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At least 253 records · Page 14Linked to original sources
PubMed1994

Anti-Fas antibody induces different types of cell death in the human histiocytic cell line, U937, and the human B cell line, B104: the role of single-strand DNA breaks and poly (ADP-ribosyl)ation in cell death.

We investigated the anti-Fas antibody-induced cell death in two different types of human cell lines, U937 and B104. IFN-gamma increased the surface expression of Fas antigen and susceptibility to anti-Fas Ab-induced cell death of B104 and U937 cells. Anti-Fas Ab-induced death of U937 and B104 cells required neither a Ca2+ influx nor macromolecular synthesis. U937 cells treated with anti-Fas Ab represented apoptosis with DNA fragmentation, whereas anti-Fas Ab-treated B104 cells did not. Single-strand DNA breaks, however, appeared in the B104 cells. Zinc ions prevented DNA fragmentation and the morphological features of apoptosis in anti-Fas Ab-treated U937 cells, but did not inhibit cell death. However, zinc ions, when used in combination with the poly(ADP-ribosyl)ation inhibitors, inhibited anti-Fas Ab-induced U937 cell death. The inhibitors by themselves did not inhibit anti-Fas Ab-induced U937 cell death, but did inhibit anti-Fas Ab-induced B104 cell death. A substantial decrease in NAD pools was observed in anti-Fas Ab-treated B104 and U937 cells in parallel with the increase of DNA strand breaks before cell death became apparent. These results suggest the involvement of single-strand DNA breaks and poly(ADP-ribosyl)ation in the mechanisms of anti-Fas Ab-induced U937 and B104 cell death.

Antigens, Surface↗
PubMed2004

Direct binding of Fas-associated death domain (FADD) to the tumor necrosis factor-related apoptosis-inducing ligand receptor DR5 is regulated by the death effector domain of FADD.

Members of the tumor necrosis factor superfamily of receptors induce apoptosis by recruiting adaptor molecules through death domain interactions. The central adaptor molecule for these receptors is the death domain-containing protein Fas-associated death domain (FADD). FADD binds a death domain on a receptor or additional adaptor and recruits caspases to the activated receptor. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signals apoptosis through two receptors, DR4 and DR5. Although there is much interest in TRAIL, the mechanism by which FADD is recruited to the TRAIL receptors is not clear. Using a reverse two-hybrid system we previously identified mutations in the death effector domain of FADD that prevented binding to Fas/CD95. Here we show that these mutations also prevent binding to DR5. FADD-deficient Jurkat cells stably expressing these FADD mutations did not transduce TRAIL or Fas/CD95 signaling. Second site compensating mutations that restore binding to and signaling through Fas/CD95 and DR5 were also in the death effector domain. We conclude that in contrast to current models where the death domain of FADD functions independently of the death effector domain, the death effector domain of FADD comes into direct contact with both TRAIL and Fas/CD95 receptors.

Adaptor Proteins, Signal Transducing↗
PubMed2006

The death domain kinase RIP has an important role in DNA damage-induced, p53-independent cell death.

Tumor suppressor p53 plays a critical role in cellular responses, such as cell cycle arrest and apoptosis following DNA damage. DNA damage-induced cell death can be mediated by a p53-dependent or p53-independent pathway. Although p53-mediated apoptosis has been well documented, little is known about the signaling components of p53-independent cell death. Here we report that the death domain kinase, RIP (receptor-interacting protein), is important for DNA damage-induced, p53-independent cell death. DNA damage induces cell death in both wild-type and p53-/- mouse embryonic fibroblast cells. We found that RIP-/- mouse embryonic fibroblast cells, which have a mutant form of the p53 protein, are resistant to DNA damage-induced cell death. The reconstitution of RIP protein expression in RIP-/- cells restored the sensitivity of cells to DNA damage-induced cell death. We also found that RIP mediates this process through activating mitogen-activated protein kinase, JNK1. Furthermore, knocking down the expression of RIP blocked DNA damage-induced cell death in the human colon cancer cell line, p53 null HCT 116. Taken together, our study demonstrates that RIP is one of the critical components involved in mediating DNA damage-induced, p53-independent cell death.

