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Sample records for bcl-2 family member

  1. The anti-apoptotic members of the Bcl-2 family are attractive tumor-associated antigens

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    Straten, Per thor; Andersen, Mads Hald; Andersen, Mads Hald

    2010-01-01

    Anti-apoptotic members of the Bcl-2 family (Bcl-2, Bcl-X(L) and Mcl-2) are pivotal regulators of apoptotic cell death. They are all highly overexpressed in cancers of different origin in which they enhance the survival of the cancer cells. Consequently, they represent prime candidates for anti-ca...

  2. Members of the bcl-2 and caspase families regulate nuclear degeneration during chick lens fibre differentiation.

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    Wride, M A; Parker, E; Sanders, E J

    1999-09-01

    The optical clarity of the lens is ensured by the programmed removal of nuclei and other organelles from the lens fibre cells during development. The morphology of the degenerating nuclei is similar to that observed during apoptosis and is accompanied by DNA fragmentation. Proteins encoded by the bcl-2 proto-oncogene family are important in either promoting or inhibiting apoptosis, and caspases are involved in downstream proteolytic events. Here, the expression of bcl-2 family members (bcl-2, bax, bad, and bcl-x(s/l)) and caspases-1, -2, -3, -4, and -6 was investigated through a range of stages of chick lens development using immunocytochemistry, Western blotting, and affinity labelling for caspases using biotinylated caspase inhibitors. Using differentiating lens epithelial cell cultures, it was demonstrated that the addition to cultures of synthetic peptide inhibitors of caspases -1, -2, -4, -6, and -9 brought about a 50-70% reduction in the number of degenerating nuclei per unit area of culture, as assessed by image analysis. These effects were comparable to those seen when general inhibitors of caspases were added to cultures. On the other hand, inhibitors of caspases-3 and -8 were not effective in significantly reducing the number of TUNEL-labelled nuclei. Expression of the caspase substrates poly(ADP-ribose) polymerase (PARP) and the 45-kDa subunit of DNA fragmentation factor (DFF 45) was also observed in the developing lens. Western blots of cultures to which caspase inhibitors were added revealed alterations in the PARP cleavage pattern, but not in that of DFF. These results demonstrate a role for members of the bcl-2 family and caspases in the degeneration of lens fibre cell nuclei during chick secondary lens fibre development and support the proposal that this process has many characteristics in common with apoptosis. Copyright 1999 Academic Press.

  3. Micro-Economics of Apoptosis in Cancer: ncRNAs Modulation of BCL-2 Family Members.

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    Villanova, Lidia; Careccia, Silvia; De Maria, Ruggero; Fiori, Micol E

    2018-03-23

    In the last few years, non-coding RNAs (ncRNAs) have been a hot topic in cancer research. Many ncRNAs were found to regulate the apoptotic process and to play a role in tumor cell resistance to treatment. The apoptotic program is on the frontline as self-defense from cancer onset, and evasion of apoptosis has been classified as one of the hallmarks of cancer responsible for therapy failure. The B-cell lymphoma 2 (BCL-2) family members are key players in the regulation of apoptosis and mediate the activation of the mitochondrial death machinery in response to radiation, chemotherapeutic agents and many targeted therapeutics. The balance between the pro-survival and the pro-apoptotic BCL-2 proteins is strictly controlled by ncRNAs. Here, we highlight the most common mechanisms exerted by microRNAs, long non-coding RNAs and circular RNAs on the main mediators of the intrinsic apoptotic cascade with particular focus on their significance in cancer biology.

  4. Antagonizing Bcl-2 family members sensitizes neuroblastoma and Ewing's sarcoma to an inhibitor of glutamine metabolism.

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    Rachelle R Olsen

    Full Text Available Neuroblastomas (NBL and Ewing's sarcomas (EWS together cause 18% of all pediatric cancer deaths. Though there is growing interest in targeting the dysregulated metabolism of cancer as a therapeutic strategy, this approach has not been fully examined in NBL and EWS. In this study, we first tested a panel of metabolic inhibitors and identified the glutamine antagonist 6-diazo-5-oxo-L-norleucine (DON as the most potent chemotherapeutic across all NBL and EWS cell lines tested. Myc, a master regulator of metabolism, is commonly overexpressed in both of these pediatric malignancies and recent studies have established that Myc causes cancer cells to become "addicted" to glutamine. We found DON strongly inhibited tumor growth of multiple tumor lines in mouse xenograft models. In vitro, inhibition of caspases partially reversed the effects of DON in high Myc expressing cell lines, but not in low Myc expressing lines. We further showed that induction of apoptosis by DON in Myc-overexpressing cancers is via the pro-apoptotic factor Bax. To relieve inhibition of Bax, we tested DON in combination with the Bcl-2 family antagonist navitoclax (ABT-263. In vitro, this combination caused an increase in DON activity across the entire panel of cell lines tested, with synergistic effects in two of the N-Myc amplified neuroblastoma cell lines. Our study supports targeting glutamine metabolism to treat Myc overexpressing cancers, such as NBL and EWS, particularly in combination with Bcl-2 family antagonists.

  5. Molecular interactions of prodiginines with the BH3 domain of anti-apoptotic Bcl-2 family members.

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    Ali Hosseini

    Full Text Available Prodigiosin and obatoclax, members of the prodiginines family, are small molecules with anti-cancer properties that are currently under preclinical and clinical trials. The molecular target(s of these agents, however, is an open question. Combining experimental and computational techniques we find that prodigiosin binds to the BH3 domain in some BCL-2 protein families, which play an important role in the apoptotic programmed cell death. In particular, our results indicate a large affinity of prodigiosin for MCL-1, an anti-apoptotic member of the BCL-2 family. In melanoma cells, we demonstrate that prodigiosin activates the mitochondrial apoptotic pathway by disrupting MCL-1/BAK complexes. Computer simulations with the PELE software allow the description of the induced fit process, obtaining a detailed atomic view of the molecular interactions. These results provide new data to understand the mechanism of action of these molecules, and assist in the development of more specific inhibitors of anti-apoptotic BCL-2 proteins.

  6. BH3-only protein Bim inhibits activity of antiapoptotic members of Bcl-2 family when expressed in yeast.

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    Juhásová, Barbora; Mentel, Marek; Bhatia-Kiššová, Ingrid; Zeman, Igor; Kolarov, Jordan; Forte, Michael; Polčic, Peter

    2011-09-02

    Proteins of the Bcl-2 family regulate programmed cell death in mammals by promoting the release of cytochrome c from mitochondria in response to various proapoptotic stimuli. The mechanism by which BH3-only members of the family activate multidomain proapoptotic proteins Bax and Bak to form a pore in mitochondrial membranes remains under dispute. We report that cell death promoting activity of BH3-only protein Bim can be reconstituted in yeast when both Bax and antiapoptotic protein Bcl-X(L) are present, suggesting that Bim likely activates Bax indirectly by inhibiting antiapoptotic proteins. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  7. Clinical profiling of BCL-2 family members in the setting of BRAF inhibition offers a rationale for targeting de novo resistance using BH3 mimetics.

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    Dennie T Frederick

    Full Text Available While response rates to BRAF inhibitiors (BRAFi are high, disease progression emerges quickly. One strategy to delay the onset of resistance is to target anti-apoptotic proteins such as BCL-2, known to be associated with a poor prognosis. We analyzed BCL-2 family member expression levels of 34 samples from 17 patients collected before and 10 to 14 days after treatment initiation with either vemurafenib or dabrafenib/trametinib combination. The observed changes in mRNA and protein levels with BRAFi treatment led us to hypothesize that combining BRAFi with a BCL-2 inhibitor (the BH3-mimetic navitoclax would improve outcome. We tested this hypothesis in cell lines and in mice. Pretreatment mRNA levels of BCL-2 negatively correlated with maximal tumor regression. Early increases in mRNA levels were seen in BIM, BCL-XL, BID and BCL2-W, as were decreases in MCL-1 and BCL2A. No significant changes were observed with BCL-2. Using reverse phase protein array (RPPA, significant increases in protein levels were found in BIM and BID. No changes in mRNA or protein correlated with response. Concurrent BRAF (PLX4720 and BCL2 (navitoclax inhibition synergistically reduced viability in BRAF mutant cell lines and correlated with down-modulation of MCL-1 and BIM induction after PLX4720 treatment. In xenograft models, navitoclax enhanced the efficacy of PLX4720. The combination of a selective BRAF inhibitor with a BH3-mimetic promises to be an important therapeutic strategy capable of enhancing the clinical efficacy of BRAF inhibition in many patients that might otherwise succumb quickly to de novo resistance. Trial registrations: ClinicalTrials.gov NCT01006980; ClinicalTrials.gov NCT01107418; ClinicalTrials.gov NCT01264380; ClinicalTrials.gov NCT01248936; ClinicalTrials.gov NCT00949702; ClinicalTrials.gov NCT01072175.

  8. Effect of doxorubicin, oxaliplatin, and methotrexate administration on the transcriptional activity of BCL-2 family gene members in stomach cancer cells.

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    Florou, Dimitra; Patsis, Christos; Ardavanis, Alexandros; Scorilas, Andreas

    2013-07-01

    Defective apoptosis comprises the main reason for tumor aggressiveness and chemotherapy tolerance in solid neoplasias. Among the BCL-2 family members, whose mRNA or protein expression varies considerably in different human malignancies, BCL2L12 is the one for which we have recently shown its propitious prognostic value in gastric cancer. The purpose of the current work was to investigate the expression behavior of BCL2L12, BAX, and BCL-2 in human stomach adenocarcinoma cells following their exposure to anti-tumor substances. The 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide and trypan blue methods assessed the impact of doxorubicin, oxaliplatin and methotrexate on AGS cells' viability and growth. Following isolation from cells, total RNA was reverse-transcribed to cDNA. Quantification of target genes' expression was performed with real-time PCR using SYBR Green detection system. The relative changes in their mRNA levels between drug-exposed and untreated cells were calculated with the comparative Ct method (2(-ddCt)). All three drugs, as a result of their administration to AGS cancer cells for particular time intervals, provoked substantial fluctuations in the transcriptional levels of the apoptosis-related genes studied. While BAX was principally upregulated, striking similar were the notable changes regarding BCL-2 and BCL2L12 expression in our cellular system. Our findings indicate the growth suppressive effects of doxorubicin, oxaliplatin and methotrexate treatment on stomach carcinoma cells and the implication of BCL2L12, BAX, and BCL-2 expression profiles in the molecular signaling pathways triggered by chemotherapy.

  9. The Bcl-2 Family in Host-Virus Interactions.

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    Kvansakul, Marc; Caria, Sofia; Hinds, Mark G

    2017-10-06

    Members of the B cell lymphoma-2 (Bcl-2) family are pivotal arbiters of mitochondrially mediated apoptosis, a process of fundamental importance during tissue development, homeostasis, and disease. At the structural and mechanistic level, the mammalian members of the Bcl-2 family are increasingly well understood, with their interplay ultimately deciding the fate of a cell. Dysregulation of Bcl-2-mediated apoptosis underlies a plethora of diseases, and numerous viruses have acquired homologs of Bcl-2 to subvert host cell apoptosis and autophagy to prevent premature death of an infected cell. Here we review the structural biology, interactions, and mechanisms of action of virus-encoded Bcl-2 proteins, and how they impact on host-virus interactions to ultimately enable successful establishment and propagation of viral infections.

  10. Bag3 promotes resistance to apoptosis through Bcl-2 family members in non-small cell lung cancer.

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    Zhang, Yong; Wang, Jian-Hua; Lu, Qiang; Wang, Yun-Jie

    2012-01-01

    In non-small cell lung cancer (NSCLC) certain molecular characteristics, which are related to molecular alterations have been investigated. These are responsible for both the initiation and maintenance of the malignancy in lung cancer. The aim of this study was to evaluate the influence of Bag3 (Bcl-2 associated athanogene 3) in the regulation of apoptosis on NSCLC. Bag3 and Hsp70 expression were examined by immunohistochemistry to confirm their potential roles in the prevalence of NSCLC. We also established human normal bronchial epithelial cells and HOP-62 cell line as the model to analyze cell apoptosis and the expression of Hsp70, Bcl-XL and Bcl-2, which were affected by Bag3. In this study, we found that Bag3 and Hsp70 are highly expressed in few tissues and cell lines of NSCLC. Bag3 inhibits apoptosis in human normal bronchial epithelial cell lines and sustain the survival of NSCLC cells. Bag3, Hsp70, Bcl-XL and Bcl-2 are up-regulated in NSCLC cell lines. At the same time, the silencing of Bag3 results in diminishing protein levels of Bcl-XL and Bcl-2. The results of immunoprecipitation identified that Bag3 could interact with Hsp70, Bcl-XL and Bcl-2 NSCLC cells directly or indirectly. We conclude that NSCLC cells were protected from apoptosis through increasing Bag3 expression and consequently promoted the expression of Bcl-XL and Bcl-2.

  11. Bcl-2 family-regulated apoptosis in health and disease

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    Grant Dewson

    2010-04-01

    Full Text Available Grant Dewson, Ruth M KluckMolecular Genetics of Cancer Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, AustraliaAbstract: Apoptotic cell death is essential for embryonic development, tissue homeostasis, and a well-functioning immune system, with aberrant apoptosis contributing to numerous disease conditions. Inadequate cell death is a major contributing factor to tumorigenesis, while excess cell death contributes to neurodegeneration and autoimmune disease. The major pathway of apoptotic cell death, the mitochondrial pathway, is controlled by the Bcl-2 family of proteins. The members of this family, more than 17 in humans, share significant sequence and structural homology, and fulfil either prosurvival or proapoptotic roles. Specific interactions between these functionally polar proteins, and their relative expression levels, govern the susceptibility of each cell to toxic insults. Here we review the current understanding on how apoptotic cell death is controlled by this important protein family. We also discuss how excessive or insufficient cell death can contribute to disease, and how targeting the Bcl-2 family offers novel therapeutic opportunities.Keywords: apoptosis, Bcl-2, cancer, cytochrome c, mitochondria

  12. The Role of Bcl-2 Family Proteins in Therapy Responses of Malignant Astrocytic Gliomas: Bcl2L12 and Beyond

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    Fotini M. Kouri

    2012-01-01

    Full Text Available Glioblastoma (GBM is a highly aggressive and lethal brain cancer with a median survival of less than two years after diagnosis. Hallmarks of GBM tumors include soaring proliferative indices, high levels of angiogenesis, diffuse invasion into normal brain parenchyma, resistance toward therapy-induced apoptosis, and pseudopallisading necrosis. Despite the recent advances in neurosurgery, radiation therapy, and the development of targeted chemotherapeutic regimes, GBM remains one of the deadliest types of cancer. Particularly, the alkylating agent temozolomide (TMZ in combination with radiation therapy prolonged patient survival only marginally, and clinical studies assessing efficacies of targeted therapies, foremost ATP mimetics inhibiting the activity of receptor tyrosine kinases (RTKs, revealed only few initial responders; tumor recurrence is nearly universal, and salvage therapies to combat such progression remain ineffective. Consequently, myriad preclinical and clinical studies began to define the molecular mechanisms underlying therapy resistance of GBM tumors, and pointed to the Bcl-2 protein family, in particular the atypical member Bcl2-Like 12 (Bcl2L12, as important regulators of therapy-induced cell death. This review will discuss the multi-faceted modi operandi of Bcl-2 family proteins, describe their roles in therapy resistance of malignant glioma, and outline current and future drug development efforts to therapeutically target Bcl-2 proteins.

  13. Crosstalk between Bcl-2 family and Ras family small GTPases: potential cell fate regulation?

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    Kang, Jia; Pervaiz, Shazib

    2013-01-01

    Cell fate regulation is a function of diverse cell signaling pathways that promote cell survival and or inhibit cell death execution. In this regard, the role of the Bcl-2 family in maintaining a tight balance between cell death and cell proliferation has been extensively studied. The conventional dogma links cell fate regulation by the Bcl-2 family to its effect on mitochondrial permeabilization and apoptosis amplification. However, recent evidence provide a novel mechanism for death regulation by the Bcl-2 family via modulating cellular redox metabolism. For example overexpression of Bcl-2 has been shown to contribute to a pro-oxidant intracellular milieu and down-regulation of cellular superoxide levels enhanced death sensitivity of Bcl-2 overexpressing cells. Interestingly, gene knockdown of the small GTPase Rac1 or pharmacological inhibition of its activity also reverted death phenotype in Bcl-2 expressing cells. This appears to be a function of an interaction between Bcl-2 and Rac1. Similar functional associations have been described between the Bcl-2 family and other members of the Ras superfamily. These interactions at the mitochondria provide novel opportunities for strategic therapeutic targeting of drug-resistant cancers.

  14. Screening for potential targets for therapy in mesenchymal, clear cell, and dedifferentiated chondrosarcoma reveals Bcl-2 family members and TGFβ as potential targets

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    van Oosterwijk, Jolieke G; Meijer, Danielle; van Ruler, Maayke A J H

    2013-01-01

    . As in conventional chondrosarcoma, antiapoptotic proteins (Bcl-2, and/or Bcl-xl) were highly expressed in all subtypes. Inhibition with the BH-3 mimetic ABT-737 rendered dedifferentiated chondrosarcoma cell lines sensitive to doxorubicin or cisplatin. Our data indicate that antiapoptotic proteins may play...

  15. Characterization of vNr-13, the first alphaherpesvirus gene of the bcl-2 family

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    Aouacheria, Abdel; Banyai, Michelle; Rigal, Dominique; Schmidt, Carl J.; Gillet, Germain

    2003-01-01

    The Bcl-2 family, including antiapoptotic and proapoptotic members, plays key regulating roles in programmed cell death. We report the characterization of a new member of the bcl-2 family, encoded by herpesvirus of turkeys (HVT). The product of this gene shares 80% homology with Nr-13, an apoptosis inhibitor, which is overexpressed in avian cells transformed by the v-src oncogene. This new gene, that we propose to call vnr-13, is the first member of the bcl-2 family to be isolated among α-herpesviruses. Results from cells expressing the HVT-vnr-13 gene product show that the encoded protein inhibits apoptosis and also reduces the rate of cellular proliferation. Contrary to all bcl-2 homologues found in γ-herpesvirus, which are intronless, vnr-13 has the same organization as the cellular nr-13 gene. Hence, the HVT vnr-13 gene may have been acquired from a reverse transcriptase product of an unspliced precursor RNA, or via direct recombination with the host chromosomal DNA

  16. B cell lymphoma-2 (BCL-2) homology domain 3 (BH3) mimetics demonstrate differential activities dependent upon the functional repertoire of pro- and anti-apoptotic BCL-2 family proteins.

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    Renault, Thibaud T; Elkholi, Rana; Bharti, Archana; Chipuk, Jerry E

    2014-09-19

    The B cell lymphoma-2 (BCL-2) family is the key mediator of cellular sensitivity to apoptosis during pharmacological interventions for numerous human pathologies, including cancer. There is tremendous interest to understand how the proapoptotic BCL-2 effector members (e.g. BCL-2-associated X protein, BAX) cooperate with the BCL-2 homology domain only (BH3-only) subclass (e.g. BCL-2 interacting mediator of death, BIM; BCL-2 interacting-domain death agonist, BID) to induce mitochondrial outer membrane permeabilization (MOMP) and apoptosis and whether these mechanisms may be pharmacologically exploited to enhance the killing of cancer cells. Indeed, small molecule inhibitors of the anti-apoptotic BCL-2 family members have been designed rationally. However, the success of these "BH3 mimetics" in the clinic has been limited, likely due to an incomplete understanding of how these drugs function in the presence of multiple BCL-2 family members. To increase our mechanistic understanding of how BH3 mimetics cooperate with multiple BCL-2 family members in vitro, we directly compared the activity of several BH3-mimetic compounds (i.e. ABT-263, ABT-737, GX15-070, HA14.1, TW-37) in biochemically defined large unilamellar vesicle model systems that faithfully recapitulate BAX-dependent mitochondrial outer membrane permeabilization. Our investigations revealed that the presence of BAX, BID, and BIM differentially regulated the ability of BH3 mimetics to derepress proapoptotic molecules from anti-apoptotic proteins. Using mitochondria loaded with fluorescent BH3 peptides and cells treated with inducers of cell death, these differences were supported. Together, these data suggest that although the presence of anti-apoptotic BCL-2 proteins primarily dictates cellular sensitivity to BH3 mimetics, additional specificity is conferred by proapoptotic BCL-2 proteins. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. XIAP impairs mitochondrial function during apoptosis by regulating the Bcl-2 family in renal cell carcinoma.

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    Chen, Chao; Liu, Tian Shu; Zhao, Si Cong; Yang, Wen Zheng; Chen, Zong Ping; Yan, Yong

    2018-05-01

    Efficient apoptosis requires Bcl-2 family-mediated mitochondrial outer membrane permeabilization (MOMP), which releases pro-apoptotic proteins to the cytosol, activating apoptosis and inhibiting X-linked inhibitor of apoptosis protein (XIAP). XIAP is a member of the inhibitors of apoptosis protein family whose expression is elevated in many cancer types and participates in the release of pro-apoptotic proteins. To explore the association between XIAP and the Bcl-2 family, and the influence of XIAP on mitochondria, RNA interference of XIAP was performed in Caki-1 cells and the dynamic change in the levels of related proteins was compared with the original Caki-1 cells upon induction of apoptosis. Upon knockdown of XIAP, the release of cytochrome c (Cyt-c), second mitochondria-derived activator of caspase (Smac) and apoptotic protease activating factor 1 (Apaf-1) from mitochondria proceeded normally, whereas in Caki-1 cells, the release of these pro-apoptotic proteins was significantly prolonged, and incomplete. Downregulation of XIAP through small interfering RNA resulted in an increase of apoptosis and a marked decrease in Bcl-2 and Bcl-xl levels at 3 h. Additionally, the regulation of the level of XIAP protein affected the specific ratios of Bcl-2/Bax and Bcl-xl/Bax, which play decisive roles in cell death. In the present study, it was revealed that XIAP can feed back to mitochondria, delaying Cyt-c and Apaf-1 release. Furthermore, XIAP can limit the release of its inhibitor Smac with the involvement of Bcl-2 family proteins.

  18. Xanthorrhizol induced DNA fragmentation in HepG2 cells involving Bcl-2 family proteins

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    Tee, Thiam-Tsui, E-mail: thiamtsu@yahoo.com [School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor (Malaysia); Cheah, Yew-Hoong [School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor (Malaysia); Bioassay Unit, Herbal Medicine Research Center, Institute for Medical Research, Jalan Pahang, Kuala Lumpur (Malaysia); Meenakshii, Nallappan [Biology Department, Faculty of Science, Universiti Putra Malaysia, 43400 Serdang, Selangor (Malaysia); Mohd Sharom, Mohd Yusof; Azimahtol Hawariah, Lope Pihie [School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor (Malaysia)

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer We isolated xanthorrhizol, a sesquiterpenoid compound from Curcuma xanthorrhiza. Black-Right-Pointing-Pointer Xanthorrhizol induced apoptosis in HepG2 cells as observed using SEM. Black-Right-Pointing-Pointer Apoptosis in xanthorrhizol-treated HepG2 cells involved Bcl-2 family proteins. Black-Right-Pointing-Pointer DNA fragmentation was observed in xanthorrhizol-treated HepG2 cells. Black-Right-Pointing-Pointer DNA fragmentation maybe due to cleavage of PARP and DFF45/ICAD proteins. -- Abstract: Xanthorrhizol is a plant-derived pharmacologically active sesquiterpenoid compound isolated from Curcuma xanthorrhiza. Previously, we have reported that xanthorrhizol inhibited the proliferation of HepG2 human hepatoma cells by inducing apoptotic cell death via caspase activation. Here, we attempt to further elucidate the mode of action of xanthorrhizol. Apoptosis in xanthorrhizol-treated HepG2 cells as observed by scanning electron microscopy was accompanied by truncation of BID; reduction of both anti-apoptotic Bcl-2 and Bcl-X{sub L} expression; cleavage of PARP and DFF45/ICAD proteins and DNA fragmentation. Taken together, these results suggest xanthorrhizol as a potent antiproliferative agent on HepG2 cells by inducing apoptosis via Bcl-2 family members. Hence we proposed that xanthorrhizol could be used as an anti-liver cancer drug for future studies.

  19. Xanthorrhizol induced DNA fragmentation in HepG2 cells involving Bcl-2 family proteins

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    Tee, Thiam-Tsui; Cheah, Yew-Hoong; Meenakshii, Nallappan; Mohd Sharom, Mohd Yusof; Azimahtol Hawariah, Lope Pihie

    2012-01-01

    Highlights: ► We isolated xanthorrhizol, a sesquiterpenoid compound from Curcuma xanthorrhiza. ► Xanthorrhizol induced apoptosis in HepG2 cells as observed using SEM. ► Apoptosis in xanthorrhizol-treated HepG2 cells involved Bcl-2 family proteins. ► DNA fragmentation was observed in xanthorrhizol-treated HepG2 cells. ► DNA fragmentation maybe due to cleavage of PARP and DFF45/ICAD proteins. -- Abstract: Xanthorrhizol is a plant-derived pharmacologically active sesquiterpenoid compound isolated from Curcuma xanthorrhiza. Previously, we have reported that xanthorrhizol inhibited the proliferation of HepG2 human hepatoma cells by inducing apoptotic cell death via caspase activation. Here, we attempt to further elucidate the mode of action of xanthorrhizol. Apoptosis in xanthorrhizol-treated HepG2 cells as observed by scanning electron microscopy was accompanied by truncation of BID; reduction of both anti-apoptotic Bcl-2 and Bcl-X L expression; cleavage of PARP and DFF45/ICAD proteins and DNA fragmentation. Taken together, these results suggest xanthorrhizol as a potent antiproliferative agent on HepG2 cells by inducing apoptosis via Bcl-2 family members. Hence we proposed that xanthorrhizol could be used as an anti-liver cancer drug for future studies.

  20. SPATA4 Counteracts Etoposide-Induced Apoptosis via Modulating Bcl-2 Family Proteins in HeLa Cells.

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    Jiang, Junjun; Li, Liyuan; Xie, Mingchao; Fuji, Ryosuke; Liu, Shangfeng; Yin, Xiaobei; Li, Genlin; Wang, Zhao

    2015-01-01

    Spermatogenesis associated 4 (SPATA4) is a testis-specific gene first cloned by our laboratory, and plays an important role in maintaining the physiological function of germ cells. Accumulated evidence suggests that SPATA4 might be associated with apoptosis. Here we established HeLa cells that stably expressed SPATA4 to investigate the function of SPATA4 in apoptosis. SPATA4 protected HeLa cells from etoposide-induced apoptosis through the mitochondrial apoptotic pathway, in the way that SPATA4 suppressed decrease of the mitochondrial membrane potential, the release of cytochrome c, and subsequent activation of caspase-9 and -3. We further demonstrated that SPATA4 upregulated anti-apoptotic members of Bcl-2 family proteins, Bcl-2, and downregulated the pro-apoptotic member of Bcl-2 family proteins, Bax. Knockdown of SPATA4 in HeLa/SPATA4 cells could partially rescue expression levels of bcl-2 and bax. In conclusion, SPATA4 protects HeLa cells against etoposide-induced apoptosis through the mitochondrial apoptotic pathway. Our findings provide further evidence that SPATA4 plays a role in regulating apoptosis.

  1. A Review on Structures and Functions of Bcl-2 Family Proteins from Homo sapiens.

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    Sivakumar, Dakshinamurthy; Sivaraman, Thirunavukkarasu

    2016-01-01

    Cancer cells evade apoptosis, which is regulated by proteins of Bcl-2 family in the intrinsic pathways. Numerous experimental three-dimensional (3D) structures of the apoptotic proteins and the proteins bound with small chemical molecules/peptides/proteins have been reported in the literature. In this review article, the 3D structures of the Bcl-2 family proteins from Homo sapiens and as well complex structures of the anti-apoptotic proteins bound with small molecular inhibitors reported in the literature to date have been comprehensively listed out and described in detail. Moreover, the molecular mechanisms by which the Bcl-2 family proteins modulate the apoptotic processes and strategies for designing antagonists to anti-apoptotic proteins have been concisely discussed.

  2. The sensitivity of diffuse large B-cell lymphoma cell lines to histone deacetylase inhibitor-induced apoptosis is modulated by BCL-2 family protein activity.

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    Ryan C Thompson

    Full Text Available BACKGROUND: Diffuse large B-cell lymphoma (DLBCL is a genetically heterogeneous disease and this variation can often be used to explain the response of individual patients to chemotherapy. One cancer therapeutic approach currently in clinical trials uses histone deacetylase inhibitors (HDACi's as monotherapy or in combination with other agents. METHODOLOGY/PRINCIPAL FINDINGS: We have used a variety of cell-based and molecular/biochemical assays to show that two pan-HDAC inhibitors, trichostatin A and vorinostat, induce apoptosis in seven of eight human DLBCL cell lines. Consistent with previous reports implicating the BCL-2 family in regulating HDACi-induced apoptosis, ectopic over-expression of anti-apoptotic proteins BCL-2 and BCL-XL or pro-apoptotic protein BIM in these cell lines conferred further resistance or sensitivity, respectively, to HDACi treatment. Additionally, BCL-2 family antgonist ABT-737 increased the sensitivity of several DLBCL cell lines to vorinostat-induced apoptosis, including one cell line (SUDHL6 that is resistant to vorinostat alone. Moreover, two variants of the HDACi-sensitive SUDHL4 cell line that have decreased sensitivity to vorinostat showed up-regulation of BCL-2 family anti-apoptotic proteins such as BCL-XL and MCL-1, as well as decreased sensitivity to ABT-737. These results suggest that the regulation and overall balance of anti- to pro-apoptotic BCL-2 family protein expression is important in defining the sensitivity of DLBCL to HDACi-induced apoptosis. However, the sensitivity of DLBCL cell lines to HDACi treatment does not correlate with expression of any individual BCL-2 family member. CONCLUSIONS/SIGNIFICANCE: These studies indicate that the sensitivity of DLBCL to treatment with HDACi's is dependent on the complex regulation of BCL-2 family members and that BCL-2 antagonists may enhance the response of a subset of DLBCL patients to HDACi treatment.

  3. Expression of Bcl-2 family proteins and spontaneous apoptosis in normal human testis.

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    Oldereid, N B; Angelis, P D; Wiger, R; Clausen, O P

    2001-05-01

    We investigated the frequency of spontaneous apoptosis and expression of the Bcl-2 family of proteins during normal spermatogenesis in man. Testicular tissue with both normal morphology and DNA content was obtained from necro-donors and fixed in Bouin's solution. A TdT-mediated dUTP end-labelling method (TUNEL) was used for the detection of apoptotic cells. Expression of apoptosis regulatory Bcl-2 family proteins and of p53 and p21(Waf1) was assessed by immunohistochemistry. Germ cell apoptosis was detected in all testes and was mainly seen in primary spermatocytes and spermatids and in a few spermatogonia. Bcl-2 and Bak were preferentially expressed in the compartments of spermatocytes and differentiating spermatids, while Bcl-x was preferentially expressed in spermatogonia. Bax showed a preferential expression in nuclei of round spermatids, whereas Bad was only seen in the acrosome region of various stages of spermatids. Mcl-1 staining was weak without a particular pattern, whereas expression of Bcl-w, p53 and p21(Waf1) proteins was not detected by immunohistochemistry. The results show that spontaneous apoptosis occurs in all male germ cell compartments in humans. Bcl-2 family proteins are distributed preferentially within distinct germ cell compartments suggesting a specific role for these proteins in the processes of differentiation and maturation during human spermatogenesis.

  4. The role of the acidity of N-heteroaryl sulfonamides as inhibitors of bcl-2 family protein-protein interactions.

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    Touré, B Barry; Miller-Moslin, Karen; Yusuff, Naeem; Perez, Lawrence; Doré, Michael; Joud, Carol; Michael, Walter; DiPietro, Lucian; van der Plas, Simon; McEwan, Michael; Lenoir, Francois; Hoe, Madelene; Karki, Rajesh; Springer, Clayton; Sullivan, John; Levine, Kymberly; Fiorilla, Catherine; Xie, Xiaoling; Kulathila, Raviraj; Herlihy, Kara; Porter, Dale; Visser, Michael

    2013-02-14

    Overexpression of the antiapoptotic members of the Bcl-2 family of proteins is commonly associated with cancer cell survival and resistance to chemotherapeutics. Here, we describe the structure-based optimization of a series of N-heteroaryl sulfonamides that demonstrate potent mechanism-based cell death. The role of the acidic nature of the sulfonamide moiety as it relates to potency, solubility, and clearance is examined. This has led to the discovery of novel heterocyclic replacements for the acylsulfonamide core of ABT-737 and ABT-263.

