot be completed, (2) if uncertainty about components of the neurologic examination exists, (3) if a medication effect may be present, or (4) to reduce the interexamination observation period. When ancillary studies are used, a second clinical examination and apnea test should still be performed and components that can be completed must remain consistent with brain death.

  12. Adolescent Death Anxiety: The Effect of Death Education.

    ERIC Educational Resources Information Center

    Rosenthal, Nina Ribak

    1980-01-01

    An 18-week course on death and dying designed specifically for high school students significantly reduced participants' level of death anxiety. These results conflict with previous research on adolescents in which either increased anxiety or no significant differences in death anxiety were reported as a result of death education. (CM)

  13. Death Depression and Death Anxiety in HIV-Infected Males.

    ERIC Educational Resources Information Center

    Hintze, Julie; And Others

    1993-01-01

    Administered Death Anxiety Scale, Death Depression Scale, Beck Depression Inventory, State-Trait Anxiety Scale, and questionnaire assessing demographic and life-situation variables to 94 human immunodeficiency virus-infected gay men. Higher death anxiety and death depression were most highly correlated with state anxiety, trait anxiety,…

  14. Death Threat and Death Concerns in the College Student.

    ERIC Educational Resources Information Center

    Tobacyk, Jerome; Eckstein, Daniel

    1980-01-01

    Thanatology students reported significantly lesser death threat and significantly greater death concerns. Trait anxiety was found to be a significant predictor of change in death threat in the Thanatology Group, with lesser anxiety associated with greater decline in death threat. (Author)

  15. Perspectives on Death: An Experiential Course on Death Education.

    ERIC Educational Resources Information Center

    Stefan, Edwin S.

    1978-01-01

    Describes and evaluates a college psychology course on death education (thanatology). Course objectives were to help students become aware of the feelings involved in facing death, encourage discussion on the subject of death, motivate students to change their attitudes about death, and encourage practical planning for funeral arrangements.…

  16. Death Threat and Death Concerns in the College Student.

    ERIC Educational Resources Information Center

    Tobacyk, Jerome; Eckstein, Daniel

    1980-01-01

    Thanatology students reported significantly lesser death threat and significantly greater death concerns. Trait anxiety was found to be a significant predictor of change in death threat in the Thanatology Group, with lesser anxiety associated with greater decline in death threat. (Author)

  17. Perspectives on Death: An Experiential Course on Death Education.

    ERIC Educational Resources Information Center

    Stefan, Edwin S.

    1978-01-01

    Describes and evaluates a college psychology course on death education (thanatology). Course objectives were to help students become aware of the feelings involved in facing death, encourage discussion on the subject of death, motivate students to change their attitudes about death, and encourage practical planning for funeral arrangements.…

  18. Death Depression and Death Anxiety in HIV-Infected Males.

    ERIC Educational Resources Information Center

    Hintze, Julie; And Others

    1993-01-01

    Administered Death Anxiety Scale, Death Depression Scale, Beck Depression Inventory, State-Trait Anxiety Scale, and questionnaire assessing demographic and life-situation variables to 94 human immunodeficiency virus-infected gay men. Higher death anxiety and death depression were most highly correlated with state anxiety, trait anxiety,…

  19. Pathophysiological mechanisms of death resistance in colorectal carcinoma

    PubMed Central

    Huang, Ching-Ying; Yu, Linda Chia-Hui

    2015-01-01

    Colon cancers develop adaptive mechanisms to survive under extreme conditions and display hallmarks of unlimited proliferation and resistance to cell death. The deregulation of cell death is a key factor that contributes to chemoresistance in tumors. In a physiological context, balance between cell proliferation and death, and protection against cell damage are fundamental processes for maintaining gut epithelial homeostasis. The mechanisms underlying anti-death cytoprotection and tumor resistance often bear common pathways, and although distinguishing them would be a challenge, it would also provide an opportunity to develop advanced anti-cancer therapeutics. This review will outline cell death pathways (i.e., apoptosis, necrosis, and necroptosis), and discuss cytoprotective strategies in normal intestinal epithelium and death resistance mechanisms of colon tumor. In colorectal cancers, the intracellular mechanisms of death resistance include the direct alteration of apoptotic and necroptotic machinery and the upstream events modulating death effectors such as tumor suppressor gene inactivation and pro-survival signaling pathways. The autocrine, paracrine and exogenous factors within a tumor microenvironment can also instigate resistance against apoptotic and necroptotic cell death in colon cancers through changes in receptor signaling or transporter uptake. The roles of cyclooxygenase-2/prostaglandin E2, growth factors, glucose, and bacterial lipopolysaccharides in colorectal cancer will be highlighted. Targeting anti-death pathways in the colon cancer tissue might be a promising approach outside of anti-proliferation and anti-angiogenesis strategies for developing novel drugs to treat refractory tumors. PMID:26557002

  20. Cocaine-related deaths.

    PubMed

    Lora-Tamayo, C; Tena, T; Rodriguez, A

    1994-07-15

    Cocaine availability has been increasing in Spain in the past few years. A review of all the toxicological analyses carried out at the Madrid Department of the Instituto Nacional de Toxicología, with subjects who had died of drugs from 1990 to 1992, found 533 persons who had cocaine in their blood and/or tissues; 450 (84%) deaths involved cocaine and heroin together whereas 83 (16%) deaths involved cocaine with an absence of heroin. This paper reports the circumstances, cocaine and benzoylecgonine concentrations in the blood and other toxicological findings for the two major groups of deaths where cocaine was found with an absence of heroin, i.e., possible overdose cases (35 cases) and traffic accidents (23 cases).

  1. Amphetamine derivative related deaths.

    PubMed

    Lora-Tamayo, C; Tena, T; Rodríguez, A

    1997-02-28

    Amphetamine its methylendioxy (methylendioxyamphetamine methylenedioxymethylamphetamine, methylenedioxyethylamphetamine) and methoxy derivatives (p-methoxyamphetamine and p-methoxymethylamphetamine) are widely abused in Spanish society. We present here the results of a systematic study of all cases of deaths brought to the attention of the Madrid department of the Instituto Nacional de Toxicologia from 1993 to 1995 in which some of these drugs have been found in the cadaveric blood. The cases were divided into three categories: amphetamine and derivatives, amphetamines and alcohol, amphetamines and other drugs. Data on age, sex, clinical symptoms, morphological findings, circumstances of death, when known, and concentration of amphetamine derivatives, alcohol and other drugs in blood are given for each group. The information provided here may prove to be useful for the forensic interpretation of deaths which are directly or indirectly related to abuse of amphetamine derivatives.

  2. Death on Denali.

    PubMed

    Wilson, R; Mills, W J; Rodgers, D R; Propst, M T

    1978-06-01

    Between 1903 and 1975 about 1 percent of climbers on Mount McKinley (Denali) and Mount Foraker in Alaska died. In 1976 a total of ten (1.7 percent) of 587 mountaineers died, but this rate of death was not significantly higher than previously. Nineteen percent of climbers in 1976 suffered major or minor injuries, illness or death. Acute mountain sickness (AMS), frostbite and fractures were common. Thirty-three rescues or retrievals of bodies were mounted at a cost of more than $82,000. Inexperience (particularly with arctic mountaineering), poor leadership, faulty equipment and undue reliance on rescue by helicopter contributed to the alarming incidence of accident, illness and death on big peaks in Mount McKinley National Park in 1976.

  3. Death on Denali

    PubMed Central

    Wilson, Rodman; Mills, William J.; Rogers, Donald R.; Propst, Michael T.

    1978-01-01

    Between 1903 and 1975 about 1 percent of climbers on Mount McKinley (Denali) and Mount Foraker in Alaska died. In 1976 a total of ten (1.7 percent) of 587 mountaineers died, but this rate of death was not significantly higher than previously. Nineteen percent of climbers in 1976 suffered major or minor injuries, illness or death. Acute mountain sickness (AMS), frostbite and fractures were common. Thirty-three rescues or retrievals of bodies were mounted at a cost of more than $82,000. Inexperience (particularly with arctic mountaineering), poor leadership, faulty equipment and undue reliance on rescue by helicopter contributed to the alarming incidence of accident, illness and death on big peaks in Mount McKinley National Park in 1976. PMID:664648

  4. [Sexuality and death].

    PubMed

    Sapetti, Adrián

    2006-01-01

    It is intented to show two apparently antithetic poles: Sexuality and Death, in fact interpenetrate themselves, disguising the fear of death, or the desire to die, Eros' world. Different expressions of culture are analyzed, especially the one known as The Profane Time, the time for work, which is characterized by the submission to interdicts (prohibitions) and, on the other hand, the Time for Joy or The Sacred Time, characterized by the transgression of such prohibitions. Its relationship with the interdicts'violations in the sexual as well as in the death arena is analyzed in order to connect the human being's fear in the presence of the unrestraint, the overflow and the abandonment of the time established for work that would imply free sexuality. The latter is connected with some conclusions that could be considered useful in the field of Sexual Therapies, with a certain critical look at the mechanist settlement applied to those treatments.

  5. The Impact of Death Education on Fear of Death and Death Anxiety Among Human Services Students.

    PubMed

    McClatchey, Irene Searles; King, Steve

    2015-01-01

    Human services professionals will undoubtedly work with the dying and bereaved populations at one time or other. Yet, they are poorly prepared to do so since death education, that is, lessons about the human and emotional aspects of death, its implications, and subsequent bereavement issues, is often not part of their curriculum. This nonequivalent comparison group study (N = 86) examined death fear and death anxiety among human services students before and after receiving death education using the Multidimensional Fear of Death Scale. The results showed a statistically significant decrease in death anxiety among the group of students who participated in death education compared to those who did not.

  6. Death by Propofol.

    PubMed

    Diaz, James H; Kaye, Alan David

    2017-01-01

    Since its introduction in 1986, propofol ( two, 6-diisopropylphenol) , an intravenous sedative-hypnotic agent, has been utilized for the induction and maintenance of general anesthesia and conscious sedation in over 80 percent of cases; largely replacing thiopental ( sodium pentothal) over a decade ago. Unrestricted as a controlled substance, propofol's abuse potential emerged quickly and was highlighted by the death of pop singer, Michael Jackson, in 2009. In order to assess the epidemiological features of fatal propofol abuse, a descriptive analysis of the scientific literature was conducted using Internet search engines. Well-documented cases of fatal propofol abuse were stratified as unintentional or accidental deaths and as intentional deaths by suicides or homicides. Continuous variables were compared for differences by unpaired, two-tailed t-tests with statistical significance indicated by p-values less than 0.05. Of 21 fatal cases of propofol abuse, 18 (86 percent ) occurred in healthcare workers, mostly anesthesiologists and nurse anesthetists (n=14, 67 percent ). One case occurred in a layman who purchased propofol on the Internet. Seventeen deaths (81 percent ) were accidental; two were suicides (9.5 percent ) and two were homicides (9.5 percent ). Blood levels in intentional death cases were significantly greater than in accidental death cases (p less than 0.0001) all of which reflected initial therapeutic induction-level doses in the ranges of 2.0-2.5 mg/kg. Though lacking in analgesic effects, the abuse of propofol by young healthcare professionals, particularly operating room workers, has been significant; and likely underreported. Propofol is a dangerous drug with an evident abuse potential which often results in fatalities.

  7. [The death of Cleopatra].

    PubMed

    Guillemain, Bernard

    2009-01-01

    The image of a queen bitten by a snake is controversial and the facts, such as the swiftness of her death and her servants, and scientific experiments are in favour of a deadly poisoning. The author reminds that in the ancient texts the snake had sacred virtues and it was a symbolic image to embellish the suicide of the one who was sentenced to death by the Romans. Octaves set up the myth of a fatal bite which became an iconographic image for the cinema.

  8. [Near death experiences].

    PubMed

    Rubia Vila, Francisco José

    2012-01-01

    Near Death Experiences are those accounted by people who after being clinically dead return to life spontaneously or after reanimation. These experiences have been used traditionally to support the belief in the existence of the soul and of life after death. However, today neuroscience tries to explain these experiences from the scientific point of view, i.e. explaining them based on their brain substrates. Their resemblance to mystic experiences and to altered states of consciousness seems to indicate that they may be produced by hyperactivity of limbic structures caused by anoxia or hypercapnia.

  9. Death Anxiety Scales: A Dialogue.

    ERIC Educational Resources Information Center

    Lester, David; Templer, Donald

    1993-01-01

    Presents dialog among David Lester, author of first critical survey of death anxiety measures, developer of scales, and researcher about suicide and fear of death; Donald Templer, Death Anxiety Scale (DAS) creator; and journal editor. Lester and Templer discuss origins, uses, results, limitations, and future of death anxiety scales and research on…

  10. Teaching about the Death Penalty.

    ERIC Educational Resources Information Center

    Ryan, John Paul; Eden, John Michael

    1998-01-01

    Examines the reasons for the death penalty, the reasons why the death penalty attracts so much attention, whether the death penalty is applied consistently, and the evidence that the application of the death penalty may be racially biased. Provides an accompanying article on "Teaching Ideas" by Ronald A. Banaszak. (CMK)

  11. Teaching about the Death Penalty.

    ERIC Educational Resources Information Center

    Ryan, John Paul; Eden, John Michael

    1998-01-01

    Examines the reasons for the death penalty, the reasons why the death penalty attracts so much attention, whether the death penalty is applied consistently, and the evidence that the application of the death penalty may be racially biased. Provides an accompanying article on "Teaching Ideas" by Ronald A. Banaszak. (CMK)

  12. Digital Language Death

    PubMed Central

    Kornai, András

    2013-01-01

    Of the approximately 7,000 languages spoken today, some 2,500 are generally considered endangered. Here we argue that this consensus figure vastly underestimates the danger of digital language death, in that less than 5% of all languages can still ascend to the digital realm. We present evidence of a massive die-off caused by the digital divide. PMID:24167559

  13. Death of a Leader.

    ERIC Educational Resources Information Center

    McLaughlin, Thomas E.

    1994-01-01

    When Issaquah (Washington) superintendent, after battling a brain tumor, entered the hospital for the last time, school district had to develop a crisis plan to deal with the possible death of the superintendent. A contingency planning team developed a telephone tree for school officials to keep in close contact with teachers and administrators.…

  14. Death and Grief

    MedlinePlus

    ... response to a death or loss. Grief can affect our body, mind, emotions, and spirit. People might notice or show grief in several ways: Physical reactions: These might be things like changes in appetite or sleep, an upset stomach, tight chest, crying, tense muscles, ...

  15. The Death Penalty.

    ERIC Educational Resources Information Center

    Crockett, Mark

    1990-01-01

    Provides a lesson plan on the Eighth Amendment to the U.S. Constitution and the imposition of the death penalty. Focuses on the controversy concerning capital punishment and stimulates critical thinking in an analysis and discussion of eight hypothetical situations. Includes suggestions for readings, videotapes, and writing assignments. (NL)

  16. Death Penalty in America.

    ERIC Educational Resources Information Center

    Clifford, Amie L.

    1997-01-01

    Examines the legal and moral issues, controversies, and unique trial procedures involved with the death penalty. Discusses the 1972 landmark Supreme Court decision that resulted in many states abolishing this punishment, only to reintroduce it later with different provisions. Reviews the controversial case of Sam Sheppard. (MJP)

  17. Death Penalty in America.

    ERIC Educational Resources Information Center

    Clifford, Amie L.

    1997-01-01

    Examines the legal and moral issues, controversies, and unique trial procedures involved with the death penalty. Discusses the 1972 landmark Supreme Court decision that resulted in many states abolishing this punishment, only to reintroduce it later with different provisions. Reviews the controversial case of Sam Sheppard. (MJP)

  18. Sudden Infant Death Syndrome.

    ERIC Educational Resources Information Center

    Barnett, Henry L.; And Others

    There is a growing body of evidence that Sudden Infant Death Syndrome (SIDS) victims are not completely normal and healthy, as was once believed. A variety of new information from several disciplines strongly suggests that the infant who dies suddenly and unexpectedly may do so because of subtle developmental, neurologic, cardiorespiratory, and…

  19. Lifespan Attitudes toward Death.

    ERIC Educational Resources Information Center

    Walker, Gail; Maiden, Robert

    To more fully understand how attitudes toward death and dying develop and change across the lifespan, 90 male and female subjects between the ages of 2 and 18 years and 90 male and female subjects between the ages of 18 and 97 were administered questionnaires and interviews about dying. The results revealed that children's attitudes were…

  20. Sudden Infant Death Syndrome.

    ERIC Educational Resources Information Center

    Barnett, Henry L.; And Others

    There is a growing body of evidence that Sudden Infant Death Syndrome (SIDS) victims are not completely normal and healthy, as was once believed. A variety of new information from several disciplines strongly suggests that the infant who dies suddenly and unexpectedly may do so because of subtle developmental, neurologic, cardiorespiratory, and…

  1. The Death Penalty.

    ERIC Educational Resources Information Center

    Crockett, Mark

    1990-01-01

    Provides a lesson plan on the Eighth Amendment to the U.S. Constitution and the imposition of the death penalty. Focuses on the controversy concerning capital punishment and stimulates critical thinking in an analysis and discussion of eight hypothetical situations. Includes suggestions for readings, videotapes, and writing assignments. (NL)

  2. [Death of Napoleon Bonaparte].

    PubMed

    Camici, M

    2003-06-01

    The causa mortis of Napoleon Bonaparte has been vexata quaestio for a long time. The author tries to outline a picture of Napoleon from a sanitary point of view. From the report of doctor Francesco Antonmarchi who performed the autopsy, the author tries to understans the cause of death: gastric perforation due to malignant ulcer and subsequent peritonitis with pulmonary tubercolosis.

  3. Counseling and Death.

    ERIC Educational Resources Information Center

    Barry, John R.

    Increasingly, helpers are asked to counsel the dying and their relatives. The research and other literature are reviewed for information and ideas that might be helpful to a counselor; for example, research and speculation about fears of death are examined. While an awareness of such information may reassure the counselor who tries to counsel in…

  4. Death of a Leader.

    ERIC Educational Resources Information Center

    McLaughlin, Thomas E.

    1994-01-01

    When Issaquah (Washington) superintendent, after battling a brain tumor, entered the hospital for the last time, school district had to develop a crisis plan to deal with the possible death of the superintendent. A contingency planning team developed a telephone tree for school officials to keep in close contact with teachers and administrators.…

  5. Death understanding and fear of death in young children.

    PubMed

    Slaughter, Virginia; Griffiths, Maya

    2007-10-01

    The purpose of this study was to test whether the developmental acquisition of a mature concept of death, that is, understanding death as a biological event, affects young children's fear of death. Ninety children between the ages of 4 and 8 participated in an interview study in which their understanding of death and their fear of death were both assessed. Levels of general anxiety were also measured via parent report. A regression analysis indicated that more mature death understanding was associated with lower levels of death fear, when age and general anxiety were controlled. These data provide some empirical support for the widely held belief that discussing death and dying in biological terms is the best way to alleviate fear of death in young children.