Animals↗
PubMed1999

Mitochondrial regulation of cell death: mitochondria are essential for procaspase 3-p21 complex formation to resist Fas-mediated cell death.

Death receptor Fas transduces cell death signaling upon stimulation by Fas ligand, and this death signaling is mediated by caspase. Recently, we reported that the cell cycle regulator p21 interacts with procaspase 3 to resist Fas-mediated cell death. In the present study, the molecular characterization and functional region of the procaspase 3-p21 complex was further investigated. We observed the p21 expression in the mitochondrial fraction of HepG2 cells and detected Fas-mediated cell death only in the presence of actinomycin D. However, mitochondrial-DNA-lacking HepG2 (MDLH) cells showed this effect even in the absence of actinomycin D. Both p21 and procaspase 3 were expressed in MDLH cells, but the procaspase 3-p21 complex formation was not observed. Interestingly, the resistance to Fas-mediated cell death in the MDLH cells without actinomycin D was recovered after microinjection of HepG2-derived mitochondria into the MDLH cells. We conclude that mitochondria are necessary for procaspase 3-p21 complex formation and propose that the mitochondrial role during cell death is not only death induction but also death suppression.

Apoptosis↗
PubMed1992

Activation-driven T cell death. II. Quantitative differences alone distinguish stimuli triggering nontransformed T cell proliferation or death.

Clonal deletion is the major mechanism by which T cell tolerance is achieved in vivo. The process of activation-driven cell death, originally characterized with T cell hybridomas, likely represents the mechanism of clonal deletion because it shares a number of properties with the in vivo process, especially the ability to be triggered in an Ag-specific manner, the cell-autonomous nature of the response, and its sensitivity to the drug cyclosporin A. We now have extended our analysis of activation-driven cell death to clonal populations of nontransformed T cells. Activation-driven cell death can be induced in nontransformed T lymphocytes by combinations of mitogenic stimuli. In particular, two mitogenic stimuli at high dose, one a lymphokine and the other delivered via the TCR or another activation structure, are required to induce activation-driven cell death. Activation-driven cell death is an active cell suicide process with attributes typical of physiological cell death, including early nuclear disintegration and a requirement for macromolecular synthesis, and is distinct from death by factor deprivation. Susceptibility to the induction of cell death by antigenic or activating stimulation is a common aspect of most T cells and is consistent with observations that clonal deletion can occur throughout T cell ontogeny. Most importantly, the alternative cellular responses of cell death and cell proliferation in nontransformed T cells appear to be triggered solely as a function of quantitative differences in the doses of identical stimuli. This can be viewed as a dose-dependent switch that determines cell fate. Developmental regulation of this switch may explain the processes of positive and negative selection during T cell ontogeny and also provide a mechanistic rationale for a strategy of selective anti-tumor therapy.

Animals↗
PubMedDate not supplied

Brain death: resolving inconsistencies in the ethical declaration of death.

PURPOSE: The first criteria for the determination of brain death were developed in 1968 in part to address concerns that had arisen with the retrieval of organs for transplantation. Despite over 30 years of application, some professional and public doubt persists over the validity of the theoretical construct underlying this method of determining death. Our review will address historical perspectives on the development of brain death criteria, and inconsistencies in current clinical criteria. METHOD: Narrative review from selected MEDLINE references and other published sources. PRINCIPLE FINDINGS: The primary construct of the determination of death is that either cardiopulmonary or neurological function irreversibly ceases. However, there is inconsistency in the neurological criteria for death between jurisdictions, between patient populations, and in the use of confirmatory tests. These inconsistencies may cause concern in the public or profession about the validity of the determination of death by neurological criteria. CONCLUSIONS: Organ transplantation is premised on professional and public acceptance that the donor is dead. Given that the criteria for brain death or their application remain variable, we suggest that it is reasonable to consider a national consensus to address these inconsistencies. Alternatively, the standard use of confirmatory radiographic testing prior to the retrieval of organs from donors who meet clinical brain death criteria should be considered to provide conclusive evidence of permanent and irreversible loss of brain function.