  5. Targeting BCL2 Family in Human Myeloid Dendritic Cells: A Challenge to Cure Diseases with Chronic Inflammations Associated with Bone Loss

    Directory of Open Access Journals (Sweden)

    Selma Olsson Åkefeldt

    2013-01-01

    Full Text Available Rheumatoid arthritis (RA and Langerhans cell histiocytosis (LCH are common and rare diseases, respectively. They associate myeloid cell recruitment and survival in inflammatory conditions with tissue destruction and bone resorption. Manipulating dendritic cell (DC, and, especially, regulating their half-life and fusion, is a challenge. Indeed, these myeloid cells display pathogenic roles in both diseases and may be an important source of precursors for differentiation of osteoclasts, the bone-resorbing multinucleated giant cells. We have recently documented that the proinflammatory cytokine IL-17A regulates long-term survival of DC by inducing BCL2A1 expression, in addition to the constitutive MCL1 expression. We summarize bibliography of the BCL2 family members and their therapeutic targeting, with a special emphasis on MCL1 and BCL2A1, discussing their potential impact on RA and LCH. Our recent knowledge in the survival pathway, which is activated to perform DC fusion in the presence of IL-17A, suggests that targeting MCL1 and BCL2A1 in infiltrating DC may affect the clinical outcomes in RA and LCH. The development of new therapies, interfering with MCL1 and BCL2A1 expression, to target long-term surviving inflammatory DC should be translated into preclinical studies with the aim to increase the well-being of patients with RA and LCH.

  6. Bcl-2 family of proteins as drug targets for cancer chemotherapy: the long way of BH3 mimetics from bench to bedside.

    Science.gov (United States)

    Vela, Laura; Marzo, Isabel

    2015-08-01

    Bcl-2 proteins are key determinants in the life-death balance. In recent years, proteins in this family have been identified as drug targets in the design of new anti-tumor therapies. Advances in the knowledge of the mechanism of action of anti-apoptotic and pro-apoptotic members of the Bcl-2 family have enabled the development of the so-called 'BH3 mimetics'. These compounds act by inhibiting anti-apoptotic proteins of the family, imitating the function of the BH3-only subset of pro-apoptotic members. Combinations of BH3-mimetics with anti-tumor drugs are being evaluated in both preclinical models and clinical trials. Recent advances in these approaches will be reviewed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Xanthurenic acid translocates proapoptotic Bcl-2 family proteins into mitochondria and impairs mitochondrial function

    Directory of Open Access Journals (Sweden)

    Hess Otto M

    2004-04-01

    Full Text Available Abstract Background Xanthurenic acid is an endogenous molecule produced by tryptophan degradation, produced in the cytoplasm and mitochondria. Its accumulation can be observed in aging-related diseases, e.g. senile cataract and infectious disease. We previously reported that xanthurenic acid provokes apoptosis, and now present a study of the response of mitochondria to xanthurenic acid. Results Xanthurenic acid at 10 or 20 μM in culture media of human aortic smooth muscle cells induces translocation of the proteins Bax, Bak, Bclxs, and Bad into mitochondria. In 20 μM xanthurenic acid, Bax is also translocated to the nucleus. In isolated mitochondria xanthurenic acid leads to Bax and Bclxs oligomerization, accumulation of Ca2+, and increased oxygen consumption. Conclusion Xanthurenic acid interacts directly with Bcl-2 family proteins, inducing mitochondrial pathways of apoptosis and impairing mitochondrial functions.

  8. Born to be Alive: A Role for the BCL-2 Family in Melanoma Tumor Cell Survival, Apoptosis, and Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Anvekar, Rina A.; Asciolla, James J.; Missert, Derek J.; Chipuk, Jerry E., E-mail: jerry.chipuk@mssm.edu [Department of Oncological Sciences, Mount Sinai School of Medicine, New York, NY (United States); Department of Dermatology, Mount Sinai School of Medicine, New York, NY (United States); The Tisch Cancer Institute, Mount Sinai Medical Center, New York, NY (United States)

    2011-10-13

    The global incidence of melanoma has dramatically increased during the recent decades, yet the advancement of primary and adjuvant therapies has not kept a similar pace. The development of melanoma is often centered on cellular signaling that hyper-activates survival pathways, while inducing a concomitant blockade to cell death. Aberrations in cell death signaling not only promote tumor survival and enhanced metastatic potential, but also create resistance to anti-tumor strategies. Chemotherapeutic agents target melanoma tumor cells by inducing a form of cell death called apoptosis, which is governed by the BCL-2 family of proteins. The BCL-2 family is comprised of anti-apoptotic proteins (e.g., BCL-2, BCL-xL, and MCL-1) and pro-apoptotic proteins (e.g., BAK, BAX, and BIM), and their coordinated regulation and function are essential for optimal responses to chemotherapeutics. Here we will discuss what is currently known about the mechanisms of BCL-2 family function with a focus on the signaling pathways that maintain melanoma tumor cell survival. Importantly, we will critically evaluate the literature regarding how chemotherapeutic strategies directly impact on BCL-2 family function and offer several suggestions for future regimens to target melanoma and enhance patient survival.

  9. Involvement of ERK, Bcl-2 family and caspase 3 in recombinant human activin A-induced apoptosis in A549

    International Nuclear Information System (INIS)

    Wang Baiding; Feng Yuling; Song Xingbo; Liu Qingqing; Ning Yunye; Ou Xuemei; Yang Jie; Zhang Xiaohong; Wen, Fuqiang

    2009-01-01

    Background: Activins are members of the transforming growth factor-β (TGF-β) superfamily. Previous studies have shown that activin A may have a central role in regulating both apoptosis and proliferation. However, direct studies of recombination human activin A on human NSCLC A549 cells have not yet been reported. The purpose of this study was to investigate whether activin A could induce apoptosis in A549 cells and the possible mechanisms via which it worked. Methods: Cellular apoptosis induced by activin A was detected by TUNEL assay and the levels of protein expression were detected by western blot. Results: Recombination human activin A induced apoptosis in human NSCLC A549 cells in a concentrate-dependent manner. Activin A-induced A549 apoptosis was accompanied by the up-regulation of Bax, Bad and Bcl-Xs and down-regulation of Bcl-2. Moreover, activin A treatment increased the expression of its typeII receptors, activated ERK and caspase 3 in A549. These results clearly demonstrate that the induction of apoptosis by activin-A involves multiple cellular/molecular pathways and strongly suggest that pro- and anti-apoptotic Bcl-2 family proteins and caspase 3 participate in activin A-induced apoptotic process in A549 cells. On the other hand, activin A treatment had little effect on primary human small airway epithelial cells (SAECs). Conclusion: Recombination human activin A induced apoptosis in A549 cells, at least partially, through ERK and mitochondrial pathway. The result that activin A did not affect the normal SAEC revealed activin A might be considered as a potential anticancer agent and worthy of further studies

  10. [From dualism to multiplicity: seeing BCL-2 family proteins and cell death with new eyes].

    Science.gov (United States)

    Aouacheria, Abdel

    2015-01-01

    The concept of cell death has many links to the concept of death itself, defined as the opposite of life. Achievements obtained through research on apoptosis have apparently allowed us to transcend this Manichean view. Death is no longer outside, but rather inside living systems, as a constitutive force at work within the living matter. Whereas the death of cells can be positive and breed "creation" (e.g. during morphogenesis), its dysregulation can also cause or contribute to fatal diseases including cancer. It is tempting to apply this biological discourse to illuminate the relations between life and death, taken in general terms, but does this generalization actually hold? Is this discourse not essentially a metaphor? If cell death is considered as a vital aspect of various biological processes, then are we not faced with some vitalistic conception of death? Are there one or more meanings to the word "death"? Does the power to self-destruct act in opposition to other key features of living entities, or rather in juxtaposition to them? In this article, we first describe how the field of cell death has been developed on the basis of perceived and built dichotomies, mirroring the original opposition between life and death. We detail the limitations of the current paradigm of apoptosis regulation by BCL-2 family proteins, which nicely illustrate the problem of binary thinking in biology. Last, we try to show a way out of this dualistic matrix, by drawing on the notions of multiplicity, complexity, diversity, evolution and contingency. © Société de Biologie, 2016.

  11. Using Förster-Resonance Energy Transfer to Measure Protein Interactions Between Bcl-2 Family Proteins on Mitochondrial Membranes.

    Science.gov (United States)

    Pogmore, Justin P; Pemberton, James M; Chi, Xiaoke; Andrews, David W

    2016-01-01

    The Bcl-2 family of proteins regulates the process of mitochondrial outer membrane permeabilization, causing the release of cytochrome c and committing a cell to apoptosis. The majority of the functional interactions between these proteins occur at, on, or within the mitochondrial outer membrane, complicating structural studies of the proteins and complexes. As a result most in vitro studies of these protein-protein interactions use truncated proteins and/or detergents which can cause artificial interactions. Herein, we describe a detergent-free, fluorescence-based, in vitro technique to study binding between full-length recombinant Bcl-2 family proteins, particularly cleaved BID (cBID) and BCL-XL, on the membranes of purified mitochondria.

  12. Phosphatidylinositol 3-kinase is essential for kit ligand-mediated survival, whereas interleukin-3 and flt3 ligand induce expression of antiapoptotic Bcl-2 family genes

    DEFF Research Database (Denmark)

    Karlsson, Richard; Engström, Maria; Jönsson, Maria

    2003-01-01

    Cytokines such as interleukin 3 (IL-3), kit ligand (KL), and flt3 ligand (FL) promote survival of hematopoietic stem cells and myeloid progenitor cells. In many cell types, members of the Bcl-2 gene family are major regulators of survival, but the mediating mechanisms are not fully understood....... Using two myeloid progenitor cell lines, FDCP-mix and FDC-P1, as well as primary mouse bone marrow progenitors, we demonstrate that KL-mediated survival is dependent on the activation of phosphatidylinositol-3 (PI-3) kinase. The inhibitor LY294002 was able to completely abolish survival mediated by KL...

  13. Ultra-High-Throughput Screening of Natural Product Extracts to Identify Proapoptotic Inhibitors of Bcl-2 Family Proteins.

    Science.gov (United States)

    Hassig, Christian A; Zeng, Fu-Yue; Kung, Paul; Kiankarimi, Mehrak; Kim, Sylvia; Diaz, Paul W; Zhai, Dayong; Welsh, Kate; Morshedian, Shana; Su, Ying; O'Keefe, Barry; Newman, David J; Rusman, Yudi; Kaur, Harneet; Salomon, Christine E; Brown, Susan G; Baire, Beeraiah; Michel, Andrew R; Hoye, Thomas R; Francis, Subhashree; Georg, Gunda I; Walters, Michael A; Divlianska, Daniela B; Roth, Gregory P; Wright, Amy E; Reed, John C

    2014-09-01

    Antiapoptotic Bcl-2 family proteins are validated cancer targets composed of six related proteins. From a drug discovery perspective, these are challenging targets that exert their cellular functions through protein-protein interactions (PPIs). Although several isoform-selective inhibitors have been developed using structure-based design or high-throughput screening (HTS) of synthetic chemical libraries, no large-scale screen of natural product collections has been reported. A competitive displacement fluorescence polarization (FP) screen of nearly 150,000 natural product extracts was conducted against all six antiapoptotic Bcl-2 family proteins using fluorochrome-conjugated peptide ligands that mimic functionally relevant PPIs. The screens were conducted in 1536-well format and displayed satisfactory overall HTS statistics, with Z'-factor values ranging from 0.72 to 0.83 and a hit confirmation rate between 16% and 64%. Confirmed active extracts were orthogonally tested in a luminescent assay for caspase-3/7 activation in tumor cells. Active extracts were resupplied, and effort toward the isolation of pure active components was initiated through iterative bioassay-guided fractionation. Several previously described altertoxins were isolated from a microbial source, and the pure compounds demonstrate activity in both Bcl-2 FP and caspase cellular assays. The studies demonstrate the feasibility of ultra-high-throughput screening using natural product sources and highlight some of the challenges associated with this approach. © 2014 Society for Laboratory Automation and Screening.

  14. Protein phosphatase 2A mediates JS-K-induced apoptosis by affecting Bcl-2 family proteins in human hepatocellular carcinoma HepG2 cells.

    Science.gov (United States)

    Liu, Ling; Huang, Zile; Chen, Jingjing; Wang, Jiangang; Wang, Shuying

    2018-04-25

    Protein phosphatase 2A (PP2A) is an important enzyme within various signal transduction pathways. The present study was investigated PP2A mediates JS-K-induced apoptosis by affecting Bcl-2 family protein. JS-K showed diverse inhibitory effects in five HCC cell lines, especially HepG2 cells. JS-K caused a dose- and time-dependent reduction in cell viability and increased in levels of LDH release. Meanwhile, JS-K- induced apoptosis was characterized by mitochondrial membrane potential reduction, Hoechst 33342 + /PI + dual staining, release of cytochrome c (Cyt c), and activation of cleaved caspase-9/3. Moreover, JS-K-treatment could lead to the activation of protein phosphatase 2A-C (PP2A-C), decrease of anti-apoptotic Bcl-2 family-protein expression including p-Bcl-2 (Ser70), Bcl-2, Bcl-xL, and Mcl-1 as well as the increase of pro-apoptosis Bcl-2 family-protein including Bim, Bad, Bax, and Bak. Furthermore, JS-K caused a marked increase of intracellular NO levels while pre-treatment with Carboxy-PTIO (a NO scavenger) reduced the cytotoxicity effects and the apoptosis rate. Meanwhile, pre-treatment with Carboxy-PTIO attenuated the JS-K-induced up-regulation of PP2A, Cyt c, and cleaved-caspase-9/3 activation. The silencing PP2A-C by siRNA could abolish the activation of PP2A-C, down-regulation of anti-apoptotic Bcl-2 family-protein (p-Bcl-2, Bcl-2, Bcl-xL, and Mcl-1), increase of pro-apoptosis Bcl-2 family-protein (Bim, Bad, Bax, and Bak) and apoptotic-related protein (Cyt c, cleaved caspase-9/3) that were caused by JS-K in HepG2 cells. In addition, pre-treatment with OA (a PP2A inhibitor) also attenuated the above effects induced by JS-K. In summary, NO release from JS-K induces apoptosis through PP2A activation, which contributed to the regulation of Bcl-2 family proteins. © 2018 Wiley Periodicals, Inc.

  15. Association of genetic markers in the BCL-2 family of apoptosis-related genes with endometrial cancer risk in a Chinese population.

    Directory of Open Access Journals (Sweden)

    Tsogzolmaa Dorjgochoo

    Full Text Available In vitro studies have demonstrated the role of the BCL-2 family of genes in endometrial carcinogenesis. The role of genetic variants in BCL-2 genes and their interactions with non-genetic factors in the development of endometrial cancer has not been investigated in epidemiological studies.We examined the relationship between BCL-2 gene family variants and endometrial cancer risk among 1,028 patients and 1,922 age-matched community controls from Shanghai, China. We also investigated possible interactions between genetic variants and established risk factors (demographic, lifestyle and clinical. Individuals were genotyped for 86 tagging single nucleotide polymorphisms (SNPs in the BCL2, BAX, BAD and BAK1 genes.Significant associations with endometrial cancer risk were found for 9 SNPs in the BCL2 gene (P trend<0.05 for all. For SNPs rs17759659 and rs7243091 (minor allele for both: G, the associations were independent. The odds ratio was 1.27 (95% CI: 1.04-1.53 for women with AG genotype for the SNP rs17759659 and 1.82 (95% CI: 1.21-2.73 for women with the GG genotype for the SNP rs7243091. No interaction between these two SNPs and established non-genetic risk factors of endometrial cancer was noticed.Genetic polymorphisms in the BCL2 gene may be associated with the risk of endometrial cancer in Chinese women.

  16. Manganese activates the mitochondrial apoptotic pathway in rat astrocytes by modulating the expression of proteins of the Bcl-2 family.

    Science.gov (United States)

    Gonzalez, Laura E; Juknat, A Ana; Venosa, Andrea J; Verrengia, Noemi; Kotler, Mónica L

    2008-12-01

    Manganese induces the central nervous system injury leading to manganism, by mechanisms not completely understood. Chronic exposure to manganese generates oxidative stress and induces the mitochondrial permeability transition. In the present study, we characterized apoptotic cell death mechanisms associated with manganese toxicity in rat cortical astrocytes and demonstrated that (i) Mn treatment targets the mitochondria and induces mitochondrial membrane depolarization followed by cytochrome c release to the cytoplasm, (ii) Mn induces both effector caspases 3/7 and 6 as well as PARP-1 cleavage and (iii) Mn shifts the balance of cell death/survival of Bcl-2 family proteins to favor the apoptotic demise of astrocytes. Our model system using cortical rat astrocytes treated with Mn would emerge as a good tool for investigations aimed to elucidate the role of apoptosis in manganism.

  17. Arsenite induces apoptosis in human mesenchymal stem cells by altering Bcl-2 family proteins and by activating intrinsic pathway

    International Nuclear Information System (INIS)

    Yadav, Santosh; Shi Yongli; Wang Feng; Wang He

    2010-01-01

    Purpose: Environmental exposure to arsenic is an important public health issue. The effects of arsenic on different tissues and organs have been intensively studied. However, the effects of arsenic on bone marrow mesenchymal stem cells (MSCs) have not been reported. This study is designed to investigate the cell death process caused by arsenite and its related underlying mechanisms on MSCs. The rationale is that absorbed arsenic in the blood circulation can reach to the bone marrow and may affect the cell survival of MSCs. Methods: MSCs of passage 1 were purchased from Tulane University, grown till 70% confluency level and plated according to the experimental requirements followed by treatment with arsenite at various concentrations and time points. Arsenite (iAs III ) induced cytotoxic effects were confirmed by cell viability and cell cycle analysis. For the presence of canonic apoptosis markers; DNA damage, exposure of intramembrane phosphotidylserine, protein and m-RNA expression levels were analyzed. Results: iAs III induced growth inhibition, G2-M arrest and apoptotic cell death in MSCs, the apoptosis induced by iAs III in the cultured MSCs was, via altering Bcl-2 family proteins and by involving intrinsic pathway. Conclusion: iAs III can induce apoptosis in bone marrow-derived MSCs via Bcl-2 family proteins, regulating intrinsic apoptotic pathway. Due to the multipotency of MSC, acting as progenitor cells for a variety of connective tissues including bone, adipose, cartilage and muscle, these effects of arsenic may be important in assessing the health risk of the arsenic compounds and understanding the mechanisms of arsenic-induced harmful effects.

  18. Targeting MUC1-C suppresses BCL2A1 in triple-negative breast cancer.

    Science.gov (United States)

    Hiraki, Masayuki; Maeda, Takahiro; Mehrotra, Neha; Jin, Caining; Alam, Maroof; Bouillez, Audrey; Hata, Tsuyoshi; Tagde, Ashujit; Keating, Amy; Kharbanda, Surender; Singh, Harpal; Kufe, Donald

    2018-01-01

    B-cell lymphoma 2-related protein A1 (BCL2A1) is a member of the BCL-2 family of anti-apoptotic proteins that confers resistance to treatment with anti-cancer drugs; however, there are presently no agents that target BCL2A1. The MUC1-C oncoprotein is aberrantly expressed in triple-negative breast cancer (TNBC) cells, induces the epithelial-mesenchymal transition (EMT) and promotes anti-cancer drug resistance. The present study demonstrates that targeting MUC1-C genetically and pharmacologically in TNBC cells results in the downregulation of BCL2A1 expression. The results show that MUC1-C activates the BCL2A1 gene by an NF-κB p65-mediated mechanism, linking this pathway with the induction of EMT. The MCL-1 anti-apoptotic protein is also of importance for the survival of TNBC cells and is an attractive target for drug development. We found that inhibiting MCL-1 with the highly specific MS1 peptide results in the activation of the MUC1-C→NF-κB→BCL2A1 pathway. In addition, selection of TNBC cells for resistance to ABT-737, which inhibits BCL-2, BCL-xL and BCL-W but not MCL-1 or BCL2A1, is associated with the upregulation of MUC1-C and BCL2A1 expression. Targeting MUC1-C in ABT-737-resistant TNBC cells suppresses BCL2A1 and induces death, which is of potential therapeutic importance. These findings indicate that MUC1-C is a target for the treatment of TNBCs unresponsive to agents that inhibit anti-apoptotic members of the BCL-2 family.

  19. An Optically Pure Apogossypolone Derivative as Potent Pan-Active Inhibitor of Anti-Apoptotic Bcl-2 Family Proteins

    International Nuclear Information System (INIS)

    Wei, Jun; Stebbins, John L.; Kitada, Shinichi; Dash, Rupesh; Zhai, Dayong; Placzek, William J.; Wu, Bainan; Rega, Michele F.; Zhang, Ziming; Barile, Elisa; Yang, Li; Dahl, Russell; Fisher, Paul B.; Reed, John C.; Pellecchia, Maurizio

    2011-01-01

    Our focus in the past several years has been on the identification of novel and effective pan-Bcl-2 antagonists. We have recently reported a series of Apogossypolone (ApoG2) derivatives, resulting in the chiral compound (±) BI97D6. We report here the synthesis and evaluation on its optically pure (−) and (+) atropisomers. Compound (−) BI97D6 potently inhibits the binding of BH3 peptides to Bcl-X L , Bcl-2, Mcl-1, and Bfl-1 with IC 50 values of 76 ± 5, 31 ± 2, 25 ± 8, and 122 ± 28 nM, respectively. In a cellular assay, compound (−) BI97D6 effectively inhibits cell growth in the PC-3 human prostate cancer and H23 human lung cancer cell lines with EC 50 values of 0.22 ± 0.08 and 0.14 ± 0.02 μM, respectively. Similarly, compound (−) BI97D6 effectively induces apoptosis in the BP3 human lymphoma cell line in a dose-dependent manner. The compound also shows little cytotoxicity against bax −/− /bak −/− cells, suggesting that it kills cancers cells predominantly via a Bcl-2 pathway. Moreover, compound (−) BI97D6 displays in vivo efficacy in both a Bcl-2-transgenic mouse model and in a prostate cancer xenograft model in mice. Therefore, compound (−) BI97D6 represents a promising drug lead for the development of novel apoptosis-based therapies for cancer.

  20. Role of reactive oxygen species and Bcl-2 family proteins in TNF-α-induced apoptosis of lymphocytes.

    Science.gov (United States)

    Ryazanceva, N V; Novickiy, V V; Zhukova, O B; Biktasova, A K; Chechina, O E; Sazonova, E V; Belkina, M V; Chasovskih, N Yu; Khaitova, Z K

    2010-08-01

    We studied the in vitro apoptosis-inducing effect of recombinant TNF-α (rTNF-α) on blood lymphocytes from healthy donors. rTNF-α-induced apoptosis was accompanied by an increase in the number of cells with low mitochondrial transmembrane potential, increased intracellular content of reactive oxygen species, reduced content of Bcl-2, Bcl-xL, and Bax proteins, and elevated Bad content. The molecular mechanisms of these changes are discussed.

  1. Expanding the Cancer Arsenal with Targeted Therapies: Disarmament of the Antiapoptotic Bcl-2 Proteins by Small Molecules.

    Science.gov (United States)

    Yap, Jeremy L; Chen, Lijia; Lanning, Maryanna E; Fletcher, Steven

    2017-02-09

    A hallmark of cancer is the evasion of apoptosis, which is often associated with the upregulation of the antiapoptotic members of the Bcl-2 family of proteins. The prosurvival function of the antiapoptotic Bcl-2 proteins is manifested by capturing and neutralizing the proapoptotic Bcl-2 proteins via their BH3 death domains. Accordingly, strategies to antagonize the antiapoptotic Bcl-2 proteins have largely focused on the development of low-molecular-weight, synthetic BH3 mimetics ("magic bullets") to disrupt the protein-protein interactions between anti- and proapoptotic Bcl-2 proteins. In this way, apoptosis has been reactivated in malignant cells. Moreover, several such Bcl-2 family inhibitors are presently being evaluated for a range of cancers in clinical trials and show great promise as new additions to the cancer armamentarium. Indeed, the selective Bcl-2 inhibitor venetoclax (Venclexta) recently received FDA approval for the treatment of a specific subset of patients with chronic lymphocytic leukemia. This review focuses on the major developments in the field of Bcl-2 inhibitors over the past decade, with particular emphasis on binding modes and, thus, the origins of selectivity for specific Bcl-2 family members.

  2. Interaction of a putative BH3 domain of clusterin with anti-apoptotic Bcl-2 family proteins as revealed by NMR spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong-Hwa; Ha, Ji-Hyang [Medical Proteomics Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of); Kim, Yul [Department of Bio and Brain Engineering, KAIST, Daejeon 305-701 (Korea, Republic of); Bae, Kwang-Hee [Medical Proteomics Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of); Park, Jae-Yong [Department of Physiology, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 660-751 (Korea, Republic of); Choi, Wan Sung [Department of Anatomy and Neurobiology, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 660-751 (Korea, Republic of); Yoon, Ho Sup [Division of Structural and Computational Biology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637511 (Singapore); Park, Sung Goo; Park, Byoung Chul [Medical Proteomics Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of); Yi, Gwan-Su, E-mail: gsyi@kaist.ac.kr [Department of Bio and Brain Engineering, KAIST, Daejeon 305-701 (Korea, Republic of); Chi, Seung-Wook, E-mail: swchi@kribb.re.kr [Medical Proteomics Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of)

    2011-05-20

    Highlights: {yields} Identification of a conserved BH3 motif in C-terminal coiled coil region of nCLU. {yields} The nCLU BH3 domain binds to BH3 peptide-binding grooves in both Bcl-X{sub L} and Bcl-2. {yields} A conserved binding mechanism of nCLU BH3 and the other pro-apoptotic BH3 peptides with Bcl-X{sub L}. {yields} The absolutely conserved Leu323 and Asp328 of nCLU BH3 domain are critical for binding to Bcl-X{sub L.} {yields} Molecular understanding of the pro-apoptotic function of nCLU as a novel BH3-only protein. -- Abstract: Clusterin (CLU) is a multifunctional glycoprotein that is overexpressed in prostate and breast cancers. Although CLU is known to be involved in the regulation of apoptosis and cell survival, the precise molecular mechanism underlying the pro-apoptotic function of nuclear CLU (nCLU) remains unclear. In this study, we identified a conserved BH3 motif in C-terminal coiled coil (CC2) region of nCLU by sequence analysis and characterized the molecular interaction of the putative nCLU BH3 domain with anti-apoptotic Bcl-2 family proteins by nuclear magnetic resonance (NMR) spectroscopy. The chemical shift perturbation data demonstrated that the nCLU BH3 domain binds to pro-apoptotic BH3 peptide-binding grooves in both Bcl-X{sub L} and Bcl-2. A structural model of the Bcl-X{sub L}/nCLU BH3 peptide complex reveals that the binding mode is remarkably similar to those of other Bcl-X{sub L}/BH3 peptide complexes. In addition, mutational analysis confirmed that Leu323 and Asp328 of nCLU BH3 domain, absolutely conserved in the BH3 motifs of BH3-only protein family, are critical for binding to Bcl-X{sub L}. Taken altogether, our results suggest a molecular basis for the pro-apoptotic function of nCLU by elucidating the residue specific interactions of the BH3 motif in nCLU with anti-apoptotic Bcl-2 family proteins.

  3. The Effects of Lycopene and Insulin on Histological Changes and the Expression Level of Bcl-2 Family Genes in the Hippocampus of Streptozotocin-Induced Diabetic Rats.

    Science.gov (United States)

    Soleymaninejad, Masoume; Joursaraei, Seyed Gholamali; Feizi, Farideh; Jafari Anarkooli, Iraj

    2017-01-01

    The aim of this study was to evaluate the effects of antioxidants lycopene and insulin on histological changes and expression of Bcl-2 family genes in the hippocampus of streptozotocin-induced type 1 diabetic rats. Forty-eight Wistar rats were divided into six groups of control (C), control treated with lycopene (CL), diabetic (D), diabetic treated with insulin (DI), diabetic treated with lycopene (DL), and diabetic treated with insulin and lycopene (DIL). Diabetes was induced by an injection of streptozotocin (60 mg/kg, IP), lycopene (4 mg/kg/day) was given to the lycopene treated groups as gavages, and insulin (Sc, 1-2 U/kg/day) was injected to the groups treated with insulin. The number of hippocampus neurons undergoing cell death in group D had significant differences with groups C and DIL ( p lycopene alone or together reduced the expression of Bax , but increased Bcl-2 and Bcl-x L levels in DI, DL, and DIL rats, especially when compared to group D ( p lycopene contribute to the prevention of cell death by reducing the expression of proapoptotic genes and increasing the expression of antiapoptotic genes in the hippocampus.

  4. Original Article: Investigation of Bcl-2 and PCNA in Hepatocellular Carcinoma: Relation to Chronic HCV

    International Nuclear Information System (INIS)

    ALENZI, F.Q.Ph.; ABBAS, M.Y.Ph.; HAMAD, A.M.; EL-SAEED, O.M.; EL-NASHAR, E.M.; AL-GHAMDI, S.S.; WYSE, R.K.H.; LOTFY, M.

    2010-01-01

    Bcl-2 family members can be functionally divided into anti-apoptotic and pro-apoptotic groups. The balance between these two groups may determine the fate of tumor cells. In hepatocellular carcinoma (HCC), this balance is often tilted towards the anti-apoptotic members in tumor cells, leading to resistance to cell death and rapid proliferation. Material and Methods: In the current study, we in-vestigated Bcl-2 and proliferating cell nuclear antigen (PCNA) immunohistochemically, using specific mono-clonal antibodies in liver tissues obtained from two patient groups. The first group included fifty patients infected with hepatitis C virus (HCV) without hepatocellular carcinoma, the other group included twenty five HCV-infected patients but with confirmed HCC. Serum Bcl-2 was assayed using enzyme immunoassay. Results: Results showed serum Bcl-2 was elevated in 82% versus 100% in HCC-free and HCC patients, respectively. Moreover, cytoplasmic staining of Bcl-2 was found in only 16% of chronic HCV patients without HCC, versus 8% in HCC patients. On the other hand, nuclear staining of PCNA was detected in 100% of HCC patients, but in none of the HCV patients without HCC. Conclusion: The results collectively suggest that in HCV-infected patients with and without HCC, apoptosis is dysregulated and proliferation activity perturbed. There may be prognostic and/or diagnostic potential in estimating Bcl-2 and PCNA proteins in these patient groups

  5. Expression of Bcl-2 in canine osteosarcoma

    Science.gov (United States)

    Piro, F.; Leonardi, L.

    2015-01-01

    Osteosarcoma (OS) is the most common primary malignancy of bone. It is responsible for 80-85% of the primary bone tumors affecting dogs and it is characterized by aggressive and invasive behavior, with a high metastatic potential. Several studies on cancer and related tumorigenesis, show an involvement of the mechanisms of programmed cell death and cell survival. Many signals seem to be involved in the related mechanism of autophagy and in particular, our interest is focused on the expression of a family of Bcl-2 that seems to be involved either in the control of biomolecular mechanisms like autophagy and apoptosis. In this study we investigated the expression of Bcl-2 in different cases of spontaneous canine osteosarcoma and the related preliminary results are described. We found Bcl-2 activity was increased in OS tissue compared to normal bone tissue. These results suggested that Bcl-2 activity may play an important role in the formation of OS and as a diagnostic for neoplastic activity. However, further research is needed to confirm the role of Bcl-2 activity in OS in canines. PMID:26623359

  6. Expression of Bcl-2 in canine osteosarcoma

    Directory of Open Access Journals (Sweden)

    F. Piro

    2015-03-01

    Full Text Available Osteosarcoma (OS is the most common primary malignancy of bone. It is responsible for 80-85% of the primary bone tumors affecting dogs and it is characterized by aggressive and invasive behavior, with a high metastatic potential. Several studies on cancer and related tumorigenesis, show an involvement of the mechanisms of programmed cell death and cell survival. Many signals seem to be involved in the related mechanism of autophagy and in particular, our interest is focused on the expression of a family of Bcl-2 that seems to be involved either in the control of biomolecular mechanisms like autophagy and apoptosis. In this study we investigated the expression of Bcl-2 in different cases of spontaneous canine osteosarcoma and the related preliminary results are described. We found Bcl-2 activity was increased in OS tissue compared to normal bone tissue. These results suggested that Bcl-2 activity may play an important role in the formation of OS and as a diagnostic for neoplastic activity. However, further research is needed to confirm the role of Bcl-2 activity in OS in canines.

  7. Hexavalent chromium-induced apoptosis of granulosa cells involves selective sub-cellular translocation of Bcl-2 members, ERK1/2 and p53

    International Nuclear Information System (INIS)

    Banu, Sakhila K.; Stanley, Jone A.; Lee, JeHoon; Stephen, Sam D.; Arosh, Joe A.; Hoyer, Patricia B.; Burghardt, Robert C.

