Psychic trauma as cause of death.

Science.gov (United States)

Terranova, C; Snenghi, R; Thiene, G; Ferrara, S D

2011-01-01

of study Psychic trauma is described as the action of 'an emotionally overwhelming factor' capable of causing neurovegetative alterations leading to transitory or persisting bodily changes. The medico-legal concept of psychic trauma and its definition as a cause in penal cases is debated. The authors present three cases of death after psychic trauma, and discuss the definition of cause within the penal ambit of identified 'emotionally overwhelming factors'. The methodological approach to ascertainment and criterion-based assessment in each case involved the following phases: (1) examination of circumstantial evidence, clinical records and documentation; (2) autopsy; (3) ascertainment of cause of death; and (4) ascertainment of psychic trauma, and its coexisting relationship with the cause of death. The results and assessment of each of the three cases are discussed from the viewpoint of the causal connotation of psychic trauma. In the cases presented, psychic trauma caused death, as deduced from assessment of the type of externally caused emotional insult, the subjects' personal characteristics and the circumstances of the event causing death. In cases of death due to psychic trauma, careful methodological ascertainment is essential, with the double aim of defining 'emotionally overwhelming factors' as a significant cause of death from the penal point of view, and of identifying the responsibility of third parties involved in the death event and associated dynamics of homicide.

[Ill-defined causes of death and unattended deaths, Brazil, 2003].

Science.gov (United States)

Santo, Augusto Hasiak

2008-01-01

We studied the distribution of deaths from ill-defined causes that occurred in Brazil during 2003, from which was identified the proportion of unattended deaths. Data were obtained from the Mortality Information System, coordinated by the Ministry of Health. Causes of death included in "Chapter XVIII - Symptoms, signs and abnormal clinical and laboratory findings, not classified elsewhere" of the International Statistical Classification of Diseases and Related Health Problems, tenth revision, were considered ill-defined, among which the category R98 identified "unattended deaths". In Brazil during 2003 the underlying causes of 13.3% of deaths were included in the Chapter of ill-defined causes, and the highest proportions of these deaths occurred in the Northeast and North Regions. Considering the total deaths from ill-defined causes, 53 % correspond to unattended deaths. This proportion increased to over 70% in the states of Maranhão, Piauí, Rio Grande do Norte, Pernambuco, Bahia, Paraíba and Alagoas. Due to the decentralized structure of data collection in the country, we believe that the municipalities bear the major responsibility, followed by the states, for upgrading the quality of mortality statistics.

The cell death factor, cell wall elicitor of rice blast fungus (Magnaporthe grisea) causes metabolic alterations including GABA shunt in rice cultured cells

OpenAIRE

Takahashi, Hideyuki; Matsumura, Hideo; Kawai-Yamada, Maki; Uchimiya, Hirofumi

2008-01-01

An elicitor derived from the cell wall of rice blast fungus (Magnaporthe grisea) causes cell death in suspension cultured cells of rice (Oryza sativa L.). To elucidate the role of M. grisea elicitor on metabolic pathway of rice cells, we performed metabolite profiling using capillary electrophoresis-mass spectrometry (CE/MS). Treatment with M. grisea elicitor increased the amounts of antioxidants and free amino acids and decreased the amount of metabolites in the tricarboxylic acid (TCA) cycl...

Cardiovascular causes of maternal sudden death. Sudden arrhythmic death syndrome is leading cause in UK.

Science.gov (United States)

Krexi, Dimitra; Sheppard, Mary N

2017-05-01

This study aims to determine the causes of sudden cardiac death during pregnancy and in the postpartum period and patients' characteristics. There are few studies in the literature. Eighty cases of sudden unexpected death due to cardiac causes in relation to pregnancy and postpartum period in a database of 4678 patients were found and examined macroscopically and microscopically. The mean age was 30±7 years with a range from 16 to 43 years. About 30% were 35 years old or older; 50% of deaths occurred during pregnancy and 50% during the postpartum period. About 59.18% were obese or overweight where body mass index data were available. The leading causes of death were sudden arrhythmic death syndrome (SADS) (53.75%) and cardiomyopathies (13.80%). Other causes include dissection of aorta or its branches (8.75%), congenital heart disease (2.50%) and valvular disease (3.75%). This study highlights sudden cardiac death in pregnancy or in the postpartum period, which is mainly due to SADS with underlying channelopathies and cardiomyopathy. We wish to raise awareness of these frequently under-recognised entities in maternal deaths and the need of cardiological screening of the family as a result of the diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

FastStats: Leading Causes of Death

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... Submit What's this? Submit Button NCHS Home Leading Causes of Death Recommend on Facebook Tweet Share Compartir Data are for the U.S. Number of deaths for leading causes of death Heart disease: 633,842 • Cancer: 595,930 • Chronic ...

Variation in causes of death in patients with non-small cell lung cancer according to stage and time since diagnosis

NARCIS (Netherlands)

Janssen-Heijnen, M. L. G.; van Erning, F. N.; De Ruysscher, D. K.; Coebergh, J. W. W.; Groen, H. J. M.

Background: Many patients with non-small cell lung cancer (NSCLC) die within the first few years of diagnosis, and considerable excess mortality remains even after 5 years. We investigated the death rate and the distribution of causes of death for NSCLC patients by age and stage at diagnosis during

Local perceptions of causes of death in rural South Africa: a comparison of perceived and verbal autopsy causes of death.

Science.gov (United States)

Hussain-Alkhateeb, Laith; Fottrell, Edward; Petzold, Max; Kahn, Kathleen; Byass, Peter

2015-01-01

Understanding how lay people perceive the causes of mortality and their associated risk factors is important for public health. In resource-limited settings, where verbal autopsy (VA) is used as the most expedient method of determining cause of death, it is important to understand how pre-existing concepts of cause of death among VA-informants may influence their VA-responses and the consequential impact on cause of death assessment. This study describes the agreement between VA-derived causes of death and informant-perceived causes and associated influential factors, which also reflects lay health literacy in this setting. Using 20 years of VA data (n=11,228) from the Agincourt Health and Demographic Surveillance System (HDSS) site in rural South Africa, we explored the agreement between the causes of death perceived by the VA-informants and those assigned by the automated Inter-VA tool. Kappa statistics and concordance correlation coefficients were applied to measure agreement at individual and population levels, respectively. Multivariable regression models were used to explore factors associated with recognised lay perceptions of causes of mortality. Agreement between informant-perceived and VA-derived causes of death at the individual level was limited, but varied substantially by cause of death. However, agreement at the population level, comparing cause-specific mortality fractions was higher, with the notable exception of bewitchment as a cause. More recent deaths, those in adults aged 15-49 years, deaths outside the home, and those associated with external causes showed higher concordance with InterVA. Overall, informant perception of causes of death was limited, but depended on informant characteristics and causes of death, and to some extent involved non-biomedical constructs. Understanding discordance between perceived and recognised causes of death is important for public health planning; low community understanding of causes of death may be

Local perceptions of causes of death in rural South Africa: a comparison of perceived and verbal autopsy causes of death

Science.gov (United States)

Hussain-Alkhateeb, Laith; Fottrell, Edward; Petzold, Max; Kahn, Kathleen; Byass, Peter

2015-01-01

Background Understanding how lay people perceive the causes of mortality and their associated risk factors is important for public health. In resource-limited settings, where verbal autopsy (VA) is used as the most expedient method of determining cause of death, it is important to understand how pre-existing concepts of cause of death among VA-informants may influence their VA-responses and the consequential impact on cause of death assessment. This study describes the agreement between VA-derived causes of death and informant-perceived causes and associated influential factors, which also reflects lay health literacy in this setting. Method Using 20 years of VA data (n=11,228) from the Agincourt Health and Demographic Surveillance System (HDSS) site in rural South Africa, we explored the agreement between the causes of death perceived by the VA-informants and those assigned by the automated Inter-VA tool. Kappa statistics and concordance correlation coefficients were applied to measure agreement at individual and population levels, respectively. Multivariable regression models were used to explore factors associated with recognised lay perceptions of causes of mortality. Results Agreement between informant-perceived and VA-derived causes of death at the individual level was limited, but varied substantially by cause of death. However, agreement at the population level, comparing cause-specific mortality fractions was higher, with the notable exception of bewitchment as a cause. More recent deaths, those in adults aged 15–49 years, deaths outside the home, and those associated with external causes showed higher concordance with InterVA. Conclusion Overall, informant perception of causes of death was limited, but depended on informant characteristics and causes of death, and to some extent involved non-biomedical constructs. Understanding discordance between perceived and recognised causes of death is important for public health planning; low community

Radiation-induced cell death by chromatin loss

International Nuclear Information System (INIS)

Campbell, I.R.; Warenius, H.M.

1989-01-01

A model is proposed which relates reproductive death of cells caused by radiation to loss of chromatin at cell division. This loss of chromatin can occur through chromosomal deletions or through the formation of asymmetrical chromosomal exchanges. It is proposed that smaller doses of radiation produce fewer chromatin breaks, which are more likely to be accurately repaired, compared with larger doses. Consequently, smaller doses of radiation are less efficient in causing cell death, leading to a shoulder on the cell survival curve. Experimental evidence supports this model, and the fit between the derived formula and experimental cell survival curves is good. The derived formula approximates to the linear-quadratic equation at low doses of radiation. (author)

Sudden unexpected death caused by stroke

DEFF Research Database (Denmark)

Ågesen, Frederik Nybye; Risgaard, Bjarke; Zachariasardóttir, Sára

2017-01-01

Background Stroke is the fifth leading cause of death in young individuals globally. Data on the burden of sudden death by stroke are sparse in the young. Aims The aim of this study was to report mortality rates, cause of death, stroke subtype, and symptoms in children and young adults who suffered....... There was a male predominance (56%) and the median age was 33 years. The incidence of sudden death by stroke in individuals aged 1-49 years was 0.19 deaths per 100,000 person-years. Stroke was hemorrhagic in 94% of cases, whereof subarachnoid hemorrhage was the cause of death in 63% of cases. Seventeen (33%) cases...... contacted the healthcare system because of neurological symptoms, whereof one was suspected of having a stroke (6%). Conclusions Sudden death by stroke in children and young adults occurs primarily due to hemorrhagic stroke. We report a high frequency of neurological symptoms prior to sudden death by stroke...

38 CFR 3.312 - Cause of death.

Science.gov (United States)

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Cause of death. 3.312... Cause of death. (a) General. The death of a veteran will be considered as having been due to a service... contributory cause of death. The issue involved will be determined by exercise of sound judgment, without...

The slow cell death response when screening chemotherapeutic agents.

Science.gov (United States)

Blois, Joseph; Smith, Adam; Josephson, Lee

2011-09-01

To examine the correlation between cell death and a common surrogate of death used in screening assays, we compared cell death responses to those obtained with the sulforhodamine B (SRB) cell protein-based "cytotoxicity" assay. With the SRB assay, the Hill equation was used to obtain an IC50 and final cell mass, or cell mass present at infinite agent concentrations, with eight adherent cell lines and four agents (32 agent/cell combinations). Cells were treated with high agent concentrations (well above the SRB IC50) and the death response determined as the time-dependent decrease in cells failing to bind both annexin V and vital fluorochromes by flow cytometry. Death kinetics were categorized as fast (5/32) (similar to the reference nonadherent Jurkat line), slow (17/32), or none (10/32), despite positive responses in the SRB assay in all cases. With slow cell death, a single exposure to a chemotherapeutic agent caused a slow, progressive increase in dead (necrotic) and dying (apoptotic) cells for at least 72 h. Cell death (defined by annexin and/or fluorochrome binding) did not correlate with the standard SRB "cytotoxicity" assay. With the slow cell death response, a single exposure to an agent caused a slow conversion from vital to apoptotic and necrotic cells over at least 72 h (the longest time point examined). Here, increasing the time of exposure to agent concentrations modestly above the SRB IC50 provides a method of maximizing cell kill. If tumors respond similarly, sustained low doses of chemotherapeutic agents, rather than a log-kill, maximum tolerated dose strategy may be an optimal strategy of maximizing tumor cell death.

HAMLET (human alpha-lactalbumin made lethal to tumor cells) triggers autophagic tumor cell death.

Science.gov (United States)

Aits, Sonja; Gustafsson, Lotta; Hallgren, Oskar; Brest, Patrick; Gustafsson, Mattias; Trulsson, Maria; Mossberg, Ann-Kristin; Simon, Hans-Uwe; Mograbi, Baharia; Svanborg, Catharina

2009-03-01

HAMLET, a complex of partially unfolded alpha-lactalbumin and oleic acid, kills a wide range of tumor cells. Here we propose that HAMLET causes macroautophagy in tumor cells and that this contributes to their death. Cell death was accompanied by mitochondrial damage and a reduction in the level of active mTOR and HAMLET triggered extensive cytoplasmic vacuolization and the formation of double-membrane-enclosed vesicles typical of macroautophagy. In addition, HAMLET caused a change from uniform (LC3-I) to granular (LC3-II) staining in LC3-GFP-transfected cells reflecting LC3 translocation during macroautophagy, and this was blocked by the macroautophagy inhibitor 3-methyladenine. HAMLET also caused accumulation of LC3-II detected by Western blot when lysosomal degradation was inhibited suggesting that HAMLET caused an increase in autophagic flux. To determine if macroautophagy contributed to cell death, we used RNA interference against Beclin-1 and Atg5. Suppression of Beclin-1 and Atg5 improved the survival of HAMLET-treated tumor cells and inhibited the increase in granular LC3-GFP staining. The results show that HAMLET triggers macroautophagy in tumor cells and suggest that macroautophagy contributes to HAMLET-induced tumor cell death.

Hyaluronan activates Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed.

Science.gov (United States)

Hsu, Li-Jin; Hong, Qunying; Chen, Shur-Tzu; Kuo, Hsiang-Lin; Schultz, Lori; Heath, John; Lin, Sing-Ru; Lee, Ming-Hui; Li, Dong-Zhang; Li, Zih-Ling; Cheng, Hui-Ching; Armand, Gerard; Chang, Nan-Shan

2017-03-21

Malignant cancer cells frequently secrete significant amounts of transforming growth factor beta (TGF-β), hyaluronan (HA) and hyaluronidases to facilitate metastasizing to target organs. In a non-canonical signaling, TGF-β binds membrane hyaluronidase Hyal-2 for recruiting tumor suppressors WWOX and Smad4, and the resulting Hyal-2/WWOX/Smad4 complex is accumulated in the nucleus to enhance SMAD-promoter dependent transcriptional activity. Yeast two-hybrid analysis showed that WWOX acts as a bridge to bind both Hyal-2 and Smad4. When WWOX-expressing cells were stimulated with high molecular weight HA, an increased formation of endogenous Hyal-2/WWOX/Smad4 complex occurred rapidly, followed by relocating to the nuclei in 20-40 min. In WWOX-deficient cells, HA failed to induce Smad2/3/4 relocation to the nucleus. To prove the signaling event, we designed a real time tri-molecular FRET analysis and revealed that HA induces the signaling pathway from ectopic Smad4 to WWOX and finally to p53, as well as from Smad4 to Hyal-2 and then to WWOX. An increased binding of the Smad4/Hyal-2/WWOX complex occurs with time in the nucleus that leads to bubbling cell death. In contrast, HA increases the binding of Smad4/WWOX/p53, which causes membrane blebbing but without cell death. In traumatic brain injury-induced neuronal death, the Hyal-2/WWOX complex was accumulated in the apoptotic nuclei of neurons in the rat brains in 24 hr post injury, as determined by immunoelectron microscopy. Together, HA activates the Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed.

Ten Leading Causes of Death and Injury

Science.gov (United States)

... Overdose Traumatic Brain Injury Violence Prevention Ten Leading Causes of Death and Injury Recommend on Facebook Tweet Share Compartir ... in Hospital Emergency Departments, United States – 2014 Leading Causes of Death Charts Causes of Death by Age Group 2016 [ ...

Water-Soluble Coenzyme Q10 Inhibits Nuclear Translocation of Apoptosis Inducing Factor and Cell Death Caused by Mitochondrial Complex I Inhibition

Directory of Open Access Journals (Sweden)

Haining Li

2014-07-01

Full Text Available The objectives of the study were to explore the mechanism of rotenone-induced cell damage and to examine the protective effects of water-soluble Coenzyme Q10 (CoQ10 on the toxic effects of rotenone. Murine hippocampal HT22 cells were cultured with mitochondrial complex I inhibitor rotenone. Water-soluble CoQ10 was added to the culture media 3 h prior to the rotenone incubation. Cell viability was determined by alamar blue, reactive oxygen species (ROS production by dihydroethidine (DHE and mitochondrial membrane potential by tetramethyl rhodamine methyl ester (TMRM. Cytochrome c, caspase-9 and apoptosis-inducing factor (AIF were measured using Western blotting after 24 h rotenone incubation. Rotenone caused more than 50% of cell death, increased ROS production, AIF nuclear translocation and reduction in mitochondrial membrane potential, but failed to cause mitochondrial cytochrome c release and caspase-9 activation. Pretreatment with water-soluble CoQ10 enhanced cell viability, decreased ROS production, maintained mitochondrial membrane potential and prevented AIF nuclear translocation. The results suggest that rotenone activates a mitochondria-initiated, caspase-independent cell death pathway. Water-soluble CoQ10 reduces ROS accumulation, prevents the fall of mitochondrial membrane potential, and inhibits AIF translocation and subsequent cell death.

Variation in causes of death in patients with non-small cell lung cancer according to stage and time since diagnosis.

Science.gov (United States)

Janssen-Heijnen, M L G; van Erning, F N; De Ruysscher, D K; Coebergh, J W W; Groen, H J M

2015-05-01

Many patients with non-small cell lung cancer (NSCLC) die within the first few years of diagnosis, and considerable excess mortality remains even after 5 years. We investigated the death rate and the distribution of causes of death for NSCLC patients by age and stage at diagnosis during long-term follow-up. All 72 021 patients aged 45-89 years diagnosed with stage I-III NSCLC between 1989 and 2008 in the Netherlands and who died up till 2011 were derived from the Netherlands Cancer Registry and linked with the database of Statistics Netherlands for underlying causes of death. Mortality ratios and proportional distribution of causes of death were calculated during 5 time periods after diagnosis of NSCLC (up to 15 years). Median follow-up was 9.6 years (range: 0-23 years). Lung cancer was the predominant cause of death in the first 6 years after diagnosis (being 80%-85% and ∼90% up to 3 years for localized and locally advanced disease, respectively, and ∼60%-75% and ∼75%-85% during years 4-6 for both stage groups, respectively). Thereafter, lung cancer as cause of death proportionally decreased with time since diagnosis, but remained over 30%. Hence, cardiovascular diseases and chronic obstructive pulmonary diseases (COPD) became more important causes of death, especially for patients aged >60 years at diagnosis (up to 34% for cardiovascular diseases and up to 19% for COPD). With time, the relative contribution of cardiovascular and COPD causes of death increased, although the absolute contribution of lung cancer remained high in non-metastatic NSCLC. Therefore, managing morbidity of these diseases remains relevant. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Methods for assessing autophagy and autophagic cell death.

Science.gov (United States)

Tasdemir, Ezgi; Galluzzi, Lorenzo; Maiuri, M Chiara; Criollo, Alfredo; Vitale, Ilio; Hangen, Emilie; Modjtahedi, Nazanine; Kroemer, Guido

2008-01-01

Autophagic (or type 2) cell death is characterized by the massive accumulation of autophagic vacuoles (autophagosomes) in the cytoplasm of cells that lack signs of apoptosis (type 1 cell death). Here we detail and critically assess a series of methods to promote and inhibit autophagy via pharmacological and genetic manipulations. We also review the techniques currently available to detect autophagy, including transmission electron microscopy, half-life assessments of long-lived proteins, detection of LC3 maturation/aggregation, fluorescence microscopy, and colocalization of mitochondrion- or endoplasmic reticulum-specific markers with lysosomal proteins. Massive autophagic vacuolization may cause cellular stress and represent a frustrated attempt of adaptation. In this case, cell death occurs with (or in spite of) autophagy. When cell death occurs through autophagy, on the contrary, the inhibition of the autophagic process should prevent cellular demise. Accordingly, we describe a strategy for discriminating cell death with autophagy from cell death through autophagy.

Prosperity as a cause of death.

Science.gov (United States)

Eyer, J

1977-01-01

The general death rate rises during business booms and falls during depressions. The causes of death involved in this variation range from infectious diseases through accidents to heart disease, cancer, and cirrhosis of the liver, and include the great majority of all causes of death. Less than 2 percent of the death rate-that for suicide and homicide-varies directly with unemployment. In the older historical data, deterioration of housing and rise of alcohol consumption on the boom may account for part of this variation. In twentieth-century cycles, the role of social stress is probably predominant. Overwork and fragmentation of community through migration are two important sources of stress which rise with the boom, and they are demonstrably related to the causes of death which show this variation.

Triglyceride-induced macrophage cell death is triggered by caspase-1.

Science.gov (United States)

Son, Sin Jee; Rhee, Ki-Jong; Lim, Jaewon; Kim, Tae Ue; Kim, Tack-Joong; Kim, Yoon Suk

2013-01-01

Triglyceride (TG) induces macrophage cell death which contributes to the development of atherosclerosis. We confirmed that exogenous TG accumulates in human THP-1 macrophages and causes cell death. TG treated THP-1 macrophages exhibited no change in tumor necrosis factor (TNF)-α, interleukin (IL)-18, macrophage inflammatory protein (MIP)-1α, and IL-1R1 receptor mRNA expression. However, there was a marked decrease in IL-1β mRNA expression but an increase in IL-1β protein secretion. Decreased expression of IL-1β mRNA and increased secretion of IL-1β protein was not the direct cause of cell death. Until now, TG was assumed to induce necrotic cell death in macrophages. Since caspase-1 is known to be involved in activation and secretion of IL-1β protein and pyroptotic cell death, next we determined whether caspase-1 is associated with TG-induced macrophage cell death. We found an increase in caspase-1 activity in TG-treated THP-1 macrophages and inhibition of caspase-1 activity using a specific inhibitor partially rescued cell death. These results suggest activation of the pyroptotic pathway by TG. This is the first report implicating the activation of caspase-1 and the triggering of the pyroptosis pathway in TG-induced macrophage cell death.

Hyaluronan activates Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed

Science.gov (United States)

Hsu, Li-Jin; Hong, Qunying; Chen, Shur-Tzu; Kuo, Hsiang-Lin; Schultz, Lori; Heath, John; Lin, Sing-Ru; Lee, Ming-Hui; Li, Dong-Zhang; Li, Zih-Ling; Cheng, Hui-Ching; Armand, Gerard; Chang, Nan-Shan

2017-01-01

Malignant cancer cells frequently secrete significant amounts of transforming growth factor beta (TGF-β), hyaluronan (HA) and hyaluronidases to facilitate metastasizing to target organs. In a non-canonical signaling, TGF-β binds membrane hyaluronidase Hyal-2 for recruiting tumor suppressors WWOX and Smad4, and the resulting Hyal-2/WWOX/Smad4 complex is accumulated in the nucleus to enhance SMAD-promoter dependent transcriptional activity. Yeast two-hybrid analysis showed that WWOX acts as a bridge to bind both Hyal-2 and Smad4. When WWOX-expressing cells were stimulated with high molecular weight HA, an increased formation of endogenous Hyal-2/WWOX/Smad4 complex occurred rapidly, followed by relocating to the nuclei in 20-40 min. In WWOX-deficient cells, HA failed to induce Smad2/3/4 relocation to the nucleus. To prove the signaling event, we designed a real time tri-molecular FRET analysis and revealed that HA induces the signaling pathway from ectopic Smad4 to WWOX and finally to p53, as well as from Smad4 to Hyal-2 and then to WWOX. An increased binding of the Smad4/Hyal-2/WWOX complex occurs with time in the nucleus that leads to bubbling cell death. In contrast, HA increases the binding of Smad4/WWOX/p53, which causes membrane blebbing but without cell death. In traumatic brain injury-induced neuronal death, the Hyal-2/WWOX complex was accumulated in the apoptotic nuclei of neurons in the rat brains in 24 hr post injury, as determined by immunoelectron microscopy. Together, HA activates the Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed. PMID:27845895

Causes of death among cancer patients.

Science.gov (United States)

Zaorsky, N G; Churilla, T M; Egleston, B L; Fisher, S G; Ridge, J A; Horwitz, E M; Meyer, J E

2017-02-01

The purpose of our study was to characterize the causes of death among cancer patients as a function of objectives: (i) calendar year, (ii) patient age, and (iii) time after diagnosis. US death certificate data in Surveillance, Epidemiology, and End Results Stat 8.2.1 were used to categorize cancer patient death as being due to index-cancer, nonindex-cancer, and noncancer cause from 1973 to 2012. In addition, data were characterized with standardized mortality ratios (SMRs), which provide the relative risk of death compared with all persons. The greatest relative decrease in index-cancer death (generally from > 60% to deaths were stable (typically >40%) among patients with cancers of the liver, pancreas, esophagus, and lung, and brain. Noncancer causes of death were highest in patients with cancers of the colorectum, bladder, kidney, endometrium, breast, prostate, testis; >40% of deaths from heart disease. The highest SMRs were from nonbacterial infections, particularly among 1,000 for lymphomas, P death from index- and nonindex-cancers varies widely among primary sites. Risk of noncancer deaths now surpasses that of cancer deaths, particularly for young patients in the year after diagnosis. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cause of death among Ghanaian adolescents in Accra using autopsy data

Directory of Open Access Journals (Sweden)

Tettey Yao

2011-09-01

Full Text Available Abstract Background There is limited data on adolescent mortality particularly from developing countries with unreliable death registration systems. This calls for the use of other sources of data to ascertain cause of adolescent mortality. The objective of this study was to describe the causes of death among Ghanaian adolescents 10 to 19 years in Accra, Ghana utilizing data from autopsies conducted in Korle Bu Teaching Hospital (KBTH. Findings Out of the 14,034 autopsies carried out from 2001 to 2003 in KBTH, 7% were among adolescents. Of the 882 deaths among adolescents analyzed, 402 (45.6% were females. There were 365 (41.4% deaths from communicable disease, pregnancy related conditions and nutritional disorders. Non-communicable diseases accounted for 362 (41% cases and the rest were attributable to injuries and external causes of morbidity and mortality. Intestinal infectious diseases and lower respiratory tract infections were the most common communicable causes of death collectively accounting for 20.5% of total deaths. Death from blood diseases was the largest (8.5% among the non-communicable conditions followed by neoplasms (7%. Males were more susceptible to injuries than females (χ2 = 13.45, p = .000. At least five out of ten specific causes of death were as a result of infections with pneumonia and typhoid being the most common. Sickle cell disease was among the top three specific causes of death. Among the females, 27 deaths (6.7% were pregnancy related with most of them being as a result of abortion. Conclusions The autopsy data from the Korle-Bu Teaching Hospital can serve as a useful source of information on adolescent mortality. Both communicable and non-communicable diseases accounted for most deaths highlighting the need for health care providers to avoid complacency in their management of adolescents presenting with these diseases.

Circadian Stress Regimes Affect the Circadian Clock and Cause Jasmonic Acid-Dependent Cell Death in Cytokinin-Deficient Arabidopsis Plants[OPEN

Science.gov (United States)

Nitschke, Silvia; Cortleven, Anne; Iven, Tim; Havaux, Michel; Schmülling, Thomas

2016-01-01

The circadian clock helps plants measure daylength and adapt to changes in the day-night rhythm. We found that changes in the light-dark regime triggered stress responses, eventually leading to cell death, in leaves of Arabidopsis thaliana plants with reduced cytokinin levels or defective cytokinin signaling. Prolonged light treatment followed by a dark period induced stress and cell death marker genes while reducing photosynthetic efficiency. This response, called circadian stress, is also characterized by altered expression of clock and clock output genes. In particular, this treatment strongly reduced the expression of CIRCADIAN CLOCK ASSOCIATED1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY). Intriguingly, similar changes in gene expression and cell death were observed in clock mutants lacking proper CCA1 and LHY function. Circadian stress caused strong changes in reactive oxygen species- and jasmonic acid (JA)-related gene expression. The activation of the JA pathway, involving the accumulation of JA metabolites, was crucial for the induction of cell death, since the cell death phenotype was strongly reduced in the jasmonate resistant1 mutant background. We propose that adaptation to circadian stress regimes requires a normal cytokinin status which, acting primarily through the AHK3 receptor, supports circadian clock function to guard against the detrimental effects of circadian stress. PMID:27354555

Causes of death of patients with lung cancer.

Science.gov (United States)

Nichols, Larry; Saunders, Rachel; Knollmann, Friedrich D

2012-12-01

The causes of death for patients with lung cancer are inadequately described. To categorize the immediate and contributing causes of death for patients with lung cancer. The autopsies from 100 patients who died of lung cancer between 1990 and February 2011 were analyzed. Tumor burden was judged the immediate cause of death in 30 cases, including 26 cases of extensive metastases and 4 cases with wholly or primarily lung tumor burden (causing respiratory failure). Infection was the immediate cause of death for 20 patients, including 8 with sepsis and 12 with pneumonia. Complications of metastatic disease were the immediate causes of death in 18 cases, including 6 cases of hemopericardium from pericardial metastases, 3 from myocardial metastases, 3 from liver metastases, and 3 from brain metastases. Other immediate causes of death were pulmonary hemorrhage (12 cases), pulmonary embolism (10 cases, 2 tumor emboli), and pulmonary diffuse alveolar damage (7 cases). From a functional (pathophysiologic) perspective, respiratory failure could be regarded as the immediate cause of death (or mechanism of death) in 38 cases, usually because of a combination of lung conditions, including emphysema, airway obstruction, pneumonia, hemorrhage, embolism, resection, and lung injury in addition to the tumor. For 94 of the 100 patients, there were contributing causes of death, with an average of 2.5 contributing causes and up to 6 contributing causes of death. The numerous and complex ways lung cancer kills patients pose a challenge for efforts to extend and improve their lives.

Can deaths in police cells be prevented? Experience from Norway and death rates in other countries.

Science.gov (United States)

Aasebø, Willy; Orskaug, Gunnar; Erikssen, Jan

2016-01-01

To describe the changes in death rates and causes of deaths in Norwegian police cells during the last 2 decades. To review reports on death rates in police cells that have been published in medical journals and elsewhere, and discuss the difficulties of comparing death rates between countries. Data on deaths in Norwegian police cells were collected retrospectively in 2002 and 2012 for two time periods: 1993-2001 (period 1) and 2003-2012 (period 2). Several databases were searched to find reports on deaths in police cells from as many countries as possible. The death rates in Norwegian police cells reduced significantly from 0.83 deaths per year per million inhabitants (DYM) in period 1 to 0.22 DYM in period 2 (p police cells reduced by about 75% over a period of approximately 10 years. This is probably mainly due to individuals with severe alcohol intoxication no longer being placed in police cells. However, there remain large methodology difficulties in comparing deaths rates between countries. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Epidermal cell death in frogs with chytridiomycosis

Directory of Open Access Journals (Sweden)

Laura A. Brannelly

2017-02-01

Full Text Available Background Amphibians are declining at an alarming rate, and one of the major causes of decline is the infectious disease chytridiomycosis. Parasitic fungal sporangia occur within epidermal cells causing epidermal disruption, but these changes have not been well characterised. Apoptosis (planned cell death can be a damaging response to the host but may alternatively be a mechanism of pathogen removal for some intracellular infections. Methods In this study we experimentally infected two endangered amphibian species Pseudophryne corroboree and Litoria verreauxii alpina with the causal agent of chytridiomycosis. We quantified cell death in the epidermis through two assays: terminal transferase-mediated dUTP nick end-labelling (TUNEL and caspase 3/7. Results Cell death was positively associated with infection load and morbidity of clinically infected animals. In infected amphibians, TUNEL positive cells were concentrated in epidermal layers, correlating to the localisation of infection within the skin. Caspase activity was stable and low in early infection, where pathogen loads were light but increasing. In animals that recovered from infection, caspase activity gradually returned to normal as the infection cleared. Whereas, in amphibians that did not recover, caspase activity increased dramatically when infection loads peaked. Discussion Increased cell death may be a pathology of the fungal parasite, likely contributing to loss of skin homeostatic functions, but it is also possible that apoptosis suppression may be used initially by the pathogen to help establish infection. Further research should explore the specific mechanisms of cell death and more specifically apoptosis regulation during fungal infection.

Potential misclassification of causes of death from COPD

DEFF Research Database (Denmark)

Jensen, Henriette Hvide; Godtfredsen, Nina Skavlan; Lange, Peter

2006-01-01

Little is known about causes of death in chronic obstructive pulmonary disease (COPD) and the validity of mortality statistics in COPD. The present authors examined causes of death using data from the Copenhagen City Heart Study. Of the 12,979 subjects with sufficient data from the baseline...... examination during 1976-1978, 6,709 died before 2001. Of these, 242 died with COPD as cause of death. Among subjects with at least severe COPD at baseline, only 24.9% had COPD as cause of death and, in almost half of the cases where COPD was listed as cause of death, the subject had a normal forced expiratory...... COPD, CMH and smoking were predictors of COPD as underlying cause of death, ORs 2.3 (1.5-3.7) and 2.2 (1.4-3.6), respectively. It was concluded that chronic obstructive pulmonary disease is underreported on death certificates, that biases in the use of chronic obstructive pulmonary disease as cause...

Modelling radiation-induced cell death and tumour re-oxygenation: local versus global and instant versus delayed cell death

International Nuclear Information System (INIS)

Gago-Arias, Araceli; Espinoza, Ignacio; Sánchez-Nieto, Beatriz; Aguiar, Pablo; Pardo-Montero, Juan

2016-01-01

The resistance of hypoxic cells to radiation, due to the oxygen dependence of radiosensitivity, is well known and must be taken into account to accurately calculate the radiation induced cell death. A proper modelling of the response of tumours to radiation requires deriving the distribution of oxygen at a microscopic scale. This usually involves solving the reaction-diffusion equation in tumour voxels using a vascularization distribution model. Moreover, re-oxygenation arises during the course of radiotherapy, one reason being the increase of available oxygen caused by cell killing, which can turn hypoxic tumours into oxic. In this work we study the effect of cell death kinetics in tumour oxygenation modelling, analysing how it affects the timing of re-oxygenation, surviving fraction and tumour control. Two models of cell death are compared, an instantaneous cell killing, mimicking early apoptosis, and a delayed cell death scenario in which cells can die shortly after being damaged, as well as long after irradiation. For each of these scenarios, the decrease in oxygen consumption due to cell death can be computed globally (macroscopic voxel average) or locally (microscopic). A re-oxygenation model already used in the literature, the so called full re-oxygenation, is also considered. The impact of cell death kinetics and re-oxygenation on tumour responses is illustrated for two radiotherapy fractionation schemes: a conventional schedule, and a hypofractionated treatment. The results show large differences in the doses needed to achieve 50% tumour control for the investigated cell death models. Moreover, the models affect the tumour responses differently depending on the treatment schedule. This corroborates the complex nature of re-oxygenation, showing the need to take into account the kinetics of cell death in radiation response models. (paper)

Death certificates underestimate infections as proximal causes of death in the U.S.

Directory of Open Access Journals (Sweden)

Sushant Govindan

Full Text Available Death certificates are a primary data source for assessing the population burden of diseases; however, there are concerns regarding their accuracy. Diagnosis-Related Group (DRG coding of a terminal hospitalization may provide an alternative view. We analyzed the rate and patterns of disagreement between death certificate data and hospital claims for patients who died during an inpatient hospitalization.We studied respondents from the Health and Retirement Study (a nationally representative sample of older Americans who had an inpatient death documented in the linked Medicare claims from 1993-2007. Causes of death abstracted from death certificates were aggregated to the standard National Center for Health Statistics List of 50 Rankable Causes of Death. Centers for Medicare and Medicaid Services (CMS-DRGs were manually aggregated into a parallel classification. We then compared the two systems via 2×2, focusing on concordance. Our primary analysis was agreement between the two data sources, assessed with percentages and Cohen's kappa statistic.2074 inpatient deaths were included in our analysis. 36.6% of death certificate cause-of-death codes agreed with the reason for the terminal hospitalization in the Medicare claims at the broad category level; when re-classifying DRGs without clear alignment as agreements, the concordance only increased to 61%. Overall Kappa was 0.21, or "fair." Death certificates in this cohort redemonstrated the conventional top 3 causes of death as diseases of the heart, malignancy, and cerebrovascular disease. However, hospitalization claims data showed infections, diseases of the heart, and cerebrovascular disease as the most common diagnoses for the same terminal hospitalizations.There are significant differences between Medicare claims and death certificate data in assigning cause of death for inpatients. The importance of infections as proximal causes of death is underestimated by current death certificate

Causes of death in long-term survivors of head and neck cancer.

Science.gov (United States)

Baxi, Shrujal S; Pinheiro, Laura C; Patil, Sujata M; Pfister, David G; Oeffinger, Kevin C; Elkin, Elena B

2014-05-15

Survivors of head and neck squamous cell carcinoma (HNSCC) face excess mortality from multiple causes. We used the population-based Surveillance, Epidemiology, and End Results (SEER) cancer registry data to evaluate the causes of death in patients with nonmetastatic HNSCC diagnosed between 1992 and 2005 who survived at least 3 years from diagnosis (long-term survivors). We used competing-risks proportional hazards regression to estimate probabilities of death from causes: HNSCC, second primary malignancy (SPM) excluding HNSCC, cardiovascular disease, and other causes. We identified 35,958 three-year survivors of HNSCC with a median age at diagnosis of 60 years (range = 18-100 years) and a median follow-up of 7.7 years (range = 3-18 years). There were 13,120 deaths during the study period. Death from any cause at 5 and 10 years was 15.4% (95% confidence interval [CI] = 15.0%-15.8%) and 41.0% (95% CI = 40.4%-41.6%), respectively. There were 3852 HNSCC deaths including both primary and subsequent head and neck tumors. The risk of death from HNSCC was greater in patients with nasopharynx or hypopharynx cancer and in patients with locally advanced disease. SPM was the leading cause of non-HNSCC death, and the most common sites of SPM death were lung (53%), esophagus (10%), and colorectal (5%) cancer. Many long-term HNSCC survivors die from cancers other than HNSCC and from noncancer causes. Routine follow-up care for HNSCC survivors should expand beyond surveillance for recurrent and new head and neck cancers. © 2014 American Cancer Society.

Live-cell visualization of gasdermin D-driven pyroptotic cell death.

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Rathkey, Joseph K; Benson, Bryan L; Chirieleison, Steven M; Yang, Jie; Xiao, Tsan S; Dubyak, George R; Huang, Alex Y; Abbott, Derek W

2017-09-01

Pyroptosis is a form of cell death important in defenses against pathogens that can also result in a potent and sometimes pathological inflammatory response. During pyroptosis, GSDMD (gasdermin D), the pore-forming effector protein, is cleaved, forms oligomers, and inserts into the membranes of the cell, resulting in rapid cell death. However, the potent cell death induction caused by GSDMD has complicated our ability to understand the biology of this protein. Studies aimed at visualizing GSDMD have relied on expression of GSDMD fragments in epithelial cell lines that naturally lack GSDMD expression and also lack the proteases necessary to cleave GSDMD. In this work, we performed mutagenesis and molecular modeling to strategically place tags and fluorescent proteins within GSDMD that support native pyroptosis and facilitate live-cell imaging of pyroptotic cell death. Here, we demonstrate that these fusion proteins are cleaved by caspases-1 and -11 at Asp-276. Mutations that disrupted the predicted p30-p20 autoinhibitory interface resulted in GSDMD aggregation, supporting the oligomerizing activity of these mutations. Furthermore, we show that these novel GSDMD fusions execute inflammasome-dependent pyroptotic cell death in response to multiple stimuli and allow for visualization of the morphological changes associated with pyroptotic cell death in real time. This work therefore provides new tools that not only expand the molecular understanding of pyroptosis but also enable its direct visualization. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Causes of death among females-investigating beyond maternal causes: a community-based longitudinal study.

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Melaku, Yohannes Adama; Weldearegawi, Berhe; Aregay, Alemseged; Tesfay, Fisaha Haile; Abreha, Loko; Abera, Semaw Ferede; Bezabih, Afework Mulugeta

2014-09-10

In developing countries, investigating mortality levels and causes of death among all age female population despite the childhood and maternal related deaths is important to design appropriate and tailored interventions and to improve survival of female residents. Under Kilite-Awlealo Health and Demographic Surveillance System, we investigated mortality rates and causes of death in a cohort of female population from 1st of January 2010 to 31st of December 2012. At the baseline, 33,688 females were involved for the prospective follow-up study. Households under the study were updated every six months by fulltime surveillance data collectors to identify vital events, including deaths. Verbal Autopsy (VA) data were collected by separate trained data collectors for all identified deaths in the surveillance site. Trained physicians assigned underlining causes of death using the 10th edition of International Classification of Diseases (ICD). We assessed overall, age- and cause-specific mortality rates per 1000 person-years. Causes of death among all deceased females and by age groups were ranked based on cause specific mortality rates. Analysis was performed using Stata Version 11.1. During the follow-up period, 105,793.9 person-years of observation were generated, and 398 female deaths were recorded. This gave an overall mortality rate of 3.76 (95% confidence interval (CI): 3.41, 4.15) per 1,000 person-years. The top three broad causes of death were infectious and parasitic diseases (1.40 deaths per 1000 person-years), non-communicable diseases (0.98 deaths per 1000 person-years) and external causes (0.36 per 1000 person-years). Most deaths among reproductive age female were caused by Human Deficiency Virus/Acquired Immune Deficiency Virus (HIV/AIDS) and tuberculosis (0.14 per 1000 person-years for each cause). Pregnancy and childbirth related causes were responsible for few deaths among women of reproductive age--3 out of 73 deaths (4.1%) or 5.34 deaths per 1,000 person

Model of transition between causes of death.

Science.gov (United States)

Damiani, P; Aubenque, M

1975-06-01

This paper describes an attempt to estimate the probabilities of transition between various major causes of death during the period 1954-1962. The regression coefficients have been estimated from French département death rates for ten main or typical causes of death, assessed by sex for the age group 45-64 years.

[Cause of late death in liver transplant recipients].

Science.gov (United States)

Coelho, Júlio Cézar Uili; Parolin, Mônica B; Matias, Jorge Eduardo Fouto; Jorge, Fernando Marcus Felipe; Canan Júnior, Lady Wilson

2003-01-01

The objective is to present the causes of late death in patients subjected to liver transplantation. A total of 209 patients were subjected to 223 liver transplantations (14 retransplantations). The computerized study protocol sheets were evaluated to determine the causes of late death (> 6 months after transplantation). Of the 209 patients, 30 had late death. Ductopenic rejection (chronic rejection) was the most common cause and it was observed in 10 patients. Time after transplantation at the moment of death of this group of patients varied from 11 to 57 months, with an average of 29 months. Seven patients died at the hospital admission of hepatic retransplantation. Other causes of late death were sepsis, lymphoproliferative disease, chronic renal insufficiency, and hepatic insufficiency. The most common cause of late death after liver transplantation is ductopenic rejection, followed by complications of retransplantation and sepsis. Death owing to ductopenic rejection may occur even many years after transplantation.

Competing causes of death: an analysis using multiple-cause-of-death data from The Netherlands

NARCIS (Netherlands)

Mackenbach, J. P.; Kunst, A. E.; Lautenbach, H.; Bijlsma, F.; Oei, Y. B.

1995-01-01

The standard methodology for cause-elimination life tables assumes that the various causes of death are statistically unrelated to one another, so that the mortality risks of those who are saved from an eliminated cause equal the risks of dying from other causes which are observed for the general

Reliability of cause of death coding: an international comparison.

Science.gov (United States)

Antini, Carmen; Rajs, Danuta; Muñoz-Quezada, María Teresa; Mondaca, Boris Andrés Lucero; Heiss, Gerardo

2015-07-01

This study evaluates the agreement of nosologic coding of cardiovascular causes of death between a Chilean coder and one in the United States, in a stratified random sample of death certificates of persons aged ≥ 60, issued in 2008 in the Valparaíso and Metropolitan regions, Chile. All causes of death were converted to ICD-10 codes in parallel by both coders. Concordance was analyzed with inter-coder agreement and Cohen's kappa coefficient by level of specification ICD-10 code for the underlying cause and the total causes of death coding. Inter-coder agreement was 76.4% for all causes of death and 80.6% for the underlying cause (agreement at the four-digit level), with differences by the level of specification of the ICD-10 code, by line of the death certificate, and by number of causes of death per certificate. Cohen's kappa coefficient was 0.76 (95%CI: 0.68-0.84) for the underlying cause and 0.75 (95%CI: 0.74-0.77) for the total causes of death. In conclusion, causes of death coding and inter-coder agreement for cardiovascular diseases in two regions of Chile are comparable to an external benchmark and with reports from other countries.

First assumptions and overlooking competing causes of death

DEFF Research Database (Denmark)

Leth, Peter Mygind; Andersen, Anh Thao Nguyen

2014-01-01

Determining the most probable cause of death is important, and it is sometimes tempting to assume an obvious cause of death, when it readily presents itself, and stop looking for other competing causes of death. The case story presented in the article illustrates this dilemma. The first assumption...... of cause of death, which was based on results from bacteriology tests, proved to be wrong when the results from the forensic toxicology testing became available. This case also illustrates how post mortem computed tomography (PMCT) findings of radio opaque material in the stomach alerted the pathologist...

Causes of death in patients with chronic sarcoidosis.