  6. Effects of Death Education on Fear of Death and Attitudes towards Death and Life.

    ERIC Educational Resources Information Center

    Leviton, Dan; Fretz, Bruce

    1978-01-01

    Students in a death education course were compared with students of sex education and introductory psychology. After the death education course, students viewed death as more approachable, and wished to experience death in a more interpersonal as compared to a technological context. (Author)

  7. Actin as Deathly Switch? How Auxin Can Suppress Cell-Death Related Defence

    PubMed Central

    Chang, Xiaoli; Riemann, Michael; Liu, Qiong; Nick, Peter

    2015-01-01

    Plant innate immunity is composed of two layers – a basal immunity, and a specific effector-triggered immunity, which is often accompanied by hypersensitive cell death. Initiation of cell death depends on a complex network of signalling pathways. The phytohormone auxin as central regulator of plant growth and development represents an important component for the modulation of plant defence. In our previous work, we showed that cell death is heralded by detachment of actin from the membrane. Both, actin response and cell death, are triggered by the bacterial elicitor harpin in grapevine cells. In this study we investigated, whether harpin-triggered actin bundling is necessary for harpin-triggered cell death. Since actin organisation is dependent upon auxin, we used different auxins to suppress actin bundling. Extracellular alkalinisation and transcription of defence genes as the basal immunity were examined as well as cell death. Furthermore, organisation of actin was observed in response to pharmacological manipulation of reactive oxygen species and phospholipase D. We find that induction of defence genes is independent of auxin. However, auxin can suppress harpin-induced cell death and also counteract actin bundling. We integrate our findings into a model, where harpin interferes with an auxin dependent pathway that sustains dynamic cortical actin through the activity of phospholipase D. The antagonism between growth and defence is explained by mutual competition for signal molecules such as superoxide and phosphatidic acid. Perturbations of the auxin-actin pathway might be used to detect disturbed integrity of the plasma membrane and channel defence signalling towards programmed cell death. PMID:25933033

  8. Actin as deathly switch? How auxin can suppress cell-death related defence.

    PubMed

    Chang, Xiaoli; Riemann, Michael; Liu, Qiong; Nick, Peter

    2015-01-01

    Plant innate immunity is composed of two layers--a basal immunity, and a specific effector-triggered immunity, which is often accompanied by hypersensitive cell death. Initiation of cell death depends on a complex network of signalling pathways. The phytohormone auxin as central regulator of plant growth and development represents an important component for the modulation of plant defence. In our previous work, we showed that cell death is heralded by detachment of actin from the membrane. Both, actin response and cell death, are triggered by the bacterial elicitor harpin in grapevine cells. In this study we investigated, whether harpin-triggered actin bundling is necessary for harpin-triggered cell death. Since actin organisation is dependent upon auxin, we used different auxins to suppress actin bundling. Extracellular alkalinisation and transcription of defence genes as the basal immunity were examined as well as cell death. Furthermore, organisation of actin was observed in response to pharmacological manipulation of reactive oxygen species and phospholipase D. We find that induction of defence genes is independent of auxin. However, auxin can suppress harpin-induced cell death and also counteract actin bundling. We integrate our findings into a model, where harpin interferes with an auxin dependent pathway that sustains dynamic cortical actin through the activity of phospholipase D. The antagonism between growth and defence is explained by mutual competition for signal molecules such as superoxide and phosphatidic acid. Perturbations of the auxin-actin pathway might be used to detect disturbed integrity of the plasma membrane and channel defence signalling towards programmed cell death.

  9. Deaths from complications of unsafe abortion: misclassified second trimester deaths.

    PubMed

    Walker, Dilys; Campero, Lourdes; Espinoza, Henry; Hernández, Bernardo; Anaya, Luis; Reynoso, Sofia; Langer, Ana

    2004-11-01

    This study measured the contribution of abortion-related deaths to overall maternal mortality and calculated the underestimation of maternal mortality using verbal autopsy and clinical record review where available. We reviewed 807 death certificates of women aged 12-50 who died in 2001 in two sites of about 1.5 million inhabitants each in the state of Morelos (primarily rural) and the municipality of Nezahualcóyotl (primarily urban) in the state of Mexico. Deaths were classified as definite, possible or non-maternal deaths. Finally we identified abortion-related deaths and calculated the underestimation of maternal mortality. Among 326 possible maternal deaths, we encountered five misclassified cases: one spontaneous abortion and four non-abortion maternal deaths. Among 32 registered maternal deaths, we found four misclassified cases that were actually second trimester, abortion-related deaths. There were no officially registered abortion-related deaths in either Morelos or Nezahualcóyotl, making the overall underestimation of abortion mortality 100%. Abortion contributed 13.5% of all maternal deaths. The overall underestimation of maternal mortality was 13.55%, higher in Morelos (21.7%). There were no unregistered maternal deaths in Nezahualcóyotl. Unsafe abortion continues to be an important cause of maternal mortality, though first trimester deaths appear to be decreasing. We identified domestic violence as an important cause of death among pregnant and post-partum women, and two abortion-related suicides, and believe these should be reconsidered as indirect maternal deaths. The misclassification of second trimester abortion deaths as maternal deaths from other causes is an obstacle to preventing them.

  10. Cell death and tendinopathy.

    PubMed

    Yuan, Jun; Wang, Min-Xia; Murrell, George A C

    2003-10-01

    Apoptosis and necrosis are presently recognized as the two major types of physiological and pathological cell death. Apoptosis is a tightly regulated cell deletion process that differs morphologically and biochemically from necrotic cell death. Tendinopathy is defined as a tendon injury that originates from intrinsic and extrinsic etiological factors. Excessive apoptosis has recently been described in degenerative tendon. The increased number of apoptotic tendon cells in degenerative tendon tissue could affect the rate of collagen synthesis and repair. Impaired or dysfunctional protein synthesis may lead to weaker tendon tissue and eventually increase the risk for tendon rupture. Clearly, there are many details to insert into this pathway, but there is hope that if the fine details of the pathway can be fleshed out, then strategies may be able to be developed to break the cycle at one or more points and prevent or treat tendinopathy more effectively.

  11. Death by necrosis

    PubMed Central

    Syntichaki, Popi; Tavernarakis, Nektarios

    2002-01-01

    Cells suffer necrotic death when exposed to extreme environmental conditions, adverse and excessive stimuli, or when deleterious mutations are encoded in their genetic material. Unlike apoptosis, which involves a highly regulated and elaborate network of biochemical events and cascades, necrosis has been considered generally to be a chaotic decadence process that effects the inexorable demise of cells otherwise not destined to die. This grim prospect is now slowly being overturned, mostly by exciting new findings in two simple model organisms, Caenorhabditis elegans and Drosophila melanogaster. Despite the wide spectrum of necrosis-initiating conditions, evidence is accumulating that execution of necrotic or neurodegenerative cell death may be carried out by a finite common set of mechanisms. PMID:12101090

  12. Death from Nitrous Oxide.

    PubMed

    Bäckström, Björn; Johansson, Bengt; Eriksson, Anders

    2015-11-01

    Nitrous oxide is an inflammable gas that gives no smell or taste. It has a history of abuse as long as its clinical use, and deaths, although rare, have been reported. We describe two cases of accidental deaths related to voluntary inhalation of nitrous oxide, both found dead with a gas mask covering the face. In an attempt to find an explanation to why the victims did not react properly to oncoming hypoxia, we performed experiments where a test person was allowed to breath in a closed system, with or without nitrous oxide added. Vital signs and gas concentrations as well as subjective symptoms were recorded. The experiments indicated that the explanation to the fact that neither of the descendents had reacted to oncoming hypoxia and hypercapnia was due to the inhalation of nitrous oxide. This study raises the question whether nitrous oxide really should be easily, commercially available.

  13. ER stress-induced cell death mechanisms

    PubMed Central

    Sano, Renata; Reed, John C.

    2013-01-01

    The endoplasmic-reticulum (ER) stress response constitutes a cellular process that is triggered by a variety of conditions that disturb folding of proteins in the ER. Eukaryotic cells have developed an evolutionarily conserved adaptive mechanism, the unfolded protein response (UPR), which aims to clear unfolded proteins and restore ER homeostasis. In cases where ER stress cannot be reversed, cellular functions deteriorate, often leading to cell death. Accumulating evidence implicates ER stress-induced cellular dysfunction and cell death as major contributors to many diseases, making modulators of ER stress pathways potentially attractive targets for therapeutics discovery. Here, we summarize recent advances in understanding the diversity of molecular mechanisms that govern ER stress signaling in health and disease. PMID:23850759

  14. Death, medicine & bioethics.

    PubMed

    Hunt, G

    1994-12-01

    The assumptions of philosophy need scrutiny as much the assumptions of medicine do. Scrutiny shows that the philosophical method of bioethics is compromised, for it shares certain fundamental assumptions with medicine itself. To show this requires an unorthodox style of philosophy--a literary one. To show the compromised status of bioethics the paper discusses some seminal utilitarian discussions of the definition of death, of whether it is a bad thing, and of when it ought to occur.

  15. Atypical autoerotic deaths

    SciTech Connect

    Gowitt, G.T.; Hanzlick, R.L. )

    1992-06-01

    So-called typical' autoerotic fatalities are the result of asphyxia due to mechanical compression of the neck, chest, or abdomen, whereas atypical' autoeroticism involves sexual self-stimulation by other means. The authors present five atypical autoerotic fatalities that involved the use of dichlorodifluoromethane, nitrous oxide, isobutyl nitrite, cocaine, or compounds containing 1-1-1-trichloroethane. Mechanisms of death are discussed in each case and the pertinent literature is reviewed.

  16. Sudden death of feedlot cattle.

    PubMed

    Glock, R D; DeGroot, B D

    1998-01-01

    Sudden deaths or the sudden death syndrome are perceived as major concerns in cattle feedlots because most of these deaths occur in cattle near market weight. Etiology and preventive measures are poorly defined. The current literature indicates that sudden deaths are associated most commonly with digestive upsets. Death is thought to be the result of interactions between factors including acidosis, bloat, and endotoxemia. Trauma, peracute interstitial pneumonia, and other identifiable events are specifically defined but relatively uncommon. Enterotoxemia is of questionable significance as a cause of sudden deaths.

  17. Donation after circulatory death.

    PubMed

    Manara, A R; Murphy, P G; O'Callaghan, G

    2012-01-01

    Donation after circulatory death (DCD) describes the retrieval of organs for the purposes of transplantation that follows death confirmed using circulatory criteria. The persisting shortfall in the availability of organs for transplantation has prompted many countries to re-introduce DCD schemes not only for kidney retrieval but increasingly for other organs with a lower tolerance for warm ischaemia such as the liver, pancreas, and lungs. DCD contrasts in many important respects to the current standard model for deceased donation, namely donation after brain death. The challenge in the practice of DCD includes how to identify patients as suitable potential DCD donors, how to support and maintain the trust of bereaved families, and how to manage the consequences of warm ischaemia in a fashion that is professionally, ethically, and legally acceptable. Many of the concerns about the practice of both controlled and uncontrolled DCD are being addressed by increasing professional consensus on the ethical and legal justification for many of the interventions necessary to facilitate DCD. In some countries, DCD after the withdrawal of active treatment accounts for a substantial proportion of deceased organ donors overall. Where this occurs, there is an increased acceptance that organ and tissue donation should be considered a routine part of end-of-life care in both intensive care unit and emergency department.

  18. Immunogenic cell death.

    PubMed

    Garg, Abhishek D; Dudek-Peric, Aleksandra M; Romano, Erminia; Agostinis, Patrizia

    2015-01-01

    Currently, it is widely acknowledged that a proactive anticancer immunosurveillance mechanism takes part in the rejection of neoplastic lesions before they progress towards a benign or malignant tumour. However in cases of very aggressive neoplastic lesions consisting of cells with high mutational diversity, cancer cell variants might be formed that are capable of evading host defence systems against uncontrolled proliferation and anticancer immunosurveillance. This is mainly accomplished through the exhibition of low immunogenicity, which is a particularly important stumbling block in the revival of long-lasting as well as stable anticancer immunity. Recently, it has emerged emphatically that inciting a cancer cell death routine, associated with the activation of danger signalling pathways evoking emission of damage-associated molecular patterns (DAMPs), markedly increases the immunogenicity of dying cancer cells. This cell death pathway has been termed "immunogenic cell death" (ICD). In the present review we introduce this concept and discuss its characteristics in detail. We also discuss in detail the various molecular, immunological and operational determinants of ICD.

  19. Module Configuration

    DOEpatents

    Oweis, Salah; D'Ussel, Louis; Chagnon, Guy; Zuhowski, Michael; Sack, Tim; Laucournet, Gaullume; Jackson, Edward J.

    2002-06-04

    A stand alone battery module including: (a) a mechanical configuration; (b) a thermal management configuration; (c) an electrical connection configuration; and (d) an electronics configuration. Such a module is fully interchangeable in a battery pack assembly, mechanically, from the thermal management point of view, and electrically. With the same hardware, the module can accommodate different cell sizes and, therefore, can easily have different capacities. The module structure is designed to accommodate the electronics monitoring, protection, and printed wiring assembly boards (PWAs), as well as to allow airflow through the module. A plurality of modules may easily be connected together to form a battery pack. The parts of the module are designed to facilitate their manufacture and assembly.

  20. From Death to Death Certificate: What do the Dead say?

    PubMed

    Gill, James R

    2017-03-01

    This is an overview of medicolegal death investigation and death certification. Postmortem toxicological analysis, particularly for ethanol and drugs of abuse, plays a large role in the forensic investigation of natural and unnatural deaths. Postmortem drug concentrations must be interpreted in light of the autopsy findings and circumstances. Interpretations of drug and ethanol concentrations are important for death certification, but they also may be important for other stakeholders such as police, attorneys, public health practitioners, and the next-of-kin.

  1. ANTIGENIC MODULATION

    PubMed Central

    Old, Lloyd J.; Stockert, Elisabeth; Boyse, Edward A.; Kim, Jae Ho

    1968-01-01

    Antigenic modulation (the loss of TL antigens from TL+ cells exposed to TL antibody in the absence of lytic complement) has been demonstrated in vitro. An ascites leukemia, phenotype TL.1,2,3, which modulates rapidly and completely when incubated with TL antiserum in vitro, was selected for further study of the phenomenon. Over a wide range of TL antibody concentrations modulation at 37°C was detectable within 10 min and was complete within approximately 1 hr. The cells were initially sensitized to C' by their contact with antibody, thereafter losing this sensitivity to C' lysis together with their sensitivity to TL antibody and C' in the cytotoxic test. The capacity of the cells to undergo modulation was abolished by actinomycin D and by iodoacetamide, and by reducing the temperature of incubation to 0°C. Thus modulation apparently is an active cellular process. Antigens TL. 1,2, and 3 are all modulated by anti-TL.1,3 serum and by anti-TL.3 serum. This modulation affects all three TL components together, even when antibody to one or two of them is lacking. aAnti-TL.2 serum does not induce modulation and in fact impairs modulation by the other TL antibodies. The influence of the TL phenotype of cells upon the demonstrable content of H-2 (D region) isoantigen, first shown in cells modulated in vivo, has been observed with cells modulated in vitro. Cells undergoing modulation show a progressive increase in H-2 (D region) antigen over a period of 4 hr, with no change in H-2 antigens of the K region. Restoration of the TL+ phenotype of modulated cells after removal of antibody is less rapid than TL+ → TL- modulation and may require several cell divisions. PMID:5636556

  2. [Intensity modulated radiotherapy for head and neck cancer, dose constraint for normal tissue: Cochlea vestibular apparatus and brainstem].

    PubMed

    Guimas, V; Thariat, J; Graff-Cailleau, P; Boisselier, P; Pointreau, Y; Pommier, P; Montbarbon, X; Laude, C; Racadot, S

    2016-10-01

    Modern techniques such as intensity modulated radiation therapy (IMRT) have been proven to significantly decrease the dose delivered to the cochleovestibular apparatus, limiting consecutive toxicity especially for sensorineural hearing loss. However, recent data still report a 42% rate of radio-induced hypoacusia underscoring the need to protect the cochleovestibular apparatus. Due to the small size of the cochlea, a precise dose-volume analysis could not be performed, and recommendations only refer to the mean dose. Confusing factors such as age, concomitant chemotherapy, primary site and tumor stage should be taken into account at the time of treatment planning. (Non-coplanar) VMAT and tomotherapy have been proven better at sparing the cochlea in comparison with 3D CRT. Brainstem radio-induced injuries were poorly studied because of their infrequency and the difficulty of distinguishing between necrosis and tumor progression in the case of a primary tumor located at the base of skull. The following toxicities have been described: brainstem focal radionecrosis, cognitive disorders without dementia, cranial nerve injuries and sensori motor disability. Maximal dose to the brainstem should be kept to < 54Gy for conventional fractionation. This dose could be exceeded (no more than 10mL should receive more than 59Gy), provided this hot spot is located in the peripheral area of the organ. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  3. Death preparedness: a concept analysis.

    PubMed

    McLeod-Sordjan, Renee

    2014-05-01

    To report analysis of the concept death preparedness in the context of end-of-life shared decisions and communication. Forty percent of older people require decision-making and communication in the final days of life. Elaborate defence mechanisms have yielded a public consciousness that no longer passively views death acceptance, but instead has a defensive orientation of preparedness. The term 'death preparedness' depicts this death attitude. Concept analysis. Data were collected over 3 months in 2013. A series of searches of scholarly peer-reviewed literature published in English were conducted of multiple databases. Specific keywords included such phrases as: death acceptance, death avoidance, death rejection, death preparedness, resolution of life, breaking bad news and readiness to die. Walker and Avant's method was chosen as a deductive method to distinguish between the defining attributes of death preparedness and its relevant attributes. Death preparedness involves a transition of facilitated communication with a healthcare provider that leads to awareness and/or acceptance of end of life, as evidenced by an implementation of a plan. An appraisal of attitudes towards death and one's mortality precedes the concept, followed by an improved quality of death and dignity at end of life. The concept of death preparedness in the process of dying should be the focus of research to explore areas to improve advanced directive planning and acceptance of palliation for chronic health conditions. © 2013 John Wiley & Sons Ltd.

  4. A Death in the Family: Death as a Zen Concept

    ERIC Educational Resources Information Center

    Black, Helen K.; Rubinstein, Robert L.

    2013-01-01

    This study is based on original research that explored family reaction to the death of an elderly husband and father. We interviewed 34 families (a family included a widow and two adult biological children) approximately 6 to 10 months after the death. In one-on-one interviews, we discussed family members' initial reaction to the death, how the…

  5. Death Sentences: A Content Analysis of Children's Death Literature

    ERIC Educational Resources Information Center

    Poling, Devereaux A.; Hupp, Julie M.

    2008-01-01

    A multidimensional concept of death must include biological, sociocultural, and emotional components. Children glean information about death in many ways, one of which is through books. In this study, the authors compared the 3 dimensions of death-related information (irreversibility, inevitability, nonfunctionality) in 24 young children's picture…

  6. A Death in the Family: Death as a Zen Concept

    ERIC Educational Resources Information Center

    Black, Helen K.; Rubinstein, Robert L.

    2013-01-01

    This study is based on original research that explored family reaction to the death of an elderly husband and father. We interviewed 34 families (a family included a widow and two adult biological children) approximately 6 to 10 months after the death. In one-on-one interviews, we discussed family members' initial reaction to the death, how the…

  7. Death Sentences: A Content Analysis of Children's Death Literature

    ERIC Educational Resources Information Center

    Poling, Devereaux A.; Hupp, Julie M.