    2011-01-01

    Hexavalent chromium (CrVI) has been widely used in industries throughout the world. Increased usage of CrVI and atmospheric emission of CrVI from catalytic converters of automobiles, and its improper disposal causes various health hazards including female infertility. Recently we have reported that lactational exposure to CrVI induced a delay/arrest in follicular development at the secondary follicular stage. In order to investigate the underlying mechanism, primary cultures of rat granulosa cells were treated with 10 μM potassium dichromate (CrVI) for 12 and 24 h, with or without vitamin C pre-treatment for 24 h. The effects of CrVI on intrinsic apoptotic pathway(s) were investigated. Our data indicated that CrVI: (i) induced DNA fragmentation and increased apoptosis, (ii) increased cytochrome c release from the mitochondria to cytosol, (iii) downregulated anti-apoptotic Bcl-2, Bcl-XL, HSP70 and HSP90; upregulated pro-apoptotic BAX and BAD, (iv) altered translocation of Bcl-2, Bcl-XL, BAX, BAD, HSP70 and HSP90 to the mitochondria, (v) upregulated p-ERK and p-JNK, and selectively translocated p-ERK to the mitochondria and nucleus, (vi) activated caspase-3 and PARP, and (vii) increased phosphorylation of p53 at ser-6, ser-9, ser-15, ser-20, ser-37, ser-46 and ser-392, increased p53 transcriptional activation, and downregulated MDM-2. Vitamin C pre-treatment mitigated CrVI effects on apoptosis and related pathways. Our study, for the first time provides a clear insight into the effect of CrVI on multiple pathways that lead to apoptosis of granulosa cells which could be mitigated by vitamin C.

  8. [Apoptosis-modulating effects of heat shock proteins: the influence of Hsp27 chaperone on TBA Bcl-2 family proteins in Jurkat cell line].

    Science.gov (United States)

    Riazantseva, N V; Kaĭgorodova, E V; Maroshkina, A N; Belkina, M V; Novitskiĭ, V V

    2012-01-01

    The in vitro phosphorylated and non-phosphorylated Hsp27 forms concentrations and Bcl-2 proteins affected by Hsp27 inhibition were studied in Jurkat-line tumor cells and healthy donor mononuclear lymphocytes by Western blotting technique. The Hsp27 inhibition causes the increase of intracellular Bax protein concentration and the decrease of Bcl-2 level leading to an increase of apoptotic changes in Jurkat line cells.

  9. Expression of Bcl-2 in canine osteosarcoma | Piro | Open Veterinary ...

    African Journals Online (AJOL)

    Many signals seem to be involved in the related mechanism of autophagy and in particular, our interest is focused on the expression of a family of Bcl-2 that seems to be involved either in the control of biomolecular mechanisms like autophagy and apoptosis. In this study we investigated the expression of Bcl-2 in different ...

  10. Alpha-helical destabilization of the Bcl-2-BH4-domain peptide abolishes its ability to inhibit the IP3 receptor.

    Directory of Open Access Journals (Sweden)

    Giovanni Monaco

    Full Text Available The anti-apoptotic Bcl-2 protein is the founding member and namesake of the Bcl-2-protein family. It has recently been demonstrated that Bcl-2, apart from its anti-apoptotic role at mitochondrial membranes, can also directly interact with the inositol 1,4,5-trisphosphate receptor (IP3R, the primary Ca(2+-release channel in the endoplasmic reticulum (ER. Bcl-2 can thereby reduce pro-apoptotic IP3R-mediated Ca(2+ release from the ER. Moreover, the Bcl-2 homology domain 4 (Bcl-2-BH4 has been identified as essential and sufficient for this IP3R-mediated anti-apoptotic activity. In the present study, we investigated whether the reported inhibitory effect of a Bcl-2-BH4 peptide on the IP 3R1 was related to the distinctive α-helical conformation of the BH4 domain peptide. We therefore designed a peptide with two glycine "hinges" replacing residues I14 and V15, of the wild-type Bcl-2-BH4 domain (Bcl-2-BH4-IV/GG. By comparing the structural and functional properties of the Bcl-2-BH4-IV/GG peptide with its native counterpart, we found that the variant contained reduced α-helicity, neither bound nor inhibited the IP 3R1 channel, and in turn lost its anti-apoptotic effect. Similar results were obtained with other substitutions in Bcl-2-BH4 that destabilized the α-helix with concomitant loss of IP3R inhibition. These results provide new insights for the further development of Bcl-2-BH4-derived peptides as specific inhibitors of the IP3R with significant pharmacological implications.

  11. Prometaphase arrest-dependent phosphorylation of Bcl-2 family proteins and activation of mitochondrial apoptotic pathway are associated with 17α-estradiol-induced apoptosis in human Jurkat T cells.

    Science.gov (United States)

    Han, Cho Rong; Jun, Do Youn; Kim, Yoon Hee; Lee, Ji Young; Kim, Young Ho

    2013-10-01

    In Jurkat T cell clone (JT/Neo), G2/M arrest, apoptotic sub-G1 peak, mitochondrial membrane potential (Δψm) loss, and TUNEL-positive DNA fragmentation were induced following exposure to 17α-estradiol (17α-E2), whereas none of these events (except for G2/M arrest) were induced in Jurkat cells overexpressing Bcl-2 (JT/Bcl-2). Under these conditions, phosphorylation at Thr161 and dephosphorylation at Tyr15 of Cdk1, upregulation of cyclin B1 level, histone H1 phosphorylation, Cdc25C phosphorylation at Thr-48, Bcl-2 phosphorylation at Thr-56 and Ser-70, Mcl-1 phosphorylation, and Bim phosphorylation were detected in the presence of Bcl-2 overexpression. However, the 17α-E2-induced upregulation of Bak levels, activation of Bak, activation of caspase-3, and PARP degradation were abrogated by Bcl-2 overexpression. In the presence of the G1/S blocking agent hydroxyurea, 17α-E2 failed to induce G2/M arrest and all apoptotic events including Cdk1 activation and phosphorylation of Bcl-2, Mcl-1 and Bim. The 17α-E2-induced phosphorylation of Bcl-2 family proteins and mitochondrial apoptotic events were suppressed by a Cdk1 inhibitor but not by aurora A and aurora B kinase inhibitors. Immunofluorescence microscopic analysis showed that an aberrant bipolar microtubule array, incomplete chromosome congression at the metaphase plate, and prometaphase arrest, which was reversible, were the underlying factors for 17α-E2-induced mitotic arrest. The in vitro microtubule polymerization assay showed that 17α-E2 could directly inhibit microtubule formation. These results show that the apoptogenic activity of 17α-E2 was due to the impaired mitotic spindle assembly causing prometaphase arrest and prolonged Cdk1 activation, the phosphorylation of Bcl-2, Mcl-1 and Bim, and the activation of Bak and mitochondria-dependent caspase cascade. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Family members' experiences of autopsy

    NARCIS (Netherlands)

    Oppewal, F; Meyboom-de Jong, B

    Background. The experiences of family members will teach us how to handle an autopsy, the ultimate quality assessment tool. Objective. The aim of this study was to determine surviving family members' experience of autopsy. Method. Seven GPs were asked to approach surviving family members of

  13. Apoptosis and the BCL-2 gene family - patterns of expression and prognostic value in STAGE I and II follicular center lymphoma

    International Nuclear Information System (INIS)

    Logsdon, Mark D.; Meyn, Raymond E.; Besa, Pelayo C.; Pugh, William C.; Stephens, L. Clifton; Peters, Lester J.; Milas, Luka; Cox, James D.; Cabanillas, Fernando; Brisbay, Shawn; Andersen, Margret; McDonnell, Timothy J.

    1999-01-01

    Purpose: The prognostic significance of spontaneous levels of apoptosis and Bcl-2, Bax, and Bcl-x protein expression in follicular center lymphoma (FCL) is unknown. The objectives of this retrospective study were (1) to investigate the relationship between pretreatment apoptosis levels and long-term treatment outcome in patients with Stage I and II FCL; (2) to define the incidence and patterns of Bax and Bcl-x protein expression in human FC; and (3) to determine the relationship of Bcl-2, Bax, and Bcl-x expression with spontaneous apoptosis levels and clinical outcome in localized FCL. Methods and Materials: Between 1974 and 1988, 144 patients with Stage I or II FCL were treated. Hematoxylin and eosin (H and E) stained tissue sections of pretreatment specimens were retrieved for 96 patients. Treatment consisted of regional radiation therapy (XRT) for 25 patients, combined modality therapy (CMT) consisting of combination chemotherapy and XRT for 57 patients, and other treatments for 14 patients. Median follow-up for living patients was nearly 12 years. The apoptotic index (AI) was calculated by dividing the number of apoptotic cells by the total number of cells counted and multiplying by 100. Expression of Bcl-2, Bax, and Bcl-x proteins was assessed using immunohistochemistry. Results: The mean and median AI values for the entire group were 0.53 and 0.4, respectively (range: 0-5.2). The AI strongly correlated with cytologic grade, with mean AI values of 0.25 for grade 1, 0.56 for grade 2, and 0.84 for grade 3 (p < 0.0005; Kendall correlation). A positive correlation was present between grouped AI and grouped mitotic index (MI) (p = 0.014). For patients treated with CMT, an AI < 0.4 correlated with improved freedom from relapse (FFR) (p = 0.0145) and overall survival (OS) (p = 0.0081). An AI < 0.4 did not correlate with clinical outcome for the entire cohort or for patients receiving XRT only. Staining of tumor follicles for the Bcl-2 protein was positive, variable

  14. Communication Among Melanoma Family Members

    Science.gov (United States)

    Bowen, Deborah J; Albrecht, Terrance; Hay, Jennifer; Eggly, Susan; Harris-Wei, Julie; Meischke, Hendrika; Burke, Wylie

    2017-01-01

    Interventions to improve communication among family members may facilitate information flow about familial risk and preventive health behaviors. This is a secondary analysis of the effects of an interactive website intervention aimed at increasing communication frequency and agreement about health risk among melanoma families. Participants were family units, consisting of one family member with melanoma identified from a previous research study (the case) and an additional first degree relative and a parent of a child 0–17. Family triads were randomized to receive access to the website intervention or to serve as control families. Family communication frequency and agreement about melanoma prevention behaviors and beliefs were measured at baseline and again at one year post randomization. Intervention participants of all three types significantly increased the frequency of communication to their first degree relatives (Parents, siblings, children; range =14–18 percentage points; all pcommunication about cancer risk. PMID:28248624

  15. Analyse bioinformatique des protéines BCL-2 et développement de la base de connaissance dédiée, BCL2DB

    OpenAIRE

    Rech de Laval , Valentine

    2013-01-01

    BCL-2 proteins play an essential role in the decision of life or death of animal cells. They control the induction of apoptosis (programmed cell death) in the mitochondrial pathway via regulators having opposite functions: anti- or pro-apoptotic. Proteins containing one or more Bcl-2 homology domains (BHl-4) are systematically classified in this family. Through bioinformatics and phylogenetic analysis, we revisited the different criteria for protein inclusion in the BCL-2 group and proposed a...

  16. Cellular responses to a prolonged delay in mitosis are determined by a DNA damage response controlled by Bcl-2 family proteins.

    Science.gov (United States)

    Colin, Didier J; Hain, Karolina O; Allan, Lindsey A; Clarke, Paul R

    2015-03-01

    Anti-cancer drugs that disrupt mitosis inhibit cell proliferation and induce apoptosis, although the mechanisms of these responses are poorly understood. Here, we characterize a mitotic stress response that determines cell fate in response to microtubule poisons. We show that mitotic arrest induced by these drugs produces a temporally controlled DNA damage response (DDR) characterized by the caspase-dependent formation of γH2AX foci in non-apoptotic cells. Following exit from a delayed mitosis, this initial response results in activation of DDR protein kinases, phosphorylation of the tumour suppressor p53 and a delay in subsequent cell cycle progression. We show that this response is controlled by Mcl-1, a regulator of caspase activation that becomes degraded during mitotic arrest. Chemical inhibition of Mcl-1 and the related proteins Bcl-2 and Bcl-xL by a BH3 mimetic enhances the mitotic DDR, promotes p53 activation and inhibits subsequent cell cycle progression. We also show that inhibitors of DDR protein kinases as well as BH3 mimetics promote apoptosis synergistically with taxol (paclitaxel) in a variety of cancer cell lines. Our work demonstrates the role of mitotic DNA damage responses in determining cell fate in response to microtubule poisons and BH3 mimetics, providing a rationale for anti-cancer combination chemotherapies.

  17. Bcl-2 prevents loss of mitochondria in CCCP-induced apoptosis

    International Nuclear Information System (INIS)

    Graaf, Aniek O. de; Heuvel, Lambert P. van den; Dijkman, Henry B.P.M.; Abreu, Ronney A. de; Birkenkamp, Kim U.; Witte, Theo de; Reijden, Bert A. van der; Smeitink, Jan A.M.; Jansen, Joop H.

    2004-01-01

    Bcl-2 family proteins regulate apoptosis at the level of mitochondria. To examine the mechanism of Bcl-2 function, we investigated the effects of the protonophore carbonyl cyanide m-chlorophenyl hydrazone (CCCP) on two hematopoietic cell lines and Bcl-2 overexpressing transfectants. CCCP directly interferes with mitochondrial function and induces apoptosis. We show that Bcl-2 inhibits apoptosis and that the antiapoptotic effect of Bcl-2 takes place upstream of caspase activation and nuclear changes associated with apoptosis, since these were markedly inhibited in cells overexpressing Bcl-2. Bcl-2 does not prevent the decrease in mitochondrial membrane potential nor the alterations in cellular ATP content induced by CCCP in FL5.12 and Jurkat cells. A higher number of mitochondria was observed in untreated Bcl-2 transfected cells compared to parental cells, as shown by electron microscopy. Exposure to CCCP induced a dramatic decrease in the number of mitochondria and severely disrupted mitochondrial ultrastructure, with apparent swelling and loss of cristae in parental cells. Bcl-2 clearly diminished the disruption of mitochondrial structure and preserved a higher number of mitochondria. These data suggest that CCCP induces apoptosis by structural disruption of mitochondria and that Bcl-2 prevents apoptosis and mitochondrial degeneration by preserving mitochondrial integrity

  18. Bcl-2 prevents loss of mitochondria in CCCP-induced apoptosis.

    Science.gov (United States)

    de Graaf, Aniek O; van den Heuvel, Lambert P; Dijkman, Henry B P M; de Abreu, Ronney A; Birkenkamp, Kim U; de Witte, Theo; van der Reijden, Bert A; Smeitink, Jan A M; Jansen, Joop H

    2004-10-01

    Bcl-2 family proteins regulate apoptosis at the level of mitochondria. To examine the mechanism of Bcl-2 function, we investigated the effects of the protonophore carbonyl cyanide m-chlorophenyl hydrazone (CCCP) on two hematopoietic cell lines and Bcl-2 overexpressing transfectants. CCCP directly interferes with mitochondrial function and induces apoptosis. We show that Bcl-2 inhibits apoptosis and that the antiapoptotic effect of Bcl-2 takes place upstream of caspase activation and nuclear changes associated with apoptosis, since these were markedly inhibited in cells overexpressing Bcl-2. Bcl-2 does not prevent the decrease in mitochondrial membrane potential nor the alterations in cellular ATP content induced by CCCP in FL5.12 and Jurkat cells. A higher number of mitochondria was observed in untreated Bcl-2 transfected cells compared to parental cells, as shown by electron microscopy. Exposure to CCCP induced a dramatic decrease in the number of mitochondria and severely disrupted mitochondrial ultrastructure, with apparent swelling and loss of cristae in parental cells. Bcl-2 clearly diminished the disruption of mitochondrial structure and preserved a higher number of mitochondria. These data suggest that CCCP induces apoptosis by structural disruption of mitochondria and that Bcl-2 prevents apoptosis and mitochondrial degeneration by preserving mitochondrial integrity.

  19. Identification and characterization of the Bcl-2- associated ...

    African Journals Online (AJOL)

    Identification and characterization of the Bcl-2- associated athanogene (BAG) protein family in rice. ... Data obtained from real-time PCR of OsBAG genes under heat stress showed that maximum induction in the expression of all the genes occurred after one hour exposure to heat stress, while reduction in the expression ...

  20. A component of green tea (-)-epigallocatechin-3-gallate, promotes apoptosis in T24 human bladder cancer cells via modulation of the PI3K/Akt pathway and Bcl-2 family proteins

    International Nuclear Information System (INIS)

    Qin Jie; Xie Liping; Zheng Xiangyi; Wang Yunbin; Bai Yu; Shen Huafeng; Li Longcheng; Dahiya, Rajvir

    2007-01-01

    Bladder cancer is the fourth most common cancer in men and ninth most common in women. It has a protracted course of progression and is thus an ideal candidate for chemoprevention strategies and trials. This study was conducted to evaluate the chemopreventive/antiproliferative potential of (-)-epigallocatechin gallate (EGCG, the major phytochemical in green tea) against bladder cancer and its mechanism of action. Using the T24 human bladder cancer cell line, we found that EGCG treatment caused dose- and time-dependent inhibition of cellular proliferation and cell viability, and induced apoptosis. Mechanistically, EGCG inhibits phosphatidylinositol 3'-kinase/Akt activation that, in turn, results in modulation of Bcl-2 family proteins, leading to enhanced apoptosis of T24 cells. These findings suggest that EGCG may be an important chemoprevention agent for the management of bladder cancer

  1. Bcl-2 inhibitors potentiate the cytotoxic effects of radiation in Bcl-2 overexpressing radioresistant tumor cells

    International Nuclear Information System (INIS)

    Hara, Takamitsu; Omura-Minamisawa, Motoko; Chao Cheng; Nakagami, Yoshihiro; Ito, Megumi; Inoue, Tomio

    2005-01-01

    Purpose: Bcl-2, an inhibitor of apoptosis frequently shows elevated expression in human tumors, thus resulting in resistance to radiation therapy. Therefore, inhibiting Bcl-2 function may enhance the radiosensitivity of tumor cells. Tetrocarcin A (TC-A) and bcl-2 antisense oligonucleotides exhibit antitumor activity by inhibiting Bcl-2 function and transcription, respectively. We investigated whether these antitumor agents would enhance the cytotoxic effects of radiation in tumor cells overexpressing Bcl-2. Methods and materials: We used HeLa/bcl-2 cells, a stable Bcl-2-expressing cell line derived from wild-type HeLa (HeLa/wt) cells. Cells were incubated with TC-A and bcl-2 antisense oligonucleotides for 24 h after irradiation, and cell viability was then determined. Apoptotic cells were quantified by flow cytometric assay. Results: The HeLa/bcl-2 cells were more resistant to radiation than HeLa/wt cells. At concentrations that are not inherently cytotoxic, both TC-A and bcl-2 antisense oligonucleotides increased the cytotoxic effects of radiation in HeLa/bcl-2 cells, but not in HeLa/wt cells. However, in HeLa/bcl-2 cells, additional treatment with TC-A in combination with radiation did not significantly increase apoptosis. Conclusions: The present results suggest that TC-A and bcl-2 antisense oligonucleotides reduce radioresistance of tumor cells overexpressing Bcl-2. Therefore, a combination of radiotherapy and Bcl-2 inhibitors may prove to be a useful therapeutic approach for treating tumors that overexpress Bcl-2

  2. Mito-priming as a method to engineer Bcl-2 addiction.

    Science.gov (United States)

    Lopez, Jonathan; Bessou, Margaux; Riley, Joel S; Giampazolias, Evangelos; Todt, Franziska; Rochegüe, Tony; Oberst, Andrew; Green, Douglas R; Edlich, Frank; Ichim, Gabriel; Tait, Stephen W G

    2016-02-02

    Most apoptotic stimuli require mitochondrial outer membrane permeabilization (MOMP) in order to execute cell death. As such, MOMP is subject to tight control by Bcl-2 family proteins. We have developed a powerful new technique to investigate Bcl-2-mediated regulation of MOMP. This method, called mito-priming, uses co-expression of pro- and anti-apoptotic Bcl-2 proteins to engineer Bcl-2 addiction. On addition of Bcl-2 targeting BH3 mimetics, mito-primed cells undergo apoptosis in a rapid and synchronous manner. Using this method we have comprehensively surveyed the efficacy of BH3 mimetic compounds, identifying potent and specific MCL-1 inhibitors. Furthermore, by combining different pro- and anti-apoptotic Bcl-2 pairings together with CRISPR/Cas9-based genome editing, we find that tBID and PUMA can preferentially kill in a BAK-dependent manner. In summary, mito-priming represents a facile and robust means to trigger mitochondrial apoptosis.

  3. Knock-down of NDRG2 sensitizes cervical cancer Hela cells to cisplatin through suppressing Bcl-2 expression

    International Nuclear Information System (INIS)

    Liu, Junye; Guo, Guozhen; Yang, Le; Zhang, Jian; Zhang, Jing; Chen, Yongbin; Li, Kangchu; Li, Yurong; Li, Yan; Yao, Libo

    2012-01-01

    NDRG2, a member of N-Myc downstream regulated gene family, plays some roles in cellular stress, cell differentiation and tumor suppression. We have found that NDRG2 expression in cervical cancer Hela cells increases significantly upon stimulation with cisplatin, the most popular chemotherapeutic agent currently used for the treatment of advanced cervical cancer. This interesting phenomenon drove us to evaluate the role of NDRG2 in chemosensitivity of Hela cells. In the present study, RNA interference was employed to down-regulate NDRG2 expression in Hela cells. RT-PCR and Western blot were used to detect expression of NDRG2, Bcl-2 and Bax in cancer cells. Real-time PCR was applied to detect miR-15b and miR-16 expression levels. Drug sensitivity was determined with MTT assay. Cell cloning efficiency was evaluated by Colony-forming assay. Apoptotic cells were detected with annexin V staining and flow cytometry. In vitro drug sensitivity assay revealed that suppression of NDRG2 could sensitize Hela cells to cisplatin. Down-regulation of NDRG2 didn’t influence the colony-forming ability but promoted cisplatin-induced apoptosis of Hela cells. Inhibition of NDRG2 in Hela cells was accompanied by decreased Bcl-2 protein level. However, Bcl-2 mRNA level was not changed in Hela cells with down-regulation of NDRG2. Further study indicated that miR-15b and miR-16, two microRNAs targetting Bcl-2, were significantly up-regulated in NDRG2-suppressed Hela cells. These data suggested that down-regulation of NDRG2 could enhance sensitivity of Hela cells to cisplatin through inhibiting Bcl-2 protein expression, which might be mediated by up-regulating miR-15b and miR-16

  4. Active fragments from pro- and antiapoptotic BCL-2 proteins have distinct membrane behavior reflecting their functional divergence.

    Directory of Open Access Journals (Sweden)

    Yannis Guillemin

    Full Text Available BACKGROUND: The BCL-2 family of proteins includes pro- and antiapoptotic members acting by controlling the permeabilization of mitochondria. Although the association of these proteins with the outer mitochondrial membrane is crucial for their function, little is known about the characteristics of this interaction. METHODOLOGY/PRINCIPAL FINDINGS: Here, we followed a reductionist approach to clarify to what extent membrane-active regions of homologous BCL-2 family proteins contribute to their functional divergence. Using isolated mitochondria as well as model lipid Langmuir monolayers coupled with Brewster Angle Microscopy, we explored systematically and comparatively the membrane activity and membrane-peptide interactions of fragments derived from the central helical hairpin of BAX, BCL-xL and BID. The results show a connection between the differing abilities of the assayed peptide fragments to contact, insert, destabilize and porate membranes and the activity of their cognate proteins in programmed cell death. CONCLUSION/SIGNIFICANCE: BCL-2 family-derived pore-forming helices thus represent structurally analogous, but functionally dissimilar membrane domains.

  5. BCL2 genotypes and prostate cancer survival

    Energy Technology Data Exchange (ETDEWEB)

    Renner, Wilfried [Medical University of Graz, Clinical Institute of Medical and Chemical Laboratory Diagnostics, Graz (Austria); Langsenlehner, Uwe [GKK Outpatient Department, Division of Internal Medicine, Graz (Austria); Krenn-Pilko, Sabine; Langsenlehner, Tanja [Medical University of Graz, Department of Therapeutic Radiology and Oncology, Graz (Austria); Eder, Petra [University Hospital Wuerzburg, Department of Internal Medicine I, Wuerzburg (Germany)

    2017-06-15

    The antiapoptotic B-cell lymphoma 2 (BCL2) gene is a key player in cancer development and progression. A functional single-nucleotide polymorphism (c.-938C>A, rs2279115) in the inhibitory P2 BCL2 gene promoter has been associated with clinical outcomes in various types of cancer. Aim of the present study was to analyze the role of BCL2-938C>A genotypes in prostate cancer mortality. The association between BCL2-938C>A (rs2279115) genotypes and prostate cancer outcome was studied within the prospective PROCAGENE study comprising 702 prostate cancer patients. During a median follow-up time of 92 months, 120 (17.1%) patients died. A univariate Cox regression model showed a significant association of the CC genotype with reduced cancer-specific survival (CSS; hazard ratio, HR, 2.13, 95% confidence interval, CI, 1.10-4.12; p = 0.024) and overall survival (OS; HR 2.34, 95% CI 1.58-3.47; p < 0.001). In a multivariate Cox regression model including age at diagnosis, risk group, and androgen deprivation therapy, the CC genotype remained a significant predictor of poor CSS (HR 2.05, 95% CI 1.05-3.99; p = 0.034) and OS (HR 2.25, 95% CI 1.51-3.36; p < 0.001). This study provides evidence that the homozygous BCL2-938 CC genotype is associated with OS and C in prostate cancer patients. (orig.) [German] Das antiapoptotische Gen B cell lymphoma 2 (BCL2) spielt eine Schluesselrolle in der Entstehung und Progression von Krebserkrankungen. Ein funktioneller Einzelnukleotid-Polymorphismus (c.-938C>A, rs2279115) im inhibitorischen P2-BCL2-Promotor wurde mit dem klinischen Outcome verschiedener Krebserkrankungen verknuepft. Ziel der vorliegenden Studie war die Untersuchung der Rolle von BCL2-938C>A-Genotypen fuer die Mortalitaet bei Patienten mit Prostatakarzinom. Der Zusammenhang zwischen BCL2-938C>A-Genotypen (rs2279115) und dem Outcome bei Prostatakrebs wurde in der prospektiven PROCAGENE-Studie, die 702 Patienten mit Prostatakarzinom umfasste, untersucht. Waehrend der medianen

  6. Cycloheximide and actinomycin D delay death and affect bcl-2, bax, and Ice gene expression in astrocytes under in vitro ischemia.

    Science.gov (United States)

    Yu, Albert Cheung Hoi; Yung, Hon Wa; Hui, Michael Hung Kit; Lau, Lok Ting; Chen, Xiao Qian; Collins, Richard A

    2003-10-15

    An in vitro ischemia model was established and the effect of the metabolic inhibitors cycloheximide (CHX) and actinomycin D (ActD) on apoptosis in astrocytes under ischemia studied. CHX decreased by 75% the number of cells dying after 6 hr of ischemia compared with control cultures. TdT-mediated dUTP nick end labelling (TUNEL) staining of comparable cultures was reduced by 40%. ActD decreased cell death by 60% compared with controls. The number of TUNEL-positive cells was reduced by 38%. The nuclear shrinkage in TUNEL-positive astrocytes in control cultures did not occur in ActD-treated astrocytes, indicating that nuclear shrinkage and DNA fragmentation during apoptosis are two unrelated processes. Expression of bcl-2 (alpha and beta), bax, and Ice in astrocytes under similar ischemic conditions, as measured by quantitative reverse transcription-polymerase chain reaction, indicated that ischemia down-regulated bcl-2 (alpha and beta) and bax. Ice was initially down-regulated from 0 to 4 hr, before returning to control levels after 8 hr of ischemia. ActD decreased the expression of these genes. CHX reduced the expression of bcl-2 (alpha and beta) but increased bax and Ice expression. It is hypothesized that the balance of proapoptotic (Bad, Bax) and antiapoptotic (Bcl-2, Bcl-Xl) proteins determines apoptosis. The data suggest that the ratio of Bcl-2/Bad in astrocytes following ActD and CHX treatment does not decrease as much in untreated cells during ischemia. Our data indicate that it is the ratio of Bcl-2 family members that plays a critical role in determining ischemia-induced apoptosis. It is also important to note that ischemia-induced apoptosis involves the regulation of RNA and protein synthesis. Copyright 2003 Wiley-Liss, Inc.

  7. Immunogenicity of Bcl-2 in patients with cancer

    DEFF Research Database (Denmark)

    Andersen, Mads Hald; Svane, Inge Marie; Kvistborg, Pia

    2005-01-01

    patients suffering from unrelated tumor types (ie, pancreatic cancer, breast cancer, acute myeloid leukemia [AML], and chronic lymphocytic leukemia [CLL]). Additionally, we show that these Bcl-2-reactive T cells are indeed peptide-specific, cytotoxic effector cells. Thus, Bcl-2 may serve as an important......B-cell lymphoma 2 (Bcl-2) is a pivotal regulator of apoptotic cell death and it is overexpressed in many cancers. Consequently, the Bcl-2 protein is an attractive target for drug design, and Bcl-2-specific antisense oligonucleotides or small-molecule Bcl-2 inhibitors have shown broad anticancer......-2 in cancer and the fact that immune escape by down-regulation or loss of expression of this protein would impair sustained tumor growth makes Bcl-2 a very attractive target for anticancer immunotherapy. Herein, we describe spontaneous T-cell reactivity against Bcl-2 in peripheral blood from...

  8. No dramatic age-related loss of hair cells and spiral ganglion neurons in Bcl-2 over-expression mice or Bax null mice

    Directory of Open Access Journals (Sweden)

    Ohlemiller Kevin K

    2010-07-01

    Full Text Available Abstract Age-related decline of neuronal function is associated with age-related structural changes. In the central nervous system, age-related decline of cognitive performance is thought to be caused by synaptic loss instead of neuronal loss. However, in the cochlea, age-related loss of hair cells and spiral ganglion neurons (SGNs is consistently observed in a variety of species, including humans. Since age-related loss of these cells is a major contributing factor to presbycusis, it is important to study possible molecular mechanisms underlying this age-related cell death. Previous studies suggested that apoptotic pathways were involved in age-related loss of hair cells and SGNs. In the present study, we examined the role of Bcl-2 gene in age-related hearing loss. In one transgenic mouse line over-expressing human Bcl-2, there were no significant differences between transgenic mice and wild type littermate controls in their hearing thresholds during aging. Histological analysis of the hair cells and SGNs showed no significant conservation of these cells in transgenic animals compared to the wild type controls during aging. These data suggest that Bcl-2 overexpression has no significant effect on age-related loss of hair cells and SGNs. We also found no delay of age-related hearing loss in mice lacking Bax gene. These findings suggest that age-related hearing loss is not through an apoptotic pathway involving key members of Bcl-2 family.

  9. BCL2-BH4 antagonist BDA-366 suppresses human myeloma growth.

    Science.gov (United States)

    Deng, Jiusheng; Park, Dongkyoo; Wang, Mengchang; Nooka, Ajay; Deng, Qiaoya; Matulis, Shannon; Kaufman, Jonathan; Lonial, Sagar; Boise, Lawrence H; Galipeau, Jacques; Deng, Xingming

    2016-05-10

    Multiple myeloma (MM) is a heterogeneous plasma cell malignancy and remains incurable. B-cell lymphoma-2 (BCL2) protein correlates with the survival and the drug resistance of myeloma cells. BH3 mimetics have been developed to disrupt the binding between BCL2 and its pro-apoptotic BCL2 family partners for the treatment of MM, but with limited therapeutic efficacy. We recently identified a small molecule BDA-366 as a BCL2 BH4 domain antagonist, converting it from an anti-apoptotic into a pro-apoptotic molecule. In this study, we demonstrated that BDA-366 induces robust apoptosis in MM cell lines and primary MM cells by inducing BCL2 conformational change. Delivery of BDA-366 substantially suppressed the growth of human MM xenografts in NOD-scid/IL2Rγnull mice, without significant cytotoxic effects on normal hematopoietic cells or body weight. Thus, BDA-366 functions as a novel BH4-based BCL2 inhibitor and offers an entirely new tool for MM therapy.

  10. Mapping of the bcl-2 oncogene on mouse chromosome 1.

    Science.gov (United States)

    Mock, B A; Givol, D; D'Hoostelaere, L A; Huppi, K; Seldin, M F; Gurfinkel, N; Unger, T; Potter, M; Mushinski, J F

    1988-01-01

    Two bcl-2 alleles have been identified in inbred strains of mice by restriction fragment length polymorphism (RFLP). Analysis of a bcl-2 RFLP in a series of bilineal congenic strains (C.D2), developed as a tool for chromosomal mapping studies, revealed linkage of bcl-2 to the Idh-1/Pep-3 region of murine chromosome 1. The co-segregation of bcl-2 alleles with allelic forms of two other chromosome 1 loci, Ren-1,2 and Spna-1, in a set of back-cross progeny, positions bcl-2 7.8 cM centromeric from Ren-1,2.