Science.gov (United States)

Hu, Xiaowen; Carmona, Eva M; Yi, Eunhee S; Pellikka, Patricia A; Ryu, Jay

2016-10-07

Sarcoidosis is a multi-system, granulomatous disorder of unknown etiology that is associated with a variable prognosis and sometimes results in death. There are conflicting reports regarding the causes of death in patients with sarcoidosis. Forty-four consecutive patients with sarcoidosis who underwent an autopsy (35 patients) or died at Mayo Clinic (Rochester, MN, USA) over a 20-yr period, from January 1, 1994 to December 31, 2013 were analyzed. The median age at death was 63 years (range, 33-94 years) and there were 22 (50%) women. Sarcoidosis had not been clinically diagnosed in 16 (36%) patients before death. Fifteen deaths (34%) were related to sarcoidosis and included seven deaths (16%) from cardiac sarcoidosis and four deaths (9%) from progressive pulmonary sarcoidosis. Other sarcoidosis-related causes of death included advanced hepatic sarcoidosis (5%) and opportunistic infections (5%) related to immunosuppressive therapy for treating sarcoidosis. Among seven patients dying from cardiac sarcoidosis, three had been diagnosed with sarcoidosis during life and cardiac involvement was known in two of them. Six of seven deaths from cardiac sarcoidosis occurred in the autopsied cohort while all four deaths from pulmonary sarcoidosis occurred in those not autopsied. In the majority of patients dying with sarcoidosis the cause of death is unrelated to sarcoidosis. Cardiac involvement is the most common cause of sarcoidosis-related deaths in patients subjected to postmortem examination and was usually undiagnosed during life. The cause distribution of death in patients with sarcoidosis differed depending on whether autopsy was performed.

Programmed cell death for defense against anomaly and tumor formation

International Nuclear Information System (INIS)

Kondo, Sohei; Norimura, Toshiyuki; Nomura, Taisei

1995-01-01

Cell death after exposure to low-level radiation is often considered evidence that radiation is poisonous, however small the dose. Evidence has been accumulating to support the notion that cell death after low-level exposure to radiation results from activation of suicidal genes open-quote programmed cell death close-quote or open-quote apoptosis close-quote - for the health of the whole body. This paper gives experimental evidence that embryos of fruit flies and mouse fetuses have potent defense mechanisms against teratogenic or tumorigenic injury caused by radiation and carcinogens, which function through programmed cell death

[Cause-of-death statistics and ICD, quo vadis?

Science.gov (United States)

Eckert, Olaf; Vogel, Ulrich

2018-07-01

The International Statistical Classification of Diseases and Related Health Problems (ICD) is the worldwide binding standard for generating underlying cause-of-death statistics. What are the effects of former revisions of the ICD on underlying cause-of-death statistics and which opportunities and challenges are becoming apparent in a possible transition process from ICD-10 to ICD-11?This article presents the calculation of the exploitation grade of ICD-9 and ICD-10 in the German cause-of-death statistics and quality of documentation. Approximately 67,000 anonymized German death certificates are processed by Iris/MUSE and official German cause-of-death statistics are analyzed.In addition to substantial changes in the exploitation grade in the transition from ICD-9 to ICD-10, regional effects become visible. The rate of so-called "ill-defined" conditions exceeds 10%.Despite substantial improvement of ICD revisions there are long-known deficits in the coroner's inquest, filling death certificates and quality of coding. To make better use of the ICD as a methodological framework for mortality statistics and health reporting in Germany, the following measures are necessary: 1. General use of Iris/MUSE, 2. Establishing multiple underlying cause-of-death statistics, 3. Introduction of an electronic death certificate, 4. Improvement of the medical assessment of cause of death.Within short time the WHO will release the 11th revision of the ICD that will provide additional opportunities for the development of underlying cause-of-death statistics and their use in science, public health and politics. A coordinated effort including participants in the process and users is necessary to meet the related challenges.

Causes of death in long-term survivors of non-small cell lung cancer: A regional Surveillance, Epidemiology, and End Results study.

Science.gov (United States)

Kanitkar, Amaraja A; Schwartz, Ann G; George, Julie; Soubani, Ayman O

2018-01-01

Survival from lung cancer is improving. There are limited data on the causes of death in 5-year survivors of lung cancer. The aim of this study is to explore the causes of death in long-term survivors of non-small cell lung cancer (NSCLC) and describe the odds of dying from causes other than lung cancer in this patient population. An analysis of 5-year survivors of newly diagnosed NSCLC from 1996 to 2007, in Metropolitan Detroit included in Surveillance, Epidemiology, and End Results program, was done. Of 23,059 patients identified, 3789 (16.43%) patients were alive at 5-year period (long-term survivors) and 1897 (50.06%) patients died in the later follow-up period (median 88 months; range 1-219 months). The causes of death besides lung cancer were observed in 55.2% of these patients. The most common causes of death were cardiovascular diseases (CVDs) (16%), chronic obstructive pulmonary diseases (11%), and other malignancies (8%). Patients older than 65 years, males, and those who underwent surgery for treatment of lung cancer faced a greater likelihood of death by other causes as compared to lung cancer (OR: 1.45, 95% confidence interval [CI]: 1.18-1.77; OR: 1.24, 95% CI: 1.02-1.51; and OR: 1.39, 95% CI: 1.06-1.82, respectively). Five-year survivors of NSCLC more commonly die from causes such as CVDs, lung diseases, and other malignancies. Aggressive preventive and therapeutic measures of these diseases may further improve the outcome in this patient population.

Potential misclassification of causes of death from COPD

DEFF Research Database (Denmark)

Jensen, Henriette Hvide; Godtfredsen, Nina Skavlan; Lange, Peter

2006-01-01

Little is known about causes of death in chronic obstructive pulmonary disease (COPD) and the validity of mortality statistics in COPD. The present authors examined causes of death using data from the Copenhagen City Heart Study. Of the 12,979 subjects with sufficient data from the baseline...... examination during 1976-1978, 6,709 died before 2001. Of these, 242 died with COPD as cause of death. Among subjects with at least severe COPD at baseline, only 24.9% had COPD as cause of death and, in almost half of the cases where COPD was listed as cause of death, the subject had a normal forced expiratory...... volume in one second /forced vital capacity ratio at baseline. In COPD patients, having COPD on the death certificate was associated with chronic mucus hypersecretion (CMH) at baseline, an odds ratio (OR) of 3.6 (95% confidence interval 1.7-7.7), and being female (OR 2.7 (1.3-5.6)). In subjects without...

Early cell death detection with digital holographic microscopy.

Directory of Open Access Journals (Sweden)

Nicolas Pavillon

Full Text Available BACKGROUND: Digital holography provides a non-invasive measurement of the quantitative phase shifts induced by cells in culture, which can be related to cell volume changes. It has been shown previously that regulation of cell volume, in particular as it relates to ionic homeostasis, is crucially involved in the activation/inactivation of the cell death processes. We thus present here an application of digital holographic microscopy (DHM dedicated to early and label-free detection of cell death. METHODS AND FINDINGS: We provide quantitative measurements of phase signal obtained on mouse cortical neurons, and caused by early neuronal cell volume regulation triggered by excitotoxic concentrations of L-glutamate. We show that the efficiency of this early regulation of cell volume detected by DHM, is correlated with the occurrence of subsequent neuronal death assessed with the widely accepted trypan blue method for detection of cell viability. CONCLUSIONS: The determination of the phase signal by DHM provides a simple and rapid optical method for the early detection of cell death.

Critical role of poly(ADP-ribose) polymerase-1 in modulating the mode of cell death caused by continuous oxidative stress.

Science.gov (United States)

Son, Young-Ok; Kook, Sung-Ho; Jang, Yong-Suk; Shi, Xianglin; Lee, Jeong-Chae

2009-11-01

Continuously generated hydrogen peroxide (H(2)O(2)) inhibits typical apoptosis and instead initiates a caspase-independent, apoptosis-inducing factor (AIF)-mediated pyknotic cell death. This may be related to H(2)O(2)-mediated DNA damage and subsequent ATP depletion, although the exact mechanisms by which the mode of cell death is decided after H(2)O(2) exposure are still unclear. Accumulated evidence and our previous data led us to hypothesize that continuously generated H(2)O(2), not an H(2)O(2) bolus, induces severe DNA damage, signaling poly(ADP-ribose) polymerase-1 (PARP-1) activation, ATP depletion, and eventually caspase-independent cell death. Results from the present study support that H(2)O(2) generated continuously by glucose oxidase causes excessive DNA damage and PARP-1 activation. Blockage of PARP-1 by a siRNA transfection or by pharmacological inhibitor resulted in the significant inhibition of ATP depletion, loss of mitochondrial membrane potential, nuclear translocation of AIF and endonuclease G, and eventually conversion to caspase-dependent apoptosis. Overall, the current study demonstrates the different roles of PARP-1 inhibition in modulation of cell death according to the method of H(2)O(2) exposure, that is, continuous generation versus a direct addition. (c) 2009 Wiley-Liss, Inc.

Benzyl isothiocyanate causes FoxO1-mediated autophagic death in human breast cancer cells.

Directory of Open Access Journals (Sweden)

Dong Xiao

Full Text Available Benzyl isothiocyanate (BITC, a constituent of edible cruciferous vegetables, inhibits growth of breast cancer cells but the mechanisms underlying growth inhibitory effect of BITC are not fully understood. Here, we demonstrate that BITC treatment causes FoxO1-mediated autophagic death in cultured human breast cancer cells. The BITC-treated breast cancer cells (MDA-MB-231, MCF-7, MDA-MB-468, BT-474, and BRI-JM04 and MDA-MB-231 xenografts from BITC-treated mice exhibited several features characteristic of autophagy, including appearance of double-membrane vacuoles (transmission electron microscopy and acidic vesicular organelles (acridine orange staining, cleavage of microtubule-associated protein 1 light chain 3 (LC3, and/or suppression of p62 (p62/SQSTM1 or sequestosome 1 expression. On the other hand, a normal human mammary epithelial cell line (MCF-10A was resistant to BITC-induced autophagy. BITC-mediated inhibition of MDA-MB-231 and MCF-7 cell viability was partially but statistically significantly attenuated in the presence of autophagy inhibitors 3-methyl adenine and bafilomycin A1. Stable overexpression of Mn-superoxide dismutase, which was fully protective against apoptosis, conferred only partial protection against BITC-induced autophagy. BITC treatment decreased phosphorylation of mTOR and its downstream targets (P70s6k and 4E-BP1 in cultured MDA-MB-231 and MCF-7 cells and MDA-MB-231 xenografts, but activation of mTOR by transient overexpression of its positive regulator Rheb failed to confer protection against BITC-induced autophagy. Autophagy induction by BITC was associated with increased expression and acetylation of FoxO1. Furthermore, autophagy induction and cell growth inhibition resulting from BITC exposure were significantly attenuated by small interfering RNA knockdown of FoxO1. In conclusion, the present study provides novel insights into the molecular circuitry of BITC-induced cell death involving FoxO1-mediated autophagy.

Maitotoxin-induced liver cell death involving loss of cell ATP following influx of calcium

International Nuclear Information System (INIS)

Kutty, R.K.; Singh, Y.; Santostasi, G.; Krishna, G.

1989-01-01

Maitotoxin, one of the most potent marine toxins known, produced cell death in cultures of rat hepatocytes with a TD50 of 80 pM at 24 hr. The cell death, as indicated by a dose- and time-dependent leakage of lactate dehydrogenase (LDH), was also associated with the leakage of [14C]adenine nucleotides from hepatocytes prelabeled with [14C]-adenine. The toxic effect of maitotoxin was completely abolished by the omission of calcium from the culture medium. The cell death induced by maitotoxin increased with increasing concentrations of calcium in the medium. Treatment of hepatocytes with low concentrations of the toxin (less than 0.5 ng/ml) resulted in increases in 45Ca influx into the cells. At higher concentrations of maitotoxin (greater than 1ng/ml), the initial increase in 45Ca influx was followed by the release of the 45Ca from the cells into the medium. Since the 45Ca release paralleled the LDH leakage, the release of calcium was due to cell death. The 45Ca influx, [14C]adenine nucleotide leakage, and LDH leakage were effectively inhibited by verapamil, a calcium channel blocker. Maitotoxin also induced a time- and dose-dependent loss of ATP from hepatocytes, which preceded the [14C]adenine nucleotide and LDH leakage. Thus, it appears that the cell death resulting from maitotoxin treatment is caused by the elevated intracellular calcium, which in turn inhibits mitochondrial oxidative phosphorylation causing depletion of cell ATP. Loss of cell ATP may be the causative event in the maitotoxin-induced cell death

Gastrointestinal causes of sudden unexpected death: A review.

Science.gov (United States)

Menezes, Ritesh G; Ahmed, Saba; Pasha, Syed Bilal; Hussain, Syed Ather; Fatima, Huda; Kharoshah, Magdy A; Madadin, Mohammed

2018-01-01

Gastrointestinal conditions are a less common cause of sudden unexpected death when compared to other conditions such as cardiovascular conditions, but they are equally important. Various congenital and acquired gastrointestinal conditions that have resulted in sudden unexpected death are discussed. The possible lethal mechanisms behind each condition, along with any associated risk factors or secondary diseases, have been described. Through this article, we aim to highlight the need for physicians to prevent death in such conditions by ensuring that subclinical cases are diagnosed correctly before it is too late and by providing timely and efficacious treatment to the patient concerned. In addition, this review would certainly benefit the forensic pathologist while dealing with cases of sudden unexpected death due to gastrointestinal causes. This article is a review of the major gastrointestinal causes of sudden unexpected death. In addition, related fatal cases encountered occasionally in forensic autopsy practice are also included. There are several unusual and rare causes of life-threatening gastrointestinal bleeding that may lead to sudden unexpected death to cover all the entities in detail. Nevertheless, this article is a general guide to the topic of gastrointestinal causes of sudden unexpected death.

[Toxicomania: death beyond risk. Analysis of cause-of-death in drug addicts].

Science.gov (United States)

Jeanmonod, R; Fryc, O

1990-11-03

Violent deaths are of considerable importance among young adults, since they account for half the deaths in this age group (average age 26.4 years). Suicide and accidents (both categories including drug overdoses) are the most frequent categories of deaths from non-natural causes, while in the USA deaths by homicide are also of considerable importance. Current repressive policies have not brought the problem of drug addiction under control. Each year deaths by overdose among drug abusers occur. Nevertheless, 40% of deaths among drug addicts are from other causes, principally accidents and suicides. In the near future, AIDS may well account for the majority of deaths among drug addicts, thus adding to the mortality from overdose, both accidental and suicidal. Has the time come to reconsider the problem of drug abuse and to find radical solutions which would previously have been unthinkable?

Activation of peroxisome proliferator-activated receptor-γ (PPARγ) induces cell death through MAPK-dependent mechanism in osteoblastic cells

International Nuclear Information System (INIS)

Kim, Sung Hun; Yoo, Chong Il; Kim, Hui Taek; Park, Ji Yeon; Kwon, Chae Hwa; Keun Kim, Yong

2006-01-01

The present study was undertaken to determine the role of the mitogen-activated protein kinase (MAPK) subfamilies in cell death induced by PPARγ agonists in osteoblastic cells. Ciglitazone and troglitazone, PPARγ agonists, resulted in a concentration- and time-dependent cell death, which was largely attributed to apoptosis. But a PPARα agonist ciprofibrate did not affect the cell death. Ciglitazone caused reactive oxygen species (ROS) generation and ciglitazone-induced cell death was prevented by antioxidants, suggesting an important role of ROS generation in the ciglitazone-induced cell death. ROS generation and cell death induced by ciglitazone were inhibited by the PPARγ antagonist GW9662. Ciglitazone treatment caused activation of extracellular signal-regulated kinase (ERK) and p38. Activation of ERK was dependent on epidermal growth factor receptor (EGFR) and that of p38 was independent. Ciglitazone-induced cell death was significantly prevented by PD98059, an inhibitor of ERK upstream kinase MEK1/2, and SB203580, a p38 inhibitor. Ciglitazone treatment increased Bax expression and caused a loss of mitochondrial membrane potential, and its effect was prevented by N-acetylcysteine, PD98059, and SB203580. Ciglitazone induced caspase activation, which was prevented by PD98059 and SB203580. The general caspase inhibitor z-DEVD-FMK and the specific inhibitor of caspases-3 DEVD-CHO exerted the protective effect against the ciglitazone-induced cell death. The EGFR inhibitors AG1478 and suramin protected against the ciglitazone-induced cell death. Taken together, these findings suggest that the MAPK signaling pathways play an active role in mediating the ciglitazone-induced cell death of osteoblasts and function upstream of a mitochondria-dependent mechanism. These data may provide a novel insight into potential therapeutic strategies for treatment of osteoporosis

Causes of death in 2877 patients with myelodysplastic syndromes.

Science.gov (United States)

Nachtkamp, Kathrin; Stark, Romina; Strupp, Corinna; Kündgen, Andrea; Giagounidis, Aristoteles; Aul, Carlo; Hildebrandt, Barbara; Haas, Rainer; Gattermann, Norbert; Germing, Ulrich

2016-05-01

Patients with myelodysplastic syndromes face a poor prognosis. The exact causes of death have not been described properly in the past. We performed a retrospective analysis of causes of death using data of 3792 patients in the Düsseldorf registry who have been followed up for a median time of 21 months. Medical files as well as death certificates were screened and primary care physicians were contacted. Death after AML evolution, infection, and bleeding was considered to be clearly disease-related. Further categories of causes of death were heart failure, other possibly disease-related reasons, such as hemochromatosis, disease-independent reasons as well as cases with unclear causes of death. Median age at the time of diagnosis was 71 years. At the time of analysis, 2877 patients (75.9 %) had deceased. In 1212 cases (42.1 %), the exact cause of death could not be ascertained. From 1665 patients with a clearly documented cause of death, 1388 patients (83.4 %) succumbed directly disease-related (AML (46.6 %), infection (27.0 %), bleeding (9.8 %)), whereas 277 patients (16.6 %) died for reasons not directly related with myelodysplastic syndromes (MDS), including 132 patients with cardiac failure, 77 non-disease-related reasons, 23 patients with solid tumors, and 45 patients with possibly disease-related causes like hemochromatosis. Correlation with IPSS, IPSS-R, and WPSS categories showed a proportional increase of disease-related causes of death with increasing IPSS/IPSS-R/WPSS risk category. Likewise, therapy-related MDS were associated with a higher percentage of disease-related causes of death than primary MDS. This reflects the increasing influence of the underlying disease on the cause of death with increasing aggressiveness of the disease.

Late Mortality and Causes of Death among Long-Term Survivors after Allogeneic Stem Cell Transplantation.

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Atsuta, Yoshiko; Hirakawa, Akihiro; Nakasone, Hideki; Kurosawa, Saiko; Oshima, Kumi; Sakai, Rika; Ohashi, Kazuteru; Takahashi, Satoshi; Mori, Takehiko; Ozawa, Yukiyasu; Fukuda, Takahiro; Kanamori, Heiwa; Morishima, Yasuo; Kato, Koji; Yabe, Hiromasa; Sakamaki, Hisashi; Taniguchi, Shuichi; Yamashita, Takuya

2016-09-01

We sought to assess the late mortality risks and causes of death among long-term survivors of allogeneic hematopoietic stem cell transplantation (HCT). The cases of 11,047 relapse-free survivors of a first HCT at least 2 years after HCT were analyzed. Standardized mortality ratios (SMR) were calculated and specific causes of death were compared with those of the Japanese population. Among relapse-free survivors at 2 years, overall survival percentages at 10 and 15 years were 87% and 83%, respectively. The overall risk of mortality was significantly higher compared with that of the general population. The risk of mortality was significantly higher from infection (SMR = 57.0), new hematologic malignancies (SMR = 2.2), other new malignancies (SMR = 3.0), respiratory causes (SMR = 109.3), gastrointestinal causes (SMR = 3.8), liver dysfunction (SMR = 6.1), genitourinary dysfunction (SMR = 17.6), and external or accidental causes (SMR = 2.3). The overall annual mortality rate showed a steep decrease from 2 to 5 years after HCT; however, the decrease rate slowed after 10 years but was still higher than that of the general population at 20 years after HCT. SMRs in the earlier period of 2 to 4 years after HCT and 5 years or longer after HCT were 16.1 and 7.4, respectively. Long-term survivors after allogeneic HCT are at higher risk of mortality from various causes other than the underlying disease that led to HCT. Screening and preventive measures should be given a central role in reducing the morbidity and mortality of HCT recipients on long-term follow-up. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

NCHS - Potentially Excess Deaths from the Five Leading Causes of Death

Data.gov (United States)

U.S. Department of Health & Human Services — Potentially Excess Deaths from the Five Leading Causes of Death in Nonmetropolitan and Metropolitan Areas, United States, 2005-2015. Mortality data for U.S....

Using multiple cause-of-death data to investigate associations and causality between conditions listed on the death certificate.

Science.gov (United States)

Redelings, Matthew D; Wise, Matthew; Sorvillo, Frank

2007-07-01

Death rarely results from only one cause, and it can be caused by a variety of factors. Multiple cause-of-death data files can list as many as 20 contributing causes of death in addition to the reported underlying cause of death. Analysis of multiple cause-of-death data can provide information on associations between causes of death, revealing common combinations of events or conditions which lead to death. Additionally, physicians report the causal train of events through which they believe that different conditions or events may have led to each other and ultimately caused death. In this paper, the authors discuss methods used in studying associations between reported causes of death and in investigating commonly reported causal pathways between events or conditions listed on the death certificate.

Knockout of Arabidopsis accelerated-cell-death11 encoding a sphingosine transfer protein causes activation of programmed cell death and defense

DEFF Research Database (Denmark)

Brodersen, Peter; Petersen, Morten; Pike, Helen M

2002-01-01

by avirulent pathogens. Global transcriptional changes during programmed cell death (PCD) and defense activation in acd11 were monitored by cDNA microarray hybridization. The PCD and defense pathways activated in acd11 are salicylic acid (SA) dependent, but do not require intact jasmonic acid or ethylene...

Comparison of death certificate and autopsy diagnoses - Hiroshima. [Cause of death

Energy Technology Data Exchange (ETDEWEB)

Stone, R S; Anderson, Jr, P S

1960-09-14

In this report evaluation of the death certificates has been on the basis of comparison with recorded autopsy diagnoses without review of the latter. An attempt has been made to evaluate limitations inherent in this method. The cases analyzed here represent the ABCC Hiroshima autopsy series from 1949 through 1959. Post mortem examinations on stillbirths and neonatal deaths that were collected during the years 1948 through 1953 were excluded from consideration because such cases are not pertinent to the general problems under study. With this limitation 1304 cases were available for matching. In 139 of these cases the death certificates were not available through the mechanisms of the overall study, so 1165 cases remained. Before comparisons are made the most important questions that must be answered about the materials and methods of the present investigation are: (1) is the autopsy-death certificate series a representative sample of all deaths in the population; (2) are the autopsy diagnoses correct; (3) are the death certificates properly understood and coded; and (4) are biologically meaningful groupings chosen for comparison between autopsy cause of death and death certificate cause of death. Because it is not possible to provide exact answers to all of these questions the doubt that they raise must be admitted but evaluated in the perspective of that part of the answer which is known.

Expression of death receptor 4 induces caspase-independent cell death in MMS-treated yeast.

Science.gov (United States)

Kang, Mi-Sun; Lee, Sung-Keun; Park, Chang-Shin; Kang, Ju-Hee; Bae, Sung-Ho; Yu, Sung-Lim

2008-11-14

DR4, a tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor, is a key element in the extrinsic pathway of TRAIL/TRAIL receptor-related apoptosis that exerts a preferential toxic effect against tumor cells. However, TRAIL and DR4 are expressed in various normal cells, and recent studies indicate that DR4 has a number of non-apoptotic functions. In this study, we evaluated the effects of human DR4 expression in yeast to determine the function of DR4 in normal cells. The expression of DR4 in yeast caused G1 arrest, which resulted in transient growth inhibition. Moreover, treatment of DR4-expressing yeast with a DNA damaging agent, MMS, elicited drastic, and sustained cell growth inhibition accompanied with massive apoptotic cell death. Further analysis revealed that cell death in the presence of DNA damage and DR4 expression was not dependent on the yeast caspase, YCA1. Taken together, these results indicate that DR4 triggers caspase-independent programmed cell death during the response of normal cells to DNA damage.

Risk factors and causes of sudden noncardiac death

DEFF Research Database (Denmark)

Risgaard, Bjarke; Lynge, Thomas Hadberg; Wissenberg, Mads

2015-01-01

was to report the risk factors and causes of SNCD. METHODS: We conducted a retrospective, nationwide study including all deaths between 2000 and 2006 of individuals aged 1-35 years and all deaths between 2007 and 2009 of individuals aged 1-49 years. Two physicians identified all sudden death cases through.......3-2.3; OR 3.0, 95% CI 2.0-4.4; and OR 4.3, 95% CI 2.5-7.4, respectively). The most common cause of SNCD was pulmonary disease (n = 115 [40%]). CONCLUSION: Sudden death among individuals aged caused by noncardiac diseases in 28% of cases. Risk factors were female sex, age, and the absence......BACKGROUND: On the performance of an autopsy, sudden deaths may be divided into 2 classifications: (1) sudden cardiac deaths and (2) sudden noncardiac deaths (SNCDs). Families of SNCD victims should not be followed up as a means of searching for cardiac disease. OBJECTIVE: The purpose of this study...

Pregnancy related causes of deaths in Ghana: a 5-year retrospective study.

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Der, E M; Moyer, C; Gyasi, R K; Akosa, A B; Tettey, Y; Akakpo, P K; Blankson, A; Anim, J T

2013-12-01

Data on maternal mortality varies by region and data source. Accurate local-level data are essential to appreciate its burden. This study uses autopsy results to assess maternal mortality causes in southern Ghana. Autopsy log books of the Department of Pathology, Korle-Bu Teaching Hospital Mortuary were reviewed from 2004 through 2008 for pregnancy related deaths. Data were entered into a database and analyzed using SPSS statistical software (Version 19). Of 5,247 deaths among women aged 15-49, 12.1% (634) were pregnancy-related. Eighty one percent of pregnancy-related deaths (517) occurred in the community or within 24 hours of admission to a health facility and 18.5% (117) occurred in a health facility. Out of 634 pregnancy-related deaths, 79.5% (504) resulted from direct obstetric causes, including: haemorrhage (21.8%), abortion (20.8%), hypertensive disorders (19.4%), ectopic gestation (8.7%), uterine rupture (4.3%) and genital tract sepsis (2.5%). The remaining 20.5% (130) resulted from indirect obstetric causes, including: infections outside the genital tract, (9.2%), anemia (2.8%), sickle cell disease (2.7%), pulmonary embolism (1.9%) and disseminated intravascular coagulation (1.3%). The top five causes of maternal death were: haemorrhage (21.8%), abortion (20.7%), hypertensive disorders (19.4%), infections (9.1%) and ectopic gestation (8.7%). Ghana continues to have persistently high levels of preventable causes of maternal deaths. Community based studies, on maternal mortality are urgently needed in Ghana, since our autopsy studies indicates that 81% of deaths recorded in this study occurred in the community or within 24 hours of admission to a health facility.

Insulin receptor substrate-1 prevents autophagy-dependent cell death caused by oxidative stress in mouse NIH/3T3 cells

Directory of Open Access Journals (Sweden)

Chan Shih-Hung

2012-07-01

Full Text Available Abstract Background Insulin receptor substrate (IRS-1 is associated with tumorigenesis; its levels are elevated in several human cancers. IRS-1 protein binds to several oncogene proteins. Oxidative stress and reactive oxygen species (ROS are involved in the initiation and progression of cancers. Cancer cells produce greater levels of ROS than normal cells do because of increased metabolic stresses. However, excessive production of ROS kills cancer cells. Autophagy usually serves as a survival mechanism in response to stress conditions, but excessive induction of autophagy results in cell death. In addition to inducing necrosis and apoptosis, ROS induces autophagic cell death. ROS inactivates IRS-1 mediated signaling and reduces intracellular IRS-1 concentrations. Thus, there is a complex relationship between IRS-1, ROS, autophagy, and cancer. It is not fully understood how cancer cells grow rapidly and survive in the presence of high ROS levels. Methods and results In this study, we established mouse NIH/3T3 cells that overexpressed IRS-1, so mimicking cancers with increased IRS-1 expression levels; we found that the IRS-1 overexpressing cells grow more rapidly than control cells do. Treatment of cells with glucose oxidase (GO provided a continuous source of ROS; low dosages of GO promoted cell growth, while high doses induced cell death. Evidence for GO induced autophagy includes increased levels of isoform B-II microtubule-associated protein 1 light chain 3 (LC3, aggregation of green fluorescence protein-tagged LC3, and increased numbers of autophagic vacuoles in cells. Overexpression of IRS-1 resulted in inhibition of basal autophagy, and reduced oxidative stress-induced autophagy and cell death. ROS decreased the mammalian target of rapamycin (mTOR/p70 ribosomal protein S6 kinase signaling, while overexpression of IRS-1 attenuated this inhibition. Knockdown of autophagy-related gene 5 inhibited basal autophagy and diminished oxidative stress

Characterization of a serine protease-mediated cell death program activated in human leukemia cells

International Nuclear Information System (INIS)

O'Connell, A.R.; Holohan, C.; Torriglia, A.; Lee, B.F.; Stenson-Cox, C.

2006-01-01

Tightly controlled proteolysis is a defining feature of apoptosis and caspases are critical in this regard. Significant roles for non-caspase proteases in cell death have been highlighted. Staurosporine causes a rapid induction of apoptosis in virtually all mammalian cell types. Numerous studies demonstrate that staurosporine can activate cell death under caspase-inhibiting circumstances. The aim of this study was to investigate the proteolytic mechanisms responsible for cell death under these conditions. To that end, we show that inhibitors of serine proteases can delay cell death in one such system. Furthermore, through profiling of proteolytic activation, we demonstrate, for the first time, that staurosporine activates a chymotrypsin-like serine protease-dependent cell death in HL-60 cells independently, but in parallel with the caspase controlled systems. Features of the serine protease-mediated system include cell shrinkage and apoptotic morphology, regulation of caspase-3, altered nuclear morphology, generation of an endonuclease and DNA degradation. We also demonstrate a staurosporine-induced activation of a putative 16 kDa chymotrypsin-like protein during apoptosis

Cigarette Smoke-Induced Cell Death Causes Persistent Olfactory Dysfunction in Aged Mice

Directory of Open Access Journals (Sweden)

Rumi Ueha

2018-06-01

Full Text Available Introduction: Exposure to cigarette smoke is a cause of olfactory dysfunction. We previously reported that in young mice, cigarette smoke damaged olfactory progenitors and decreased mature olfactory receptor neurons (ORNs, then, mature ORNs gradually recovered after smoking cessation. However, in aged populations, the target cells in ORNs by cigarette smoke, the underlying molecular mechanisms by which cigarette smoke impairs the regenerative ORNs, and the degree of ORN regeneration after smoking cessation remain unclear.Objectives: To explore the effects of cigarette smoke on the ORN cell system using an aged mouse model of smoking, and to investigate the extent to which smoke-induced damage to ORNs recovers following cessation of exposure to cigarette smoke in aged mice.Methods: We intranasally administered a cigarette smoke solution (CSS to 16-month-old male mice over 24 days, then examined ORN existence, cell survival, changes of inflammatory cytokines in the olfactory epithelium (OE, and olfaction using histological analyses, gene analyses and olfactory habituation/dishabituation tests.Results: CSS administration reduced the number of mature ORNs in the OE and induced olfactory dysfunction. These changes coincided with an increase in the number of apoptotic cells and Tumor necrosis factor (TNF expression and a decrease in Il6 expression. Notably, the reduction in mature ORNs did not recover even on day 28 after cessation of treatment with CSS, resulting in persistent olfactory dysfunction.Conclusion: In aged mice, by increasing ORN death, CSS exposure could eventually overwhelm the regenerative capacity of the OE, resulting in continued reduction in the number of mature ORNs and olfactory dysfunction.

Causes and circumstances of death in pulmonary arterial hypertension.

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Tonelli, Adriano R; Arelli, Vineesha; Minai, Omar A; Newman, Jennie; Bair, Nancy; Heresi, Gustavo A; Dweik, Raed A

2013-08-01

The causes and circumstances surrounding death are understudied in patients with pulmonary arterial hypertension (PAH). We sought to determine the specific reasons and characteristics surrounding the death of patients with PAH. All deaths of patients with pulmonary hypertension (PH) followed in the Cleveland Clinic Pulmonary Vascular Program were prospectively reviewed by the PH team. A total of 84 patients with PAH (age 58 ± 14 yr; 73% females) who died between June 2008 and May 2012 were included. PH was determined to be the direct cause of death (right heart failure or sudden death) in 37 (44%) patients; PH contributed to but did not directly cause death in 37 (44%) patients; and the death was not related to PH in the remaining cases (n = 7; 8.3%). In three (3.6%) patients the final cause of death could not be adequately assessed. Most patients died in a healthcare environment and most received PH-specific therapies. In our cohort, 50% of all patients with PAH and 75.7% of those who died of right heart failure received parenteral prostanoid therapy. Less than half of patients had advanced healthcare directives. Most patients with PAH in our cohort died of their disease; however, right ventricular failure or sudden death was the sole cause of death in less than half of patients.

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018

OpenAIRE

Galluzzi, L; Vitale, I; Aaronson, Sa; Abrams, Jm; Adam, D; Agostinis, P; Alnemri, Es; Altucci, L; Amelio, I; Andrews, Dw; Annicchiarico-Petruzzelli, M; Antonov, Av; Arama, E; Baehrecke, Eh; Barlev, Na

2018-01-01

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. A...

Strangulation and Its Role in Multiple Causes of Death.

Science.gov (United States)

Hlavaty, Leigh; Sung, LokMan

2017-12-01

Forensic pathologists have a duty to determine the cause and manner of death and are bound by international guidelines in the completion of the death certificate. Sometimes, there are complex circumstances surrounding a death that cannot be captured in the structure of the death certificate and its requirement of listing only 1 cause of death per line. Cases may have multiple causes of death with comorbid medical conditions or inflicted injuries that equally contribute to the ultimate demise. Compared with other forms of homicide, autopsy evidence of strangulation will often be found with other life-threatening traumatic injuries. The Wayne County Medical Examiner's Office conducted a retrospective study of strangulation cases that came into the office from mid-2007 to the end of 2016. The purpose of the study was to examine patterns of injuries in strangulation cases and identify those with additional traumatic injuries of commensurate extent that required incorporation into the cause of death. A total of 43 strangulation cases were found, of which there were equal numbers of ligature and manual strangulations (19 each) and 5 cases in which the method was not specified, and decedents were divided: 63% female and 37% male. Fourteen of these cases were recognized to have multiple causes of death, where blunt force trauma was the most common additional cause, and the sex distribution weighed heavily toward the female (approximately 79%).

Childhood deaths from external causes in Estonia, 2001-2005.

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Väli, Marika; Lang, Katrin; Soonets, Ruth; Talumäe, Marika; Grjibovski, Andrej M

2007-07-17

In 2000, the overall rate of injury deaths in children aged 0-14 was 28.7 per 100000 in Estonia, which is more than 5 times higher than the corresponding rate in neighbouring Finland. This paper describes childhood injury mortality in Estonia by cause and age groups, and validates registration of these deaths in the Statistical Office of Estonia against the autopsy data. The data on causes of all child deaths in Estonia in 2001-2005 were abstracted from the autopsy protocols at the Estonian Bureau of Forensic Medicine. Average annual mortality rates per 100,000 were calculated. Coverage (proportion of the reported injury deaths from the total number of injury deaths) and accuracy (proportion of correctly classified injury deaths) of the registration of causes of death in Statistical Office of Estonia were assessed by comparing the Statistical Office of Estonia data with the data from Estonian Bureau of Forensic Medicine. Average annual mortality from external causes in 0-14 years-old children in Estonia was 19.1 per 100,000. Asphyxia and transport accidents were the major killers followed by poisoning and suicides. Relative contribution of these causes varied greatly between age groups. Intent of death was unknown for more than 10% of injury deaths. Coverage and accuracy of registration of injury deaths by Statistical Office of Estonia were 91.5% and 95.3%, respectively. Childhood mortality from injuries in Estonia is among the highest in the EU. The number of injury deaths in Statistical Office of Estonia is slightly underestimated mostly due to misclassification for deaths from diseases. Accuracy of the Statistical Office of Estonia data was high with some underestimation of intentional deaths. Moreover, high proportion of death with unknown intent suggests underestimation of intentional deaths. Reduction of injury deaths should be given a high priority in Estonia. More information on circumstances around death is needed to enable establishing the intent of death.

Leading Causes of Death in Females United States

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... and Health Issues at Work Health Equity Leading Causes of Death in Females, United States Recommend on Facebook Tweet ... to current and previous listings for the leading causes of death in females in the United States. Please note ...

Causes of death behind low life expectancy of Danish women

DEFF Research Database (Denmark)

Jacobsen, Rune; Keiding, Niels; Lynge, Elsebeth

2006-01-01

AIMS: The authors examined causes of death contributing to the relatively high mortality of Danish women born 1915-45, and evaluated the impact of smoking related causes of death. METHODS: Age-period-cohort analysis of mortality of Danish women aged 40-89 in 1960-98. Estimate of the negative...... curvature in parabola patterns for 50 causes of death. RESULTS: A total of 34 causes of death contributed to the relatively high mortality for women born 1915-45. The main contribution came from smoking-related causes of death. CONCLUSION: The results indicate a high smoking prevalence to be the main...

Primary Causes of Death After Permanent Prostate Brachytherapy

International Nuclear Information System (INIS)

Bittner, Nathan; Merrick, Gregory S.; Galbreath, Robert W.; Butler, Wayne M.; Wallner, Kent E.; Allen, Zachariah A.; Brammer, Sarah G.; Moyad, Mark

2008-01-01

Purpose: To evaluate the primary causes of death in low-risk (low-risk), intermediate-risk (intermediate-risk), and high-risk (high-risk) patients undergoing permanent prostate brachytherapy with or without supplemental therapies. Methods and Materials: From April 1995 through November 2004, a total of 1,354 consecutive patients underwent prostate brachytherapy. All patients underwent brachytherapy >3 years before analysis. Of the patients, 532 (39.3%) received androgen deprivation therapy and 703 (51.9%) received supplemental radiation therapy. The median follow-up was 5.4 years. Multiple parameters were evaluated as predictors of cause-specific, biochemical progression-free, and overall survival. Results: The 10-year cause-specific survival was 97.0% (99.7%, 99.0%, and 90.1% for low-risk, intermediate-risk, and high-risk patients). Overall survival was 76.7% (82.5%, 78.3%, and 67.6% for low-, intermediate-, and high-risk patients, respectively). The cumulative death rate for cardiovascular disease was 11.5% (8.7%, 9.3%, and 19.8% for low-, intermediate-, and high-risk patients). The death rate from second malignancies (nonprostate cancer) was 7.2% and was not substantially different when stratified by risk group. Death from all other causes was 6.5% for the entire cohort but 1.3%, 5.0%, and 10.8% for low-, intermediate-, and high-risk patients. In multivariate analysis, death from prostate cancer was best predicted by Gleason score and risk group, whereas death from cardiovascular disease, nonprostate cancer, and all other causes were most closely related to patient age and tobacco use. Conclusions: Although cardiovascular mortality was the predominant cause of death, prostate cancer was responsible for approximately 10% of all deaths. In particular, overall survival was poorest in the high-risk group. Although high-risk patients were most likely to die of prostate cancer, the divergence in overall survival between high-risk and lower-risk patients primarily

Death certificate data and causes of death in patients with parkinsonism.

Science.gov (United States)

Moscovich, Mariana; Boschetti, Gabriela; Moro, Adriana; Teive, Helio A G; Hassan, Anhar; Munhoz, Renato P

2017-08-01

Assessment of variables related to mortality in Parkinson disease (PD) and other parkinsonian syndromes relies, among other sources, on accurate death certificate (DC) documentation. We assessed the documentation of the degenerative disorder on DCs and evaluated comorbidities and causes of death among parkinsonian patients. Demographic and clinical data were systematically and prospectively collected on deceased patients followed at a tertiary movement disorder clinic. DCs data included the documentation of parkinsonism, causes, and place of death. Among 138 cases, 84 (60.9%) male, mean age 77.9 years, mean age of onset 66.7, and mean disease duration 10.9 years. Clinical diagnoses included PD (73.9%), progressive supranuclear palsy (10.9%), multiple system atrophy (7.2%), Lewy body dementia (7.2%) and corticobasal degeneration (0.7%). Psychosis occurred in 60.1% cases, dementia in 48.5%. Most PD patients died due to heterogeneous causes before reaching advanced stages. Non-PD parkinsonian patients died earlier due to causes linked to the advanced neurodegenerative process. PD was documented in 38.4% of DCs with different forms of inconsistencies. That improved, but remained significant when it was signed by a specialist. More than half of PD cases died while still ambulatory and independent, after a longer disease course and due to causes commonly seen in that age group. Deaths among advanced PD patients occurred due to causes similar to what we found in non-PD cases. These findings can be useful for clinical, prognostic and counseling purposes. Underlying parkinsonian disorders are poorly documented in DCs, undermining its' use as sources of data collection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Apoptosis and tumor cell death in response to HAMLET (human alpha-lactalbumin made lethal to tumor cells).

Science.gov (United States)

Hallgren, Oskar; Aits, Sonja; Brest, Patrick; Gustafsson, Lotta; Mossberg, Ann-Kristin; Wullt, Björn; Svanborg, Catharina

2008-01-01

HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a molecular complex derived from human milk that kills tumor cells by a process resembling programmed cell death. The complex consists of partially unfolded alpha-lactalbumin and oleic acid, and both the protein and the fatty acid are required for cell death. HAMLET has broad antitumor activity in vitro, and its therapeutic effect has been confirmed in vivo in a human glioblastoma rat xenograft model, in patients with skin papillomas and in patients with bladder cancer. The mechanisms of tumor cell death remain unclear, however. Immediately after the encounter with tumor cells, HAMLET invades the cells and causes mitochondrial membrane depolarization, cytochrome c release, phosphatidyl serine exposure, and a low caspase response. A fraction of the cells undergoes morphological changes characteristic of apoptosis, but caspase inhibition does not rescue the cells and Bcl-2 overexpression or altered p53 status does not influence the sensitivity of tumor cells to HAMLET. HAMLET also creates a state of unfolded protein overload and activates 20S proteasomes, which contributes to cell death. In parallel, HAMLET translocates to tumor cell nuclei, where high-affinity interactions with histones cause chromatin disruption, loss of transcription, and nuclear condensation. The dying cells also show morphological changes compatible with macroautophagy, and recent studies indicate that macroautophagy is involved in the cell death response to HAMLET. The results suggest that HAMLET, like a hydra with many heads, may interact with several crucial cellular organelles, thereby activating several forms of cell death, in parallel. This complexity might underlie the rapid death response of tumor cells and the broad antitumor activity of HAMLET.

Causes of electrical deaths and injuries among construction workers.

Science.gov (United States)

McCann, Michael; Hunting, Katherine L; Murawski, Judith; Chowdhury, Risana; Welch, Laura

2003-04-01

Contact with electrical current is the fourth leading cause of deaths of construction workers. This study evaluates electrical deaths and injuries to construction workers. Two sources of data were analyzed in detail: (1) 1,019 electrical deaths identified by the Bureau of Labor Statistics, Census of Fatal Occupational Injuries (CFOI) for the years 1992-1998; and (2) 61 electrical injuries identified between November 1, 1990 and December 31, 1998 from a George Washington University Emergency Department injury surveillance database. Contact with "live" electrical wiring, equipment, and light fixtures was the main cause of electrical deaths and injuries among electrical workers, followed by contact with overhead power lines. Among non-electrical workers, contact with overhead power lines was the major cause of death. Other causes included contact with energized metal objects, machinery, power tools, and portable lights. Arc flash or blast caused 31% of electrical injuries among construction workers, but less than 2% of electrical deaths. Adoption of a lockout/tagout standard for construction, and training for non-electrical workers in basic electrical safety would reduce the risk of electrical deaths and injuries in construction. Further research is needed on ways to prevent electrical deaths and injuries while working "live". Copyright 2003 Wiley-Liss, Inc.

Prostate cancer, prostate cancer death, and death from other causes, among men with metabolic aberrations.

Science.gov (United States)

Häggström, Christel; Stocks, Tanja; Nagel, Gabriele; Manjer, Jonas; Bjørge, Tone; Hallmans, Göran; Engeland, Anders; Ulmer, Hanno; Lindkvist, Björn; Selmer, Randi; Concin, Hans; Tretli, Steinar; Jonsson, Håkan; Stattin, Pär

2014-11-01

Few previous studies of metabolic aberrations and prostate cancer risk have taken into account the fact that men with metabolic aberrations have an increased risk of death from causes other than prostate cancer. The aim of this study was to calculate, in a real-life scenario, the risk of prostate cancer diagnosis, prostate cancer death, and death from other causes. In the Metabolic Syndrome and Cancer Project, prospective data on body mass index, blood pressure, glucose, cholesterol, and triglycerides were collected from 285,040 men. Risks of prostate cancer diagnosis, prostate cancer death, and death from other causes were calculated by use of competing risk analysis for men with normal (bottom 84%) and high (top 16%) levels of each factor, and a composite score. During a mean follow-up period of 12 years, 5,893 men were diagnosed with prostate cancer, 1,013 died of prostate cancer, and 26,328 died of other causes. After 1996, when prostate-specific antigen testing was introduced, men up to age 80 years with normal metabolic levels had 13% risk of prostate cancer, 2% risk of prostate cancer death, and 30% risk of death from other causes, whereas men with metabolic aberrations had corresponding risks of 11%, 2%, and 44%. In contrast to recent studies using conventional survival analysis, in a real-world scenario taking risk of competing events into account, men with metabolic aberrations had lower risk of prostate cancer diagnosis, similar risk of prostate cancer death, and substantially higher risk of death from other causes compared with men who had normal metabolic levels.