    2008-01-01

    A multidimensional concept of death must include biological, sociocultural, and emotional components. Children glean information about death in many ways, one of which is through books. In this study, the authors compared the 3 dimensions of death-related information (irreversibility, inevitability, nonfunctionality) in 24 young children's picture…

  8. 188Rhenium-induced cell death and apoptosis in a panel of tumor cell lines

    NASA Astrophysics Data System (ADS)

    Antoccia, Antonio; Banzato, Alessandra; Bello, Michele; Bollini, Dante; De Notaristefani, Francesco; Giron, Cecilia; Mazzi, Ulderico; Alafort, Laura Melendez; Moschini, Giuliano; Nadali, Anna; Navarria, Francesco; Perrotta, Andrea; Rosato, Antonio; Tanzarella, Caterina; Uzunov, Nikolay

    2007-02-01

    Assessment of "in vitro" tumor growth inhibition and radiobiological effects, such as apoptosis, have been evaluated in human neoplastic cells of different histotypes (H460 lung cancer cells, U87 glioblastoma, LnCaP prostate tumor cells) treated using solutions of 188Rhenium-perrhenate. The MTT assay, which measures mitochondrial metabolism in the entire cell culture is a recognized test for cytotoxicity and was used in cells exposed 48-72 h to specific activities ranged from 37 to 148 GBq/l. Whereas H460 and LnCaP were particularly sensitive to treatment, U87 glioblastoma cells behaved as radioresistant ones. However, evaluation of 188Re-induced apoptosis indicated that this kind of cell death contributed only marginally to the reduction in cell viability of H460 and LNCaP lines, suggesting the existence of protective mechanisms against apoptosis. In this respect, the membrane receptor, CD44, whose expression is dysregulated in most malignant cell types has proven to alter the response of cancer cells to apoptotic stimuli, including ionizing radiation. Cell samples decorated with a FITC-labelled CD44 antibody indicated, that in H460 and U87 cells the CD44(+) correlated well with an apoptosis-resistant response. Conversely, LnCap cells proven as CD44(-) did not display however sensitivity to radio-induced apoptosis.

  9. Overdose Deaths Among Homeless Persons

    MedlinePlus

    ... Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription ... death, outnumbering deaths from all other drugs (including heroin) combined. Of the opioids contributing to overdoses in ...

  10. Childhood Deaths from Physical Abuse.

    ERIC Educational Resources Information Center

    Kasim, Mohd. Sham; and Others

    1995-01-01

    This paper describes 30 cases of childhood deaths caused by physical abuse in Kuala Lumpur, Malaysia. Data presented include ethnic origins, age, causes of death, identity of perpetrators, and marital situation of parents. (DB)

  11. Death in Denmark: a reply.

    PubMed Central

    Lamb, D

    1991-01-01

    This reply to Martyn Evans's support for a cardiac-centered concept of death attempts to meet some objections to the brainstem definition of death. Evans's appeal to Wittgenstein's philosophy is also criticised. PMID:1870081

  12. Self-related consequences of death fear and death denial.

    PubMed

    Cozzolino, Philip J; Blackie, Laura E R; Meyers, Lawrence S

    2014-01-01

    This study explores self-related outcomes (e.g., esteem, self-concept clarity, existential well-being) as a function of the interaction between self-reported levels of death fear and death denial. Consistent with the idea that positive existential growth can come from individuals facing, rather than denying, their mortality (Cozzolino, 2006 ), the authors observed that not fearing and denying death can bolster important positive components of the self. That is, individuals low in death denial and death fear evidenced an enhanced self that is valued, clearly conceived, efficacious, and that has meaning and purpose.

  13. On social death: ostracism and the accessibility of death thoughts.

    PubMed

    Steele, Caroline; Kidd, David C; Castano, Emanuele

    2015-01-01

    Being rejected, excluded, or simply ignored is a painful experience. Ostracism researchers have shown its powerful negative consequences (Williams, 2007), and sociologists have referred to such experiences as social death (Bauman, 1992). Is this is just a metaphor or does being ostracized make death more salient in people's minds? An experiment was conducted in which participants experienced ostracism or inclusion using the Cyberball manipulation, and the accessibility of death-related thoughts was measured via a word-stem completion puzzle. Results showed enhanced death-thought accessibility in the ostracism condition, as well as a negative effect of dispositional self-esteem on the accessibility of death-related thoughts.

  14. The Death Anxiety of Gays.

    ERIC Educational Resources Information Center

    Templer, Donald I.; And Others

    1984-01-01

    Examined the influence of sex and age on death anxiety in 165 male and 95 female homosexuals who completed the Death Anxiety Scale. Results showed gay males and females had almost identical DAS scores. No relationship was found between age and death anxiety. (JAC)

  15. Deaths: Final Data for 1998.

    ERIC Educational Resources Information Center

    Murphy, Sherry L.

    2000-01-01

    This report presents final 1998 data on U.S. deaths and death rates according to demographic and medical characteristics such as age, sex, race, Hispanic origin, marital status, educational attainment, injury at work, state of residence, and cause of death. Trends and patterns in general mortality, life expectancy, and infant and maternal…

  16. Death: Realism in Children's Books.

    ERIC Educational Resources Information Center

    Danielson, Kathy Everts

    In the past, books for children treated death fearfully, morbidly, and didactically, but now children's literature treats death in a more realistic manner and is sensitive to its emotional aspects. Current theories suggest that children perceive death differently at various ages. G. P. Koocher (1973) used J. Piaget's cognitive stages as the basis…

  17. Helping Students Cope with Death.

    ERIC Educational Resources Information Center

    Rodabough, Tillman

    1980-01-01

    Classroom teachers need to understand the broad differences that exist between a child's perception of death and that of an adult and should be prepared to confront and cope with the effects of death and grief upon students. Children's perceptions of death and ways in which the teacher can help the child with his grief are described. (JN)

  18. Teaching about Death to Undergraduates.

    ERIC Educational Resources Information Center

    Pine, Vanderlyn R.; And Others

    Development, implementation, and teaching of a college-level course on dying and death are described. The authors review their own experiences in becoming involved with death education and describe teaching methods, problems, and content of their current course in dying and death at the State University of New York, College at New Paltz. Because…

  19. Teaching about Death to Undergraduates.

    ERIC Educational Resources Information Center

    Pine, Vanderlyn R.; And Others

    Development, implementation, and teaching of a college-level course on dying and death are described. The authors review their own experiences in becoming involved with death education and describe teaching methods, problems, and content of their current course in dying and death at the State University of New York, College at New Paltz. Because…

  20. Eartkquake Death Tolls

    NASA Astrophysics Data System (ADS)

    Knopoff, Leon; Sornette, Didier

    1995-12-01

    In the risk and insurance literature, the (one-point) distributions of losses in natural disasters have been proposed to be characterized by “fat tail” power laws, i.e. very large destruction may occur with a non-vanishing rate. A naive hypothesis of uncorrelated Poissonian occurrence would suggest that the losses are solely characterized by the properties of the underlying power law distributions, i.e. the longer we wait, the more dramatic will be the largest disaster, which could be as much as a finite fraction of the total population or the total wealth of a country. We find indeed that the numbers Z of deaths in the very largest earthquakes of this century can be described by a power law distribution P(Z)simeq Z^{-(1+δ)} with δ=1.0±0.3, implying an unbounded behavior for the most devastating earthquakes. However, the distribution of the number of deaths per capita in each country in this century has a well-defined maximum value, suggesting that the naive extrapolation of the power law distribution is incorrect and that the understanding of correlations is necessary to ascertain the level of risk from natural disasters. The one-point distributions only provide an upper bound of the expected risk. We propose a speculative model to explain the correlations between deaths in large earthquakes and their countries of occurrence: we suggest that large ancient civilizations that have matured into large present-day populations were the beneficiaries of isolation from marauders due to the relative geographic protection by tectonic processes largely of an orogenic nature.

  1. Sudden death of entanglement.

    PubMed

    Yu, Ting; Eberly, J H

    2009-01-30

    A new development in the dynamical behavior of elementary quantum systems is the surprising discovery that correlation between two quantum units of information called qubits can be degraded by environmental noise in a way not seen previously in studies of dissipation. This new route for dissipation attacks quantum entanglement, the essential resource for quantum information as well as the central feature in the Einstein-Podolsky-Rosen so-called paradox and in discussions of the fate of Schrödinger's cat. The effect has been labeled ESD, which stands for early-stage disentanglement or, more frequently, entanglement sudden death. We review recent progress in studies focused on this phenomenon.

  2. Death, dying, and domination.

    PubMed

    Spindelman, Marc

    2008-06-01

    This Article critiques conventional liberal arguments for the right to die on liberal grounds. It contends that these arguments do not go far enough to recognize and address private, and in particular structural, forms of domination. It presents an alternative that does, which is thus more respectful of true freedom in the context of death and dying, and also more consistent with liberalism. After discussing obstacles to the achievement of a right to die that encompasses freedom from both public and private domination, the Article closes with a significant reform project within bioethics that might help bring it about.

  3. Module Evaluation

    DTIC Science & Technology

    2006-02-01

    various testing methodologies for the evaluation and characterization of Transmit /Receive (T/R) modules for phased array radars. Discussed are techniques...for characterizing T/R modules in transmit and receive modes under ideal and emulated operation environments. Further, techniques for life testing...characteristics of T/R modules developed during the early and mid 1980’s. Data provided shows the performance in terms of gain and phase for both transmit

  4. A good death.

    PubMed

    Hold, Judith L

    2017-02-01

    On a day to day basis, nurses are facing more ethical dilemmas during end-of-life care resulting in not being able to actualize a good death for patients. The purpose of this study was to explore how experienced hospice nurses resolve day to day ethical dilemmas during end-of-life care. The study used a qualitative narrative approach. Through purposeful sampling, a total of six experienced hospice nurse participated. Ethical considerations: Approval from the researcher's university Institutional Review Board for ethical review was obtained. Using core story creation, several different ethical dilemmas were identified divulging struggles with key stakeholders including family members and providers. Thematic analysis generated three main themes: Ethics within Practice, Ethical Knowledge, and Ethical Solutions. The participants told their stories depicting a keen awareness of ethical conflicts situated by contextual factors including social, political, and personal issues. The nurses' deliberations were informed through formal, experiential, and intuitive knowledge. Ethical predicaments were resolved by either following rules or choosing acts of resistance. A better understanding was obtained on how experienced hospice nurses successfully resolve ethical dilemmas culminating in better deaths for patients.

  5. Sudden infant death syndrome.

    PubMed

    Moon, Rachel Y; Horne, Rosemary S C; Hauck, Fern R

    2007-11-03

    Despite declines in prevalence during the past two decades, sudden infant death syndrome (SIDS) continues to be the leading cause of death for infants aged between 1 month and 1 year in developed countries. Behavioural risk factors identified in epidemiological studies include prone and side positions for infant sleep, smoke exposure, soft bedding and sleep surfaces, and overheating. Evidence also suggests that pacifier use at sleep time and room sharing without bed sharing are associated with decreased risk of SIDS. Although the cause of SIDS is unknown, immature cardiorespiratory autonomic control and failure of arousal responsiveness from sleep are important factors. Gene polymorphisms relating to serotonin transport and autonomic nervous system development might make affected infants more vulnerable to SIDS. Campaigns for risk reduction have helped to reduce SIDS incidence by 50-90%. However, to reduce the incidence even further, greater strides must be made in reducing prenatal smoke exposure and implementing other recommended infant care practices. Continued research is needed to identify the pathophysiological basis of SIDS.

  6. Sudden infant death syndrome

    PubMed Central

    Hunt, Carl E.; Hauck, Fern R.

    2006-01-01

    Sudden infant death syndrome (SIDS) continues to be the most common cause of postneonatal infant death. SIDS is a complex, multifactorial disorder, the cause of which is still not fully understood. However, much is known now about environmental risk factors, some of which are modifiable. These include maternal and antenatal risk factors such as smoking during pregnancy, as well as infant-related risk factors such as non-supine sleeping position and soft bedding. Emerging evidence also substantiates an expanding number of genetic risk factors. Interactions between environmental and genetic risk factors may be of critical importance in determining an infant's actual risk of SIDS. Although no practical way exists to identify which infants will die of SIDS, nor is there a safe and proven prevention strategy even if identification were feasible, reducing exposure to modifiable risk factors has helped to lower the incidence of SIDS. Current challenges include wider dissemination of guidelines to all people who care for infants, dissemination of guidelines in culturally appropriate ways, and surveillance of SIDS trends and other outcomes associated with implementation of these guidelines. PMID:16785462

  7. PDT: death pathways

    NASA Astrophysics Data System (ADS)

    Kessel, David

    2007-02-01

    Cellular targets of photodynamic therapy include mitochondria, lysosomes, the endoplasmic reticulum (ER) and the plasma membrane. PDT can evoke necrosis, autophagy and apoptosis, or combinations of these, depending on the PDT dose, the site(s) of photodamage and the cellular phenotype. It has been established that loss of viability occurs even when the apoptotic program is inhibited. Studies assessing effects of ER or mitochondrial photodamage, involving loss of Bcl-2 function, indicate that low-dose PDT elicited a rapid autophagic response in L1210 cells. This was attributed to the ability of autophagy to recycle photodamaged organelles, and there was partial protection from loss of viability. This effect was not observed in L1210/Atg7, where autophagy was silenced. At higher PDT doses, apoptotic cells were observed within 60 min in both cell lines, but more so in L1210. The ability of L1210 cells to undergo autophagy did not offer protection from cell death at the higher PDT dose. Previous studies had indicated that autophagy can contribute to cell death, since L1210 cells that do not undergo an initial apoptotic response often contain multiple autophagic vacuoles 24 hr later. With L1210/Atg7, apoptosis alone may account for the loss of viability at an LD 90 PDT dose.

  8. Sudden infant death syndrome.

    PubMed

    Adams, Stephen M; Ward, Chad E; Garcia, Karla L

    2015-06-01

    Sudden infant death syndrome (SIDS) is the sudden unexpected death of a child younger than one year during sleep that cannot be explained after a postmortem evaluation including autopsy, a thorough history, and scene evaluation. The incidence of SIDS has decreased more than 50% in the past 20 years, largely as a result of the Back to Sleep campaign. The most important risk factors relate to the sleep environment. Prone and side sleeping positions are significantly more dangerous than the supine position. Bed sharing with a parent is strongly correlated with an increased risk of SIDS, especially in infants younger than 12 weeks. Apparent life-threatening events are not a risk factor for SIDS. Parents should place infants on their backs to sleep, should not share a bed, and should avoid exposing the infant to tobacco smoke. Other risk-reducing measures include using a firm crib mattress, breastfeeding, keeping vaccinations up to date, avoiding overheating due to overbundling, avoiding soft bedding, and considering the use of a pacifier during sleep once breastfeeding is established. One consequence of the Back to Sleep campaign is a significant increase in the incidence of occipital flattening. Infants who develop a flat spot should be placed with the head facing alternating directions each time he or she is put to bed. Supervised prone positioning while the infant is awake, avoiding excessive use of carriers, and upright positioning while awake are also recommended.

  9. Happiness and Death Distress: Two Separate Factors

    ERIC Educational Resources Information Center

    Abdel-Khalek, Ahmed M.

    2005-01-01

    The aim of the present study was to explore the relationship between happiness and death distress (death anxiety, death depression, and death obsession) in 275 volunteer Kuwaiti undergraduates. They responded to the Oxford Happiness Inventory, the Death Anxiety Scale, the Arabic Scale of Death Anxiety, the Death Depression Scale-Revised, and the…

  10. Pathological fear of cot death.

    PubMed

    Weightman, H; Dalal, B M; Brockington, I F

    1998-01-01

    Cot death (sudden infant death syndrome) is one of the most common causes of death in the first year of life. Four cases with a pathological fear of cot death are presented. All the patients were depressed and in 2 cases the fear of cot death had an obsessional quality. In all cases there were complications during pregnancy (miscarriage, threatened abortion, recurrent vomiting in last trimester). In 1 case, the patient knew 3 mothers who had suffered cot deaths; in another, the infant was gravely ill in the neonatal period. Pathological fear of cot death can be recognised by the presence of two central features - overvigilance and excessive nocturnal checking of the baby's breathing. Therapeutic interventions are discussed.

  11. Role of polyphenols in cell death control.

    PubMed

    Giovannini, Claudio; Masella, Roberta

    2012-05-01

    Dietary consumption of fruit, vegetables, fish, and olive oil has been demonstrated to exert beneficial effects on human health. This finding may be due to the high content of antioxidant compounds including polyphenols. Current evidence strongly supports a contribution of polyphenols to the prevention of several chronic degenerative diseases such as cancer, atherosclerosis and cardiovascular diseases, central nervous system disorders, as well as aging. Apoptosis is a genetically controlled and evolutionarily conserved form of cell death of critical importance for the maintenance of tissue homeostasis in the adult organism. The malfunction of the death machinery may play a primary role in various pathologic processes, leading to proliferative or degenerative diseases. Polyphenols can interact with specific steps and/or proteins regulating the apoptotic process in different ways depending on their concentration, the cell system, the type or stage of the pathological process. Because of their ability to modulate cell death, polyphenols have been proposed as chemopreventive and therapeutic agents. This paper reviews and discusses the last 3-year findings related to the principal molecular mechanisms involved in the control of the balance between apoptosis and cell proliferation exerted by polyphenols.

  12. Death by water intoxication.

    PubMed

    Gardner, John W

    2002-05-01

    With recent emphasis on increased water intake during exercise for the prevention of dehydration and exertional heat illness, there has been an increase in cases of hyponatremia related to excessive water intake. This article reviews several recent military cases and three deaths that have occurred as a result of overhydration, with resultant hyponatremia and cerebral edema. All of these cases are associated with more than 5 L (usually 10-20 L) of water intake during a period of a few hours. The importance of maintaining adequate hydration in exertional heat illness prevention cannot be overemphasized, but excessive fluid intake may lead to life-threatening hyponatremia. Current guidelines provide safety by limiting fluid intake during times of heavy sweating to 1 to 1.5 L per hour.

  13. Death Valley, California

    NASA Technical Reports Server (NTRS)

    1994-01-01

    This is an image of Death Valley, California, centered at 36.629 degrees north latitude, 117.069 degrees west longitude. The image shows Furnace Creek alluvial fan and Furnace Creek Ranch at the far right, and the sand dunes near Stove Pipe Wells at the center. The dark fork-shaped feature between Furnace Creek fan and the dunes is a smooth flood-plain which encloses Cottonball Basin. The bright dots near the center of the image are corner refectors that have been set-up to calibrate the radar as the Shuttle passes overhead with the SIR-C/X-SAR system. The Jet Propulsion Laboratory alternative photo number is P-43883.

  14. Death, time, and psychosis.

    PubMed

    Lombardi, Riccardo

    2013-08-01

    Working through the awareness of death and the consciousness of time, it is hypothesized, plays a decisive role in the analytic process and in the mental growth of psychotic analysands, as well as in the integration of the psychotic areas in healthier patients. Clinical material is presented from a psychotic woman treated analytically, four sessions a week, for twelve years. The patient suffered several acute relapses, during which the analytic work was not interrupted. Her fourth psychotic episode in the course of analysis, which involved a delusion about gray men and the theft of time, is explored in particular depth. This phase fostered the patient's recognition of the value of time, together with the acquisition of her own center of psychosensory integration, the basis of an ability to learn from experience.

  15. Death Valley, California

    NASA Technical Reports Server (NTRS)

    1994-01-01

    This is an image of Death Valley, California, centered at 36.629 degrees north latitude, 117.069 degrees west longitude. The image shows Furnace Creek alluvial fan and Furnace Creek Ranch at the far right, and the sand dunes near Stove Pipe Wells at the center. The dark fork-shaped feature between Furnace Creek fan and the dunes is a smooth flood-plain which encloses Cottonball Basin. The bright dots near the center of the image are corner refectors that have been set-up to calibrate the radar as the Shuttle passes overhead with the SIR-C/X-SAR system. The Jet Propulsion Laboratory alternative photo number is P-43883.