  11. A Family Affair : Explaining Co-Working By Family Members

    NARCIS (Netherlands)

    Ruijter, Esther de; Lippe, Tanja van der; Raub, Werner; Weessie, Jeroen

    2008-01-01

    This study focuses on co-working by intimate partners and other family members in entrepreneurs’ businesses. We hypothesize that co-working by family is beneficial because it reduces trust problems associated with employment relations. On the other hand, co-working is risky because co-working family

  12. Immunogenicity of Bcl-2 in patients with cancer

    DEFF Research Database (Denmark)

    Andersen, Mads Hald; Svane, Inge Marie; Kvistborg, Pia

    2005-01-01

    activities in preclinical models and are currently in several clinical trials. The clinical application of immunotherapy against cancer is rapidly moving forward in multiple areas, including the adoptive transfer of anti-tumor-reactive T cells and the use of "therapeutic" vaccines. The overexpression of Bcl......-2 in cancer and the fact that immune escape by down-regulation or loss of expression of this protein would impair sustained tumor growth makes Bcl-2 a very attractive target for anticancer immunotherapy. Herein, we describe spontaneous T-cell reactivity against Bcl-2 in peripheral blood from......B-cell lymphoma 2 (Bcl-2) is a pivotal regulator of apoptotic cell death and it is overexpressed in many cancers. Consequently, the Bcl-2 protein is an attractive target for drug design, and Bcl-2-specific antisense oligonucleotides or small-molecule Bcl-2 inhibitors have shown broad anticancer...

  13. Estradiol increases the Bax/Bcl-2 ratio and induces apoptosis in the anterior pituitary gland.

    Science.gov (United States)

    Zaldivar, Verónica; Magri, María Laura; Zárate, Sandra; Jaita, Gabriela; Eijo, Guadalupe; Radl, Daniela; Ferraris, Jimena; Pisera, Daniel; Seilicovich, Adriana

    2009-01-01

    Estrogens are recognized as acting as modulators of pituitary cell renewal, sensitizing cells to mitogenic and apoptotic signals, thus participating in anterior pituitary homeostasis during the estrous cycle. The balance of pro- and antiapoptotic proteins of the Bcl-2 family is known to regulate cell survival and apoptosis. In order to understand the mechanisms underlying apoptosis during the estrous cycle, we evaluated the expression of the proapoptotic protein Bax and the antiapoptotic proteins Bcl-2 and Bcl-xL in the anterior pituitary gland in cycling female rats as well as the influence of estradiol on the expression of these proteins in anterior pituitary cells of ovariectomized rats. As determined by Western blot, the expression of Bax was higher in anterior pituitary glands from rats at proestrus than at diestrus I, Bcl-2 protein levels showed no difference and Bcl-xL expression was lower, thus increasing the Bax/Bcl-2 ratio at proestrus. Assessed by annexin V binding and flow cytometry, the percentage of apoptotic anterior pituitary cells was higher in rats at proestrus than at diestrus I. Chronic estrogen treatment in ovariectomized rats enhanced the Bax/Bcl-2 ratio and induced apoptosis. Moreover, incubation of cultured anterior pituitary cells from ovariectomized rats with 17beta-estradiol for 24 h increased the Bax/Bcl-2 ratio, decreased Bcl-xL expression and induced apoptosis. Our results demonstrate that estradiol increases the ratio between proapoptotic and antiapoptotic proteins of the Bcl-2 family. This effect could participate in the sensitizing action of estrogens to proapoptotic stimuli and therefore be involved in the high apoptotic rate observed at proestrus in the anterior pituitary gland.

  14. Grief elaboration in families with handicapped member.

    Science.gov (United States)

    Calandra, C; Finocchiaro, G; Raciti, L; Alberti, A

    1992-01-01

    Families with handicapped member seem to follow the same five stages (rejection and isolation, anger, dealing with the problem, depression, acceptance) of Kubler-Ross grief elaboration theory while dealing with the narcissistic wound of a handicapped child. Some of these families show a block in one of the stages. The effort of psychotherapy is to remove the block and let them reach the last stage. In this paper families under systemic psychotherapeutic treatment are analyzed, who had in common the birth of a child with low or modest invalidating signs and psychotic or autistic features. The families structure did not show the characteristics of a psychotic family. Nevertheless either one or both parents ignored the evidence of their child disease and they built a "disease-incongrous" wait around the child, trying to push away the painful reality. The authors explain the importance of this approach for the improvement of the autistic traits.

  15. Apoptosis in differentiating C2C12 muscle cells selectively targets Bcl-2-deficient myotubes

    Science.gov (United States)

    Schoneich, Christian; Dremina, Elena; Galeva, Nadezhda; Sharov, Victor

    2014-01-01

    Muscle cell apoptosis accompanies normal muscle development and regeneration, as well as degenerative diseases and aging. C2C12 murine myoblast cells represent a common model to study muscle differentiation. Though it was already shown that myogenic differentiation of C2C12 cells is accompanied by enhanced apoptosis in a fraction of cells, either the cell population sensitive to apoptosis or regulatory mechanisms for the apoptotic response are unclear so far. In the current study we characterize apoptotic phenotypes of different types of C2C12 cells at all stages of differentiation, and report here that myotubes of differentiated C2C12 cells with low levels of anti-apoptotic Bcl-2 expression are particularly vulnerable to apoptosis even though they are displaying low levels of pro-apoptotic proteins Bax, Bak and Bad. In contrast, reserve cells exhibit higher levels of Bcl-2 and high resistance to apoptosis. The transfection of proliferating myoblasts with Bcl-2 prior to differentiation did not protect against spontaneous apoptosis accompanying differentiation of C2C12 cell but led to Bcl-2 overexpression in myotubes and to significant protection from apoptotic cell loss caused by exposure to hydrogen peroxide. Overall, our data advocate for a Bcl-2-dependent mechanism of apoptosis in differentiated muscle cells. However, downstream processes for spontaneous and hydrogen peroxide induced apoptosis are not completely similar. Apoptosis in differentiating myoblasts and myotubes is regulated not through interaction of Bcl-2 with pro-apoptotic Bcl-2 family proteins such as Bax, Bak, and Bad. PMID:24129924

  16. The dying child and surviving family members.

    Science.gov (United States)

    Shrier, D K

    1980-12-01

    This overview of death and dying focuses on the dying child and surviving family members. Children's concepts of death at different developmental stages are reviewed. These range from an inability to distinguish death from other forms of separation prior to age 3, through partial concepts of death until, by age 10 to 15 years, children are able to conceptualize death as universal, inevitable and final. The importance of adults assisting in the child's growing comprehension of death is stressed. The stages of grief and mourning, as outlined by Kubler-Ross, are reviewed from the perspective of the child and family: denial, anger, bargaining, depression and acceptance. Recognition is given to the variations in coping styles among different family members. The special circumstances related to the death of an infant and the impact of the death of a child on the surviving siblings are discussed. Specific helpful interventions to assist families in coping with mourning are described. The death of a child remains one of the most painful and difficult events for a family and its physician to accept.

  17. Sensory loss amongst old family members

    DEFF Research Database (Denmark)

    Rasmussen, Jon Dag; Winther, Ida Wentzel

    2018-01-01

    and their close family. Our tentative findings point towards a prominence of different insecurities and discomforts in social life that directly links to the decreased sensory abilities. Experiences of being ‘lost’, ‘set afloat’ and disconnected in everyday life interactions are broadly described by all...... on the old people suffering a decline in sensory abilities, but also on family members as individual loss becomes collective loss in the context of family and kinship. The paper presentation takes its point of departure in rough pieces of empirical material (e.g. film-clips, sound......-clips/montage and ethnographic description) and through exposition of tentative analysis and research findings we aim to initiate a discussion around central themes of the work....

  18. Targeted BCL2 inhibition effectively inhibits neuroblastoma tumour growth

    NARCIS (Netherlands)

    Lamers, Fieke; Schild, Linda; den Hartog, Ilona J. M.; Ebus, Marli E.; Westerhout, Ellen M.; Ora, Ingrid; Koster, Jan; Versteeg, Rogier; Caron, Huib N.; Molenaar, Jan J.

    2012-01-01

    Genomic aberrations of key regulators of the apoptotic pathway have hardly been identified in neuroblastoma. We detected high BCL2 mRNA and protein levels in the majority of neuroblastoma tumours by Affymetrix expression profiling and Tissue Micro Array analysis. This BCL2 mRNA expression is

  19. Targeting anti-apoptotic Bcl-2 by AT-101 to increase radiation efficacy: data from in vitro and clinical pharmacokinetic studies in head and neck cancer

    International Nuclear Information System (INIS)

    Zerp, Shuraila F.; Stoter, T. Rianne; Hoebers, Frank J. P.; Brekel, Michiel W. M. van den; Dubbelman, Ria; Kuipers, Gitta K.; Lafleur, M. Vincent M.; Slotman, Ben J.; Verheij, Marcel

    2015-01-01

    Pro-survival Bcl-2 family members can promote cancer development and contribute to treatment resistance. Head and neck squamous cell carcinoma (HNSCC) is frequently characterized by overexpression of anti-apoptotic Bcl-2 family members. Increased levels of these anti-apoptotic proteins have been associated with radio- and chemoresistance and poor clinical outcome. Inhibition of anti-apoptotic Bcl-2 family members therefore represents an appealing strategy to overcome resistance to anti-cancer therapies. The aim of this study was to evaluate combined effects of radiation and the pan-Bcl-2 inhibitor AT-101 in HNSCC in vitro. In addition, we determined human plasma levels of AT-101 obtained from a phase I/II trial, and compared these with the effective in vitro concentrations to substantiate therapeutic opportunities. We examined the effect of AT-101, radiation and the combination on apoptosis induction and clonogenic survival in two HNSCC cell lines that express the target proteins. Apoptosis was assessed by bis-benzimide staining to detect morphological nuclear changes and/or by propidium iodide staining and flow-cytometry analysis to quantify sub-diploid apoptotic nuclei. The type of interaction between AT-101 and radiation was evaluated by calculating the Combination Index (CI) and by performing isobolographic analysis. For the pharmacokinetic analysis, plasma AT-101 levels were measured by HPLC in blood samples collected from patients enrolled in our clinical phase I/II study. These patients with locally advanced HNSCC were treated with standard cisplatin-based chemoradiotherapy and received dose-escalating oral AT-101 in a 2-weeks daily schedule every 3 weeks. In vitro results showed that AT-101 enhances radiation-induced apoptosis with CI’s below 1.0, indicating synergy. This effect was sequence-dependent. Clonogenic survival assays demonstrated a radiosensitizing effect with a DEF 37 of 1.3 at sub-apoptotic concentrations of AT-101. Pharmacokinetic analysis

  20. Prognostic Importance of Bcl-2 Expression in Colon Cancer

    Directory of Open Access Journals (Sweden)

    Arsenal Alikanoðlu

    2012-09-01

    Full Text Available Aim: TNM classification, that had been established according to pathologic and anatomic characteristics of the lesion , is the most important factor in decision of adjuvant therapy in colon cancer. Despite curative resection, recurrence can ocur with a rate of 20-30% in early stage disease. Therefore efficieny of TNM classification is controversial. In recent years ,significance of molecular characteristics of the tumors besides their anatomic and pathologic characteristics in determining the biological behaviour and response to treatment have been discussed. In our study, relation between expression of Bcl-2 and the other known prognostic factors in colon cancer had been searched. Material and Method: Patients who had been followed up in our clinic were enrolled in this study. Expression of Bcl-2 was searched by immunohistochemical method. Results: A total of 52, 19 (%36.5 female and 33 (%63.5 male patients were enrolled in this study. Bcl-2 expression was found positive in 7 (%13.5 and negative in 45 (%86.5 patients. Statistically no significant relationship was found between Bcl-2 expression and sex, stage, regional lymph node involvement, presence of distant metastasis and histologic grade. Discussion: In our study, although not in a statistical significance, we found that Bcl-2 expression is related to early stage disease. Bcl-2 is a low-priced and easily accessible prognostic marker. We think that establishing expression of Bcl-2 by immunohistohemistry may play a role in determining prognosis of patients with colon cancer.

  1. A plant Bcl-2-associated athanogene is proteolytically activated to confer fungal resistance

    Directory of Open Access Journals (Sweden)

    Mehdi Kabbage

    2016-04-01

    Full Text Available The Bcl-2-associated athanogene (BAG family is a multifunctional group of proteins involved in numerous cellular functions ranging from apoptosis to tumorigenesis. These proteins are evolutionarily conserved and encode a characteristic region known as the BAG domain. BAGs function as adapter proteins forming complexes with signaling molecules and molecular chaperones. In humans, a role for BAG proteins has been suggested in tumor growth, HIV infection, and neurodegenerative diseases; as a result, the BAGs are attractive targets for therapeutic interventions, and their expression in cells may serve as a predictive tool for disease development. The Arabidopsis genome contains seven homologs of BAG family proteins (Figure 1, including four with a domain organization similar to animal BAGs (BAG1-4. The remaining three members (BAG5-7 contain a predicted calmodulin-binding motif near the BAG domain, a feature unique to plant BAG proteins that possibly reflects divergent mechanisms associated with plant-specific functions. As reported for animal BAGs, plant BAGs also regulate several stress and developmental processes (Figure 2. The recent article by Li et al. focuses on the role of BAG6 in plant innate immunity. This study shows that BAG6 plays a key role in basal plant defense against fungal pathogens. Importantly, this work further shows that BAG6 is proteolytically activated to induce autophagic cell death and resistance in plants. This finding underscores the importance of proteases in the execution of plant cell death, yet little is known about proteases and their substrates in plants.

  2. Ten Warning Signs Your Older Family Member May Need Help

    Science.gov (United States)

    ... Warning Signs Your Older Family Member May Need Help Changes in physical and cognitive abilities that may ... and their family members, friends, and caregivers. To help in determining when an older adult may need ...

  3. The relationship between mental health workers and family members

    NARCIS (Netherlands)

    van de Bovenkamp, H.M.; Trappenburg, M.J.

    2010-01-01

    Objective To study the relationship between family members and mental health care workers to learn more about the support available to family members of mental health patients. Methods Eighteen interviews were conducted with family members, seven with professionals and two with patients.

  4. Mental Wellbeing of Family Members of Autistic Adults

    Science.gov (United States)

    Herrema, Renske; Garland, Deborah; Osborne, Malcolm; Freeston, Mark; Honey, Emma; Rodgers, Jacqui

    2017-01-01

    Family members are often the primary caregiver for autistic adults and this responsibility may impact on the carer's wellbeing and quality of life. 109 family members of autistic adults completed an online survey assessing their wellbeing relating to their caring role for their autistic relative. Family members who were supporting an autistic…

  5. Metformin combined with aspirin significantly inhibit pancreatic cancer cell growth in vitro and in vivo by suppressing anti-apoptotic proteins Mcl-1 and Bcl-2

    Science.gov (United States)

    Yue, Wen; Zheng, Xi; Lin, Yong; Yang, Chung S.; Xu, Qing; Carpizo, Darren; Huang, Huarong; DiPaola, Robert S.; Tan, Xiang-Lin

    2015-01-01

    Metformin and aspirin have been studied extensively as cancer preventive or therapeutic agents. However, the effects of their combination on pancreatic cancer cells have not been investigated. Herein, we evaluated the effects of metformin and aspirin, alone or in combination, on cell viability, migration, and apoptosis as well as the molecular changes in mTOR, STAT3 and apoptotic signaling pathways in PANC-1 and BxPC3 cells. Metformin and aspirin, at relatively low concentrations, demonstrated synergistically inhibitory effects on cell viability. Compared to the untreated control or individual drug, the combination of metformin and aspirin significantly inhibited cell migration and colony formation of both PANC-1 and BxPC-3 cells. Metformin combined with aspirin significantly inhibited the phosphorylation of mTOR and STAT3, and induced apoptosis as measured by caspase-3 and PARP cleavage. Remarkably, metformin combined with aspirin significantly downregulated the anti-apoptotic proteins Mcl-1 and Bcl-2, and upregulated the pro-apoptotic proteins Bim and Puma, as well as interrupted their interactions. The downregulation of Mcl-1 and Bcl-2 was independent of AMPK or STAT3 pathway but partially through mTOR signaling and proteasome degradation. In a PANC-1 xenograft mouse model, we demonstrated that the combination of metformin and aspirin significantly inhibited tumor growth and downregulated the protein expression of Mcl-1 and Bcl-2 in tumors. Taken together, the combination of metformin and aspirin significantly inhibited pancreatic cancer cell growth in vitro and in vivo by regulating the pro- and anti-apoptotic Bcl-2 family members, supporting the continued investigation of this two drug combination as chemopreventive or chemotherapeutic agents for pancreatic cancer. PMID:26056043

  6. Inhibition of early 99mTc-MIBI uptake by Bcl-2 anti-apoptotic protein overexpression in untreated breast carcinoma

    International Nuclear Information System (INIS)

    Del Vecchio, Silvana; Zannetti, Antonella; Aloj, Luigi; Caraco, Corradina; Ciarmiello, Andrea; Salvatore, Marco

    2003-01-01

    Lack of technetium-99m methoxyisobutylisonitrile ( 99m Tc-MIBI) uptake is consistently reported to predict poor response to subsequent chemotherapy in a variety of human malignant tumours. Since 99m Tc-MIBI accumulates within mitochondria, which also play a central role in apoptosis through the integration of death signals by Bcl-2 family members, we tested whether early 99m Tc-MIBI uptake is affected by alterations of the apoptotic pathway. Forty-two breast cancer patients were intravenously injected with 740 MBq of 99m Tc-MIBI and planar images were obtained 10 min post injection with the patients in the prone lateral position. Ten carcinomas failed to accumulate 99m Tc-MIBI and could not be visualised on scintigraphic images despite being larger than 1.8 cm (MIBI negative). Thirty-two of the 42 breast carcinomas showed focal uptake of 99m Tc-MIBI (MIBI positive), and 10 min tumour-to-background ratios (T/B) varied between 1.14 and 6.93. The apoptotic index, the rate of proliferation, and the expression of the anti-apoptotic Bcl-2 protein and pro-apoptotic Bax protein were assessed in surgically excised tumours. All MIBI-negative carcinomas showed a dramatic and statistically significant reduction in the apoptotic index as compared with MIBI-positive lesions (mean±SD, 0.14±0.15 vs 1.28±0.83, P 99m Tc-MIBI in breast carcinomas is affected by alterations of apoptotic pathway. High levels of Bcl-2, despite the stabilisation of mitochondrial membrane potentials, prevent accumulation of 99m Tc-MIBI in tumour cells. In conclusion, absent or reduced early 99m Tc-MIBI uptake in large tumours may indicate a Bcl-2-mediated resistance to chemo- and radiotherapy. (orig.)

  7. Family Members' Reports of the Technology Use of Family Members with Intellectual and Developmental Disabilities

    Science.gov (United States)

    Palmer, S. B.; Wehmeyer, M. L.; Davies, D. K.; Stock, S. E.

    2012-01-01

    Background: A nationwide survey of family members of people with intellectual and developmental disabilities ranging in age from birth through adulthood was conducted to replicate a similar effort by Wehmeyer and update the knowledge base concerning technology use by people with intellectual and developmental disabilities. Method: Survey responses…

  8. Bcl-2 antisense therapy in B-cell malignancies.

    Science.gov (United States)

    Chanan-Khan, Asher

    2005-07-01

    Bcl-2 is an apoptosis regulating protein, overexpression of which is associated with chemotherapy resistant disease, aggressive clinical course, and poor survival in patients with B-cell lymphoproliferative disorders. Overexpression of Bcl-2 protein results in an aberrant intrinsic apoptotic pathway that confers a protective effect on malignant cells against a death signal (e.g., chemotherapy or radiotherapy). Downregulation of this oncoprotein, thus, represents a possible new way to target clinically aggressive disease. Preclinical studies have shown that this oncoprotein can be effectively decreased by Bcl-2 antisense in malignant lymphoid cells and can reverse chemotherapy resistance, as well as enhance the anti-apoptotic potential of both chemotherapeutic and biologic agents. Ongoing clinical trials are exploring the role of Bcl-2 downregulation with oblimersen (Bcl-2 antisense) in patients with non-Hodgkin's lymphoma, chronic lymphocytic leukemia and multiple myeloma. Early results from these studies are promising and support the proof of the principle. As these studies are completed and mature data emerges, the role of Bcl-2 antisense therapy in the treatment of B-cell malignancies will become clearer.

  9. Bcl-2 Protein Expression in Egyptian Acute Myeloid Leukemia

    International Nuclear Information System (INIS)

    El-Shakankiry, N.; El-Sayed, Gh.M.M.; El-Maghraby, Sh.; Moneer, M.M.

    2009-01-01

    Objective: The primary cause of treatment failure in acute myeloid leukemia (AML) is the emergence of both resistant disease and early relapse. The bcl-2 gene encodes a 26-kDa protein that promotes cell survival by blocking programmed cell death (apoptosis). In the present study, bcl-2 protein expression was evaluated in newly diagnosed AML patients and correlated with the induction of remission and overall survival (OS), in an attempt to define patients who might benefit from modified therapeutic strategies. Patients and methods: Pretreatment cellular bcl-2 protein expression was measured in bone marrow samples obtained from 68 patients of newly diagnosed acute myeloid leukemia and 10 healthy controls by western blotting. Results: The mean bcl-2 protein expression was significantly higher in patients (0.68610.592) compared to controls (0.313±0.016) (p=0.002). The overall survival for patients with mean bcl-2 expression of less, and more than or equal to 0.315, was 67% and 56%, respectively, with no significant difference between the two groups 0»=0.86). Conclusion: Even though we did not observe a significant difference in overall survival between patients with high and low levels of bcl-2, modulation of this protein might still be considered as an option for enhancing the effectiveness of conventional chemotherapy.

  10. Increased expression of Bcl-2 during mucous cell metaplasia induced by endotoxin and ozone

    Energy Technology Data Exchange (ETDEWEB)

    Tesfaigzi, J.; Ray, L.M.; Hotchkiss, J.A. [Michigan State Univ., East Lansing, MI (United States)] [and others

    1995-12-01

    Apoptosis or programmed cell death is accompanied by characteristic morphological changes that distinguish apoptosis from other forms of cell death. These changes include DNA fragmentation, chromatin condensation, cell shrinkage, cell surface pseudopodia, and finally the cellular collapse into membrane-enclosed apoptotic bodies which are rapidly engulfed by macrophages or neighboring cells. Although the morphological features of apoptotic cells are well studied, the biochemical events that control apoptosis are not understood. Programmed cell death is triggered by a variety of pathways that are initiated by different stimuli including noxious agents, DNA damage, the activation of TNF receptors, or the withdrawl of growth factors. The central process of programmed cell death involves a cascade of biochemical events that begins with the initiation of a family of cysteine proteases, including the interleukin-1-{Beta}-converting enzyme, CPP-32, and Apopain. The ratio of Bax, a death-inducer gene, to Bcl-2, an apoptosis suppressor gene, determines whether or not the main apoptotic pathyway is blocked. Apoptosis is suppressed if the ratio of Bcl-2/Bax is > 1, and cells undergo apoptosis if the ratio is < 1. The overexpression of Bcl-2 has been shown to block the apoptotic program triggered by a variety of agents. Therefore, Bcl-2 must be involved in blocking the central pathway of the cell death program. In conclusion, this study showed that high levels of Bcl-2 were detected in some mucous cells at specific time points during mucous cell metaplasia, and this expression was reduced at later time points or was absent after remodeling of this epithelium.

  11. In vivo efficacy of the Bcl-2 antagonist ABT-737 against aggressive Myc-driven lymphomas

    OpenAIRE

    Mason, Kylie D.; Vandenberg, Cassandra J.; Scott, Clare L.; Wei, Andrew H.; Cory, Suzanne; Huang, David C. S.; Roberts, Andrew W.

    2008-01-01

    Deregulated Myc expression drives many human cancers, including Burkitt's lymphoma and a highly aggressive subset of diffuse large cell lymphomas. Myc-driven tumors often display resistance to chemotherapeutics because of acquisition of mutations that impair the apoptosis pathway regulated by the Bcl-2 protein family. Given the need to identify new therapies for such lymphomas, we have evaluated the efficacy of ABT-737, a small molecule that mimics the action of the BH3-only proteins, natural...

  12. Perceived Family Resources Based on Number of Members with ADHD

    Science.gov (United States)

    Corwin, Melinda; Mulsow, Miriam; Feng, Du

    2012-01-01

    Objective: This study examines how the number of family members with ADHD affects other family members' perceived resources. Method: A total of 40 adolescents diagnosed with ADHD and their mothers, fathers, and adolescent siblings living in the household participated. Hierarchical linear modeling was used to analyze family-level data from a total…

  13. Bcl-2 overexpression: effects on transmembrane calcium movement

    International Nuclear Information System (INIS)

    Rangaswami, Arun A.; Premack, Brett; Walleczek, Jan; Killoran, Pamela; Gardner, Phyllis; Knox, Susan J.

    1996-01-01

    Purpose/Objective: High levels of expression of the proto-oncogene bcl-2 and its 26 kD protein product Bcl-2 have been correlated with the inhibition of apoptosis and the increased resistance of tumor cells to cytotoxic drugs and ionizing radiation. Unfortunately, the specific mechanism of action of Bcl-2 remains poorly understood. In the studies described here, the role of intracellular calcium fluxes and plasma membrane calcium cycling in the induction of apoptosis, and the effect of Bcl-2 expression on the modulation of transmembrane calcium fluxes following treatment of cells with cytotoxic agents were studied. The relationship between intracellular calcium release, capacitive calcium entry, and the plasma membrane potential were also investigated. Materials and Methods: Human B-cell lymphoma (PW) and human promyelocytic leukemia (HL60) cell lines were transfected with Bcl-2 and a control vector. The Bcl-2 transfectants over expressed the Bcl-2 onco-protein and were more resistant to irradiation than the control cells. Cells were loaded with fluorescent indicators indo-1 and fura-2 AM to quantify the cytosolic calcium concentration and subsequent calcium responses to a variety of cytotoxic stimuli, including the microsomal ATPase inhibitor, thapsigargin, using fluorometric measurements. Comparisons of resting and stimulated cytosolic calcium concentrations were made between the parental, neomycin control, and bcl-2 transfected cells. In order to determine the actual calcium influx rate, cells were loaded with either indo-1 or fura-2 and then exposed to 0.1 mM extracellular manganese, which enters the cells through calcium influx channels and quenches the fluorescent signal in proportion to the calcium influx rate. In order to determine the role of the membrane potential in driving calcium influx, cells were treated with either 0.1 μM Valinomycin or isotonic potassium chloride to either hyper polarize or depolarize the resting membrane potential, and the

  14. BH3-only proteins and BH3 mimetics induce autophagy by competitively disrupting the interaction between Beclin 1 and Bcl-2/Bcl-X(L).

    Science.gov (United States)

    Maiuri, Maria Chiara; Criollo, Alfredo; Tasdemir, Ezgi; Vicencio, José Miguel; Tajeddine, Nicolas; Hickman, John A; Geneste, Olivier; Kroemer, Guido

    2007-01-01

    Beclin 1 has recently been identified as novel BH3-only protein, meaning that it carries one Bcl-2-homology-3 (BH3) domain. As other BH3-only proteins, Beclin 1 interacts with anti-apoptotic multidomain proteins of the Bcl-2 family (in particular Bcl-2 and its homologue Bcl-X(L)) by virtue of its BH3 domain, an amphipathic alpha-helix that binds to the hydrophobic cleft of Bcl-2/Bcl-X(L). The BH3 domains of other BH3-only proteins such as Bad, as well as BH3-mimetic compounds such as ABT737, competitively disrupt the inhibitory interaction between Beclin 1 and Bcl-2/Bcl-X(L). This causes autophagy of mitochondria (mitophagy) but not of the endoplasmic reticulum (reticulophagy). Only ER-targeted (not mitochondrion-targeted) Bcl-2/Bcl-X(L) can inhibit autophagy induced by Beclin 1, and only Beclin 1-Bcl-2/Bcl-X(L) complexes present in the ER (but not those present on heavy membrane fractions enriched in mitochondria) are disrupted by ABT737. These findings suggest that the Beclin 1-Bcl-2/Bcl-X(L) complexes that normally inhibit autophagy are specifically located in the ER and point to an organelle-specific regulation of autophagy. Furthermore, these data suggest a spatial organization of autophagy and apoptosis control in which BH3-only proteins exert two independent functions. On the one hand, they can induce apoptosis, by (directly or indirectly) activating the mitochondrion-permeabilizing function of pro-apoptotic multidomain proteins from the Bcl-2 family. On the other hand, they can activate autophagy by liberating Beclin 1 from its inhibition by Bcl-2/Bcl-X(L) at the level of the endoplasmic reticulum.

  15. Coping Strategies of Family Members of Hospitalized Psychiatric Patients

    Directory of Open Access Journals (Sweden)

    Phyllis M. Eaton

    2011-01-01

    Full Text Available This exploratory research paper investigated the coping strategies of families of hospitalized psychiatric patients and identified their positive and negative coping strategies. In this paper, the coping strategies of 45 family members were examined using a descriptive, correlational, mixed method research approach. Guided by the Neuman Systems Model and using the Family Crisis Oriented Personal Evaluation Scales and semistructured interviews, this paper found that these family members used more emotion-focused coping strategies than problem-focused coping strategies. The common coping strategies used by family members were communicating with immediate family, acceptance of their situation, passive appraisal, avoidance, and spirituality. The family members also utilized resources and support systems, such as their immediate families, mental health care professionals, and their churches.

  16. Expanding access to naloxone for family members: The Massachusetts experience.

    Science.gov (United States)

    Bagley, Sarah M; Forman, Leah S; Ruiz, Sarah; Cranston, Kevin; Walley, Alexander Y

    2018-05-01

    The Massachusetts Department of Public Health Overdose Education and Naloxone Distribution Program provides overdose education and naloxone rescue kits to people at risk for overdose and bystanders, including family members. Using Massachusetts Department of Public Health data, the aims are to: (i) describe characteristics of family members who receive naloxone; (ii) identify where family members obtain naloxone; and (iii) describe characteristics of rescues by family members. We conducted a retrospective review using program enrollee information collected on a standardised form between 2008 and 2015. We calculated descriptive statistics, including demographics, current substance use, enrolment location, history of witnessed overdoses and rescue attempt characteristics. We conducted a stratified analysis comparing family members who used drugs with those who did not. Family members were 27% of total program enrollees (n = 10 883/40 801). Family members who reported substance use (n = 4679) were 35.6 years (mean), 50.6% female, 76.3% non-Hispanic white, 75.6% had witnessed an overdose, and they obtained naloxone most frequently at HIV prevention programs. Family members who did not report substance use (n = 6148) were 49.2 years (mean), 73.8% female, 87.9% non-Hispanic white, 35.3% had witnessed an overdose, and they obtained naloxone most frequently at community meetings. Family members were responsible for 20% (n = 860/4373) of the total rescue attempts. The Massachusetts experience demonstrates that family members can be active participants in responding to the overdose epidemic by rescuing family members and others. Targeted intervention strategies for families should be included in efforts to expand overdose education and naloxone in Massachusetts. © 2017 Australasian Professional Society on Alcohol and other Drugs.

  17. B1-induced caspase-independent apoptosis in MCF-7 cells is mediated by down-regulation of Bcl-2 via p53 binding to P2 promoter TATA box

    International Nuclear Information System (INIS)

    Liang Xin; Xu Ke; Xu Yufang; Liu Jianwen; Qian Xuhong

    2011-01-01

    The Bcl-2 family contains a panel of proteins which are conserved regulators of apoptosis in mammalian cells, like the anti-apoptotic protein Bcl-2. According to its significant role in altering susceptibility to apoptosis, the deciphering of the mechanism of Bcl-2 expression modulation may be crucial for identifying therapeutics strategies for cancer. Treatment with naphthalimide-based DNA intercalators, including M2-A and R16, generally leads to a decrease in Bcl-2 intracellular amounts. Whereas the interest for these chemotherapeutics is accompanied by advances in the fundamental understanding of their anticancer properties, the molecular mechanism underlying changes in Bcl-2 expression remains poorly understood. We report here that p53 contributes to Bcl-2 down-regulation induced by B1, a novel naphthalimide-based DNA intercalating agent. Indeed, the decrease in Bcl-2 protein levels observed during B1-induced apoptosis was correlated to the decrease in mRNA levels, as a result of the inhibition of Bcl-2 transcription and promoter activity. In this context, we evaluated p53 contribution in the Bcl-2 transcriptional down-regulation. We found a significant increase of p53 binding to P 2 promoter TATA box in MCF7 cells by chromatin immunoprecipitation. These data suggest that B1-induced caspase-independent apoptosis in MCF-7 cells is associated with the activation of p53 and the down-regulation of Bcl-2. Our study strengthens the links between p53 and Bcl-2 at a transcriptional level, upon naphthalimide-based DNA intercalator treatment. - Research highlights: → B1 induced apoptosis in MCF-7 cells, following a transcriptional decrease in Bcl-2. → B1 treatment triggered p53 activation and leads to a p53-dependent down-regulation of Bcl-2. → B1 induced significant increase of p53 binding to Bcl-2 P 2 promoter TATA box.