Effects of epigallocatechin gallate on ultra-violet-induced cell death in PC12 cells

International Nuclear Information System (INIS)

Takahashi, Hideo; Seki, Sakiko; Sakamoto, Naotaka; Nakagawa, Shigeki

2002-01-01

We examined the effects of catechin on ultra-violet-induced cell death in PC12 cells. PC12 cells were irradiated by ultra-violet C (254 nm) (UVC). We found that the lactate dehydrogenase (LDH) activities in culture media and lipid peroxide in PC12 cells, which indicate cell death and cell membrane damage, respectively, were increased by UVC irradiation in a time-dependent manner. Cell death was gradually stimulated for 9 hours of cultivation after a UVC irradiation period of 10 or 30 min. Epigallocatechin gallate (EGCG), which is one of the main catechins found in green tea, suppressed the increase in LDH activity in culture medium and also inhibited the formation of lipid peroxide. IκB, a member of the cell death signaling system, was phosphorylated at 1 hour after 10 min of UVC irradiation. Stimulation of phosphorylation of IκB by UVC was suppressed by the addition of EGCG. We concluded that EGCG protects the PC12 cell from cell damage caused by UVC irradiation. (author)

Pregnancy-associated Death - Clarifying the Cause of Death and Medico-legal Assessments in Accusations of Malpractice.

Science.gov (United States)

Dettmeyer, Reinhard; Lang, Juliane; Amberg, Rainer; Zedler, Barbara; Schulz, Ronald; Birngruber, Christoph

2018-02-01

Pregnancy-associated deaths are extremely rare in Germany. Most deaths are from natural causes, and a range of causes are possible. The deaths of 22 women who died of pregnancy-associated causes and who were autopsied in the Institute of Forensic Medicine of Justus-Liebig University Gießen between 1992 and 2016 were analyzed. The autopsy results and histological examinations for the majority of women who died of pregnancy-associated causes between 1992 and 2016 showed that they had died of natural causes, although complications of pregnancy were a leading cause of death. The death of a pregnant woman should not automatically raise the suspicion of malpractice, although the question does arise in cases of bleeding complications only detected at very late stages. Experts must prove that a real mistake was made during treatment and provide evidence of the causality between malpractice and patient death. Particularly when well-known complications of pregnancy were present, this is only the case if poor monitoring resulted in the complication being detected too late or if treatment was not in accordance with accepted standards of care. The majority of pregnancy-associated deaths are from natural causes and the death of a pregnant woman does not mean that medical malpractice was involved, although this accusation is often levelled in cases where rupture was not immediately diagnosed or in cases of fatal postpartum hemorrhage.

UV-Induced Cell Death in Plants

Science.gov (United States)

Nawkar, Ganesh M.; Maibam, Punyakishore; Park, Jung Hoon; Sahi, Vaidurya Pratap; Lee, Sang Yeol; Kang, Chang Ho

2013-01-01

Plants are photosynthetic organisms that depend on sunlight for energy. Plants respond to light through different photoreceptors and show photomorphogenic development. Apart from Photosynthetically Active Radiation (PAR; 400–700 nm), plants are exposed to UV light, which is comprised of UV-C (below 280 nm), UV-B (280–320 nm) and UV-A (320–390 nm). The atmospheric ozone layer protects UV-C radiation from reaching earth while the UVR8 protein acts as a receptor for UV-B radiation. Low levels of UV-B exposure initiate signaling through UVR8 and induce secondary metabolite genes involved in protection against UV while higher dosages are very detrimental to plants. It has also been reported that genes involved in MAPK cascade help the plant in providing tolerance against UV radiation. The important targets of UV radiation in plant cells are DNA, lipids and proteins and also vital processes such as photosynthesis. Recent studies showed that, in response to UV radiation, mitochondria and chloroplasts produce a reactive oxygen species (ROS). Arabidopsis metacaspase-8 (AtMC8) is induced in response to oxidative stress caused by ROS, which acts downstream of the radical induced cell death (AtRCD1) gene making plants vulnerable to cell death. The studies on salicylic and jasmonic acid signaling mutants revealed that SA and JA regulate the ROS level and antagonize ROS mediated cell death. Recently, molecular studies have revealed genes involved in response to UV exposure, with respect to programmed cell death (PCD). PMID:23344059

Cell Death in C. elegans Development.

Science.gov (United States)

Malin, Jennifer Zuckerman; Shaham, Shai

2015-01-01

Cell death is a common and important feature of animal development, and cell death defects underlie many human disease states. The nematode Caenorhabditis elegans has proven fertile ground for uncovering molecular and cellular processes controlling programmed cell death. A core pathway consisting of the conserved proteins EGL-1/BH3-only, CED-9/BCL2, CED-4/APAF1, and CED-3/caspase promotes most cell death in the nematode, and a conserved set of proteins ensures the engulfment and degradation of dying cells. Multiple regulatory pathways control cell death onset in C. elegans, and many reveal similarities with tumor formation pathways in mammals, supporting the idea that cell death plays key roles in malignant progression. Nonetheless, a number of observations suggest that our understanding of developmental cell death in C. elegans is incomplete. The interaction between dying and engulfing cells seems to be more complex than originally appreciated, and it appears that key aspects of cell death initiation are not fully understood. It has also become apparent that the conserved apoptotic pathway is dispensable for the demise of the C. elegans linker cell, leading to the discovery of a previously unexplored gene program promoting cell death. Here, we review studies that formed the foundation of cell death research in C. elegans and describe new observations that expand, and in some cases remodel, this edifice. We raise the possibility that, in some cells, more than one death program may be needed to ensure cell death fidelity. © 2015 Elsevier Inc. All rights reserved.

[Maternal deaths due to infectious cause, results from the French confidential enquiry into maternal deaths, 2010-2012].

Science.gov (United States)

Rigouzzo, A; Tessier, V; Zieleskiewicz, L

2017-12-01

Over the period 2010-2012, maternal mortality from infectious causes accounted for 5% of maternal deaths by direct causes and 16% of maternal deaths by indirect causes. Among the 22 deaths caused by infection occurred during this period, 6 deaths were attributed to direct causes from genital tract origin, confirming thus the decrease in direct maternal deaths by infection during the last ten years. On the contrary, indirect maternal deaths by infection, from extragenital origin, doubled during the same period, with 16 deaths in the last triennium, dominated by winter respiratory infections, particularly influenza: the 2009-2010 influenza A (H1N1) virus pandemic was the leading cause of indirect maternal mortality by infection during the studied period. The main infectious agents involved in maternal deaths from direct causes were Streptococcus A, Escherichia Coli and Clostridium perfringens: these bacterias were responsible for toxic shock syndrome, severe sepsis, secondary in some cases to cellulitis or necrotizing fasciitis. Of the 6 deaths due to direct infection, 4 were considered avoidable because of inadequate management: delayed or missed diagnosis, delayed or inadequate initiation of a specific medical and/or surgical treatment. Of the 16 indirect maternal deaths due to infection causes, the most often involved infectious agents were influenza A (H1N1) virus and Streptococcus pneumonia with induced purpura fulminans: the absence of influenza vaccination during pregnancy, delayed diagnosis and emergency initiation of a specific treatment, were the main contributory factors to these deaths and their avoidability in 70% of the cases analyzed. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Causes of Death According to Death Certificates in Individuals with Dementia: A Cohort from the Swedish Dementia Registry.

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Garcia-Ptacek, Sara; Kåreholt, Ingemar; Cermakova, Pavla; Rizzuto, Debora; Religa, Dorota; Eriksdotter, Maria

2016-11-01

The causes of death in dementia are not established, particularly in rarer dementias. The aim of this study is to calculate risk of death from specific causes for a broader spectrum of dementia diagnoses. Cohort study. Swedish Dementia Registry (SveDem), 2007-2012. Individuals with incident dementia registered in SveDem (N = 28,609); median follow-up 741 days. Observed deaths were 5,368 (19%). Information on number of deaths and causes of mortality was obtained from death certificates. Odds ratios for the presence of dementia on death certificates were calculated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox hazards regression for cause-specific mortality, using Alzheimer's dementia (AD) as reference. Hazard ratios for death for each specific cause of death were compared with hazard ratios of death from all causes (P-values from t-tests). The most frequent underlying cause of death in this cohort was cardiovascular (37%), followed by dementia (30%). Dementia and cardiovascular causes appeared as main or contributory causes on 63% of certificates, followed by respiratory (26%). Dementia was mentioned less in vascular dementia (VaD; 57%). Compared to AD, cardiovascular mortality was higher in individuals with VaD than in those with AD (HR = 1.82, 95% CI = 1.64-2.02). Respiratory death was higher in individuals with Lewy body dementia (LBD, including Parkinson's disease dementia and dementia with Lewy bodies, HR = 2.16, 95% CI = 1.71-2.71), and the risk of respiratory death was higher than expected from the risk for all-cause mortality. Participants with frontotemporal dementia were more likely to die from external causes of death than those with AD (HR = 2.86, 95% CI = 1.53-5.32). Dementia is underreported on death certificates as main and contributory causes. Individuals with LBD had a higher risk of respiratory death than those with AD. © 2016 The Authors. The Journal of the American Geriatrics Society published by Wiley

Causes of death among full term stillbirths and early neonatal deaths in the Region of Southern Denmark.

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Basu, Millie Nguyen; Johnsen, Iben Birgit Gade; Wehberg, Sonja; Sørensen, Rikke Guldberg; Barington, Torben; Nørgård, Bente Mertz

2018-02-23

We examined the causes of death amongst full term stillbirths and early neonatal deaths. Our cohort includes women in the Region of Southern Denmark, who gave birth at full term to a stillborn infant or a neonate who died within the first 7 days from 2010 through 2014. Demographic, biometric and clinical variables were analyzed to assess the causes of death using two classification systems: causes of death and associated conditions (CODAC) and a Danish system based on initial causes of fetal death (INCODE). A total of 95 maternal-infant cases were included. Using the CODAC and INCODE classification systems, we found that the causes of death were unknown in 59/95 (62.1%). The second most common cause of death in CODAC was congenital anomalies in 10/95 (10.5%), similar to INCODE with fetal, genetic, structural and karyotypic anomalies in 11/95 (11.6%). The majority of the mothers were healthy, primiparous, non-smokers, aged 20-34 years and with a normal body mass index (BMI). Based on an unselected cohort from an entire region in Denmark, the cause of stillbirth and early neonatal deaths among full term infants remained unknown for the vast majority.

Leading Causes of Death among Asian American Subgroups (2003-2011.

Directory of Open Access Journals (Sweden)

Katherine G Hastings

Full Text Available Our current understanding of Asian American mortality patterns has been distorted by the historical aggregation of diverse Asian subgroups on death certificates, masking important differences in the leading causes of death across subgroups. In this analysis, we aim to fill an important knowledge gap in Asian American health by reporting leading causes of mortality by disaggregated Asian American subgroups.We examined national mortality records for the six largest Asian subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese and non-Hispanic Whites (NHWs from 2003-2011, and ranked the leading causes of death. We calculated all-cause and cause-specific age-adjusted rates, temporal trends with annual percent changes, and rate ratios by race/ethnicity and sex. Rankings revealed that as an aggregated group, cancer was the leading cause of death for Asian Americans. When disaggregated, there was notable heterogeneity. Among women, cancer was the leading cause of death for every group except Asian Indians. In men, cancer was the leading cause of death among Chinese, Korean, and Vietnamese men, while heart disease was the leading cause of death among Asian Indians, Filipino and Japanese men. The proportion of death due to heart disease for Asian Indian males was nearly double that of cancer (31% vs. 18%. Temporal trends showed increased mortality of cancer and diabetes in Asian Indians and Vietnamese; increased stroke mortality in Asian Indians; increased suicide mortality in Koreans; and increased mortality from Alzheimer's disease for all racial/ethnic groups from 2003-2011. All-cause rate ratios revealed that overall mortality is lower in Asian Americans compared to NHWs.Our findings show heterogeneity in the leading causes of death among Asian American subgroups. Additional research should focus on culturally competent and cost-effective approaches to prevent and treat specific diseases among these growing diverse populations.

Leading Causes of Death among Asian American Subgroups (2003-2011).

Science.gov (United States)

Hastings, Katherine G; Jose, Powell O; Kapphahn, Kristopher I; Frank, Ariel T H; Goldstein, Benjamin A; Thompson, Caroline A; Eggleston, Karen; Cullen, Mark R; Palaniappan, Latha P

2015-01-01

Our current understanding of Asian American mortality patterns has been distorted by the historical aggregation of diverse Asian subgroups on death certificates, masking important differences in the leading causes of death across subgroups. In this analysis, we aim to fill an important knowledge gap in Asian American health by reporting leading causes of mortality by disaggregated Asian American subgroups. We examined national mortality records for the six largest Asian subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) and non-Hispanic Whites (NHWs) from 2003-2011, and ranked the leading causes of death. We calculated all-cause and cause-specific age-adjusted rates, temporal trends with annual percent changes, and rate ratios by race/ethnicity and sex. Rankings revealed that as an aggregated group, cancer was the leading cause of death for Asian Americans. When disaggregated, there was notable heterogeneity. Among women, cancer was the leading cause of death for every group except Asian Indians. In men, cancer was the leading cause of death among Chinese, Korean, and Vietnamese men, while heart disease was the leading cause of death among Asian Indians, Filipino and Japanese men. The proportion of death due to heart disease for Asian Indian males was nearly double that of cancer (31% vs. 18%). Temporal trends showed increased mortality of cancer and diabetes in Asian Indians and Vietnamese; increased stroke mortality in Asian Indians; increased suicide mortality in Koreans; and increased mortality from Alzheimer's disease for all racial/ethnic groups from 2003-2011. All-cause rate ratios revealed that overall mortality is lower in Asian Americans compared to NHWs. Our findings show heterogeneity in the leading causes of death among Asian American subgroups. Additional research should focus on culturally competent and cost-effective approaches to prevent and treat specific diseases among these growing diverse populations.

NCHS - Leading Causes of Death: United States

Data.gov (United States)

U.S. Department of Health & Human Services — This dataset presents the age-adjusted death rates for the 10 leading causes of death in the United States beginning in 1999. Data are based on information from all...

The influence of the surface chemistry of silver nanoparticles on cell death

International Nuclear Information System (INIS)

Sur, Ilknur; Altunbek, Mine; Kahraman, Mehmet; Culha, Mustafa

2012-01-01

The influence of the surface chemistry of silver nanoparticles (AgNPs) on p53 mediated cell death was evaluated using human dermal fibroblast (HDF) and lung cancer (A549) cells. The citrate reduced AgNPs (C-AgNPs) were modified with either lactose (L-AgNPs) or a 12-base long oligonucleotide (O-AgNPs). Both unmodified and modified AgNPs showed increased concentration and time dependent cytotoxicity and genotoxicity causing an increased p53 up-regulation within 6 h and led to apoptotic or necrotic cell deaths. The C-AgNPs induced more cytotoxicity and cellular DNA damage than the surface modified AgNPs. Modifying the C-AgNPs with lactose or the oligonucleotide reduced both necrotic and apoptotic cell deaths in the HDF cells. The C-AgNPs caused an insignificant necrosis in A549 cells whereas the modified AgNPs caused necrosis and apoptosis in both cell types. Compared to the O-AgNPs, the L-AgNPs triggered more cellular DNA damage, which led to up-regulation of p53 gene inducing apoptosis in A549 cells compared to HDF cells. This suggests that the different surface chemistries of the AgNPs cause different cellular responses that may be important not only for their use in medicine but also for reducing their toxicity. (paper)

Apoptosis-inducing factor plays a critical role in caspase-independent, pyknotic cell death in hydrogen peroxide-exposed cells.

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Son, Young-Ok; Jang, Yong-Suk; Heo, Jung-Sun; Chung, Wan-Tae; Choi, Ki-Choon; Lee, Jeong-Chae

2009-06-01

It has been proposed that continuously generated hydrogen peroxide (H(2)O(2)) inhibits typical apoptosis and instead initiates an alternate, apoptosis-inducing factor (AIF)-dependent process. Aside from the role of AIF, however, the detailed morphological characterization of H(2)O(2)-induced cell death is not complete. This study examined the cellular mechanism(s) by which the continuous presence of H(2)O(2) induces cell death. We also further analyzed the precise role of AIF by inhibiting its expression with siRNA. Exposure of cells to H(2)O(2) generated by glucose oxidase caused mitochondrion-mediated, caspase-independent cell death. In addition, H(2)O(2) exposure resulted in cell shrinkage and chromatin condensation without nuclear fragmentation, indicating that H(2)O(2) stimulates a pyknotic cell death. Further analysis of AIF-transfected cells clearly demonstrated that nuclear translocation of AIF is the most important event required for nuclear condensation, phosphatidyl serine translocation, and ultimately cell death in H(2)O(2)-exposed cells. Furthermore, ATP was rapidly and severely depleted in cells exposed to H(2)O(2) generated by glucose oxidase but not by H(2)O(2) added as a bolus. Suppression of the H(2)O(2)-mediated ATP depletion by 3-aminobenzamide led to a significant increase of nuclear fragmentation in glucose oxidase-exposed cells. Collectively, these findings suggest that an acute energy reduction by H(2)O(2) causes caspase-independent and AIF-dependent cell death.

Top 10 Causes of Death in the World

Science.gov (United States)

... the-top-10-causes-of-death","@context":"http://schema.org","@type":"Article"}; العربية 中文 français русский español ... income countries have systems in place for collecting information on causes of death. Many low- and middle- ...

Causes of death among full term stillbirths and early neonatal deaths in the Region of Southern Denmark

DEFF Research Database (Denmark)

Basu, Millie; Johnsen, Iben Birgit Gade; Wehberg, Sonja

2018-01-01

OBJECTIVE: We examined the causes of death amongst full term stillbirths and early neonatal deaths. METHODS: Our cohort includes women in the Region of Southern Denmark, who gave birth at full term to a stillborn infant or a neonate who died within the first 7 days from 2010 through 2014. Demogra......OBJECTIVE: We examined the causes of death amongst full term stillbirths and early neonatal deaths. METHODS: Our cohort includes women in the Region of Southern Denmark, who gave birth at full term to a stillborn infant or a neonate who died within the first 7 days from 2010 through 2014....... Demographic, biometric and clinical variables were analyzed to assess the causes of death using two classification systems: causes of death and associated conditions (CODAC) and a Danish system based on initial causes of fetal death (INCODE). RESULTS: A total of 95 maternal-infant cases were included. Using...

Causes of adult female deaths in Bangladesh: findings from two National Surveys.

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Nahar, Quamrun; El Arifeen, Shams; Jamil, Kanta; Streatfield, Peter Kim

2015-09-18

Assessment of causes of death and changes in pattern of causes of death over time are needed for programmatic purposes. Limited national level data exist on the adult female causes of death in Bangladesh. Using data from two nationally representation surveys, the 2001 and 2010 Bangladesh Maternal Mortality Surveys (BMMS), the paper examines the causes of adult female death, aged 15-49 years, and changes in the patterns of these deaths. In both surveys, all household deaths three years prior to the survey were identified. Adult female deaths were then followed by a verbal autopsy (VA) using the WHO structured questionnaire. Two physicians independently reviewed the VA forms to assign a cause of death using the ICD-10; in case of disagreement, a third physician made an independent review and assigned a cause of death. The overall mortality rates for women aged 15-49 in 2001 and 2010 were 182 per 100,000 and 120 per 100,000 respectively. There is a shift in the pattern of causes of death during the period covered by the two surveys. In the 2001 survey, the main causes of death were maternal (20 %), followed by diseases of the circulatory system (15 %), malignancy (14 %) and infectious diseases (13 %). However, in the 2010 survey, malignancies were the leading cause (21 %), followed by diseases of the circulatory system (16 %), maternal causes (14 %) and infectious diseases (8 %). While maternal deaths remained the number one cause of death among 20-34 years old in both surveys, unnatural deaths were the main cause for teenage deaths, and malignancies were the main cause of death for older women. Although there is an increasing trend in the proportion of women who died in hospitals, in both surveys most women died at home (74 % in 2001 and 62 % in 2010). The shift in the pattern of causes of adult female deaths is in agreement with the overall change in the disease pattern from communicable to non-communicable diseases in Bangladesh. Suicide and other violent deaths as

Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection

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Doitsh, Gilad; Galloway, Nicole L. K.; Geng, Xin; Yang, Zhiyuan; Monroe, Kathryn M.; Zepeda, Orlando; Hunt, Peter W.; Hatano, Hiroyu; Sowinski, Stefanie; Muñoz-Arias, Isa; Greene, Warner C.

2014-01-01

The pathway causing CD4 T-cell death in HIV-infected hosts remains poorly understood although apoptosis has been proposed as a key mechanism. We now show that caspase-3-mediated apoptosis accounts for the death of only a small fraction of CD4 T cells corresponding to those that are both activated and productively infected. The remaining over 95% of quiescent lymphoid CD4 T cells die by caspase-1-mediated pyroptosis triggered by abortive viral infection. Pyroptosis corresponds to an intensely inflammatory form of programmed cell death in which cytoplasmic contents and pro-inflammatory cytokines, including IL-1β, are released. This death pathway thus links the two signature events in HIV infection--CD4 T-cell depletion and chronic inflammation--and creates a pathogenic vicious cycle in which dying CD4 T cells release inflammatory signals that attract more cells to die. This cycle can be broken by caspase 1 inhibitors shown to be safe in humans, raising the possibility of a new class of `anti-AIDS' therapeutics targeting the host rather than the virus.

Programmed cell death

Energy Technology Data Exchange (ETDEWEB)

NONE

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.

Methylglyoxal-bis(guanylhydrazone), a polyamine analogue, sensitized γ-radiation-induced cell death in HL-60 leukemia cells Sensitizing effect of MGBG on γ-radiation-induced cell death.

Science.gov (United States)

Kim, Jin Sik; Lee, Jin; Chung, Hai Won; Choi, Han; Paik, Sang Gi; Kim, In Gyu

2006-09-01

Methylglyoxal-bis(guanylhydrazone) (MGBG), a polyamine analogue, has been known to inhibit the biosynthesis of polyamines, which are important in cell proliferation. We showed that MGBG treatment significantly affected γ-radiation-induced cell cycle transition (G(1)/G(0)→S→G(2)/M) and thus γ-radiation-induced cell death. As determined by micronuclei and comet assay, we showed that it sensitized the cytotoxic effect induced by γ-radiation. One of the reasons is that polyamine depletion by MGBG treatment did not effectively protect against the chemical (OH) or physical damage to DNA caused by γ-radiation. Through in vitro experiment, we confirmed that DNA strand breaks induced by γ-radiation was prevented more effectively in the presence of polyamines (spermine and spermidine) than in the absence of polyamines. MGBG also blocks the cell cycle transition caused by γ-radiation (G(2) arrest), which helps protect cells by allowing time for DNA repair before entry into mitosis or apoptosis, via the down regulation of cyclin D1, which mediates the transition from G(1) to S phase of cell cycle, and ataxia telangiectasia mutated, which is involved in the DNA sensing, repair and cell cycle check point. Therefore, the abrogation of G(2) arrest sensitizes cells to the effect of γ-radiation. As a result, γ-radiation-induced cell death increased by about 2.5-3.0-fold in cells treated with MGBG. However, exogenous spermidine supplement partially relieved this γ-radiation-induced cytotoxicity and cell death. These findings suggest a potentially therapeutic strategy for increasing the cytotoxic efficacy of γ-radiation.

Stem cell death and survival in heart regeneration and repair.

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Abdelwahid, Eltyeb; Kalvelyte, Audrone; Stulpinas, Aurimas; de Carvalho, Katherine Athayde Teixeira; Guarita-Souza, Luiz Cesar; Foldes, Gabor

2016-03-01

Cardiovascular diseases are major causes of mortality and morbidity. Cardiomyocyte apoptosis disrupts cardiac function and leads to cardiac decompensation and terminal heart failure. Delineating the regulatory signaling pathways that orchestrate cell survival in the heart has significant therapeutic implications. Cardiac tissue has limited capacity to regenerate and repair. Stem cell therapy is a successful approach for repairing and regenerating ischemic cardiac tissue; however, transplanted cells display very high death percentage, a problem that affects success of tissue regeneration. Stem cells display multipotency or pluripotency and undergo self-renewal, however these events are negatively influenced by upregulation of cell death machinery that induces the significant decrease in survival and differentiation signals upon cardiovascular injury. While efforts to identify cell types and molecular pathways that promote cardiac tissue regeneration have been productive, studies that focus on blocking the extensive cell death after transplantation are limited. The control of cell death includes multiple networks rather than one crucial pathway, which underlies the challenge of identifying the interaction between various cellular and biochemical components. This review is aimed at exploiting the molecular mechanisms by which stem cells resist death signals to develop into mature and healthy cardiac cells. Specifically, we focus on a number of factors that control death and survival of stem cells upon transplantation and ultimately affect cardiac regeneration. We also discuss potential survival enhancing strategies and how they could be meaningful in the design of targeted therapies that improve cardiac function.

Childhood deaths from external causes in Estonia, 2001–2005

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Väli, Marika; Lang, Katrin; Soonets, Ruth; Talumäe, Marika; Grjibovski, Andrej M

2007-01-01

Background In 2000, the overall rate of injury deaths in children aged 0–14 was 28.7 per 100000 in Estonia, which is more than 5 times higher than the corresponding rate in neighbouring Finland. This paper describes childhood injury mortality in Estonia by cause and age groups, and validates registration of these deaths in the Statistical Office of Estonia against the autopsy data. Methods The data on causes of all child deaths in Estonia in 2001–2005 were abstracted from the autopsy protocols at the Estonian Bureau of Forensic Medicine. Average annual mortality rates per 100,000 were calculated. Coverage (proportion of the reported injury deaths from the total number of injury deaths) and accuracy (proportion of correctly classified injury deaths) of the registration of causes of death in Statistical Office of Estonia were assessed by comparing the Statistical Office of Estonia data with the data from Estonian Bureau of Forensic Medicine. Results Average annual mortality from external causes in 0–14 years-old children in Estonia was 19.1 per 100,000. Asphyxia and transport accidents were the major killers followed by poisoning and suicides. Relative contribution of these causes varied greatly between age groups. Intent of death was unknown for more than 10% of injury deaths. Coverage and accuracy of registration of injury deaths by Statistical Office of Estonia were 91.5% and 95.3%, respectively. Conclusion Childhood mortality from injuries in Estonia is among the highest in the EU. The number of injury deaths in Statistical Office of Estonia is slightly underestimated mostly due to misclassification for deaths from diseases. Accuracy of the Statistical Office of Estonia data was high with some underestimation of intentional deaths. Moreover, high proportion of death with unknown intent suggests underestimation of intentional deaths. Reduction of injury deaths should be given a high priority in Estonia. More information on circumstances around death is

Childhood deaths from external causes in Estonia, 2001–2005

Directory of Open Access Journals (Sweden)

Soonets Ruth

2007-07-01

Full Text Available Abstract Background In 2000, the overall rate of injury deaths in children aged 0–14 was 28.7 per 100000 in Estonia, which is more than 5 times higher than the corresponding rate in neighbouring Finland. This paper describes childhood injury mortality in Estonia by cause and age groups, and validates registration of these deaths in the Statistical Office of Estonia against the autopsy data. Methods The data on causes of all child deaths in Estonia in 2001–2005 were abstracted from the autopsy protocols at the Estonian Bureau of Forensic Medicine. Average annual mortality rates per 100,000 were calculated. Coverage (proportion of the reported injury deaths from the total number of injury deaths and accuracy (proportion of correctly classified injury deaths of the registration of causes of death in Statistical Office of Estonia were assessed by comparing the Statistical Office of Estonia data with the data from Estonian Bureau of Forensic Medicine. Results Average annual mortality from external causes in 0–14 years-old children in Estonia was 19.1 per 100,000. Asphyxia and transport accidents were the major killers followed by poisoning and suicides. Relative contribution of these causes varied greatly between age groups. Intent of death was unknown for more than 10% of injury deaths. Coverage and accuracy of registration of injury deaths by Statistical Office of Estonia were 91.5% and 95.3%, respectively. Conclusion Childhood mortality from injuries in Estonia is among the highest in the EU. The number of injury deaths in Statistical Office of Estonia is slightly underestimated mostly due to misclassification for deaths from diseases. Accuracy of the Statistical Office of Estonia data was high with some underestimation of intentional deaths. Moreover, high proportion of death with unknown intent suggests underestimation of intentional deaths. Reduction of injury deaths should be given a high priority in Estonia. More information on

Sensory hair cell death and regeneration in fishes

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Jerry D. Monroe

2015-04-01

Full Text Available Sensory hair cells are specialized mechanotransductive receptors required for hearing and vestibular function. Loss of hair cells in humans and other mammals is permanent and causes reduced hearing and balance. In the early 1980’s, it was shown that hair cells continue to be added to the inner ear sensory epithelia in cartilaginous and bony fishes. Soon thereafter, hair cell regeneration was documented in the chick cochlea following acoustic trauma. Since then, research using chick and other avian models has led to great insights into hair cell death and regeneration. However, with the rise of the zebrafish as a model organism for studying disease and developmental processes, there has been an increased interest in studying sensory hair cell death and regeneration in its lateral line and inner ears. Advances derived from studies in zebrafish and other fish species include understanding the effect of ototoxins on hair cells and finding otoprotectants to mitigate ototoxin damage, the role of cellular proliferation versus direct transdifferentiation during hair cell regeneration, and elucidating cellular pathways involved in the regeneration process. This review will summarize research on hair cell death and regeneration using fish models, indicate the potential strengths and weaknesses of these models, and discuss several emerging areas of future studies.

The shape of the global causes of death

Directory of Open Access Journals (Sweden)

Dorling Danny

2007-10-01

Full Text Available Abstract Background World maps can provide an instant visual overview of the distribution of diseases and deaths. Results There is a particular geography to each type of death: in some places many thousands of deaths are caused by a particular condition, whilst other equally populous areas have few to no deaths from the same cause. Conclusion Physicians and other health professionals often specialise in the specifics of causes, symptoms and effects. For some practitioners gaining a worldview of disease burden complements smaller scale medical knowledge of where and how people are affected by each condition. Maps can make health related information much more accessible to planners and the general public than can tables, text, or even graphs. Ten cartograms based on World Health Organisation Burden of Disease data are introduced here; alongside seven based on data from other sources. The Burden of Disease cartograms are the latest in a much larger collection of social, economic and health world maps.

Leading Causes of Death in Males United States, 2010

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... What’s this? Submit What’s this? Submit Button Leading Causes of Death in Males and Females, United States Recommend on ... to current and previous listings for the leading causes of death for males and females in the United States. ...

Exposure to Inorganic Mercury Causes Oxidative Stress, Cell Death, and Functional Deficits in the Motor Cortex.

Science.gov (United States)

Teixeira, Francisco B; de Oliveira, Ana C A; Leão, Luana K R; Fagundes, Nathália C F; Fernandes, Rafael M; Fernandes, Luanna M P; da Silva, Márcia C F; Amado, Lilian L; Sagica, Fernanda E S; de Oliveira, Edivaldo H C; Crespo-Lopez, Maria E; Maia, Cristiane S F; Lima, Rafael R

2018-01-01

Mercury is a toxic metal that can be found in the environment in three different forms - elemental, organic and inorganic. Inorganic mercury has a lower liposolubility, which results in a lower organism absorption and reduced passage through the blood-brain barrier. For this reason, exposure models that use inorganic mercury in rats in order to evaluate its effects on the central nervous system are rare, especially in adult subjects. This study investigated if a chronic exposure to low doses of mercury chloride (HgCl2), an inorganic form of mercury, is capable of promoting motor alterations and neurodegenerative in the motor cortex of adult rats. Forty animals were exposed to a dose of 0.375 mg/kg/day, for 45 days. They were then submitted to motor evaluation and euthanized to collect the motor cortex. Measurement of mercury deposited in the brain parenchyma, evaluation of oxidative balance, quantification of cellular cytotoxicity and apoptosis and density of mature neurons and astrocytes of the motor cortex were performed. It was observed that chronic exposure to inorganic mercury caused a decrease in balance and fine motor coordination, formation of mercury deposits and oxidative stress verified by the increase of lipoperoxidation and nitrite concentration and a decrease of the total antioxidant capacity. In addition, we found that this model of exposure to inorganic mercury caused cell death by cytotoxicity and induction of apoptosis with a decreased number of neurons and astrocytes in the motor cortex. Our results provide evidence that exposure to inorganic mercury in low doses, even in spite of its poor ability to cross biological barriers, is still capable of inducing motor deficits, cell death by cytotoxicity and apoptosis, and oxidative stress in the motor cortex of adult rats.

Exposure to Inorganic Mercury Causes Oxidative Stress, Cell Death, and Functional Deficits in the Motor Cortex

Directory of Open Access Journals (Sweden)

Francisco B. Teixeira

2018-05-01

Full Text Available Mercury is a toxic metal that can be found in the environment in three different forms – elemental, organic and inorganic. Inorganic mercury has a lower liposolubility, which results in a lower organism absorption and reduced passage through the blood–brain barrier. For this reason, exposure models that use inorganic mercury in rats in order to evaluate its effects on the central nervous system are rare, especially in adult subjects. This study investigated if a chronic exposure to low doses of mercury chloride (HgCl2, an inorganic form of mercury, is capable of promoting motor alterations and neurodegenerative in the motor cortex of adult rats. Forty animals were exposed to a dose of 0.375 mg/kg/day, for 45 days. They were then submitted to motor evaluation and euthanized to collect the motor cortex. Measurement of mercury deposited in the brain parenchyma, evaluation of oxidative balance, quantification of cellular cytotoxicity and apoptosis and density of mature neurons and astrocytes of the motor cortex were performed. It was observed that chronic exposure to inorganic mercury caused a decrease in balance and fine motor coordination, formation of mercury deposits and oxidative stress verified by the increase of lipoperoxidation and nitrite concentration and a decrease of the total antioxidant capacity. In addition, we found that this model of exposure to inorganic mercury caused cell death by cytotoxicity and induction of apoptosis with a decreased number of neurons and astrocytes in the motor cortex. Our results provide evidence that exposure to inorganic mercury in low doses, even in spite of its poor ability to cross biological barriers, is still capable of inducing motor deficits, cell death by cytotoxicity and apoptosis, and oxidative stress in the motor cortex of adult rats.

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018

NARCIS (Netherlands)

Galluzzi, Lorenzo; Vitale, Ilio; Aaronson, Stuart A.; Abrams, John M.; Adam, Dieter; Agostinis, Patrizia; Alnemri, Emad S.; Altucci, Lucia; Amelio, Ivano; Andrews, David W.; Annicchiarico-Petruzzelli, Margherita; Antonov, Alexey V.; Arama, Eli; Baehrecke, Eric H.; Barlev, Nickolai A.; Bazan, Nicolas G.; Bernassola, Francesca; Bertrand, Mathieu J. M.; Bianchi, Katiuscia; Blagosklonny, Mikhail V.; Blomgren, Klas; Borner, Christoph; Boya, Patricia; Brenner, Catherine; Campanella, Michelangelo; Candi, Eleonora; Carmona-Gutierrez, Didac; Cecconi, Francesco; Chan, Francis K.-M.; Chandel, Navdeep S.; Cheng, Emily H.; Chipuk, Jerry E.; Cidlowski, John A.; Ciechanover, Aaron; Cohen, Gerald M.; Conrad, Marcus; Cubillos-Ruiz, Juan R.; Czabotar, Peter E.; D'Angiolella, Vincenzo; Dawson, Ted M.; Dawson, Valina L.; de Laurenzi, Vincenzo; de Maria, Ruggero; Debatin, Klaus-Michael; DeBerardinis, Ralph J.; Deshmukh, Mohanish; Di Daniele, Nicola; Di Virgilio, Francesco; Dixit, Vishva M.; Dixon, Scott J.; Duckett, Colin S.; Dynlacht, Brian D.; El-Deiry, Wafik S.; Elrod, John W.; Fimia, Gian Maria; Fulda, Simone; García-Sáez, Ana J.; Garg, Abhishek D.; Garrido, Carmen; Gavathiotis, Evripidis; Golstein, Pierre; Gottlieb, Eyal; Green, Douglas R.; Greene, Lloyd A.; Gronemeyer, Hinrich; Gross, Atan; Hajnoczky, Gyorgy; Hardwick, J. Marie; Harris, Isaac S.; Hengartner, Michael O.; Hetz, Claudio; Ichijo, Hidenori; Jäättelä, Marja; Joseph, Bertrand; Jost, Philipp J.; Juin, Philippe P.; Kaiser, William J.; Karin, Michael; Kaufmann, Thomas; Kepp, Oliver; Kimchi, Adi; Kitsis, Richard N.; Klionsky, Daniel J.; Knight, Richard A.; Kumar, Sharad; Lee, Sam W.; Lemasters, John J.; Levine, Beth; Linkermann, Andreas; Lipton, Stuart A.; Lockshin, Richard A.; López-Otín, Carlos; Lowe, Scott W.; Luedde, Tom; Lugli, Enrico; MacFarlane, Marion; Madeo, Frank; Malewicz, Michal; Malorni, Walter; Manic, Gwenola; Marine, Jean-Christophe; Martin, Seamus J.; Martinou, Jean-Claude; Medema, Jan Paul; Mehlen, Patrick; Meier, Pascal; Melino, Sonia; Miao, Edward A.; Molkentin, Jeffery D.; Moll, Ute M.; Muñoz-Pinedo, Cristina; Nagata, Shigekazu; Nuñez, Gabriel; Oberst, Andrew; Oren, Moshe; Overholtzer, Michael; Pagano, Michele; Panaretakis, Theocharis; Pasparakis, Manolis; Penninger, Josef M.; Pereira, David M.; Pervaiz, Shazib; Peter, Marcus E.; Piacentini, Mauro; Pinton, Paolo; Prehn, Jochen H. M.; Puthalakath, Hamsa; Rabinovich, Gabriel A.; Rehm, Markus; Rizzuto, Rosario; Rodrigues, Cecilia M. P.; Rubinsztein, David C.; Rudel, Thomas; Ryan, Kevin M.; Sayan, Emre; Scorrano, Luca; Shao, Feng; Shi, Yufang; Silke, John; Simon, Hans-Uwe; Sistigu, Antonella; Stockwell, Brent R.; Strasser, Andreas; Szabadkai, Gyorgy; Tait, Stephen W. G.; Tang, Daolin; Tavernarakis, Nektarios; Thorburn, Andrew; Tsujimoto, Yoshihide; Turk, Boris; Vanden Berghe, Tom; Vandenabeele, Peter; Vander Heiden, Matthew G.; Villunger, Andreas; Virgin, Herbert W.; Vousden, Karen H.; Vucic, Domagoj; Wagner, Erwin F.; Walczak, Henning; Wallach, David; Wang, Ying; Wells, James A.; Wood, Will; Yuan, Junying; Zakeri, Zahra; Zhivotovsky, Boris; Zitvogel, Laurence; Melino, Gerry; Kroemer, Guido

2018-01-01

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell

Certified causes of death in patients with mesothelioma in South East England

Directory of Open Access Journals (Sweden)

Peto Julian

2009-01-01

Full Text Available Abstract Background Mesothelioma is a highly fatal cancer that is caused by exposure to asbestos fibres. In many populations, the occurrence of mesothelioma is monitored with the use of mortality data from death certification. We examine certified causes of death of patients who have been diagnosed with mesothelioma, and assess the validity of death certification data as a proxy for mesothelioma incidence. Methods We extracted mesothelioma registrations in the South East of England area between 2000 and 2004 from the Thames Cancer Registry database. We retained for analysis 2200 patients who had died at the time of analysis, after having excluded seven dead cases where the causes of death were not known to the cancer registry. The 2200 deaths were classified hierarchically to identify (1 mesothelioma deaths, (2 deaths certified as lung cancer deaths or (3 deaths from unspecified cancer, and (4 deaths from other causes. Results 87% of the patients had mesothelioma mentioned on the death certificate. 6% had no mention of mesothelioma but included lung cancer as a cause of death. Another 6% had no mention of mesothelioma or lung cancer, but included an unspecified cancer as a cause of death. Lastly, 2% had other causes of death specified on the death certificate. Conclusion This analysis suggests that official mortality data may underestimate the true occurrence of mesothelioma by around 10%.

Nonthermal-plasma-mediated animal cell death

Science.gov (United States)

Kim, Wanil; Woo, Kyung-Chul; Kim, Gyoo-Cheon; Kim, Kyong-Tai

2011-01-01

Animal cell death comprising necrosis and apoptosis occurred in a well-regulated manner upon specific stimuli. The physiological meanings and detailed molecular mechanisms of cell death have been continuously investigated over several decades. Necrotic cell death has typical morphological changes, such as cell swelling and cell lysis followed by DNA degradation, whereas apoptosis shows blebbing formation and regular DNA fragmentation. Cell death is usually adopted to terminate cancer cells in vivo. The current strategies against tumour are based on the induction of cell death by adopting various methods, including radiotherapy and chemotherapeutics. Among these, radiotherapy is the most frequently used treatment method, but it still has obvious limitations. Recent studies have suggested that the use of nonthermal air plasma can be a prominent method for inducing cancer cell death. Plasma-irradiated cells showed the loss of genomic integrity, mitochondrial dysfunction, plasma membrane damage, etc. Tumour elimination with plasma irradiation is an emerging concept in cancer therapy and can be accelerated by targeting certain tumour-specific proteins with gold nanoparticles. Here, some recent developments are described so that the mechanisms related to plasma-mediated cell death and its perspectives in cancer treatment can be understood.

Nonthermal-plasma-mediated animal cell death

Energy Technology Data Exchange (ETDEWEB)

Kim, Wanil; Woo, Kyung-Chul; Kim, Kyong-Tai [Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, San 31, Hyoja Dong, Pohang 790-784 (Korea, Republic of); Kim, Gyoo-Cheon, E-mail: ktk@postech.ac.kr [Department of Oral Anatomy and Cell Biology, School of Dentistry, Pusan National University, Yangsan 626-810 (Korea, Republic of)

2011-01-12

Animal cell death comprising necrosis and apoptosis occurred in a well-regulated manner upon specific stimuli. The physiological meanings and detailed molecular mechanisms of cell death have been continuously investigated over several decades. Necrotic cell death has typical morphological changes, such as cell swelling and cell lysis followed by DNA degradation, whereas apoptosis shows blebbing formation and regular DNA fragmentation. Cell death is usually adopted to terminate cancer cells in vivo. The current strategies against tumour are based on the induction of cell death by adopting various methods, including radiotherapy and chemotherapeutics. Among these, radiotherapy is the most frequently used treatment method, but it still has obvious limitations. Recent studies have suggested that the use of nonthermal air plasma can be a prominent method for inducing cancer cell death. Plasma-irradiated cells showed the loss of genomic integrity, mitochondrial dysfunction, plasma membrane damage, etc. Tumour elimination with plasma irradiation is an emerging concept in cancer therapy and can be accelerated by targeting certain tumour-specific proteins with gold nanoparticles. Here, some recent developments are described so that the mechanisms related to plasma-mediated cell death and its perspectives in cancer treatment can be understood. (topical review)

Nonthermal-plasma-mediated animal cell death

International Nuclear Information System (INIS)

Kim, Wanil; Woo, Kyung-Chul; Kim, Kyong-Tai; Kim, Gyoo-Cheon

2011-01-01

Animal cell death comprising necrosis and apoptosis occurred in a well-regulated manner upon specific stimuli. The physiological meanings and detailed molecular mechanisms of cell death have been continuously investigated over several decades. Necrotic cell death has typical morphological changes, such as cell swelling and cell lysis followed by DNA degradation, whereas apoptosis shows blebbing formation and regular DNA fragmentation. Cell death is usually adopted to terminate cancer cells in vivo. The current strategies against tumour are based on the induction of cell death by adopting various methods, including radiotherapy and chemotherapeutics. Among these, radiotherapy is the most frequently used treatment method, but it still has obvious limitations. Recent studies have suggested that the use of nonthermal air plasma can be a prominent method for inducing cancer cell death. Plasma-irradiated cells showed the loss of genomic integrity, mitochondrial dysfunction, plasma membrane damage, etc. Tumour elimination with plasma irradiation is an emerging concept in cancer therapy and can be accelerated by targeting certain tumour-specific proteins with gold nanoparticles. Here, some recent developments are described so that the mechanisms related to plasma-mediated cell death and its perspectives in cancer treatment can be understood. (topical review)

Modulation of genes involved in inflammation and cell death in atherosclerosis-susceptible mice

NARCIS (Netherlands)

Zadelaar, Anna Susanne Maria

2006-01-01

In this thesis we focus on atherosclerosis as the main cause of cardiovascular disease. Since inflammation and cell death are important processes in the onset and progression of atherosclerosis, we investigate the role of several genes involved in inflammation and cell death in the vessel wall and

Mortality and causes of death in first admitted schizophrenic patients

DEFF Research Database (Denmark)

Mortensen, P B; Juel, K

1993-01-01

Although many studies have shown an increased mortality in schizophrenic patients, the literature provides little information about mortality from specific causes in relation to age, gender, and duration of illness. This study examined mortality and causes of death in a total national sample...... of 9156 first admitted schizophrenic patients. Suicide accounted for 50% of deaths in men and 35% of deaths in women. Suicide risk was particularly increased during the first year of follow-up. Death from natural causes, with the exception of cancer and cerebrovascular diseases, was increased. Suicide...