  16. Death Valley, California

    NASA Image and Video Library

    1994-04-11

    STS059-S-026 (11 April 1994) --- This is an image of Death Valley, California, centered at 36.629 degrees north latitude, 117.069 degrees west longitude. The image shows Furnace Creek alluvial fan and Furnace Creek Ranch at the far right, and the sand dunes near Stove Pipe Wells at the center. The dark fork-shaped feature between Furnace Creek fan and the dunes is a smooth flood-plain which encloses Cottonball Basin. The SIR-C/X-SAR supersite is an area of extensive field investigations and has been visited by both Space Radar Lab astronaut crews. Elevations in the Valley range from 70 meters below sea level, the lowest in the United States, to more than 3300 meters above sea level. Scientists are using SIR-C/X-SAR data from Death Valley to help answer a number of different questions about the Earth's geology. One question concerns how alluvial fans are formed and change through time under the influence of climatic changes and earthquakes. Alluvial fans are gravel deposits that wash down from the mountains over time. They are visible in the image as circular, fan-shaped bright areas extending into the darker valley floor from the mountains. Information about the alluvial fans help scientists study Earth's ancient climate. Scientists know the fans are bulit up through climatic and tectonic processes and they will use the SIR-C/X-SAR data to understand the nature and rates of weathering processes on the fans, soil formation, and the transport of sand and dust by the wind. SIR-C/X-SAR's sensitivity to centimeter-scale (or inch-scale) roughness provides detailed maps of surface texture. Such information can be used to study the occurrence and movement of dust storms and sand dunes. the goal of these studies is to gain a better understanding of the record of past climatic changes and the effects of those changes on a sensitive environment. This may lead to a better ability to predict future response of the land to different potential global cimate-change scenarios

  17. Deaths: leading causes for 2000.

    PubMed

    Anderson, Robert N

    2002-09-16

    This report presents final 2000 data on the 10 leading causes of death in the United States by age, race, sex, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements the annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 States and the District of Columbia in 2000. Causes of death classified by the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) are ranked according to the number of deaths assigned to rankable causes. In 2000 the 10 leading causes of death were (in rank order) Diseases of heart; Malignant neoplasms; Cerebrovascular diseases; Chronic lower respiratory diseases; Accidents (unintentional injuries); Diabetes mellitus; Influenza and pneumonia; Alzheimer's disease; Nephritis, nephrotic syndrome and nephrosis; and Septicemia and accounted for nearly 80 percent of all deaths occurring in the United States. Differences in the rankings are evidently by age, sex, race, and Hispanic origin. Leading causes of infant death for 2000 were (in rank order) Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birthweight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Newborn affected by complications of placenta, cord and membranes; Respiratory distress of newborn; Accidents (unintentional injuries); Bacterial sepsis of newborn; Diseases of the circulatory system; and Intrauterine hypoxia and birth asphyxia. Important variation in the leading causes of infant death is noted for the neonatal and postneonatal periods.

  18. Dead Cert: Measuring Cell Death.

    PubMed

    Crowley, Lisa C; Marfell, Brooke J; Scott, Adrian P; Boughaba, Jeanne A; Chojnowski, Grace; Christensen, Melinda E; Waterhouse, Nigel J

    2016-12-01

    Many cells in the body die at specific times to facilitate healthy development or because they have become old, damaged, or infected. Defects in cells that result in their inappropriate survival or untimely death can negatively impact development or contribute to a variety of human pathologies, including cancer, AIDS, autoimmune disorders, and chronic infection. Cell death may also occur following exposure to environmental toxins or cytotoxic chemicals. Although this is often harmful, it can be beneficial in some cases, such as in the treatment of cancer. The ability to objectively measure cell death in a laboratory setting is therefore essential to understanding and investigating the causes and treatments of many human diseases and disorders. Often, it is sufficient to know the extent of cell death in a sample; however, the mechanism of death may also have implications for disease progression, treatment, and the outcomes of experimental investigations. There are a myriad of assays available for measuring the known forms of cell death, including apoptosis, necrosis, autophagy, necroptosis, anoikis, and pyroptosis. Here, we introduce a range of assays for measuring cell death in cultured cells, and we outline basic techniques for distinguishing healthy cells from apoptotic or necrotic cells-the two most common forms of cell death. We also provide personal insight into where these assays may be useful and how they may or may not be used to distinguish apoptotic cell death from other death modalities. © 2016 Cold Spring Harbor Laboratory Press.

  19. Deaths: Leading Causes for 2011.

    PubMed

    Heron, Melonie

    2015-07-27

    This report presents final 2011 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements ‘‘Deaths: Final Data for 2011,’’ the National Center for Health Statistics’ annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2011. Causes of death classified by the International Classification of Diseases, 10th Revision (ICD–10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2011, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Cerebrovascular diseases; Accidents (unintentional injuries); Alzheimer’s disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Intentional self-harm (suicide). They accounted for 74% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2011 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods. All material appearing in this report is in the public domain and may be reproduced or copied without permission

  20. Deaths: Leading Causes for 2013.

    PubMed

    Heron, Melonie

    2016-02-16

    This report presents final 2013 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements "Deaths: Final Data for 2013," the National Center for Health Statistics’ annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2013. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD–10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2013, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Accidents (unintentional injuries); Cerebrovascular diseases; Alzheimer’s disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Intentional self-harm (suicide). They accounted for 74% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2013 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Newborn affected by maternal complications of pregnancy; Sudden infant death syndrome; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as

  1. Deaths: Leading Causes for 2012.

    PubMed

    Heron, Melonie

    2015-08-31

    This report presents final 2012 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements "Deaths: Final Data for 2012," the National Center for Health Statistics' annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2012. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD-10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2012, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Cerebrovascular diseases; Accidents (unintentional injuries); Alzheimer's disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Intentional self-harm (suicide). These causes accounted for 74% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2012 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods.

  2. Dynamic Neural Processing of Linguistic Cues Related to Death

    PubMed Central

    Ma, Yina; Qin, Jungang; Han, Shihui

    2013-01-01

    Behavioral studies suggest that humans evolve the capacity to cope with anxiety induced by the awareness of death’s inevitability. However, the neurocognitive processes that underlie online death-related thoughts remain unclear. Our recent functional MRI study found that the processing of linguistic cues related to death was characterized by decreased neural activity in human insular cortex. The current study further investigated the time course of neural processing of death-related linguistic cues. We recorded event-related potentials (ERP) to death-related, life-related, negative-valence, and neutral-valence words in a modified Stroop task that required color naming of words. We found that the amplitude of an early frontal/central negativity at 84–120 ms (N1) decreased to death-related words but increased to life-related words relative to neutral-valence words. The N1 effect associated with death-related and life-related words was correlated respectively with individuals’ pessimistic and optimistic attitudes toward life. Death-related words also increased the amplitude of a frontal/central positivity at 124–300 ms (P2) and of a frontal/central positivity at 300–500 ms (P3). However, the P2 and P3 modulations were observed for both death-related and negative-valence words but not for life-related words. The ERP results suggest an early inverse coding of linguistic cues related to life and death, which is followed by negative emotional responses to death-related information. PMID:23840787

  3. A primatological perspective on death.

    PubMed

    Anderson, James R

    2011-05-01

    Some questions that arise from observations of responses to dead and dying individuals by nonhuman primates are discussed, focusing on psychological issues. The phenomenon of transport and care of dead infants is reviewed, along with the consequences of the mother dying for orphaned offspring. It is argued that particular attention should be paid to how the context of a death affects individuals, for example, traumatic accidental or predation-induced death versus peaceful death following illness. Some primates kill others of their own or other species, which raises additional questions about death awareness and empathy. Observations from both the field and captivity can contribute toward a better understanding of the psychological meaning of death for primates. Some aspects of death awareness recognized by developmental psychologists might help guide research efforts in this area.

  4. Sudden cardiac death in adolescents.

    PubMed

    Ellison, Stefanie R

    2015-03-01

    Adolescent sudden cardiac death is rare. When it occurs, it is devastating to families and communities because of the unexpected nature of the death and the age of the victim. It is especially troubling because these patients are seemingly healthy compared with their adult counterparts who die from coronary artery disease. This article reviews the incidence, etiology, prevalence, risk, screening, and prevention strategies for the sudden cardiac death of adolescents. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. DNA Damage Induced Neuronal Death

    DTIC Science & Technology

    1999-10-01

    Experiments are proposed to examine the molecular mechanism by which mustard chemical warfare agents induce neuronal cell death . DNA damage is the...proposed underlying mechanism of mustard-induced neuronal cell death . We propose a novel research strategy to test this hypothesis by using mice with...perturbed DNA repair to explore the relationship between mustard-induced DNA damage and neuronal cell death . Initial in vitro studies (Years 1, 2 & 3

  6. Death anxiety among Lebanese samples.

    PubMed

    Abdel-Khalek, A M

    1991-06-01

    An Arabic version of the Templer Death Anxiety Scale was administered to 673 Lebanese volunteer subjects (164 boys, 165 girls in secondary school, 170 men, 174 women undergraduates). Females attained higher mean death anxiety scores than males. The Lebanese samples had either the same or a lower mean score on death anxiety than their Arab peers, that is, Egyptians and Kuwaitians and also US samples. Split-half reliabilities ranged from .57 to .68.

  7. Deaths: leading causes for 2009.

    PubMed

    Heron, Melonie

    2012-10-26

    This report presents final 2009 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements the Division of Vital Statistics' annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2009. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD-10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2009, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Cerebrovascular diseases; Accidents (unintentional injuries); Alzheimer's disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Intentional self-harm (suicide). These causes accounted for approximately 75% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2009 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods.

  8. Deaths: leading causes for 2010.

    PubMed

    Heron, Melonie

    2013-12-20

    This report presents final 2010 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements the Division of Vital Statistics' annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2010. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD-10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2010, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Cerebrovascular diseases; Accidents (unintentional injuries); Alzheimer's disease; Diabetes mellitus; Nephritis, nephrotic syndrome and nephrosis; Influenza and pneumonia; and Intentional self-harm (suicide). These 10 causes accounted for 75% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2010 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Necrotizing enterocolitis of newborn. Important variations in the leading causes of infant death are noted for the neonatal and post-neonatal periods. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source

  9. Birthday and date of death.

    PubMed Central

    Angermeyer, M C; Kühn, L; Osterwald, P

    1987-01-01

    The relation between birthday and date of death has so far been studied from two different perspectives: birthdays were either conceived of as emotionally invested deadlines motivating people to ward off their death which causes a 'dip' in death rates before their birthday, or they were considered as stressful events leading to an increase of mortality on or after their birthday. Using a collection of biographies of famous people from the whole world and another of well-known Swiss citizens we tested hypotheses derived from these assumptions. Neither the 'death-dip' hypotheses nor the 'birthday stress' hypothesis was supported by our results. PMID:3655631

  10. [Genetics of sudden unexplained death].

    PubMed

    Campuzano, Oscar; Allegue, Catarina; Brugada, Ramon

    2014-03-20

    Sudden unexplained death is defined by death without a conclusive diagnosis after autopsy and it is responsible for a large percentage of sudden deaths. The progressive interaction between genetics and forensics in post-mortem studies has identified inheritable alterations responsible for pathologies associated with arrhythmic sudden death. The genetic diagnosis of the deceased enables the undertaking of preventive measures in family members, many of them asymptomatic but at risk. The implications of this multidisciplinary translational medical approach are complex, requiring the dedication of a specialized team.

  11. Death competence: an ethical imperative.

    PubMed

    Gamino, Louis A; Ritter, R Hal

    2012-01-01

    The authors argued that death competence, defined as specialized skill in tolerating and managing clients' problems related to dying, death, and bereavement, is a necessary prerequisite for ethical practice in grief counseling. A selected review of the literature tracing the underpinnings of this concept reveals how a robust construct of death competence evolved. Using the vehicle of a case study, the authors analyzed an example of empathic failure resulting from an apparent lack of death competence on the part of a mental health provider to illustrate the importance of this characteristic in delivering clinically effective and ethically sensitive grief counseling.

  12. The death of a person.

    PubMed

    Hershenov, David B

    2006-04-01

    Drawing upon Lynne Baker's idea of the person derivatively possessing the properties of a constituting organism, I argue that even if persons aren't identical to living organisms, they can each literally die a biological death. Thus we can accept that we're not essentially organisms and can still die without having to admit that there are two concepts and criteria of death as Jeff McMahan and Robert Veatch do. Furthermore, we can accept James Bernat's definition of "death" without having to insist, as he does, that persons are identical to organisms or that persons can only die metaphorical deaths.

  13. Modulated Entry

    NASA Technical Reports Server (NTRS)

    Grant, Frederick C.

    1960-01-01

    The technique of modulation, or variable coefficients, is discussed and the analytical formulation is reviewed. Representative numerical results of the use of modulation are shown for the lifting and nonlifting cases. These results include the effects of modulation on peak acceleration, entry corridor, and heat absorption. Results are given for entry at satellite speed and escape speed. The indications are that coefficient modulation on a vehicle with good lifting capability offers the possibility of sizable loading reductions or, alternatively, wider corridors; thus, steep entries become practical from the loading standpoint. The amount of steepness depends on the acceptable heating penalty. The price of sizable fractions of the possible gains does not appear to be excessive.

  14. History of brain death as death: 1968 to the present.

    PubMed

    De Georgia, Michael A

    2014-08-01

    The concept of brain death was formulated in 1968 in the landmark report A Definition of Irreversible Coma. While brain death has been widely accepted as a determination of death throughout the world, many of the controversies that surround it have not been settled. Some may be rooted in a misconstruction about the history of brain death. The concept evolved as a result of the convergence of several parallel developments in the second half of the 20th century including advances in resuscitation and critical care, research into the underlying physiology of consciousness, and growing concerns about technology, medical futility, and the ethics of end of life care. Organ transplantation also developed in parallel, and though it clearly benefited from a new definition of death, it was not a principal driving force in its creation. Since 1968, the concept of brain death has been extensively analyzed, debated, and reworked. Still there remains much misunderstanding and confusion, especially in the general public. In this comprehensive review, I will trace the evolution of the definition of brain death as death from 1968 to the present, providing background, history and context.

  15. Education for Death, or Death Becomes Less a Stranger.

    ERIC Educational Resources Information Center

    Leviton, Dan

    The purpose of this paper is to describe 1.) the Death Education and Suicide Behavior course offered at the University of Maryland; 2.) the comments of the students both before and after the course as a means of determining any effect of the course; and 3.) some insights gained from teaching taboo topics such as human death and sexuality. The…

  16. Children's concept of death and sibling death from trauma.

    PubMed

    Mahon, M M

    1993-10-01

    Factors influencing children's concept of death (their understanding of finality, inevitability, and universality) were examined. A bereaved group of 29 siblings (5 to 12 years of age) of children who died from trauma were interviewed 13 to 17 months after their sibling's death. A comparison group (n = 29) of nonbereaved siblings who had not experienced a sibling's death was matched for age, race, gender, and sociodemographic background. Demographic data, a Piagetian developmental assessment, and a concept of death assessment incorporating vignettes were used to collect data. The experience of sibling death from trauma did not significantly influence acquisition of an accurate concept of death; developmental level (p = 0.0001) and age (p = 0.0003) were significant predictors. Of the 5-year-old subjects in this study, 45.7% had an accurate concept of death, as did > 60% of 6-, 7-, and 8-year-old subjects, 100% of 9-, 11-, and 12-year-old subjects, and 90% of 10-year-old subjects. This reflects an understanding of death at a much younger age than reported by previous researchers.

  17. Expressing death risk as condensed life experience and death intensity.

    PubMed

    Ioannidis, John P A

    2013-08-01

    Some risk exposures, including many medical and surgical procedures, typically carry hazards of death that are difficult to convey and appreciate in absolute terms. I propose presenting the death risk as a condensed life experience (i.e., the equivalent amount of life T that would carry the same cumulative mortality hazard for a person of the same age and sex based on life tables). For example, if the risk of death during an elective 1-hour procedure is 0.01%, and same-age and same-sex people have a 0.01% death risk over 1 month, one can inform the patient that "this procedure carries the same death risk as living 1 month of normal life." Comparative standards from other risky activities or from a person with the same disease at the same stage and same predictive profile could also be used. A complementary metric that may be useful to consider is the death intensity. The death intensity λ is the hazard function that shows the fold-risk estimate of dying compared with the reference person. The death intensity can vary substantially for different phases of the event, operation, or procedure (e.g., intraoperative, early postoperative, late postoperative), and this variability may also be useful to convey. T will vary depending on the time window for which it is computed. I present examples for calculating T and λ using literature data on accidents, ascent to Mount Everest, and medical and surgical procedures.

  18. Death revisited: rethinking death and the dead donor rule.

    PubMed

    Iltis, Ana Smith; Cherry, Mark J

    2010-06-01

    Traditionally, people were recognized as being dead using cardio-respiratory criteria: individuals who had permanently stopped breathing and whose heart had permanently stopped beating were dead. Technological developments in the middle of the twentieth century and the advent of the intensive care unit made it possible to sustain cardio-respiratory and other functions in patients with severe brain injury who previously would have lost such functions permanently shortly after sustaining a brain injury. What could and should physicians caring for such patients do? Significant advances in human organ transplantation also played direct and indirect roles in discussions regarding the care of such patients. Because successful transplantation requires that organs be removed from cadavers shortly after death to avoid organ damage due to loss of oxygen, there has been keen interest in knowing precisely when people are dead so that organs could be removed. Criteria for declaring death using neurological criteria developed, and today a whole brain definition of death is widely used and recognized by all 50 states in the United States as an acceptable way to determine death. We explore the ongoing debate over definitions of death, particularly over brain death or death determined using neurological criteria, and the relationship between definitions of death and organ transplantation.

  19. Death Attitudes among Mid-Life Women.

    ERIC Educational Resources Information Center

    Richardson, Virginia; Sands, Roberta

    1987-01-01

    Examined death attitudes among 74 female college reentry students aged 30 through 49. Found relationships between: (1) developmental factors and death concern, death as interpersonal loss, and death as dimension of time; (2) age and death anticipation; and (3) income and death denial. Results suggest importance of considering both developmental…

  20. A Good Death.

    PubMed

    Powell, Tia; Hulkower, Adira

    2017-01-01

    A good death is hard to find. Family members tell us that loved ones die in the wrong place-the hospital-and do not receive high-quality care at the end of life. This issue of the Hastings Center Report offers two articles from authors who strive to provide good end-of-life care and to prevent needless suffering. We agree with their goals, but we have substantial reservations about the approaches they recommend. Respect for the decisions of patients and their surrogates is a relatively new and still vulnerable aspect of medical care. For thousands of years, patients and surrogates had no say in medical decision-making. Today, standards support shared decision-making, but these articles both carve out exceptions to those standards, limiting the rights of patients and families in decisions about specific end-of-life treatments. As bioethics consultants in an acute care setting, we frequently confront conflicts similar to those described by Jeffrey Berger and by Ellen Robinson and colleagues. In such cases, our service emphasizes redoubled efforts at communication and mediation. Focusing on goals and values, rather than interventions, produces the best possible collaboration in health care decision-making. Cases in which we would overturn a surrogate's recommendations regarding palliative sedation or do-not-resuscitate orders are rare and require careful processes and clear evidence that the surrogate's choice is contrary to patient values.