  18. Posttraumatic stress disorder in women with war missing family members.

    Science.gov (United States)

    Baraković, Devla; Avdibegović, Esmina; Sinanović, Osman

    2014-12-01

    Research in crisis areas indicate that survivors' responses to the forced disappearance of family members are similar to reactions to other traumatic events. The aim of this study was to determine the presence of symptoms of posttraumatic stress disorder (PTSD) in women with war missing family members in Bosnia and Herzegovina 18 years after the war in this region (1992-1995). The study included 160 women aged 47.1±14.0 from three regions of Bosnia and Herzegovina. It was carried out in the period from April 2010 to May 2011. Of the 160 participants, 120 women had a war missing family member and 40 women had no war missing family members. The Harvard Trauma Questionnaire (HTQ), the Beck Depression Inventory (BDI) and the Hamilton Anxiety Rating Scale (HAMA) were used for data collection. Basic socio-demographic data and data concerning the missing family members were also collected. Women with war missing family members experienced significantly more traumatic war experiences (18.43±5.27 vs 6.57±4.34, pfamily members. Women with war missing family members showed significantly more severe PTSD symptoms. Based on the results of this study, it was determined that the forced disappearance of a family member is an ambiguous situation that can be characterized as a traumatic experience.

  19. Exploring the stigma related experiences of family members of ...

    African Journals Online (AJOL)

    Celenkosini Thembelenkosini Nxumalo

    a cycle of disability on the part of the patient and family. Purpose: To explore the stigma .... prevention of stigmatisation of people with mental illness and their families in rural ... as a family member's accounts of stigma related feelings, situations or ..... ishment from the family as a reason for the bad behaviour. The participants ...

  20. Dying in the Hospital: Perspectives of family members.

    Science.gov (United States)

    Dose, Ann Marie; Carey, Elise C; Rhudy, Lori M; Chiu, Yichen; Frimannsdottir, Katrin; Ottenberg, Abigale L; Koenig, Barbara A

    2015-01-01

    Although most patients express a preference to die at home, many (over 30 percent) still die in hospital. This study's purpose was to explore the experience of hospital death from the perspective of patients' family members. interviews were conducted with family members of patients who had died at hospitals affiliated with a large tertiary referral centre in the United States. Content analysis was used to analyze findings. We interviewed 30 family members by phone. Themes were arranged by time frame: before death, time of death, and after death. Families do not interpret clinical cues leading up to death in the same way healthcare providers do; families need clear and direct explanations from providers. Clinicians should assess patient and family understandings of prognosis and communicate clearly and directly. Family members value being with their loved one at the time of death, and they value spending time with the body after death; this should be facilitated in clinical practice.

  1. Inhibitory effects of Bcl-2 on mitochondrial respiration

    Czech Academy of Sciences Publication Activity Database

    Vrbacký, M.; Krijt, J.; Drahota, Zdeněk; Mělková, Z.

    2003-01-01

    Roč. 52, č. 5 (2003), s. 545-554 ISSN 0862-8408 R&D Projects: GA ČR GA301/00/1259; GA MZd NC5463 Institutional research plan: CEZ:AV0Z5011922 Keywords : apoptosis * mitochondria * Bcl-2 Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 0.939, year: 2003

  2. Support for Teens When a Family Member has Cancer

    Science.gov (United States)

    When a parent, brother, or sister has been diagnosed with cancer, family members need extra support. Information to help teens learn how to cope, talk with family members, manage stress, and get support from counselors when a loved one has been diagnosed with, or is being treated for, cancer.

  3. MicroRNA-99 family members suppress Homeobox A1 expression in epithelial cells.

    Directory of Open Access Journals (Sweden)

    Dan Chen

    Full Text Available The miR-99 family is one of the evolutionarily most ancient microRNA families, and it plays a critical role in developmental timing and the maintenance of tissue identity. Recent studies, including reports from our group, suggested that the miR-99 family regulates various physiological processes in adult tissues, such as dermal wound healing, and a number of disease processes, including cancer. By combining 5 independent genome-wide expression profiling experiments, we identified a panel of 266 unique transcripts that were down-regulated in epithelial cells transfected with miR-99 family members. A comprehensive bioinformatics analysis using 12 different sequence-based microRNA target prediction algorithms revealed that 81 out of these 266 down-regulated transcripts are potential direct targets for the miR-99 family. Confirmation experiments and functional analyses were performed to further assess 6 selected miR-99 target genes, including mammalian Target of rapamycin (mTOR, Homeobox A1 (HOXA1, CTD small phosphatase-like (CTDSPL, N-myristoyltransferase 1 (NMT1, Transmembrane protein 30A (TMEM30A, and SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 (SMARCA5. HOXA1 is a known proto-oncogene, and it also plays an important role in embryonic development. The direct targeting of the miR-99 family to two candidate binding sequences located in the HOXA1 mRNA was confirmed using a luciferase reporter gene assay and a ribonucleoprotein-immunoprecipitation (RIP-IP assay. Ectopic transfection of miR-99 family reduced the expression of HOXA1, which, in consequence, down-regulated the expression of its downstream gene (i.e., Bcl-2 and led to reduced proliferation and cell migration, as well as enhanced apoptosis. In summary, we identified a number of high-confidence miR-99 family target genes, including proto-oncogene HOXA1, which may play an important role in regulating epithelial cell proliferation and

  4. MicroRNA-99 family members suppress Homeobox A1 expression in epithelial cells.

    Science.gov (United States)

    Chen, Dan; Chen, Zujian; Jin, Yi; Dragas, Dragan; Zhang, Leitao; Adjei, Barima S; Wang, Anxun; Dai, Yang; Zhou, Xiaofeng

    2013-01-01

    The miR-99 family is one of the evolutionarily most ancient microRNA families, and it plays a critical role in developmental timing and the maintenance of tissue identity. Recent studies, including reports from our group, suggested that the miR-99 family regulates various physiological processes in adult tissues, such as dermal wound healing, and a number of disease processes, including cancer. By combining 5 independent genome-wide expression profiling experiments, we identified a panel of 266 unique transcripts that were down-regulated in epithelial cells transfected with miR-99 family members. A comprehensive bioinformatics analysis using 12 different sequence-based microRNA target prediction algorithms revealed that 81 out of these 266 down-regulated transcripts are potential direct targets for the miR-99 family. Confirmation experiments and functional analyses were performed to further assess 6 selected miR-99 target genes, including mammalian Target of rapamycin (mTOR), Homeobox A1 (HOXA1), CTD small phosphatase-like (CTDSPL), N-myristoyltransferase 1 (NMT1), Transmembrane protein 30A (TMEM30A), and SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 (SMARCA5). HOXA1 is a known proto-oncogene, and it also plays an important role in embryonic development. The direct targeting of the miR-99 family to two candidate binding sequences located in the HOXA1 mRNA was confirmed using a luciferase reporter gene assay and a ribonucleoprotein-immunoprecipitation (RIP-IP) assay. Ectopic transfection of miR-99 family reduced the expression of HOXA1, which, in consequence, down-regulated the expression of its downstream gene (i.e., Bcl-2) and led to reduced proliferation and cell migration, as well as enhanced apoptosis. In summary, we identified a number of high-confidence miR-99 family target genes, including proto-oncogene HOXA1, which may play an important role in regulating epithelial cell proliferation and migration during

  5. Depression: Supporting a Family Member or Friend

    Science.gov (United States)

    ... Accessed July 9, 2015. Helping someone with a mood disorder. Depression and Bipolar Support Alliance. http://www.dbsalliance.org/site/PageServer?pagename=help_friends_family. Accessed July 9, 2015. Suicide warning signs. American Foundation for Suicide Prevention. https:// ...

  6. SS-A/Ro52 promotes apoptosis by regulating Bcl-2 production

    International Nuclear Information System (INIS)

    Jauharoh, Siti Nur Aisyah; Saegusa, Jun; Sugimoto, Takeshi; Ardianto, Bambang; Kasagi, Shimpei; Sugiyama, Daisuke; Kurimoto, Chiyo; Tokuno, Osamu; Nakamachi, Yuji; Kumagai, Shunichi; Kawano, Seiji

    2012-01-01

    Highlights: ► Ro52 low HeLa cells are resistant to apoptosis upon various stimulations. ► Ro52 is upregulated by IFN-α, etoposide, or IFN-γ and anti-Fas Ab. ► Ro52-mediated apoptosis is independent of p53. ► Ro52 selectively regulates Bcl-2 expression. -- Abstract: SS-A/Ro52 (Ro52), an autoantigen in systemic autoimmune diseases such as systemic lupus erythematosus and Sjögren’s syndrome, has E3 ligase activity to ubiquitinate proteins that protect against viral infection. To investigate Ro52’s role during stress, we transiently knocked it down in HeLa cells by siRo52 transfection. We found that Ro52 low HeLa cells were significantly more resistant to apoptosis than wild-type HeLa cells when stimulated by H 2 O 2 - or diamide-induced oxidative stress, IFN-α, IFN-γ and anti-Fas antibody, etoposide, or γ-irradiation. Furthermore, Ro52-mediated apoptosis was not influenced by p53 protein level in HeLa cells. Depleting Ro52 in HeLa cells caused Bcl-2, but not other Bcl-2 family molecules, to be upregulated. Taken together, our data showed that Ro52 is a universal proapoptotic molecule, and that its proapoptotic effect does not depend on p53, but is exerted through negative regulation of the anti-apoptotic protein Bcl-2. These findings shed light on a new physiological role for Ro52 that is important to intracellular immunity.

  7. SS-A/Ro52 promotes apoptosis by regulating Bcl-2 production

    Energy Technology Data Exchange (ETDEWEB)

    Jauharoh, Siti Nur Aisyah [Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, Hyogo 650-0017 (Japan); Faculty of Medicine and Health Science, Syarif Hidayatullah State Islamic University, Jakarta 15412 (Indonesia); Saegusa, Jun; Sugimoto, Takeshi [Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, Hyogo 650-0017 (Japan); Ardianto, Bambang [Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, Hyogo 650-0017 (Japan); Department of Child Health, Faculty of Medicine, Gadjah Mada University, Yogyakarta 55282 (Indonesia); Kasagi, Shimpei; Sugiyama, Daisuke; Kurimoto, Chiyo [Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, Hyogo 650-0017 (Japan); Tokuno, Osamu; Nakamachi, Yuji [Department of Laboratory Medicine, Kobe University Hospital, Hyogo 650-0017 (Japan); Kumagai, Shunichi [Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, Hyogo 650-0017 (Japan); Kawano, Seiji, E-mail: sjkawano@med.kobe-u.ac.jp [Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, Hyogo 650-0017 (Japan); Department of Laboratory Medicine, Kobe University Hospital, Hyogo 650-0017 (Japan)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Ro52{sup low} HeLa cells are resistant to apoptosis upon various stimulations. Black-Right-Pointing-Pointer Ro52 is upregulated by IFN-{alpha}, etoposide, or IFN-{gamma} and anti-Fas Ab. Black-Right-Pointing-Pointer Ro52-mediated apoptosis is independent of p53. Black-Right-Pointing-Pointer Ro52 selectively regulates Bcl-2 expression. -- Abstract: SS-A/Ro52 (Ro52), an autoantigen in systemic autoimmune diseases such as systemic lupus erythematosus and Sjoegren's syndrome, has E3 ligase activity to ubiquitinate proteins that protect against viral infection. To investigate Ro52's role during stress, we transiently knocked it down in HeLa cells by siRo52 transfection. We found that Ro52{sup low} HeLa cells were significantly more resistant to apoptosis than wild-type HeLa cells when stimulated by H{sub 2}O{sub 2}- or diamide-induced oxidative stress, IFN-{alpha}, IFN-{gamma} and anti-Fas antibody, etoposide, or {gamma}-irradiation. Furthermore, Ro52-mediated apoptosis was not influenced by p53 protein level in HeLa cells. Depleting Ro52 in HeLa cells caused Bcl-2, but not other Bcl-2 family molecules, to be upregulated. Taken together, our data showed that Ro52 is a universal proapoptotic molecule, and that its proapoptotic effect does not depend on p53, but is exerted through negative regulation of the anti-apoptotic protein Bcl-2. These findings shed light on a new physiological role for Ro52 that is important to intracellular immunity.

  8. Military Personnel: Medical, Family Support, and Educational Services Are Available for Exceptional Family Members

    National Research Council Canada - National Science Library

    Crosse, Marcia

    2007-01-01

    The Department of Defense's (DOD) Exceptional Family Member Program (EFMP) is a mandatory enrollment program for active duty servicemembers who have family members with special medical needs. The Ronald W...

  9. Homologous recombination control by the anti-apoptotic onco-protein Bcl-2

    International Nuclear Information System (INIS)

    Dumay, A.

    2003-12-01

    This research thesis deals with the different biological mechanisms, notably the repair and apoptosis mechanisms induced by irradiation in cells. After a presentation of the genotoxic stress and DNA repair mechanisms, the author discusses the cellular response to a DNA double-strand break, and the regulation of these response mechanisms (how a cellular response emerges: life or death). The next part deals with the apoptosis (cell death by necrosis or apoptosis), and presents the BCL-2 protein family. Results are then reported on laboratory studies of the effect of this protein family

  10. Gendering Guilt among Dependent Family Members' Caregivers.

    Science.gov (United States)

    Brea, Maria-Teresa; Albar, María-Jesús; Casado-Mejia, Rosa

    2016-11-17

    This study analyzes guilt among family caregivers of dependent patients, from a gender perspective. A qualitative design was used, conducting in-depth interviews and focus groups. Using purposive sampling, we selected 73 family caregivers and 23 health professionals (family medicine, community nursing, and social work) from the Primary Care District of Seville. The content of the information collected was analyzed in terms of the following categories: a) guilt for abandoning family and friends; b) guilt for the relationship with the dependent person; and c) guilt for placing the relative in a nursing home. To validate the findings, data sources, methodological techniques, and researchers' disciplines were all triangulated. Results indicated that women report more guilt than men for abandoning family and friends, and because of their relationship with the dependent person. However, with respect to nursing home placement, no difference was observed as a function of gender. The high incidence of caregiver guilt needs to be addressed by health professionals to avoid the emergence of other mental health issues.

  11. Members of FOX family could be drug targets of cancers.

    Science.gov (United States)

    Wang, Jinhua; Li, Wan; Zhao, Ying; Kang, De; Fu, Weiqi; Zheng, Xiangjin; Pang, Xiaocong; Du, Guanhua

    2018-01-01

    FOX families play important roles in biological processes, including metabolism, development, differentiation, proliferation, apoptosis, migration, invasion and longevity. Here we are focusing on roles of FOX members in cancers, FOX members and drug resistance, FOX members and stem cells. Finally, FOX members as drug targets of cancer treatment were discussed. Future perspectives of FOXC1 research were described in the end. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Exploring the stigma related experiences of family members of ...

    African Journals Online (AJOL)

    The stigma of families is seen in the form of assignment of blame, social isolation and rejection. This stigma subsequently perpetuates a cycle of disability on the part of the patient and family. Purpose: To explore the stigma related experiences of family members of persons with mental illness in a selected community in the ...

  13. Bcl2-associated Athanogene 3 Interactome Analysis Reveals a New Role in Modulating Proteasome Activity*

    Science.gov (United States)

    Chen, Ying; Yang, Li-Na; Cheng, Li; Tu, Shun; Guo, Shu-Juan; Le, Huang-Ying; Xiong, Qian; Mo, Ran; Li, Chong-Yang; Jeong, Jun-Seop; Jiang, Lizhi; Blackshaw, Seth; Bi, Li-Jun; Zhu, Heng; Tao, Sheng-Ce; Ge, Feng

    2013-01-01

    Bcl2-associated athanogene 3 (BAG3), a member of the BAG family of co-chaperones, plays a critical role in regulating apoptosis, development, cell motility, autophagy, and tumor metastasis and in mediating cell adaptive responses to stressful stimuli. BAG3 carries a BAG domain, a WW domain, and a proline-rich repeat (PXXP), all of which mediate binding to different partners. To elucidate BAG3's interaction network at the molecular level, we employed quantitative immunoprecipitation combined with knockdown and human proteome microarrays to comprehensively profile the BAG3 interactome in humans. We identified a total of 382 BAG3-interacting proteins with diverse functions, including transferase activity, nucleic acid binding, transcription factors, proteases, and chaperones, suggesting that BAG3 is a critical regulator of diverse cellular functions. In addition, we characterized interactions between BAG3 and some of its newly identified partners in greater detail. In particular, bioinformatic analysis revealed that the BAG3 interactome is strongly enriched in proteins functioning within the proteasome-ubiquitination process and that compose the proteasome complex itself, suggesting that a critical biological function of BAG3 is associated with the proteasome. Functional studies demonstrated that BAG3 indeed interacts with the proteasome and modulates its activity, sustaining cell survival and underlying resistance to therapy through the down-modulation of apoptosis. Taken as a whole, this study expands our knowledge of the BAG3 interactome, provides a valuable resource for understanding how BAG3 affects different cellular functions, and demonstrates that biologically relevant data can be harvested using this kind of integrated approach. PMID:23824909

  14. On sensory loss amongst old family members

    DEFF Research Database (Denmark)

    Winther, Ida Wentzel; Rasmussen, Jon Dag

    family. Our tentative findings point towards a prominence of different insecurities and discomforts in social life that directly links to the decreased sensory abilities. Experiences of being ‘lost’, ‘set afloat’ and disconnected in everyday life interactions are broadly described by all of the followed...... exposition of tentative analysis and research findings we aim to initiate a discussion around central themes of the work....

  15. Coping with stigma by association and family burden among family members of people with mental illness.

    Science.gov (United States)

    van der Sanden, Remko L M; Stutterheim, Sarah E; Pryor, John B; Kok, Gerjo; Bos, Arjan E R

    2014-10-01

    In this study, we explored stigma by association, family burden, and their impact on the family members of people with mental illness. We also studied the ways in which family members coped with these phenomena. We conducted semistructured interviews with 23 immediate family members of people with mental illness. Participants reported various experiences of stigma by association and family burden. Social exclusion, being blamed, not being taken seriously, time-consuming caregiving activities, and exhaustion appeared to be the predominant forms of stigma by association and family burden experienced by the participants. The participants used problem-focused and emotion-focused coping strategies, separately or simultaneously, to cope with the negative impact of stigma by association and family burden. The results suggest that family members should have access to services to address these problems. Social, instrumental, and emotional support should be given to family members by community members and mental health professionals.

  16. Pan-Bcl-2 inhibitor obatoclax delays cell cycle progression and blocks migration of colorectal cancer cells.

    Directory of Open Access Journals (Sweden)

    Bruno Christian Koehler

    Full Text Available Despite the fact that new treatment regimes have improved overall survival of patients challenged by colorectal cancer (CRC, prognosis in the metastatic situation is still restricted. The Bcl-2 family of proteins has been identified as promising anti cancer drug target. Even though small molecules targeting Bcl-2 proteins are in clinical trials, little is known regarding their effects on CRC. The aim of this study was to preclinically investigate the value of ABT-737 and Obatoclax as anticancer drugs for CRC treatment. The effects of the BH3-mimetics ABT-737 and Obatoclax on CRC cells were assessed using viability and apoptosis assays. Wound healing migration and boyden chamber invasion assays were applied. 3-dimensional cell cultures were used for long term assessment of invasion and proliferation. Clinically relevant concentrations of pan-Bcl-2 inhibitor Obatoclax did not induce cell death. In contrast, the BH3-mimetic ABT-737 induced apoptosis in a dose dependent manner. Obatoclax caused a cell line specific slowdown of CRC cell growth. Furthermore, Obatoclax, but not ABT-737, recovered E-Cadherin expression and led to impaired migration and invasion of CRC cells. The proliferative capacity and invasiveness of CRC cells was strikingly inhibited by low dose Obatoclax in long term 3-dimensional cell cultures. Obatoclax, but not ABT-737, caused a G1-phase arrest accompanied by a downregulation of Cyclin D1 and upregulation of p27 and p21. Overexpression of Mcl-1, Bcl-xL or Bcl-2 reversed the inhibitory effect of Obatoclax on migration but failed to restore the proliferative capacity of Obatoclax-treated CRC cells. The data presented indicate broad and multifaceted antitumor effects of the pan-Bcl-2 inhibitor Obatoclax on CRC cells. In contrast to ABT-737, Obatoclax inhibited migration, invasion and proliferation in sublethal doses. In summary, this study recommends pan-Bcl-2 inhibition as a promising approach for clinical trials in CRC.

  17. THE EXPRESSION OF Bcl-2 AND PRO-CASPASE 3 IN HEAD AND NECK SQUAMOUS CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    Andrej Cör

    2002-12-01

    Full Text Available Background. Head and neck squamous cell carcinoma (HNSCC is the sixth most common cancer and accounts for 6% of cancers worldwide. A better understanding of its biology could lead to improved treatment options. Generally, the goal of cancer treatment is to abolish cell proliferation and to induce necrotic or aptoptotic cell death. Apoptosis has been recognized as a key mechanism of tumour cell elimination. Different apoptotic signals converge to induce caspase cascade activation. Caspase 3 is the central executioner caspase and is necessary for effective apoptotic cell death. Bcl-2 protein family regulates apoptosis. The Bcl-2 protein itself is a product of a proto-oncogene and has an antiapoptotic action.Methods. In our study, the expression of Bcl-2 and pro-caspase 3 by immunohistochemistry in 28 HNSCC graded into well, moderately and poorly differentiated cancers were investigated.Results. Our results of Bcl-2 expression confirm and extend previous reports in which Bcl-2 over-expression has been recognised as an important parameter in HNSCC biological behaviour. Three of 28 tumours (11% showed significant Bcl-2 expression. Two of them were poorly and one was moderately differentiated. Pro-caspase 3 immunoreactivity was confined mainly to the cytoplasm. Absent or low pro-caspase 3 immunoreactivity was found only in 1 of 6 well differentiated and in 1of 10 moderately differentiated tumours in contrast to 5 of 12 poorly differentiated tumours. In six of 12 poorly differentiated tumours procasapse 3 immunoreactivity was strongly positive. In two cases hyperplastic epithelium was strongly positive in contrast to adjacent HNSCC in the same slide which was completely negative for pro-caspase 3.Conclusions. Our results indicate downregulation of pro-caspase 3 expression, especially in poorly differentiated HNSCC. Further studies are needed to test whether this is related to HNSCC behaviour and predict treatment outcome.

  18. Technical nursing students interacting with family members of hospitalized children

    Directory of Open Access Journals (Sweden)

    Juliana Yukari Takahashi Onishi

    Full Text Available ABSTRACT Objective: To understand technical nursing students' meaning of interacting with family members of hospitalized children. Method: Symbolic Interactionism was used as the theoretical framework and Qualitative Content Analysis was the methodological procedure. A total of eight graduates from an institution situated in the city of Osasco, Sao Paulo state, participated in this study. Data were collected through semi-structured interviews. Results: A total of five representative themes were revealed: Dealing with difficult situations with family members; Perceiving oneself to be unprepared to interact with family members; Family members being a helpful tool; Developing strategies to obtain a good interaction with family members; and Teachers being facilitators of the interaction with family members. Final considerations: To be acquainted with this experience has led to the understanding of the need to include the theme of family care in the curriculum of the Technical Nursing Course. Additionally, the present study contributed to reflections on the importance of such knowledge for this population and to the development of future studies, as this theme has been scarcely explored in the literature.

  19. Technical nursing students interacting with family members of hospitalized children.

    Science.gov (United States)

    Onishi, Juliana Yukari Takahashi; Ribeiro, Circéa Amália; Silva, Maria Cristina Ferreira Carlos Rodrigues da; Borba, Regina Issuzu Hirooka de

    2017-01-01

    To understand technical nursing students' meaning of interacting with family members of hospitalized children. Symbolic Interactionism was used as the theoretical framework and Qualitative Content Analysis was the methodological procedure. A total of eight graduates from an institution situated in the city of Osasco, Sao Paulo state, participated in this study. Data were collected through semi-structured interviews. A total of five representative themes were revealed: Dealing with difficult situations with family members; Perceiving oneself to be unprepared to interact with family members; Family members being a helpful tool; Developing strategies to obtain a good interaction with family members; and Teachers being facilitators of the interaction with family members. To be acquainted with this experience has led to the understanding of the need to include the theme of family care in the curriculum of the Technical Nursing Course. Additionally, the present study contributed to reflections on the importance of such knowledge for this population and to the development of future studies, as this theme has been scarcely explored in the literature.

  20. Space weathering of small Koronis family members

    Science.gov (United States)

    Thomas, Cristina A.; Rivkin, Andrew S.; Trilling, David E.; Enga, Marie-therese; Grier, Jennifer A.

    2011-03-01

    The space weathering process and its implications for the relationships between S- and Q-type asteroids and ordinary chondrite meteorites is an often debated topic in asteroid science. Q-type asteroids have been shown to display the best spectral match to ordinary chondrites (McFadden, L.A., Gaffey, M.J., McCord, T.B. [1985]. Science 229, 160-163). While the Q-types and ordinary chondrites share some spectral features with S-type asteroids, the S-types have significantly redder spectral slopes than the Q-types in visible and near-infrared wavelengths. This reddening of spectral slope is attributed to the effects of space weathering on the observed surface composition. The analysis by Binzel et al. (Binzel, R.P., Rivkin, A.S., Stuart, J.S., Harris, A.W., Bus, S.J., Burbine, T.H. [2004]. Icarus 170, 259-294) provided a missing link between the Q- and S-type bodies in near-Earth space by showing a reddening of spectral slope in objects from 0.1 to 5 km that corresponded to a transition from Q-type to S-type asteroid spectra, implying that size, and therefore surface age, is related to the relationship between S- and Q-types. The existence of Q-type asteroids in the main-belt was not confirmed until Mothé-Diniz and Nesvorny (Mothé-Diniz, T., Nesvorny, D. [2008]. Astron. Astrophys. 486, L9-L12) found them in young S-type clusters. The young age of these families suggest that the unweathered surface could date to the formation of the family. This leads to the question of whether older S-type main-belt families can contain Q-type objects and display evidence of a transition from Q- to S-type. To answer this question we have carried out a photometric survey of the Koronis family using the Kitt Peak 2.1 m telescope. This provides a unique opportunity to compare the effects of the space weathering process on potentially ordinary chondrite-like bodies within a population of identical initial conditions. We find a trend in spectral slope for objects 1-5 km that shows the

  1. Patient and family members perspectives on radioactive iodine treatment

    Energy Technology Data Exchange (ETDEWEB)

    McGrath, P.; Fitch, M.I. [Toronto-Sunnybrook Regional Cancer Centre, Toronto, Ontario (Canada)

    1999-08-01

    This report documents the findings of a survey of patients who received radioactive iodine therapy and their family members. The main objective of the survey was to gain an understanding of the experience of receiving radioactive iodine from the patient and family's perspective. The data from this study helped to inform the ARCP and GMA as they developed AC-9 - Principles of the management of radionuclide therapies. A survey was distributed to 700 patients and family members through physicians at 8 sites across Canada. Locations included: Newfoundland, Nova Scotia, Ontario (2 sites), Quebec (2 sites), Manitoba and British Columbia. A total of 190 patients and 140 family members returned completed surveys. Data was analyzed separately for individuals treated as inpatients and those treated as outpatients. The results of the survey provided a perspective from patients and families about their experiences regarding radioactive iodine therapy. The data indicate variation in patients' and family members' perspectives about how precautions are to be implemented. Both patients and family members expressed the desire for more information regarding many aspects of the treatment experience. The results have implications for the development of patient information, continuing education (in particular in the areas of precaution), the provision of access to supportive and counselling services, and the importance of looking at the individual situations of patients and their families. (author)

  2. Patient and family members perspectives on radioactive iodine treatment

    International Nuclear Information System (INIS)

    McGrath, P.; Fitch, M.I.

    1999-08-01

    This report documents the findings of a survey of patients who received radioactive iodine therapy and their family members. The main objective of the survey was to gain an understanding of the experience of receiving radioactive iodine from the patient and family's perspective. The data from this study helped to inform the ARCP and GMA as they developed AC-9 - Principles of the management of radionuclide therapies. A survey was distributed to 700 patients and family members through physicians at 8 sites across Canada. Locations included: Newfoundland, Nova Scotia, Ontario (2 sites), Quebec (2 sites), Manitoba and British Columbia. A total of 190 patients and 140 family members returned completed surveys. Data was analyzed separately for individuals treated as inpatients and those treated as outpatients. The results of the survey provided a perspective from patients and families about their experiences regarding radioactive iodine therapy. The data indicate variation in patients' and family members' perspectives about how precautions are to be implemented. Both patients and family members expressed the desire for more information regarding many aspects of the treatment experience. The results have implications for the development of patient information, continuing education (in particular in the areas of precaution), the provision of access to supportive and counselling services, and the importance of looking at the individual situations of patients and their families. (author)

  3. Death at the Worksite: Helping Grieving Family Members

    Science.gov (United States)

    ... Grief at Work Working Through Grief About Us Death at the Worksite: Helping Grieving Family Members By ... fatal heart attacks occur in the workplace. Other deaths — from accidents, for example — can also happen during ...

  4. Mental Wellbeing of Family Members of Autistic Adults.

    Science.gov (United States)

    Herrema, Renske; Garland, Deborah; Osborne, Malcolm; Freeston, Mark; Honey, Emma; Rodgers, Jacqui

    2017-11-01

    Family members are often the primary caregiver for autistic adults and this responsibility may impact on the carer's wellbeing and quality of life. 109 family members of autistic adults completed an online survey assessing their wellbeing relating to their caring role for their autistic relative. Family members who were supporting an autistic relative with co-occurring mental health difficulties and who they reported as unprepared for the future, self-reported higher levels of worry, depression, anxiety and stress, and poorer quality of life. These findings emphasise the importance of support for family members of autistic adults, whether through external services to support their relative or individual mental health support for the carer.

  5. Spectra of small Koronis family members

    Science.gov (United States)

    Thomas, C.; Rivkin, A.; Trilling, D.; Moskovitz, N.

    2014-07-01

    The space-weathering process and its implications for the relationships between S- and Q-type asteroids and ordinary chondrite meteorites are long-standing problems in asteroid science. Although the visible and near-infrared spectra of S- and Q-type objects qualitatively show the same absorption features and quantitatively show evidence of the same minerals, the S types display increased spectral slopes and muted absorption features compared to the Q types. This spectral mismatch is consistent with the effects of the space weathering process. Binzel et al. provided the missing link between Q- and S-type bodies in near-Earth space by showing a reddening of spectral slope in objects from 0.1 to 5 km that corresponded to the transition from Q- to S-type spectra. This result implied that size, and therefore age, is related to the relationship between Q- and S-type. The existence of Q-type objects in the main belt was not confirmed until Mothe-Diniz and Nesvorny (2008) found them in young S-type clusters. To investigate the trend from Q to S in the main belt, we examined space weathering within the old main-belt Koronis family using a spectrophotometric survey (Rivkin et al. 2011, Thomas et al. 2011). Rivkin et al. (2011) identified several potential Q-type objects within the Koronis family. Our Q-type candidates were identified using broad-band spectrophotometry and could not be taxonomically classified on that basis alone. We obtained follow-up visible and near-infrared spectral observations of our potential Q-type objects, (26970) Elias, (45610) 2000 DJ_{48}, and (37411) 2001 XF_{152}, using Gemini and Magellan. We will present the results of these spectral follow-up observations. Observations of (26970) Elias demonstrate that the object is more consistent with the average Q-type spectrum than the average S-type spectrum.

  6. Understanding type 2 diabetes: including the family member's perspective.

    LENUS (Irish Health Repository)

    White, Patricia

    2012-02-01

    PURPOSE: The purpose of this study was to examine the relationship between psychological and social factors and diabetes outcomes in people with type 2 diabetes and their family members. METHODS: A total of 153 patients with type 2 diabetes were assessed at a diabetes outpatient clinic and postal questionnaires were sent to nominated family members. The measures examined were diabetes knowledge, social support, well-being, and illness perceptions. RESULTS: When compared with those with diabetes, family members reported lower positive well-being and lower levels of satisfaction with support. They also perceived diabetes as a more cyclical illness, which was controlled more by treatment than by the individual. Family members also reported that the person with diabetes was more emotionally distressed and knew more about diabetes than the patient had actually reported himself or herself. There were no differences between the family members of those in good or poor glycaemic control. CONCLUSIONS: This study reinforces the importance of understanding social context and illness beliefs in diabetes management. It also highlights the potential for including family members in discussions and education about diabetes management.

  7. Involvement of p38 MAPK- and JNK-modulated expression of Bcl-2 and Bax in Naja nigricollis CMS-9-induced apoptosis of human leukemia K562 cells.