Causes of death and associated conditions (Codac): a utilitarian approach to the classification of perinatal deaths.

Science.gov (United States)

Frøen, J Frederik; Pinar, Halit; Flenady, Vicki; Bahrin, Safiah; Charles, Adrian; Chauke, Lawrence; Day, Katie; Duke, Charles W; Facchinetti, Fabio; Fretts, Ruth C; Gardener, Glenn; Gilshenan, Kristen; Gordijn, Sanne J; Gordon, Adrienne; Guyon, Grace; Harrison, Catherine; Koshy, Rachel; Pattinson, Robert C; Petersson, Karin; Russell, Laurie; Saastad, Eli; Smith, Gordon C S; Torabi, Rozbeh

2009-06-10

A carefully classified dataset of perinatal mortality will retain the most significant information on the causes of death. Such information is needed for health care policy development, surveillance and international comparisons, clinical services and research. For comparability purposes, we propose a classification system that could serve all these needs, and be applicable in both developing and developed countries. It is developed to adhere to basic concepts of underlying cause in the International Classification of Diseases (ICD), although gaps in ICD prevent classification of perinatal deaths solely on existing ICD codes.We tested the Causes of Death and Associated Conditions (Codac) classification for perinatal deaths in seven populations, including two developing country settings. We identified areas of potential improvements in the ability to retain existing information, ease of use and inter-rater agreement. After revisions to address these issues we propose Version II of Codac with detailed coding instructions.The ten main categories of Codac consist of three key contributors to global perinatal mortality (intrapartum events, infections and congenital anomalies), two crucial aspects of perinatal mortality (unknown causes of death and termination of pregnancy), a clear distinction of conditions relevant only to the neonatal period and the remaining conditions are arranged in the four anatomical compartments (fetal, cord, placental and maternal).For more detail there are 94 subcategories, further specified in 577 categories in the full version. Codac is designed to accommodate both the main cause of death as well as two associated conditions. We suggest reporting not only the main cause of death, but also the associated relevant conditions so that scenarios of combined conditions and events are captured.The appropriately applied Codac system promises to better manage information on causes of perinatal deaths, the conditions associated with them, and the most

Lupus - An Unrecognized Leading Cause of Death in Young Women: Population-based Study Using Nationwide Death Certificates, 2000-2015.

Science.gov (United States)

Yen, Eric Y; Singh, Ram R

2018-04-18

Mortality statistics from the Centers for Disease Control and Prevention (CDC) is used for planning healthcare policy and allocating resources. CDC uses this data to compile its annual leading-causes-of-death ranking based on a selected list of 113 causes. SLE is not included on this list. Since the cause-of-death ranking is a useful tool for assessing the relative burden of cause-specific mortality, we ranked SLE deaths among CDC's leading causes-of-death to see whether SLE is a significant cause of death among women. Death counts were obtained from the CDC's Wide-ranging Online Data for Epidemiologic Research database in U.S. female population, and then grouped by age and race/ethnicity. Data on the leading causes-of-death were obtained from the Web-based Injury Statistics Query and Reporting System database. During 2000 to 2015, there were 28,411 female deaths with SLE recorded as the underlying or contributing causes of death. SLE ranked among the top 20 leading-causes-of-death in females between 5 and 64 years of age. SLE ranked 10 th in the 15-24 years, 14 th in the 25-34 and the 35-44 years, and 15 th in the 10-14 years age groups. Among black and Hispanic females, SLE ranked 5 th in the 15-24 years, 6 th in the 25-34 years, and 8 th -9 th in the 35-44 years age groups, after excluding the three common external injury causes of death from analysis. SLE is among the leading-causes-of-death in young women, underscoring its impact as an important public health issue. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Cell death and autophagy: Cytokines, drugs, and nutritional factors

International Nuclear Information System (INIS)

Bursch, Wilfried; Karwan, Anneliese; Mayer, Miriam; Dornetshuber, Julia; Froehwein, Ulrike; Schulte-Hermann, Rolf; Fazi, Barbara; Di Sano, Federica; Piredda, Lucia; Piacentini, Mauro; Petrovski, Goran; Fesues, Laszlo; Gerner, Christopher

2008-01-01

Cells may use multiple pathways to commit suicide. In certain contexts, dying cells generate large amounts of autophagic vacuoles and clear large proportions of their cytoplasm, before they finally die, as exemplified by the treatment of human mammary carcinoma cells with the anti-estrogen tamoxifen (TAM, ≤1 μM). Protein analysis during autophagic cell death revealed distinct proteins of the nuclear fraction including GST-π and some proteasomal subunit constituents to be affected during autophagic cell death. Depending on the functional status of caspase-3, MCF-7 cells may switch between autophagic and apoptotic features of cell death [Fazi, B., Bursch, W., Fimia, G.M., Nardacci R., Piacentini, M., Di Sano, F., Piredda, L., 2008. Fenretinide induces autophagic cell death in caspase-defective breast cancer cells. Autophagy 4(4), 435-441]. Furthermore, the self-destruction of MCF-7 cells was found to be completed by phagocytosis of cell residues [Petrovski, G., Zahuczky, G., Katona, K., Vereb, G., Martinet, W., Nemes, Z., Bursch, W., Fesues, L., 2007. Clearance of dying autophagic cells of different origin by professional and non-professional phagocytes. Cell Death Diff. 14 (6), 1117-1128]. Autophagy also constitutes a cell's strategy of defense upon cell damage by eliminating damaged bulk proteins/organelles. This biological condition may be exemplified by the treatment of MCF-7 cells with a necrogenic TAM-dose (10 μM), resulting in the lysis of almost all cells within 24 h. However, a transient (1 h) challenge of MCF-7 cells with the same dose allowed the recovery of cells involving autophagy. Enrichment of chaperones in the insoluble cytoplasmic protein fraction indicated the formation of aggresomes, a potential trigger for autophagy. In a further experimental model HL60 cells were treated with TAM, causing dose-dependent distinct responses: 1-5 μM TAM, autophagy predominant; 7-9 μM, apoptosis predominant; 15 μM, necrosis. These phenomena might be

[Analysis of death causes among infants in Guangzhou from 2010 to 2013].

Science.gov (United States)

Shen, Jichuan; Wang, Ming; Dong, Hang; Zhou, Qin

2014-06-01

To analyze the main death causes among infants in Guangzhou in 2010-2013 and to provide an objective and scientific basis for risk communication of public health emergencies in the future. Descriptive epidemiological method was used to analyze the death causes among infants reported in Guangzhou from the National Death Registration Reporting Information System. The death causes among infants were classified by the 10th international classification of diseases (ICD-10). The constitution and rank order of death causes among infants were analyzed according to the underlying causes of deaths. A total of 4 880 cases of infant deaths were reported in Guangzhou from 2010 to 2013 and infant deaths in floating population were 1.8 (3 135/1 745) times of registered population. The deaths of male infants were 1.73 (3 094/1 786) times of female infants. The neonatal group accounted for 52.32% (2 553/4 880) of total infant deaths and early neonatal group accounted for 64.86% (1 656/2 553) of total neonatal deaths. The top five causes of infant deaths followed by perinatal diseases, congenital malformations, respiratory diseases (mainly pneumonia), accidental deaths and communicable diseases. The mortality ratios were respectively 44.12% (2 153 cases) , 24.73% (1 207 cases), 6.86% (335 cases), 3.48% (170 cases), 3.01% (147 cases) , and no vaccine-related death case was reported. The primary cause of infant deaths in Guangzhou 2010-2013 was perinatal diseases.

Alternative Cell Death Pathways and Cell Metabolism

Directory of Open Access Journals (Sweden)

Simone Fulda

2013-01-01

Full Text Available While necroptosis has for long been viewed as an accidental mode of cell death triggered by physical or chemical damage, it has become clear over the last years that necroptosis can also represent a programmed form of cell death in mammalian cells. Key discoveries in the field of cell death research, including the identification of critical components of the necroptotic machinery, led to a revised concept of cell death signaling programs. Several regulatory check and balances are in place in order to ensure that necroptosis is tightly controlled according to environmental cues and cellular needs. This network of regulatory mechanisms includes metabolic pathways, especially those linked to mitochondrial signaling events. A better understanding of these signal transduction mechanisms will likely contribute to open new avenues to exploit our knowledge on the regulation of necroptosis signaling for therapeutic application in the treatment of human diseases.

[Analysis on death causes of residents in Anhui province, 2013].

Science.gov (United States)

He, Qin; Chen, Yeji; Dai, Dan; Xu, Wei; Xing, Xiuya; Liu, Zhirong

2015-09-01

To analyze the demographic characteristics and the death causes of the residents in Anhui province, and provide evidence for the disease prevention and control. Using descriptive epidemiological analysis, the demographic characteristics and death data of the national disease surveillance points (DSPs) in Anhui province in 2013 were analyed by areas. The aging of the population was observed in all the areas in Anhui, which was most obvious in Jianghuai, followed by Wannan and Huaibei. The overall mortality was 627.10/100 000. The mortalities of diseases varied with sex, area and age. Among the 3 areas, the overall mortality, chronic disease mortality and injury mortality were highest in Huaibei and lowest in Wannan. The area specific difference in mortality of infectious diseases was small. Regardless of areas or the types of diseases, the mortality was higher in males than in females. Deaths caused by diseases with unknown origins were common in residents aged >65 years. The mortality of chronic diseases was higher in residents aged >45 years, especially in those aged 65-84 years. The mortality of injuries was higher in age groups >15 years and >45 years. The mortality of infectious diseases peaked at both young age group and old age group. The top five death causes were cerebrovascular diseases, malignant tumors, heart diseases, respiratory diseases and injuries. Regardless of sex or area, the major death causes were similar, but the ranks were slightly different. The major death causes varied in different age groups, but they were similar in same age group in different areas. The major death causes were diseases originated in perinatal period, and congenital malformations, deformations and chromosomal abnormalities in children aged death causes in children aged 1-14 years were injuries, diseases originated in perinatal period, congenital malformations, deformations and chromosomal abnormalities. Injuries and malignant tumors were the first and second death causes

Death of Lactobacillus acidophilus caused by incorporated /sup 3/H-thymine during incubation without amino acids

Energy Technology Data Exchange (ETDEWEB)

Koukalova, B [Ceskoslovenska Akademie Ved, Brno. Biofysikalni Ustav

1976-01-01

If the cells of Lactobacillus acidophilus R-26 incorporated /sup 3/H-thymine (specific radioactivity 1.57 Ci/mmol or 3.15 Ci/mmol), their transfer to a medium without essential amino acids resulted in their death. This death may result from cell damage caused by the disintegration of tritium which cannot be effectively repaired under conditions of amino acid deprivation. Experimental conditions make it possible to explain this death either as a result of the inhibition of protein or RNA synthesis, or of the absence of amino acids. These possibilities were tested in experiments, in which the synthesis of proteins and RNA was inhibited by specific inhibitors in the presence of amino acids. Under these conditions no death of cells was detected, thus indicating that free amino acids are important in the repair of radiation damage.

The Danish registers of causes of death

DEFF Research Database (Denmark)

Juel, K; Helweg-Larsen, K

1999-01-01

In 1875 registration of causes of death in Denmark was established by the National Board of Health, and annual statistics of death have since been published. Until 1970 the national statistics were based upon punched cards with data collected from the death certificates. Since then the register has...... been fully computerized and includes individual based data of all deaths occurring among all residents in Denmark dying in Denmark. Furthermore, a microfilm of all death certificates from 1943 and onward is kept in the National Board of Health. The Danish Institute for Clinical Epidemiology (DICE) has...... established a computerized register of individual records of deaths in Denmark from 1943 and onwards. No other country covers computerized individual based data of death registration for such a long period, now 54 years. This paper describes the history of the registers, the data sources and access to data...

Cause of neonatal deaths in Northern Ethiopia: a prospective cohort study

Directory of Open Access Journals (Sweden)

Hayelom Gebrekirstos Mengesha

2017-01-01

Full Text Available Abstract Background Despite the significant reduction in childhood mortality, neonatal mortality has shown little or no concomitant decline worldwide. The dilemma arises in that the lack of documentation of cause of death in developing countries, where registration of vital events is virtually nonexistent. Understanding of the causes of death in neonates is important to guide public health interventions. The present study identifies the common causes of neonatal death in Ethiopia. Methods A prospective cohort study was conducted among neonates born between April 2014 and July 2014 in seven hospitals, in Tigray region, Ethiopia. Mothers were interviewed by midwifes respecting risk factors and infant survival. For neonates who died in hospital, causes of death were extracted from medical records, whereas a verbal autopsy method provided presumptive assignment of cause of death for those infants who died at home. Results Of the1152 live births, there were 68 deaths (63 per 1000 live births. Two thirds of deaths were attributable to prematurity 23 (34% or asphyxia 21 (31%. Slight variance was seen between the morality patterns in early and late neonatal periods. In the early neonatal period, 37% were due to prematurity, while asphyxia (35% was more common in the late neonatal period. All infection-related deaths occurred in neonate-mother dyads from rural areas. Conclusion Prematurity, asphyxia, and infections were the leading causes of neonatal deaths in Tigray region during the study period. Causes of deaths identified during early and late neonatal mortality differed, which clearly indicates the need for responsive and evidence-based interventions and policies.

CARDIOVASCULAR CAUSES OF SUDDEN DEATH- AN AUTOPSY STUDY

Directory of Open Access Journals (Sweden)

Deepu Thankappan

2016-10-01

Full Text Available BACKGROUND Present study “Cardiovascular Causes of Sudden Death- An Autopsy Study” was a cross-sectional study conducted in Department of Forensic Medicine, Government Medical College, Kottayam, during the time period from June 1 st 2013 to June 1 st 2014. The objective of the study was to find out the cardiovascular causes of sudden deaths and to correlate the postmortem findings with the histopathological examination. 57 cases brought for postmortem examination with history suggestive of sudden natural death were taken into the study and those cases observed to have a cardiovascular cause of sudden death during autopsy were further examined and their heart specimens were subjected to histopathological examination. Then, the sociodemographic factors, postmortem findings and histopathological findings were correlated and analysed. MATERIALS AND METHODS 57 cases brought for autopsy at Department of Forensic Medicine, Government Medical College, Kottayam from 01.06.2013 to 31.05.2014 were autopsied and subjected to histopathological examination of the heart. The socio-demographic data were collected; they were analyzed and correlated with the postmortem and histopathological findings. RESULTS Out of the 57 subjects who were taken into the study, maximum number of Sudden natural deaths were in the 36-50 year age group (42.2%, 33.3% in the 51-65 year age group and 14% of cases were in the 66-80 year age group. CONCLUSION Histopathological examination of the samples showed myocardial infarction in 33.3% of cases; chronic ischaemic heart disease in 56.1% of cases and myocarditis in 19.3% of cases. The major cardiovascular cause of sudden death was ascertained as Coronary artery disease.

Disability Rating, Age at Death, and Cause of Death in U.S. Veterans with Service-Connected Conditions.

Science.gov (United States)

Maynard, Charles; Trivedi, Ranak; Nelson, Karin; Fihn, Stephan D

2018-03-26

The association between disability and cause of death in Veterans with service-connected disabilities has not been studied. The objective of this study was to compare age at death, military service and disability characteristics, including disability rating, and cause of death by year of birth. We also examined cause of death for specific service-connected conditions. This study used information from the VETSNET file, which is a snapshot of selected items from the Veterans Benefits Administration corporate database. We also used the National Death Index (NDI) for Veterans which is part of the VA Suicide Data Repository. In VETSNET, there were 758,324 Veterans who had a service-connected condition and died between the years 2004 and 2014. Using the scrambled social security number to link the two files resulted in 605,493 (80%) deceased Veterans. Age at death, sex, and underlying cause of death were obtained from the NDI for Veterans and military service characteristics and types of disability were acquired from VETSNET. We constructed age categories corresponding to period of service; birth years 1938 and earlier corresponded to Korea and World War II ("oldest"), birth years 1939-1957 to the Vietnam era ("middle"), and birth years 1958 and later to post Vietnam, Gulf War, and the more recent conflicts in Iraq and Afghanistan ("youngest"). Sixty-two percent were in the oldest age category, 34% in the middle group, and 4% in the youngest one. The overall age at death was 75 ± 13 yr. Only 1.6% of decedents were women; among women 25% were in the youngest age group, while among men only 4% were in the youngest group. Most decedents were enlisted personnel, and 60% served in the U.S. Army. Nearly 61% had a disability rating of >50% and for the middle age group 54% had a disability rating of 100%. The most common service-connected conditions were tinnitus, hearing loss, and post-traumatic stress disorder (PTSD). In the oldest group, nearly half of deaths were due to

Glutathione in Cancer Cell Death

Energy Technology Data Exchange (ETDEWEB)

Ortega, Angel L. [Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 17 Av. Blasco Ibanez, 46010 Valencia (Spain); Mena, Salvador [Green Molecular SL, Pol. Ind. La Coma-Parc Cientific, 46190 Paterna, Valencia (Spain); Estrela, Jose M., E-mail: jose.m.estrela@uv.es [Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 17 Av. Blasco Ibanez, 46010 Valencia (Spain)

2011-03-11

Glutathione (L-γ-glutamyl-L-cysteinyl-glycine; GSH) in cancer cells is particularly relevant in the regulation of carcinogenic mechanisms; sensitivity against cytotoxic drugs, ionizing radiations, and some cytokines; DNA synthesis; and cell proliferation and death. The intracellular thiol redox state (controlled by GSH) is one of the endogenous effectors involved in regulating the mitochondrial permeability transition pore complex and, in consequence, thiol oxidation can be a causal factor in the mitochondrion-based mechanism that leads to cell death. Nevertheless GSH depletion is a common feature not only of apoptosis but also of other types of cell death. Indeed rates of GSH synthesis and fluxes regulate its levels in cellular compartments, and potentially influence switches among different mechanisms of death. How changes in gene expression, post-translational modifications of proteins, and signaling cascades are implicated will be discussed. Furthermore, this review will finally analyze whether GSH depletion may facilitate cancer cell death under in vivo conditions, and how this can be applied to cancer therapy.

Causes and predictors of death in cerebral venous thrombosis

NARCIS (Netherlands)

Canhão, Patrícia; Ferro, José M.; Lindgren, Arne G.; Bousser, Marie-Germaine; Stam, Jan; Barinagarrementeria, Fernando

2005-01-01

Background and Purpose - The causes of death of patients with cerebral venous thrombosis (CVT) have not been systematically addressed in previous studies. We aimed to analyze the causes and predictors of death during the acute phase of CVT in the International Study on Cerebral Vein and Dural Sinus

Causes of death in a contemporary adult congenital heart disease cohort.

Science.gov (United States)

Yu, Christopher; Moore, Benjamin M; Kotchetkova, Irina; Cordina, Rachael L; Celermajer, David S

2018-04-17

The life expectancy of patients with congenital heart disease (CHD) has significantly improved with advances in their paediatric medical care. Mortality patterns are changing as a result. Our study aims to describe survival and causes of death in a contemporary cohort of adult patients with CHD. We reviewed 3068 patients in our adult CHD database (age ≥16 years, seen at least once in our centre between 2000 and 2015), and documented the number and causes of death, via Australia's National Death Index. Survival and mortality patterns were analysed by complexity of CHD and by underlying congenital diagnosis. Our cohort comprised 3068 adult patients (53% male). The distribution of patients (per the Bethesda classification) was 47% simple, 34% moderate and 18% complex (1% not classifiable). Over a median follow-up of 6.2 years (IQR 3.5-10.4), 341 patients (11%) died with an incidence of 0.4 deaths/100 patient years (py). Survival was significantly worse with increasing complexity of CHD (pdeaths/100 py with a median age of death 70 years, and in the complex group was 1.0 death/100 py with a median age of death 34 years. Overall, non-cardiac causes of death outnumbered cardiac causes, at 54% and 46%, respectively. The leading single cause of death was heart failure (17%), followed by malignancy (13%). Simple adult CHD patients mostly died due to non-cardiac causes such as malignancy. Perioperative mortality only accounted for 5% of deaths. Premature death is common in adults with CHD. Although heart failure remains the most common cause of death, in the contemporary era in a specialist CHD centre, non-cardiac related deaths outnumber cardiac deaths, particularly in those with simple CHD lesions. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Drug induced mortality: a multiple cause approach on Italian causes of death Register

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Francesco Grippo

2015-04-01

Full Text Available Background: Drug-related mortality is a complex phenomenon that has several health, social and economic effects. In this paper trends of drug-induced mortality in Italy are analysed. Two approaches have been followed: the traditional analysis of the underlying cause of death (UC (data refers to the Istat mortality database from 1980 to 2011, and the multiple cause (MCanalysis, that is the analysis of all conditions reported on the death certificate (data for 2003-2011 period.Methods: Data presented in this paper are based on the Italian mortality register. The selection of Icd codes used for the analysis follows the definition of the European Monitoring Centre for Drugs and Drug Addiction. Using different indicators (crude and standardized rates, ratio multiple to underlying, the results obtained from the two approaches (UC and MC have been compared. Moreover, as a measure of association between drug-related causes and specific conditions on the death certificate, an estimation of the age-standardized relative risk (RR has been used.Results: In the years 2009-2011, the total number of certificates whit mention of drug use was 1,293, 60% higher than the number UC based. The groups of conditions more strongly associated with drug-related causes are the mental and behavioral disorders (especially alcohol consumption, viral hepatitis, cirrhosis and fibrosis of liver, AIDS and endocarditis.Conclusions : The analysis based on multiple cause approach shows, for the first time, a more detailed picture of the drug related death; it allows to better describe the mortality profiles and to re-evaluate  the contribution of a specific cause to death.

Polycation-mediated integrated cell death processes

DEFF Research Database (Denmark)

Parhamifar, Ladan; Andersen, Helene; Wu, Linping

2014-01-01

standard. PEIs are highly efficient transfectants, but depending on their architecture and size they induce cytotoxicity through different modes of cell death pathways. Here, we briefly review dynamic and integrated cell death processes and pathways, and discuss considerations in cell death assay design...

Bar represses dPax2 and decapentaplegic to regulate cell fate and morphogenetic cell death in Drosophila eye.

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Jongkyun Kang

Full Text Available The coordinated regulation of cell fate and cell survival is crucial for normal pattern formation in developing organisms. In Drosophila compound eye development, crystalline arrays of hexagonal ommatidia are established by precise assembly of diverse cell types, including the photoreceptor cells, cone cells and interommatidial (IOM pigment cells. The molecular basis for controlling the number of cone and IOM pigment cells during ommatidial pattern formation is not well understood. Here we present evidence that BarH1 and BarH2 homeobox genes are essential for eye patterning by inhibiting excess cone cell differentiation and promoting programmed death of IOM cells. Specifically, we show that loss of Bar from the undifferentiated retinal precursor cells leads to ectopic expression of Prospero and dPax2, two transcription factors essential for cone cell specification, resulting in excess cone cell differentiation. We also show that loss of Bar causes ectopic expression of the TGFβ homolog Decapentaplegic (Dpp posterior to the morphogenetic furrow in the larval eye imaginal disc. The ectopic Dpp expression is not responsible for the formation of excess cone cells in Bar loss-of-function mutant eyes. Instead, it causes reduction in IOM cell death in the pupal stage by antagonizing the function of pro-apoptotic gene reaper. Taken together, this study suggests a novel regulatory mechanism in the control of developmental cell death in which the repression of Dpp by Bar in larval eye disc is essential for IOM cell death in pupal retina.

DNA fragmentation and cell death mediated by T cell antigen receptor/CD3 complex on a leukemia T cell line.

Science.gov (United States)

Takahashi, S; Maecker, H T; Levy, R

1989-10-01

An anti-T cell receptor (TcR) monoclonal antibody (mAb), LC4, directed against a human leukemic T cell line, SUP-T13, caused DNA fragmentation ("apoptosis") and cell death upon binding to this cell line. Cross-linking of receptor molecules was necessary for this effect since F(ab')2, but not Fab', fragments of LC4 could induce cell death. Five anti-CD3 mAb tested also caused apoptosis, but only when they were presented on a solid phase. Interestingly, soluble anti-CD3 mAb induced calcium flux and had an additive effect on the calcium flux and interleukin 2 receptor expression induced by LC4, but these anti-CD3 mAb reversed the growth inhibition and apoptosis caused by LC4. The calcium ionophore A23187, but not the protein kinase C activator phorbol 12-myristate 13-acetate (PMA), also induced apoptosis, suggesting that protein kinase C activation alone does not cause apoptosis, although PMA is growth inhibitory. These results suggest that two distinct biological phenomena can accompany stimulation of the TcR/CD3 complex. In both cases, calcium flux and interleukin 2 receptor expression is induced, but only in one case is apoptosis and cell death seen. The signal initiating apoptosis can be selectively prevented by binding CD3 portion of the receptor in this cell line. This difference in signals mediated by the TcR/CD3 complex may be important in explaining the process of thymic selection, as well as in choosing anti-TcR mAb for therapeutic use.

Foodborne cereulide causes beta-cell dysfunction and apoptosis.

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Roman Vangoitsenhoven

Full Text Available To study the effects of cereulide, a food toxin often found at low concentrations in take-away meals, on beta-cell survival and function.Cell death was quantified by Hoechst/Propidium Iodide in mouse (MIN6 and rat (INS-1E beta-cell lines, whole mouse islets and control cell lines (HepG2 and COS-1. Beta-cell function was studied by glucose-stimulated insulin secretion (GSIS. Mechanisms of toxicity were evaluated in MIN6 cells by mRNA profiling, electron microscopy and mitochondrial function tests.24 h exposure to 5 ng/ml cereulide rendered almost all MIN6, INS-1E and pancreatic islets apoptotic, whereas cell death did not increase in the control cell lines. In MIN6 cells and murine islets, GSIS capacity was lost following 24 h exposure to 0.5 ng/ml cereulide (P<0.05. Cereulide exposure induced markers of mitochondrial stress including Puma (p53 up-regulated modulator of apoptosis, P<0.05 and general pro-apoptotic signals as Chop (CCAAT/-enhancer-binding protein homologous protein. Mitochondria appeared swollen upon transmission electron microscopy, basal respiration rate was reduced by 52% (P<0.05 and reactive oxygen species increased by more than twofold (P<0.05 following 24 h exposure to 0.25 and 0.50 ng/ml cereulide, respectively.Cereulide causes apoptotic beta-cell death at low concentrations and impairs beta-cell function at even lower concentrations, with mitochondrial dysfunction underlying these defects. Thus, exposure to cereulide even at concentrations too low to cause systemic effects appears deleterious to the beta-cell.

Evaluation of autopsy imaging (postmortem CT) to presume causes of death

International Nuclear Information System (INIS)

Nishihara, Keisuke; Sugihara, Shuji; Morioka, Nobuo; Sato, Shinya; Tsukamoto, Kazumichi; Ogawa, Toshihide

2010-01-01

A total of 123 patients arrived at the emergency room in a state of cardiopulmonary arrest were examined by CT after death. Forty one patients (33.3%) were presumed the causes of death by autopsy imaging (Ai). Only 30 patients (24.4%) could be presumed causes of death with postmortem inspection and clinical information. However, presumption rate of cause of death was improved up to 46.3% (22.0 points increase) by adding information provided in Ai. (author)

Akebia saponin PA induces autophagic and apoptotic cell death in AGS human gastric cancer cells.

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Xu, Mei-Ying; Lee, Dong Hwa; Joo, Eun Ji; Son, Kun Ho; Kim, Yeong Shik

2013-09-01

In this study, we investigated the anticancer mechanism of akebia saponin PA (AS), a natural product isolated from Dipsacus asperoides in human gastric cancer cell lines. It was shown that AS-induced cell death is caused by autophagy and apoptosis in AGS cells. The apoptosis-inducing effect of AS was characterized by annexin V/propidium (PI) staining, increase of sub-G1 phase and caspase-3 activation, while the autophagy-inducing effect was indicated by the formation of cytoplasmic vacuoles and microtubule-associated protein 1 light chain-3 II (LC3-II) conversion. The autophagy inhibitor bafilomycin A1 (BaF1) decreased AS-induced cell death and caspase-3 activation, but caspase-3 inhibitor Ac-DEVD-CHO did not affect LC3-II accumulation or AS-induced cell viability, suggesting that AS induces autophagic cell death and autophagy contributes to caspase-3-dependent apoptosis. Furthermore, AS activated p38/c-Jun N-terminal kinase (JNK), which could be inhibited by BaF1, and caspase-3 activation was attenuated by both SB202190 and SP600125, indicating that AS-induced autophagy promotes mitogen-activated protein kinases (MAPKs)-mediated apoptosis. Taken together, these results demonstrate that AS induces autophagic and apoptotic cell death and autophagy plays the main role in akebia saponin PA-induced cell death. Copyright © 2013 Elsevier Ltd. All rights reserved.

Childhood death rates declined in Sweden from 2000 to 2014 but deaths from external causes were not always investigated.

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Otterman, Gabriel; Lahne, Klara; Arkema, Elizabeth V; Lucas, Steven; Janson, Staffan; Hellström-Westas, Lena

2018-03-08

Countries that conduct systematic child death reviews report a high proportion of modifiable characteristics among deaths from external causes, and this study examined the trends in Sweden. We analysed individual-level data on external, ill-defined and unknown causes from the Swedish cause of death register from 2000 to 2014, and mortality rates were estimated for children under the age of one and for those aged 1-14 and 15-17 years. Child deaths from all causes were 7914, and 2006 (25%) were from external, ill-defined and unknown causes: 610 (30%) were infants, 692 (34%) were 1-14 and 704 (35%) were 15-17. The annual average was 134 cases (range 99-156) during the study period. Mortality rates from external, ill-defined and unknown causes in children under 18 fell 19%, from 7.4 to 6.0 per 100 000 population. A sizeable number of infant deaths (8.0%) were registered without a death certificate during the study period, but these counts were lower in children aged 1-14 (1.3%) and 15-17 (0.9%). Childhood deaths showed a sustained decline from 2000 to 2014 in Sweden and a quarter were from external, ill-defined or unknown causes. Systematic, interagency death reviews could yield information that could prevent future deaths. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Causes of Death Associated With Prolonged TV Viewing

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Keadle, Sarah K.; Moore, Steven C.; Sampson, Joshua N.; Xiao, Qian; Albanes, Demetrius; Matthews, Charles E.

2015-01-01

Introduction TV viewing is the most prevalent sedentary behavior and is associated with increased risk of cardiovascular disease and cancer mortality, but the association with other leading causes of death is unknown. This study examined the association between TV viewing and leading causes of death in the U.S. Methods A prospective cohort of 221,426 individuals (57% male) aged 50–71 years who were free of chronic disease at baseline (1995–1996), 93% white, with an average BMI of 26.7 (SD=4.4) kg/m2 were included. Participants self-reported TV viewing at baseline and were followed until death or December 31, 2011. Hazard ratios (HRs) and 95% CIs for TV viewing and cause-specific mortality were estimated using Cox proportional hazards regression. Analyses were conducted in 2014–2015. Results After an average follow-up of 14.1 years, adjusted mortality risk for a 2-hour/day increase in TV viewing was significantly higher for the following causes of death (HR [95% CI]): cancer (1.07 [1.03, 1.11); heart disease (1.23 [1.17, 1.29]); chronic obstructive pulmonary disease (1.28 [1.14, 1.43]); diabetes (1.56 [1.33, 1.83]); influenza/pneumonia (1.24 [1.02, 1.50]); Parkinson disease (1.35 [1.11, 1.65]); liver disease (1.33 [1.05, 1.67]); and suicide (1.43 [1.10, 1.85]. Mortality associations persisted in stratified analyses with important potential confounders, reducing causation concerns. Conclusions This study shows the breadth of mortality outcomes associated with prolonged TV viewing, and identifies novel associations for several leading causes of death. TV viewing is a prevalent discretionary behavior that may be a more important target for public health intervention than previously recognized. Trial Registration ClinicalTrials.gov number, NCT00340015 PMID:26215832

A theoretical model of naturally occurring cell death in the nervous system

OpenAIRE

Galli, Resta; Resta, Giovanni

1991-01-01

Throughout the animal kingdom, the formation of the nervous system involves the elimination of many cells, soon after their generation. This phenomenon, known as naturally occurring cell death, has precise time schedules, is observed in the vast majority of nervous structures and causes the 1oss of 15 - 85% of the neurones generated initially. Elimination of erroneous projections, as well as proper size matching between connecting structures can be achieved through cell death. However if elim...

Causes of death and associated conditions (Codac – a utilitarian approach to the classification of perinatal deaths

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Harrison Catherine

2009-06-01

Full Text Available Abstract A carefully classified dataset of perinatal mortality will retain the most significant information on the causes of death. Such information is needed for health care policy development, surveillance and international comparisons, clinical services and research. For comparability purposes, we propose a classification system that could serve all these needs, and be applicable in both developing and developed countries. It is developed to adhere to basic concepts of underlying cause in the International Classification of Diseases (ICD, although gaps in ICD prevent classification of perinatal deaths solely on existing ICD codes. We tested the Causes of Death and Associated Conditions (Codac classification for perinatal deaths in seven populations, including two developing country settings. We identified areas of potential improvements in the ability to retain existing information, ease of use and inter-rater agreement. After revisions to address these issues we propose Version II of Codac with detailed coding instructions. The ten main categories of Codac consist of three key contributors to global perinatal mortality (intrapartum events, infections and congenital anomalies, two crucial aspects of perinatal mortality (unknown causes of death and termination of pregnancy, a clear distinction of conditions relevant only to the neonatal period and the remaining conditions are arranged in the four anatomical compartments (fetal, cord, placental and maternal. For more detail there are 94 subcategories, further specified in 577 categories in the full version. Codac is designed to accommodate both the main cause of death as well as two associated conditions. We suggest reporting not only the main cause of death, but also the associated relevant conditions so that scenarios of combined conditions and events are captured. The appropriately applied Codac system promises to better manage information on causes of perinatal deaths, the conditions

Causes of death and associated conditions (Codac) – a utilitarian approach to the classification of perinatal deaths

Science.gov (United States)

Frøen, J Frederik; Pinar, Halit; Flenady, Vicki; Bahrin, Safiah; Charles, Adrian; Chauke, Lawrence; Day, Katie; Duke, Charles W; Facchinetti, Fabio; Fretts, Ruth C; Gardener, Glenn; Gilshenan, Kristen; Gordijn, Sanne J; Gordon, Adrienne; Guyon, Grace; Harrison, Catherine; Koshy, Rachel; Pattinson, Robert C; Petersson, Karin; Russell, Laurie; Saastad, Eli; Smith, Gordon CS; Torabi, Rozbeh

2009-01-01

A carefully classified dataset of perinatal mortality will retain the most significant information on the causes of death. Such information is needed for health care policy development, surveillance and international comparisons, clinical services and research. For comparability purposes, we propose a classification system that could serve all these needs, and be applicable in both developing and developed countries. It is developed to adhere to basic concepts of underlying cause in the International Classification of Diseases (ICD), although gaps in ICD prevent classification of perinatal deaths solely on existing ICD codes. We tested the Causes of Death and Associated Conditions (Codac) classification for perinatal deaths in seven populations, including two developing country settings. We identified areas of potential improvements in the ability to retain existing information, ease of use and inter-rater agreement. After revisions to address these issues we propose Version II of Codac with detailed coding instructions. The ten main categories of Codac consist of three key contributors to global perinatal mortality (intrapartum events, infections and congenital anomalies), two crucial aspects of perinatal mortality (unknown causes of death and termination of pregnancy), a clear distinction of conditions relevant only to the neonatal period and the remaining conditions are arranged in the four anatomical compartments (fetal, cord, placental and maternal). For more detail there are 94 subcategories, further specified in 577 categories in the full version. Codac is designed to accommodate both the main cause of death as well as two associated conditions. We suggest reporting not only the main cause of death, but also the associated relevant conditions so that scenarios of combined conditions and events are captured. The appropriately applied Codac system promises to better manage information on causes of perinatal deaths, the conditions associated with them, and the

E-Cigarette Aerosol Exposure Induces Reactive Oxygen Species, DNA Damage, and Cell Death in Vascular Endothelial Cells.

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Anderson, Chastain; Majeste, Andrew; Hanus, Jakub; Wang, Shusheng

2016-12-01

Cigarette smoking remains one of the leading causes of preventable death worldwide. Vascular cell death and dysfunction is a central or exacerbating component in the majority of cigarette smoking related pathologies. The recent development of the electronic nicotine delivery systems known as e-cigarettes provides an alternative to conventional cigarette smoking; however, the potential vascular health risks of e-cigarette use remain unclear. This study evaluates the effects of e-cigarette aerosol extract (EAE) and conventional cigarette smoke extract (CSE) on human umbilical vein endothelial cells (HUVECs). A laboratory apparatus was designed to produce extracts from e-cigarettes and conventional cigarettes according to established protocols for cigarette smoking. EAE or conventional CSE was applied to human vascular endothelial cells for 4-72 h, dependent on the assay. Treated cells were assayed for reactive oxygen species, DNA damage, cell viability, and markers of programmed cell death pathways. Additionally, the anti-oxidants α-tocopherol and n-acetyl-l-cysteine were used to attempt to rescue e-cigarette induced cell death. Our results indicate that e-cigarette aerosol is capable of inducing reactive oxygen species, causing DNA damage, and significantly reducing cell viability in a concentration dependent fashion. Immunofluorescent and flow cytometry analysis indicate that both the apoptosis and programmed necrosis pathways are triggered by e-cigarette aerosol treatment. Additionally, anti-oxidant treatment provides a partial rescue of the induced cell death, indicating that reactive oxygen species play a causal role in e-cigarette induced cytotoxicity. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

p53 dependent apoptotic cell death induces embryonic malformation in Carassius auratus under chronic hypoxia.

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Paramita Banerjee Sawant

Full Text Available Hypoxia is a global phenomenon affecting recruitment as well as the embryonic development of aquatic fauna. The present study depicts hypoxia induced disruption of the intrinsic pathway of programmed cell death (PCD, leading to embryonic malformation in the goldfish, Carrasius auratus. Constant hypoxia induced the early expression of pro-apoptotic/tumor suppressor p53 and concomitant expression of the cell death molecule, caspase-3, leading to high level of DNA damage and cell death in hypoxic embryos, as compared to normoxic ones. As a result, the former showed delayed 4 and 64 celled stages and a delay in appearance of epiboly stage. Expression of p53 efficiently switched off expression of the anti-apoptotic Bcl-2 during the initial 12 hours post fertilization (hpf and caused embryonic cell death. However, after 12 hours, simultaneous downregulation of p53 and Caspase-3 and exponential increase of Bcl-2, caused uncontrolled cell proliferation and prevented essential programmed cell death (PCD, ultimately resulting in significant (p<0.05 embryonic malformation up to 144 hpf. Evidences suggest that uncontrolled cell proliferation after 12 hpf may have been due to downregulation of p53 abundance, which in turn has an influence on upregulation of anti-apoptotic Bcl-2. Therefore, we have been able to show for the first time and propose that hypoxia induced downregulation of p53 beyond 12 hpf, disrupts PCD and leads to failure in normal differentiation, causing malformation in gold fish embryos.

Light Influences How the Fungal Toxin Deoxynivalenol Affects Plant Cell Death and Defense Responses

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Khairul I. Ansari

2014-02-01

Full Text Available The Fusarium mycotoxin deoxynivalenol (DON can cause cell death in wheat (Triticum aestivum, but can also reduce the level of cell death caused by heat shock in Arabidopsis (Arabidopsis thaliana cell cultures. We show that 10 μg mL−1 DON does not cause cell death in Arabidopsis cell cultures, and its ability to retard heat-induced cell death is light dependent. Under dark conditions, it actually promoted heat-induced cell death. Wheat cultivars differ in their ability to resist this toxin, and we investigated if the ability of wheat to mount defense responses was light dependent. We found no evidence that light affected the transcription of defense genes in DON-treated roots of seedlings of two wheat cultivars, namely cultivar CM82036 that is resistant to DON-induced bleaching of spikelet tissue and cultivar Remus that is not. However, DON treatment of roots led to genotype-dependent and light-enhanced defense transcript accumulation in coleoptiles. Wheat transcripts encoding a phenylalanine ammonia lyase (PAL gene (previously associated with Fusarium resistance, non-expressor of pathogenesis-related genes-1 (NPR1 and a class III plant peroxidase (POX were DON-upregulated in coleoptiles of wheat cultivar CM82036 but not of cultivar Remus, and DON-upregulation of these transcripts in cultivar CM82036 was light enhanced. Light and genotype-dependent differences in the DON/DON derivative content of coleoptiles were also observed. These results, coupled with previous findings regarding the effect of DON on plants, show that light either directly or indirectly influences the plant defense responses to DON.

Survival and death causes in differentiated thyroid carcinoma

NARCIS (Netherlands)

Eustatia-Rutten, Carmen F. A.; Corssmit, Eleonora P. M.; Biermasz, Nienke R.; Pereira, Alberto M.; Romijn, Johannes A.; Smit, Johannes W.

2006-01-01

Survival studies in differentiated thyroid carcinoma (DTC) may be biased because they have been performed in heterogeneous populations. In addition, specific death causes in DTC have not been documented well in the literature. The aim of our study was to investigate survival and specific death

Role of mitochondria-associated hexokinase II in cancer cell death induced by 3-Bromopyruvate

Science.gov (United States)

Chen, Zhao; Zhang, Hui; Lu, Weiqin; Huang, Peng

2009-01-01

Summary It has long been observed that cancer cells rely more on glycolysis to generate ATP and actively use certain glycolytic metabolic intermediates for biosynthesis. Hexokinase II (HKII) is a key glycolytic enzyme that plays a role in the regulation of the mitochondria-initiated apoptotic cell death. As a potent inhibitor of hexokinase, 3-bromopyruvate (3-BrPA) is known to inhibit cancer cell energy metabolism and trigger cell death, supposedly through depletion of cellular ATP. The current study showed that 3-BrPA caused a covalent modification of HKII protein and directly triggered its dissociation from mitochondria, leading to a specific release of apoptosis-inducing factor (AIF) from the mitochondria to cytosol and eventual cell death. Co-immunoprecipitation revealed a physical interaction between HKII and AIF. Using a competitive peptide of HKII, we showed that the dissociation of hexokinase II from mitochondria alone could cause apoptotic cell death, especially in the mitochondria-deficient ρ0 cells that highly express HKII. Interestingly, the dissociation of HKII itself did no directly affect the mitochondrial membrane potential, ROS generation, and oxidative phosphorylation. Our study suggests that the physical association between HKII and AIF is important for the normal localization of AIF in the mitochondria, and disruption of this protein complex by 3-BrPA leads to their release from the mitochondria and eventual cell death. PMID:19285479

Increased mast cell tryptase in sudden infant death - anaphylaxis, hypoxia or artefact?

Science.gov (United States)

Edston, E; Gidlund, E; Wickman, M; Ribbing, H; Van Hage-Hamsten, M

1999-12-01

Increased concentrations of mast cell tryptase in post mortem blood have frequently been observed in sudden infant deaths but the cause of this has not yet been clarified. The aim was to evaluate factors (immunological, morphological and anamnestic data) behind the observed increase in mast cell tryptase in sudden infant deaths with elevated tryptase. Mast cell tryptase and total immunoglobulin (Ig) E were measured in post mortem sera from 44 infants younger than 1.5 years. Radioallergosorbent tests were performed for possible allergens (mixture for relevant food allergens, Phadiatop and latex). IgG subclasses, IgM, and complement factors (C3, C4 and factor B) were measured with radial immunodiffusion. Mast cells, labelled with antibodies against mast cell tryptase, were counted in the lungs and heart. The circumstances of death and medical history of the deceased infant and family were obtained through police and hospital records. In 40% of the SIDS cases tryptase was elevated (>10 microg/L). Total IgE in serum was increased in 33% compared with clinical reference values but showed no association with mast cell tryptase. RAST tests were positive in three cases. In one of these cases both tryptase and total IgE were elevated. The only variable that was associated with high tryptase values was prone position at death (P Children with elevated total IgE also displayed high concentrations of IgG1 and IgG2. Infants who died in the spring had significantly higher IgE than the others (P < or = 0.05). The results do not support the hypothesis that the elevated tryptase concentrations in sudden infant death are caused by allergy. The association between prone position at death and elevated tryptase could hypothetically be explained by mast cell degranulation due to, for example, a hypoxic stimulus in these infants.

Rational development of a cytotoxic peptide to trigger cell death.

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Boohaker, Rebecca J; Zhang, Ge; Lee, Michael W; Nemec, Kathleen N; Santra, Santimukul; Perez, J Manuel; Khaled, Annette R

2012-07-02

Defects in the apoptotic machinery can contribute to tumor formation and resistance to treatment, creating a need to identify new agents that kill cancer cells by alternative mechanisms. To this end, we examined the cytotoxic properties of a novel peptide, CT20p, derived from the C-terminal, alpha-9 helix of Bax, an amphipathic domain with putative membrane binding properties. Like many antimicrobial peptides, CT20p contains clusters of hydrophobic and cationic residues that could enable the peptide to associate with lipid membranes. CT20p caused the release of calcein from mitochondrial-like lipid vesicles without disrupting vesicle integrity and, when expressed as a fusion protein in cells, localized to mitochondria. The amphipathic nature of CT20p allowed it to be encapsulated in polymeric nanoparticles (NPs) that have the capacity to harbor targeting molecules, dyes or drugs. The resulting CT20p-NPs proved an effective killer, in vitro, of colon and breast cancer cells, and in vivo, using a murine breast cancer tumor model. By introducing CT20p to Bax deficient cells, we demonstrated that the peptide's lethal activity was independent of endogenous Bax. CT20p also caused an increase in the mitochondrial membrane potential that was followed by plasma membrane rupture and cell death, without the characteristic membrane asymmetry associated with apoptosis. We determined that cell death triggered by the CT20p-NPs was minimally dependent on effector caspases and resistant to Bcl-2 overexpression, suggesting that it acts independently of the intrinsic apoptotic death pathway. Furthermore, use of CT20p with the apoptosis-inducing drug, cisplatin, resulted in additive toxicity. These results reveal the novel features of CT20p that allow nanoparticle-mediated delivery to tumors and the potential application in combination therapies to activate multiple death pathways in cancer cells.