  1. Causes of death in Vanuatu.

    PubMed

    Carter, Karen; Tovu, Viran; Langati, Jeffrey Tila; Buttsworth, Michael; Dingley, Lester; Calo, Andy; Harrison, Griffith; Rao, Chalapati; Lopez, Alan D; Taylor, Richard

    2016-01-01

    The population of the Pacific Melanesian country of Vanuatu was 234,000 at the 2009 census. Apart from subsistence activities, economic activity includes tourism and agriculture. Current completeness of vital registration is considered too low to be usable for national statistics; mortality and life expectancy (LE) are derived from indirect demographic estimates from censuses/surveys. Some cause of death (CoD) data are available to provide information on major causes of premature death. Deaths 2001-2007 were coded for cause (ICDv10) for ages 0-59 years from: hospital separations (HS) (n = 636), hospital medical certificates (MC) of death (n = 1,169), and monthly reports from community health facilities (CHF) (n = 1,212). Ill-defined causes were 3 % for hospital deaths and 20 % from CHF. Proportional mortality was calculated by cause (excluding ill-defined) and age group (0-4, 5-14 years), and also by sex for 15-59 years. From total deaths by broad age group and sex from 1999 and 2009 census analyses, community deaths were estimated by deduction of hospital deaths MC. National proportional mortality by cause was estimated by a weighted average of MC and CHF deaths. National estimates indicate main causes of deaths <5 years were: perinatal disorders (45 %) and malaria, diarrhea, and pneumonia (27 %). For 15-59 years, main causes of male deaths were: circulatory disease 27 %, neoplasms 13 %, injury 13 %, liver disease 10 %, infection 10 %, diabetes 7 %, and chronic respiratory disease 7 %; and for females: neoplasms 29 %, circulatory disease 15 %, diabetes 10 %, infection 9 %, and maternal deaths 8 %. Infection included tuberculosis, malaria, and viral hepatitis. Liver disease (including hepatitis and cancer) accounted for 18 % of deaths in adult males and 9 % in females. Non-communicable disease (NCD), including circulatory disease, diabetes, neoplasm, and chronic respiratory disease, accounted for 52 % of premature deaths in adult

  2. Elderly deaths in Ankara, Turkey.

    PubMed

    Akar, Taner; Karapirli, Mustafa; Akcan, Ramazan; Demirel, Birol; Akduman, Barış; Dursun, Ahmet Zahit; Sari, Serhat; Özkök, Alper

    2014-01-01

    According to World Health Organization, the life expectancy at birth is increasing. An increase in life expectancy might result in increased morbidity and mortality in elderly. The increase in the elderly population also leads to an increase in medico-legal problems, as well. Autopsy is of high importance for determination of cause of death in clinical and forensic cases. The purpose of this study was to find out general characteristics elderly deaths by examining forensic autopsy records. Out of 7033 forensic autopsies performed between years of 2007 and 2011, 1324 were elderly deaths and were included in the scope of the study. The records of public prosecutor office, crime scene investigation and autopsy findings were examined. The majority of victims (70.6%) were male, while 29.4% were female, with a male to female ratio of 2.4/1. Victims' ages ranged between 65 and 96 years, and the mean age was 74.8 years. A great number of presented elderly deaths were due to unnatural causes, followed by natural deaths cases. Out of unnatural deaths, 63.2% were related to accidents, 23.7% were suicides, and remaining 13.1% were homicides. More than half (56.6%) of all suicidal deaths were due to hanging. Of natural deaths, the majority (82.7%) were due to cardiovascular system disease. In the presented series the cause of death was determined in 90.9% of all elderly deaths, which validates the need for a forensic autopsy. Data obtained through autopsy procedures is of high importance for death statistics.

  3. Deaths: leading causes for 1999.

    PubMed

    Anderson, R N

    2001-10-12

    This report presents final 1999 data on the 10 leading causes of death in the United States by age, race, sex, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements the annual report of final mortality statistics and responds to an increasing volume of requests by data users for leading-cause tables with more age and race detail than previously published. Data in this report are based on information from all death certificates filed in the 50 States and the District of Columbia in 1999. Causes of death classified by the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) are ranked according to the number of deaths assigned to rankable causes. Age categories used to present leading causes of death in this report represent a substantial expansion from the age categories previously used to present leading-cause data in the annual report of final mortality statistics. In 1999 the 10 leading causes of death were (in rank order) Diseases of heart; Malignant neoplasms; Cerebrovascular diseases; Chronic lower respiratory diseases; Accidents; Diabetes mellitus; Influenza and pneumonia; Alzheimer's disease; Nephritis, nephrotic syndrome, and nephrosis; and Septicemia and accounted for nearly 80 percent of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 1999 were (in rank order) Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birthweight, not elsewhere classified; Sudden infant death syndrome; newborn affected by maternal complications of pregnancy; Respiratory distress of newborn; Newborn affected by complications of placenta, cord, and membranes; Accidents; Bacterial sepsis of newborn; Diseases of the circulatory system; and Atelectasis. Important variation in the leading

  4. Causes of death in Minamata disease: analysis of death certificates.

    PubMed

    Tamashiro, H; Akagi, H; Arakaki, M; Futatsuka, M; Roht, L H

    1984-01-01

    The causes of death in Minamata disease were analyzed and compared with those of control subjects. Of the 1422 Minamata disease patients in the Kumamoto Prefecture, 378 had died by the end of 1980. Of these 378, the first death occurred in 1954 with a peak incidence in 1956 when Minamata disease was officially reported for the first time. The number of deaths increased rapidly after 1972 with a second peak in 1976. The male:female ratio was 1.8:1 and the mean age-at-death was 67.2 years (SD = +/- 18.65). The mean age-at-death was younger in the cases of the initial outbreak than in those recently. There were, on the average, 2.8 causes of death per person. Of these cases, 157 (41.5%) had Minamata disease indicated on the death certificate, though 64 (16.9%) had Minamata disease coded as the underlying cause. Minamata disease and the noninflammatory diseases of the central nervous system (CNS) were the main underlying causes of death between 1954 and 1969, while, in the multiple cause data, pneumonia and non-ischemic heart disease were the most prevalent. Cerebrovascular diseases (18.0%) were the main underlying causes of death followed by malignant neoplasms (14.7%), cardiovascular diseases (14.1%) and Minamata disease (14.1%) in 1970 or later, while cardiovascular diseases (18.6%), Minamata disease (14.5%), cerebrovascular diseases (10.4%) and malignant neoplasms (7.1%) were the major multiple causes of death. As compared with the control, the proportions of deaths due to noninflammatory diseases of CNS and pneumonia were higher in the initial outbreak. Although the difference in the causes of death was less apparent recently, malignant neoplasms and hypertensive diseases tended to be lower. These results suggest that there is a need for a long-term follow-up of Minamata disease patients. The data also show the potential value of multiple causes of death coding in analyses of mortality.

  5. Death Anxiety and Mental Ability.

    ERIC Educational Resources Information Center

    Templer, Donald I.; Salter, Charles A.

    1979-01-01

    Measures of death anxiety, the Thrustone Interest Inventory, the A-B Scale, and the SAT and ACT aptitude tests, were taken among college students. The implications are discussed in terms of a theoretical five-component biosocial model and its relationship to death anxiety. (Author)

  6. Counselling via a "Death Perspective."

    ERIC Educational Resources Information Center

    Seeman, Howard

    1986-01-01

    Points out the progress in the clinical literature in helping people deal with the event of death but argues there is great neglect in the literature regarding viewing death as a perspective, and its valuable clinical use. By referring to Heidegger's contributions to existential psychology, explains what is meant by this perspective and its…

  7. Brain death: the European perspective.

    PubMed

    Citerio, Giuseppe; Murphy, Paul G

    2015-04-01

    Some of the seminal steps toward the recognition and definition of brain death were European. There is a general consensus on both the medical concept of brain death in Europe as well as the minimum fundamental clinical standards that are required for its diagnosis-the absence of consciousness, brainstem reflexes, and the ability to breathe in the absence of reversible or confounding conditions. Two aspects of brain death determination are addressed in this article. The authors analyze how brain death is diagnosed across Europe, identifying both the similarities and differences that exist between countries (the latter mainly concerning ancillary tests, timing, and the number of physicians involved in the brain death determination). In addition, they describe the very considerable variations in when brain death determinations are made between and within individual European countries, and propose that they are due to differences in the end-of-life care practices in patients with irreversible brain injuries, medical attitudes, and organ donation practices. Although legislation is available to standardize the brain death diagnosis process in most individual European countries, there are still disparities across Europe as a whole. The current variation in practice makes a continental consensus for the definition of brain death imperative.

  8. Death Competence: An Ethical Imperative

    ERIC Educational Resources Information Center

    Gamino, Louis A.; Ritter, R. Hal, Jr.

    2012-01-01

    The authors argued that death competence, defined as specialized skill in tolerating and managing clients' problems related to dying, death, and bereavement, is a necessary prerequisite for ethical practice in grief counseling. A selected review of the literature tracing the underpinnings of this concept reveals how a robust construct of death…

  9. Child Abuse and Cot Deaths.

    ERIC Educational Resources Information Center

    Newlands, Mary; Emery, John S.

    1991-01-01

    A search was made of confidential health department records in Great Britain for abused children, or children at risk for abuse, with siblings who had died of Sudden Infant Death Syndrome (SIDS). An association was found between child abuse and about 10 percent of deaths of children diagnosed as SIDS. (BRM)

  10. Death: A Part of Life.

    ERIC Educational Resources Information Center

    Otero, George G.; Harris, Zoanne

    This two-part curriculum unit includes 20 slides depicting Days of the Dead in Mexico and the United States. The unit is designed to help middle school students compare customs and practices associated with death throughout the world in a way that promotes understanding of the values and needs that produce and are reinforced by death rituals and…

  11. Cancer therapy: Death by magnetism

    NASA Astrophysics Data System (ADS)

    Dobson, Jon

    2012-12-01

    A magnetic on/off switch for cell-death signalling in cancer cells is developed using antibodies conjugated to magnetic nanoparticles. The control of cell death in in vivo systems is demonstrated by a tell-tale morphological change within the zebrafish.

  12. Death Outlook and Social Issues.

    ERIC Educational Resources Information Center

    Feifel, Herman; Schag, Daniel

    1980-01-01

    Examined the hypothesis that there is a relationship between outlook on death and orientation toward mercy killing, abortion, suicide, and euthanasia. Some relationships between death attitudes and perspectives on the social issues emphasized the need to consider specific circumstances as well as abstract concepts. (Author)

  13. Death Education and Grief Counseling.

    ERIC Educational Resources Information Center

    Mille, Nancy A.

    This paper explores ways in which school counselors can help young people with death-related concerns. It is often assumed that school counselors have the necessary skills for working with students who experience grief, but most graduate counseling curricula do not require courses in death education; thus, many counselors feel uncomfortable in…

  14. Goals in Teaching About Death.

    ERIC Educational Resources Information Center

    Klass, Dennis; Gordon, Audrey

    This guide provides a set of goals and guidelines for teachers who are introducing "death and dying" into the school curriculum. These goals are: (1) to provide factual information concerning legal, medical, and sociological practices; (2) to give insight into personal feelings and family dynamics when death occurs; (3) to provide consumer…

  15. Sudden death in Steinert's disease.

    PubMed

    Fayssoil, A; Nardi, O

    2009-08-14

    Steinert's disease is an autosomal dominant neuromuscular disorder. Heart involvement is characterized by conduction system abnormalities, supraventricular and ventricular arrhythmias. Patients with Steinert's disease are reported to have a higher incidence of sudden death. Preventing sudden death is crucial in this disease. It relies on non-invasive and/or invasive approach for risk stratification.

  16. Death Competence: An Ethical Imperative

    ERIC Educational Resources Information Center

    Gamino, Louis A.; Ritter, R. Hal, Jr.

    2012-01-01

    The authors argued that death competence, defined as specialized skill in tolerating and managing clients' problems related to dying, death, and bereavement, is a necessary prerequisite for ethical practice in grief counseling. A selected review of the literature tracing the underpinnings of this concept reveals how a robust construct of death…

  17. Sudden death in eating disorders.

    PubMed

    Jáuregui-Garrido, Beatriz; Jáuregui-Lobera, Ignacio

    2012-01-01

    Eating disorders are usually associated with an increased risk of premature death with a wide range of rates and causes of mortality. "Sudden death" has been defined as the abrupt and unexpected occurrence of fatality for which no satisfactory explanation of the cause can be ascertained. In many cases of sudden death, autopsies do not clarify the main cause. Cardiovascular complications are usually involved in these deaths. The purpose of this review was to report an update of the existing literature data on the main findings with respect to sudden death in eating disorders by means of a search conducted in PubMed. The most relevant conclusion of this review seems to be that the main causes of sudden death in eating disorders are those related to cardiovascular complications. The predictive value of the increased QT interval dispersion as a marker of sudden acute ventricular arrhythmia and death has been demonstrated. Eating disorder patients with severe cardiovascular symptoms should be hospitalized. In general, with respect to sudden death in eating disorders, some findings (eg, long-term eating disorders, chronic hypokalemia, chronically low plasma albumin, and QT intervals >600 milliseconds) must be taken into account, and it must be highlighted that during refeeding, the adverse effects of hypophosphatemia include cardiac failure. Monitoring vital signs and performing electrocardiograms and serial measurements of plasma potassium are relevant during the treatment of eating disorder patients.

  18. Death Outlook and Social Issues.

    ERIC Educational Resources Information Center

    Feifel, Herman; Schag, Daniel

    1980-01-01

    Examined the hypothesis that there is a relationship between outlook on death and orientation toward mercy killing, abortion, suicide, and euthanasia. Some relationships between death attitudes and perspectives on the social issues emphasized the need to consider specific circumstances as well as abstract concepts. (Author)

  19. Individual Defenses against Death Anxiety.

    ERIC Educational Resources Information Center

    Firestone, Robert W.

    1993-01-01

    Proposes that death anxiety is related to degree of individuation and self-actualization. Sees concerns about death increasing as people relinquish defenses, reach new levels of differentiation of self, and expand their lives and personal power. Notes that therapeutic progress poses existential dilemma. (Author/NB)

  20. Death: A Part of Life.

    ERIC Educational Resources Information Center

    Otero, George G.; Harris, Zoanne

    This two-part curriculum unit includes 20 slides depicting Days of the Dead in Mexico and the United States. The unit is designed to help middle school students compare customs and practices associated with death throughout the world in a way that promotes understanding of the values and needs that produce and are reinforced by death rituals and…

  1. Electric fences and accidental death.

    PubMed

    Burke, Michael; Odell, Morris; Bouwer, Heinrich; Murdoch, Adam

    2017-03-28

    Deaths which occur in association with agricultural electric fences are very rare. In fact, electric fences have undoubtedly saved numerous human and animal lives by safely and reliably keeping livestock confined to their fields and enclosures and thus preventing motor vehicle incidents when livestock get onto roads and highways. Accidental and intentional human contact with electric fences occurs regularly and causes little more than transient discomfort, however, on exceptional occasions, contact with electric fences appears to be directly related to the death of the individual. The precise pathophysiological cause of these deaths is unclear. We present two cases of deaths associated with electric fences, discuss the possible pathophysiological mechanisms in these cases, and suggest a universal approach to the medico-legal investigation and documentation of these deaths.

  2. Paediatric deaths in Kuala Lumpur.

    PubMed

    Kumar, Virendra; Jumali, Ismail Bin

    2006-10-01

    The main aim of this study was to determine the causes and epidemiological aspects of paediatric death. Data was collected on 143 cases of paediatric death from a total of 2,895 autopsies performed in University Malaya Medical Centre (UMMC), Kuala Lumpur, over a five-year period from 2000 to 2004. There were 78 males and 65 females. The largest number of cases (32.9%) were stillborn. The highest proportion of cases (30.1%) were Chinese. The majority of cases of paediatric death were non-traumatic (74.8%) of which intrauterine death (IUD) was the most common (32.9%). Amongst the traumatic deaths (25.2%), accidental injury (23.8%) was observed in the majority of cases.

  3. Estimating risks of perinatal death.

    PubMed

    Smith, Gordon C S

    2005-01-01

    The relative and absolute risks of perinatal death that are estimated from observational studies are used frequently in counseling about obstetric intervention. The statistical basis for these estimates therefore is crucial, but many studies are seriously flawed. In this review, a number of aspects of the approach to the estimation of the risk of perinatal death are addressed. Key factors in the analysis include (1) the definition of the cause of the death, (2) differentiation between antepartum and intrapartum events, (3) the use of the appropriate denominator for the given cause of death, (4) the assessment of the cumulative risk where appropriate, (5) the use of appropriate statistical tests, (6) the stratification of analysis of delivery-related deaths by gestational age, and (7) the specific features of multiple pregnancy, which include the correct determination of the timing of antepartum stillbirth and the use of paired statistical tests when outcomes are compared in relation to the birth order of twin pairs.

  4. When Brain Death Belies Belief.

    PubMed

    Yanke, Greg; Rady, Mohamed Y; Verheijde, Joseph L

    2016-12-01

    The case of Jahi McMath has reignited a discussion concerning how society should define death. Despite pronouncing McMath brain dead based on the American Academy of Neurology criteria, the court ordered continued mechanical ventilation to accommodate the family's religious beliefs. Recent case law suggests that the potential for a successful challenge to the neurologic criteria of death provisions of the Uniform Determination of Death Act are greater than ever in the majority of states that have passed religious freedom legislation. As well, because standard ethical claims regarding brain death are either patently untrue or subject to legitimate dispute, those whose beliefs do not comport with the brain death standard should be able to reject it.

  5. Facility Death Review of Maternal and Neonatal Deaths in Bangladesh

    PubMed Central

    Biswas, Animesh; Rahman, Fazlur; Eriksson, Charli; Halim, Abdul; Dalal, Koustuv

    2015-01-01

    Objectives To explore the experiences, acceptance, and effects of conducting facility death review (FDR) of maternal and neonatal deaths and stillbirths at or below the district level in Bangladesh. Methods This was a qualitative study with healthcare providers involved in FDRs. Two districts were studied: Thakurgaon district (a pilot district) and Jamalpur district (randomly selected from three follow-on study districts). Data were collected between January and November 2011. Data were collected from focus group discussions, in-depth interviews, and document review. Hospital administrators, obstetrics and gynecology consultants, and pediatric consultants and nurses employed in the same departments of the respective facilities participated in the study. Content and thematic analyses were performed. Results FDR for maternal and neonatal deaths and stillbirths can be performed in upazila health complexes at sub-district and district hospital levels. Senior staff nurses took responsibility for notifying each death and conducting death reviews with the support of doctors. Doctors reviewed the FDRs to assign causes of death. Review meetings with doctors, nurses, and health managers at the upazila and district levels supported the preparation of remedial action plans based on FDR findings, and interventions were planned accordingly. There were excellent examples of improved quality of care at facilities as a result of FDR. FDR also identified gaps and challenges to overcome in the near future to improve maternal and newborn health. Discussion FDR of maternal and neonatal deaths is feasible in district and upazila health facilities. FDR not only identifies the medical causes of a maternal or neonatal death but also explores remediable gaps and challenges in the facility. FDR creates an enabled environment in the facility to explore medical causes of deaths, including the gaps and challenges that influence mortality. FDRs mobilize health managers at upazila and district

  6. Firefighting Module

    NASA Technical Reports Server (NTRS)

    1978-01-01

    NASA and the U.S. Coast Guard are working jointly to develop a helicopter transportable firefighting module that can shave precious minutes in combating shipboard or harbor fires. The program was undertaken in 1975, after a series of disastrous fires on oil tankers indicated a need for a lightweight, self-contained system that could be moved quickly to the scene of a fire. A prototype module was delivered to the Coast Guard last year and service testing is under way. The compact module weighs little more than a ton but it contains everything needed to fight a fire. The key component is a high output pump, which delivers up to 2,000 gallons of sea water a minute; the pump can be brought up to maximum output in only one minute after turning on the power source, a small Allison gas turbine engine. The module also contains hose, a foam nozzle and a spray nozzle, three sets of protective clothing for firefighters, and fuel for three hours operation. Designed to be assembled without special tools, the module can be set up for operation in less than 20 minutes.

  7. Firefighting Module

    NASA Technical Reports Server (NTRS)

    1980-01-01

    Aviation Power Supply's mobile firefighting module called Firefly II is mounted on a trailer pulled by a pickup truck. Trailer unit has two three- inch water cannons, and the pickup carries a six inch cannon. Completely self contained, module pumps 3,000 gallons of water a minute from hydrants or open bodies of water. Stream can go as far as 400 feet or can be employed in a high-loft mode to reach the tops of tall refinery towers. Compact Firefly II weighs only 2,500 pounds when fully fueled. Key component is a specially designed two stage pump. Power for the pump is generated by a gas turbine engine. Module also includes an electronic/pump controller, multiple hose connections, up to 1,500 feet of hose and fuel for four hours operation. Firefly trailer can be backed onto specially-built large fireboat.