Brain Death↗
PubMed2004

Current burden of sudden cardiac death: multiple source surveillance versus retrospective death certificate-based review in a large U.S. community.

OBJECTIVES: We sought to determine the annual incidence of sudden cardiac death (SCD) in the general population using a prospective approach. To assess the validity of retrospective surveillance, a simultaneous comparison was made with a death certificate-based method of determining SCD incidence. BACKGROUND: Accurate surveillance and characterization of SCD in the general population is likely to significantly facilitate current and future community-based preventive and therapeutic interventions. METHODS: We performed a prospective evaluation of SCD among all residents of Multnomah County, Oregon (population 660,486) using multiple sources of surveillance. A comprehensive analysis of circumstances of death, medical records, and available autopsy data was performed. Comparisons were made with a retrospective, death certificate-based determination of SCD incidence using International Classification of Diseases-Version 10 codes and location of death. RESULTS: Between February 1, 2002, and January 31, 2003, 353 residents suffered SCD (incidence 53 of 100,000; median age 69 years, 57% male) accounting for 5.6% of overall mortality. Of these, 75 cases (21%) were identified using sources other than first responders. Resuscitation was attempted in 237 cases (67%) and successful (survival to hospital discharge) in 28 (8%). The retrospective death certificate-based review yielded 1,007 cases (incidence 153 of 100,000; median age 81 years, 51% male), and the positive predictive value of this methodology was 19%. CONCLUSIONS: Sudden cardiac death accounts for 5.6% of annual mortality, and prospective evaluation in the general population appears to be feasible. The use of multiple sources of ascertainment and information significantly enhances phenotyping of SCD cases. Retrospective death certificate-based surveillance results in significant overestimation of SCD incidence.

Adolescent↗
PubMed1999

Repeated neonatal deaths in families with special reference to causes of death.

It is recognized that one infant death in a family indicates an increased risk of death of a subsequent sibling. This study examines which cause of death of a sibling is related to the mortality of the younger sibling and when. Longitudinal vital events data from the maternal and child health and family planning (MCH-FP) project and the comparison areas in Matlab, Bangladesh, were used. Primary causes of 868 neonatal deaths and 624 post-neonatal deaths resulting from 18,865 singleton live births in 1989-92 and those (967 as neonates and 708 as post-neonates) of their immediate elder siblings were categorised into infectious and non-infectious diseases. Multinomial logistic regression was used to estimate the risk of younger siblings dying in each age period from infectious and non-infectious diseases given the age and cause of deaths of older siblings and controlling for other biosocial correlates of infant mortality. A neonatal death of non-infectious causes in a family was twice as likely to be followed by another one occurring at the same age from similar causes compared with a surviving infant followed by a neonatal death from non-infectious causes. The MCH-FP project, though successful in reducing the risk of neonatal and post-neonatal mortality from infectious diseases, did not reduce the risk of dying from non-infectious diseases.

Bangladesh↗
PubMed2005

Cisplatin inactivation of caspases inhibits death ligand-induced cell death in vitro and fulminant liver damage in mice.