Sulfated lentinan induced mitochondrial dysfunction leads to programmed cell death of tobacco BY-2 cells.

Science.gov (United States)

Wang, Jie; Wang, Yaofeng; Shen, Lili; Qian, Yumei; Yang, Jinguang; Wang, Fenglong

2017-04-01

Sulphated lentinan (sLTN) is known to act as a resistance inducer by causing programmed cell death (PCD) in tobacco suspension cells. However, the underlying mechanism of this effect is largely unknown. Using tobacco BY-2 cell model, morphological and biochemical studies revealed that mitochondrial reactive oxygen species (ROS) production and mitochondrial dysfunction contribute to sLNT induced PCD. Cell viability, and HO/PI fluorescence imaging and TUNEL assays confirmed a typical cell death process caused by sLNT. Acetylsalicylic acid (an ROS scavenger), diphenylene iodonium (an inhibitor of NADPH oxidases) and protonophore carbonyl cyanide p-trifluoromethoxyphenyl hydrazone (a protonophore and an uncoupler of mitochondrial oxidative phosphorylation) inhibited sLNT-induced H 2 O 2 generation and cell death, suggesting that ROS generation linked, at least partly, to a mitochondrial dysfunction and caspase-like activation. This conclusion was further confirmed by double-stained cells with the mitochondria-specific marker MitoTracker RedCMXRos and the ROS probe H 2 DCFDA. Moreover, the sLNT-induced PCD of BY-2 cells required cellular metabolism as up-regulation of the AOX family gene transcripts and induction of the SA biosynthesis, the TCA cycle, and miETC related genes were observed. It is concluded that mitochondria play an essential role in the signaling pathway of sLNT-induced ROS generation, which possibly provided new insight into the sLNT-mediated antiviral response, including PCD. Copyright © 2016. Published by Elsevier Inc.

[Causes of the people death from drunkenness and alcoholism].

Science.gov (United States)

Erokhin, Iu A; Paukov, V S; Kirillov, Iu A

2012-01-01

We analyzed causes of 1008 people death, who abused by alcohol. Among them 2 groups were separated out: people died due to drunkenness and due to alcoholism. The structure of the death was similar in the both groups, however depended on alcoholism stages. The major cause of the death in group of drunkenness people was acute heart insufficiency, less commonly--lung pathology, and very rarely--brain vessels pathology and liver cirrhosis. In group of people, who died due to alcoholism, lung pathology was the major cause of these deaths, acute heart insufficiency was occurred less commonly, and very rare brain pathology because of delirium tremens or alcohol withdrawal syndrome, as so liver cirrhosis with complications. Hemorrhagic pancreonecrosis after alcoholic excess was found out in both groups, but it was more often in people, who died due to drunkenness. Obtained results show importance of chronic alcoholism identification as a disease with several stages including drunkenness and alcoholism.

Self-Administered Ethanol Enema Causing Accidental Death

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Thomas Peterson

2014-01-01

Full Text Available Excessive ethanol consumption is a leading preventable cause of death in the United States. Much of the harm from ethanol comes from those who engage in excessive or hazardous drinking. Rectal absorption of ethanol bypasses the first pass metabolic effect, allowing for a higher concentration of blood ethanol to occur for a given volume of solution and, consequently, greater potential for central nervous system depression. However, accidental death is extremely rare with rectal administration. This case report describes an individual with klismaphilia whose death resulted from acute ethanol intoxication by rectal absorption of a wine enema.

An Ursolic Acid Derived Small Molecule Triggers Cancer Cell Death through Hyperstimulation of Macropinocytosis.

Science.gov (United States)

Sun, Lin; Li, Bin; Su, Xiaohui; Chen, Ge; Li, Yaqin; Yu, Linqian; Li, Li; Wei, Wanguo

2017-08-10

Macropinocytosis is a transient endocytosis that internalizes extracellular fluid and particles into vacuoles. Recent studies suggest that hyperstimulation of macropinocytosis can induce a novel nonapoptotic cell death, methuosis. In this report, we describe the identification of an ursolic acid derived small molecule (compound 17), which induces cancer cell death through hyperstimulation of macropinocytosis. 17 causes the accumulation of vacuoles derived from macropinosomes based on transmission electron microscopy, time-lapse microscopy, and labeling with extracellular fluid phase tracers. The vacuoles induced by 17 separate from other cytoplasmic compartments but acquire some characteristics of late endosomes and lysosomes. Inhibiting hyperstimulation of macropinocytosis with the specific inhibitor amiloride blocks cell death, implicating that 17 leads to cell death via macropinocytosis, which is coincident with methuosis. Our results uncovered a novel cell death pathway involved in the activity of 17, which may provide a basis for further development of natural-product-derived scaffolds for drugs that trigger cancer cell death by methuosis.

Ultra-violet B (UVB)-induced skin cell death occurs through a cyclophilin D intrinsic signaling pathway

International Nuclear Information System (INIS)

Ji, Chao; Yang, Bo; Yang, Zhi; Tu, Ying; Yang, Yan-li; He, Li; Bi, Zhi-Gang

2012-01-01

Highlights: ► UVB radiated skin keratinocytes show cyclophilin D (Cyp-D) upregulation. ► NAC inhibits UVB induced Cyp-D expression, while H 2 O 2 facilitates it. ► Cyp-D-deficient cells are significantly less susceptible to UVB induced cell death. ► Over-expression of Cyp-D causes spontaneous keratinocytes cell death. -- Abstract: UVB-induced skin cell damage involves the opening of mitochondrial permeability transition pore (mPTP), which leads to both apoptotic and necrotic cell death. Cyclophilin D (Cyp-D) translocation to the inner membrane of mitochondrion acts as a key component to open the mPTP. Our Western-Blot results in primary cultured human skin keratinocytes and in HaCaT cell line demonstrated that UVB radiation and hydrogen peroxide (H 2 O 2 ) induced Cyp-D expression, which was inhibited by anti-oxidant N-acetyl cysteine (NAC). We created a stable Cyp-D deficiency skin keratinocytes by expressing Cyp-D-shRNA through lentiviral infection. Cyp-D-deficient cells were significantly less susceptible than their counterparts to UVB- or H 2 O 2 -induced cell death. Further, cyclosporine A (Cs-A), a Cyp-D inhibitor, inhibited UVB- or H 2 O 2 -induced keratinocytes cell death. Reversely, over-expression of Cyp-D in primary keratinocytes caused spontaneous keratinocytes cell death. These results suggest Cyp-D’s critical role in UVB/oxidative stress-induced skin cell death.

Role of apoptosis and necrosis in cell death induced by nanoparticle-mediated photothermal therapy

International Nuclear Information System (INIS)

Pattani, Varun P.; Shah, Jay; Atalis, Alexandra; Sharma, Anirudh; Tunnell, James W.

2015-01-01

Current cancer therapies can cause significant collateral damage due to a lack of specificity and sensitivity. Therefore, we explored the cell death pathway response to gold nanorod (GNR)-mediated photothermal therapy as a highly specific cancer therapeutic to understand the role of apoptosis and necrosis during intense localized heating. By developing this, we can optimize photothermal therapy to induce a maximum of ‘clean’ cell death pathways, namely apoptosis, thereby reducing external damage. GNRs were targeted to several subcellular localizations within colorectal tumor cells in vitro, and the cell death pathways were quantitatively analyzed after photothermal therapy using flow cytometry. In this study, we found that the cell death response to photothermal therapy was dependent on the GNR localization. Furthermore, we demonstrated that nanorods targeted to the perinuclear region irradiated at 37.5 W/cm 2 laser fluence rate led to maximum cell destruction with the ‘cleaner’ method of apoptosis, at similar percentages as other anti-cancer targeted therapies. We believe that this indicates the therapeutic potential for GNR-mediated photothermal therapy to treat cancer effectively without causing damage to surrounding tissue

Role of apoptosis and necrosis in cell death induced by nanoparticle-mediated photothermal therapy

Energy Technology Data Exchange (ETDEWEB)

Pattani, Varun P., E-mail: varun.pattani@utexas.edu; Shah, Jay; Atalis, Alexandra; Sharma, Anirudh; Tunnell, James W. [The University of Texas at Austin, Department of Biomedical Engineering (United States)

2015-01-15

Current cancer therapies can cause significant collateral damage due to a lack of specificity and sensitivity. Therefore, we explored the cell death pathway response to gold nanorod (GNR)-mediated photothermal therapy as a highly specific cancer therapeutic to understand the role of apoptosis and necrosis during intense localized heating. By developing this, we can optimize photothermal therapy to induce a maximum of ‘clean’ cell death pathways, namely apoptosis, thereby reducing external damage. GNRs were targeted to several subcellular localizations within colorectal tumor cells in vitro, and the cell death pathways were quantitatively analyzed after photothermal therapy using flow cytometry. In this study, we found that the cell death response to photothermal therapy was dependent on the GNR localization. Furthermore, we demonstrated that nanorods targeted to the perinuclear region irradiated at 37.5 W/cm{sup 2} laser fluence rate led to maximum cell destruction with the ‘cleaner’ method of apoptosis, at similar percentages as other anti-cancer targeted therapies. We believe that this indicates the therapeutic potential for GNR-mediated photothermal therapy to treat cancer effectively without causing damage to surrounding tissue.

Causes of Death Among 379 Patients With Hemophilia: A Developing Country's Report.

Science.gov (United States)

Mansouritorghabeh, Hassan; Rahimi, Hossein; Mohades, Seyed Tahereh; Behboudi, Maryam

2018-05-01

There are steps to achieve an optimum life for patients with hemophilia in developing countries, and awareness of the pattern of death in patients with hemophilia is a prerequisite for any health-care program. Owing to the lack of any data on the pattern of death in patients with hemophilia from developing countries, the current study was done to address common causes of death, and the spectrum of causes of death among individuals with hemophilia A and B. To address the pattern of death in northeast of Iran, we retrospectively collected demographic data regarding deceased patients with hemophilia A and B. Overall, among 379 people with hemophilia A and B, there were 46 deaths. Thirty-two deaths happened in the severe forms of the diseases. The obtained results show the patterns of death in the patients studied are not as parallel as some reports from the developed countries. Traumatic and spontaneous bleeding events were the main causes of death. The trend of death shows a decrease in the current decade post better therapeutic facilities. Evaluation of causes of death in hemophilia can be a useful indicator for managing the efficacy of health care in the current patients.

Mitochondrial and Cell Death Mechanisms in Neurodegenerative Diseases

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Lee J. Martin

2010-03-01

Full Text Available Alzheimer’s disease (AD, Parkinson’s disease (PD and amyotrophic lateral sclerosis (ALS are the most common human adult-onset neurodegenerative diseases. They are characterized by prominent age-related neurodegeneration in selectively vulnerable neural systems. Some forms of AD, PD, and ALS are inherited, and genes causing these diseases have been identified. Nevertheless, the mechanisms of the neuronal cell death are unresolved. Morphological, biochemical, genetic, as well as cell and animal model studies reveal that mitochondria could have roles in this neurodegeneration. The functions and properties of mitochondria might render subsets of selectively vulnerable neurons intrinsically susceptible to cellular aging and stress and overlying genetic variations, triggering neurodegeneration according to a cell death matrix theory. In AD, alterations in enzymes involved in oxidative phosphorylation, oxidative damage, and mitochondrial binding of Aβ and amyloid precursor protein have been reported. In PD, mutations in putative mitochondrial proteins have been identified and mitochondrial DNA mutations have been found in neurons in the substantia nigra. In ALS, changes occur in mitochondrial respiratory chain enzymes and mitochondrial cell death proteins. Transgenic mouse models of human neurodegenerative disease are beginning to reveal possible principles governing the biology of selective neuronal vulnerability that implicate mitochondria and the mitochondrial permeability transition pore. This review summarizes how mitochondrial pathobiology might contribute to neuronal death in AD, PD, and ALS and could serve as a target for drug therapy.

Non-chemotoxic induction of cancer cell death using magnetic nanowires

Directory of Open Access Journals (Sweden)

Contreras MF

2015-03-01

Full Text Available Maria F Contreras,1 Rachid Sougrat,2 Amir Zaher,3 Timothy Ravasi,1,3 Jürgen Kosel3 1Division of Biological and Environmental Sciences and Engineering, 2Advanced Nanofabrication Imaging and Characterization, 3Division of Computer, Electrical and Mathematical Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal, Kingdom of Saudi Arabia Abstract: In this paper, we show that magnetic nanowires with weak magnetic fields and low frequencies can induce cell death via a mechanism that does not involve heat production. We incubated colon cancer cells with two concentrations (2.4 and 12 µg/mL of nickel nanowires that were 35 nm in diameter and exposed the cells and nanowires to an alternating magnetic field (0.5 mT and 1 Hz or 1 kHz for 10 or 30 minutes. This low-power field exerted a force on the magnetic nanowires, causing a mechanical disturbance to the cells. Transmission electron microscopy images showed that the nanostructures were internalized into the cells within 1 hour of incubation. Cell viability studies showed that the magnetic field and the nanowires separately had minor deleterious effects on the cells; however, when combined, the magnetic field and nanowires caused the cell viability values to drop by up to 39%, depending on the strength of the magnetic field and the concentration of the nanowires. Cell membrane leakage experiments indicated membrane leakage of 20%, suggesting that cell death mechanisms induced by the nanowires and magnetic field involve some cell membrane rupture. Results suggest that magnetic nanowires can kill cancer cells. The proposed process requires simple and low-cost equipment with exposure to only very weak magnetic fields for short time periods. Keywords: cell death induction, low frequency alternating magnetic field, nanomedicine, nanowire internalization, nickel nanowires

Staurosporine induces different cell death forms in cultured rat astrocytes

International Nuclear Information System (INIS)

Simenc, Janez; Lipnik-Stangelj, Metoda

2012-01-01

Astroglial cells are frequently involved in malignant transformation. Besides apoptosis, necroptosis, a different form of regulated cell death, seems to be related with glioblastoma genesis, proliferation, angiogenesis and invasion. In the present work we elucidated mechanisms of necroptosis in cultured astrocytes, and compared them with apoptosis, caused by staurosporine. Cultured rat cortical astrocytes were used for a cell death studies. Cell death was induced by different concentrations of staurosporine, and modified by inhibitors of apoptosis (z-vad-fmk) and necroptosis (nec-1). Different forms of a cell death were detected using flow cytometry. We showed that staurosporine, depending on concentration, induces both, apoptosis as well as necroptosis. Treatment with 10 −7 M staurosporine increased apoptosis of astrocytes after the regeneration in a staurosporine free medium. When caspases were inhibited, apoptosis was attenuated, while necroptosis was slightly increased. Treatment with 10 −6 M staurosporine induced necroptosis that occurred after the regeneration of astrocytes in a staurosporine free medium, as well as without regeneration period. Necroptosis was significantly attenuated by nec-1 which inhibits RIP1 kinase. On the other hand, the inhibition of caspases had no effect on necroptosis. Furthermore, staurosporine activated RIP1 kinase increased the production of reactive oxygen species, while an antioxidant BHA significantly attenuated necroptosis. Staurosporine can induce apoptosis and/or necroptosis in cultured astrocytes via different signalling pathways. Distinction between different forms of cell death is crucial in the studies of therapy-induced necroptosis

Cause of death in former miners of uranium mines

International Nuclear Information System (INIS)

Vich, Z.; Koskova, D.

1992-01-01

The mortality in a cohort of 4,803 former miners from uranium mines was analyzed with special reference to other causes of death than bronchogenic cancer. The observed frequencies of death from other causes were significantly lower than the expected rates for the period of 1968-1985 as well as in various periods of observation, this especially in the group of cardiovascular diseases, other tumors and the group of other diseases; at the same time, frequencies of death from diseases of respiratory and digestive systems and from injuries were not different from the expected rates. This may be caused by the s.c. health worker effect or by increased mortality from lung tumors at a younger age than that which is usual in the non-exposed male population. (author) 4 tabs., 14 refs

26 CFR 1.4-4 - Short taxable year caused by death.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 1 2010-04-01 2010-04-01 true Short taxable year caused by death. 1.4-4 Section... Normal Taxes and Surtaxes § 1.4-4 Short taxable year caused by death. An individual making a return for a... results from the death of the taxpayer. Tax on Corporations ...

FMSP-Nanoparticles Induced Cell Death on Human Breast Adenocarcinoma Cell Line (MCF-7 Cells: Morphometric Analysis

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Firdos Alam Khan

2018-05-01

Full Text Available Currently, breast cancer treatment mostly revolves around radiation therapy and surgical interventions, but often these treatments do not provide satisfactory relief to the patients and cause unmanageable side-effects. Nanomaterials show promising results in treating cancer cells and have many advantages such as high biocompatibility, bioavailability and effective therapeutic capabilities. Interestingly, fluorescent magnetic nanoparticles have been used in many biological and diagnostic applications, but there is no report of use of fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles in the treatment of human breast cancer cells. In the present study, we tested the effect of FMSP-nanoparticles on human breast cancer cells (MCF-7. We tested different concentrations (1.25, 12.5 and 50 µg/mL of FMSP-nanoparticles in MCF-7 cells and evaluated the nanoparticles response morphometrically. Our results revealed that FMSP-nanoparticles produced a concentration dependent effect on the cancer cells, a dose of 1.25 µg/mL produced no significant effect on the cancer cell morphology and cell death, whereas dosages of 12.5 and 50 µg/mL resulted in significant nuclear augmentation, disintegration, chromatic condensation followed by dose dependent cell death. Our results demonstrate that FMSP-nanoparticles induce cell death in MCF-7 cells and may be a potential anti-cancer agent for breast cancer treatment.

Psychosocial therapy and causes of death after deliberate self-harm

DEFF Research Database (Denmark)

Birkbak, J; Stuart, E A; Lind, B D

2016-01-01

BACKGROUND: Psychosocial therapy after deliberate self-harm might be associated with reduced risk of specific causes of death. METHOD: In this matched cohort study, we included patients, who after an episode of deliberate self-harm received psychosocial therapy at a Suicide Prevention Clinic...... in Denmark between 1992 and 2010. We used propensity score matching in a 1:3 ratio to select a comparison group from 59 046 individuals who received standard care. National Danish registers supplied data on specific causes of death over a 20-year follow-up period. RESULTS: At the end of follow-up, 391 (6.......5-448.4) for mental or behavioural disorders as a cause of death, 111.1 (95% CI 79.2-210.5) for alcohol-related causes and 96.8 (95% CI 69.1-161.8) for other diseases and medical conditions. CONCLUSIONS: Our findings indicate that psychosocial therapy after deliberate self-harm might reduce long-term risk of death...

Long-term mortality and causes of death among hospitalized Swedish drug users.

Science.gov (United States)

Fugelstad, Anna; Annell, Anders; Ågren, Gunnar

2014-06-01

To study long-term mortality and causes of death in a cohort of drug users in relation to main type of drug use and HIV-status. A total of 1640 hospitalized drug users in Stockholm was followed up from 1985 to the end of 2007. The mortality was compared with the general Swedish population and hazard ratios (HR) for the main risk indicators were calculated. The causes of death were studied, using information from death certificates. 630 persons died during the observation period. The Standard Mortality Ratio (SMR) was 16.1 (males 13.8, females 18.5). The crude mortality rate was 2.0 % (males 2.2% and females 1.5%). The mortality rate was higher in heroin users than among amphetamine users, HR 1.96, controlled for age and other risk factors. The mortality rate among individuals infected with the human immunodeficiency virus (HIV) was high (4.9 %), HR 2.64, compared with HIV-negative individuals. Most of the deaths were from other causes than acquired immune deficiency syndrome. One-third of deaths (227) were caused by heroin intoxication. The number of deaths from HIV-related causes decreased after 1996, when highly active anti-retroviral therapy was introduced. In all, there were 92 HIV-related deaths. Deaths from natural causes increased during the observation period. The SMR was highest for cardiovascular and gastrointestinal diseases. The results indicate a correlation between amphetamine use and death from cerebral haemorrhage. A high proportion of natural deaths were alcohol-related. The death rate among illicit drug users was persistently high. Alcohol consumption was a contributing factor to premature death. © 2014 the Nordic Societies of Public Health.

Spontaneous and radiation induced cell death in HeLa S3 human carcinoma

International Nuclear Information System (INIS)

Zaric, B.; Milosavljevic, B.; Radojcic, M.

2001-01-01

Radiation biologists have classified radiation-induced cell death based on cell proliferative capacity to either mitotic or interphase death. Cytologists have revealed two morphologically and biochemically diverse forms of cell death, apoptosis and necrosis. While the knowledge of the former is already well exploited by radiologists, cell susceptibility to apoptosis and necrosis is still under investigation. We studied characteristics of spontaneous cell death, and dose dependence and time course of radiation-induced cell death of human uterine cervix epitheloid carcinoma HeLaS 3 in culture. Cells were irradiated with 2-40 Gy of γ-rays. The effect on growth, viability, morphology and genomic DNA structure were followed 24-72 h after irradiation. Cell viability was evaluated by trypan-blue exclusion assay and cell morphology by in situ DNA staining with propidium iodide. Cell genomic DNA fragmentation pattern was determined by electrophoresis on 2% agarose gels. At all cell densities 25-35% cells were PI positive and their DNA was fragmented to a high molecular size (≥20 kbp), but the internucleosomal ladder was not observed. A significant decrease in viability to 33% was observed 72 h post 40 Gy irradiation. It corresponded to 55% of PI positive cells. A smear of smaller DNA fragments (0.1-1 kbp), 24 h after 10-20 Gy irradiation was considered as proof that the dominant form of radiation-induced cell death was necrosis. It was concluded that the dominant form of radiation-induced cell death in HeLaS 3 population was necrosis and the radiation dose which caused 50% of cell death after 72 h (termed ND 50 ) was between 30-40 Gy. (author)

Non-chemotoxic induction of cancer cell death using magnetic nanowires

KAUST Repository

Contreras, Maria F.; Sougrat, Rachid; Zaher, Amir Omar; Ravasi, Timothy; Kosel, Jü rgen

2015-01-01

In this paper, we show that magnetic nanowires with weak magnetic fields and low frequencies can induce cell death via a mechanism that does not involve heat production. We incubated colon cancer cells with two concentrations (2.4 and 12 μg/mL) of nickel nanowires that were 35 nm in diameter and exposed the cells and nanowires to an alternating magnetic field (0.5 mT and 1 Hz or 1 kHz) for 10 or 30 minutes. This low-power field exerted a force on the magnetic nanowires, causing a mechanical disturbance to the cells. Transmission electron microscopy images showed that the nanostructures were internalized into the cells within 1 hour of incubation. Cell viability studies showed that the magnetic field and the nanowires separately had minor deleterious effects on the cells; however, when combined, the magnetic field and nanowires caused the cell viability values to drop by up to 39%, depending on the strength of the magnetic field and the concentration of the nanowires. Cell membrane leakage experiments indicated membrane leakage of 20%, suggesting that cell death mechanisms induced by the nanowires and magnetic field involve some cell membrane rupture. Results suggest that magnetic nanowires can kill cancer cells. The proposed process requires simple and low-cost equipment with exposure to only very weak magnetic fields for short time periods. © 2015 Contreras et al.

Non-chemotoxic induction of cancer cell death using magnetic nanowires

KAUST Repository

Contreras, Maria F.

2015-03-01

In this paper, we show that magnetic nanowires with weak magnetic fields and low frequencies can induce cell death via a mechanism that does not involve heat production. We incubated colon cancer cells with two concentrations (2.4 and 12 μg/mL) of nickel nanowires that were 35 nm in diameter and exposed the cells and nanowires to an alternating magnetic field (0.5 mT and 1 Hz or 1 kHz) for 10 or 30 minutes. This low-power field exerted a force on the magnetic nanowires, causing a mechanical disturbance to the cells. Transmission electron microscopy images showed that the nanostructures were internalized into the cells within 1 hour of incubation. Cell viability studies showed that the magnetic field and the nanowires separately had minor deleterious effects on the cells; however, when combined, the magnetic field and nanowires caused the cell viability values to drop by up to 39%, depending on the strength of the magnetic field and the concentration of the nanowires. Cell membrane leakage experiments indicated membrane leakage of 20%, suggesting that cell death mechanisms induced by the nanowires and magnetic field involve some cell membrane rupture. Results suggest that magnetic nanowires can kill cancer cells. The proposed process requires simple and low-cost equipment with exposure to only very weak magnetic fields for short time periods. © 2015 Contreras et al.

Causes of Death among AIDS Patients after Introduction of Free Combination Antiretroviral Therapy (cART in Three Chinese Provinces, 2010-2011.

Directory of Open Access Journals (Sweden)

Liyan Wang

Full Text Available Although AIDS-related deaths have had significant economic and social impact following an increased disease burden internationally, few studies have evaluated the cause of AIDS-related deaths among patients with AIDS on combination anti-retroviral therapy (cART in China. This study examines the causes of death among AIDS-patients in China and uses a methodology to increase data accuracy compared to the previous studies on AIDS-related mortality in China, that have taken the reported cause of death in the National HIV Registry at face-value.Death certificates/medical records were examined and a cross-sectional survey was conducted in three provinces to verify the causes of death among AIDS patients who died between January 1, 2010 and June 30, 2011. Chi-square analysis was conducted to examine the categorical variables by causes of death and by ART status. Univariate and multivariate logistic regression were used to evaluate factors associated with AIDS-related death versus non-AIDS related death.This study used a sample of 1,109 subjects. The average age at death was 44.5 years. AIDS-related deaths were significantly higher than non-AIDS and injury-related deaths. In the sample, 41.9% (465/1109 were deceased within a year of HIV diagnosis and 52.7% (584/1109 of the deceased AIDS patients were not on cART. For AIDS-related deaths (n = 798, statistically significant factors included CD4 count <200 cells/mm3 at the time of cART initiation (AOR 1.94, 95%CI 1.24-3.05, ART naïve (AOR 1.69, 95%CI 1.09-2.61; p = 0.019 and age <39 years (AOR 2.96, 95%CI 1.77-4.96.For the AIDS patients that were deceased, only those who initiated cART while at a CD4 count ≥200 cells/mm3 were less likely to die from AIDS-related causes compared to those who didn't initiate ART at all.

Long-term mortality and causes of death associated with Staphylococcus aureus bacteremia

DEFF Research Database (Denmark)

Gotland, N; Uhre, M L; Mejer, N

2016-01-01

OBJECTIVES: Data describing long-term mortality in patients with Staphylococcus aureus bacteremia (SAB) is scarce. This study investigated risk factors, causes of death and temporal trends in long-term mortality associated with SAB. METHODS: Nationwide population-based matched cohort study...... respiratory disease, nervous system disease, unknown causes, psychiatric disorders, cardiovascular disease and senility. Over time, rates of death decreased or were stable for all disease categories except for musculoskeletal and skin disease where a trend towards an increase was seen. CONCLUSION: Long......-term mortality after SAB was high but decreased over time. SAB cases were more likely to die of eight specific causes of death and less likely to die of five other causes of death compared to controls. Causes of death decreased for most disease categories. Risk factors associated with long-term mortality were...

Fisetin and luteolin protect human retinal pigment epithelial cells from oxidative stress-induced cell death and regulate inflammation

Science.gov (United States)

Hytti, Maria; Piippo, Niina; Korhonen, Eveliina; Honkakoski, Paavo; Kaarniranta, Kai; Kauppinen, Anu

2015-01-01

Degeneration of retinal pigment epithelial (RPE) cells is a clinical hallmark of age-related macular degeneration (AMD), the leading cause of blindness among aged people in the Western world. Both inflammation and oxidative stress are known to play vital roles in the development of this disease. Here, we assess the ability of fisetin and luteolin, to protect ARPE-19 cells from oxidative stress-induced cell death and to decrease intracellular inflammation. We also compare the growth and reactivity of human ARPE-19 cells in serum-free and serum-containing conditions. The absence of serum in the culture medium did not prevent ARPE-19 cells from reaching full confluency but caused an increased sensitivity to oxidative stress-induced cell death. Both fisetin and luteolin protected ARPE-19 cells from oxidative stress-induced cell death. They also significantly decreased the release of pro-inflammatory cytokines into the culture medium. The decrease in inflammation was associated with reduced activation of MAPKs and CREB, but was not linked to NF- κB or SIRT1. The ability of fisetin and luteolin to protect and repair stressed RPE cells even after the oxidative insult make them attractive in the search for treatments for AMD. PMID:26619957

Ultra-violet B (UVB)-induced skin cell death occurs through a cyclophilin D intrinsic signaling pathway

Energy Technology Data Exchange (ETDEWEB)

Ji, Chao [Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210024, Jiangsu (China); Yang, Bo [Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040 (China); Yang, Zhi; Tu, Ying [Department of Dermatology, The First Affiliated Hospital of Kunming Medical University, Yunnan Provincial Institute of Dermatology, Kunming 650032, Yunnan (China); Yang, Yan-li [Department of Otorhinolaryngology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210024, Jiangsu (China); He, Li, E-mail: heli2662@yahoo.com.cn [Department of Otorhinolaryngology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210024, Jiangsu (China); Bi, Zhi-Gang, E-mail: eltonbibenqhospital@yahoo.com.cn [Department of Dermatology, BenQ Medical Center, Nanjing Medical University, Nanjing 210019, Jiangsu (China)

2012-09-07

Highlights: Black-Right-Pointing-Pointer UVB radiated skin keratinocytes show cyclophilin D (Cyp-D) upregulation. Black-Right-Pointing-Pointer NAC inhibits UVB induced Cyp-D expression, while H{sub 2}O{sub 2} facilitates it. Black-Right-Pointing-Pointer Cyp-D-deficient cells are significantly less susceptible to UVB induced cell death. Black-Right-Pointing-Pointer Over-expression of Cyp-D causes spontaneous keratinocytes cell death. -- Abstract: UVB-induced skin cell damage involves the opening of mitochondrial permeability transition pore (mPTP), which leads to both apoptotic and necrotic cell death. Cyclophilin D (Cyp-D) translocation to the inner membrane of mitochondrion acts as a key component to open the mPTP. Our Western-Blot results in primary cultured human skin keratinocytes and in HaCaT cell line demonstrated that UVB radiation and hydrogen peroxide (H{sub 2}O{sub 2}) induced Cyp-D expression, which was inhibited by anti-oxidant N-acetyl cysteine (NAC). We created a stable Cyp-D deficiency skin keratinocytes by expressing Cyp-D-shRNA through lentiviral infection. Cyp-D-deficient cells were significantly less susceptible than their counterparts to UVB- or H{sub 2}O{sub 2}-induced cell death. Further, cyclosporine A (Cs-A), a Cyp-D inhibitor, inhibited UVB- or H{sub 2}O{sub 2}-induced keratinocytes cell death. Reversely, over-expression of Cyp-D in primary keratinocytes caused spontaneous keratinocytes cell death. These results suggest Cyp-D's critical role in UVB/oxidative stress-induced skin cell death.

Causes of death among undocumented migrants in Sweden, 1997–2010

Directory of Open Access Journals (Sweden)

Anna Wahlberg

2014-06-01

Full Text Available Background: Undocumented migrants are one of the most vulnerable groups in Swedish society, where they generally suffer from poor health and limited health care access. Due to their irregular status, such migrants are an under-researched group and are not included in the country's Cause of Death Register (CDR. Objective: To determine the causes of death among undocumented migrants in Sweden and to ascertain whether there are patterns in causes of death that differ between residents and undocumented migrants. Design: This is a cross-sectional study of death certificates issued from 1997 to 2010 but never included in the CDR from which we established our study sample of undocumented migrants. As age adjustments could not be performed due to lack of data, comparisons between residents and undocumented migrants were made at specific age intervals, based on the study sample's mean age at death±a half standard deviation. Results: Out of 7,925 individuals surveyed, 860 were classified as likely to have been undocumented migrants. External causes (49.8% were the most frequent cause of death, followed by circulatory system diseases, and then neoplasms. Undocumented migrants had a statistically significant increased risk of dying from external causes (odds ratio [OR] 3.57, 95% confidence interval [CI]: 2.83–4.52 and circulatory system diseases (OR 2.20, 95% CI: 1.73–2.82 compared to residents, and a lower risk of dying from neoplasms (OR 0.07, 95% CI: 0.04–0.14. Conclusions: We believe our study is the first to determine national figures on causes of death of undocumented migrants. We found inequity in health as substantial differences in causes of death between undocumented migrants and residents were seen. Legal ambiguities regarding health care provision must be addressed if equity in health is to be achieved in a country otherwise known for its universal health coverage.

[Methuosis: a novel type of cell death].

Science.gov (United States)

Cai, Hongbing; Liu, Jinkun; Fan, Qin; Li, Xin

2013-12-01

Cell death is a major physiological or pathological phenomenon in life activities. The classic forms of cell death include apoptosis, necrosis, and autophagy. Recently, a novel type of cell death has been observed and termed as methuosis, in which excessive stimuli can induce cytoplasmic uptake and accumulation of small bubbles that gradually merge into giant vacuoles, eventually leading to decreased cellular metabolic activity, cell membrane rupture and cell death. In this article, we describe the nomenclature, morphological characteristics and underlying mechanisms of methuosis, compare methuosis with autophagy, oncosis and paraptosis, and review the related researches.

Acrolein Disrupts Tight Junction Proteins and Causes Endoplasmic Reticulum Stress-Mediated Epithelial Cell Death Leading to Intestinal Barrier Dysfunction and Permeability.

Science.gov (United States)

Chen, Wei-Yang; Wang, Min; Zhang, Jingwen; Barve, Shirish S; McClain, Craig J; Joshi-Barve, Swati

2017-12-01

Increasing evidence suggests that environmental and dietary factors can affect intestinal epithelial integrity leading to gut permeability and bacterial translocation. Intestinal barrier dysfunction is a pathogenic process associated with many chronic disorders. Acrolein is an environmental and dietary pollutant and a lipid-derived endogenous metabolite. The impact of acrolein on the intestine has not been investigated before and is evaluated in this study, both in vitro and in vivo. Our data demonstrate that oral acrolein exposure in mice caused damage to the intestinal epithelial barrier, resulting in increased permeability and subsequently translocation of bacterial endotoxin-lipopolysaccharide into the blood. Similar results were seen in vitro using established Caco-2 cell monolayers wherein acrolein decreased barrier function and increased permeability. Acrolein also caused the down-regulation and/or redistribution of three representative tight junction proteins (ie, zonula occludens-1, Occludin, Claudin-1) that critically regulate epithelial paracellular permeability. In addition, acrolein induced endoplasmic reticulum stress-mediated death of epithelial cells, which is an important mechanism contributing to intestinal barrier damage/dysfunction, and gut permeability. Overall, we demonstrate that exposure to acrolein affects the intestinal epithelium by decrease/redistribution of tight junction proteins and endoplasmic reticulum stress-mediated epithelial cell death, thereby resulting in loss of barrier integrity and function. Our findings highlight the adverse consequences of environmental and dietary pollutants on intestinal barrier integrity/function with relevance to gut permeability and the development of disease. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Morphological classification of plant cell deaths.

Science.gov (United States)

van Doorn, W G; Beers, E P; Dangl, J L; Franklin-Tong, V E; Gallois, P; Hara-Nishimura, I; Jones, A M; Kawai-Yamada, M; Lam, E; Mundy, J; Mur, L A J; Petersen, M; Smertenko, A; Taliansky, M; Van Breusegem, F; Wolpert, T; Woltering, E; Zhivotovsky, B; Bozhkov, P V

2011-08-01

Programmed cell death (PCD) is an integral part of plant development and of responses to abiotic stress or pathogens. Although the morphology of plant PCD is, in some cases, well characterised and molecular mechanisms controlling plant PCD are beginning to emerge, there is still confusion about the classification of PCD in plants. Here we suggest a classification based on morphological criteria. According to this classification, the use of the term 'apoptosis' is not justified in plants, but at least two classes of PCD can be distinguished: vacuolar cell death and necrosis. During vacuolar cell death, the cell contents are removed by a combination of autophagy-like process and release of hydrolases from collapsed lytic vacuoles. Necrosis is characterised by early rupture of the plasma membrane, shrinkage of the protoplast and absence of vacuolar cell death features. Vacuolar cell death is common during tissue and organ formation and elimination, whereas necrosis is typically found under abiotic stress. Some examples of plant PCD cannot be ascribed to either major class and are therefore classified as separate modalities. These are PCD associated with the hypersensitive response to biotrophic pathogens, which can express features of both necrosis and vacuolar cell death, PCD in starchy cereal endosperm and during self-incompatibility. The present classification is not static, but will be subject to further revision, especially when specific biochemical pathways are better defined.

An evaluation of the effects of long term cryopreservation, cause of death, and time between death and donation on heart valve leaflet viability

International Nuclear Information System (INIS)

Strachan, K.

1999-01-01

The protocol for cryopreservation of allograft heart valves at the Donor Tissue Bank of Victoria was based on validation studies on the viability of the heart valve leaflets at the time of processing. The heart block is removed within 24 hours of death and the aor-tic and pulmonary valves trimmed immediately following retrieval. Following this processing, the valves are incubated in antibiotics at 30 degree C for 6 to 8 hours before being frozen in 10% DMSO at a controlled rate. A sample of tricuspid valve leaflet is placed in Krebs solution at the time of trimfning and is used for viability studies. Leaflet viability studies have been perfon-ned on all heart valves retrieved from 1993 to the present day at the Donor Tissue Bank of Victoria. Viability involves a qualitative assessment of the cellular outgrowth by leaflet fibroblasts, this assessment ranging from '-' for no outgrowth to '++++' for maximum outgrowth. Surgeons do not request valves with any particular viability and will use them whether they are viable or not. This evaluation was to determine the effects of long-term cryopreservation, cause of death, and also time lapse of heart removal following death on the viability of the retrieved leaflets. The aim of investigating the effects of long-term cryopreservation was to determine whether there was any correlation between initial viability and viability following storage for several months to several years. It was also decided to investigate whether there was any correlation between time length between death and heart retrieval and the viability. It was also thought that the cause of death may have had an effect on the viability, for example, did death by carbon monoxide poisoning have an effect on the viability of heart valve cells. Heart valves, which had been cryopreserved but could not be transplanted for various reasons were used to study the effects of cryopreservation in this study. These were thawed according to protocol and a sample of the valve

Rates of intentionally caused and road crash deaths of US citizens abroad.

Science.gov (United States)

Sherry, Melissa K; Mossallam, Mahmoud; Mulligan, Matthew; Hyder, Adnan A; Bishai, David

2015-04-01

Currently, little is known about rates of death by cause and country among US travellers. Understanding the risk by cause and country is imperative to risk communication and the development of risk reduction strategies. Publicly available data on non-natural deaths of US citizens abroad were gathered from January 2003 to December 2009 from the US Department of State's Department Bureau of Consular Affairs. Traveller information was gathered from the US Department of Commerce Office of Travel and Tourism for the same time period. Rates of death were calculated by dividing the number of non-natural deaths of US citizens abroad by the number of US outbound visits for each country. A total of 5417 non-natural death events were retrieved between 2003 and 2009 from the US State Department. Intentionally caused death rates ranged from 21.44 per 1 000 000 visits in the Philippines to 0 per 1 000 000 visits in several countries; the majority of countries had fewer than five intentionally caused deaths per 1 000 000 visits. Rates of road traffic crashes were higher than rates of intentionally caused deaths in almost every instance. Thailand had the highest rate of deaths due to road traffic crashes (16.49 per 1 000 000), followed by Vietnam, Morocco and South Africa (15.12 per 1 000 000, 11.96 per 1 000 000 and 10.90 per 1 000 000, respectively). Motorcycle deaths account for most of the heightened risk observed in Thailand and Vietnam. The leading cause of non-natural deaths in US travellers abroad was road crashes, which exceeds intentional injury as the leading cause of non-natural deaths in almost every country where US citizens travel. Southeast Asia had the highest unintentional injury death rates for US citizens abroad due to the high rates of deaths from motorcycle crashes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Blockage of spontaneous Ca2+ oscillation causes cell death in intraerythrocitic Plasmodium falciparum.

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Masahiro Enomoto

Full Text Available Malaria remains one of the world's most important infectious diseases and is responsible for enormous mortality and morbidity. Resistance to antimalarial drugs is a challenging problem in malaria control. Clinical malaria is associated with the proliferation and development of Plasmodium parasites in human erythrocytes. Especially, the development into the mature forms (trophozoite and schizont of Plasmodium falciparum (P. falciparum causes severe malaria symptoms due to a distinctive property, sequestration which is not shared by any other human malaria. Ca(2+ is well known to be a highly versatile intracellular messenger that regulates many different cellular processes. Cytosolic Ca(2+ increases evoked by extracellular stimuli are often observed in the form of oscillating Ca(2+ spikes (Ca(2+ oscillation in eukaryotic cells. However, in lower eukaryotic and plant cells the physiological roles and the molecular mechanisms of Ca(2+ oscillation are poorly understood. Here, we showed the observation of the inositol 1,4,5-trisphospate (IP(3-dependent spontaneous Ca(2+ oscillation in P. falciparum without any exogenous extracellular stimulation by using live cell fluorescence Ca(2+ imaging. Intraerythrocytic P. falciparum exhibited stage-specific Ca(2+ oscillations in ring form and trophozoite stages which were blocked by IP(3 receptor inhibitor, 2-aminoethyl diphenylborinate (2-APB. Analyses of parasitaemia and parasite size and electron micrograph of 2-APB-treated P. falciparum revealed that 2-APB severely obstructed the intraerythrocytic maturation, resulting in cell death of the parasites. Furthermore, we confirmed the similar lethal effect of 2-APB on the chloroquine-resistant strain of P. falciparum. To our best knowledge, we for the first time showed the existence of the spontaneous Ca(2+ oscillation in Plasmodium species and clearly demonstrated that IP(3-dependent spontaneous Ca(2+ oscillation in P. falciparum is critical for the development

CDC WONDER: Mortality - Underlying Cause of Death

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U.S. Department of Health & Human Services — The CDC WONDER Mortality - Underlying Cause of Death online database is a county-level national mortality and population database spanning the years since 1979. Data...

Causes of death in familial adenomatous polyposis

DEFF Research Database (Denmark)

Galle, T S; Juel, K; Bülow, S

1999-01-01

The prognosis in familial adenomatous polyposis (FAP) has improved over the past decades owing to a reduction in the prevalence of colorectal cancer, resulting from effective early screening. During the same period several polyposis registers have recorded an increasing number of deaths due to du...... to duodenal/periampullary cancer and desmoid tumours. The aim of this study was to examine the causes of death with special emphasis on duodenal/periampullary cancer.......The prognosis in familial adenomatous polyposis (FAP) has improved over the past decades owing to a reduction in the prevalence of colorectal cancer, resulting from effective early screening. During the same period several polyposis registers have recorded an increasing number of deaths due...

Causes of deaths data, linkages and big data perspectives.

Science.gov (United States)

Rey, Grégoire; Bounebache, Karim; Rondet, Claire

2018-07-01

The study of cause-specific mortality data is one of the main sources of information for public health monitoring. In most industrialized countries, when a death occurs, it is a legal requirement that a medical certificate based on the international form recommended by World Health Organization's (WHO) is filled in by a physician. The physician reports the causes of death that directly led or contributed to the death on the death certificate. The death certificate is then forwarded to a coding office, where each cause is coded, and one underlying cause is defined, using the rules of the International Classification of Diseases and Related Health Problems, now in its 10th Revision (ICD-10). Recently, a growing number of countries have adopted, or have decided to adopt, the coding software Iris, developed and maintained by an international consortium 1 . This whole standardized production process results in a high and constantly increasing international comparability of cause-specific mortality data. While these data could be used for international comparisons and benchmarking of global burden of diseases, quality of care and prevention policies, there are also many other ways and methods to explore their richness, especially when they are linked with other data sources. Some of these methods are potentially referring to the so-called "big data" field. These methods could be applied both to the production of the data, to the statistical processing of the data, and even more to process these data linked to other databases. In the present note, we depict the main domains in which this new field of methods could be applied. We focus specifically on the context of France, a 65 million inhabitants country with a centralized health data system. Finally we will insist on the importance of data quality, and the specific problematics related to death certification in the forensic medicine domain. Copyright © 2016 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All

Autophagic cell death: Loch Ness monster or endangered species?

Science.gov (United States)

Shen, Han-Ming; Codogno, Patrice

2011-05-01

The concept of autophagic cell death was first established based on observations of increased autophagic markers in dying cells. The major limitation of such a morphology-based definition of autophagic cell death is that it fails to establish the functional role of autophagy in the cell death process, and thus contributes to the confusion in the literature regarding the role of autophagy in cell death and cell survival. Here we propose to define autophagic cell death as a modality of non-apoptotic or necrotic programmed cell death in which autophagy serves as a cell death mechanism, upon meeting the following set of criteria: (i) cell death occurs without the involvement of apoptosis; (ii) there is an increase of autophagic flux, and not just an increase of the autophagic markers, in the dying cells; and (iii) suppression of autophagy via both pharmacological inhibitors and genetic approaches is able to rescue or prevent cell death. In light of this new definition, we will discuss some of the common problems and difficulties in the study of autophagic cell death and also revisit some well-reported cases of autophagic cell death, aiming to achieve a better understanding of whether autophagy is a real killer, an accomplice or just an innocent bystander in the course of cell death. At present, the physiological relevance of autophagic cell death is mainly observed in lower eukaryotes and invertebrates such as Dictyostelium discoideum and Drosophila melanogaster. We believe that such a clear definition of autophagic cell death will help us study and understand the physiological or pathological relevance of autophagic cell death in mammals.