  8. Firefighting Module

    NASA Technical Reports Server (NTRS)

    1981-01-01

    Aviation Power Supply's mobile firefighting module called Firefly II is mounted on a trailer pulled by a pickup truck. Trailer unit has two three- inch water cannons, and the pickup carries a six inch cannon. Completely self contained, module pumps 3,000 gallons of water a minute from hydrants or open bodies of water. Stream can go as far as 400 feet or can be employed in a high-loft mode to reach the tops of tall refinery towers. Compact Firefly II weighs only 2,500 pounds when fully fueled. Key component is a specially designed two stage pump. Power for the pump is generated by a gas turbine engine. Module also includes an electronic/pump controller, multiple hose connections, up to 1,500 feet of hose and fuel for four hours operation. Firefly trailer can be backed onto specially-built large fireboat.

  9. Firefighting Module

    NASA Astrophysics Data System (ADS)

    1981-01-01

    Aviation Power Supply's mobile firefighting module called Firefly II is mounted on a trailer pulled by a pickup truck. Trailer unit has two three- inch water cannons, and the pickup carries a six inch cannon. Completely self contained, module pumps 3,000 gallons of water a minute from hydrants or open bodies of water. Stream can go as far as 400 feet or can be employed in a high-loft mode to reach the tops of tall refinery towers. Compact Firefly II weighs only 2,500 pounds when fully fueled. Key component is a specially designed two stage pump. Power for the pump is generated by a gas turbine engine. Module also includes an electronic/pump controller, multiple hose connections, up to 1,500 feet of hose and fuel for four hours operation. Firefly trailer can be backed onto specially-built large fireboat.

  10. Firefighting Module

    NASA Astrophysics Data System (ADS)

    1980-01-01

    Aviation Power Supply's mobile firefighting module called Firefly II is mounted on a trailer pulled by a pickup truck. Trailer unit has two three- inch water cannons, and the pickup carries a six inch cannon. Completely self contained, module pumps 3,000 gallons of water a minute from hydrants or open bodies of water. Stream can go as far as 400 feet or can be employed in a high-loft mode to reach the tops of tall refinery towers. Compact Firefly II weighs only 2,500 pounds when fully fueled. Key component is a specially designed two stage pump. Power for the pump is generated by a gas turbine engine. Module also includes an electronic/pump controller, multiple hose connections, up to 1,500 feet of hose and fuel for four hours operation. Firefly trailer can be backed onto specially-built large fireboat.

  11. The Effects of Selected Death Education Curriculum Models on Death Anxiety and Death Acceptance.

    ERIC Educational Resources Information Center

    Combs, Don C.

    1981-01-01

    A comparison of the effects of didactic and experiential death education curriculums show no decrease in death anxiety from mid- to posttesting for any treatment group. Anxiety was increased from pre- to mid-testing for some students. Results may be due to model deficiencies. Further research is suggested. (JAC)

  12. Thermionic modules

    DOEpatents

    King, Donald B.; Sadwick, Laurence P.; Wernsman, Bernard R.

    2002-06-18

    Modules of assembled microminiature thermionic converters (MTCs) having high energy-conversion efficiencies and variable operating temperatures manufactured using MEMS manufacturing techniques including chemical vapor deposition. The MTCs incorporate cathode to anode spacing of about 1 micron or less and use cathode and anode materials having work functions ranging from about 1 eV to about 3 eV. The MTCs also exhibit maximum efficiencies of just under 30%, and thousands of the devices and modules can be fabricated at modest costs.

  13. Hypochondriasis and fear of death.

    PubMed

    Noyes, Russell; Stuart, Scott; Longley, Susan L; Langbehn, Douglas R; Happel, Rachel L

    2002-08-01

    Although fear of death has been linked to hypochondriasis, the relationship of this fear to the disorder has received little study. To address this deficiency, we administered a fear of death scale along with measures of hypochondriasis, including the Whiteley Index and Somatic Symptom Inventory, to 162 general medical outpatients. Partial correlations, controlling for age, between the fear of death scale and both the Whiteley Index and Somatic Symptom Inventory were strongly positive. A factor analysis of the fear of death scale yielded three dimensions-fear of dying, loss of meaning, and fear of separation-that were also highly correlated with hypochondriasis. Fear of death and hypochondriasis showed comparable relationships to age and gender as well as to personality dimensions measured by the NEO Five-Factor Inventory. Fear of death appears to be an integral part of hypochondriasis. Its presence lends support to three models of hypochondriasis-the perceptual, existential, and interpersonal-that correspond to the dimensions of fear of death.

  14. Psychosocial Aspects of the Sudden Infant Death Syndrome ("Cot Death").

    ERIC Educational Resources Information Center

    Bluglass, Kerry

    1981-01-01

    Reviews literature on reactions of parents and siblings to Sudden Infant Death Syndrome (SIDS). The prospects for prolonged, adverse reactions are considered, and professional concerns regarding abnormal adaptation are noted. (Author/DB)

  15. Methadone related deaths compared to all prescription related deaths.

    PubMed

    Lev, Roneet; Petro, Sean; Lee, Ariella; Lee, Oren; Lucas, Jonathan; Castillo, Edward M; Egnatios, Jeremy; Vilke, Gary M

    2015-12-01

    Methadone is increasingly implicated in unintentional overdose deaths. Despite major interventions, rates continue to remain high. One primary intervention, Prescription Drug Monitoring Programs (PDMP) are limited in their ability to impact this epidemic due to federal law restricting Opioid Treatment Programs (OTPs) from sharing data to PDMPs, despite being a major source of Methadone dispensing. This retrospective, observational study analyzed all prescription-related deaths occurring in San Diego County during the year 2013 with a specific focus on methadone-related deaths. All patients designated by medical examiner to have died by unintentional prescription were then referenced in the California PDMP, the Controlled Substance Utilization Review and Evaluation System (CURES). As a whole, patients who died had a high number of average prescriptions, 21, and averaged 4.5 different providers, and three different pharmacies. Methadone-related deaths (MRD) accounted for 46 out of the 254 total patient deaths (18.1%). Methadone prescriptions were found in 14 patients with PDMP reports, 10 of who had methadone on toxicology report. Notably, 100% of methadone prescribed by primary care specialists. MRD patients were less likely to have toxicology reports matching PDMP data compared to other related drug deaths (20.6 vs. 61.2%, p<0.0001). Of the 46 methadone deaths, only 10 (29.4%) had prescriptions for methadone recorded in the database. Out of the 51 patients with only one drug recorded at death, methadone was most common (n=12; 23.5%). While all deaths had a notably high rate of chronic prescriptions at death (68.8% compared to 2% for all patients in CURES), there was no significant difference between MRD and other drug-related deaths (73.5 vs. 67.8%, p=0.68, respectively). MRD patients were less likely than other drug patients to have matching PDMP data without any illicit substance or alcohol (14.7 vs. 41.4%, p=0.003, respectively). Methadone is a long

  16. [Brain death--a certain sign of death].

    PubMed

    Angstwurm, H

    1990-10-01

    Brain death means a complete and irreversible loss of all brain activity during intensive care with mechanical ventilation. On autopsy is seen an ischemic infarct of the whole brain following the stopped blood flow in the intracranial cavity after the elevation of the pressure. With brain death a human being loses two characteristics of its earthly life, the physical base needed for his spirit and his soul in this world, and the integration, the unity as the independent and self-contained organism.

  17. Ferroptosis: Death by Lipid Peroxidation.

    PubMed

    Yang, Wan Seok; Stockwell, Brent R

    2016-03-01

    Ferroptosis is a regulated form of cell death driven by loss of activity of the lipid repair enzyme glutathione peroxidase 4 (GPX4) and subsequent accumulation of lipid-based reactive oxygen species (ROS), particularly lipid hydroperoxides. This form of iron-dependent cell death is genetically, biochemically, and morphologically distinct from other cell death modalities, including apoptosis, unregulated necrosis, and necroptosis. Ferroptosis is regulated by specific pathways and is involved in diverse biological contexts. Here we summarize the discovery of ferroptosis, the mechanism of ferroptosis regulation, and its increasingly appreciated relevance to both normal and pathological physiology.

  18. [The death of Ignatius Loyola].

    PubMed

    Huguier, Michel; Lacaine, Francois

    2011-12-01

    A recent examination of a bilioportal fistula led us to suspect a link between this case and the death of Ignatius of Loyola. Realdo Colombo, professor of anatomy, eviscerated Ignatius prior to his embalming In his book De re anatomica, published in 1559, he wrote that he extracted stones from the portal vein of the venerable Ignatius. Before his death, Ignatius suffered from epigastric pain and fever (Monumenta historica societatis Jesu). Colombo latin text is difficult to interpret and the data are meager. Other possible causes of Ignatius' death include gastroduodenal ulcer, tuberculosis and hyperparathyroidism, but despite of rarity bilioportal fistula is the best guess.

  19. Tryptophanless Death in Bacillus subtilis

    PubMed Central

    Majerfeld, Irene; Barlati, Sergio; Ciferri, Orio

    1970-01-01

    A decline in colony-forming ability is observed in actively growing cultures of a tryptophan arginine auxotroph of Bacillus subtilis after removal of tryptophan (tryptophanless death). This phenomenon can be prevented by simultaneous starvation of the other required amino acid or by chloramphenicol administered in bacteriostatic concentration but not by actinomycin. Addition of tryptophan analogues not only prevents the death but also allows recovery of the cells that have lost the ability to form colonies on solid media. The term tryptophanless death is therefore inappropriate. Chloramphenicol but not actinomycin inhibits the recovery brought about by tryptophan analogues. PMID:4189906

  20. Wealth transfer through voluntary death.

    PubMed

    Fung, K K

    1993-01-01

    Today, the hopelessly ill who are insured must choose between futile treatment and prolonged morbidity. Legalizing physician-assisted death for the hopelessly ill would broaden patient choice and conserve scarce resources. To ensure that the saved resources will not be re-channeled to more futile treatments for other hopelessly ill patients, those who choose dignified passage should be allowed to determine how the saving from their refusal to a prolonged death is to be re-deployed. Converting projected entitlements into death benefits at a discount would not only reduce health-care and retirements costs but improve allocation of scarce resources.

  1. Antioxidant gene therapy against neuronal cell death

    PubMed Central

    Navarro-Yepes, Juliana; Zavala-Flores, Laura; Annadurai, Anandhan; Wang, Fang; Skotak, Maciej; Chandra, Namas; Li, Ming; Pappa, Aglaia; Martinez-Fong, Daniel; Razo, Luz Maria Del; Quintanilla-Vega, Betzabet; Franco, Rodrigo

    2014-01-01

    Oxidative stress is a common hallmark of neuronal cell death associated with neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, as well as brain stroke/ischemia and traumatic brain injury. Increased accumulation of reactive species of both oxygen (ROS) and nitrogen (RNS) has been implicated in mitochondrial dysfunction, energy impairment, alterations in metal homeostasis and accumulation of aggregated proteins observed in neurodegenerative disorders, which lead to the activation/modulation of cell death mechanisms that include apoptotic, necrotic and autophagic pathways. Thus, the design of novel antioxidant strategies to selectively target oxidative stress and redox imbalance might represent important therapeutic approaches against neurological disorders. This work reviews the evidence demonstrating the ability of genetically encoded antioxidant systems to selectively counteract neuronal cell loss in neurodegenerative diseases and ischemic brain damage. Because gene therapy approaches to treat inherited and acquired disorders offer many unique advantages over conventional therapeutic approaches, we discussed basic research/clinical evidence and the potential of virus-mediated gene delivery techniques for antioxidant gene therapy. PMID:24333264

  2. Cardiac innervation and sudden cardiac death.

    PubMed

    Fukuda, Keiichi; Kanazawa, Hideaki; Aizawa, Yoshiyasu; Ardell, Jeffrey L; Shivkumar, Kalyanam

    2015-06-05

    Afferent and efferent cardiac neurotransmission via the cardiac nerves intricately modulates nearly all physiological functions of the heart (chronotropy, dromotropy, lusitropy, and inotropy). Afferent information from the heart is transmitted to higher levels of the nervous system for processing (intrinsic cardiac nervous system, extracardiac-intrathoracic ganglia, spinal cord, brain stem, and higher centers), which ultimately results in efferent cardiomotor neural impulses (via the sympathetic and parasympathetic nerves). This system forms interacting feedback loops that provide physiological stability for maintaining normal rhythm and life-sustaining circulation. This system also ensures that there is fine-tuned regulation of sympathetic-parasympathetic balance in the heart under normal and stressed states in the short (beat to beat), intermediate (minutes to hours), and long term (days to years). This important neurovisceral/autonomic nervous system also plays a major role in the pathophysiology and progression of heart disease, including heart failure and arrhythmias leading to sudden cardiac death. Transdifferentiation of neurons in heart failure, functional denervation, cardiac and extracardiac neural remodeling has also been identified and characterized during the progression of disease. Recent advances in understanding the cellular and molecular processes governing innervation and the functional control of the myocardium in health and disease provide a rational mechanistic basis for the development of neuraxial therapies for preventing sudden cardiac death and other arrhythmias. Advances in cellular, molecular, and bioengineering realms have underscored the emergence of this area as an important avenue of scientific inquiry and therapeutic intervention. © 2015 American Heart Association, Inc.

  3. Apoptosis and caspases regulate death and inflammation in sepsis.

    PubMed

    Hotchkiss, Richard S; Nicholson, Donald W

    2006-11-01

    Although the prevailing concept has been that mortality in sepsis results from an unbridled hyper-inflammatory cytokine-mediated response, the failure of more than 30 clinical trials to treat sepsis by controlling this cytokine response requires a 'rethink' of the molecular mechanism underpinning the development of sepsis. As we discuss here, remarkable new studies indicate that most deaths from sepsis are actually the result of a substantially impaired immune response that is due to extensive death of immune effector cells. Rectification of this apoptotic-inflammatory imbalance using modulators of caspases and other components of the cell-death pathway have shown striking efficacy in stringent animal models of sepsis, indicating an entirely novel path forward for the clinical treatment of human sepsis.

  4. Centrality of host cell death in plant-microbe interactions.

    PubMed

    Dickman, Martin B; Fluhr, Robert

    2013-01-01

    Programmed cell death (PCD) is essential for proper growth, development, and cellular homeostasis in all eukaryotes. The regulation of PCD is of central importance in plant-microbe interactions; notably, PCD and features associated with PCD are observed in many host resistance responses. Conversely, pathogen induction of inappropriate cell death in the host results in a susceptible phenotype and disease. Thus, the party in control of PCD has a distinct advantage in these battles. PCD processes appear to be of ancient origin, as indicated by the fact that many features of cell death strategy are conserved between animals and plants; however, some of the details of death execution differ. Mammalian core PCD genes, such as caspases, are not present in plant genomes. Similarly, pro- and antiapoptotic mammalian regulatory elements are absent in plants, but, remarkably, when expressed in plants, successfully impact plant PCD. Thus, subtle structural similarities independent of sequence homology appear to sustain operational equivalence. The vacuole is emerging as a key organelle in the modulation of plant PCD. Under different signals for cell death, the vacuole either fuses with the plasmalemma membrane or disintegrates. Moreover, the vacuole appears to play a key role in autophagy; evidence suggests a prosurvival function for autophagy, but other studies propose a prodeath phenotype. Here, we describe and discuss what we know and what we do not know about various PCD pathways and how the host integrates signals to activate salicylic acid and reactive oxygen pathways that orchestrate cell death. We suggest that it is not cell death as such but rather the processes leading to cell death that contribute to the outcome of a given plant-pathogen interaction.

  5. Attitudes Toward Death, Anxiety, and Social Desirability

    ERIC Educational Resources Information Center

    Dickstein, Louis S.

    1978-01-01

    Undergraduates (34 males and 34 females) completed four scales of attitudes toward death including the Death Concern Scale, Templer Death Anxiety Scale, Tolor and Reznikoff Death Anxiety Scale, and Fear of Death and Dying Scale. Four scales showed moderate commonality reflecting 35 percent variance for males and females. (Author)

  6. 38 CFR 3.211 - Death.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Death. 3.211 Section 3..., Compensation, and Dependency and Indemnity Compensation Evidence Requirements § 3.211 Death. Death should be... community where death occurred. (2) A copy of a coroner's report of death or a verdict of a coroner's jury...

  7. 32 CFR 700.815 - Deaths.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 5 2014-07-01 2014-07-01 false Deaths. 700.815 Section 700.815 National Defense... § 700.815 Deaths. The commanding officer, in the event of the death of any person within his or her command, shall ensure that the cause of death and the circumstances under which death occurred are...

  8. 32 CFR 700.815 - Deaths.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 5 2010-07-01 2010-07-01 false Deaths. 700.815 Section 700.815 National Defense... § 700.815 Deaths. The commanding officer, in the event of the death of any person within his or her command, shall ensure that the cause of death and the circumstances under which death occurred are...

  9. 32 CFR 700.815 - Deaths.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 5 2011-07-01 2011-07-01 false Deaths. 700.815 Section 700.815 National Defense... § 700.815 Deaths. The commanding officer, in the event of the death of any person within his or her command, shall ensure that the cause of death and the circumstances under which death occurred are...

  10. 38 CFR 3.211 - Death.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Death. 3.211 Section 3..., Compensation, and Dependency and Indemnity Compensation Evidence Requirements § 3.211 Death. Death should be... community where death occurred. (2) A copy of a coroner's report of death or a verdict of a coroner's jury...

  11. 38 CFR 3.211 - Death.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Death. 3.211 Section 3..., Compensation, and Dependency and Indemnity Compensation Evidence Requirements § 3.211 Death. Death should be... community where death occurred. (2) A copy of a coroner's report of death or a verdict of a coroner's jury...

  12. 32 CFR 700.815 - Deaths.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 5 2012-07-01 2012-07-01 false Deaths. 700.815 Section 700.815 National Defense... § 700.815 Deaths. The commanding officer, in the event of the death of any person within his or her command, shall ensure that the cause of death and the circumstances under which death occurred are...

  13. 38 CFR 3.211 - Death.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Death. 3.211 Section 3..., Compensation, and Dependency and Indemnity Compensation Evidence Requirements § 3.211 Death. Death should be... community where death occurred. (2) A copy of a coroner's report of death or a verdict of a coroner's jury...

  14. 38 CFR 3.211 - Death.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Death. 3.211 Section 3..., Compensation, and Dependency and Indemnity Compensation Evidence Requirements § 3.211 Death. Death should be... community where death occurred. (2) A copy of a coroner's report of death or a verdict of a coroner's jury...

  15. 32 CFR 700.815 - Deaths.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 5 2013-07-01 2013-07-01 false Deaths. 700.815 Section 700.815 National Defense... § 700.815 Deaths. The commanding officer, in the event of the death of any person within his or her command, shall ensure that the cause of death and the circumstances under which death occurred are...