Cisplatin is a platinum-containing chemotherapeutic drug that has been widely used to treat various human cancers. It acts by forming inter- and intracross-links of DNA, which is believed to be a major cause for its therapeutic efficacy. However, little attention has been paid to the effect of cisplatin on death ligand-induced cell death. Here we demonstrate that cisplatin inhibits death ligand-induced cell death in cell lines in a p53-independent manner. This inhibitory effect of cisplatin on cell death is direct, whereby cisplatin forms a complex with caspases leading to their inactivation. The cisplatin-caspase complex is reversed by the addition of reducing agent dithiothreitol, and caspase activity is regained. In addition, cisplatin shows a death-inhibition effect in in vivo animal models of fulminant liver damage induced by Fas activation and lipopolysaccharide-induced liver shock mediated by tumor necrosis factor-alpha. Together, we demonstrate that cisplatin inhibits cell death induced by death ligands in cell lines and in mice through caspase inactivation.

Animals↗
PubMedDate not supplied

Relationship of recollections of first death experience to current death attitudes.

Previous research (Dickinson, 1992) has investigated adults' memories of their first childhood experience with death. The present study extended this work to examine the relationship of various qualitative aspects of the first experience with death to current death attitudes. College students (196 females, 101 males) described their first childhood death experience and provided memories of: (a) who died; (b) whether parental discussion of death had occurred; (c) whether they had unanswered questions at the time; and (d) whether they had cried at the time. They then completed the Death Attitude Profile-Revised (DAP-R; Wong, Reker, & Gesser, 1994). Results indicated that although boys and girls did not respond differently to the first death experience, gender did appear to moderate the relationship between the qualities of this experience and current death attitudes.

Adult↗
PubMedDate not supplied

Death anxiety and personal growth in adolescents experiencing the death of a grandparent.

Relationships between bereavement following the death of a grandparent and adolescent death anxiety levels were examined using Hogan's Inventory of Bereavement and the revised Death Anxiety Scale within private schools. Of the 226 adolescent respondents (aged 11-18) who completed questionnaires, 124 had experienced the death of a grandparent. The regression model indicated that grief due to bereavement was found to be significantly associated with death anxiety. The factors of personal growth, gender, time since death, and numbers of deaths experienced were not found to be significant predictors within the model. The findings encourage further exploration into the nature of the grandparent-adolescent relationship as well as the impact of type of death experienced.

Adolescent↗
PubMed2001

Regional differences in stillbirth and neonatal death rate in Sweden with a cause-of-death specific analysis.

UNLABELLED: Regional differences in stillbirth and neonatal death rates in Sweden were studied and a cause-of-death analysis was done in the 4 counties (among 24) with an increased mortality. The study is based on a computerized evaluation of infant cause of death, using a slightly modified Wigglesworth classification and a hierarchical classification (NICE: Neonatal and Intrauterine death Classification according to Etiology). Differences between the identified counties with respect to specific causes of death were demonstrated. CONCLUSION: There are differences between Swedish counties with respect to the risk for stillbirth or neonatal death. The NICE cause-of-death classification can be used for the routine surveillance of stillbirths and neonatal deaths in a population and can help in pinpointing weak elements in antenatal, delivery and neonatal care.

Cause of Death↗
PubMed1997

A computer-based method for cause of death classification in stillbirths and neonatal deaths.

BACKGROUND: In large-scale epidemiological studies of stillbirths and neonatal deaths a method is needed to replace detailed medical record audits in order to determine the cause of death. METHODS: A computer-based method is presented for determination of the cause of death in stillbirths and in neonatal deaths. It utilizes information in the Swedish medical registries. The study comprises 6044 dead infants born in Sweden from 1983-1990. For each infant the program determines 31 basic characteristics which are important in deciding the cause of death. Based on these characteristics a modified Wigglesworth's classification is used to find the cause of death. The validity of the method was checked by comparing the computer generated information with information obtained by scrutinizing medical records for a 10% representative sample (603 infants). RESULTS: Specificity and sensitivity for each basic characteristic varied, but for the modified Wigglesworth cause of death classification the concordance was 88%. The weakest data refer to intrauterine deaths, where pertinent information was often missing in the medical registries. CONCLUSION: The method can be used for large-scale epidemiological studies.

Cause of Death↗