Triptolide induces lysosomal-mediated programmed cell death in MCF-7 breast cancer cells

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Owa C

2013-09-01

Full Text Available Chie Owa, Michael E Messina Jr, Reginald HalabyDepartment of Biology, Montclair State University, Montclair, NJ, USABackground: Breast cancer is a major cause of death; in fact, it is the most common type, in order of the number of global deaths, of cancer in women worldwide. This research seeks to investigate how triptolide, an extract from the Chinese herb Tripterygium wilfordii Hook F, induces apoptosis in MCF-7 human breast cancer cells. Accumulating evidence suggests a role for lysosomal proteases in the activation of apoptosis. However, there is also some controversy regarding the direct participation of lysosomal proteases in activation of key apoptosis-related caspases and release of mitochondrial cytochrome c. In the present study, we demonstrate that triptolide induces an atypical, lysosomal-mediated apoptotic cell death in MCF-7 cells because they lack caspase-3.Methods: MCF-7 cell death was characterized via cellular morphology, chromatin condensation, 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide colorimetric cell growth inhibition assay and the expression levels of proapoptotic proteins. Acridine orange and LysoTracker® staining were performed to visualize lysosomes. Lysosomal enzymatic activity was monitored using an acid phosphatase assay and western blotting of cathepsin B protein levels in the cytosolic fraction, which showed increased enzymatic activity in drug-treated cells.Results: These experiments suggest that triptolide-treated MCF-7 cells undergo atypical apoptosis and that, during the early stages, lysosomal enzymes leak into the cytosol, indicating lysosomal membrane permeability.Conclusion: Our results suggest that further studies are warranted to investigate triptolide's potential as an anticancer therapeutic agent.Keywords: triptolide, MCF-7 breast cancer cells, apoptosis, lysosomes, lysosomal membrane permeabilization (LMP

Use of the Coding Causes of Death in HIV in the classification of deaths in Northeastern Brazil.

Science.gov (United States)

Alves, Diana Neves; Bresani-Salvi, Cristiane Campello; Batista, Joanna d'Arc Lyra; Ximenes, Ricardo Arraes de Alencar; Miranda-Filho, Demócrito de Barros; Melo, Heloísa Ramos Lacerda de; Albuquerque, Maria de Fátima Pessoa Militão de

2017-01-01

Describe the coding process of death causes for people living with HIV/AIDS, and classify deaths as related or unrelated to immunodeficiency by applying the Coding Causes of Death in HIV (CoDe) system. A cross-sectional study that codifies and classifies the causes of deaths occurring in a cohort of 2,372 people living with HIV/AIDS, monitored between 2007 and 2012, in two specialized HIV care services in Pernambuco. The causes of death already codified according to the International Classification of Diseases were recoded and classified as deaths related and unrelated to immunodeficiency by the CoDe system. We calculated the frequencies of the CoDe codes for the causes of death in each classification category. There were 315 (13%) deaths during the study period; 93 (30%) were caused by an AIDS-defining illness on the Centers for Disease Control and Prevention list. A total of 232 deaths (74%) were related to immunodeficiency after application of the CoDe. Infections were the most common cause, both related (76%) and unrelated (47%) to immunodeficiency, followed by malignancies (5%) in the first group and external causes (16%), malignancies (12 %) and cardiovascular diseases (11%) in the second group. Tuberculosis comprised 70% of the immunodeficiency-defining infections. Opportunistic infections and aging diseases were the most frequent causes of death, adding multiple disease burdens on health services. The CoDe system increases the probability of classifying deaths more accurately in people living with HIV/AIDS. Descrever o processo de codificação das causas de morte em pessoas vivendo com HIV/Aids, e classificar os óbitos como relacionados ou não relacionados à imunodeficiência aplicando o sistema Coding Causes of Death in HIV (CoDe). Estudo transversal, que codifica e classifica as causas dos óbitos ocorridos em uma coorte de 2.372 pessoas vivendo com HIV/Aids acompanhadas entre 2007 e 2012 em dois serviços de atendimento especializado em HIV em

Causes of death in a contemporary cohort of patients with invasive aspergillosis.

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Carolina Garcia-Vidal

Full Text Available Information regarding the processes leading to death in patients with invasive aspergillosis (IA is lacking. We sought to determine the causes of death in these patients, the role that IA played in the cause, and the timing of death. The factors associated with IA-related mortality are also analyzed. We conducted a multicenter study (2008-2011 of cases of proven and probable IA. The causes of death and whether mortality was judged to be IA-related or IA-unrelated were determined by consensus using a six-member review panel. A multivariate analysis was performed to determine risk factors for IA-related death. Of 152 patients with IA, 92 (60.5% died. Mortality was judged to be IA-related in 62 cases and IA-unrelated in 30. The most common cause of IA-related death was respiratory failure (50/62 patients, caused primarily by Aspergillus infection, although also by concomitant infections or severe comorbidities. Progression of underlying disease and bacteremic shock were the most frequent causes of IA-unrelated death. IA-related mortality accounted for 98% and 87% of deaths within the first 14 and 21 days, respectively. Liver disease (HR 4.54; 95% CI, 1.69-12.23 was independently associated with IA-related mortality, whereas voriconazole treatment was associated with reduced risk of death (HR 0.43; 95% CI, 0.20-0.93. In conclusion, better management of lung injury after IA diagnosis is the main challenge for physicians to improve IA outcomes. There are significant differences in causes and timing between IA-related and IA-unrelated mortality and these should be considered in future research to assess the quality of IA care.

CDC WONDER: Mortality - Multiple Cause of Death

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U.S. Department of Health & Human Services — The Mortality - Multiple Cause of Death data on CDC WONDER are county-level national mortality and population data spanning the years 1999-2006. These data are...

Immunogenic Cell Death Induced by Ginsenoside Rg3: Significance in Dendritic Cell-based Anti-tumor Immunotherapy.

Science.gov (United States)

Son, Keum-Joo; Choi, Ki Ryung; Lee, Seog Jae; Lee, Hyunah

2016-02-01

Cancer is one of the leading causes of morbidity and mortality worldwide; therefore there is a need to discover new therapeutic modules with improved efficacy and safety. Immune-(cell) therapy is a promising therapeutic strategy for the treatment of intractable cancers. The effectiveness of certain chemotherapeutics in inducing immunogenic tumor cell death thus promoting cancer eradication has been reported. Ginsenoside Rg3 is a ginseng saponin that has antitumor and immunomodulatory activity. In this study, we treated tumor cells with Rg3 to verify the significance of inducing immunogenic tumor cell death in antitumor therapy, especially in DC-based immunotherapy. Rg3 killed the both immunogenic (B16F10 melanoma cells) and non-immunogenic (LLC: Lewis Lung Carcinoma cells) tumor cells by inducing apoptosis. Surface expression of immunogenic death markers including calreticulin and heat shock proteins and the transcription of relevant genes were increased in the Rg3-dying tumor. Increased calreticulin expression was directly related to the uptake of dying tumor cells by dendritic cells (DCs): the proportion of CRT(+) CD11c(+) cells was increased in the Rg3-treated group. Interestingly, tumor cells dying by immunogenic cell death secreted IFN-γ, an effector molecule for antitumor activity in T cells. Along with the Rg3-induced suppression of pro-angiogenic (TNF-α) and immunosuppressive cytokine (TGF-β) secretion, IFN-γ production from the Rg3-treated tumor cells may also indicate Rg3 as an effective anticancer immunotherapeutic strategy. The data clearly suggests that Rg3-induced immunogenic tumor cell death due its cytotoxic effect and its ability to induce DC function. This indicates that Rg3 may be an effective immunotherapeutic strategy.

Porcine circovirus-2 capsid protein induces cell death in PK15 cells

Energy Technology Data Exchange (ETDEWEB)

Walia, Rupali; Dardari, Rkia, E-mail: rdardari@ucalgary.ca; Chaiyakul, Mark; Czub, Markus

2014-11-15

Studies have shown that Porcine circovirus (PCV)-2 induces apoptosis in PK15 cells. Here we report that cell death is induced in PCV2b-infected PK15 cells that express Capsid (Cap) protein and this effect is enhanced in interferon gamma (IFN-γ)-treated cells. We further show that transient PCV2a and 2b-Cap protein expression induces cell death in PK15 cells at rate similar to PCV2 infection, regardless of Cap protein localization. These data suggest that Cap protein may have the capacity to trigger different signaling pathways involved in cell death. Although further investigation is needed to gain deeper insights into the nature of the pathways involved in Cap-induced cell death, this study provides evidence that PCV2-induced cell death in kidney epithelial PK15 cells can be mapped to the Cap protein and establishes the need for future research regarding the role of Cap-induced cell death in PCV2 pathogenesis. - Highlights: • IFN-γ enhances PCV2 replication that leads to cell death in PK15 cells. • IFN-γ enhances nuclear localization of the PCV2 Capsid protein. • Transient PCV2a and 2b-Capsid protein expression induces cell death. • Cell death is not dictated by specific Capsid protein sub-localization.

Algorithms for enhancing public health utility of national causes-of-death data

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Pourmalek Farshad

2010-05-01

Full Text Available Abstract Background Coverage and quality of cause-of-death (CoD data varies across countries and time. Valid, reliable, and comparable assessments of trends in causes of death from even the best systems are limited by three problems: a changes in the International Statistical Classification of Diseases and Related Health Problems (ICD over time; b the use of tabulation lists where substantial detail on causes of death is lost; and c many deaths assigned to causes that cannot or should not be considered underlying causes of death, often called garbage codes (GCs. The Global Burden of Disease Study and the World Health Organization have developed various methods to enhance comparability of CoD data. In this study, we attempt to build on these approaches to enhance the utility of national cause-of-death data for public health analysis. Methods Based on careful consideration of 4,434 country-years of CoD data from 145 countries from 1901 to 2008, encompassing 743 million deaths in ICD versions 1 to 10 as well as country-specific cause lists, we have developed a public health-oriented cause-of-death list. These 56 causes are organized hierarchically and encompass all deaths. Each cause has been mapped from ICD-6 to ICD-10 and, where possible, they have also been mapped to the International List of Causes of Death 1-5. We developed a typology of different classes of GCs. In each ICD revision, GCs have been identified. Target causes to which these GCs should be redistributed have been identified based on certification practice and/or pathophysiology. Proportionate redistribution, statistical models, and expert algorithms have been developed to redistribute GCs to target codes for each age-sex group. Results The fraction of all deaths assigned to GCs varies tremendously across countries and revisions of the ICD. In general, across all country-years of data available, GCs have declined from more than 43% in ICD-7 to 24% in ICD-10. In some regions, such

Singapore grouper iridovirus, a large DNA virus, induces nonapoptotic cell death by a cell type dependent fashion and evokes ERK signaling.

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Huang, Xiaohong; Huang, Youhua; Ouyang, Zhengliang; Xu, Lixiao; Yan, Yang; Cui, Huachun; Han, Xin; Qin, Qiwei

2011-08-01

Virus induced cell death, including apoptosis and nonapoptotic cell death, plays a critical role in the pathogenesis of viral diseases. Singapore grouper iridovirus (SGIV), a novel iridovirus of genus Ranavirus, causes high mortality and heavy economic losses in grouper aquaculture. Here, using fluorescence microscopy, electron microscopy and biochemical assays, we found that SGIV infection in host (grouper spleen, EAGS) cells evoked nonapoptotic programmed cell death (PCD), characterized by appearance of cytoplasmic vacuoles and distended endoplasmic reticulum, in the absence of DNA fragmentation, apoptotic bodies and caspase activation. In contrast, SGIV induced typical apoptosis in non-host (fathead minnow, FHM) cells, as evidenced by caspase activation and DNA fragmentation, suggesting that SGIV infection induced nonapoptotic cell death by a cell type dependent fashion. Furthermore, viral replication was essential for SGIV induced nonapoptotic cell death, but not for apoptosis. Notably, the disruption of mitochondrial transmembrane potential (ΔΨm) and externalization of phosphatidylserine (PS) were not detected in EAGS cells but in FHM cells after SGIV infection. Moreover, the extracellular signal-regulated kinase (ERK) signaling was involved in SGIV infection induced nonapoptotic cell death and viral replication. This is a first demonstration of ERK-mediated nonapoptotic cell death induced by a DNA virus. These findings contribute to understanding the mechanisms of iridovirus pathogenesis.

CDC WONDER: Mortality - Multiple Cause of Death

Data.gov (United States)

U.S. Department of Health & Human Services — The Mortality - Multiple Cause of Death data on CDC WONDER are county-level national mortality and population data spanning the years 1999-2009. Data are based on...

Radiation-induced cell death in embryogenic cells of coniferous plants

International Nuclear Information System (INIS)

Watanabe, Yoshito; Homma-Takeda, Shino; Yukawa, Masae; Nishimura, Yoshikazu; Sasamoto, Hamako; Takahagi, Masahiko

2004-01-01

Reproductive processes are particularly radiosensitive in plant development, which was clearly illustrated in reduction of seed formation in native coniferous plants around Chernobyl after the nuclear accident. For the purpose to investigate the effects of ionizing radiation on embryonic formation in coniferous plants, we used an embryo-derived embryogenic cell culture of a Japanese native coniferous plant, Japanese cedar (Cryplomeria japonica). The embryogenic cells were so radiosensitive that most of the cells died by X-ray irradiation of 5 Gy. This indicated that the embryogenic cells are as radiosensitive as some mammalian cells including lymphocytes. We considered that this type of radiosensitive cell death in the embryogenic cells should be responsible for reproductive damages of coniferous plants by low dose of ionizing radiation. The cell death of the embryogenic cells was characteristic of nuclear DNA fragmentation, which is typically observed in radiation-induced programmed cell death, i.e. apoptosis, in mammalian cells. On the other hand, cell death with nuclear DNA fragmentation did not develop by X-ray irradiation in vegetative cells including meristematic cells of Japanese cedar. This suggests that an apoptosis-like programmed cell death should develop cell-specifically in embryogenic cells by ionizing radiation. The abortion of embryogenic cells may work to prevent transmission of radiation-induced genetic damages to the descendants. (author)

Arabidopsis GRI is involved in the regulation of cell death induced by extracellular ROS.

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Wrzaczek, Michael; Brosché, Mikael; Kollist, Hannes; Kangasjärvi, Jaakko

2009-03-31

Reactive oxygen species (ROS) have important functions in plant stress responses and development. In plants, ozone and pathogen infection induce an extracellular oxidative burst that is involved in the regulation of cell death. However, very little is known about how plants can perceive ROS and regulate the initiation and the containment of cell death. We have identified an Arabidopsis thaliana protein, GRIM REAPER (GRI), that is involved in the regulation of cell death induced by extracellular ROS. Plants with an insertion in GRI display an ozone-sensitive phenotype. GRI is an Arabidopsis ortholog of the tobacco flower-specific Stig1 gene. The GRI protein appears to be processed in leaves with a release of an N-terminal fragment of the protein. Infiltration of the N-terminal fragment of the GRI protein into leaves caused cell death in a superoxide- and salicylic acid-dependent manner. Analysis of the extracellular GRI protein yields information on how plants can initiate ROS-induced cell death during stress response and development.

A multicenter study of outcome in systemic lupus erythematosus. II. Causes of death.

Science.gov (United States)

Rosner, S; Ginzler, E M; Diamond, H S; Weiner, M; Schlesinger, M; Fries, J F; Wasner, C; Medsger, T A; Ziegler, G; Klippel, J H; Hadler, N M; Albert, D A; Hess, E V; Spencer-Green, G; Grayzel, A; Worth, D; Hahn, B H; Barnett, E V

1982-06-01

Causes of death were examined for 1,103 systemic lupus erythematosus patients who were followed from 1965 to 1978 at 9 centers that participated in the Lupus Survival Study Group. A total of 222 patients (20%) died. Lupus-related organ system involvement (mainly active nephritis) and infection were the most frequent primary causes of death. Causes of death were similar throughout the followup period. Hemodialysis had little impact on the length of survival for patients with nephritis. Active central nervous system disease and myocardial infarction were infrequent causes of death. There were no deaths from malignancy.

[Causes of death in amyotrophic lateral sclerosis : Results from the Rhineland-Palatinate ALS registry].

Science.gov (United States)

Wolf, J; Safer, A; Wöhrle, J C; Palm, F; Nix, W A; Maschke, M; Grau, A J

2017-08-01

Amyotrophic lateral sclerosis (ALS) is associated with an increased mortality. Knowledge of possible causes of death could lead to an individualization of the palliative treatment concept and result in a differentiated palliative treatment pathway. Currently, only few systematic data are available on the heterogeneity of causes of death associated with ALS. Analysis of the various causes of death in a prospective population-based German cohort of ALS patients. Analysis of data of the Rhineland-Palatinate ALS registry in which newly diagnosed patients who had been identified between October 2009 and September 2012 were prospectively enrolled and followed up at regular intervals. From this prospective cohort study the causes of death were elicited based on information provided by the attending physicians, family members and by means of death certificates registered by the regional health authorities in Rhineland-Palatinate. Out of 200 ALS patients registered 148 died between register initiation on 1 October 2009 and the end of follow-up on 30 September 2015 (78 males and 70 females, death rate 74%). The most frequent cause of death was respiratory failure as a consequence of weakness of respiratory muscles (n = 91, 61%). Less frequent causes of death were pneumonia (n = 13, 9%), terminal cachexia (n = 9, 6%) and death from cardiovascular causes including sudden death (n = 9, 6%). Cases of suicide were rare (n = 3, 2%) as were deaths due to concurrent diseases (n = 2). In 21 cases (14%) the exact cause of death could not be clarified. Differences in the causes of death only showed a tendency towards the ALS phenotype. Respiratory failure was the cause of death in all patients with a respiratory phenotype and in 78% of patients with flail arm syndrome. Despite the low number of patients (8%) with additional frontotemporal dementia (FTD) a distinct difference in causes of death between those with and without FTD could be observed. Death due to respiratory

Early death in active professional athletes: Trends and causes.

Science.gov (United States)

Lemez, S; Wattie, N; Baker, J

2016-05-01

The objective of the study was to examine mortality trends and causes of death among professional athletes from the four major sports in North America who died during their playing careers. 205 deceased athletes who were registered as active when they died from the National Basketball Association (NBA), National Football League (NFL), National Hockey League (NHL), and Major League Baseball (MLB) were examined. Results were compared with the Canadian and U.S. general population. The leading causes of death in players reflected the leading causes of death in the Canadian and U.S. general population (i.e., car accidents). Descriptively, NFL and NBA players had a higher likelihood of dying in a car accident (OR 1.75, 95% CI: 0.91-3.36) compared with NHL and MLB players. In addition, NFL and NBA players had a significantly higher likelihood of dying from a cardiac-related illness (OR 4.44, 95% CI: 1.59-12.43). Mortality trends were disproportionate to team size. Overall, death in active athletes is low. Out of 53 400 athletes who have historically played in the four leagues, only 205 died while active (0.38%). Future examinations into the trends and causes of mortality in elite athlete populations will create a better understanding of health-related risks in elite sport. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Non-Canonical Cell Death Induced by p53

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Atul Ranjan

2016-12-01

Full Text Available Programmed cell death is a vital biological process for multicellular organisms to maintain cellular homeostasis, which is regulated in a complex manner. Over the past several years, apart from apoptosis, which is the principal mechanism of caspase-dependent cell death, research on non-apoptotic forms of programmed cell death has gained momentum. p53 is a well characterized tumor suppressor that controls cell proliferation and apoptosis and has also been linked to non-apoptotic, non-canonical cell death mechanisms. p53 impacts these non-canonical forms of cell death through transcriptional regulation of its downstream targets, as well as direct interactions with key players involved in these mechanisms, in a cell type- or tissue context-dependent manner. In this review article, we summarize and discuss the involvement of p53 in several non-canonical modes of cell death, including caspase-independent apoptosis (CIA, ferroptosis, necroptosis, autophagic cell death, mitotic catastrophe, paraptosis, and pyroptosis, as well as its role in efferocytosis which is the process of clearing dead or dying cells.

Social inequalities in causes of death amenable to health care in Norway

Directory of Open Access Journals (Sweden)

Camilla Hem

2007-01-01

Full Text Available Objective: Investigate if there are educational inequalities in causes of death considered amenable to health care in Norway and compare this with non-amenable causes. Methods: The study used the concept of “amenable mortality”, which here includes 34 specific causes of death. A linked data file, with information from the Norwegian Causes of Death Registry and the Educational Registry was analyzed. The study population included the whole Norwegian population in two age groups of interest (25-49 and 50-74 years. Information on deaths was from the period 1990-2001. Education was recorded in 1990 and it was grouped in four categories as: basic, lower secondary, higher secondary and higher. In the study men and women were analysed seperately. The analysis was conducted for all amenable causes pooled with and without ischemic heart disease. A Cox proportional hazard regression model was fitted to estimate hazard rate ratios. Results: The study showed educational differences in mortality from causes of death considered amenable to health care, in both age groups and sexes. This was seen both when including and excluding ischemic heart disease. The effect sizes were comparable for amenable and non-amenable causes in both age groups and sexes. Conclusions: This study revealed systematic higher risk of death in lower educational groups in causes of death considered amenable to health care. This indicates potential weaknesses in equitable provision of health care for the Norwegian population. Additional research is needed to identify domains within the health care system of particular concern.

Using expert knowledge to incorporate uncertainty in cause-of-death assignments for modeling of cause-specific mortality

Science.gov (United States)

Walsh, Daniel P.; Norton, Andrew S.; Storm, Daniel J.; Van Deelen, Timothy R.; Heisy, Dennis M.

2018-01-01

Implicit and explicit use of expert knowledge to inform ecological analyses is becoming increasingly common because it often represents the sole source of information in many circumstances. Thus, there is a need to develop statistical methods that explicitly incorporate expert knowledge, and can successfully leverage this information while properly accounting for associated uncertainty during analysis. Studies of cause-specific mortality provide an example of implicit use of expert knowledge when causes-of-death are uncertain and assigned based on the observer's knowledge of the most likely cause. To explicitly incorporate this use of expert knowledge and the associated uncertainty, we developed a statistical model for estimating cause-specific mortality using a data augmentation approach within a Bayesian hierarchical framework. Specifically, for each mortality event, we elicited the observer's belief of cause-of-death by having them specify the probability that the death was due to each potential cause. These probabilities were then used as prior predictive values within our framework. This hierarchical framework permitted a simple and rigorous estimation method that was easily modified to include covariate effects and regularizing terms. Although applied to survival analysis, this method can be extended to any event-time analysis with multiple event types, for which there is uncertainty regarding the true outcome. We conducted simulations to determine how our framework compared to traditional approaches that use expert knowledge implicitly and assume that cause-of-death is specified accurately. Simulation results supported the inclusion of observer uncertainty in cause-of-death assignment in modeling of cause-specific mortality to improve model performance and inference. Finally, we applied the statistical model we developed and a traditional method to cause-specific survival data for white-tailed deer, and compared results. We demonstrate that model selection

Postmortem computed tomography for diagnosis of cause of death in male prisoners

International Nuclear Information System (INIS)

Sohail, S.; Khan, Q.S.; Mirza, F.H.

2010-01-01

To determine the utility of postmortem CT (PMCT) examination in establishing the cause of death among male prisoners dying in Karachi jails. A descriptive study was carried out from February 2006 to September 2007, CT Scan section, Civil Hospital Karachi and the Mortuary, Dow Medical College, Dow University of Health Sciences, Karachi. Adult male prisoners dying in the Karachi central prison and referred to the study setting for determining the cause of death for medico legal purpose were included. Female prisoners and those cases where the final report of cause of death was not available were excluded. CT scan of the vital body regions (head, neck, thorax, abdomen and pelvis) was carried out in all cases. The scan was read and reported by two radiologists. Anatomical dissection based autopsy was carried out by the forensic expert. Final report regarding the cause of death was issued by the forensic expert based on the combined findings, histopathology, toxicology results and circumstantial evidence. The CT scan and autopsy findings were compared and percentage agreement was determined using kappa statistics. There were 14 cases in all with mean age of 41.2 +- 17 years. The alleged mode of death was custodial torture in all cases. CT scan determined the cause of death to be natural cardio-respiratory failure in 10, strangulation in 01, pulmonary tuberculosis (TB) in 02 and trauma to spine in 01 case. The autopsy determined natural death in 11 and pulmonary TB in 02 and asphyxia in 01. The percentage agreement between CT and autopsy was 92% (k=0.92) and between CT and finalized cause of death was 100% (k=1.0). PMCT is as effective as dissection autopsy in identifying pulmonary infections and natural causes of death. It is more effective in identifying vertebral fractures which may exclude hanging and corroborate trauma to spine (JPMA 60:4; 2010). (author)

Mitochondrial fission proteins regulate programmed cell death in yeast.

Science.gov (United States)

Fannjiang, Yihru; Cheng, Wen-Chih; Lee, Sarah J; Qi, Bing; Pevsner, Jonathan; McCaffery, J Michael; Hill, R Blake; Basañez, Gorka; Hardwick, J Marie

2004-11-15

The possibility that single-cell organisms undergo programmed cell death has been questioned in part because they lack several key components of the mammalian cell death machinery. However, yeast encode a homolog of human Drp1, a mitochondrial fission protein that was shown previously to promote mammalian cell death and the excessive mitochondrial fragmentation characteristic of apoptotic mammalian cells. In support of a primordial origin of programmed cell death involving mitochondria, we found that the Saccharomyces cerevisiae homolog of human Drp1, Dnm1, promotes mitochondrial fragmentation/degradation and cell death following treatment with several death stimuli. Two Dnm1-interacting factors also regulate yeast cell death. The WD40 repeat protein Mdv1/Net2 promotes cell death, consistent with its role in mitochondrial fission. In contrast to its fission function in healthy cells, Fis1 unexpectedly inhibits Dnm1-mediated mitochondrial fission and cysteine protease-dependent cell death in yeast. Furthermore, the ability of yeast Fis1 to inhibit mitochondrial fission and cell death can be functionally replaced by human Bcl-2 and Bcl-xL. Together, these findings indicate that yeast and mammalian cells have a conserved programmed death pathway regulated by a common molecular component, Drp1/Dnm1, that is inhibited by a Bcl-2-like function.

Rapid generation of mitochondrial superoxide induces mitochondrion-dependent but caspase-independent cell death in hippocampal neuronal cells that morphologically resembles necroptosis

International Nuclear Information System (INIS)

Fukui, Masayuki; Choi, Hye Joung; Zhu, Bao Ting

2012-01-01

Studies in recent years have revealed that excess mitochondrial superoxide production is an important etiological factor in neurodegenerative diseases, resulting from oxidative modifications of cellular lipids, proteins, and nucleic acids. Hence, it is important to understand the mechanism by which mitochondrial oxidative stress causes neuronal death. In this study, the immortalized mouse hippocampal neuronal cells (HT22) in culture were used as a model and they were exposed to menadione (also known as vitamin K 3 ) to increase intracellular superoxide production. We found that menadione causes preferential accumulation of superoxide in the mitochondria of these cells, along with the rapid development of mitochondrial dysfunction and cellular ATP depletion. Neuronal death induced by menadione is independent of the activation of the MAPK signaling pathways and caspases. The lack of caspase activation is due to the rapid depletion of cellular ATP. It was observed that two ATP-independent mitochondrial nucleases, namely, AIF and Endo G, are released following menadione exposure. Silencing of their expression using specific siRNAs results in transient suppression (for ∼ 12 h) of mitochondrial superoxide-induced neuronal death. While suppression of the mitochondrial superoxide dismutase expression markedly sensitizes neuronal cells to mitochondrial superoxide-induced cytotoxicity, its over-expression confers strong protection. Collectively, these findings showed that many of the observed features associated with mitochondrial superoxide-induced cell death, including caspase independency, rapid depletion of ATP level, mitochondrial release of AIF and Endo G, and mitochondrial swelling, are distinctly different from those of apoptosis; instead they resemble some of the known features of necroptosis. -- Highlights: ► Menadione causes mitochondrial superoxide accumulation and injury. ► Menadione-induced cell death is caspase-independent, due to rapid depletion of ATP

Rapid generation of mitochondrial superoxide induces mitochondrion-dependent but caspase-independent cell death in hippocampal neuronal cells that morphologically resembles necroptosis

Energy Technology Data Exchange (ETDEWEB)

Fukui, Masayuki; Choi, Hye Joung; Zhu, Bao Ting, E-mail: BTZhu@kumc.edu

2012-07-15

Studies in recent years have revealed that excess mitochondrial superoxide production is an important etiological factor in neurodegenerative diseases, resulting from oxidative modifications of cellular lipids, proteins, and nucleic acids. Hence, it is important to understand the mechanism by which mitochondrial oxidative stress causes neuronal death. In this study, the immortalized mouse hippocampal neuronal cells (HT22) in culture were used as a model and they were exposed to menadione (also known as vitamin K{sub 3}) to increase intracellular superoxide production. We found that menadione causes preferential accumulation of superoxide in the mitochondria of these cells, along with the rapid development of mitochondrial dysfunction and cellular ATP depletion. Neuronal death induced by menadione is independent of the activation of the MAPK signaling pathways and caspases. The lack of caspase activation is due to the rapid depletion of cellular ATP. It was observed that two ATP-independent mitochondrial nucleases, namely, AIF and Endo G, are released following menadione exposure. Silencing of their expression using specific siRNAs results in transient suppression (for ∼ 12 h) of mitochondrial superoxide-induced neuronal death. While suppression of the mitochondrial superoxide dismutase expression markedly sensitizes neuronal cells to mitochondrial superoxide-induced cytotoxicity, its over-expression confers strong protection. Collectively, these findings showed that many of the observed features associated with mitochondrial superoxide-induced cell death, including caspase independency, rapid depletion of ATP level, mitochondrial release of AIF and Endo G, and mitochondrial swelling, are distinctly different from those of apoptosis; instead they resemble some of the known features of necroptosis. -- Highlights: ► Menadione causes mitochondrial superoxide accumulation and injury. ► Menadione-induced cell death is caspase-independent, due to rapid depletion of

Fas/Fas ligand regulation mediates cell death in human Ewing's sarcoma cells treated with melatonin

Science.gov (United States)

García-Santos, G; Martin, V; Rodríguez-Blanco, J; Herrera, F; Casado-Zapico, S; Sánchez-Sánchez, A M; Antolín, I; Rodríguez, C

2012-01-01

Background: Despite recent advances in cancer therapy, the 5-year survival rate for Ewing's sarcoma is still very low, and new therapeutic approaches are necessary. It was found previously that melatonin induces cell death in the Ewing's sarcoma cell line, SK-N-MC, by activating the extrinsic apoptotic pathway. Methods: Melatonin actions were analysed by metabolic viability/survival cell assays, flow cytometry, quantitative PCR for mRNA expression, western blot for protein activation/expression and electrophoretic mobility shift assay for transcription factor activation. Results: Melatonin increases the expression of Fas and its ligand Fas L, this increase being responsible for cell death induced by the indolamine. Melatonin also produces a transient increase in intracellular oxidants and activation of the redox-regulated transcription factor Nuclear factor-kappaB. Inhibition of such activation prevents cell death and Fas/Fas L upregulation. Cytotoxic effect and Fas/Fas L regulation occur in all Ewing's cell lines studied, and do not occur in the other tumour cell lines studied where melatonin does not induce cell death. Conclusion: Our data offers new insights in the study of alternative therapeutic strategies in the treatment of Ewing's sarcoma. Further attention deserves to be given to the differences in the cellular biology of sensitive tumours that could explain the cytotoxic effect of melatonin and the increase in the level of free radicals caused by this molecule, in particular cancer types. PMID:22382690

Epilepsy, excess deaths and years of life lost from external causes.

Science.gov (United States)

Nevalainen, Olli; Simola, Mikko; Ansakorpi, Hanna; Raitanen, Jani; Artama, Miia; Isojärvi, Jouko; Auvinen, Anssi

2016-05-01

We systematically quantified excess mortality in epilepsy patients by cause of death using the population-attributable fraction and epilepsy-attributable years of potential life lost (YPLL) by age 75 years at ages 15 and over. We updated and undertook a re-review of mortality studies from our previous systematic review following PRISMA guidelines to identify cohort studies of general epilepsy populations reporting a relative risk (RR) of death by cause relative to the background rates in the population. Studies on epilepsy prevalence were identified through published reviews. Country-specific mortality figures were obtained from the WHO World Mortality Database. We performed a pooled analysis with the DerSimonian-Laird random effects method. In countries with very high Human Development Indices, epilepsy contributed to 0.5-1.1 % of all deaths in the total population. Among external causes, suicides (RR 2.9, 95 % confidence interval 2.2-3.8; I(2) 52 %) were the major contributor to YPLL, corresponding to 6.7 % and 4.2 % of excess YPLL due to epilepsy in the United States (US) and in the United Kingdom (UK) in 2010, with 541 (346-792) and 44 (28-65) excess suicide cases, respectively. Fatal accidental falls were more common, with 813 (610-1064) and 95 (71-125) excess deaths in the US and in the UK, but these caused only 2.0 % of excess YPLL as they occurred in older age groups. Suicides were the most important external cause of death in epilepsy patients in terms of excess YPLL, whereas other external causes were either more common in older ages or caused less excess deaths.

A chalcone-related small molecule that induces methuosis, a novel form of non-apoptotic cell death, in glioblastoma cells

OpenAIRE

Overmeyer, Jean H; Young, Ashley M; Bhanot, Haymanti; Maltese, William A

2011-01-01

Abstract Background Methuosis is a unique form of non-apoptotic cell death triggered by alterations in the trafficking of clathrin-independent endosomes, ultimately leading to extreme vacuolization and rupture of the cell. Results Here we describe a novel chalcone-like molecule, 3-(2-methyl-1H- indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (MIPP) that induces cell death with the hallmarks of methuosis. MIPP causes rapid accumulation of vacuoles derived from macropinosomes, based on time-lapse mi...

Early death, late death and repair factor in three human tumour cell lines

International Nuclear Information System (INIS)

Courdi, A.; Gioanni, J.; Mari, D.; Chauvel, P.

1997-01-01

The in vivo colony method used to generate survival curves following exposure to ionizing irradiation allows to score large clones, representing surviving cells, and small colonies, representing late reproductive death. By subtraction, early-dying cells can be estimated. In the three human tumour cell lines examined, we have observed that early cell death is a major mode of action of irradiation. The contribution of early cell death to total mortality increases as the dose increases. Moreover, repair due to dose-splitting and delayed plating in densely-inhibited cells is not observed in early-dying cells. (authors)

A CRISPR-Based Screen Identifies Genes Essential for West-Nile-Virus-Induced Cell Death.

Science.gov (United States)

Ma, Hongming; Dang, Ying; Wu, Yonggan; Jia, Gengxiang; Anaya, Edgar; Zhang, Junli; Abraham, Sojan; Choi, Jang-Gi; Shi, Guojun; Qi, Ling; Manjunath, N; Wu, Haoquan

2015-07-28

West Nile virus (WNV) causes an acute neurological infection attended by massive neuronal cell death. However, the mechanism(s) behind the virus-induced cell death is poorly understood. Using a library containing 77,406 sgRNAs targeting 20,121 genes, we performed a genome-wide screen followed by a second screen with a sub-library. Among the genes identified, seven genes, EMC2, EMC3, SEL1L, DERL2, UBE2G2, UBE2J1, and HRD1, stood out as having the strongest phenotype, whose knockout conferred strong protection against WNV-induced cell death with two different WNV strains and in three cell lines. Interestingly, knockout of these genes did not block WNV replication. Thus, these appear to be essential genes that link WNV replication to downstream cell death pathway(s). In addition, the fact that all of these genes belong to the ER-associated protein degradation (ERAD) pathway suggests that this might be the primary driver of WNV-induced cell death. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Tabulador de causas múltiplas de morte Multiple causes- of-death tabulator

Directory of Open Access Journals (Sweden)

Augusto H. Santo

1999-08-01

Full Text Available O uso de causas múltiplas de morte vem sendo atualmente preconizado para descrever e analisar os determinantes patológicos da mortalidade em populações, como complemento ao uso tradicional da causa básica de morte. O estudo das causas múltiplas pode realizar-se por meio da apresentação de todas as menções das causas básicas e associadas de morte e por meio de associações de causas. Um programa para microcomputador foi desenvolvido para processar bancos de dados contendo as causas de morte informadas no Modelo Internacional de Atestado Médico de Causa de Morte, denominado Tabulador de Causas Múltiplas, que gera uma tabela matriz a partir da qual podem ser derivadas as demais formas de apresentação e análise, além de poder ser usado como instrumento de crítica dos dados de mortalidade.The use of multiple-causes-of-death is currently being recommended in order to describe and analyze the pathological determinants of mortality in populations, as a supplement to the traditional use of the underlying cause of death. Multiple-causes-of-death can be studied by presenting all underlying and associated causes mentioned, and by means of associations of causes of death. Microcomputer software has been developed to process data files containing causes of death informed by physicians on the International Form of Medical Certificate of Causes of Death. The Multiple Cause of Death Tabulator software generates a matrix table from which the above forms of presentation and analysis can be achieved and mortality data be edited.

Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

Science.gov (United States)

2015-01-10

to all-cause mortality based on draws from the uncertainty distributions. Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute differences between countries decreased but relative differences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative differences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100,000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over

Morphological classification of plant cell deaths

DEFF Research Database (Denmark)

van Doorn, W.G.; Beers, E.P.; Dangl, J.L.

2011-01-01

, which can express features of both necrosis and vacuolar cell death, PCD in starchy cereal endosperm and during self-incompatibility. The present classification is not static, but will be subject to further revision, especially when specific biochemical pathways are better defined....... the classification of PCD in plants. Here we suggest a classification based on morphological criteria. According to this classification, the use of the term 'apoptosis' is not justified in plants, but at least two classes of PCD can be distinguished: vacuolar cell death and necrosis. During vacuolar cell death...

Drosophila Ninjurin A induces nonapoptotic cell death.

Directory of Open Access Journals (Sweden)

Sarah Broderick

Full Text Available Ninjurins are conserved transmembrane proteins that are upregulated across species in response to injury and stress. Their biological functions are not understood, in part because there have been few in vivo studies of their function. We analyzed the expression and function of one of three Drosophila Ninjurins, NijA. We found that NijA protein is redistributed to the cell surface in larval immune tissues after septic injury and is upregulated by the Toll pathway. We generated a null mutant of NijA, which displayed no detectable phenotype. In ectopic expression studies, NijA induced cell death, as evidenced by cell loss and acridine orange staining. These dying cells did not display hallmarks of apoptotic cells including TUNEL staining and inhibition by p35, indicating that NijA induced nonapoptotic cell death. In cell culture, NijA also induced cell death, which appeared to be cell autonomous. These in vivo studies identify a new role for the Ninjurin family in inducing nonapoptotic cell death.

Causes of death after traumatic spinal cord injury-a 70-year British study.

Science.gov (United States)

Savic, G; DeVivo, M J; Frankel, H L; Jamous, M A; Soni, B M; Charlifue, S

2017-10-01

Retrospective and prospective observational. Analyse causes of death after traumatic spinal cord injury (tSCI) in persons surviving the first year post injury, and establish any trend over time. Two spinal centres in Great Britain. The sample consisted of 5483 patients with tSCI admitted to Stoke Mandeville and Southport spinal centres who were injured between 1943 and 2010, survived first year post injury, had residual neurological deficit on discharge and were British residents. Mortality information, including causes of death, was collected up to 31 December 2014. Age-standardised cause-specific mortality rates were calculated for selected causes of death, and included trends over time and comparison with the general population. In total, 2322 persons (42.3% of the sample) died, with 2170 (93.5%) having a reliable cause of death established. The most frequent causes of death were respiratory (29.3% of all certified causes), circulatory, including cardiovascular and cerebrovascular diseases (26.7%), neoplasms (13.9%), urogenital (11.5%), digestive (5.3%) and external causes, including suicides (4.5%). Compared to the general population, age-standardised cause-specific mortality rates were higher for all causes, especially skin, urogenital and respiratory; rates showed improvement over time for suicides, circulatory and urogenital causes, no significant change for neoplasms, and increase for skin and respiratory causes. Leading causes of death after tSCI in persons surviving the first year post injury were respiratory, circulatory, neoplasms and urogenital. Cause-specific mortality rates showed improvement over time for most causes, but were still higher than the general population rates, especially for skin, urinary and respiratory causes.

Radiation induced cell death in cervical squamous cell carcinoma. An immunohistochemical and ultrastructural study

International Nuclear Information System (INIS)

Atari, Eio; Toda, Takayoshi; Sadi, A.M.; Egawa, Haruhiko; Moromizato, Hidehiko; Mamadi, T.; Kiyuna, Masaya

1998-01-01

To study the process of cell death in cervical squamous cell carcinoma (SCC) after radiation, an ultrastructural and immunohistochemical study was performed. Paraffin-embedded tissue blocks of biopsy samples pre- and post-radiation stage III SCC (n=15) were collected. Irradiation caused varying ultrastructural changes including nuclear and cytoplasmic disorganization suggesting cell necrosis. Immunohistochemically, the pre-radiation specimens showed no positive reaction for tumor necrosis factor-alpha (TNF-α), tumor necrosis factor-receptor (TNF-γ) or Fas. C-fos, p53 and bcl-2 showed positive reactions in only a few non-irradiated specimens. All of the irradiated specimens showed a positive reaction for TNF-α, and variable positive reactions were observed for TNF-γ, Fas, p53, c-fos and bcl-2. These results suggest that TNF-α, TNF-γ, and c-fos are responsible for radiation induced cell death in cervical SCC. (author)

Factors Associated with Pneumonia-caused Death in Older Adults with Autopsy-confirmed Dementia.

Science.gov (United States)

Manabe, Toshie; Mizukami, Katsuyoshi; Akatsu, Hiroyasu; Hashizume, Yoshio; Ohkubo, Takayoshi; Kudo, Koichiro; Hizawa, Nobuyuki

2017-01-01

Objective A better understanding of risk factors for pneumonia-caused death may help to improve the clinical management of dementia. Methods A retrospective observational study was conducted by reviewing the medical charts and autopsy reports of 204 patients who were admitted to hospital, underwent a post-mortem examination, and who were neuropathologically diagnosed with dementia. The risk factors for pneumonia-caused death were examined both as underlying and immediate causes of death using logistic regression models. Results A high frequency of pneumonia-caused death was observed both in underlying- (37.3%) and immediate- (44.1%) cause of death, but varied according to the subtypes of dementia. The factors related to pneumonia-caused death (underlying) were subtypes of dementia; Alzheimer's disease (odds ratio [OR], 2.891; 95% confidence interval [CI], 1.459-5.730); argyrophilic grain disease (OR, 3.148; 95% CI, 0.937-10.577); and progressive supranuclear palsy (OR, 34.921; 95% CI, 3.826-318.775), dysphagia (OR, 2.045; 95% CI, 1.047-3.994), diabetes mellitus (OR, 3.084; 95% CI, 1.180-8.061) and conversely related with heart failure (OR, 0.149; 95% CI, 0.026-0.861). Factors relating to pneumonia-caused death (immediate) were incidence of pneumonia during hospitalizations (OR, 32.579; 95%CI, 4.308-246.370), gender-male (OR, 2.060; 95% CI, 1.098-3.864), and conversely related with malignant neoplasm (OR, 0.220; 95% CI, 0.058-0.840). Conclusion The different factors relating to the pneumonia-caused death were evaluated depending on whether pneumonia was the underlying- or immediate-cause of death. Strengthening clinical management on dysphagia and diabetes mellitus, and preventing incidence of pneumonia during hospitalization appear to be the important for the terminal stage of hospitalized patients with dementia.

[Research on causes of death in Latin America].

Science.gov (United States)

Chackiel, J

1987-08-01

The use of vital statistics data to study causes of death in Latin America is examined. It is shown that reliable data are available for Argentina, Chile, Costa Rica, Cuba, and Uruguay and that relatively good data are available for Guatemala, Mexico, and Venezuela. Consideration is given to different approaches to the analysis of such data in order to provide additional information concerning the diseases that contribute to mortality. The possiblity of using the data in conceptual models in order to identify the socioeconomic and biological factors affecting mortality is noted. Consideration is also given to how the analysis of data on causes of death can be used to improve mortality projections by sex and age.

Endoplasmic reticulum involvement in yeast cell death

International Nuclear Information System (INIS)

Nicanor Austriaco, O.

2012-01-01

Yeast cells undergo programed cell death (PCD) with characteristic markers associated with apoptosis in mammalian cells including chromatin breakage, nuclear fragmentation, reactive oxygen species generation, and metacaspase activation. Though significant research has focused on mitochondrial involvement in this phenomenon, more recent work with both Saccharomyces cerevisiae and Schizosaccharomyces pombe has also implicated the endoplasmic reticulum (ER) in yeast PCD. This minireview provides an overview of ER stress-associated cell death (ER-SAD) in yeast. It begins with a description of ER structure and function in yeast before moving to a discussion of ER-SAD in both mammalian and yeast cells. Three examples of yeast cell death associated with the ER will be highlighted here including inositol starvation, lipid toxicity, and the inhibition of N-glycosylation. It closes by suggesting ways to further examine the involvement of the ER in yeast cell death.

Effects of ethanol on pancreatic beta-cell death: interaction with glucose and fatty acids.