    Science.gov (United States)

    Chen, Ying-Jung; Liu, Wen-Hsin; Kao, Pei-Hsiu; Wang, Jeh-Jeng; Chang, Long-Sen

    2010-06-15

    CMS-9, a phospholipase A(2) (PLA(2)) isolated from Naja nigricollis venom, induced apoptosis of human leukemia K562 cells, characterized by mitochondrial depolarization, modulation of Bcl-2 family members, cytochrome c release and activation of caspases 9 and 3. Moreover, an increase in intracellular Ca2+ concentration and the production of reactive oxygen species (ROS) was noted. Pretreatment with BAPTA-AM (Ca2+ chelator) and N-acetylcysteine (NAC, ROS scavenger) proved that Ca2+ was an upstream event in inducing ROS generation. Upon exposure to CMS-9, activation of p38 MAPK and JNK was observed in K562 cells. BAPTA-AM or NAC abrogated CMS-9-elicited p38 MAPK and JNK activation, and rescued viability of CMS-9-treated K562 cells. SB202190 (p38 MAPK inhibitor) and SP600125 (JNK inhibitor) suppressed CMS-9-induced dissipation of mitochondrial membrane potential, Bcl-2 down-regulation, Bax up-regulation and increased mitochondrial translocation of Bax. Inactivation of PLA(2) activity reduced drastically the cytotoxicity of CMS-9, and a combination of lysophosphatidylcholine and stearic acid mimicked the cytotoxic effects of CMS-9. Taken together, our data suggest that CMS-9-induced apoptosis of K562 cells is catalytic activity-dependent and is mediated through mitochondria-mediated death pathway triggered by Ca2+/ROS-evoked p38 MAPK and JNK activation. 2010 Elsevier Ltd. All rights reserved.

  8. REGISTRATION OF VEHICLES IN SWITZERLAND: MEMBERS OF THE FAMILY OF A MEMBER OF THE PERSONNEL

    CERN Multimedia

    Service des Relations avec les Pays Hôtes

    1999-01-01

    The Permanent Mission of Switzerland to the International Organisations in Geneva has informed CERN that members of the family of a member of the personnel who hold a carte delégitimation or a Ci permit may not register a vehicle in Switzerland. Only those members of the family who are of Swiss nationality or hold an ordinary permit (e.g. a 'B' or 'C' permit) may register vehicles in their own names.Relations with the Host States Servicehttp://www.cern.ch/relations/Tel. 72848

  9. Registered Nurses working together with family members of older people.

    Science.gov (United States)

    Weman, Karin; Fagerberg, Ingegerd

    2006-03-01

    The aim of the study was to reach a more profound understanding, through looking at nurses' working situation, of those factors that influence how nurses are able to work together with family members of older people living in nursing homes or similar facilities. Working with the care of older people as a Registered Nurse provides a varied job with many challenges. Nurses have to co-operate with family members of those in community health care. Co-operation is important and necessary for all involved. Nurses working in elder care in a geographically defined area received a questionnaire with three open-ended questions, on the difficulties and/or problems involved with working together with family members, and the positive or negative aspects of this co-operation. Analysis was carried out using the latent content analysis method. Three themes, problems within the system, interaction with families and caring in nursing work, are presented with categories and their subcategories. The nurses wanted their superior to be a nurse so that their working situation would be better understood. Appreciation from their superior and family members was also a very important part of their work as nurses in community health care. The frequent changes and the lack of time in the work of elder care often put nurses under considerable psychological pressure. For the most part family members are a resource for the elder, but sometimes they will avoid contact, which will make co-operating difficult. Registered Nurses and family members are dependent on each other in their care of the elder. Relevance to clinical practice. More attention should be paid to the working situation of Registered Nurses in community health care, and their ability to work together with family members of older people.

  10. Family members' unique perspectives of the family: examining their scope, size, and relations to individual adjustment.

    Science.gov (United States)

    Jager, Justin; Bornstein, Marc H; Putnick, Diane L; Hendricks, Charlene

    2012-06-01

    Using the McMaster Family Assessment Device (Epstein, Baldwin, & Bishop, 1983) and incorporating the perspectives of adolescent, mother, and father, this study examined each family member's "unique perspective" or nonshared, idiosyncratic view of the family. We used a modified multitrait-multimethod confirmatory factor analysis that (a) isolated for each family member's 6 reports of family dysfunction the nonshared variance (a combination of variance idiosyncratic to the individual and measurement error) from variance shared by 1 or more family members and (b) extracted common variance across each family member's set of nonshared variances. The sample included 128 families from a U.S. East Coast metropolitan area. Each family member's unique perspective generalized across his or her different reports of family dysfunction and accounted for a sizable proportion of his or her own variance in reports of family dysfunction. In addition, after holding level of dysfunction constant across families and controlling for a family's shared variance (agreement regarding family dysfunction), each family member's unique perspective was associated with his or her own adjustment. Future applications and competing alternatives for what these "unique perspectives" reflect about the family are discussed. PsycINFO Database Record (c) 2012 APA, all rights reserved.

  11. Family Members' Unique Perspectives of the Family: Examining their Scope, Size, and Relations to Individual Adjustment

    Science.gov (United States)

    Jager, Justin; Bornstein, Marc H.; Diane, L. Putnick; Hendricks, Charlene

    2012-01-01

    Using the Family Assessment Device (FAD; Epstein, Baldwin, & Bishop, 1983) and incorporating the perspectives of adolescent, mother, and father, this study examined each family member's “unique perspective” or non-shared, idiosyncratic view of the family. To do so we used a modified multitrait-multimethod confirmatory factor analysis that (1) isolated for each family member's six reports of family dysfunction the non-shared variance (a combination of variance idiosyncratic to the individual and measurement error) from variance shared by one or more family members and (2) extracted common variance across each family member's set of non-shared variances. The sample included 128 families from a U.S. East Coast metropolitan area. Each family member's unique perspective generalized across his or her different reports of family dysfunction and accounted for a sizable proportion of his or her own variance in reports of family dysfunction. Additionally, after holding level of dysfunction constant across families and controlling for a family's shared variance (agreement regarding family dysfunction), each family member's unique perspective was associated with his or her own adjustment. Future applications and competing alternatives for what these “unique perspectives” reflect about the family are discussed. PMID:22545933

  12. BET inhibition silences expression of MYCN and BCL2 and induces cytotoxicity in neuroblastoma tumor models.

    Directory of Open Access Journals (Sweden)

    Anastasia Wyce

    Full Text Available BET family proteins are epigenetic regulators known to control expression of genes involved in cell growth and oncogenesis. Selective inhibitors of BET proteins exhibit potent anti-proliferative activity in a number of hematologic cancer models, in part through suppression of the MYC oncogene and downstream Myc-driven pathways. However, little is currently known about the activity of BET inhibitors in solid tumor models, and whether down-regulation of MYC family genes contributes to sensitivity. Here we provide evidence for potent BET inhibitor activity in neuroblastoma, a pediatric solid tumor associated with a high frequency of MYCN amplifications. We treated a panel of neuroblastoma cell lines with a novel small molecule inhibitor of BET proteins, GSK1324726A (I-BET726, and observed potent growth inhibition and cytotoxicity in most cell lines irrespective of MYCN copy number or expression level. Gene expression analyses in neuroblastoma cell lines suggest a role of BET inhibition in apoptosis, signaling, and N-Myc-driven pathways, including the direct suppression of BCL2 and MYCN. Reversal of MYCN or BCL2 suppression reduces the potency of I-BET726-induced cytotoxicity in a cell line-specific manner; however, neither factor fully accounts for I-BET726 sensitivity. Oral administration of I-BET726 to mouse xenograft models of human neuroblastoma results in tumor growth inhibition and down-regulation MYCN and BCL2 expression, suggesting a potential role for these genes in tumor growth. Taken together, our data highlight the potential of BET inhibitors as novel therapeutics for neuroblastoma, and suggest that sensitivity is driven by pleiotropic effects on cell growth and apoptotic pathways in a context-specific manner.

  13. Mental health and family relations among people who inject drugs and their family members in Vietnam.

    Science.gov (United States)

    Li, Li; Tuan, Nguyen Anh; Liang, Li-Jung; Lin, Chunqing; Farmer, Shu C; Flore, Martin

    2013-11-01

    This article explores the association of people who inject drugs and their family members in terms of mental health and family relations. The objective was to understand the family context and its impact on people who inject drugs in a family-oriented culture in Vietnam. Cross-sectional assessment data were gathered from 83 people who inject drugs and 83 of their family members recruited from four communes in Phú Thọ province, Vietnam. Depressive symptoms and family relations were measured for both people who inject drugs and family members. Internalized shame and drug-using behavior were reported by people who inject drugs, and caregiver burden was reported by family members. We found that higher level of drug using behavior of people who inject drugs was significantly associated with higher depressive symptoms and lower family relations reported by themselves as well as their family members. Family relations reported by people who inject drugs and their family members were positively correlated. The findings highlight the need for interventions that address psychological distress and the related challenges faced by family members of people who inject drugs. The article has policy implication which concludes with an argument for developing strategies that enhance the role of families in supporting behavioral change among people who inject drugs. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Strategies needed to involve men, other family members.

    Science.gov (United States)

    Barnett, B

    1998-01-01

    Women typically do not make decisions about contraceptive use and family planning on their own, and many women often have little, if any, decision-making power in the home. Strategies are therefore needed to empower women, educate family members, and involve men in reproductive health programs. Policymakers should expand the range of male services and encourage the greater use of male contraceptive methods. Furthermore, health programs should include counseling to help men and women improve their communications skills and conduct education campaigns to inform men about the roles they can play in family planning. Men should also learn about the side effects of both male and female methods, since concern over method side effects can frustrate their support of family planning. Appropriate strategies can be tailored to meet individual group needs. Programs in Madagascar, Bangladesh, Honduras, and Nepal are described as examples of how the support of family members can positively affect family planning use and reproductive health.

  15. G3139, a Bcl-2 antisense oligodeoxynucleotide, induces clinical responses in VAD refractory myeloma

    NARCIS (Netherlands)

    van de Donk, N. W. C. J.; de Weerdt, O.; Veth, G.; Eurelings, M.; van Stralen, E.; Frankel, S. R.; Hagenbeek, A.; Bloem, A. C.; Lokhorst, H. M.

    2004-01-01

    Expression of Bcl-2 in multiple myeloma is associated with resistance to chemotherapeutic drugs. Conversely, suppression of Bcl-2 enhanced the chemosensitivity of myeloma cells in vitro. G3139 is an antisense oligodeoxynucleotide targeted to the first six codons of the Bcl-2 mRNA open reading frame.

  16. Si dios quiere: Hispanic families' experiences of caring for a seriously mentally ill family member.

    Science.gov (United States)

    Guarnaccia, P J; Parra, P; Deschamps, A; Milstein, G; Argiles, N

    1992-06-01

    Among Hispanics, the family is viewed as the primary care giver for seriously mentally ill family members. This paper reports on a study of minority families' conceptions of serious mental illness, of their interaction with mental health resources, and on the burdens experienced by families in caring for a seriously mentally ill family member. The focus of this paper is on Hispanic families in New Jersey, with some comparative data from other ethnic group families. Families' conceptions of serious mental illness are explored and analyzed to demonstrate the importance of concepts of nervios and fallo mental in shaping families' responses to their ill family member. Social support systems for families are also explored with particular attention to the role of religious institutions and religious healing as a major source of solace.

  17. Onco-miR-24 regulates cell growth and apoptosis by targeting BCL2L11 in gastric cancer

    Directory of Open Access Journals (Sweden)

    Haiyang Zhang

    2016-01-01

    Full Text Available ABSTRACT Gastric cancer is one of the most common malignancies worldwide; however, the molecular mechanism in tumorigenesis still needs exploration. BCL2L11 belongs to the BCL-2 family, and acts as a central regulator of the intrinsic apoptotic cascade and mediates cell apoptosis. Although miRNAs have been reported to be involved in each stage of cancer development, the role of miR-24 in GC has not been reported yet. In the present study, miR-24 was found to be up-regulated while the expression of BCL2L11 was inhibited in tumor tissues of GC. Studies from both in vitro and in vivo shown that miR-24 regulates BCL2L11 expression by directly binding with 3′UTR of mRNA, thus promoting cell growth, migration while inhibiting cell apoptosis. Therefore, miR-24 is a novel onco-miRNA that can be potential drug targets for future clinical use.

  18. Orphan Nuclear Receptor NR4A1 Binds a Novel Protein Interaction Site on Anti-apoptotic B Cell Lymphoma Gene 2 Family Proteins.

    Science.gov (United States)

    Godoi, Paulo H C; Wilkie-Grantham, Rachel P; Hishiki, Asami; Sano, Renata; Matsuzawa, Yasuko; Yanagi, Hiroko; Munte, Claudia E; Chen, Ya; Yao, Yong; Marassi, Francesca M; Kalbitzer, Hans R; Matsuzawa, Shu-Ichi; Reed, John C

    2016-07-01

    B cell lymphoma gene 2 (Bcl-2) family proteins are key regulators of programmed cell death and important targets for drug discovery. Pro-apoptotic and anti-apoptotic Bcl-2 family proteins reciprocally modulate their activities in large part through protein interactions involving a motif known as BH3 (Bcl-2 homology 3). Nur77 is an orphan member of the nuclear receptor family that lacks a BH3 domain but nevertheless binds certain anti-apoptotic Bcl-2 family proteins (Bcl-2, Bfl-1, and Bcl-B), modulating their effects on apoptosis and autophagy. We used a combination of NMR spectroscopy-based methods, mutagenesis, and functional studies to define the interaction site of a Nur77 peptide on anti-apoptotic Bcl-2 family proteins and reveal a novel interaction surface. Nur77 binds adjacent to the BH3 peptide-binding crevice, suggesting the possibility of cross-talk between these discrete binding sites. Mutagenesis of residues lining the identified interaction site on Bcl-B negated the interaction with Nur77 protein in cells and prevented Nur77-mediated modulation of apoptosis and autophagy. The findings establish a new protein interaction site with the potential to modulate the apoptosis and autophagy mechanisms governed by Bcl-2 family proteins. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Bcl-2 silencing attenuates hypoxia-induced apoptosis resistance in pulmonary microvascular endothelial cells.

    Science.gov (United States)

    Cao, Yongmei; Jiang, Zhen; Zeng, Zhen; Liu, Yujing; Gu, Yuchun; Ji, Yingying; Zhao, Yupeng; Li, Yingchuan

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a life-threatening disorder that ultimately causes heart failure. While the underlying causes of this condition are not well understood, previous studies suggest that the anti-apoptotic nature of pulmonary microvascular endothelial cells (PMVECs) in hypoxic environments contributes to PAH pathogenesis. In this study, we focus on the contribution of Bcl-2 and hypoxia response element (HRE) to apoptosis-resistant endothelial cells and investigate the mechanism. PMVECs obtained from either normal rats or apoptosis-resistant PMVECs obtained from PAH rats were transduced with recombinant lentiviral vectors carrying either Bcl-2-shRNA or HRE combined Bcl-2-shRNA, and then cultured these cells for 24 h under hypoxic (5% O2) or normoxic (21% O2) conditions. In normal PMVECs, Bcl-2-shRNA or HRE combined with Bcl-2-shRNA transduction successfully decreased Bcl-2 expression, while increasing apoptosis as well as caspase-3 and P53 expression in a normoxic environment. In a hypoxic environment, the effects of Bcl-2-shRNA treatment on cell apoptosis, and on Bcl-2, caspase-3, P53 expression were significantly suppressed. Conversely, HRE activation combined with Bcl-2-shRNA transduction markedly enhanced cell apoptosis and upregulated caspase-3 and P53 expression, while decreasing Bcl-2 expression. Furthermore, in apoptosis-resistant PMVECs, HRE-mediated Bcl-2 silencing effectively enhanced cell apoptosis and caspase-3 activity. The apoptosis rate was significantly depressed when Lv-HRE-Bcl-2-shRNA was combined with Lv-P53-shRNA or Lv-caspase3-shRNA transduction in a hypoxic environment. These results suggest that HRE-mediated Bcl-2 inhibition can effectively attenuate hypoxia-induced apoptosis resistance in PMVECs by downregulating Bcl-2 expression and upregulating caspase-3 and P53 expression. This study therefore reveals critical insight into potential therapeutic targets for treating PAH.

  20. Distribution and origins of members of the Family Portulacaceae ...

    African Journals Online (AJOL)

    The present day distribution of members of the family Portulacaceae shows that whilst some genera such as Portulaca L., and to some extent Montia L. and Talinum Adanson are cosmopolitan in distribution, others such as Ceraria Pearson and Stephens, Lyallia Hooker fil., Portulacaria Jacquin, Silvaea Philippi and ...

  1. [Life lessons of eight families donating organs of deceased family members].

    Science.gov (United States)

    Avilés R, Lissette; Rivera M, M Soledad; Catoni S, María Isabel

    2014-06-01

    Most organ donors are already death. Therefore family members become an essential link in the final decision for organ donation. To get acquainted about the life lessons of people who accepted donating an organ of a deceased family member. Qualitative research, in depth interviews to eight families that accepted donating an organ of a deceased family member. The interviews were analyzed using the method proposed by Streubert et al and modified by Rivera. The life lessons are described in six comprehensive categories. The painful experience changed towards the feeling that the loved one remains alive. This sensation generated a sense of pride in family members and sensitized them towards the painful experience of other people. Therefore, a desire to help and improve as humans beings was awakened. A compassionate approach towards families donating organs with improve organ donation and humanize the process.

  2. Energetic heavy ions overcome tumor radioresistance caused by overexpression of Bcl-2

    International Nuclear Information System (INIS)

    Hamada, Nobuyuki; Hara, Takamitsu; Omura-Minamisawa, Motoko; Funayama, Tomoo; Sakashita, Tetsuya; Sora, Sakura; Yokota, Yuichiro; Nakano, Takashi

    2008-01-01

    Background and purpose: Overexpression of Bcl-2 is frequent in human cancers and has been associated with radioresistance. Here we investigated the potential impact of heavy ions on Bcl-2 overexpressing tumors. Materials and methods: Bcl-2 cells (Bcl-2 overexpressing HeLa cells) and Neo cells (neomycin resistant gene-expressing HeLa cells) exposed to γ-rays or heavy ions were assessed for the clonogenic survival, apoptosis and cell cycle distribution. Results: Whereas Bcl-2 cells were more resistant to γ-rays (0.2 keV/μm) and helium ions (16.2 keV/μm) than Neo cells, heavy ions (76.3-1610 keV/μm) yielded similar survival regardless of Bcl-2 overexpression. Carbon ions (108 keV/μm) decreased the difference in the apoptotic incidence between Bcl-2 and Neo cells, and prolonged G 2 /M arrest that occurred more extensively in Bcl-2 cells than in Neo cells. Conclusions: High-LET heavy ions overcome tumor radioresistance caused by Bcl-2 overexpression, which may be explained at least in part by the enhanced apoptotic response and prolonged G 2 /M arrest. Thus, heavy-ion therapy may be a promising modality for Bcl-2 overexpressing radioresistant tumors

  3. Strengths of families to limit relapse in mentally ill family members

    African Journals Online (AJOL)

    Tlhalefi T. Tlhowe

    The purpose of this research was to explore and describe the strengths of .... In this review family strengths refer to qualities of families with a mentally ill .... they thought that their mentally ill family members were just acting out when ..... techniques, creative communication and praise as strengths. .... International Journal of.

  4. Family Decision Making: Benefits to Persons with Developmental Disabilities and Their Family Members

    Science.gov (United States)

    Neely-Barnes, Susan; Graff, J. Carolyn; Marcenko, Maureen; Weber, Lisa

    2008-01-01

    Family involvement in planning and choosing services has become a key intervention concept in developmental disability services. This study (N = 547) modeled patterns of family decision making and assessed benefits to persons with developmental disabilities (DDs) and their family members. A latent profile analysis identified 4 classes that were…

  5. Strengths of families to limit relapse in mentally ill family members ...

    African Journals Online (AJOL)

    Background: Relapse prevention in mental health care is important. Utilising the strengths of families can be a valuable approach in relapse prevention. Studies on family strengths have been conducted but little has been done on the strengths of family members to help limit relapse in mental health care users. The purpose ...

  6. Family presence during resuscitation: A descriptive study with Iranian nurses and patients' family members.

    Science.gov (United States)

    Zali, Mahnaz; Hassankhani, Hadi; Powers, Kelly A; Dadashzadeh, Abbas; Rajaei Ghafouri, Rouzbeh

    2017-09-01

    Family presence during resuscitation (FPDR) has advantages for the patients' family member to be present at the bedside. However, FPDR is not regularly practiced by nurses, especially in low to middle income countries. The purpose of this study was to determine Iranian nurses' and family members' attitudes towards FPDR. In a descriptive study, data was collected from the random sample of 178 nurses and 136 family members in four hospitals located in Iran. A 27-item questionnaire was used to collect data on attitudes towards FPDR, and descriptive and correlational analyses were conducted. Of family members, particularly the women, 57.2% (n=78) felt it is their right to experience FPDR and that it has many advantages for the family; including the ability to see that everything was done and worry less. However, 62.5% (n=111) of the nurses disagreed with an adult implementation of FPDR. Nurses perceived FPDR to have many disadvantages. Family members becoming distressed and interfering with the patient which may prolong the resuscitation effort. Nurses with prior education on FPDR were more willing to implement it. FPDR was desired by the majority of family members. To meet their needs, it is important to improve Iranian nurses' views about the advantages of the implementation of FPDR. Education on FPDR is recommended to improve Iranian nurses' views about the advantages of the implementation of FPDR. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Bcl-2 antisense therapy in B-cell malignant proliferative disorders.

    Science.gov (United States)

    Chanan-Khan, Asher; Czuczman, Myron S

    2004-08-01

    Overexpression of Bcl-2 oncogene has been clinically associated with an aggressive clinical course, chemotherapy and radiotherapy resistance, and poor survival in patients with malignant B-cell disorders. Patients with relapsed or refractory chronic lymphocytic leukemia, multiple myeloma, or non-Hodgkin's lymphoma have limited therapeutic options. Preclinical and early clinical data have shown that Bcl-2 oncoprotein can be decreased by Bcl-2 antisense therapy. Also, downregulation of Bcl-2 protein can result in reversal of chemotherapy resistance and improved antitumor activity of biologic agents. Various clinical trials are evaluating the role of targeting Bcl-2 as a mechanism to enhance the antitumor potential of chemotherapy and immunotherapy. Early results from these clinical studies are encouraging and confirm the proof of principle for antisense therapy. As current data mature, these trials will hopefully validate preliminary results and establish Bcl-2 antisense as an important addition to the current armamentarium used in the treatment of patients with B-cell neoplasms.

  8. Insider Research with Family Members who have a Member Living with Rare Cancer

    Directory of Open Access Journals (Sweden)

    Jan Foster PhD

    2009-12-01

    Full Text Available In this article the author explores insider research in relation to family members facing a diagnosis of rare cancer, using her experiences as one such family member undertaking doctoral research into journeys similar to hers. The “insider” issue is explored through three realms: the ethical realm, including issues of “fitness” to undertake the research; the methodological realm, including how data are obtained and used; and the trustworthiness realm, including research rigor. The exploration of her insider experiences includes personal challenges in relation to facing familiar emotionally charged experiences, insights gained as a result of her insider status, and her ability to join with participants in ways that might not be possible for an outsider. In the paper the author challenges taken-for-granted assumptions that trustworthiness can be assured only from the position of “objective” researcher. Rather, this analysis places knowledge gained through the processes and products of research as constituted and contextualized.

  9. Expression of Bcl-2 and Bax in extrahepatic biliary tract carcinoma and dysplasia

    Science.gov (United States)

    Li, Sheng-Mian; Yao, Shu-Kun; Yamamura, Nobuyoshi; Nakamura, Toshitsugu

    2003-01-01

    AIM: To compare the difference of expression of Bcl-2 and Bax in extrahepatic biliary tract carcinoma and dysplasia, and to analyze the role of Bcl-2 and Bax proteins in the progression from dysplasia to carcinoma and to evaluate the correlation of Bcl-2/Bax protein expression with the biological behaviors. METHODS: Expressions of Bcl-2 and Bax were examined immunohistochemically in 27 cases of extrahepatic biliary tract carcinomas (bile duct carcinoma: n = 21, carcinoma of ampulla of Vater: n = 6), and 10 cases of atypical dysplasia. Five cases of normal biliary epithelial tissues were used as controls. A semiquantitative scoring system was used to assess the Bcl-2 and Bax reactivity. RESULTS: The expression of Bcl-2 was observed in 10 out of 27 (37.0%) invasive carcinomas, 1 out of 10 dysplasias, none out of 5 normal epithelial tissues. Bax expression rate was 74.1% (20/27) in invasive carcinoma, 30% (3/10) in dysplasia, and 40% (2/5) in normal biliary epithelium. Bcl-2 and Bax activities were more intense in carcinoma than in dysplasia, with no significant difference in Bcl-2 expression (P = 0.110), and significant difference in Bax expression (P = 0.038). Level of Bax expression was higher in invasive carcinoma than in dysplasia and normal tissue (P = 0.012). Bcl-2 expression was correlated to Bax expression (P = 0.0059). However, Bcl-2/Bax expression had no correlation with histological subtype, grade of differentiation, or level of invasion. CONCLUSION: Increased Bcl-2/Bax expression from dysplasia to invasive tumors supports the view that this is the usual route for the development of extrahepatic biliary tract carcinoma. Bcl-2/Bax may be involved, at least in part, in the apoptotic activity in extrahepatic biliary carcinoma. PMID:14606101

  10. Stress experiences of family members of registered sex offenders.

    Science.gov (United States)

    Tewksbury, Richard; Levenson, Jill

    2009-01-01

    The collateral consequences of sex offender registration and notification (SORN) have been well established, although little evidence has supported the efficacy of SORN. Based on the belief that family members provide some of the most consistent, important, and intense forms of support for criminal offenders in general and registered sex offenders (RSOs) more specifically, the experiences of sanctions, losses, and stresses of these individuals is examined. Using survey responses from 584 individuals known to visit online support and advocacy groups for RSOs and their loved ones, this study identifies the stress levels and stressors experienced by this population. Findings show that family members of RSOs experience high levels of social isolation, fear, shame, property damage, and forced residential relocation. Perceived stress is significantly higher for those who are of lower economic means, feel isolated, have high levels of fear and shame/embarrassment, or were forced to move. (c) 2009 John Wiley & Sons, Ltd.

  11. Predictive value of bcl-2 immunoreactivity in prostate cancer patients treated with radiotherapy

    International Nuclear Information System (INIS)

    Bylund, A.; Widmark, A.; Stattin, P.; Bergh, A.

    1998-01-01

    Background and purpose: Recent experimental evidence suggests that overexpression of bcl-2, a protein functioning by blocking apoptosis, may influence the treatment outcome in human tumours, including prostate cancer. To test the clinical implications of this hypothesis, tumours from patients with prostate cancer treated with external beam radiotherapy were investigated for bcl-2 immunoreactivity (IR) and correlated with prognosis and treatment outcome. Materials and methods: Bcl-2 IR was evaluated in archival tumour specimens obtained through transurethral resection from 42 patients with localized prostate cancer (T0-T4, N0 and M0). Bcl-2 IR expression was related to stage, grade and cancer-specific survival. Specimens were obtained prior to administrating routine radiotherapy for all patients. Results: Bcl-2 IR was present in 19/42 (45%) tumours. The bcl-2-positive patients had a significantly longer cancer-specific survival than the bcl-2-negative patients (10.3 versus 3.4 years, P<0.04). At follow-up (7-19 years), nine patients were still alive, 26 patients had died of prostate cancer and seven patients had died of other causes. Conclusions: This study indicates that pre-treatment bcl-2 overexpression is related to a favourable outcome in prostate cancer treated with radiotherapy. Low bcl-2 along with a high stage may be a predictor of poor prognosis and these patients might benefit from additional treatment. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  12. Size distributions of member asteroids in seven Hirayama families

    International Nuclear Information System (INIS)

    Mikami, Takao; Ishida, Keiichi.

    1990-01-01

    The size distributions of asteroids in the seven Hirayama families are studied for newly assigned member asteroids in the diameter range of about 10 to 100 km. The size distributions for the different families are expressed by the power-law functions with distinctly different power-law indices. The power-law indices for families with small mean orbital inclinations are about 2.5 to 3.0. On the other hand, the power-law indices for families with large mean orbital inclinations are significantly smaller than 2.5. This indicates that the smaller asteroids were removed preferentially from these families after their formation. It is thought that the smaller asteroids left behind the families were dispersed into the main belt. It is consistent with the fact that the power-law index for the size distribution of asteroids with diameters smaller than 25 km in the main belt is larger than the power-law indices for the size distributions of asteroids in the families. This segregation due to the asteroid size can be caused by a drag force caused by the ambient matter deposited on the invariable place of the solar system during the early evolutionary stage. (author)

  13. The challenges of reintegration for service members and their families.

    Science.gov (United States)

    Danish, Steven J; Antonides, Bradley J

    2013-10-01

    The ongoing wars in Afghanistan and Iraq have posed a number of reintegration challenges to service members. Much of the research focuses on those service members experiencing psychological problems and being treated at the VA. In this article, we contend that much of the distress service members experience occurs following deployment and is a consequence of the difficulties encountered during their efforts to successfully reintegrate into their families and communities. We propose a new conceptual framework for intervening in this reintegration distress that is psycho-educational in nature as well as a new delivery model for providing such services. An example of this new intervention framework is presented. © 2013 American Orthopsychiatric Association.

  14. Whole exome sequencing identified 1 base pair novel deletion in BCL2-associated athanogene 3 (BAG3) gene associated with severe dilated cardiomyopathy (DCM) requiring heart transplant in multiple family members.

    Science.gov (United States)

    Rafiq, Muhammad Arshad; Chaudhry, Ayeshah; Care, Melanie; Spears, Danna A; Morel, Chantal F; Hamilton, Robert M

    2017-03-01

    Dilated cardiomyopathy (DCM) is characterized by dilation and impaired contraction of the left ventricle or both ventricles. Among hereditary DCM, the genetic causes are heterogeneous, and include mutations encoding cytoskeletal, nucleoskeletal, mitochondrial, and calcium-handling proteins. We report three severely affected males, in a four-generation pedigree, with DCM phenotype who underwent cardiac transplant. Cardiomegaly with marked biventricular dilation and fibrosis were noticeable histopathological findings. The affected males had tested negative on a 46-gene pancardiomyopathy panel. Whole Exome Sequencing (WES) was performed to reveal mutation in the gene responsible in generation of DCM phenotypes. The 1-bp (Chr10:121435979delC; c.913delC) novel heterozygous deletion in exon 4 of BAG3, was identified in three affected males, resulted in frame-shift and a premature termination codon (p.Met306-Stop) producing a truncated BAG3 protein lacking functionally important PXXP and BAG domains. WES data were further utilized to map 10 SNP markers around the discovered mutation to generate shared disease haplotype in all affected individuals encompassing 11 Mb on 10q25.3-26.2 harboring BAG3. Finally genotypes were inferred for the unavailable/deceased individuals in the pedigrees. Here we propose that Chr10:121435979delC in BAG3 is a causal mutation in these subjects. Our and earlier studies indicate that BAG3 mutations are associated with DCM phenotypes. BAG3 should be added to cardiomyopathy gene panels for screening of DCM patients, and patients previously considered gene elusive should undergo sequencing of the BAG3 gene. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. Distribution of transglutaminase family members in mouse whole body sections.

    Science.gov (United States)

    Tatsukawa, Hideki; Abe, Natsumi; Ohashi, Shintaro; Hitomi, Kiyotaka

    2015-11-27

    Transglutaminases (TGs) comprise a protein family in which the members catalyze the formation of isopeptide bonds between glutamine and lysine residues in various proteins. Eight enzymes have been identified and designated as factor XIII (FXIII) and TG1-7. Expression studies of four major members, i.e., FXIII, TG1, TG2, and TG3, have been performed in a relatively large number of mammalian tissues in comparison with those on the other isozymes. The structural and biochemical characteristics of these individual isozymes and expression analyses of TG family in some tissue extracts have been reported, but there have been no simultaneous comparative analyses of both their mRNA and protein expression patterns in tissues distributions. Thus, we developed novel experimental systems for in situ hybridization using cryofilm attached to whole body sections of neonatal mice, thereby obtaining data regarding the tissue distributions of the major TG isozymes. In this study, we performed the first detailed comparative analysis of the mRNA and protein distribution studies of TG family members in a wide range of mouse tissues. These data will be helpful for elucidating the unknown physiological and pathological functions of TGs. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Stromal-dependent tumor promotion by MIF family members.

    Science.gov (United States)

    Mitchell, Robert A; Yaddanapudi, Kavitha

    2014-12-01

    Solid tumors are composed of a heterogeneous population of cells that interact with each other and with soluble and insoluble factors that, when combined, strongly influence the relative proliferation, differentiation, motility, matrix remodeling, metabolism and microvessel density of malignant lesions. One family of soluble factors that is becoming increasingly associated with pro-tumoral phenotypes within tumor microenvironments is that of the migration inhibitory factor family which includes its namesake, MIF, and its only known family member, D-dopachrome tautomerase (D-DT). This review seeks to highlight our current understanding of the relative contributions of a variety of immune and non-immune tumor stromal cell populations and, within those contexts, will summarize the literature associated with MIF and/or D-DT. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. [Music in human terminality: the family members' conceptions].