  16. Constructing Death: Three Pathographies about Dying.

    ERIC Educational Resources Information Center

    Hawkins, Anne Hunsaker

    1991-01-01

    Discusses three pathographies as models for the "good death." In each, the author organizes the phenomena associated with the illness and death of a spouse from cancer into a coherent pattern. The result is three different paradigms of the experience of dying: "ritual death,""victorious death," and "one's own death." (Author/LLL)

  17. Spinal reflexes in brain death.

    PubMed

    Beckmann, Yesim; Çiftçi, Yeliz; Incesu, Tülay Kurt; Seçil, Yaprak; Akhan, Galip

    2014-12-01

    Spontaneous and reflex movements have been described in brain death and these unusual movements might cause uncertainties in diagnosis. In this study we evaluated the presence of spinal reflexes in patients who fulfilled the criteria for brain death. Thirty-two (22 %) of 144 patients presented unexpected motor movements spontaneously or during examinations. These patients exhibited the following signs: undulating toe, increased deep tendon reflexes, plantar responses, Lazarus sign, flexion-withdrawal reflex, facial myokymia, neck-arm flexion, finger jerks and fasciculations. In comparison, there were no significant differences in age, sex, etiology of brain death and hemodynamic laboratory findings in patients with and without reflex motor movement. Spinal reflexes should be well recognized by physicians and it should be born in mind that brain death can be determined in the presence of spinal reflexes.

  18. Brain death: the Asian perspective.

    PubMed

    Chua, Hoe Chin; Kwek, Tong Kiat; Morihara, Hirofumi; Gao, Daiquan

    2015-04-01

    Asia is the largest and most populous continent in the world with people from many diverse ethnic groups, religions and government systems. The authors surveyed 14 countries accounting for the majority of Asia's population and found that, although the concept of brain death is widely accepted, there is wide variability in the criteria for certification. Although most Asian countries have adopted the "whole-brain" concept of brain death, most countries with past colonial links to the United Kingdom follow the UK "brainstem" concept of brain death. Despite this difference, most countries require only neurologic testing of irreversible coma and absent brainstem reflexes as criteria for certification of brain death. Variability exists in the number of personnel required, qualifications of certifying doctors, need for repeat examination, minimum time interval between examinations, and requirement for and choice of confirmatory tests.

  19. Genetics of sudden cardiac death.

    PubMed

    Bezzina, Connie R; Lahrouchi, Najim; Priori, Silvia G

    2015-06-05

    Sudden cardiac death occurs in a broad spectrum of cardiac pathologies and is an important cause of mortality in the general population. Genetic studies conducted during the past 20 years have markedly illuminated the genetic basis of the inherited cardiac disorders associated with sudden cardiac death. Here, we review the genetic basis of sudden cardiac death with a focus on the current knowledge on the genetics of the primary electric disorders caused primarily by mutations in genes encoding ion channels, and the cardiomyopathies, which have been attributed to mutations in genes encoding a broader category of proteins, including those of the sarcomere, the cytoskeleton, and desmosomes. We discuss the challenges currently faced in unraveling genetic factors that predispose to sudden cardiac death in the setting of sequela of coronary artery disease and present the genome-wide association studies conducted in recent years on electrocardiographic parameters, highlighting their potential in uncovering new biological insights into cardiac electric function.

  20. Actual innocence: is death different?

    PubMed

    Acker, James R

    2009-01-01

    Supreme Court jurisprudence relies heavily on the premise that "death is different" from other criminal sanctions, and that capital cases entail commensurately demanding standards of reliability. Although invoked most frequently with respect to sentencing, both precedent and logic suggest that heightened reliability applies as well to guilt determination in capital trials. Nevertheless, recurrent and highly visible wrongful convictions in capital cases have affected public opinion, contributed to a precipitous decline in new death sentences, and led to calls for reforms designed to guard against the risk of executing innocent persons. This article examines the implications of the "death is different" doctrine for the problem of wrongful convictions in both capital and non-capital cases. It argues that innovations designed to enhance reliability in the special context of death-penalty prosecutions are important in their own right, but relevant new safeguards also should extend to criminal cases generally, where innocent people are similarly at risk and wrongful convictions are far more prevalent.

  1. Sudden death in Marfan syndrome.

    PubMed

    Hugar, Basappa S; Praveen, Shivaramareddy; Kainoor, Sunil K; Shetty, Akshith Raj S

    2014-07-01

    Marfan syndrome is an autosomal dominant genetic disorder of the connective tissue. The most serious complications of this syndrome are defects of the heart valves and aorta. Aneurysms of thoracic aorta are known to develop in Marfan syndrome. Other causes for development of aneurysms of the thoracic aorta are trauma, infections, valve and arch anomalies, genetic disorders, and atherosclerosis. These aneurysms upon rupture may lead to sudden deaths. They are usually detected during routine screening or follow-up of such persons suffering from Marfan syndrome and upon death will be certified by the treating physician. Thus, an autopsy surgeon rarely comes across such deaths. One such case of sudden death due to cardiac tamponade consequent upon rupture of dissecting aortic aneurysm in a 33-year-old male who complained of throbbing pains in the chest, radiating to back, became breathless, cyanotic and died on the way to hospital is being presented here.

  2. Fournier gangrene and unexpected death.

    PubMed

    Bury, Danielle; Byard, Roger W

    2012-11-01

    Fournier gangrene represents a rare but progressive perineal infection that may result in rapid death. A 70-year-old man with poorly controlled diabetes mellitus and alcohol abuse is reported who was found unexpectedly dead. He had last been contacted the night before his death. At autopsy, the most striking finding was deep necrotic ulceration of the scrotum with exposure of underlying deep muscles and testicles, with blood cultures positive for Escherichia coli. Death was, therefore, attributed to necrotic ulceration/gangrene of the perineum (Fournier gangrene) that was due to E. coli sepsis with underlying contributing factors of diabetes mellitus and alcoholism. In addition there was morbid obesity (body mass index 46.9), cirrhosis of the liver, and marked focal coronary artery atherosclerosis with significant cardiomegaly. Fournier gangrene may be an extremely aggressive condition that can result in rapid death, as was demonstrated by the rapid progression in the reported case.

  3. Death Due to Myocardial Bridging.

    PubMed

    Ural, M Numan; Eren, Filiz; Inanir, Nursel Türkmen; Eren, Bülent; Vojtisek, Tomas; Gürses, Murat Serdar

    2015-06-01

    Myocardial bridging is a congenital coronary pathology described as a segment of coronary artery which courses through the myocardial wall beneath the muscle bridge. Although the myocardial bridging prognosis is benign, have been also reported sudden death in medical literature. ¬A 30-year-old married woman was found dead at her home. After local prosecutors' investigation the death was declared as suspicious and forensic autopsy was obliged. The left anterior descending coronary artery was detected embedded deeply in the myocardium 2 cm from its coronary ostial origin. There were no other pathology to explain death. We analyzed sudden death case occurred because of myocardial bridging and the pathophysiological mechanisms in the light of medico-legal literature.

  4. Dowry death: implications of law.

    PubMed

    Latha, K S; Narendra, R

    1998-04-01

    The giving of dowry on marriage is a widespread custom in India, but the attitude of society towards this practice is neither uniform nor consistent. 'Dowry death' is the result of a unique form of violence suffered by Indian women. The existing legal provisions relating to dowry and dowry deaths are summarized, and the role of the Indian Penal Code is discussed. Case reports are presented.

  5. In the shadow of death.

    PubMed

    Meissner, W W

    1995-08-01

    Death dogged Vincent's footsteps throughout his life, and formed a core component of his unconscious fantasy system. It cast a lugubrious shadow over all of his undertakings--he found little joy and less love in life. It found its way onto his canvases, both directly--the grinning death's head--and indirectly. It found expression in his portrayals of sowers and reapers, in his representations of trees--especially the highly symbolic treatments of cypresses--in the menacing crows hovering over storm-darkened fields of wheat, and finally in the images of Christ, suffering and dead, held in the embrace of a loving and grieving mother. If death was a bottomless pit that haunted him with its terrors, it was also a siren song that drew him ever closer to his destiny, ever closer to the edge of the pit. The power of that attraction lies in his identification with the dead Vincent whose place he had taken and whose name he bore. It was through that identification, and through the passageway of suffering and death that he would surcease in the arms of a loving and accepting mother whose warm embrace he had sought throughout his odyssey, but in vain. It was to be gained only in and through death. It was only through death that he would find rest from his pain and would gain the heavenly reward of his suffering in eternal love and bliss.

  6. The interplay between chronic kidney disease, sudden cardiac death, and ventricular arrhythmias

    PubMed Central

    Pun, Patrick H.

    2014-01-01

    Chronic kidney disease patients face an increased risk of cardiovascular disease mortality, and the risk of sudden cardiac death increases as kidney function declines. Risk factors for sudden cardiac death are poorly understood and understudied among chronic kidney disease patients. In the general population, coronary heart disease-associated risk factors are the most important determinants of sudden cardiac death risk, but among chronic kidney disease patients, there is evidence that these factors play a much smaller role. Complex relationships between chronic kidney disease-specific risk factors, structural heart disease, and arrhythmic triggers contribute to the high risk of sudden cardiac death and ventricular arrhythmias, and modulate the effectiveness of available therapies. This review examines recent data on the epidemiology, pathophysiology, and mechanisms of sudden cardiac death among patients with chronic kidney disease and examines current evidence regarding the use of pharmacologic and device-based therapies for management of sudden cardiac death risk. PMID:25443573

  7. Firefighting Module

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Firefly II pump module is NASA's Marshall Space Flight Center's commercial offshoot of a NASA/US Coast Guard program involving development of a lightweight, helicopter-transportable firefighting module for a quick response in combating shipboard or harbor fires. Operable on land or water, the Amphib One is equipped with 3 water cannons. When all 3 are operating, unit pumps more than 3,000 gallons a minute. Newly developed model used by U.S. Coast Guard can pump 5,000 gallons per minute. It was designed for applications such as firefighting onboard ship fires, emergency dockside water pumping, dewatering ships in danger of sinking, flood control, and emergency water supply at remote locations.

  8. Thermoelectric module

    DOEpatents

    Kortier, William E.; Mueller, John J.; Eggers, Philip E.

    1980-07-08

    A thermoelectric module containing lead telluride as the thermoelectric mrial is encapsulated as tightly as possible in a stainless steel canister to provide minimum void volume in the canister. The lead telluride thermoelectric elements are pressure-contacted to a tungsten hot strap and metallurgically bonded at the cold junction to iron shoes with a barrier layer of tin telluride between the iron shoe and the p-type lead telluride element.

  9. Linear modulator

    NASA Technical Reports Server (NTRS)

    1972-01-01

    A study of frequency division multiplexing (FDM) systems was made for the purpose of determining the system performance that can be obtained with available state of the art components. System performance was evaluated on the basis of past experience, system analysis, and component evaluation. The system study was specifically directed to the area of FDM systems using subcarrier channel frequencies from 4 kHz to 200 kHz and channel information bandwidths of dc to 1, 2, 4, 8, and 16 kHz. The evaluation also assumes that the demodulation will be from a tape recorder which produces frequency modulation of + or - 1% on the signal due to the tape recorder wow and flutter. For the modulation system it is assumed that the pilot and carrier channel frequencies are stable to within + or - .005% and that the FM on the channel carriers is negligible. The modulator system was evaluated for the temperature range of -20 degree to +85 degree while the demodulator system was evaluated for operation at room temperature.

  10. Avoidable global cancer deaths and total deaths from smoking.

    PubMed

    Jha, Prabhat

    2009-09-01

    On the basis of current consumption patterns, approximately 450 million adults will be killed by smoking between 2000 and 2050. At least half of these adults will die between 30 and 69 years of age, losing decades of productive life. Cancer and the total deaths due to smoking have fallen sharply in men in high-income countries but will rise globally unless current smokers, most of whom live in low- and middle-income countries, stop smoking before or during middle age. Tripling the taxes on tobacco could rapidly raise cessation rates and deter the initiation of smoking. Higher taxes, regulations on smoking and information for consumers could avoid at least 115 million smoking-associated deaths in the next few decades, including around 25 million cancer deaths.

  11. Exploring Children's Understanding of Death: Through Drawings and the Death Concept Questionnaire

    ERIC Educational Resources Information Center

    Bonoti, Fotini; Leondari, Angeliki; Mastora, Adelais

    2013-01-01

    To investigate whether children's understanding of the concept of death varies as a function of death experience and age, 52 children aged 7, 9, and 11 years (26 had a personal death experience), drew a picture reflecting the meaning of the word death and completed the Death Concept Questionnaire for examination of Human and Animal Death. The…

  12. Exploring Children's Understanding of Death: Through Drawings and the Death Concept Questionnaire

    ERIC Educational Resources Information Center

    Bonoti, Fotini; Leondari, Angeliki; Mastora, Adelais

    2013-01-01

    To investigate whether children's understanding of the concept of death varies as a function of death experience and age, 52 children aged 7, 9, and 11 years (26 had a personal death experience), drew a picture reflecting the meaning of the word death and completed the Death Concept Questionnaire for examination of Human and Animal Death. The…

  13. Novel Quorum-Sensing Peptides Mediating Interspecies Bacterial Cell Death

    PubMed Central

    Kumar, Sathish; Kolodkin-Gal, Ilana; Engelberg-Kulka, Hanna

    2013-01-01

    ABSTRACT Escherichia coli mazEF is a toxin-antitoxin stress-induced module mediating cell death. It requires the quorum-sensing signal (QS) “extracellular death factor” (EDF), the penta-peptide NNWNN (EcEDF), enhancing the endoribonucleolytic activity of E. coli toxin MazF. Here we discovered that E. coli mazEF-mediated cell death could be triggered by QS peptides from the supernatants (SN) of the Gram-positive bacterium Bacillus subtilis and the Gram-negative bacterium Pseudomonas aeruginosa. In the SN of B. subtilis, we found one EDF, the hexapeptide RGQQNE, called BsEDF. In the SN of P. aeruginosa, we found three EDFs: the nonapeptide INEQTVVTK, called PaEDF-1, and two hexadecapeptides, VEVSDDGSGGNTSLSQ, called PaEDF-2, and APKLSDGAAAGYVTKA, called PaEDF-3. When added to a diluted E. coli cultures, each of these peptides acted as an interspecies EDF that triggered mazEF-mediated death. Furthermore, though their sequences are very different, each of these EDFs amplified the endoribonucleolytic activity of E. coli MazF, probably by interacting with different sites on E. coli MazF. Finally, we suggest that EDFs may become the basis for a new class of antibiotics that trigger death from outside the bacterial cells. PMID:23736285

  14. Forensic Analysis of Parachute Deaths.

    PubMed

    Burke, Michael Philip; Chitty, Johannes

    2017-03-01

    Deaths associated with parachuting are very uncommon. However, these deaths do tend to be "high profile" in the traditional and social media. When forensic pathologists examine the deceased after a fatal parachuting incident, the anatomical cause of death is usually not in question. For most forensic pathologists, it is usually the case that we will have very limited knowledge of parachuting equipment or the mechanics of a typical successful parachute jump. As such, the investigation of the death should involve a multidisciplinary approach with an appropriate expert providing the formal forensic examination of the parachuting equipment. We have endeavored to describe, in simple terms, the usual components of a typical parachute rig, a précis of the sequence of events in a routine skydive and BASE jump, and the various types of malfunctions that may occur. Last, we present a case report of a BASE jump fatality to illustrate how an expert examination of the BASE jumper's gear aided the medicolegal investigation of the death with some important aspects in the forensic examination of the jumper's equipment.

  15. Completing Death Certificates from an EMR: Analysis of a Novel Public-Private Partnership

    PubMed Central

    Tripp, Jacob S.; Duncan, Jeffrey D.; Finch, Leisa; Huff, Stanley M.

    2015-01-01

    With the objective of increasing electronic death registration, Intermountain Healthcare and the Utah Office of Vital Records and Statistics have developed a system enabling death certification from within Intermountain’s electronic medical record (EMR), consisting of an EMR module and an HL7 interface. Comparison of post-intervention death certification at Intermountain Healthcare against a baseline study found a slight increase in the percentage of deaths certified electronically (73% pre vs. 77% post). Analysis of deaths certified using the EMR-module found that they were completed significantly sooner than those certified on paper or using the state’s web-based electronic death registration system (EDRS) (Mean time: Paper = 114.72 hours, EDRS = 81.84 hours, EMR = 43.92 hours; p < 0.0001). EMR-certified deaths also contained significantly more causes of deaths than either alternative method (Mean number of causes: Paper = 3.9 causes, EDRS = 4.0 causes, EMR = 5.5 causes; p < 0.0001). PMID:26958261

  16. Photovoltaic module and module arrays

    DOEpatents

    Botkin, Jonathan; Graves, Simon; Lenox, Carl J. S.; Culligan, Matthew; Danning, Matt

    2013-08-27

    A photovoltaic (PV) module including a PV device and a frame, The PV device has a PV laminate defining a perimeter and a major plane. The frame is assembled to and encases the laminate perimeter, and includes leading, trailing, and side frame members, and an arm that forms a support face opposite the laminate. The support face is adapted for placement against a horizontal installation surface, to support and orient the laminate in a non-parallel or tilted arrangement. Upon final assembly, the laminate and the frame combine to define a unitary structure. The frame can orient the laminate at an angle in the range of 3.degree.-7.degree. from horizontal, and can be entirely formed of a polymeric material. Optionally, the arm incorporates integral feature(s) that facilitate interconnection with corresponding features of a second, identically formed PV module.

  17. Photovoltaic module and module arrays

    DOEpatents

    Botkin, Jonathan [El Cerrito, CA; Graves, Simon [Berkeley, CA; Lenox, Carl J. S. [Oakland, CA; Culligan, Matthew [Berkeley, CA; Danning, Matt [Oakland, CA

    2012-07-17

    A photovoltaic (PV) module including a PV device and a frame. The PV device has a PV laminate defining a perimeter and a major plane. The frame is assembled to and encases the laminate perimeter, and includes leading, trailing, and side frame members, and an arm that forms a support face opposite the laminate. The support face is adapted for placement against a horizontal installation surface, to support and orient the laminate in a non-parallel or tilted arrangement. Upon final assembly, the laminate and the frame combine to define a unitary structure. The frame can orient the laminate at an angle in the range of 3.degree.-7.degree. from horizontal, and can be entirely formed of a polymeric material. Optionally, the arm incorporates integral feature(s) that facilitate interconnection with corresponding features of a second, identically formed PV module.

  18. Life Experience with Death: Relation to Death Attitudes and to the Use of Death-Related Memories

    ERIC Educational Resources Information Center

    Bluck, Susan; Dirk, Judith; Mackay, Michael M.; Hux, Ashley

    2008-01-01

    The study examines the relation of death experience to death attitudes and to autobiographical memory use. Participants (N = 52) completed standard death attitude measures and wrote narratives about a death-related autobiographical memory and (for comparison) a memory of a low point. Self-ratings of the memory narratives were used to assess their…

  19. Life Experience with Death: Relation to Death Attitudes and to the Use of Death-Related Memories

    ERIC Educational Resources Information Center

    Bluck, Susan; Dirk, Judith; Mackay, Michael M.; Hux, Ashley

    2008-01-01

    The study examines the relation of death experience to death attitudes and to autobiographical memory use. Participants (N = 52) completed standard death attitude measures and wrote narratives about a death-related autobiographical memory and (for comparison) a memory of a low point. Self-ratings of the memory narratives were used to assess their…

  20. Altruism and physician assisted death.

    PubMed

    Gunderson, M; Mayo, D J

    1993-06-01

    We assume that a statute permitting physician assisted death has been passed. We note that the rationale for the passage of such a statute would be respect for individual autonomy, the avoidance of suffering and the possibility of death with dignity. We deal with two moral issues that will arise once such a law is passed. First, we argue that the rationale for passing an assistance in dying law in the first place provides a justification for assisting patients to die who are motivated by altruistic reasons as well as patients who are motivated by reasons of self-interest. Second, we argue that the reasons for passing a physician assisted death law in the first place justify extending the law to cover some nonterminal patients as well as terminal patients.