Science.gov (United States)

Dembele, Korami; Nguyen, K Hoa; Hernandez, Tiffany A; Nyomba, B L Grégoire

2009-04-01

Western lifestyle plays an important role in the prevalence of type 2 diabetes by causing insulin resistance and pancreatic beta-cell dysfunction, a prerequisite for the development of diabetes. High fat diet and alcohol are major components of the western diet. The aim of the present study was to investigate the effects of ethanol and fatty acids on beta-cell survival and metabolism. We treated the rat beta-cell line RINm5F with ethanol, a mixture of palmitic and oleic acids, or both. Reactive oxygen species (ROS) were determined by (5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate) (CM-H2DCFDA) fluorescence assay, and mitochondrial activity was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) reduction assay and by determining ATP production. Cell viability was assessed with a cell counter and trypan blue exclusion, and the mode of cell death by Hoechst33342 and propidium iodide staining. With both ethanol and fatty acid treatments, MTT reduction and ATP production decreased, whereas ROS production increased. Ethanol treatment had no effect on cell number, whereas fatty acid treatment reduced the cell number. Cell incubation with ethanol, fatty acids, or both increased the number of Hoechst 33342-positive nuclei. However, the majority of nuclei from fatty acid-treated cells were stained with propidium iodide, indicating a loss of plasma membrane integrity. We conclude that both ethanol and fatty acids generate cellular oxidative stress, and affect mitochondrial function in RINm5F beta-cells. However, ethanol causes beta-cell death by apoptosis, whereas fatty acids cause cell death predominantly by necrosis. It is not known whether these results are applicable to human beta-cells.

Oxidative stress activates the TRPM2-Ca2+-CaMKII-ROS signaling loop to induce cell death in cancer cells.

Science.gov (United States)

Wang, Qian; Huang, Lihong; Yue, Jianbo

2017-06-01

High intracellular levels of reactive oxygen species (ROS) cause oxidative stress that results in numerous pathologies, including cell death. Transient potential receptor melastatin-2 (TRPM2), a Ca 2+ -permeable cation channel, is mainly activated by intracellular adenosine diphosphate ribose (ADPR) in response to oxidative stress. Here we studied the role and mechanisms of TRPM2-mediated Ca 2+ influx on oxidative stress-induced cell death in cancer cells. We found that oxidative stress activated the TRPM2-Ca 2+ -CaMKII cascade to inhibit early autophagy induction, which ultimately led to cell death in TRPM2 expressing cancer cells. On the other hand, TRPM2 knockdown switched cells from cell death to autophagy for survival in response to oxidative stress. Moreover, we found that oxidative stress activated the TRPM2-CaMKII cascade to further induce intracellular ROS production, which led to mitochondria fragmentation and loss of mitochondrial membrane potential. In summary, our data demonstrated that oxidative stress activates the TRPM2-Ca 2+ -CaMKII-ROS signal loop to inhibit autophagy and induce cell death. Copyright © 2016 Elsevier B.V. All rights reserved.

Validation of verbal autopsy: determination of cause of deaths in Malaysia 2013

OpenAIRE

Shubash Shander Ganapathy; Khoo Yi Yi; Mohd Azahadi Omar; Mohamad Fuad Mohamad Anuar; Chandrika Jeevananthan; Chalapati Rao

2017-01-01

Abstract Background Mortality statistics by age, sex and cause are the foundation of basic health data required for health status assessment, epidemiological research and formation of health policy. Close to half the deaths in Malaysia occur outside a health facility, are not attended by medical personnel, and are given a lay opinion as to the cause of death, leading to poor quality of data from vital registration. Verbal autopsy (VA) is a very useful tool in diagnosing broad causes of deaths...

Curcumin induces autophagic cell death in Spodoptera frugiperda cells.

Science.gov (United States)

Veeran, Sethuraman; Shu, Benshui; Cui, Gaofeng; Fu, Shengjiao; Zhong, Guohua

2017-06-01

The increasing interest in the role of autophagy (type II cell death) in the regulation of insect toxicology has propelled study of investigating autophagic cell death pathways. Turmeric, the rhizome of the herb Curcuma longa (Mañjaḷ in Tamil, India and Jiānghuáng in Chinese) have been traditionally used for the pest control either alone or combination with other botanical pesticides. However, the mechanisms by which Curcuma longa or curcumin exerts cytotoxicity in pests are not well understood. In this study, we investigated the potency of Curcuma longa (curcumin) as a natural pesticide employing Sf9 insect line. Autophagy induction effect of curcumin on Spodoptera frugiperda (Sf9) cells was investigated using various techniques including cell proliferation assay, morphology analysis with inverted phase contrast microscope and Transmission Electron Microscope (TEM) analysis. Autophagy was evaluated using the fluorescent dye monodansylcadaverine (MDC). Cell death measurement was examined using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) within the concentrations of 5-15μg/mL. Curcumin inhibited the growth of the Sf9 cells and induced autophagic cell death in a time and dose dependent manner. Staining the cells with MDC showed the presence of autophagic vacuoles while increased in a dose and time dependent manner. At the ultrastructural level transmission electron microscopy, cells revealed massive autophagy vacuole accumulation and absence of chromatin condensation. Protein expression levels of ATG8-I and ATG8-II, well-established markers of autophagy related protein were elevated in a time dependent manner after curcumin treatment. The present study proves that curcumin induces autophagic cell death in Sf9 insect cell line and this is the first report of cytotoxic effect of curcumin in insect cells and that will be utilized as natural pesticides in future. Copyright © 2017. Published by Elsevier Inc.

Activation-induced cell death of dendritic cells is dependent on sphingosine kinase 1

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Anja eSchwiebs

2016-04-01

Full Text Available Sphingosine 1-phosphate (S1P is an immune modulatory lipid mediator and has been implicated in numerous pathophysiological processes. S1P is produced by sphingosine kinase 1 (Sphk1 and Sphk2. Dendritic cells (DCs are central for the direction of immune responses and crucially involved in autoimmunity and cancerogenesis. In this study we examined the function and survival of bone marrow-derived DCs under long-term inflammatory stimulation. We observed that differentiated cells undergo activation-induced cell death upon LPS stimulation with an increased metabolic activity shortly after stimulation, followed by a rapid activation of caspase 3 and subsequent augmented apoptosis. Importantly, we highlight a profound role of Sphk1 in secretion of inflammatory cytokines and survival of dendritic cells that might be mediated by a change in sphingolipid levels as well as by a change in STAT3 expression. Cell growth during differentiation of Sphk1-deficient cells treated with the functional S1P receptor antagonist FTYP was reduced. Importantly, in dendritic cells we did not observe a compensatory regulation of Sphk2 mRNA in Sphk1-deficient cells. Instead, we discovered a massive increase in Sphk1 mRNA concentration upon long-term stimulation with LPS in wild type cells that might function as an attempt to rescue from inflammation-caused cell death. Taken together, in this investigation we describe details of a crucial involvement of sphingolipids and Sphk1 in activation-induced cell death during long-term immunogenic activity of DCs that might play an important role in autoimmunity and might explain the differences in immune response observed in in vivo studies of Sphk1 modulation.

Fluvastatin mediated breast cancer cell death: a proteomic approach to identify differentially regulated proteins in MDA-MB-231 cells.

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Anantha Koteswararao Kanugula

Full Text Available Statins are increasingly being recognized as anti-cancer agents against various cancers including breast cancer. To understand the molecular pathways targeted by fluvastatin and its differential sensitivity against metastatic breast cancer cells, we analyzed protein alterations in MDA-MB-231 cells treated with fluvastatin using 2-DE in combination with LC-MS/MS. Results revealed dys-regulation of 39 protein spots corresponding to 35 different proteins. To determine the relevance of altered protein profiles with breast cancer cell death, we mapped these proteins to major pathways involved in the regulation of cell-to-cell signaling and interaction, cell cycle, Rho GDI and proteasomal pathways using IPA analysis. Highly interconnected sub networks showed that vimentin and ERK1/2 proteins play a central role in controlling the expression of altered proteins. Fluvastatin treatment caused proteolysis of vimentin, a marker of epithelial to mesenchymal transition. This effect of fluvastatin was reversed in the presence of mevalonate, a downstream product of HMG-CoA and caspase-3 inhibitor. Interestingly, fluvastatin neither caused an appreciable cell death nor did modulate vimentin expression in normal mammary epithelial cells. In conclusion, fluvastatin alters levels of cytoskeletal proteins, primarily targeting vimentin through increased caspase-3- mediated proteolysis, thereby suggesting a role for vimentin in statin-induced breast cancer cell death.

Changes in causes of death among persons with AIDS: San Francisco, California, 1996-2011.

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Schwarcz, Sandra K; Vu, Annie; Hsu, Ling Chin; Hessol, Nancy A

2014-10-01

The increased life expectancy among HIV-infected persons treated with combination antiretroviral therapy (ART), risk behaviors, and co-morbidities associated with ART place HIV-infected persons at risk for non-HIV-related causes of death. We used the San Francisco HIV/AIDS registry to identify deaths that occurred from January 1996 through December 2011. Temporal trends in AIDS- and non-AIDS-related mortality rates, the proportion of underlying and contributory causes of death, and the ratio of observed deaths in the study population to expected number of deaths among California men aged 20-79 (standardized mortality ratio [SMR]) of underlying causes of death were examined. A total of 5338 deaths were identified. The annual AIDS-related death rate (per 100 deaths) declined from 10.8 in 1996 to 0.9 in 2011 (pdeath rate from non-AIDS-related causes declined from 2.1 in 1996 to 0.9 in 2011 (pdeaths due to all types of heart disease combined, all non-AIDS cancers combined, mental disorders resulting from substance abuse, drug overdose, suicide and chronic obstructive pulmonary disease increased significantly over time. The SMRs for liver diseased decreased significantly over time but remained elevated. Our data highlight the importance of age-related causes of death as well as deaths from causes that are, at least in part, preventable.

A Novel Hydroxamate-Based Compound WMJ-J-09 Causes Head and Neck Squamous Cell Carcinoma Cell Death via LKB1-AMPK-p38MAPK-p63-Survivin Cascade.

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Yen, Chia-Sheng; Choy, Cheuk-Sing; Huang, Wei-Jan; Huang, Shiu-Wen; Lai, Pin-Ye; Yu, Meng-Chieh; Shiue, Ching; Hsu, Ya-Fen; Hsu, Ming-Jen

2018-01-01

Growing evidence shows that hydroxamate-based compounds exhibit broad-spectrum pharmacological properties including anti-tumor activity. However, the precise mechanisms underlying hydroxamate derivative-induced cancer cell death remain incomplete understood. In this study, we explored the anti-tumor mechanisms of a novel aliphatic hydroxamate-based compound, WMJ-J-09, in FaDu head and neck squamous cell carcinoma (HNSCC) cells. WMJ-J-09 induced G2/M cell cycle arrest and apoptosis in FaDu cells. These actions were associated with liver kinase B1 (LKB1), AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (p38MAPK) activation, transcription factor p63 phosphorylation, as well as modulation of p21 and survivin. LKB1-AMPK-p38MAPK signaling blockade reduced WMJ-J-09's enhancing effects in p63 phosphorylation, p21 elevation and survivin reduction. Moreover, WMJ-J-09 caused an increase in α-tubulin acetylation and interfered with microtubule assembly. Furthermore, WMJ-J-09 suppressed the growth of subcutaneous FaDu xenografts in vivo . Taken together, WMJ-J-09-induced FaDu cell death may involve LKB1-AMPK-p38MAPK-p63-survivin signaling cascade. HDACs inhibition and disruption of microtubule assembly may also contribute to WMJ-J-09's actions in FaDu cells. This study suggests that WMJ-J-09 may be a potential lead compound and warrant the clinical development in the treatment of HNSCC.

Lysosomal cell death at a glance

DEFF Research Database (Denmark)

Aits, Sonja; Jaattela, Marja

2013-01-01

Lysosomes serve as the cellular recycling centre and are filled with numerous hydrolases that can degrade most cellular macromolecules. Lysosomal membrane permeabilization and the consequent leakage of the lysosomal content into the cytosol leads to so-called "lysosomal cell death". This form...... of cell death is mainly carried out by the lysosomal cathepsin proteases and can have necrotic, apoptotic or apoptosis-like features depending on the extent of the leakage and the cellular context. This article summarizes our current knowledge on lysosomal cell death with an emphasis on the upstream...... mechanisms that lead to lysosomal membrane permeabilization....

Causes and prevention of sudden cardiac death in the elderly.

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Tung, Patricia; Albert, Christine M

2013-03-01

Sudden cardiac death (SCD) is a major cause of mortality in elderly individuals owing to a high prevalence of coronary heart disease, systolic dysfunction, and congestive heart failure (CHF). Although the incidence of SCD increases with age, the proportion of cardiac deaths that are sudden decreases owing to high numbers of other cardiac causes of death in elderly individuals. Implantable cardioverter-defibrillator (ICD) therapy has been demonstrated to improve survival and prevent SCD in selected patients with systolic dysfunction and CHF. However, ICD therapy in elderly patients might not be effective because of a greater rate of pulseless electrical activity underlying SCD and other competing nonarrhythmic causes of death in this population. Although under-represented in randomized trials of ICD use, elderly patients comprise a substantial proportion of the population that qualifies for and receives an ICD for primary prevention under current guidelines. Cardiac resynchronization therapy (CRT), which has been demonstrated to reduce mortality in selected populations with heart failure, is also more commonly used in this group of patients than in younger individuals. In this Review, we examine the causes of SCD in elderly individuals, and discuss the existing evidence for effectiveness of ICD therapy and CRT in this growing population.

Understanding cell cycle and cell death regulation provides novel weapons against human diseases.

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Wiman, K G; Zhivotovsky, B

2017-05-01

Cell division, cell differentiation and cell death are the three principal physiological processes that regulate tissue homoeostasis in multicellular organisms. The growth and survival of cells as well as the integrity of the genome are regulated by a complex network of pathways, in which cell cycle checkpoints, DNA repair and programmed cell death have critical roles. Disruption of genomic integrity and impaired regulation of cell death may both lead to uncontrolled cell growth. Compromised cell death can also favour genomic instability. It is becoming increasingly clear that dysregulation of cell cycle and cell death processes plays an important role in the development of major disorders such as cancer, cardiovascular disease, infection, inflammation and neurodegenerative diseases. Research achievements in these fields have led to the development of novel approaches for treatment of various conditions associated with abnormalities in the regulation of cell cycle progression or cell death. A better understanding of how cellular life-and-death processes are regulated is essential for this development. To highlight these important advances, the Third Nobel Conference entitled 'The Cell Cycle and Cell Death in Disease' was organized at Karolinska Institutet in 2016. In this review we will summarize current understanding of cell cycle progression and cell death and discuss some of the recent advances in therapeutic applications in pathological conditions such as cancer, neurological disorders and inflammation. © 2017 The Association for the Publication of the Journal of Internal Medicine.

Constitutive activation of extracellular signal-regulated kinase predisposes diffuse large B-cell lymphoma cell lines to CD40-mediated cell death

DEFF Research Database (Denmark)

Hollmann, C Annette; Owens, Trevor; Nalbantoglu, Josephine

2006-01-01

CD40 promotes survival, proliferation, and differentiation of normal B cells but can cause activation-induced cell death in malignant B lymphocytes. CD40 ligand and anti-CD40 antibodies have been used successfully to induce apoptosis in lymphoma lines both in vitro and in xenograft tumor models. ...

Endosomal sorting complexes required for ESCRTing cells toward death during neurogenesis, neurodevelopment and neurodegeneration.

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Kaul, Zenia; Chakrabarti, Oishee

2018-03-25

The endosomal sorting complexes required for transport (ESCRT) proteins help in the recognition, sorting and degradation of ubiquitinated cargoes from the cell surface, long-lived proteins or aggregates, and aged organelles present in the cytosol. These proteins take part in the endo-lysosomal system of degradation. The ESCRT proteins also play an integral role in cytokinesis, viral budding and mRNA transport. Many neurodegenerative diseases are caused by toxic accumulation of cargo in the cell, which causes stress and ultimately leads to neuronal death. This accumulation of cargo occurs because of defects in the endo-lysosomal degradative pathway-loss of function of ESCRTs has been implicated in this mechanism. ESCRTs also take part in many survival processes, lack of which can culminate in neuronal cell death. While the role played by the ESCRT proteins in maintaining healthy neurons is known, their role in neurodegenerative diseases is still poorly understood. In this review, we highlight the importance of ESCRTs in maintaining healthy neurons and then suggest how perturbations in many of the survival mechanisms governed by these proteins could eventually lead to cell death; quite often these correlations are not so obviously laid out. Extensive neuronal death eventually culminates in neurodegeneration. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Causes of death of German refugee children in 1945].

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Lylloff, K

2000-02-28

In the last months of the second World War, 250,000 German refugees landed in Denmark. A third of them were children under the age of 15. Seven thousand German refugee children under the age of five died in Denmark in 1945. Using birth certificates and death certificates from the Danish national archives and burial lists from the German refugee cemetaries I have collected data to reveal causes of death, age distributions and time of the deaths of the 7000 fatal cases among children under the age of five. Three thousand children under the age of one, 2000 children one year old and 2000 children 2-4 years old died. Most of them died just before and after the German surrender, but many died in the months following the German surrender. The infant mortality was extremely high all during 1945. The infants died from diseases due to malnutrition, but the older the children the more likely the causes of death were due to infectious diseases such as pneumonia, measles, diphtheria and gastroenteritis.

Long-Term Causes of Death and Excess Mortality After Carotid Artery Ligation.

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Ibrahim, Tarik F; Jahromi, Behnam Rezai; Miettinen, Joonas; Raj, Rahul; Andrade-Barazarte, Hugo; Goehre, Felix; Kivisaari, Riku; Lehto, Hanna; Hernesniemi, Juha

2016-06-01

Carotid artery ligation (CAL) is used to treat large and complex intracranial aneurysms. However, little is known about long-term survival and causes of death in patients who undergo the procedure. This study was intended to evaluate if patients who have undergone CAL have long-term excess mortality and what the causes of death are. All patients were treated at Helsinki University Hospital between 1937 and 2009. Patients who had undergone CAL and survived ≥1 year after the procedure were included in the cohort. Follow-up was until death or 2015 (2711 patient-years). Causes of death were reviewed and relative survival ratios calculated using the Ederer II method and a matched population. There was 12% excess mortality in all patients 20 years after CAL and 22% after 30 years. A higher proportion of the patients who had subarachnoid hemorrhage (SAH) died during follow-up compared with unruptured patients undergoing CAL. Cardiovascular disease and cerebrovascular accident were the leading causes of death. Patients with unruptured aneurysms did not experience as much excess mortality as those who had an SAH. The higher proportion of deaths observed in ruptured patients may be partly because of long-term excess mortality conferred by the SAH itself or SAH risk factors. Although the entire population did display excess mortality compared with the general population, this may be because of shared risk factors for aneurysm development and rupture and the cause of death. Copyright © 2016 Elsevier Inc. All rights reserved.

BID links ferroptosis to mitochondrial cell death pathways

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Sandra Neitemeier

2017-08-01

Full Text Available Ferroptosis has been defined as an oxidative and iron-dependent pathway of regulated cell death that is distinct from caspase-dependent apoptosis and established pathways of death receptor-mediated regulated necrosis. While emerging evidence linked features of ferroptosis induced e.g. by erastin-mediated inhibition of the Xc- system or inhibition of glutathione peroxidase 4 (Gpx4 to an increasing number of oxidative cell death paradigms in cancer cells, neurons or kidney cells, the biochemical pathways of oxidative cell death remained largely unclear. In particular, the role of mitochondrial damage in paradigms of ferroptosis needs further investigation.In the present study, we find that erastin-induced ferroptosis in neuronal cells was accompanied by BID transactivation to mitochondria, loss of mitochondrial membrane potential, enhanced mitochondrial fragmentation and reduced ATP levels. These hallmarks of mitochondrial demise are also established features of oxytosis, a paradigm of cell death induced by Xc- inhibition by millimolar concentrations of glutamate. Bid knockout using CRISPR/Cas9 approaches preserved mitochondrial integrity and function, and mediated neuroprotective effects against both, ferroptosis and oxytosis. Furthermore, the BID-inhibitor BI-6c9 inhibited erastin-induced ferroptosis, and, in turn, the ferroptosis inhibitors ferrostatin-1 and liproxstatin-1 prevented mitochondrial dysfunction and cell death in the paradigm of oxytosis. These findings show that mitochondrial transactivation of BID links ferroptosis to mitochondrial damage as the final execution step in this paradigm of oxidative cell death. Keywords: Ferroptosis, BID, Mitochondria, CRISPR, Oxytosis, Neuronal death

Validation of verbal autopsy: determination of cause of deaths in Malaysia 2013.

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Ganapathy, Shubash Shander; Yi Yi, Khoo; Omar, Mohd Azahadi; Anuar, Mohamad Fuad Mohamad; Jeevananthan, Chandrika; Rao, Chalapati

2017-08-11

Mortality statistics by age, sex and cause are the foundation of basic health data required for health status assessment, epidemiological research and formation of health policy. Close to half the deaths in Malaysia occur outside a health facility, are not attended by medical personnel, and are given a lay opinion as to the cause of death, leading to poor quality of data from vital registration. Verbal autopsy (VA) is a very useful tool in diagnosing broad causes of deaths for events that occur outside health facilities. This article reports the development of the VA methods and our principal finding from a validation study. A cross sectional study on nationally representative sample deaths that occurred in Malaysia during 2013 was used. A VA questionnaire suitable for local use was developed. Trained field interviewers visited the family members of the deceased at their homes and conducted face to face interviews with the next of kin. Completed questionnaires were reviewed by trained physicians who assigned multiple and underlying causes. Reference diagnoses for validation were obtained from review of medical records (MR) available for a sample of the overall study deaths. Corresponding MR diagnosis with matched sample of the VA diagnosis were available in 2172 cases for the validation study. Sensitivity scores were good (>75%) for transport accidents and certain cancers. Moderate sensitivity (50% - 75%) was obtained for ischaemic heart disease (64%) and cerebrovascular disease (72%). The validation sample for deaths due to major causes such as ischaemic heart disease, pneumonia, breast cancer and transport accidents show low cause-specific mortality fraction (CSMF) changes. The scores obtained for the top 10 leading site-specific cancers ranged from average to good. We can conclude that VA is suitable for implementation for deaths outside the health facilities in Malaysia. This would reduce ill-defined mortality causes in vital registration data, and yield more

Congenital infantile myofibroma causing intrauterine death in a twin

Science.gov (United States)

Aye, Christina Yi Ling; Gould, Steve; Akinsola, S Adeyemi

2011-01-01

While infantile myofibromatosis is the most common mesenchymal tumour of infancy, only around 300 cases have been reported. The authors report a 33-year-old para 1 with an uncomplicated, dichorionic diamniotic twin pregnancy who was diagnosed with an intrauterine death of one twin at 36+5 weeks gestation. At caesarean section, a macerated male stillborn weighing 2.72 kg was delivered. Postmortem examination revealed a pedunculated lesion attached to the left shoulder and underlying muscle consistent with a congenital myofibroma. The cause of death was postulated to be haemorrhage from the tumour surface causing fetal anaemia. PMID:22674951

Networked T cell death following macrophage infection by Mycobacterium tuberculosis.

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Stephen H-F Macdonald

Full Text Available BACKGROUND: Depletion of T cells following infection by Mycobacterium tuberculosis (Mtb impairs disease resolution, and interferes with clinical test performance that relies on cell-mediated immunity. A number of mechanisms contribute to this T cell suppression, such as activation-induced death and trafficking of T cells out of the peripheral circulation and into the diseased lungs. The extent to which Mtb infection of human macrophages affects T cell viability however, is not well characterised. METHODOLOGY/PRINCIPAL FINDINGS: We found that lymphopenia (<1.5 × 10(9 cells/l was prevalent among culture-positive tuberculosis patients, and lymphocyte counts significantly improved post-therapy. We previously reported that Mtb-infected human macrophages resulted in death of infected and uninfected bystander macrophages. In the current study, we sought to examine the influence of infected human alveolar macrophages on T cells. We infected primary human alveolar macrophages (the primary host cell for Mtb or PMA-differentiated THP-1 cells with Mtb H37Ra, then prepared cell-free supernatants. The supernatants of Mtb-infected macrophages caused dose-dependent, caspase-dependent, T cell apoptosis. This toxic effect of infected macrophage secreted factors did not require TNF-α or Fas. The supernatant cytotoxic signal(s were heat-labile and greater than 50 kDa in molecular size. Although ESAT-6 was toxic to T cells, other Mtb-secreted factors tested did not influence T cell viability; nor did macrophage-free Mtb bacilli or broth from Mtb cultures. Furthermore, supernatants from Mycobacterium bovis Bacille de Calmette et Guerin (BCG- infected macrophages also elicited T cell death suggesting that ESAT-6 itself, although cytotoxic, was not the principal mediator of T cell death in our system. CONCLUSIONS: Mtb-Infected macrophages secrete heat-labile factors that are toxic to T cells, and may contribute to the immunosuppression seen in tuberculosis as well as

CDC WONDER: Compressed Mortality - Underlying Cause of Death

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U.S. Department of Health & Human Services — The CDC WONDER Mortality - Underlying Cause of Death online database is a county-level national mortality and population database spanning the years since 1979...

Impact of a hospital-level intervention to reduce heart disease overreporting on leading causes of death.

Science.gov (United States)

Al-Samarrai, Teeb; Madsen, Ann; Zimmerman, Regina; Maduro, Gil; Li, Wenhui; Greene, Carolyn; Begier, Elizabeth

2013-05-16

The quality of cause-of-death reporting on death certificates affects the usefulness of vital statistics for public health action. Heart disease deaths are overreported in the United States. We evaluated the impact of an intervention to reduce heart disease overreporting on other leading causes of death. A multicomponent intervention comprising training and communication with hospital staff was implemented during July through December 2009 at 8 New York City hospitals reporting excessive heart disease deaths. We compared crude, age-adjusted, and race/ethnicity-adjusted proportions of leading, underlying causes of death reported during death certification by intervention and nonintervention hospitals during preintervention (January-June 2009) and postintervention (January-June 2010) periods. We also examined trends in leading causes of death for 2000 through 2010. At intervention hospitals, heart disease deaths declined by 54% postintervention; other leading causes of death (ie, malignant neoplasms, influenza and pneumonia, cerebrovascular disease, and chronic lower respiratory diseases) increased by 48% to 232%. Leading causes of death at nonintervention hospitals changed by 6% or less. In the preintervention period, differences in leading causes of death between intervention and nonintervention hospitals persisted after controlling for race/ethnicity and age; in the postintervention period, age accounted for most differences observed between intervention and nonintervention hospitals. Postintervention, malignant neoplasms became the leading cause of premature death (ie, deaths among patients aged 35-74 y) at intervention hospitals. A hospital-level intervention to reduce heart disease overreporting led to substantial changes to other leading causes of death, changing the leading cause of premature death. Heart disease overreporting is likely obscuring the true levels of cause-specific mortality.

The control and execution of programmed cell death

International Nuclear Information System (INIS)

Begum, R.; Pathak, N.; Hasnain, S.E.; Sah, N.K.; Athar, M.

1999-01-01

Apoptosis or programmed cell death is a highly conserved genetically controlled response of metazoan cells to commit suicide. Non apoptotic programmed cell death seems to operate in single celled eukaryotes implying that evolution of PCD has preceded the evolution of multicellularity. PCD plays a crucial role in the regulation of cellular and tissue homeostasis and any aberrations in apoptosis leads to several diseases including cancer, neurodegenerative disorders and AIDS. The mechanisms by which apoptosis is controlled are varied. In some cells, members of bcl-2 family or p53 are crucial for regulating the apoptosis programme, whereas in other cells Fas ligand is more important. bcl-2 family members have a prime role in the regulation of cell death at all stages including development, whereas cell death during development is independent of p53. bcl-2 family members being localized on the outer mitochondrial membrane, control the mitochondrial homeostasis and cytochrome c redistribution and thereby regulate the cell death process. p53 promotes DNA damage mediated cell death after growth arrest and failed DNA repair. Caspases play a key role in the execution of cell death by mediating highly specific cleavages of crucial cellular proteins collectively manifesting the apoptotic phenotype. Protein inhibitors like crm A, p35 and IAPs could prevent/control apoptosis induced by a broad array of cell death stimuli by several mechanisms specially interfering in caspase activation or caspase activity. Among endonucleases, caspase activated DNase (CAD) plays a crucial role in DNA fragmentation, a biochemical hallmark of apoptosis. As regulation of cell death seems to be as complex as regulation of cell proliferation, multiple kinase mediated regulatory mechanisms might control the apoptotic process. Thus, in spite of intensive research over the past few years, the field of apoptosis still remains fertile to unravel among others, the molecular mechanisms of cytochrome c

The control and execution of programmed cell death

Energy Technology Data Exchange (ETDEWEB)

Begum, R.; Pathak, N.; Hasnain, S.E.; Sah, N.K. [National Inst. of Immunology, New Delhi (India). Eukaryotic Gene Expression Lab.; Taneja, T.K.; Mohan, M. [National Inst. of Immunology, New Delhi (India). Eukaryotic Gene Expression Lab.]|[Dept. of Medical Elementology and Toxicology, New Delhi (India); Athar, M. [Dept. of Medical Elementology and Toxicology, New Delhi (India)

1999-07-01

Apoptosis or programmed cell death is a highly conserved genetically controlled response of metazoan cells to commit suicide. Non apoptotic programmed cell death seems to operate in single celled eukaryotes implying that evolution of PCD has preceded the evolution of multicellularity. PCD plays a crucial role in the regulation of cellular and tissue homeostasis and any aberrations in apoptosis leads to several diseases including cancer, neurodegenerative disorders and AIDS. The mechanisms by which apoptosis is controlled are varied. In some cells, members of bcl-2 family or p53 are crucial for regulating the apoptosis programme, whereas in other cells Fas ligand is more important. bcl-2 family members have a prime role in the regulation of cell death at all stages including development, whereas cell death during development is independent of p53. bcl-2 family members being localized on the outer mitochondrial membrane, control the mitochondrial homeostasis and cytochrome c redistribution and thereby regulate the cell death process. p53 promotes DNA damage mediated cell death after growth arrest and failed DNA repair. Caspases play a key role in the execution of cell death by mediating highly specific cleavages of crucial cellular proteins collectivley manifesting the apoptotic phenotype. Protein inhibitors like crm A, p35 and IAPs could prevent/control apoptosis induced by a broad array of cell death stimuli by several mechanisms specially interfering in caspase activation or caspase activity. Among endonucleases, caspase activated DNase (CAD) plays a crucial role in DNA fragmentation, a biochemical hallmark of apoptosis. As regulation of cell death seems to be as complex as regulation of cell proliferation, multiple kinase mediated regulatory mechanisms might control the apoptotic process. Thus, in spite of intensive research over the past few years, the field of apoptosis still remains fertile to unravel among others, the molecular mechanisms of cytochrome c

Mitochondrial fission proteins regulate programmed cell death in yeast

OpenAIRE

Fannjiang, Yihru; Cheng, Wen-Chih; Lee, Sarah J.; Qi, Bing; Pevsner, Jonathan; McCaffery, J. Michael; Hill, R. Blake; Basañez, Gorka; Hardwick, J. Marie

2004-01-01

The possibility that single-cell organisms undergo programmed cell death has been questioned in part because they lack several key components of the mammalian cell death machinery. However, yeast encode a homolog of human Drp1, a mitochondrial fission protein that was shown previously to promote mammalian cell death and the excessive mitochondrial fragmentation characteristic of apoptotic mammalian cells. In support of a primordial origin of programmed cell death involving mitochondria, we fo...

Cancer-specific mortality, cure fraction, and noncancer causes of death among diffuse large B-cell lymphoma patients in the immunochemotherapy era.

Science.gov (United States)

Howlader, Nadia; Mariotto, Angela B; Besson, Caroline; Suneja, Gita; Robien, Kim; Younes, Naji; Engels, Eric A

2017-09-01

Survival after the diagnosis of diffuse large B-cell lymphoma (DLBCL) has been increasing since 2002 because of improved therapies; however, long-term outcomes for these patients in the modern treatment era are still unknown. Using Surveillance, Epidemiology, and End Results data, this study first assessed factors associated with DLBCL-specific mortality during 2002-2012. An epidemiologic risk profile, based on clinical and demographic characteristics, was used to stratify DLBCL cases into low-, medium-, and high-risk groups. The proportions of DLBCL cases that might be considered cured in these 3 risk groups was estimated. Risks of death due to various noncancer causes among DLBCL cases versus the general population were also calculated with standardized mortality ratios (SMRs). Overall, 8274 deaths were recorded among 18,047 DLBCL cases; 76% of the total deaths were attributed to DLBCL, and 24% were attributed to noncancer causes. The 10-year survival rates for the low-, medium-, and high-risk groups were 80%, 60%, and 36%, respectively. The estimated cure proportions for the low-, medium-, and high-risk groups were 73%, 49%, and 27%, respectively; however, these cure estimates were uncertain because of the need to extrapolate the survival curves beyond the follow-up time. Mortality risks calculated with SMRs were elevated for conditions including vascular diseases (SMR, 1.3), infections (SMR, 3.1), gastrointestinal diseases (SMR, 2.5), and blood diseases (SMR, 4.6). These mortality risks were especially high within the initial 5 years after the diagnosis and declined after 5 years. Some DLBCL patients may be cured of their cancer, but they continue to experience excess mortality from lymphoma and other noncancer causes. Cancer 2017;123:3326-34. © 2017 American Cancer Society. © 2017 American Cancer Society.

Cell death induced by hydroxyapatite on L929 fibroblast cells.

Science.gov (United States)

Inayat-Hussain, S H; Rajab, N F; Roslie, H; Hussin, A A; Ali, A M; Annuar, B O

2004-05-01

Biomaterials intended for end-use application as bone-graft substitutes have to undergo safety evaluation. In this study, we investigated the in vitro cytotoxic effects especially to determine the mode of death of two hydroxyapatite compounds (HA2, HA3) which were synthesized locally. The methods used for cytotoxicity was the standard MTT assay whereas AO/PI staining was performed to determine the mode of cell death in HA treated L929 fibroblasts. Our results demonstrated that both HA2 and HA3 were not significantly cytotoxic as more than 75% cells after 72 hours treatment were viable. Furthermore, we found that the major mode of cell death in HA treated cells was apoptosis. In conclusion, our results demonstrated that these hydroxyapatite compounds are not cytotoxic where the mode of death was primarily via apoptosis.

Systematization of the Mechanism by Which Plasma Irradiation Causes Cell Growth and Tumor Cell Death

Science.gov (United States)

Shimizu, Nobuyuki

2015-09-01

New methods and technologies have improved minimally invasive surgical treatment and saved numerous patients. Recently, plasma irradiation has been demonstrated that might be useful in medical field and the plasma irradiation device is expected to become practically applicable. Mild plasma coagulator showed some advantages such as hemostasis and adhesion reduction in experimental animal model, but the mechanism of plasma irradiation remains unclear. Our study group aim to clarify the mechanism of plasma irradiation effects, mainly focusing on oxidative stress using cultured cell lines and small animal model. First, a study using cultured cell lines showed that the culture medium that was activated by plasma irradiation (we called this kind of medium as ``PAM'' -plasma activated medium-) induced tumor cell death. Although this effect was mainly found to be due to hydrogen peroxide, the remaining portion was considered as the specific effect of the plasma irradiation and we are now studying focusing on this effect. Second, we established a mouse intra-peritoneal adhesion model and checked biological reaction that occurred in the adhesion part. Histopathological study showed inflammatory cells infiltration into adhesion part and the expression of PTX3 that might involve tissue repair around adhesion part. We also confirmed that cytokines IL-6 and IL-10 might be useful as a marker of adhesion formation in this model. Applying ``PAM'' or mild plasma irradiation in this model, we examine the effects of plasma on inflamed cells. The samples in these experiments would be applied to targeted proteomics analysis, and we aim to demonstrate the systematization of the cell's reaction by plasma irradiation.

Armet, a UPR-upregulated protein, inhibits cell proliferation and ER stress-induced cell death

International Nuclear Information System (INIS)

Apostolou, Andria; Shen Yuxian; Liang Yan; Luo Jun; Fang Shengyun

2008-01-01

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) causes ER stress that initiates the unfolded protein response (UPR). UPR activates both adaptive and apoptotic pathways, which contribute differently to disease pathogenesis. To further understand the functional mechanisms of UPR, we identified 12 commonly UPR-upregulated genes by expression microarray analysis. Here, we describe characterization of Armet/MANF, one of the 12 genes whose function was not clear. We demonstrated that the Armet/MANF protein was upregulated by various forms of ER stress in several cell lines as well as by cerebral ischemia of rat. Armet/MANF was localized in the ER and Golgi and was also a secreted protein. Silencing Armet/MANF by siRNA oligos in HeLa cells rendered cells more susceptible to ER stress-induced death, but surprisingly increased cell proliferation and reduced cell size. Overexpression of Armet/MANF inhibited cell proliferation and improved cell viability under glucose-free conditions and tunicamycin treatment. Based on its inhibitory properties for both proliferation and cell death we have demonstrated, Armet is, thus, a novel secreted mediator of the adaptive pathway of UPR

Combined effects of starvation and butyrate on autophagy-dependent gingival epithelial cell death.

Science.gov (United States)

Evans, M; Murofushi, T; Tsuda, H; Mikami, Y; Zhao, N; Ochiai, K; Kurita-Ochiai, T; Yamamoto, M; Otsuka, K; Suzuki, N

2017-06-01

Bacteria in the dental biofilm surrounding marginal gingival grooves cause periodontal diseases. Numerous bacteria within the biofilm consume nutrients from the gingival crevicular fluid. Furthermore, some gram-negative bacteria in mature dental biofilms produce butyrate. Thus, gingival epithelial cells in close proximity to mature dental biofilms are at risk of both starvation and exposure to butyrate. In the present study, we determined the combined effects of starvation and butyrate exposure on gingival epithelial cell death and the underlying mechanisms. The Ca9-22 cell line was used as an in vitro counterpart of gingival epithelial cells. Cell death was measured as the amount of total DNA in the dead cells using SYTOX Green dye, which penetrates through membranes of dead cells and emits fluorescence when it intercalates into double-stranded DNA. AMP-activated protein kinase (AMPK) activity, the amount of autophagy, and acetylation of histone H3 were determined using western blot. Gene expression levels of microtubule-associated protein 1 light chain 3b (lc3b) were determined using quantitative reverse transcription-polymerase chain reaction. Butyrate-induced cell death occurred in a dose-dependent manner whether cells were starved or fed. However, the induction of cell death was two to four times higher when cells were placed under starvation conditions compared to when they were fed. Moreover, both starvation and butyrate exposure induced AMPK activity and autophagy. While AMPK inactivation resulted in decreased autophagy and butyrate-induced cell death under conditions of starvation, AMPK activation resulted in butyrate-induced cell death when cells were fed. Combined with the results of our previous report, which demonstrated butyrate-induced autophagy-dependent cell death, the results of this study suggest that the combination of starvation and butyrate exposure activates AMPK inducing autophagy and subsequent cell death. Notably, this combination markedly

Significance of apoptotic cell death after γ-irradiation

International Nuclear Information System (INIS)

Wu, H.G.; Kim, I.H.; Ha, S.W.; Park, C.I.

2003-01-01

Full text: The objectives of this study are to investigate the significance of apoptotic death compared to total cell death after γ-ray irradiation in human Hand N cancer cell lines and to find out correlation between apoptosis and radiation sensitivity. Materials and Method: Head and neck cancer cell lines (PCI-1, PCI-13, and SNU-1066), leukemia cell line (CCRF-CEM), and fibroblast cell line (LM217) as a normal control were used for this study. Cells were irradiated using Cs-137 animal experiment irradiator. Total cell death was measured by clonogenic assay. Annexin-V staining was used to detect the fraction of apoptotic death. The resulting data was analyzed with two parameters, apoptotic index (AI) and apoptotic fraction(AF). AI is ratio of apoptotic cells to total cells, and AF is ration of apoptotic cell death to mutant frequencytion ex(Number of apoptotic cells) / (Number of total cells counted) AF = {(AI) / (1-survival fraction)} x 100 (%) Results. Surviving fraction at 2 Gy (SF2) were 0.741, 0.544, 0.313, 0.302, and 0.100 for PCI-1, PCI-13, SNU-1066, CCRF-CEM, and LM217 cell lines, respectively. Apoptosis was detected in all cell lines. Apoptotic index reached peak value at 72 hours after irradiation in head and neck cancer cell lines, and that was at 24 hours in CCRF-CEM and LM217. Total cell death increased exponentially with increasing radiation dose from 0 Gy to 8 Gy, but the change was minimal in apoptotic index (Fig. 1.). Apoptotic fractions at 2 Gy were 46%, 48%, 46%, 24%, and 19% and at 6 Gy were 20%, 33%, 35%, 17%, and 20% for PCI-1, PCI-13, SNU-1066, CCRF-CEM, and LM217, respectively. The radioresistant cell lines showed more higher apoptotic fraction at 2 Gy (Table 1.), but there was not such correlation at 6 Gy. Conclusion: All cell lines used in this study showed apoptosis after irradiation, but time course of apoptosis was different from that of leukemia cell line and normal fibroblast cell line. Reproductive cell death was more important

Disability status, mortality, and leading causes of death in the United States community population.

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Forman-Hoffman, Valerie L; Ault, Kimberly L; Anderson, Wayne L; Weiner, Joshua M; Stevens, Alissa; Campbell, Vincent A; Armour, Brian S

2015-04-01

We examined the effect of functional disability on all-cause mortality and cause-specific deaths among community-dwelling US adults. We used data from 142,636 adults who participated in the 1994-1995 National Health Interview Survey-Disability Supplement eligible for linkage to National Death Index records from 1994 to 2006 to estimate the effects of disability on mortality and leading causes of death. Adults with any disability were more likely to die than adults without disability (19.92% vs. 10.94%; hazard ratio=1.51, 95% confidence interval, 1.45-1.57). This association was statistically significant for most causes of death and for most types of disability studied. The leading cause of death for adults with and without disability differed (heart disease and malignant neoplasms, respectively). Our results suggest that all-cause mortality rates are higher among adults with disabilities than among adults without disabilities and that significant associations exist between several types of disability and cause-specific mortality. Interventions are needed that effectively address the poorer health status of people with disabilities and reduce the risk of death.

Chronological shifts and changing causes of death after radiotherapy for early-stage oral cancer.

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Fujisawa, Rina; Shibuya, Hitoshi; Harata, Naoki; Yuasa-Nakagawa, Keiko; Toda, Kazuma; Hayashi, Keiji

2014-02-01

Following recent improvements in the curability of oral cancer, chronological shifts and changes in the causes of death after treatment have been observed. We conducted a review of the post-treatment causes of death following radiotherapy for oral cancers. The medical records of 966 patients with early-stage (stage I and II) oral cancer treated at our institute between 1980 and 2001 were reviewed, and the chronological shifts and changes in the causes of death after radiotherapy were assessed. Of the 966 patients enrolled in this study, 365 have died to date. Two hundred and eleven patients died of their primary malignancy; 193 of these deaths occurred within 5 years of treatment for the primary oral cancer. The second most frequent cause of death was second primary cancer (n = 90). Twenty-three patients with head and neck cancers and 18 patients with esophageal cancers died within 10 years of radiotherapy, and six patients with lung cancers died after more than 10 years. Within the first 5 years following treatment, the major cause of death was the primary oral cancer. After 5-10 years, a second primary cancer, such as head and neck cancer or esophageal cancer, became the leading cause of death. Over a 10-year period, the proportion of deaths from a second primary cancer in the lung was significant. We have demonstrated that there are chronological shifts and changes in the causes of death following treatment for early-stage oral cancer.

Diverse Placental Pathologies as the Main Causes of Fetal Death

NARCIS (Netherlands)

Korteweg, Fleurisca J.; Erwich, Jan Jaap H. M.; Holm, Jozien P.; Ravise, Joke M.; van der Meer, Jan; Veeger, Nic J. G. M.; Timmer, Albertus; van der, Meer J.

2009-01-01

OBJECTIVE: To estimate the occurrence of placental causes of fetal death in relation to different gestational ages and their clinical manifestations during pregnancy. METHODS: In a prospective cohort study conducted from 2002 to 2006, we studied 750 couples with singleton intrauterine fetal death

Ultra-violet B (UVB)-induced skin cell death occurs through a cyclophilin D intrinsic signaling pathway.

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Ji, Chao; Yang, Bo; Yang, Zhi; Tu, Ying; Yang, Yan-li; He, Li; Bi, Zhi-Gang

2012-09-07

UVB-induced skin cell damage involves the opening of mitochondrial permeability transition pore (mPTP), which leads to both apoptotic and necrotic cell death. Cyclophilin D (Cyp-D) translocation to the inner membrane of mitochondrion acts as a key component to open the mPTP. Our Western-Blot results in primary cultured human skin keratinocytes and in HaCaT cell line demonstrated that UVB radiation and hydrogen peroxide (H(2)O(2)) induced Cyp-D expression, which was inhibited by anti-oxidant N-acetyl cysteine (NAC). We created a stable Cyp-D deficiency skin keratinocytes by expressing Cyp-D-shRNA through lentiviral infection. Cyp-D-deficient cells were significantly less susceptible than their counterparts to UVB- or H(2)O(2)-induced cell death. Further, cyclosporine A (Cs-A), a Cyp-D inhibitor, inhibited UVB- or H(2)O(2)-induced keratinocytes cell death. Reversely, over-expression of Cyp-D in primary keratinocytes caused spontaneous keratinocytes cell death. These results suggest Cyp-D's critical role in UVB/oxidative stress-induced skin cell death. Copyright © 2012 Elsevier Inc. All rights reserved.