    Science.gov (United States)

    Sales, Catarina Aparecida; da Silva, Vladimir Araujo; Pilger, Calíope; Marcon, Sonia Silva

    2011-03-01

    This qualitative study was performed using the multiple case study method and Heidegger's existential phenomenology for data analysis. The objective was to understand how family members perceive the influence of musical experiences on the physical and mental health of a relative living with a terminal illness. Participants were seven individuals belonging to two families. Data collection was performed through interviews and observation from May to June 2009. Results showed that using music while providing care to beings living with cancer can provide well-being to patients as well as their caregivers. Considering the deficit of leisure and the monotony of the home environment, using music contemplates the philosophical and humanitarian precepts of palliative care, thus being characterized as a complementary resource to nursing care, as besides being a communication resource, it improves the interpersonal relationship between patients and their families.

  18. The role of BIM-EL and BCL2-α on the efficacy of erlotinib and gefitinib in lung cancer.

    Science.gov (United States)

    Simasi, Jacinta; Oelkrug, Christopher; Schubert, Andreas; Nieber, Karen; Gillissen, Adrian

    2015-04-01

    Tyrosine kinase inhibitors (TKI), erlotinib and gefitinib are small molecule inhibitors which are used for the treatment of lung cancer. But, the development of drug resistance has been reported as one of the major setbacks in oncology. This study focused on the mechanisms leading to secondary resistance by assessing the gene expression of BCL2 family proteins which are associated with the intrinsic apoptotic signaling pathway. 8 genes were investigated in erlotinib and gefitinib treated cells by real time PCR and protein analysis by western blotting. The cells were exposed to the test drugs 48h prior to RNA or protein isolation. It was observed that BIM-EL, a pro-apoptotic protein was up-regulated in cells sensitive to the drugs but not in the resistant cells. On the other hand BCL2-α, an anti-apoptotic protein was up-regulated in the resistant cells and not in the sensitive cells. BCL2-α revealed a counter-regulation effect on BIM-EL and this effect is probably one of the causes of secondary resistance to erlotinib and gefitinib. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Family Members as Third Parties in Dyadic Family Conflict: Strategies, Alliances, and Outcomes.

    Science.gov (United States)

    Vuchinich, Samuel; And Others

    1988-01-01

    Analyzes conflicts of 52 families observed during dinner. Findings suggest that family members frequently joined dyadic conflicts, they were equally likely to attempt to end or continue conflicts, they formed alliances half of the time, and their intervention strategies were related to the patterning and outcome of the conflicts. (RJC)

  20. Expression of bcl-2 in the Epithelial Lining of Odontogenic Keratocysts

    Directory of Open Access Journals (Sweden)

    Gh. Jahanshahi

    2006-03-01

    Full Text Available Statement of Problem: The aggressive nature and high recurrence rate of Odontogenic Keratocysts (OKCs may be due to unknown factors inherent in the epithelium or because of enzymatic activity in the fibrous wall. Bcl-2 protein is characterized by its ability to inhibit apoptosis.Purpose: The aim of the present study was to analyze the expression of bcl-2 protein in OKCs and to compare it with the more common radicular and dentigerous cysts. The possible relationship between inflammation and bcl-2 expression was also investigated.Materials and Methods: Formalin fixed paraffin-embedded tissue sections of 20 OKCs, 20 radicular and 20 dentigerous cysts were immunohistochemically analyzed for immunoreactivity of the bcl-2 protein.Results: Bcl-2 expression was observed in 19 OKCs (95%, one radicular cyst (5%and one dentigerous cyst (5%. There was no statistically significant relationship between inflammation and the number of bcl-2 positive cells. Immunoreactivity was mainly noted in the basal or basal/supra basal layers.Conclusion: Considering the fact that bcl-2 over expression may lead to increased survival of epithelial cells, present study may demonstrate a possible relationship between the aggressive nature of OKC and the intrinsic growth potential of its lining epithelium. Furthermore a basal/supra basal distribution of bcl-2 positive cells was seen in some odontogenic keratocysts which may have a significant impact on the behavior of this cyst.

  1. Interphase FISH detection of BCL2 rearrangement in follicular lymphoma using breakpoint-flanking probes

    NARCIS (Netherlands)

    Vaandrager, J W; Schuuring, E; Raap, T; Philippo, K; Kleiverda, K; Kluin, P

    Rearrangement of the BCL2 gene is an important parameter for the differential diagnosis of non-Hodgkin lymphomas. Although a relatively large proportion of breakpoints is clustered, many are missed by standard PCR. A FISH assay is therefore desired. Up to now, a lack of probes flanking the BCL2 gene

  2. The effect of radiation on bcl-2 and bax in hyperplastic prostatic tissues

    International Nuclear Information System (INIS)

    Ma Qingjie; Li Yuxin; Gu Xinquan; Cao Xia; Zhao Jie; Kong Xiangbo; Cai Shanyu

    2004-01-01

    Aim: To investigate the expressions of bcl-2 and bax in benign prostatic hyperplasia (BPH) and the effect of β-rays on bcl-2 and bax. Methods: The expressions of bcl-2 and bax are studied by means of immunohistochemical method in 9 normal prostate (NP) and 15 BPH and 35 patients treated with 90Sr/90Y Prostatic Hyperplasia Applicator. Results: The expressions of bcl-2 in epithelia of NP and BPH are higher than that in stroma P<0.01=. The expressions of bcl-2 in epithelia and stroma of BPH are higher than that in NP P<0.01=. The expressions of bax in epithelia of NP are higher than that in BPH P<0.05=. However ,the expressions of bcl-2 in epithelia and stroma of BPH are higher than bax P<0.01 =. Compared with the control group, the expressions of bcl-2 in epithelia and stroma of BPH treated with 90Sr/90Y Prostatic Hyperplasia Applicator decreased and the expressions of bax increased P<0.01=. Conclusion: bcl-2 gene and bax gene play an important role in the regulation of prostatic apoptosis and the treatment of β-rays can accelerate the apoptosis of prostatic tissues. (authors)

  3. Experiences of Family Members of Dying Patients Receiving Palliative Sedation.

    Science.gov (United States)

    Tursunov, Olga; Cherny, Nathan I; Ganz, Freda DeKeyser

    2016-11-01

    To describe the experience of family members of patients receiving palliative sedation at the initiation of treatment and after the patient has died and to compare these experiences over time.
. Descriptive comparative study.
. Oncology ward at Shaare Zedek Medical Center in Jerusalem, Israel.
. A convenience sample of 34 family members of dying patients receiving palliative sedation. 
. A modified version of a questionnaire describing experiences of family members with palliative sedation was administered during palliative sedation and one to four months after the patient died. Descriptive statistics were used to describe the results of the questionnaire, and appropriate statistical analyses were conducted for comparisons over time.
. Experiences of family members and time.
. Most relatives were satisfied with the sedation and staff support. Palliative sedation was experienced as an ethical way to relieve suffering. However, one-third felt that it shortened the patient's life. An explanation of the treatment was given less than half of the time and was usually given on the same day treatment was started. This explanation was given by physicians and nurses. Many felt that they were not ready for changes in the patient's condition and wanted increased opportunities to discuss the treatment with oncology care providers. No statistically significant differences in experiences were found over time. 
. Relatives' experiences of palliative sedation were generally positive and stable over time. Important experiences included timing of the initiation of sedation, timing and quality of explanations, and communication.
. Nurses should attempt to initiate discussions of the possible role of sedation in the event of refractory symptoms and follow through with continued discussions. The management of refractory symptoms at the end of life, the role of sedation, and communication skills associated with decision making related to palliative sedation should be a

  4. Herpesvirus pan encodes a functional homologue of BHRF1, the Epstein-Barr virus v-Bcl-2

    Directory of Open Access Journals (Sweden)

    Williams Tracey

    2005-02-01

    Full Text Available Abstract Background Epstein-Barr virus (EBV latently infects about 90% of the human population and is associated with benign and malignant diseases of lymphoid and epithelial origin. BHRF1, an early lytic cycle antigen, is an apoptosis suppressing member of the Bcl-2 family. In vitro studies imply that BHRF1 is dispensable for both virus replication and transformation. However, the fact that BHRF1 is highly conserved not only in all EBV isolates studied to date but also in the analogous viruses Herpesvirus papio and Herpesvirus pan that infect baboons and chimpanzees respectively, suggests BHRF1 may play an important role in vivo. Results Herpesvirus papio BHRF1 has been shown to function in an analogous manner to EBV BHRF1 in response to DNA damaging agents in human keratinocytes. In this study we show that the heterologous expression of the previously uncharacterised Herpesvirus pan BHRF1 in the human Burkitt's lymphoma cell line Ramos-BL provides similar anti-apoptotic functions to that of EBV BHRF1 in response to apoptosis triggered by serum withdrawal, etoposide treatment and ultraviolet (UV radiation. We also map the amino acid changes onto the recently solved structure of the EBV BHRF1 and reveal that these changes are unlikely to alter the 3D structure of the protein. Conclusions These findings show that the functional conservation of BHRF1 extends to a lymphoid background, suggesting that the primate virus proteins interact with cellular proteins that are themselves highly conserved across the higher primates. Further weight is added to this suggestion when we show that the difference in amino acid sequences map to regions on the 3D structure of EBV BHRF1 that are unlikely to change the conformation of the protein.

  5. TIC10/ONC201 synergizes with Bcl-2/Bcl-xL inhibition in glioblastoma by suppression of Mcl-1 and its binding partners in vitro and in vivo.

    Science.gov (United States)

    Karpel-Massler, Georg; Bâ, Maïmouna; Shu, Chang; Halatsch, Marc-Eric; Westhoff, Mike-Andrew; Bruce, Jeffrey N; Canoll, Peter; Siegelin, Markus D

    2015-11-03

    Glioblastoma is the most frequent primary brain tumor in adults. Current therapeutic options are sparse and the prognosis of patients suffering from this disease is grim. Abundance in intratumoral heterogeneity among different deregulated signaling pathways is a hallmark of glioblastoma and likely accounts for its recurrence and resistance to treatment. Glioblastomas harbor a plethora of deregulated pathways driving tumor formation and growth. In this study, we show that TIC10/ONC201, a promising compound that is currently in planned clinical development, along with Bcl-2/Bcl-xL inhibition by ABT263 yields a strong synergistic antiproliferative effect on pediatric, adult, proneural glioblastoma and glioma stem-like cells. On the molecular level, treatment with TIC10/ONC201 results in a posttranslational decrease of the anti-apoptotic Bcl-2 family member, myeloid cell leukemia 1 (Mcl-1), through modulation of the chaperone Bag3 and the deubiquitinase Usp9X. Consistently, the combination treatment of TIC10/ONC201 and ABT263 required the presence of functional BAX and BAK to drive intrinsic apoptosis, but is surprisingly independent of the extrinsic apoptotic pathway. Moreover, the expression of Noxa protein was required for efficient apoptosis induction by TIC10/ONC201 and ABT263. Importantly, the drug combination of TIC10/ONC201 and the BH3-mimetic, ABT263, led to a regression of tumors in vivo, without any notable toxicity and side effects. Overall, TIC10/ONC201 along with Bcl-2/Bcl-xL inhibition holds significant promise as a novel potential approach for the treatment of recalcitrant tumors such as glioblastoma.

  6. Identification of an HLA-A*0201 restricted Bcl2-derived epitope expressed on tumors

    DEFF Research Database (Denmark)

    Wang, Mingjun; Johansen, Britta; Nissen, Mogens H

    2006-01-01

    A large number of human tumor-associated antigen-derived peptides have been identified that are recognized by CTLs in a MHC-I restricted fashion. The apoptosis inhibitory protein Bcl2 is overexpressed in many human cancers as part of their neoplastic phenotype. Since inhibition or loss of Bcl2...... from the amino acid sequence of the Bcl2 protein and its binding affinity for HLA-A*0201 was confirmed using a biochemical binding assay. We here demonstrate that the 9-mer peptide Bcl2(85-93) induces specific CTL reactivity in immunized C57-A2K(b) or -A2D(b) tg mice. These Bcl2(85-93) specific CTLs...... react with and lyse Bcl2-expressing human colon carcinoma CCL220 cells which have been transfected with a chimeric HLA-A*0201/H2-K(b) DNA construct similar to that expressed in the transgenic mice. Based on these observations, we suggest that Bcl2(85-93) may be a target for immune therapy....

  7. The high price of depression: Family members' health conditions and health care costs.

    Science.gov (United States)

    Ray, G Thomas; Weisner, Constance M; Taillac, Cosette J; Campbell, Cynthia I

    2017-05-01

    To compare the health conditions and health care costs of family members of patients diagnosed with a Major Depressive Disorder (MDD) to family members of patients without an MDD diagnosis. Using electronic health record data, we identified family members (n=201,914) of adult index patients (n=92,399) diagnosed with MDD between 2009 and 2014 and family members (n=187,011) of matched patients without MDD. Diagnoses, health care utilization and costs were extracted for each family member. Logistic regression and multivariate models were used to compare diagnosed health conditions, health services cost, and utilization of MDD and non-MDD family members. Analyses covered the 5years before and after the index patient's MDD diagnosis. MDD family members were more likely than non-MDD family members to be diagnosed with mood disorders, anxiety, substance use disorder, and numerous other conditions. MDD family members had higher health care costs than non-MDD family members in every period analyzed, with the highest difference being in the year before the index patient's MDD diagnosis. Family members of patients with MDD are more likely to have a number of health conditions compared to non-MDD family members, and to have higher health care cost and utilization. Copyright © 2017. Published by Elsevier Inc.

  8. Witnesses to Transformation: Family Member Experiences Providing Individualized Music to Their Relatives with Dementia

    Science.gov (United States)

    Johnston, Elizabeth; Rasmusson, Xeno; Foyil, Barbara; Shopland, Patricia

    2017-01-01

    Content analysis of 35 family members stories found that sharing individualized music enhanced memory, mood and provided interactive opportunities, where family members connected and communicated with relatives who had dementia. Technology supports a positive new role for family members, who often use MP3 players (e.g. iPods), headphones,…

  9. The Bcl-2-Beclin 1 interaction in (-)-gossypol-induced autophagy versus apoptosis in prostate cancer cells.

    Science.gov (United States)

    Lian, Jiqin; Karnak, David; Xu, Liang

    2010-11-01

    Bcl-2 is a key dual regulator of autophagy and apoptosis, but how the level of Bcl-2 influences the cellular decision between autophagy and apoptosis is unclear. The natural BH3-mimetic (-)-gossypol preferentially induces autophagy in androgen-independent (AI) prostate cancer cells that have high levels of Bcl-2 and are resistant to apoptosis, whereas apoptosis is preferentially induced in androgen-dependent or -independent cells with low Bcl-2. (-)-Gossypol induces autophagy via blocking Bcl-2-Beclin 1 interaction at the endoplasmic reticulum (ER), together with downregulating Bcl-2, upregulating Beclin 1 and activating the autophagic pathway. Furthermore, (-)-gossypol-induced autophagy is Beclin 1- and Atg5-dependent. These results provide new insights into the mode of cell death induced by Bcl-2 inhibitors, which could facilitate the rational design of clinical trials by selecting patients who are most likely to benefit from the Bcl-2-targeted molecular therapy.

  10. "You Needed to Rehab...Families as Well": Family Members' Own Goals for Aphasia Rehabilitation

    Science.gov (United States)

    Howe, Tami; Davidson, Bronwyn; Worrall, Linda; Hersh, Deborah; Ferguson, Alison; Sherratt, Sue; Gilbert, Jocelyn

    2012-01-01

    Background: Aphasia affects family members in addition to the individuals with the communication disorder. In order to develop appropriate services for the relatives of people with aphasia post-stroke, their rehabilitation goals need to be identified. Aim: The aim of the current investigation was to identify the rehabilitation goals that family…

  11. [Brain injury knowledge in family members of neurosurgical patients].

    Science.gov (United States)

    Navarro-Main, Blanca; Castaño-León, Ana M; Munarriz, Pablo M; Gómez, Pedro A; Rios-Lago, Marcos; Lagares, Alfonso

    Several studies have shown misconceptions about brain injury in different populations. The aim of this study was to assess the knowledge and perceptions about brain injury of family members of neurosurgical patients in our hospital. The participants (n=81) were relatives of patients admitted to the neurosurgery department between February and August 2016. They voluntarily completed a 19-item true-false format survey about brain injury based on a translation of other questionnaires used in previous studies from other countries (USA, Canada, UK, Ireland and New Zealand). Also, some sociodemographic data were collected (age, sex, education level and the patient's pathology). Data analysis was developed through graphical modelling with a regularisation parameter plotted on a network representing the association of the items of the questionnaire from the response pattern of participants. Data analysis showed two conceptual areas with a high rate of wrong answers: behaviour and management of patients, and expectations about acquired brain injury recovery. The results obtained in this study would enable us to objectify misconceptions about acquired brain injury in patients' relatives attended in the neurosurgery department. This lack of knowledge could be a great obstacle in patients' recovery process. Therefore, we suggest placing the emphasis on the provision of information on brain injury to patients' families, especially with regard to its symptoms and course of development. Copyright © 2017 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. 29 CFR 825.124 - Needed to care for a family member or covered servicemember.

    Science.gov (United States)

    2010-07-01

    ..., DEPARTMENT OF LABOR OTHER LAWS THE FAMILY AND MEDICAL LEAVE ACT OF 1993 Coverage Under the Family and Medical Leave Act § 825.124 Needed to care for a family member or covered servicemember. (a) The medical... serious health condition, the family member is unable to care for his or her own basic medical, hygienic...

  13. Follow-Up Study to Family Members' Reactions to the Initial Special Education Meeting

    Science.gov (United States)

    Ingalls, Lawrence; Hammond, Helen; Paez, Carlos; Rodriguez, Ivan

    2016-01-01

    Family involvement is a central component of Individuals with Disabilities Education Act (IDEA). Family members are to be integrated in all aspects of the special education process. At the onset, of family involvement, it is imperative for educators to be aware of possible reactions family members may experience in this initial stage. This…

  14. Faustoviruses: Comparative genomics of new Megavirales family members

    Directory of Open Access Journals (Sweden)

    Samia eBenamar

    2016-02-01

    Full Text Available An emerging interest for the giant virus discovery process, genome sequencing and analysis has allowed an expansion of the number of known Megavirales members. Using the protist Vermamoeba sp. as cell support, a new giant virus named Faustovirus has been isolated. In this study, we describe the genome sequences of nine Faustoviruses and build a genomic comparison in order to have a comprehensive overview of genomic composition and diversity among this new virus family. The average sequence length of these viruses is 467,592.44 bp (ranging from 455,803 bp to 491,024 bp, making them the fourth largest Megavirales genome after Mimiviruses, Pandoraviruses and Pithovirus sibericum. Faustovirus genomes displayed an average G+C content of 37.14 % (ranging from 36.22% to 39.59% which is close to the G+C content range of the Asfarviridae genomes (38%. The proportion of best matches and the phylogenetic analysis suggest a shared origin with Asfarviridae without belonging to the same family. The core-gene-based phylogeny of Faustoviruses study has identified four lineages. These results were confirmed by the analysis of amino acids and COGs category distribution. The diversity of the gene composition of these lineages is mainly explained by gene deletion or acquisition and some exceptions for gene duplications. The high proportion of best matches from Bacteria and Phycodnaviridae on the pan-genome and unique genes may be explained by an interaction occurring after the separation of the lineages. The Faustovirus core-genome appears to consolidate the surrounding of 207 genes whereas the pan-genome is described as an open pan-genome, its enrichment via the discovery of new Faustoviruses is required to better seize all the genomic diversity of this family.

  15. BCL-2: Long and winding path from discovery to therapeutic target

    International Nuclear Information System (INIS)

    Schenk, Robyn L.; Strasser, Andreas; Dewson, Grant

    2017-01-01

    In 1988, the BCL-2 protein was found to promote cancer by limiting cell death rather than enhancing proliferation. This discovery set the wheels in motion for an almost 30 year journey involving many international research teams that has recently culminated in the approval for a drug, ABT-199/venetoclax/Venclexta that targets this protein in the treatment of cancer. This review will describe the long and winding path from the discovery of this protein and understanding the fundamental process of apoptosis that BCL-2 and its numerous homologues control, through to its exploitation as a drug target that is set to have significant benefit for cancer patients. - Highlights: • BCL-2 proteins control the intrinsic or mitochondrial pathway of apoptosis. • Defective apoptosis is a hallmark of cancer. • BH3-mimetics inhibit pro-survival BCL-2 proteins to induce cancer cell death. • ABT-199/venetoclax is approved for treatment of chronic lymphocytic leukaemia.

  16. Withaferin A Suppresses Anti-apoptotic BCL2, Bcl-xL, XIAP and ...

    African Journals Online (AJOL)

    apoptotic ... Quantitative real-time polymerase chain reaction (qPCR) was performed using Taq PCR Master ... Keywords: Anti-apoptotic genes, Cervical cancer, Apoptosis, Cell viability, BCL2, .... polyclonal anti-rabbit immunoglobulin HRP-linked.

  17. Effect of low dose ionizing radiation on Bcl-2 transcription level of Peyer's patches in mouse

    International Nuclear Information System (INIS)

    Liu Jiamei; Chen Dong; Zheng Yongchen; Liu Shuzheng

    2001-01-01

    Objective: To study the effect of whole body irradiation (WBI) with different doses of X-rays on apoptosis in cells of mouse Peyer's patches and its molecular mechanism. Methods: RT-PCR was used to detect the changes of Bcl-2 transcription level. Agarose electrophoresis and flow cytometry were used to detect the changes of DNA and apoptotic bodies in Peyer's patches after WBI with different doses of X-rays. Results: The apoptotic was increased and Bcl-2 transcription level was decreased in Peyer's patches after 2 Gy X-rays. The apoptotic rate was decreased and Bcl-2 transcription level was increased in Peyer's patches after 75 mGy X-rays. Conclusion: Bcl-2 participates in the regulation of radiation-induced apoptosis in Peyer's patches

  18. Female children with incarcerated adult family members at risk for lifelong neurological decline.

    Science.gov (United States)

    Brewer-Smyth, Kathleen; Pohlig, Ryan T; Bucurescu, Gabriel

    2016-07-01

    A secondary analysis of data from adult female prison inmates in the mid-Atlantic United States defined relationships between having incarcerated adult family members during childhood and neurological outcomes. Of 135 inmates, 99 (60%) had one or more incarcerated adult family members during childhood. Regression analyses revealed that having incarcerated adult family members was related to greater frequency and severity of childhood abuse and higher incidence of neurological deficits in adulthood, especially related to traumatic brain injuries, compared to those without incarcerated adult family members. Along with being role models, adult family members impact the neurological health of children throughout their life-span.

  19. Female children with incarcerated adult family members at risk for life-long neurological decline

    Science.gov (United States)

    Brewer-Smyth, Kathleen; Pohlig, Ryan T.; Bucurescu, Gabriel

    2016-01-01

    A secondary analysis of data from adult female prison inmates in the mid-Atlantic United States defined relationships between having incarcerated adult family members during childhood and neurological outcomes. Of 135 inmates, 99(73%) had one or more incarcerated adult family members during childhood. Regression analyses revealed that having incarcerated adult family members was related to greater frequency and severity of childhood abuse and higher incidence of neurological deficits in adulthood, especially related to traumatic brain injuries, compared to those without incarcerated adult family members. Along with being role models, adult family members impact the neurological health of children throughout their lifespan. PMID:26788781

  20. Increase of bcl-2 Protein Expression in Aggressive Basal Cell Carcinoma of Head and Neck

    OpenAIRE

    Cláudia CAZAL; Mariana Roesch ELY; Ana Paula Veras SOBRAL; Wilton Wilney Nascimento PADILHA

    2006-01-01

    Objective: The aim of this study was to verify the bcl-2 protein expression in 22 cutaneous basal cell carcinomas (BCC) of the head and neck, and to compare it with its aggressive behavior. Method: Tumors were histologically classified in non-aggressive (BCC 1) and aggressive (BCC 2) and then submitted to the immunohistochemistry technique with the streptavidin-biotin peroxidase method using the anti-bcl-2 antibody. Results: After proceeding to morphological analysis, sixteen tumors (72.7%) w...

  1. EGFR and Bcl-2 in gastric mucosa of children infected with Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Ewa Ryszczuk

    2016-03-01

    Full Text Available Aim: The aim of the study was to evaluate the expression of EGFR and Bcl-2 proteins as inhibitory markers of apoptosis in surface epithelial cells and gland cells of antral gastric mucosa in children infected with Helicobacter pylori according to the severity and activity of antral gastritis and to assess the correlation between the number of cells expressing EGFR and the number of cells expressing Bcl-2 in H. pylori infected children.Materials and methods: The study included 44 children: 68.2% with chronic gastritis and positive IgG against H. pylori, and 31.8% with functional disorders of the gastrointestinal tract and with normal IgG against H. pylori. The evaluation of EGFR expression in gastric mucosa was performed immunohistochemically using monoclonal mouse anti-EGFR antibody. The polyclonal antibody was used to determine the expression of anti-Bcl-2.Results: A significant increase in the number of cells expressing EGFR and Bcl-2 protein was found in the epithelial cells in severe as well as mild and moderate gastritis in the group of children infected with H. pylori. An increase in the number of cells expressing EGFR and Bcl-2 protein was also found in the epithelial cells in group I according to the activity of gastritis. There was a statistically significant positive correlation between the numbers of cells expressing EGFR and Bcl-2 in H. pylori infected children.Conclusion: Increased expression of EGFR and Bcl-2 proteins in the epithelial cells and a statistically significant positive correlation between the numbers of cells expressing EGFR and Bcl-2 in H. pylori infected children could suggest increased regeneration abilities of gastric mucosa.

  2. Discovery and molecular characterization of a Bcl-2–regulated cell death pathway in schistosomes

    OpenAIRE

    Lee, Erinna F.; Clarke, Oliver B.; Evangelista, Marco; Feng, Zhiping; Speed, Terence P.; Tchoubrieva, Elissaveta B.; Strasser, Andreas; Kalinna, Bernd H.; Colman, Peter M.; Fairlie, W. Douglas

    2011-01-01

    Schistosomiasis is an infectious disease caused by parasites of the phylum platyhelminthe. Here, we describe the identification and characterization of a Bcl-2–regulated apoptosis pathway in Schistosoma japonicum and S. mansoni. Genomic, biochemical, and cell-based mechanistic studies provide evidence for a tripartite pathway, similar to that in humans including BH3-only proteins that are inhibited by prosurvival Bcl-2–like molecules, and Bax/Bak-like proteins that facilitate mitochondrial ou...

  3. Effect of Bcl-2 rs956572 polymorphism on age-related gray matter volume changes.

    Directory of Open Access Journals (Sweden)

    Mu-En Liu

    Full Text Available The anti-apoptotic protein B-cell CLL/lymphoma 2 (Bcl-2 gene is a major regulator of neural plasticity and cellular resilience. Recently, the Bcl-2 rs956572 single nucleotide polymorphism was proposed to be a functional allelic variant that modulates cellular vulnerability to apoptosis. Our cross-sectional study investigated the genetic effect of this Bcl-2 polymorphism on age-related decreases in gray matter (GM volume across the adult lifespan. Our sample comprised 330 healthy volunteers (191 male, 139 female with a mean age of 56.2±22.0 years (range: 21-92. Magnetic resonance imaging and genotyping of the Bcl-2 rs956572 were performed for each participant. The differences in regional GM volumes between G homozygotes and A-allele carriers were tested using optimized voxel-based morphometry. The association between the Bcl-2 rs956572 polymorphism and age was a predictor of regional GM volumes in the right cerebellum, bilateral lingual gyrus, right middle temporal gyrus, and right parahippocampal gyrus. We found that the volume of these five regions decreased with increasing age (all P<.001. Moreover, the downward slope was steeper among the Bcl-2 rs956572 A-allele carriers than in the G-homozygous participants. Our data provide convergent evidence for the genetic effect of the Bcl-2 functional allelic variant in brain aging. The rs956572 G-allele, which is associated with significantly higher Bcl-2 protein expression and diminished cellular sensitivity to stress-induced apoptosis, conferred a protective effect against age-related changes in brain GM volume, particularly in the cerebellum.

  4. Patients in a persistent vegetative state attitudes and reactions of family members.

    Science.gov (United States)

    Tresch, D D; Sims, F H; Duthie, E H; Goldstein, M D

    1991-01-01

    Patients in a persistent vegetative state (PVS) constituted approximately 3% of the population in four Milwaukee nursing homes. In order to understand family members' attitudes and reactions toward such patients, 33 (92%) of 36 family members of patients in PVS contacted were studied. The age of the patients ranged from 19 to 95 with a mean age of 73.4 +/- 17.2 years, and family members' ages ranged from 41 to 89 with a mean age of 61.8 +/- 3.3 years. The etiology of the PVS varied from dementia to cerebral trauma. The mean duration of the PVS was 54 +/- 8.4 months (range 12 to 204). Family members reported that they visited patients 260 times during the first year following the onset of the PVS and were still visiting at a rate of 209 visits yearly at the time of the interview. There was no significant correlation between the frequency of the family members visits and the duration of the PVS, the patient's or family member's age, or the family member's relationship to the patient. Ninety percent of patients were considered by family members to have some awareness of pain, light or darkness, environment, taste, verbal conversation, or the family member's presence. Most family members thought they understood the patient's medical condition, and the majority did not expect the patient to improve. Nevertheless, the majority of family members wanted the patient to undergo therapeutic interventions, including transfer to the acute hospital and surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Unrecognized pediatric and adult family members of children with acute brucellosis.

    Science.gov (United States)

    Çiftdoğan, Dilek Yılmaz; Aslan, Selda

    Brucellosis is an infectious, contagious and zoonotic disease that occurs worldwide. The family members of an index case of brucellosis may be especially susceptible, due to sharing the same source of infection and similar risk factors for brucellosis. In this study, we propose to screen pediatric and adult family members of brucellosis index cases for detecting additional unrecognized infected family members. 114 family members of 41 pediatric patients with brucellosis were evaluated. All family members completed a brief questionnaire and were tested by a standard tube agglutination test (STA). The majority of family members (n=96, 84.2%) were children. Among the 114 family members, 42 (36.8%) were seropositive, and 15 (35.7%) were symptomatic. The majority of the symptomatic seropositive family members (n=12, 80%) had STA titers (≥1:640) higher than asymptomatic seropositive family members (n=9, 33%; p=0.004). The routine screening of both pediatric and adult family members of index cases is a priority in endemic areas. Using this screening approach, unrecognized family members who are seropositive for brucellosis will be identified earlier and be able to receive prompt treatment. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

  6. Combined Targeting of JAK2 and Bcl-2/Bcl-xL to Cure Mutant JAK2-Driven Malignancies and Overcome Acquired Resistance to JAK2 Inhibitors

    Directory of Open Access Journals (Sweden)

    Michaela Waibel

    2013-11-01

    Full Text Available To design rational therapies for JAK2-driven hematological malignancies, we functionally dissected the key survival pathways downstream of hyperactive JAK2. In tumors driven by mutant JAK2, Stat1, Stat3, Stat5, and the Pi3k and Mek/Erk pathways were constitutively active, and gene expression profiling of TEL-JAK2 T-ALL cells revealed the upregulation of prosurvival Bcl-2 family genes. Combining the Bcl-2/Bcl-xL inhibitor ABT-737 with JAK2 inhibitors mediated prolonged disease regressions and cures in mice bearing primary human and mouse JAK2 mutant tumors. Moreover, combined targeting of JAK2 and Bcl-2/Bcl-xL was able to circumvent and overcome acquired resistance to single-agent JAK2 inhibitor treatment. Thus, inhibiting the oncogenic JAK2 signaling network at two nodal points, at the initiating stage (JAK2 and the effector stage (Bcl-2/Bcl-xL, is highly effective and provides a clearly superior therapeutic benefit than targeting just one node. Therefore, we have defined a potentially curative treatment for hematological malignancies expressing constitutively active JAK2.

  7. Bcl-2 overexpression prevents 99mTc-MIBI uptake in breast cancer cell lines

    International Nuclear Information System (INIS)

    Aloj, Luigi; Zannetti, Antonella; Caraco, Corradina; Del Vecchio, Silvana; Salvatore, Marco

    2004-01-01

    We have previously shown a correlation between the absence of technetium-99m methoxyisobutylisonitrile ( 99m Tc-MIBI) uptake and overexpression of the anti-apoptotic protein Bcl-2 in human breast carcinoma. To establish a direct cause-effect relationship between Bcl-2 overexpression and reduced 99m Tc-MIBI uptake, MCF-7 and T47D breast cancer cell lines were stably transfected with the human Bcl-2 gene to increase intracellular protein levels and tested for 99m Tc-MIBI uptake. All clones overexpressing Bcl-2 showed a dramatic reduction of 99m Tc-MIBI uptake as compared with mock transfected control cells. Tracer uptake was promptly and partially restored by induction of apoptosis with staurosporine treatment. After 4.5 h of staurosporine treatment, a tenfold increase in 99m Tc-MIBI uptake was observed in treated as compared with untreated Bcl-2 overexpressing cells. Our findings provide a rational basis for the development of an in vivo test to detect Bcl-2 overexpression in human tumours. (orig.)