  1. Experiencing death: an insider's perspective.

    PubMed

    Paulson, Steve; Fenwick, Peter; Neal, Mary; Nelson, Kevin; Parnia, Sam

    2014-11-01

    For millennia, human beings have wondered what happens after death. What is the first-person experience of dying and being brought back to life? Technological advances in resuscitation science have now added an intriguing new chapter to the literature of out-of-body or near-death experiences by eliciting detailed and vivid accounts of those who have approached the threshold of death. Steve Paulson, executive producer and host of To the Best of Our Knowledge, moderated a discussion that included neurologist Kevin Nelson, neuropsychiatrist Peter Fenwick, emergency medicine expert Sam Parnia, and orthopedic surgeon and drowning survivor Mary Neal; they share some remarkable stories and discuss how they analyze such experiences in light of their own backgrounds and training. The following is an edited transcript of the discussion from December 11, 2013, 7:00-8:30 PM, at the New York Academy of Sciences in New York City. © 2014 New York Academy of Sciences.

  2. Constructions of Death and Levels of Death Fear.

    ERIC Educational Resources Information Center

    Epting, Franz R.; And Others

    1979-01-01

    Fear of death was measured in 60 subjects at conscious, fantasy and nonconscious levels using two different instruments. Most individuals were seen as denying fear at a conscious level, being ambivalent at mid-level, and exhibiting a fear pattern at the nonconscious level. (BP)

  3. [Pathophysiologic programming of cell death].

    PubMed

    Dobryszycka, W

    1998-01-01

    In multicellular organisms homeostasis depends on a balance between cell proliferation and cell death. In this review principles of the physiology of programmed cell death (apoptosis), i.e. biochemical features, involved genes and proteolytic enzymes, are described. Alterations in apoptosis contribute to the pathogenesis of a number of human diseases, including cancer, viral infections, inflammation, hematopoietic and immunological system defects (e.g. AIDS), neurodegenerative disorders. Specific effect on regulation of apoptosis might lead to new possibilities for treatment. Methods of quantitative determinations of apoptosis are discussed.

  4. Geriatric suicide: the preventable death.

    PubMed

    Boxwell, A O

    1988-06-01

    Suicide is the ninth-leading cause of death of the elderly, yet it is the leading cause of preventable death in this population. White males over the age of 65 are at special risk for suicide, with a suicide rate twice the national rate for all ages and six times the rate for women over age 65. The nurse practitioner is in a unique position to intervene in geriatric suicide because suicidal geriatrics typically will not seek help from mental health professionals. Rather, they will seek help from the primary caregiver. Strategies for assessment of suicide risk are presented, in addition to strategies for intervention in a suicide-related crisis.

  5. Psychiatry and the death penalty.

    PubMed Central

    Kastrup, M

    1988-01-01

    Mentally ill people are not to be judged by the same rules as the mentally fit. Prisoners evaluated medically unfit for execution must undergo psychiatric treatment until their mental health is restored. Psychiatrists are placed in an ethical dilemma when asked to judge the mental health of prisoners on death row. A high prevalence of psychiatric and neurological disorders are reported on death row. Health professionals have an important role in implementing codes of ethics prohibiting any involvement in the execution process. Resolutions have already been passed by several associations including the World Medical Association, the American Psychiatric Association and Nordic medical associations. PMID:3236345

  6. Was Sigmund Freud's death hastened?

    PubMed

    Macleod, Alastair D Sandy

    2017-08-01

    The terminal illness of Sigmund Freud has been considered by many authors to be an example of physician-enacted euthanasia. A review and a reconsideration of the published literature by Freud's doctors and biographers cast doubt on this opinion. Over his last 48 h, Freud was administered substantial morphine doses to sedate and relieve his pain. However, from a pharmacological perspective, the timing of his death would not be consistent with that of a fatal dose of opioid. Freud died a natural death. © 2017 Royal Australasian College of Physicians.

  7. Metaphysical Beliefs as Predictors of Death Anxiety.

    ERIC Educational Resources Information Center

    Naidu, R. K.; Sinha, Ambalika

    1992-01-01

    Investigated impact of four metaphysical beliefs (existence of God, attributes of God, afterlife, consequences of suffering) on death anxiety. Householders (n=120), one-half of whom lived in high exposure to death sight areas, responded to pictures depicting death and nondeath scenes to measure death anxiety. Subjects from low exposure areas…

  8. Multidimensional Treatment of Fear of Death.

    ERIC Educational Resources Information Center

    Hoelter, Jon W.

    1979-01-01

    Presents a multidimensional conception of fear of death and provides subscales for measuring suggested dimensions (fear of the dying process, of the dead, of being destroyed, for significant others, of the unknown, of conscious death, for body after death, and of premature death). Evidence for construct validity is provided. (Author/BEF)

  9. Multidimensional Treatment of Fear of Death.

    ERIC Educational Resources Information Center

    Hoelter, Jon W.

    1979-01-01

    Presents a multidimensional conception of fear of death and provides subscales for measuring suggested dimensions (fear of the dying process, of the dead, of being destroyed, for significant others, of the unknown, of conscious death, for body after death, and of premature death). Evidence for construct validity is provided. (Author/BEF)

  10. Death Education for the Health Professional.

    ERIC Educational Resources Information Center

    Benoliel, Jeanne Quint, Ed.

    1982-01-01

    Contains seven articles reviewing various death education programs for health professionals. Discusses death education in undergraduate and advanced nursing practice programs; a graduate course focusing on social, psychological, and cultural conditions influencing death; two death education programs in medical schools; and humanistic health care…

  11. Death Perception in People with Suicidal Tendencies.

    ERIC Educational Resources Information Center

    George, Veronique; Dussaucy, Edith

    The perception of death gradually develops in a child's mind, reaching maturity at about 8 or 9 years of age. A mature death concept usually means a definition which includes the perception of death as a natural process, its finality, its irreversibility, and its universality. A study was undertaken to improve knowledge about the death concept.…

  12. Early Childhood Injury Deaths in Washington State.

    ERIC Educational Resources Information Center

    Starzyk, Patricia M.

    This paper discusses data on the deaths of children aged 1-4 years in Washington State. A two-fold approach was used in the analysis. First, Washington State death certificate data for 1979-85 were used to characterize the deaths and identify hazardous situations. Second, death certificates were linked to birth certificates of children born in…

  13. Death Perception in People with Suicidal Tendencies.

    ERIC Educational Resources Information Center

    George, Veronique; Dussaucy, Edith

    The perception of death gradually develops in a child's mind, reaching maturity at about 8 or 9 years of age. A mature death concept usually means a definition which includes the perception of death as a natural process, its finality, its irreversibility, and its universality. A study was undertaken to improve knowledge about the death concept.…

  14. 38 CFR 3.460 - Death pension.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Death pension. 3.460..., Compensation, and Dependency and Indemnity Compensation Apportionments § 3.460 Death pension. Death pension... individual case in accordance with § 3.451. (b) Section 306 and old-law death pension. Appointment of...

  15. 38 CFR 3.460 - Death pension.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Death pension. 3.460..., Compensation, and Dependency and Indemnity Compensation Apportionments § 3.460 Death pension. Death pension... individual case in accordance with § 3.451. (b) Section 306 and old-law death pension. Appointment of...

  16. 38 CFR 21.7280 - Death benefit.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2013-07-01 2013-07-01 false Death benefit. 21.7280... Bill-Active Duty) Approval of Courses § 21.7280 Death benefit. (a) Overview. VA will pay a death benefit under 38 U.S.C. ch. 30 when an individual's death meets the criteria of this section; the...

  17. 38 CFR 3.460 - Death pension.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Death pension. 3.460..., Compensation, and Dependency and Indemnity Compensation Apportionments § 3.460 Death pension. Death pension... individual case in accordance with § 3.451. (b) Section 306 and old-law death pension. Appointment of...

  18. 38 CFR 21.7280 - Death benefit.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2011-07-01 2011-07-01 false Death benefit. 21.7280... Bill-Active Duty) Approval of Courses § 21.7280 Death benefit. (a) Overview. VA will pay a death benefit under 38 U.S.C. ch. 30 when an individual's death meets the criteria of this section; the...

  19. 38 CFR 21.7280 - Death benefit.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2012-07-01 2012-07-01 false Death benefit. 21.7280... Bill-Active Duty) Approval of Courses § 21.7280 Death benefit. (a) Overview. VA will pay a death benefit under 38 U.S.C. ch. 30 when an individual's death meets the criteria of this section; the...

  20. 38 CFR 3.460 - Death pension.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Death pension. 3.460..., Compensation, and Dependency and Indemnity Compensation Apportionments § 3.460 Death pension. Death pension... individual case in accordance with § 3.451. (b) Section 306 and old-law death pension. Appointment of...

  1. 38 CFR 21.7280 - Death benefit.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2014-07-01 2014-07-01 false Death benefit. 21.7280... Bill-Active Duty) Approval of Courses § 21.7280 Death benefit. (a) Overview. VA will pay a death benefit under 38 U.S.C. ch. 30 when an individual's death meets the criteria of this section; the...

  2. 38 CFR 3.460 - Death pension.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Death pension. 3.460..., Compensation, and Dependency and Indemnity Compensation Apportionments § 3.460 Death pension. Death pension... individual case in accordance with § 3.451. (b) Section 306 and old-law death pension. Appointment of...

  3. Can Suicide Be a Good Death?

    ERIC Educational Resources Information Center

    Lester, David

    2006-01-01

    The issue of whether suicide can be a good death was separated into two different questions: (1) can suicide be an appropriate death, and (2) can suicide be a rational death? Several definitions of an "appropriate" death were proposed, and suicide was seen as potentially appropriate. Similarly, several criteria for rationality were proposed and…

  4. Can Suicide Be a Good Death?

    ERIC Educational Resources Information Center

    Lester, David

    2006-01-01

    The issue of whether suicide can be a good death was separated into two different questions: (1) can suicide be an appropriate death, and (2) can suicide be a rational death? Several definitions of an "appropriate" death were proposed, and suicide was seen as potentially appropriate. Similarly, several criteria for rationality were proposed and…

  5. Deaths due to Unknown Foodborne Agents

    PubMed Central

    2004-01-01

    This study reviews the available evidence on unknown pathogenic agents transmitted in food and examines the methods that have been used to estimate that such agents cause 3,400 deaths per year in the United States. The estimate of deaths was derived from hospital discharge and death certificate data on deaths attributed to gastroenteritis of unknown cause. Fatal illnesses due to unknown foodborne agents do not always involve gastroenteritis, and gastroenteritis may not be accurately diagnosed or reported on hospital charts or death certificates. The death estimate consequently omitted deaths from unknown foodborne agents that do not cause gastroenteritis and likely overstated the number of deaths from agents that cause gastroenteritis. Although the number of deaths from unknown foodborne agents is uncertain, the possible economic cost of these deaths is so large that increased efforts to identify the causal agents are warranted. PMID:15498153

  6. Seasonality of deaths in Matlab, Bangladesh.

    PubMed

    Becker, S

    1981-09-01

    Deaths registered between 1972 and 1974 in a population of 260 000 in a rural area of Bangladesh were analysed for seasonal patterns. Age and cause of death groups were considered. The findings include: (1) The number of neonatal deaths has a peak in October but after adjustment for the seasonal pattern of births, the actual risk of neonatal morality is found to peak 2 months earlier. (2) Postneonatal deaths peak in April with above average proportions of deaths in the peak month attributed to dysentery. (3) Deaths of persons above age 45 peak in the cool season. (4) Dysentery and chronic diarrhoea deaths are highest in December. This coincides with the maximum incidence of shigella dysentery. (5) Accidental deaths are maximum in July due to increased drownings during the monsoon. The age and cause of death groups which contribute the largest proportions of total deaths are also the groups which show seasonal patterns.

  7. Normal development, oncogenesis and programmed cell death.

    PubMed

    Liebermann, D A

    1998-09-10

    Meeting's Report -- June 2, 1998, Sugarload Estate Conference Center, Philadelphia, Pennsylvania, USA. A symposium on Normal Development, Oncogenesis and Programmed Cell Death, was held at the Sugarload Estate Conference Center, Philadelphia, Pennsylvania, USA sponsored by the Fels Cancer Institute, Temple University School of Medicine, with the support of the Alliance Pharmaceutical Corporation. The symposium was organized by Drs Dan A Liebermann and Barbara Hoffman at the Fels. Invited speakers included: Dr Andrei V Gudkov (University of Illinois) who started the symposium talking about 'New cellular factors modulating the tumor suppressor function of p53'; Dr Yuri Lazebnik (Cold Spring Harbor Laboratories) spoke about 'Caspases considered as enemies within'; Dr E Premkumar Reddy (Fels Institute, Temple University) talked about recent exciting findings in his laboratory regarding 'JAK-STATs dedicated signaling pathways'; Dr Michael Greenberg (Harvard University) spoke about 'Signal transduction pathways that regulate differentiation and survival in the developing nervous system'; Dr Richard Kolesnick's (Memorial Sloan-Kettering Cancer Center) talk has been focused at 'Stress signals for apoptosis, including Ceramide and c-Jun Kinase/Stress-activated Protein Kinase'; Dr Barbara Hoffman (Fels Institute, Temple University) described research, conducted in collaboration with Dr Dan A Liebermann, aimed at deciphering the roles of 'myc, myb, and E2F as negative regulators of terminal differentiation', using hematopoietic cells as model system. Dr Daniel G Tenen (Harvard Medical School), described studies aimed at understanding the 'Regulation of hematopoietic cell development by lineage specific transcription regulators'. Dr George C Prendergast (The Wistar Institute) talked about the 'Myc-Bin1 signaling pathway in cell death and differentiation. Dr Ruth J Muschel (University of Pennsylvania) spoke about work, conducted in collaboration with Dr WG McKenna, aimed at

  8. p73 regulates DRAM-independent autophagy that does not contribute to programmed cell death.

    PubMed

    Crighton, D; O'Prey, J; Bell, H S; Ryan, K M

    2007-06-01

    Evading programmed cell death is a common event in tumour development. The p53 family member, p73, is a potent inducer of death and a determinant of chemotherapeutic response, but different to p53, is rarely mutated in cancer. Understanding cell death pathways downstream of p53 and p73 is therefore pivotal to understand both the development and treatment of malignant disease. Recently, p53 has been shown to modulate autophagy--a membrane trafficking process, which degrades long-lived proteins and organelles. This requires a p53 target gene, DRAM, and both DRAM and autophagy are critical for p53-mediated death. We report here that TA-p73 also regulates DRAM and autophagy, with different TA-p73 isoforms regulating DRAM and autophagy to varying extents. RNAi knockdown of DRAM, however, revealed that p73's modulation of autophagy is DRAM-independent. Also, p73's ability to induce death, again different to p53, is neither dependent on DRAM nor autophagy. In contrast to TA-p73, deltaN-p73 is a negative regulator of p53-induced and p73-induced autophagy, but does not affect autophagy induced by amino-acid starvation. These studies, therefore, represent not only the first report that p73 modulates autophagy but also highlight important differences in the mechanism by which starvation, p53 and p73 regulate autophagy and how this contributes to programmed cell death.

  9. Reading Guidance: Death and Grief.

    ERIC Educational Resources Information Center

    Smith, Alice Gullen

    1989-01-01

    Gives guidelines for the librarian using reading guidance (similar to bibliotherapy). Provides a nine-item annotated bibliography of novels for children and adolescents on the subject of death and grief. Appends an embryo list of categories suitable for content analysis of any file librarians might wish to keep on books suitable for use in this…

  10. Reading Guidance: Death and Grief.

    ERIC Educational Resources Information Center

    Smith, Alice Gullen

    1989-01-01

    Gives guidelines for the librarian using reading guidance (similar to bibliotherapy). Provides a nine-item annotated bibliography of novels for children and adolescents on the subject of death and grief. Appends an embryo list of categories suitable for content analysis of any file librarians might wish to keep on books suitable for use in this…

  11. Confidential inquiry into malaria deaths.

    PubMed Central

    Dürrheim, D. N.; Frieremans, S.; Kruger, P.; Mabuza, A.; de Bruyn, J. C.

    1999-01-01

    The results of a confidential inquiry into mortality attributed to malaria in South Africa's Mpumalanga Province are being used to guide the design of strategies for improving the management of cases and reducing the probability of deaths from the disease. PMID:10212518

  12. Death Penalty Issues Following Atkins

    ERIC Educational Resources Information Center

    Patton, James R.; Keyes, Denis W.

    2006-01-01

    In light of the U.S. Supreme Court's 2002 landmark decision in "Atkins v. Virginia," a diagnosis of mild mental retardation has taken on a life and death significance for people who are the most deeply involved in criminal justice. As such, each aspect of the mental retardation definition (American Association on Mental Retardation, 2002) is a…

  13. Death Penalty Issues Following Atkins

    ERIC Educational Resources Information Center

    Patton, James R.; Keyes, Denis W.

    2006-01-01

    In light of the U.S. Supreme Court's 2002 landmark decision in "Atkins v. Virginia," a diagnosis of mild mental retardation has taken on a life and death significance for people who are the most deeply involved in criminal justice. As such, each aspect of the mental retardation definition (American Association on Mental Retardation, 2002) is a…

  14. [The Sudden Infant Death Syndrome.

    ERIC Educational Resources Information Center

    Florida's Health, 1976

    1976-01-01

    This collection of articles on the Sudden Infant Death Syndrome (SIDS), drawn from a southeastern regional symposium on the subject, summarizes much of what is known about the occurrence of SIDS, including current information about its causes. The background of state action in Florida is reviewed, with emphasis on the need for increased public and…

  15. Death following crude oil aspiration.

    PubMed

    Rodriguez, M A; Martinez, M C; Martinez-Ruiz, D; Paz Giménez, M; Menéndez, M; Repetto, M

    1991-07-01

    This is a report on three deaths following oil aspiration by workers in petrol tankers. Lung aspiration was demonstrated by the presence of a yellowish-brown material in the alveolar spaces, which was difficult to identify by optic microscopy. Volatile hydrocarbons from petroleum were identified in lung samples by gas chromatography/mass spectrometry.

  16. Attitudes on Death and Dying.

    ERIC Educational Resources Information Center

    Andrus, Charles E.

    This paper explored attitudes toward death and dying revealed through interviews with members of the clergy, the medical profession, funeral directors, nursing home residents, and selected others. The sampling was small and results are not intended to be representative of the groups to which these people belong. Rather, the study may be used as a…

  17. Sudden oak death online symposium

    Treesearch

    S.D. Cohen; J., eds Juzwik

    2003-01-01

    This symposium is being made available to all who have an interest in the recent appearance of Sudden Oak Death, a plant disease with the potential to severely impact nursery growers, shippers, the lumber and wood products industry, landscapers, government programs and others. Scientific presentations dealing with the current status of the disease and ongoing research...

  18. Dyadic death: murder-suicide.

    PubMed

    Berman, A L

    1979-01-01

    Twenty homicide-suicides, drawn from death records of three major eastern United States cities, were analyzed in comparison to prior studies and samples of homicide offenders and suicide victims. Results indicated a lower incidence for this event than reported previously and several distinguishing characteristics of the murderer who subsequently commits suicide. Two primary types, from the perspective of ego fusion, are discussed.

  19. Reconstructing Death in Postmodern Society.

    ERIC Educational Resources Information Center

    Kastenbaum, Robert

    1993-01-01

    Examines interaction between emerging thanatological movement and its sociohistorical context. Notes that thanatology will take on new shape as individuals and society attempt to cope with postmodernistic forces and deconstructive mentality. Considers prospect for authentic solidarity against distress in reconstructed death system. (Author/NB)

  20. Reconstructing Death in Postmodern Society.

    ERIC Educational Resources Information Center

    Kastenbaum, Robert

    1993-01-01

    Examines interaction between emerging thanatological movement and its sociohistorical context. Notes that thanatology will take on new shape as individuals and society attempt to cope with postmodernistic forces and deconstructive mentality. Considers prospect for authentic solidarity against distress in reconstructed death system. (Author/NB)