A current life table and causes of death for insured dogs in Japan.

Science.gov (United States)

Inoue, Mai; Hasegawa, A; Hosoi, Y; Sugiura, K

2015-06-15

The life expectancies and causes of death were evaluated in 299,555 dogs insured in Japan between 1 April 2010 and 31 March 2011, of which 4169 dogs died during this period. The overall life expectancy of dogs was 13.7 years. The probability of death was high in the first year of life, lowest in the second and third years, and increased exponentially after 3 years of age. The life expectancy was 13.8 years in the death increased as dogs got older for most potential causes of death. Neoplasia resulted in the highest probability of death, especially in the large and giant breed groups. Cardiovascular system disorders were the second major cause of death and the toy group had a probability of death significantly higher than the other breed groups at age 12+. Copyright © 2015 Elsevier B.V. All rights reserved.

CDC WONDER: Detailed Mortality - Underlying Cause of Death

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U.S. Department of Health & Human Services — The Detailed Mortality - Underlying Cause of Death data on CDC WONDER are county-level national mortality and population data spanning the years 1999-2009. Data are...

Long-term prognosis and causes of death after spondylodiscitis

DEFF Research Database (Denmark)

Aagaard, Theis; Roed, Casper; Dahl, Benny

2016-01-01

BACKGROUND: Data on long-term prognosis after spondylodiscitis are scarce. The purpose of this study was to determine long-term mortality and the causes of death after spondylodiscitis. METHODS: A nationwide, population-based cohort study using national registries of patients diagnosed with non.......62), respiratory (MRR = 1.71), gastrointestinal (MRR = 3.35), musculoskeletal (MRR = 5.39) and genitourinary diseases (MRR = 3.37), but also due to trauma, poisoning and external causes (MRR = 2.78), alcohol abuse-related diseases (MRR = 5.59) and drug abuse-related diseases (6 vs 0 deaths, MRR not calculable...... ratios (MRR). RESULTS: Three hundred and sixty-five patients (24%) and 1115 individuals from the comparison cohort (15%) died. Unadjusted MRR for spondylodiscitis patients was 1.76 (95% CI = 1.57-1.98) and 1.47 (95% CI = 1.30-1.66) after adjustment for comorbidity. No deaths were observed in 128 patients...

Sudden cardiac death in adults: causes, incidence and interventions.

Science.gov (United States)

Walker, Wendy Marina

Many nurses will be familiar with the unexpected death of an adult patient following a sudden, life-threatening cardiac event. It is a situation that demands sensitive nursing care and skilled interventions to provide a foundation for recovery and promote healthy bereavement. This article examines the causes and incidence of sudden cardiac death in adults. Possible reactions of those who are suddenly bereaved are described and immediate care interventions aimed at dealing with the grief process are discussed. The article concludes by identifying ways in which the incidence of sudden cardiac death may be reduced.

Hyaluronan Protects Bovine Articular Chondrocytes against Cell Death Induced by Bupivacaine under Supraphysiologic Temperatures

Science.gov (United States)

Liu, Sen; Zhang, Qing-Song; Hester, William; O’Brien, Michael J.; Savoie, Felix H.; You, Zongbing

2013-01-01

Background Bupivacaine and supraphysiologic temperature can independently reduce cell viability of articular chondrocytes. In combination these two deleterious factors could further impair cell viability. Hypothesis Hyaluronan may protect chondrocytes from death induced by bupivacaine at supraphysiologic temperatures. Study Design Controlled laboratory study. Methods Bovine articular chondrocytes were treated with hyaluronan at physiologic (37°C) and supraphysiologic temperatures (45°C and 50°C) for one hour, and then exposed to bupivacaine for one hour at room temperature. Cell viability was assessed at three time points: immediately after treatment, six hours later, and twenty-four hours later using flow cytometry and fluorescence microscopy. The effects of hyaluronan on the levels of sulfated glycosaminoglycan in the chondrocytes were determined using Alcian blue staining. Results (1) Bupivacaine alone did not induce noticeable chondrocyte death at 37°C; (2) bupivacaine and temperature synergistically increased chondrocyte death, that is, when the chondrocytes were conditioned to 45°C and 50°C, 0.25% and 0.5% bupivacaine increased the cell death rate by 131% to 383% in comparison to the phosphate-buffered saline control group; and, (3) addition of hyaluronan reduced chondrocyte death rates to approximately 14% and 25% at 45°C and 50°C, respectively. Hyaluronan’s protective effects were still observed at six and twenty-four hours after bupivacaine treatment at 45°C. However, at 50°C, hyaluronan delayed but did not prevent the cell death caused by bupivacaine. One-hour treatment with hyaluronan significantly increased sulfated glycosaminoglycan levels in the chondrocytes. Conclusions Bupivacaine and supraphysiologic temperature synergistically increase chondrocyte death and hyaluronan may protect articular chondrocytes from death caused by bupivacaine. Clinical Relevance This study provides a rationale to perform pre-clinical and clinical studies to

Dementia in the National Cause of Death Registry in Norway 1969-2010

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Vidar Hjellvik

2012-11-01

Full Text Available Background: The prevalence of dementia is expected to increase markedly during the coming decades. Epidemiological studies involving the National Cause of Death Registry (NCDR may be useful for exploring the aetiology of dementia. We therefore wanted to study developments in the reporting of dementia in the NCDR over the last four decades.Methods: We calculated the age- and gender specific proportion of deaths with dementia reported in the NCDR (dementia deaths in the period 1969-2010, and the proportion of vascular dementia and Alzheimer’s disease deaths in 1986-2010. Separate analyses were done for deaths occurring in nursing homes in 1996-2010. The proportion of dementia deaths where dementia was coded as underlying cause of death was also calculated.Results: The proportion of dementia deaths increased more than threefold in the period 1969-2010 among women (from 4% to 15%, and more than doubled among men (from 3% to 7%. In nursing homes the proportion increased from 17% to 26% for women and from 13% to 18% for men. The proportion of dementia deaths with Alzheimer’s disease reported in the NCDR increased from practically zero in 1986 to a maximum of 28% in 2005. The proportion of dementia deaths with dementia as underlying cause of death increased from a minimum of 6% in 1972 to a maximum of 51% in 2009.Conclusion: Although the reporting of dementia in the NCDR increased markedly from 1969 to 2010, dementia is still under-reported for old people and for deaths occurring in nursing homes when compared to prevalence estimates.

Ionizing radiation-induced cell death

International Nuclear Information System (INIS)

Szumiel, I.

1994-01-01

Selected aspects of radiation-induced cell death, connected with signal transduction pathways are reviewed. Cell death is defined as insufficiency of the cellular signal transducing system to maintain the cell's physiological functions. The insufficiency may be due to impaired signal reception and/or transduction, lack or erroneous transcription activation, and eventual cellular ''misexpression'' of the signal. The molecular basis of this insufficiency would be damage to genomic (but also other cellular) structures and closing of specific signalling pathways or opening of others (like those leading to apoptosis). I describe experimental data that suggest an important role of RAS/NFI and p53/p105 Rb proteins in cell cycle control-coupled responses to DNA damage. (Author)

Gene expression analysis of cell death induction by Taurolidine in different malignant cell lines

International Nuclear Information System (INIS)

Chromik, Ansgar M; Weyhe, Dirk; Mittelkötter, Ulrich; Uhl, Waldemar; Hahn, Stephan A; Daigeler, Adrien; Flier, Annegret; Bulut, Daniel; May, Christina; Harati, Kamran; Roschinsky, Jan; Sülberg, Dominique

2010-01-01

The anti-infective agent Taurolidine (TRD) has been shown to have cell death inducing properties, but the mechanism of its action is largely unknown. The aim of this study was to identify potential common target genes modulated at the transcriptional level following TRD treatment in tumour cell lines originating from different cancer types. Five different malignant cell lines (HT29, Chang Liver, HT1080, AsPC-1 and BxPC-3) were incubated with TRD (100 μM, 250 μM and 1000 μM). Proliferation after 8 h and cell viability after 24 h were analyzed by BrdU assay and FACS analysis, respectively. Gene expression analyses were carried out using the Agilent -microarray platform to indentify genes which displayed conjoint regulation following the addition of TRD in all cell lines. Candidate genes were subjected to Ingenuity Pathways Analysis and selected genes were validated by qRT-PCR and Western Blot. TRD 250 μM caused a significant inhibition of proliferation as well as apoptotic cell death in all cell lines. Among cell death associated genes with the strongest regulation in gene expression, we identified pro-apoptotic transcription factors (EGR1, ATF3) as well as genes involved in the ER stress response (PPP1R15A), in ubiquitination (TRAF6) and mitochondrial apoptotic pathways (PMAIP1). This is the first conjoint analysis of potential target genes of TRD which was performed simultaneously in different malignant cell lines. The results indicate that TRD might be involved in different signal transduction pathways leading to apoptosis

Distinct mortality profile in systemic sclerosis: a death certificate study in Rio de Janeiro, Brazil (2006-2015) using a multiple causes of death analysis.

Science.gov (United States)

de Rezende, Rodrigo Poubel Vieira; Gismondi, Ronaldo Altenburg; Maleh, Haim Cesar; de Miranda Coelho, Elisa Mendes; Vieira, Carol Sartori; Rosa, Maria Luiza Garcia; Mocarzel, Luis Otavio

2017-12-16

The objective of this study was to assess the mortality profile related to SSc in the state of Rio de Janeiro, Brazil. We retrospectively examined all registered deaths in the region (2006-2015 period) in which the diagnosis of SSc was mentioned on any line of the death certificates (underlying cause of death [UCD], n = 223; non-UCD, n = 151). Besides the analysis of gender, age, and the causes of death, we also compared the mortality from UCDs between individuals whose death causes included SSc (cases) and those whose death causes did not include SSc (deceased controls). For the latter comparison, we used the mortality odds ratio to approximate the cause-specific standardized mortality ratio. We identified 1495 death causes among the 374 SSc cases. The mean age at death of the SSc cases (85% women) was significantly lower than that of the controls (n = 1,294,117) (58.7 vs. 65.5 years, respectively). The main death causes were circulatory system diseases, infections, and respiratory diseases (36%, 34%, and 21% of SSc cases, respectively). Compared to the deceased controls, there were proportionally more deaths among the SSc cases from pulmonary arterial hypertension, lung fibrosis, septicemia, gastrointestinal hemorrhage, other systemic connective tissue diseases, and heart failure (for death age causes in this predominantly non-Caucasian sample of SSc patients. Of interest, the percentage of infection-related deaths in our report was about three times higher than that in SSc studies with predominantly Caucasian populations.

Maternal and pregnancy-related death: causes and frequencies in an autopsy study population.

Science.gov (United States)

Buschmann, Claas; Schmidbauer, Martina; Tsokos, Michael

2013-09-01

Maternal deaths during pregnancy, both from pregnancy-related or other causes, are rare in Western industrialized countries. In this study we report maternal and pregnancy-related deaths in a large autopsy population focusing on medical history, autopsy findings and histological examinations. Medico-legal autopsy files (n = 11,270) from the Institute of Legal Medicine and Forensic Sciences, University Medical Centre Charité, University of Berlin, and the State Institute of Legal and Social Medicine, Berlin, from 2005 to 2010 were reviewed. All female cases between 15 and 49 years were checked for maternal and pregnancy-related death, and deaths of pregnant women from non-natural causes were also included. Fatalities that met the chosen criteria were classified as "direct gestational death," "indirect gestational death" or "non-gestational death." 13 female fatalities (0.12 %) met the chosen criteria (median age 28 years ± 6.87 SD). Eight (61.5 %) women died in-hospital, four (30.8 %) at home, and one woman died in public. Three cases (23.1 %) were "non-gestational deaths," and one case (7.7 %) remained unclear after autopsy and additional examinations. Of the remaining nine cases, six cases (46.5 %) were "direct gestational deaths," and two cases (15.4 %) were "indirect gestational deaths." One case (7.7 %) was not to be defined as "late maternal death," but the cause of death seemed to be directly related to previous gestation ["(very) late maternal death"]. Maternal deaths during pregnancy, both from pregnancy-related or other causes, remain an uncommon event in routine forensic autopsy practice. We report on the collection and analysis of maternal and pregnancy-related deaths in a large autopsy population, with particular attention to the phenomenology of pregnancy, pathophysiological changes in different organ systems and their detection, and the forensic autopsy assessment.

Polytrauma in the elderly: predictors of the cause and time of death

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Muwanga Cyrus

2010-05-01

Full Text Available Abstract Background Increasing age and significant pre-existing medical conditions (PMCs are independent risk factors associated with increased mortality after trauma. Our aim was to review all trauma deaths, identifying the cause and the relation to time from injury, ISS, age and PMCs. Methods A retrospective analysis of trauma deaths over a 6-year period at the study centre was conducted. Information was obtained from the Trauma Audit and Research Network (TARN dataset, hospital records, death certificates and post-mortem reports. The time and cause of death, ISS, PMCs were analysed for two age groups ( Results Patients ≥ 65 years old were at an increased risk of death (OR 6.4, 95% CI 5.2-7.8, p 15 and died within the first 24 hours of admission, irrespective of age, from causes directly related to their injuries. Twelve patients with an ISS of Conclusion Elderly patients with minor injuries and PMCs have an increased risk of death relative to their younger counterparts and are more likely to die of medical complications late in their hospital admission.

Inhibition of thromboxane synthase induces lung cancer cell death via increasing the nuclear p27

Energy Technology Data Exchange (ETDEWEB)

Leung, Kin Chung; Hsin, Michael K.Y.; Chan, Joey S.Y.; Yip, Johnson H.Y.; Li, Mingyue; Leung, Billy C.S. [Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong); Mok, Tony S.K. [Department of Clinical Oncology, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong); Warner, Timothy D. [The William Harvey Research Institute, Queen Mary University of London, London (United Kingdom); Underwood, Malcolm J. [Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong); Chen, George G., E-mail: gchen@cuhk.edu.hk [Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong)

2009-10-15

The role of thromboxane in lung carcinogenesis is not clearly known, though thromboxane B2 (TXB{sub 2}) level is increased and antagonists of thromboxane receptors or TXA2 can induce apoptosis of lung cancer cells. p27, an atypical tumor suppressor, is normally sequestered in the nucleus. The increased nuclear p27 may result in apoptosis of tumor cells. We hypothesize that the inhibition of thromboxane synthase (TXS) induces the death of lung cancer cells and that such inhibition is associated with the nuclear p27 level. Our experiment showed that the inhibition of TXS significantly induced the death or apoptosis in lung cancer cells. The activity of TXS was increased in lung cancer. The nuclear p27 was remarkably reduced in lung cancer tissues. The inhibition of TXS caused the cell death and apoptosis of lung cancer cells, likely via the elevation of the nuclear p27 since the TXS inhibition promoted the nuclear p27 level and the inhibition of p27 by its siRNA recovered the cell death induced by TXS inhibition. Collectively, lung cancer cells produce high levels of TXB{sub 2} but their nuclear p27 is markedly reduced. The inhibition of TXS results in the p27-related induction of cell death in lung cancer cells.

Inhibition of thromboxane synthase induces lung cancer cell death via increasing the nuclear p27

International Nuclear Information System (INIS)

Leung, Kin Chung; Hsin, Michael K.Y.; Chan, Joey S.Y.; Yip, Johnson H.Y.; Li, Mingyue; Leung, Billy C.S.; Mok, Tony S.K.; Warner, Timothy D.; Underwood, Malcolm J.; Chen, George G.

2009-01-01

The role of thromboxane in lung carcinogenesis is not clearly known, though thromboxane B2 (TXB 2 ) level is increased and antagonists of thromboxane receptors or TXA2 can induce apoptosis of lung cancer cells. p27, an atypical tumor suppressor, is normally sequestered in the nucleus. The increased nuclear p27 may result in apoptosis of tumor cells. We hypothesize that the inhibition of thromboxane synthase (TXS) induces the death of lung cancer cells and that such inhibition is associated with the nuclear p27 level. Our experiment showed that the inhibition of TXS significantly induced the death or apoptosis in lung cancer cells. The activity of TXS was increased in lung cancer. The nuclear p27 was remarkably reduced in lung cancer tissues. The inhibition of TXS caused the cell death and apoptosis of lung cancer cells, likely via the elevation of the nuclear p27 since the TXS inhibition promoted the nuclear p27 level and the inhibition of p27 by its siRNA recovered the cell death induced by TXS inhibition. Collectively, lung cancer cells produce high levels of TXB 2 but their nuclear p27 is markedly reduced. The inhibition of TXS results in the p27-related induction of cell death in lung cancer cells.

Blockade of maitotoxin-induced oncotic cell death reveals zeiosis

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Schilling William P

2002-01-01

Full Text Available Abstract Background Maitotoxin (MTX initiates cell death by sequentially activating 1 Ca2+ influx via non-selective cation channels, 2 uptake of vital dyes via formation of large pores, and 3 release of lactate dehydrogenase, an indication of cell lysis. MTX also causes formation of membrane blebs, which dramatically dilate during the cytolysis phase. To determine the role of phospholipase C (PLC in the cell death cascade, U73122, a specific inhibitor of PLC, and U73343, an inactive analog, were examined on MTX-induced responses in bovine aortic endothelial cells. Results Addition of either U73122 or U73343, prior to MTX, produced a concentration-dependent inhibition of the cell death cascade (IC50 ≈ 1.9 and 0.66 μM, respectively suggesting that the effect of these agents was independent of PLC. Addition of U73343 shortly after MTX, prevented or attenuated the effects of the toxin, but addition at later times had little or no effect. Time-lapse videomicroscopy showed that U73343 dramatically altered the blebbing profile of MTX-treated cells. Specifically, U73343 blocked bleb dilation and converted the initial blebbing event into "zeiosis", a type of membrane blebbing commonly associated with apoptosis. Cells challenged with MTX and rescued by subsequent addition of U73343, showed enhanced caspase-3 activity 48 hr after the initial insult, consistent with activation of the apoptotic program. Conclusions Within minutes of MTX addition, endothelial cells die by oncosis. Rescue by addition of U73343 shortly after MTX showed that a small percentage of cells are destined to die by oncosis, but that a larger percentage survive; cells that survive the initial insult exhibit zeiosis and may ultimately die by apoptotic mechanisms.

Vitamin D and Death by Sunshine

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Rebecca S. Mason

2013-01-01

Full Text Available Exposure to sunlight is the major cause of skin cancer. Ultraviolet radiation (UV from the sun causes damage to DNA by direct absorption and can cause skin cell death. UV also causes production of reactive oxygen species that may interact with DNA to indirectly cause oxidative DNA damage. UV increases accumulation of p53 in skin cells, which upregulates repair genes but promotes death of irreparably damaged cells. A benefit of sunlight is vitamin D, which is formed following exposure of 7-dehydrocholesterol in skin cells to UV. The relatively inert vitamin D is metabolized to various biologically active compounds, including 1,25-dihydroxyvitamin D3. Therapeutic use of vitamin D compounds has proven beneficial in several cancer types, but more recently these compounds have been shown to prevent UV-induced cell death and DNA damage in human skin cells. Here, we discuss the effects of vitamin D compounds in skin cells that have been exposed to UV. Specifically, we examine the various signaling pathways involved in the vitamin D-induced protection of skin cells from UV.

Neuroprotective Effects of Germinated Brown Rice against Hydrogen Peroxide Induced Cell Death in Human SH-SY5Y Cells

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Shahid Iqbal

2012-08-01

Full Text Available The neuroprotective and antioxidative effects of germinated brown rice (GBR, brown rice (BR and commercially available γ-aminobutyric acid (GABA against cell death induced by hydrogen peroxide (H₂O₂ in human neuroblastoma SH-SY5Y cells have been investigated. Results show that GBR suppressed H₂O₂-mediated cytotoxicity and induced G0/G1 phase cell cycle arrest in SH-SY5Y cells. Moreover, GBR reduced mitochondrial membrane potential (MMP and prevented phosphatidylserine (PS translocation in SH-SY5Y cells, key features of apoptosis, and subsequent cell death. GBR exhibited better neuroprotective and antioxidative activities as compared to BR and GABA. These results indicate that GBR possesses high antioxidative activities and suppressed cell death in SH-SY5Y cells by blocking the cell cycle re-entry and apoptotic mechanisms. Therefore, GBR could be developed as a value added functional food to prevent neurodegenerative diseases caused by oxidative stress and apoptosis.

Intracellular cholesterol level regulates sensitivity of glioblastoma cells against temozolomide-induced cell death by modulation of caspase-8 activation via death receptor 5-accumulation and activation in the plasma membrane lipid raft.

Science.gov (United States)

Yamamoto, Yutaro; Tomiyama, Arata; Sasaki, Nobuyoshi; Yamaguchi, Hideki; Shirakihara, Takuya; Nakashima, Katsuhiko; Kumagai, Kosuke; Takeuchi, Satoru; Toyooka, Terushige; Otani, Naoki; Wada, Kojiro; Narita, Yoshitaka; Ichimura, Koichi; Sakai, Ryuichi; Namba, Hiroki; Mori, Kentaro

2018-01-01

Development of resistance against temozolomide (TMZ) in glioblastoma (GBM) after continuous treatment with TMZ is one of the critical problems in clinical GBM therapy. Intracellular cholesterol regulates cancer cell biology, but whether intracellular cholesterol is involved in TMZ resistance of GBM cells remains unclear. The involvement of intracellular cholesterol in acquired resistance against TMZ in GBM cells was investigated. Intracellular cholesterol levels were measured in human U251 MG cells with acquired TMZ resistance (U251-R cells) and TMZ-sensitive control U251 MG cells (U251-Con cells), and found that the intracellular cholesterol level was significantly lower in U251-R cells than in U251-Con cells. In addition, treatment by intracellular cholesterol remover, methyl-beta cyclodextrin (MβCD), or intracellular cholesterol inducer, soluble cholesterol (Chol), regulated TMZ-induced U251-Con cell death in line with changes in intracellular cholesterol level. Involvement of death receptor 5 (DR5), a death receptor localized in the plasma membrane, was evaluated. TMZ without or with MβCD and/or Chol caused accumulation of DR5 into the plasma membrane lipid raft and formed a complex with caspase-8, an extrinsic caspase cascade inducer, reflected in the induction of cell death. In addition, treatment with caspase-8 inhibitor or knockdown of DR5 dramatically suppressed U251-Con cell death induced by combination treatment with TMZ, MβCD, and Chol. Combined treatment of Chol with TMZ reversed the TMZ resistance of U251-R cells and another GBM cell model with acquired TMZ resistance, whereas clinical antihypercholesterolemia agents at physiological concentrations suppressed TMZ-induced cell death of U251-Con cells. These findings suggest that intracellular cholesterol level affects TMZ treatment of GBM mediated via a DR5-caspase-8 mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.

Mortality atlas of the main causes of death in Switzerland, 2008-2012.

Science.gov (United States)

Chammartin, Frédérique; Probst-Hensch, Nicole; Utzinger, Jürg; Vounatsou, Penelope

2016-01-01

Analysis of the spatial distribution of mortality data is important for identification of high-risk areas, which in turn might guide prevention, and modify behaviour and health resources allocation. This study aimed to update the Swiss mortality atlas by analysing recent data using Bayesian statistical methods. We present average pattern for the major causes of death in Switzerland. We analysed Swiss mortality data from death certificates for the period 2008-2012. Bayesian conditional autoregressive models were employed to smooth the standardised mortality rates and assess average patterns. Additionally, we developed models for age- and gender-specific sub-groups that account for urbanisation and linguistic areas in order to assess their effects on the different sub-groups. We describe the spatial pattern of the major causes of death that occurred in Switzerland between 2008 and 2012, namely 4 cardiovascular diseases, 10 different kinds of cancer, 2 external causes of death, as well as chronic respiratory diseases, Alzheimer's disease, diabetes, influenza and pneumonia, and liver diseases. In-depth analysis of age- and gender-specific mortality rates revealed significant disparities between urbanisation and linguistic areas. We provide a contemporary overview of the spatial distribution of the main causes of death in Switzerland. Our estimates and maps can help future research to deepen our understanding of the spatial variation of major causes of death in Switzerland, which in turn is crucial for targeting preventive measures, changing behaviours and a more cost-effective allocation of health resources.

Cerebrovascular and hypertensive diseases as multiple causes of death in Brazil from 2004 to 2013.

Science.gov (United States)

Villela, P B; Klein, C H; Oliveira, G M M

2018-06-02

The proportion of deaths attributed to hypertensive diseases (HYPDs) was only 50% of that registered for cerebrovascular diseases (CBVDs) in 2013 in Brazil. This article aims to evaluate mortality related to HYPDs and CBVDs as multiple causes of death, in Brazil from 2004 to 2013. Analysis of historical series of secondary data obtained from Brazilian official registries. Data about the deaths were obtained from the Mortality Information System of the Brazilian Ministry of Health, available on the DATASUS website. CBVDs and HYPDs were evaluated according to their mentions as the underlying cause of death or entry in any line of the death certificates (DCs), according to their International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes. When CBVDs were the underlying causes of death, HYPDs were mentioned in 40.9% of the DCs. When HYPDs were the underlying causes of death, CBVDs were mentioned in only 5.0%. When CBVDs were mentioned without HYPDs, they were selected as the underlying cause of death 74.4% of the time. When HYPDs were mentioned in DCs without CBVDs, HYPDs were selected 30.0% of the time. In 2004, the frequency of any mention of HYPDs relative to the frequency of HYPDs cited as underlying causes increased fourfold and was followed by a plateau until 2013. In contrast, the frequency of any mention of CBVDs relative to the frequency of CBVDs as underlying causes decreased in the same period. Because this study was based on DC records, it was limited by the way these documents were completed, which may have included lack of record of the causes related to the sequence that culminated in death. When deaths related to HYPDs were evaluated as multiple causes of death, they were mentioned up to four times more often than when they were selected as underlying causes of death. This reinforces the need for better control of hypertension to prevent deaths. Copyright © 2018 The Royal Society for Public Health. Published by

Trends in causes of death among children under 5 in Bangladesh, 1993-2004: an exercise applying a standardized computer algorithm to assign causes of death using verbal autopsy data

Directory of Open Access Journals (Sweden)

Walker Neff

2011-08-01

Full Text Available Abstract Background Trends in the causes of child mortality serve as important global health information to guide efforts to improve child survival. With child mortality declining in Bangladesh, the distribution of causes of death also changes. The three verbal autopsy (VA studies conducted with the Bangladesh Demographic and Health Surveys provide a unique opportunity to study these changes in child causes of death. Methods To ensure comparability of these trends, we developed a standardized algorithm to assign causes of death using symptoms collected through the VA studies. The original algorithms applied were systematically reviewed and key differences in cause categorization, hierarchy, case definition, and the amount of data collected were compared to inform the development of the standardized algorithm. Based primarily on the 2004 cause categorization and hierarchy, the standardized algorithm guarantees comparability of the trends by only including symptom data commonly available across all three studies. Results Between 1993 and 2004, pneumonia remained the leading cause of death in Bangladesh, contributing to 24% to 33% of deaths among children under 5. The proportion of neonatal mortality increased significantly from 36% (uncertainty range [UR]: 31%-41% to 56% (49%-62% during the same period. The cause-specific mortality fractions due to birth asphyxia/birth injury and prematurity/low birth weight (LBW increased steadily, with both rising from 3% (2%-5% to 13% (10%-17% and 10% (7%-15%, respectively. The cause-specific mortality rates decreased significantly due to neonatal tetanus and several postneonatal causes (tetanus: from 7 [4-11] to 2 [0.4-4] per 1,000 live births (LB; pneumonia: from 26 [20-33] to 15 [11-20] per 1,000 LB; diarrhea: from 12 [8-17] to 4 [2-7] per 1,000 LB; measles: from 5 [2-8] to 0.2 [0-0.7] per 1,000 LB; injury: from 11 [7-17] to 3 [1-5] per 1,000 LB; and malnutrition: from 9 [6-13] to 5 [2-7]. Conclusions

TRPV2 activation induces apoptotic cell death in human T24 bladder cancer cells: a potential therapeutic target for bladder cancer.

Science.gov (United States)

Yamada, Takahiro; Ueda, Takashi; Shibata, Yasuhiro; Ikegami, Yosuke; Saito, Masaki; Ishida, Yusuke; Ugawa, Shinya; Kohri, Kenjiro; Shimada, Shoichi

2010-08-01

To investigate the functional expression of the transient receptor potential vanilloid 2 (TRPV2) channel protein in human urothelial carcinoma (UC) cells and to determine whether calcium influx into UC cells through TRPV2 is involved in apoptotic cell death. The expression of TRPV2 mRNA in bladder cancer cell lines (T24, a poorly differentiated UC cell line and RT4, a well-differentiated UC cell line) was analyzed using reverse transcriptase-polymerase chain reaction. The calcium permeability of TRPV2 channels in T24 cells was investigated using a calcium imaging assay that used cannabidiol (CBD), a relatively selective TRPV2 agonist, and ruthenium red (RuR), a nonselective TRPV channel antagonist. The death of T24 or RT4 cells in the presence of CBD was evaluated using a cellular viability assay. Apoptosis of T24 cells caused by CBD was confirmed using an annexin-V assay and small interfering RNA (siRNA) silencing of TRPV2. TRPV2 mRNA was abundantly expressed in T24 cells. The expression level in UC cells was correlated with high-grade disease. The administration of CBD increased intracellular calcium concentrations in T24 cells. In addition, the viability of T24 cells progressively decreased with increasing concentrations of CBD, whereas RT4 cells were mostly unaffected. Cell death occurred via apoptosis caused by continuous influx of calcium through TRPV2. TRPV2 channels in UC cells are calcium-permeable and the regulation of calcium influx through these channels leads directly to the death of UC cells. TRPV2 channels in UC cells may be a potential new therapeutic target, especially in higher-grade UC cells. Copyright 2010 Elsevier Inc. All rights reserved.

Cell death in Pseudomonas aeruginosa biofilm development

DEFF Research Database (Denmark)

Webb, J.S.; Thompson, L.S.; James, S.

2003-01-01

Bacteria growing in biofilms often develop multicellular, three-dimensional structures known as microcolonies. Complex differentiation within biofilms of Pseudomonas aeruginosa occurs, leading to the creation of voids inside microcolonies and to the dispersal of cells from within these voids....... However, key developmental processes regulating these events are poorly understood. A normal component of multicellular development is cell death. Here we report that a repeatable pattern of cell death and lysis occurs in biofilms of P. aeruginosa during the normal course of development. Cell death...... occurred with temporal and spatial organization within biofilms, inside microcolonies, when the biofilms were allowed to develop in continuous-culture flow cells. A subpopulation of viable cells was always observed in these regions. During the onset of biofilm killing and during biofilm development...

The anti-cell death FNK protein protects cells from death induced by freezing and thawing

International Nuclear Information System (INIS)

Sudo, Kentaro; Asoh, Sadamitsu; Ohsawa, Ikuroh; Ozaki, Daiya; Yamagata, Kumi; Ito, Hiromoto; Ohta, Shigeo

2005-01-01

The FNK protein, constructed from anti-apoptotic Bcl-x L with enhanced activity, was fused with the protein transduction domain (PTD) of the HIV/Tat protein to mediate the delivery of FNK into cells. The fusion protein PTD-FNK was introduced into chondrocytes in isolated articular cartilage-bone sections, cultured neurons, and isolated bone marrow mononuclear cells to evaluate its ability to prevent cell death induced by freezing and thawing. PTD-FNK protected the cells from freeze-thaw damage in a concentration-dependent manner. Addition of PTD-FNK with conventional cryoprotectants (dimethyl sulfoxide and hydroxyethyl starch) increased surviving cell numbers around 2-fold compared with controls treated only with the cryoprotectants. Notably, PTD-FNK allowed CD34 + cells among bone marrow mononuclear cells to survive more efficiently (12-fold more than the control cells) from two successive freeze-thaw cycles. Thus, PTD-FNK prevented cell death induced by freezing and thawing, suggesting that it provides for the successful cryopreservation of biological materials

[Sudden Cardiac Death of Young Persons: Risk Factors, Causes, Morphological Equivalents].

Science.gov (United States)

Shilova, M A; Mamedov, M N

2015-01-01

The article contains literature review on the problem of causes of sudden cardiac death (SCD) among young people as well as results of author's own retrospective study of deaths of persons before 39 years based on forensic autopsies performed during 10 year period. The study of structure and dynamics of causes of death, its risk factors and the role of connective tissue dysplasia in development of terminal symptomocomlexes allowed to establish that main mechanism of SCD in young people was arrhythmogenic developing as a response to provoking factors--physical effort, psychoemotional stress, consumption of light alcoholic beverages.

Cause of death and potentially avoidable deaths in Australian adults with intellectual disability using retrospective linked data.

Science.gov (United States)

Trollor, Julian; Srasuebkul, Preeyaporn; Xu, Han; Howlett, Sophie

2017-02-07

To investigate mortality and its causes in adults over the age of 20 years with intellectual disability (ID). Retrospective population-based standardised mortality of the ID and Comparison cohorts. The ID cohort comprised 42 204 individuals who registered for disability services with ID as a primary or secondary diagnosis from 2005 to 2011 in New South Wales (NSW). The Comparison cohort was obtained from published deaths in NSW from the Australian Bureau of Statistics (ABS) from 2005 to 2011. We measured and compared Age Standardised Mortality Rate (ASMR), Comparative Mortality Figure (CMF), years of productive life lost (YPLL) and proportion of deaths with potentially avoidable causes in an ID cohort with an NSW general population cohort. There were 19 362 adults in the ID cohort which experienced 732 (4%) deaths at a median age of 54 years. Age Standardised Mortality Rates increased with age for both cohorts. Overall comparative mortality figure was 1.3, but was substantially higher for the 20-44 (4.0) and 45-64 (2.3) age groups. YPLL was 137/1000 people in the ID cohort and 49 in the comparison cohort. Cause of death in ID cohort was dominated by respiratory, circulatory, neoplasm and nervous system. After recoding deaths previously attributed to the aetiology of the disability, 38% of deaths in the ID cohort and 17% in the comparison cohort were potentially avoidable. Adults with ID experience premature mortality and over-representation of potentially avoidable deaths. A national system of reporting of deaths in adults with ID is required. Inclusion in health policy and services development and in health promotion programmes is urgently required to address premature deaths and health inequalities for adults with ID. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Validation of verbal autopsy: determination of cause of deaths in Malaysia 2013

Directory of Open Access Journals (Sweden)

Shubash Shander Ganapathy

2017-08-01

Full Text Available Abstract Background Mortality statistics by age, sex and cause are the foundation of basic health data required for health status assessment, epidemiological research and formation of health policy. Close to half the deaths in Malaysia occur outside a health facility, are not attended by medical personnel, and are given a lay opinion as to the cause of death, leading to poor quality of data from vital registration. Verbal autopsy (VA is a very useful tool in diagnosing broad causes of deaths for events that occur outside health facilities. This article reports the development of the VA methods and our principal finding from a validation study. Methods A cross sectional study on nationally representative sample deaths that occurred in Malaysia during 2013 was used. A VA questionnaire suitable for local use was developed. Trained field interviewers visited the family members of the deceased at their homes and conducted face to face interviews with the next of kin. Completed questionnaires were reviewed by trained physicians who assigned multiple and underlying causes. Reference diagnoses for validation were obtained from review of medical records (MR available for a sample of the overall study deaths. Results Corresponding MR diagnosis with matched sample of the VA diagnosis were available in 2172 cases for the validation study. Sensitivity scores were good (>75% for transport accidents and certain cancers. Moderate sensitivity (50% - 75% was obtained for ischaemic heart disease (64% and cerebrovascular disease (72%. The validation sample for deaths due to major causes such as ischaemic heart disease, pneumonia, breast cancer and transport accidents show low cause-specific mortality fraction (CSMF changes. The scores obtained for the top 10 leading site-specific cancers ranged from average to good. Conclusion We can conclude that VA is suitable for implementation for deaths outside the health facilities in Malaysia. This would reduce ill

Sensitization by wortmannin of heat- or X-ray induced cell death in cultured Chinese hamster V79 cells

International Nuclear Information System (INIS)

Tomita, Masanori; Suzuki, Norio; Matsumoto, Yoshihisa; Hirano, Kazuya; Umeda, Noriko; Sakai, Kazuo

2000-01-01

Here we found that wortmannin sensitized Chinese hamster V79 cells to hyperthermic treatment at 44.0 deg C as determined either by colony formation assay or by dye exclusion assay. Wortmannin enhanced heat-induced cell death accompanying cleavage of poly (ADP-ribose) polymerases (PARP). Additionally, the induction of heat shock protein HSP70 was suppressed and delayed in wortmannin-treated cells. Heat sensitizing effect of wortmannin was obvious at more than 5 or 10 μM of final concentrations, while radiosensitization was apparent at 5 μM. Requirement for high concentration of wortmannin, i.e., order of μM, suggests a possible role of certain protein kinases, such as DNA-PK and/or ATM among PI3-kinase family. The sensitization was minimal when wortmannin was added at the end of heat treatment. This was similar to the case of X-ray. Since heat-induced cell death and PARP cleavage preceded HSP70 induction phenomenon, the sensitization to the hyperthermic treatment was considered mainly caused by enhanced apoptotic cell death rather than secondary to suppression or delay by wortmannin of HSP70 induction. Further, in the present system radiosensitization by wortmannin was also at least partly mediated through enhancement of apoptotic cell death. (author)

Mechanisms of Betulinic acid‐induced cell death

NARCIS (Netherlands)

Potze, L.

2015-01-01

The scope of this thesis was to investigate the mechanisms by which BetA induces cell death in cancer cells in more detail. At the start of the studies described in this thesis several questions urgently needed an answer. Although BetA induces cell death via apoptosis, when blocking this form of

Vitamin K3 triggers human leukemia cell death through hydrogen peroxide generation and histone hyperacetylation.

Science.gov (United States)

Lin, Changjun; Kang, Jiuhong; Zheng, Rongliang

2005-10-01

Vitamin K3 (VK3) is a well-known anticancer agent, but its mechanism remains elusive. In the present study, VK3 was found to simultaneously induce cell death, reactive oxygen species (ROS) generation, including superoxide anion (O2*-) and hydrogen peroxide (H2O2) generation, and histone hyperacetylation in human leukemia HL-60 cells in a concentration- and time-dependent manner. Catalase (CAT), an antioxidant enzyme that specifically scavenges H2O2, could significantly diminish both histone acetylation increase and cell death caused by VK3, whereas superoxide dismutase (SOD), an enzyme that specifically eliminates O2*-, showed no effect on both of these, leading to the conclusion that H2O2 generation, but not O2*- generation, contributes to VK3-induced histone hyperacetylation and cell death. This conclusion was confirmed by the finding that enhancement of VK3-induced H2O2 generation by vitamin C (VC) could significantly promote both the histone hyperacetylation and cell death. Further studies suggested that histone hyperacetylation played an important role in VK3-induced cell death, since sodium butyrate, a histone deacetylase (HDAC) inhibitor, showed no effect on ROS generation, but obviously potentiated VK3-induced histone hyperacetylation and cell death. Collectively, these results demonstrate a novel mechanism for the anticancer activity of VK3, i.e., VK3 induced tumor cell death through H2O2 generation, which then further induced histone hyperacetylation.

Determination of the underlying cause of death in three multicenter international HIV clinical trials

DEFF Research Database (Denmark)

Lifson, Alan R; Lundgren, Jens; Belloso, Waldo H

2008-01-01

PURPOSE: Describe processes and challenges for an Endpoint Review Committee (ERC) in determining and adjudicating underlying causes of death in HIV clinical trials. METHOD: Three randomized HIV trials (two evaluating interleukin-2 and one treatment interruption) enrolled 11,593 persons from 36...... information or supporting documentation to determine cause of death. Half (51%) of deaths reviewed by the ERC required follow-up adjudication; consensus was eventually always reached. CONCLUSION: ERCs can successfully provide blinded, independent, and systematic determinations of underlying cause of death...

BID links ferroptosis to mitochondrial cell death pathways.

Science.gov (United States)

Neitemeier, Sandra; Jelinek, Anja; Laino, Vincenzo; Hoffmann, Lena; Eisenbach, Ina; Eying, Roman; Ganjam, Goutham K; Dolga, Amalia M; Oppermann, Sina; Culmsee, Carsten

2017-08-01

Ferroptosis has been defined as an oxidative and iron-dependent pathway of regulated cell death that is distinct from caspase-dependent apoptosis and established pathways of death receptor-mediated regulated necrosis. While emerging evidence linked features of ferroptosis induced e.g. by erastin-mediated inhibition of the X c - system or inhibition of glutathione peroxidase 4 (Gpx4) to an increasing number of oxidative cell death paradigms in cancer cells, neurons or kidney cells, the biochemical pathways of oxidative cell death remained largely unclear. In particular, the role of mitochondrial damage in paradigms of ferroptosis needs further investigation. In the present study, we find that erastin-induced ferroptosis in neuronal cells was accompanied by BID transactivation to mitochondria, loss of mitochondrial membrane potential, enhanced mitochondrial fragmentation and reduced ATP levels. These hallmarks of mitochondrial demise are also established features of oxytosis, a paradigm of cell death induced by X c - inhibition by millimolar concentrations of glutamate. Bid knockout using CRISPR/Cas9 approaches preserved mitochondrial integrity and function, and mediated neuroprotective effects against both, ferroptosis and oxytosis. Furthermore, the BID-inhibitor BI-6c9 inhibited erastin-induced ferroptosis, and, in turn, the ferroptosis inhibitors ferrostatin-1 and liproxstatin-1 prevented mitochondrial dysfunction and cell death in the paradigm of oxytosis. These findings show that mitochondrial transactivation of BID links ferroptosis to mitochondrial damage as the final execution step in this paradigm of oxidative cell death. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Caspase-independent cell death mediated by apoptosis-inducing factor (AIF) nuclear translocation is involved in ionizing radiation induced HepG2 cell death

Energy Technology Data Exchange (ETDEWEB)

Sun, Hengwen [Department of Radiation, Cancer Center of Guangdong General Hospital (Guangdong Academy of Medical Science), Guangzhou, 510080, Guangdong (China); Yang, Shana; Li, Jianhua [Department of Physiology, Guangzhou Medical University, Guangzhou, 510182, Guangdong (China); Zhang, Yajie [Department of Pathology, Guangzhou Medical University, Guangzhou, 510182, Guangdong (China); Gao, Dongsheng [Department of Oncology, Guangdong Medical College Affiliated Pengpai Memorial Hospital, Hai Feng, 516400, Gungdong (China); Zhao, Shenting, E-mail: zhaoshenting@126.com [Department of Physiology, Guangzhou Medical University, Guangzhou, 510182, Guangdong (China)

2016-03-25

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. The aim of radiotherapy is to eradicate cancer cells with ionizing radiation. Except for the caspase-dependent mechanism, several lines of evidence demonstrated that caspase-independent mechanism is directly involved in the cell death responding to irradiation. For this reason, defining the contribution of caspase-independent molecular mechanisms represents the main goal in radiotherapy. In this study, we focused on the role of apoptosis-inducing factor (AIF), the caspase-independent molecular, in ionizing radiation induced hepatocellular carcinoma cell line (HepG2) cell death. We found that ionizing radiation has no function on AIF expression in HepG2 cells, but could induce AIF release from the mitochondria and translocate into nuclei. Inhibition of AIF could reduce ionizing radiation induced HepG2 cell death. These studies strongly support a direct relationship between AIF nuclear translocation and radiation induced cell death. What's more, AIF nuclear translocation is caspase-independent manner, but not caspase-dependent manner, in this process. These new findings add a further attractive point of investigation to better define the complex interplay between caspase-independent cell death and radiation therapy. - Highlights: • AIF nuclear translocation is involved in ionizing radiation induced hepatocellular carcinoma cell line HepG2 cell death. • AIF mediated cell death induced by ionizing radiation is caspase-independent. • Caspase-independent pathway is involved in ionzing radiation induced HepG2 cell death.

Caspase-independent cell death mediated by apoptosis-inducing factor (AIF) nuclear translocation is involved in ionizing radiation induced HepG2 cell death

International Nuclear Information System (INIS)

Sun, Hengwen; Yang, Shana; Li, Jianhua; Zhang, Yajie; Gao, Dongsheng; Zhao, Shenting

2016-01-01

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. The aim of radiotherapy is to eradicate cancer cells with ionizing radiation. Except for the caspase-dependent mechanism, several lines of evidence demonstrated that caspase-independent mechanism is directly involved in the cell death responding to irradiation. For this reason, defining the contribution of caspase-independent molecular mechanisms represents the main goal in radiotherapy. In this study, we focused on the role of apoptosis-inducing factor (AIF), the caspase-independent molecular, in ionizing radiation induced hepatocellular carcinoma cell line (HepG2) cell death. We found that ionizing radiation has no function on AIF expression in HepG2 cells, but could induce AIF release from the mitochondria and translocate into nuclei. Inhibition of AIF could reduce ionizing radiation induced HepG2 cell death. These studies strongly support a direct relationship between AIF nuclear translocation and radiation induced cell death. What's more, AIF nuclear translocation is caspase-independent manner, but not caspase-dependent manner, in this process. These new findings add a further attractive point of investigation to better define the complex interplay between caspase-independent cell death and radiation therapy. - Highlights: • AIF nuclear translocation is involved in ionizing radiation induced hepatocellular carcinoma cell line HepG2 cell death. • AIF mediated cell death induced by ionizing radiation is caspase-independent. • Caspase-independent pathway is involved in ionzing radiation induced HepG2 cell death.