  8. Involvement of p53 and Bcl-2 in sensory cell degeneration in aging rat cochleae.

    Science.gov (United States)

    Xu, Yang; Yang, Wei Ping; Hu, Bo Hua; Yang, Shiming; Henderson, Donald

    2017-06-01

    p53 and Bcl-2 (B-cell lymphoma 2) are involved in the process of sensory cell degeneration in aging cochleae. To determine molecular players in age-related hair cell degeneration, this study examined the changes in p53 and Bcl-2 expression at different stages of apoptotic and necrotic death of hair cells in aging rat cochleae. Young (3-4 months) and aging (23-24 months) Fisher 344/NHsd rats were used. The thresholds of the auditory brainstem response (ABR) were measured to determine the auditory function. Immunolabeling was performed to determine the expression of p53 and Bcl-2 proteins in the sensory epithelium. Propidium iodide staining was performed to determine the morphologic changes in hair cell nuclei. Aging rats exhibited a significant elevation in ABR thresholds at all tested frequencies (p aging hair cells showing the early signs of apoptotic changes in their nuclei. The Bcl-2 expression increase was also observed in hair cells displaying early signs of necrosis. As the hair cell degenerative process advanced, p53 and Bcl-2 immunoreactivity became reduced or absent. In the areas where no detectable nuclear staining was present, p53 and Bcl-2 immunoreactivity was absent.

  9. THE EXPRESSION AND CLINICAL VALUE OF APOPTOSIS CONTROL GENE Bcl-2 AND Bax IN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    ZHENG Jun; YAO Zhen-xiang; ZHANG Jing

    1999-01-01

    Objective: To study the expression and clinical value of apoptosis control gene bcl-2 and bax in breast cancer.Methods: Protein bax and bcl-2 in 41 breast cancers obtained from operations in our hospital in 1996 were detected using ABC immunohistochemical stain assay and compared with 10 cases with normal breast tissues.Results: The positive rate of bax in normal breast tissue was 90% and in breast cancer was 59%, with a significant statistical difference between them (P<0.05), but there was no statistical difference in bcl-2 protein expression. Among the 41 breast cancer, the group with lymph node metastasis (21 cases) had obviously low bax expression (43%) and high bcl-2 expression (76%), showing significant difference to the group without lymph node metastasis (P<0.05).Conclusion: The antiapoptosis function of bcl-2 was stronger than bax in breast cancer. Protein bax and bcl-2 assay may be useful in understanding the biological behaviors of breast cancer.

  10. Interaction between Na-K-ATPase and Bcl-2 proteins BclXL and Bak.

    Science.gov (United States)

    Lauf, Peter K; Alqahtani, Tariq; Flues, Karin; Meller, Jaroslaw; Adragna, Norma C

    2015-01-01

    In silico analysis predicts interaction between Na-K-ATPase (NKA) and Bcl-2 protein canonical BH3- and BH1-like motifs, consistent with NKA inhibition by the benzo-phenanthridine alkaloid chelerythrine, a BH3 mimetic, in fetal human lens epithelial cells (FHLCs) (Lauf PK, Heiny J, Meller J, Lepera MA, Koikov L, Alter GM, Brown TL, Adragna NC. Cell Physiol Biochem 31: 257-276, 2013). This report establishes proof of concept: coimmunoprecipitation and immunocolocalization showed unequivocal and direct physical interaction between NKA and Bcl-2 proteins. Specifically, NKA antibodies (ABs) coimmunoprecipitated BclXL (B-cell lymphoma extra large) and BAK (Bcl-2 antagonist killer) proteins in FHLCs and A549 lung cancer cells. In contrast, both anti-Bcl-2 ABs failed to pull down NKA. Notably, the molecular mass of BAK1 proteins pulled down by NKA and BclXL ABs appeared to be some 4-kDa larger than found in input monomers. In silico analysis predicts these higher molecular mass BAK1 proteins as alternative splicing variants, encoding 42 amino acid (aa) larger proteins than the known 211-aa long canonical BAK1 protein. These BAK1 variants may constitute a pool separate from that forming mitochondrial pores by specifically interacting with NKA and BclXL proteins. We propose a NKA-Bcl-2 protein ternary complex supporting our hypothesis for a special sensor role of NKA in Bcl-2 protein control of cell survival and apoptosis. Copyright © 2015 the American Physiological Society.

  11. Mental Health and Family Relations: Correlated Reports from People Who Inject Drugs and their Family Members in Vietnam

    Science.gov (United States)

    Li, Li; Tuan, Nguyen Anh; Liang, Li-Jung; Lin, Chunqing; Farmer, Shu C.; Flore, Martin

    2013-01-01

    Background This article explores the association of people who inject drugs and their family members in terms of mental health and family relations. The objective was to understand the family context and its impact on people who inject drugs in a family-oriented culture in Vietnam. Methods Cross-sectional assessment data were gathered from 83 people who inject drugs and 83 of their family members recruited from four communes in Phú Thọ province, Vietnam. Depressive symptoms and family relations were measured for both people who inject drugs and family members. Internalized shame and drug-using behavior were reported by people who inject drugs, and caregiver burden was reported by family members. Results We found that higher level of drug using behavior of people who inject drugs was significantly associated with higher depressive symptoms and lower family relations reported by themselves as well as their family members. Family relations reported by people who inject drugs and their family members were positively correlated. Conclusion The findings highlight the need for interventions that address psychological distress and the related challenges faced by family members of people who inject drugs. The article has policy implication which concludes with an argument for developing strategies that enhance the role of families in supporting behavioral change of people who inject drugs. PMID:23910167

  12. Bcl-2 associated athanogene 5 (Bag5) is overexpressed in prostate cancer and inhibits ER-stress induced apoptosis

    International Nuclear Information System (INIS)

    Bruchmann, Anja; Roller, Corinna; Walther, Tamara Vanessa; Schäfer, Georg; Lehmusvaara, Sara; Visakorpi, Tapio; Klocker, Helmut; Cato, Andrew C B; Maddalo, Danilo

    2013-01-01

    The Bag (Bcl-2 associated athanogene) family of proteins consists of 6 members sharing a common, single-copied Bag domain through which they interact with the molecular chaperone Hsp70. Bag5 represents an exception in the Bag family since it consists of 5 Bag domains covering the whole protein. Bag proteins like Bag1 and Bag3 have been implicated in tumor growth and survival but it is not known whether Bag5 also exhibits this function. Bag5 mRNA and protein expression levels were investigated in prostate cancer patient samples using real-time PCR and immunoblot analyses. In addition immunohistological studies were carried out to determine the expression of Bag5 in tissue arrays. Analysis of Bag5 gene expression was carried out using one-way ANOVA and Bonferroni’s Multiple Comparison test. The mean values of the Bag5 stained cells in the tissue array was analyzed by Mann-Whitney test. Functional studies of the role of Bag5 in prostate cancer cell lines was performed using overexpression and RNA interference analyses. Our results show that Bag5 is overexpressed in malignant prostate tissue compared to benign samples. In addition we could show that Bag5 levels are increased following endoplasmic reticulum (ER)-stress induction, and Bag5 relocates from the cytoplasm to the ER during this process. We also demonstrate that Bag5 interacts with the ER-resident chaperone GRP78/BiP and enhances its ATPase activity. Bag5 overexpression in 22Rv.1 prostate cancer cells inhibited ER-stress induced apoptosis in the unfolded protein response by suppressing PERK-eIF2-ATF4 activity while enhancing the IRE1-Xbp1 axis of this pathway. Cells expressing high levels of Bag5 showed reduced sensitivity to apoptosis induced by different agents while Bag5 downregulation resulted in increased stress-induced cell death. We have therefore shown that Bag5 is overexpressed in prostate cancer and plays a role in ER-stress induced apoptosis. Furthermore we have identified GRP78/BiP as a novel

  13. MRAS: A Close but Understudied Member of the RAS Family.

    Science.gov (United States)

    Young, Lucy C; Rodriguez-Viciana, Pablo

    2018-01-08

    MRAS is the closest relative to the classical RAS oncoproteins and shares most regulatory and effector interactions. However, it also has unique functions, including its ability to function as a phosphatase regulatory subunit when in complex with SHOC2 and protein phosphatase 1 (PP1). This phosphatase complex regulates a crucial step in the activation cycle of RAF kinases and provides a key coordinate input required for efficient ERK pathway activation and transformation by RAS. MRAS mutations rarely occur in cancer but deregulated expression may play a role in tumorigenesis in some settings. Activating mutations in MRAS (as well as SHOC2 and PP1) do occur in the RASopathy Noonan syndrome, underscoring a key role for MRAS within the RAS-ERK pathway. MRAS also has unique roles in cell migration and differentiation and has properties consistent with a key role in the regulation of cell polarity. Further investigations should shed light on what remains a relatively understudied RAS family member. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

  14. Redundant roles of PRDM family members in zebrafish craniofacial development.

    Science.gov (United States)

    Ding, Hai-Lei; Clouthier, David E; Artinger, Kristin B

    2013-01-01

    PRDM proteins are evolutionary conserved Zn-Finger transcription factors that share a characteristic protein domain organization. Previous studies have shown that prdm1a is required for the specification and differentiation of neural crest cells in the zebrafish. Here we examine other members of this family, specifically prdm3, 5, and 16, in the differentiation of the zebrafish craniofacial skeleton. prdm3 and prdm16 are strongly expressed in the pharyngeal arches, while prdm5 is expressed specifically in the area of the forming neurocranium. Knockdown of prdm3 and prdm16 results in a reduction in the neural crest markers dlx2a and barx1 and defects in both the viscerocranium and the neurocranium. The knockdown of prdm3 and prdm16 in combination is additive in the neurocranium, but not in the viscerocranium. Injection of sub-optimal doses of prdm1a with prdm3 or prdm16 Morpholinos together leads to more severe phenotypes in the viscerocranium and neurocranium. prdm5 mutants have defects in the neurocranium and prdm1a and prdm5 double mutants also show more severe phenotypes. Overall, our data reveal that prdm3, 5, and 16 are involved in the zebrafish craniofacial development and that prdm1a may interact with prdm3, 5, and 16 in the formation of the craniofacial skeleton in zebrafish. Copyright © 2012 Wiley Periodicals, Inc.

  15. Niclosamide, an anti-helminthic molecule, downregulates the retroviral oncoprotein Tax and pro-survival Bcl-2 proteins in HTLV-1-transformed T lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Di [Penn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA 17033 (United States); Yuan, Yunsheng [Penn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA 17033 (United States); Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai (China); Chen, Li [Pharmacy College, Fujian University of Traditional Chinese Medicine, Fuzhou (China); Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Liu, Xin; Belani, Chandra [Penn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA 17033 (United States); Cheng, Hua, E-mail: hcheng@ihv.umaryland.edu [Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Department Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201 (United States)

    2015-08-14

    Adult T cell leukemia and lymphoma (ATL) is a highly aggressive form of hematological malignancy and is caused by chronic infection of human T cell leukemia virus type 1 (HTLV-1). The viral genome encodes an oncogenic protein, Tax, which plays a key role in transactivating viral gene transcription and in deregulating cellular oncogenic signaling to promote survival, proliferation and transformation of virally infected T cells. Hence, Tax is a desirable therapeutic target, particularly at early stage of HTLV-1-mediated oncogenesis. We here show that niclosamide, an anti-helminthic molecule, induced apoptosis of HTLV-1-transformed T cells. Niclosamide facilitated degradation of the Tax protein in proteasome. Consistent with niclosamide-mediated Tax degradation, this compound inhibited activities of MAPK/ERK1/2 and IκB kinases. In addition, niclosamide downregulated Stat3 and pro-survival Bcl-2 family members such as Mcl-1 and repressed the viral gene transcription of HTLV-1 through induction of Tax degradation. Since Tax, Stat3 and Mcl-1 are crucial molecules for promoting survival and growth of HTLV-1-transformed T cells, our findings demonstrate a novel mechanism of niclosamide in inducing Tax degradation and downregulating various cellular pro-survival molecules, thereby promoting apoptosis of HTLV-1-associated leukemia cells. - Highlights: • Niclosamide is a promising therapeutic candidate for adult T cell leukemia. • Niclosamide employs a novel mechanism through proteasomal degradation of Tax. • Niclosamide downregulates certain cellular pro-survival molecules.

  16. Emotional disorders in pairs of patients and their family members during and after ICU stay.

    Directory of Open Access Journals (Sweden)

    Renata Rego Lins Fumis

    Full Text Available INTRODUCTION: Patients and family members undergo different experiences of suffering from emotional disorders during ICU stay and after ICU discharge. The purpose of this study was to compare the incidence of anxiety, depression and post-traumatic stress disorder (PTSD symptoms in pairs (patient and respective family member, during stay at an open visit ICU and at 30 and 90-days post-ICU discharge. We hypothesized that there was a positive correlation with the severity of symptoms among pairs and different patterns of suffering over time. METHODS: A prospective study was conducted in a 22-bed adult general ICU including patients with >48 hours stay. The Hospital Anxiety and Depression Scale (HADS was completed by the pairs (patients/respective family member. Interviews were made by phone at 30 and 90-days post-ICU discharge using the Impact of Event Scale (IES and the HADS. Multivariate models were constructed to predict IES score at 30 days for patients and family members. RESULTS: Four hundred and seventy one family members and 289 patients were interviewed in the ICU forming 184 pairs for analysis. Regarding HADS score, patients presented less symptoms than family members of patients who survived and who deceased at 30 and 90-days (p<0.001. However, family members of patients who deceased scored higher anxiety and depression symptoms (p = 0.048 at 90-days when compared with family members of patients who survived. Patients and family members at 30-days had a similar IES score, but it was higher in family members at 90-days (p = 0.019. For both family members and patients, age and symptoms of anxiety and depression during ICU were the major determinants for PTSD at 30-days. CONCLUSIONS: Anxiety, depression and PTSD symptoms were higher in family members than in the patients. Furthermore, these symptoms in family members persisted at 3 months, while they decreased in patients.

  17. Bcl-2 protein expression in mucoepidermoid carcinoma of salivary glands: a single institution experience.

    Science.gov (United States)

    Janjua, Omer Sefvan; Qureshi, Sana Mehmood; Khan, Tariq Sarfraz; Alamgir, Wajiha

    2012-01-01

    Mucoepidermoid carcinoma is the most common salivary gland tumor with varying behavior among different histopathological grades. The objective of this study was to determine the expression of Bcl-2 protein in mucoepidermoid carcinoma (MEC) and to correlate with histological grades. The records of 40 cases of MEC were collected from the histopathology department. Fresh slides were prepared and fresh diagnoses were made using the grading criteria for MEC. Immunohistochemical markers for Bcl-2 were applied and the results analyzed using the chi-square test. Of 40 cases, 20 were males and 20 were females. The range in age of the patients was 6 to 67 years mean (SD) was 42.6 (1.85) years. Twenty-two were low grade (55%), 11 high grade (27.5%) and 7 (17.5%) were intermediate grade MEC. Among these 40 cases, Bcl-2 expression was positive in 24 cases and negative in 16 cases. In 22 cases of low-grade MEC, 19 were positive while only 3 were negative. In high-grade tumors, all 11 cases were found to have a negative expression of Bcl-2 protein. In intermediate-grade MEC, 5 cases showed positive expression while only 2 cases showed negative expression. Bcl-2 protein expression showed positive expression in low-grade and negative expression in high-grade MEC. Intermediate grade showed more than 50% positive results for Bcl-2. Correlation between grades of MEC and expression of Bcl-2 is statistically significant and can be used for the depicting the prognosis of MEC along with other prognostic and clinico-pathological parameters.

  18. Regulatory effect of Bcl-2 in ultraviolet radiation-induced apoptosis of the mouse crystalline lens.

    Science.gov (United States)

    Dong, Yuchen; Zheng, Yajuan; Xiao, Jun; Zhu, Chao; Zhao, Meisheng

    2016-03-01

    The aim of the present study was to analyze the role of Bcl-2 during the process of apoptosis in the mouse crystalline lens. In total, 12 normal mice served as the control group and 12 Bcl-2 knockout (K.O) mice served as the experimental group. The mouse crystalline lens was sampled for the detection of Bcl-2 and caspase-3 expression following exposure to ultraviolet (UV) radiation. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine Bcl-2 expression in the groups of normal mice receiving UV radiation or not receiving UV radiation. Samples of the murine crystalline lens were microscopically harvested and analyzed using western blotting. Apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Furthermore, caspase 3 activity was examined using enzyme-linked immunosorbent assay kits, and RT-qPCR was used to analyze caspase-3 expression levels. The results of the present study demonstrated that there was no statistically significant difference in the level of Bcl-2 gene transcription between the two groups. In addition, UV radiation did not change the macrostructure of the crystalline lens in the group of normal mice or the group of Bcl-2 K.O mice. The results of the TUNEL assay indicated that the normal-UV group exhibited a more significant apoptosis level compared with the Bcl-2 K.O-UV group. Furthermore, the mRNA expression level of caspase-3 in the normal-UV group was significantly higher compared with the normal-nonUV group (Plens.

  19. Bcl-2 expression during the development and degeneration of RCS rat retinae.

    Science.gov (United States)

    Sharma, R K

    2001-12-14

    In various hereditary retinal degenerations, including that in Royal College of Surgeons (RCS) rats, the photoreceptors ultimately die by apoptosis. Bcl-2 is one of the genes, which regulates apoptosis and is thought to promote survival of cells. This study has investigated the developmental expression of Bcl-2 in RCS rat, which is a well-studied animal model for hereditary retinal degeneration. An antibody against Bcl-2 was used for its immunohistochemical localization in dystrophic RCS rat retinae from postnatal (PN) days 4, 7, 13, 35, 45, 70, 202 and 14 months. Results were compared with Bcl-2 localization in congenic non-dystrophic rats from PN 4, 7, 13, 44, 202 and 14 months. Bcl-2 immunoreactivity in non-dystrophic retinae was already present in PN 4 retinae in the nerve fiber layer (presumably in the endfeet of immature Müller cells) and in the proximal parts of certain radially aligned neuroepithelial cells/immature Müller cell radial processes. With increasing age the immunoreactivity in relatively more mature Müller cell radial processes spread distally towards the outer retina and between PN 13 and 44 it reached the adult distribution. No cell bodies in the ganglion cell layer were found to be immunoreactive. Expression of Bcl-2 immunoreactivity in dystrophic RCS rat retinae closely resembled that of non-dystrophic retinae. No immunoreactivity was seen in photoreceptors or retinal pigment epithelium in dystrophic or non-dystrophic retinae. In conclusion, Bcl-2 expression is not altered, either in terms of its chronology or the cell type expressing it, during retinal degeneration in RCS rats.

  20. Phospholipase D1 increases Bcl-2 expression during neuronal differentiation of rat neural stem cells.

    Science.gov (United States)

    Park, Shin-Young; Ma, Weina; Yoon, Sung Nyo; Kang, Min Jeong; Han, Joong-Soo

    2015-01-01

    We studied the possible role of phospholipase D1 (PLD1) in the neuronal differentiation, including neurite formation of neural stem cells. PLD1 protein and PLD activity increased during neuronal differentiation. Bcl-2 also increased. Downregulation of PLD1 by transfection with PLD1 siRNA or a dominant-negative form of PLD1 (DN-PLD1) inhibited both neurite outgrowth and Bcl-2 expression. PLD activity was dramatically reduced by a PLCγ (phospholipase Cγ) inhibitor (U73122), a Ca(2+)chelator (BAPTA-AM), and a PKCα (protein kinase Cα) inhibitor (RO320432). Furthermore, treatment with arachidonic acid (AA) which is generated by the action of PLA2 (phospholipase A2) on phosphatidic acid (a PLD1 product), increased the phosphorylation of p38 MAPK and CREB, as well as Bcl-2 expression, indicating that PLA2 is involved in the differentiation process resulting from PLD1 activation. PGE2 (prostaglandin E2), a cyclooxygenase product of AA, also increased during neuronal differentiation. Moreover, treatment with PGE2 increased the phosphorylation of p38 MAPK and CREB, as well as Bcl-2 expression, and this effect was inhibited by a PKA inhibitor (Rp-cAMP). As expected, inhibition of p38 MAPK resulted in loss of CREB activity, and when CREB activity was blocked with CREB siRNA, Bcl-2 production also decreased. We also showed that the EP4 receptor was required for the PKA/p38MAPK/CREB/Bcl-2 pathway. Taken together, these observations indicate that PLD1 is activated by PLCγ/PKCα signaling and stimulate Bcl-2 expression through PLA2/Cox2/EP4/PKA/p38MAPK/CREB during neuronal differentiation of rat neural stem cells.

  1. Experiences of the families concerning organ donation of a family member with brain death

    Science.gov (United States)

    Yousefi, Hojatollah; Roshani, Asieh; Nazari, Fatemeh

    2014-01-01

    Background: In recent years, the lack of organ for transplantation has resulted in health planners and authorities in all countries, including Iran, paying serious attention to the issue. Despite the above-mentioned fact, families with a member affected by brain death are not interested in organ donation. Objective: This study is aimed at making an investigation into the decision-making process of organ donation in families with brain death. Also, the research is aimed at investigating how the deterrent and facilitating factors in the process of organ donation can be made. Materials and Methods: The current research is a qualitative study with descriptive exploratory approach. Data were collected through unstructured interviews with 10 family members who gave consent to organ donation of their family members in 2012. Purposeful sampling processes began in March 2012 and lasted up to June 2012. Simultaneously, thematic approach was used in analyzing the data. Results: Data analysis led to finding 24 categories and 11 themes, which fell into two categories: facilitating and deterrent factors. The five main deterrent themes included the five themes of prohibiting factors that were shock, hope for recovery, unknown process, and conflict of opinions, and worrying association. The six main facilitating themes included humanistic desires, immortality, culture making, satisfaction of the deceased, assurance, and eternal honor. Conclusion: The findings indicated that there is ambiguity and different interpretations on brain death. The research also showed that using the experiences of donator families can provide practical and applied solutions to facilitate the process of organ donation and solve the problems faced by the health care system. PMID:24949074

  2. Positive family history of aortic dissection dramatically increases dissection risk in family members.

    Science.gov (United States)

    Ma, Wei-Guo; Chou, Alan S; Mok, Salvior C M; Ziganshin, Bulat A; Charilaou, Paris; Zafar, Mohammad A; Sieller, Richard S; Tranquilli, Maryann; Rizzo, John A; Elefteriades, John A

    2017-08-01

    Although family members of patients with aortic dissection (AoD) are believed to be at higher risk of AoD, the prognostic value of family history (FH) of aortic dissection (FHAD) in family members of patients with AoD has not been studied rigorously. We seek examine how much a positive FHAD increases the risk of developing new aortic dissection (AoD) among first-degree relatives. Patients with AoD at our institution were analyzed for information of FHAD. Positive FHAD referred to that AoD occurred in index patient and one or more first-degree relatives. Negative FHAD was defined as the condition in which only one case of AoD (the index patient) occurred in the family. The age at AoD, exposure years in adulthood before AoD, and annual probability of AoD among first-degree relatives were compared between patients with negative and positive FHADs. FHAD was positive in 32 and negative in 68 among the 100 AoD patients with detailed family history information. Mean age at dissection was 59.9±14.7years. Compared to negative FHAD, patients with positive FHAD dissected at significantly younger age (54.7±16.8 vs 62.4±13.0years, p=0.013), had more AoD events in first-degree relatives (2.3±0.6 vs 1.0±0.0, pfamily members, with a higher annual probability of aortic dissection, a shorter duration of "exposure time" before dissection occurs and a lower mean age at time of dissection. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  3. Experiences of the families concerning organ donation of a family member with brain death.

    Science.gov (United States)

    Yousefi, Hojatollah; Roshani, Asieh; Nazari, Fatemeh

    2014-05-01

    In recent years, the lack of organ for transplantation has resulted in health planners and authorities in all countries, including Iran, paying serious attention to the issue. Despite the above-mentioned fact, families with a member affected by brain death are not interested in organ donation. This study is aimed at making an investigation into the decision-making process of organ donation in families with brain death. Also, the research is aimed at investigating how the deterrent and facilitating factors in the process of organ donation can be made. The current research is a qualitative study with descriptive exploratory approach. Data were collected through unstructured interviews with 10 family members who gave consent to organ donation of their family members in 2012. Purposeful sampling processes began in March 2012 and lasted up to June 2012. Simultaneously, thematic approach was used in analyzing the data. Data analysis led to finding 24 categories and 11 themes, which fell into two categories: facilitating and deterrent factors. The five main deterrent themes included the five themes of prohibiting factors that were shock, hope for recovery, unknown process, and conflict of opinions, and worrying association. The six main facilitating themes included humanistic desires, immortality, culture making, satisfaction of the deceased, assurance, and eternal honor. The findings indicated that there is ambiguity and different interpretations on brain death. The research also showed that using the experiences of donator families can provide practical and applied solutions to facilitate the process of organ donation and solve the problems faced by the health care system.

  4. Military service absences and family members' mental health: A timeline followback assessment.

    Science.gov (United States)

    Rodriguez, Aubrey J; Margolin, Gayla

    2015-08-01

    Although military service, and particularly absence due to deployment, has been linked to risk for depression and anxiety among some spouses and children of active duty service members, there is limited research to explain the heterogeneity in family members' reactions to military service stressors. The current investigation introduces the Timeline Followback Military Family Interview (TFMFI) as a clinically useful strategy to collect detailed time-linked information about the service member's absences. Two dimensions of parent absence--the extent to which absences coincide with important family events and cumulative time absent--were tested as potential risks to family members' mental health. Data from 70 mother-adolescent pairs revealed that the number of important family events missed by the service member was linked to elevated youth symptoms of depression, even when accounting for the number of deployments and cumulative duration of the service member's absence. However, youth who reported more frequent contact with the service member during absences were buffered from the effects of extensive absence. Mothers' symptoms were associated with the cumulative duration of the service members' time away, but not with family events missed by the service member. These results identify circumstances that increase the risk for mental health symptoms associated with military family life. The TFMFI provides an interview-based strategy for clinicians wishing to understand military family members' lived experience during periods of service-member absence. (c) 2015 APA, all rights reserved).

  5. The impact of appearance-related teasing by family members.

    Science.gov (United States)

    Keery, Helene; Boutelle, Kerri; van den Berg, Patricia; Thompson, J Kevin

    2005-08-01

    This study evaluated the prevalence and effects of teasing by family members on body dissatisfaction, eating disturbance, and psychological functioning. Self-report data were collected from 372 middle school girls who were part of a larger study in a Tampa Bay, Florida area middle school (mean age: 12.6 years; 85% Caucasian). Twenty-three percent of participants reported appearance-related teasing by a parent, and 12% were teased by a parent about being heavy. Nineteen percent of the girls reported appearance-related teasing by fathers, 13% reported appearance-related teasing by mothers, and 29% reported appearance-related teasing by siblings. After controlling for body mass index (BMI) and maternal teasing, paternal teasing was a significant predictor of body dissatisfaction, comparison, thin-ideal internalization, restriction, bulimic behaviors, self-esteem, and depression. After controlling for BMI and paternal teasing, maternal teasing was a significant predictor of depression. After controlling for BMI and maternal teasing, paternal teasing significantly increased the odds of having a sibling who teases. Girls who reported being teased by at least one sibling demonstrated significantly higher levels of body dissatisfaction, comparison, thin-ideal internalization, restriction, bulimic behaviors, depression, and significantly lower levels of self-esteem than those girls who reported they were not teased by their siblings. Frequency of teasing was associated with higher levels of negative outcomes. This study has implications for treatment and prevention of eating disorders. The results suggest that health care providers should assess appearance-related teasing in their patients' lives to identify girls who may be at risk for body image and eating disturbance and poor psychological functioning.

  6. The impact of leader-member exchange (LMX) on work-family interference and work-family facilitation

    NARCIS (Netherlands)

    L.G. Tummers (Lars); B.A.C. Bronkhorst (Babette)

    2014-01-01

    markdownabstract__Abstract__ Purpose – We analyze the effects of leadership on work-family spillovers. Specifically, we analyze the relationships between leadership (leader-member exchange, LMX) with one negative work-family spillover effect (work-family interference) and one positive work-family

  7. The impact of leader-member exchange (LMX) on work-family interference and work-family facilitation

    OpenAIRE

    Tummers, Lars; Bronkhorst, Babette

    2014-01-01

    markdownabstract__Abstract__ Purpose – We analyze the effects of leadership on work-family spillovers. Specifically, we analyze the relationships between leadership (leader-member exchange, LMX) with one negative work-family spillover effect (work-family interference) and one positive work-family spillover effect (work-family facilitation). We hypothesize that LMX influences work-family spillover via different mediators, rather than one all-encompassing mediator, such as empowerment. Design/m...

  8. The studies on thyrocyte apoptosis and expression of Bcl-2 and Bax in Hashimoto's thyroiditis

    International Nuclear Information System (INIS)

    Zhao Yaping; Wang Jialing; Fan Zhiyong; Liu Zehong; Wu HeJun; Zhou Wei; Jia Meizhai

    2003-01-01

    To investigate the thyrocyte apoptosis, the expression of Bcl-2, Bax and the relationship between apoptosis and the pathogenesis in Hashimoto's thyroiditis (HT), 41 HT thyroid and 10 normal thyroid specimens were selected. The level of apoptosis was detected by TUNEL methods. The expression and distribution of Bcl-2 and Bax were detected using immunohistochemical methods and analyzed by Mias99 pathological image system. Immunohistochemical staining was carried out using S-P kit. The Result showed that an increased level of apoptosis was observed in Hashimoto's glands. The apoptosis mainly distributed in thyroid follicles destruction area. This was associated with increased Bax expression. The strongly positive Bcl-2 staining was observed in the thyrocyte of intact thyroid follicles. The ratios of positive granule area and total light density of Bcl-2 to those of Bax in HT thyroid follicle area were lower than those in normal thyroid. The apoptosis of thyrocyte induced by dysregulation of Bcl-2 and Bax may be involved in the pathogeneses of HT

  9. Female children with incarcerated adult family members at risk for life-long neurological decline

    OpenAIRE

    Brewer-Smyth, Kathleen; Pohlig, Ryan T.; Bucurescu, Gabriel

    2016-01-01

    A secondary analysis of data from adult female prison inmates in the mid-Atlantic United States defined relationships between having incarcerated adult family members during childhood and neurological outcomes. Of 135 inmates, 99(73%) had one or more incarcerated adult family members during childhood. Regression analyses revealed that having incarcerated adult family members was related to greater frequency and severity of childhood abuse and higher incidence of neurological deficits in adult...

  10. Suicidal Ideation and Distress in Family Members Bereaved by Suicide in Portugal

    OpenAIRE

    Santos, Sara; Campos, Rui; Tavares, Sofia

    2015-01-01

    The present study assessed the impact of suicide and distress on suicidal ideation in a sample of 93 Portuguese family members bereaved by suicide. A control community sample of 102 adults also participated. After controlling for educational level, those bereaved by the suicide of a family member were found to have higher levels of suicidal ideation. Forty-two percent of family members had Suicide Ideation Questionnaire scores at or above the cutoff point. General distress, dep...

  11. Resilience in families in which a member has been diagnosed with schizophrenia.

    Science.gov (United States)

    Bishop, M; Greeff, A P

    2015-09-01

    Due to the extensive focus of the literature on the burden placed on families in which a member has been diagnosed with a mental illness such as schizophrenia, there is a need to identify factors that may help these families to be resilient and adapt to their crisis. The aim of this study was to identify family resilience qualities in families in which a member has been diagnosed with schizophrenia. The study comprised 42 families, represented by 33 parents and 9 siblings of the diagnosed family member. Families were recruited from three support groups within the Cape Metropolitan area, Western Cape, South Africa. Qualitative data were obtained through an open-ended question and quantitative data were collected with seven self-report questionnaires. The following family resilience qualities were identified: family income; finding support in their community; family togetherness; family communication style during crises; affirming and supportive communication patterns; family hardiness; commitment to the family; reframing crises as a challenge; and an internal locus of control within the family. The findings may be used by professionals and support group facilitators to enhance the resilience and functioning of families living with a member with schizophrenia. With approximately 1% of the world's population diagnosed with schizophrenia, it is clear that many families are affected when a member has been diagnosed. There is a need to identify factors that may help these families to be resilient. The aim of this study was to identify family resilience qualities in families in which a member has been diagnosed with schizophrenia. The following family resilience qualities were identified as resources that helped them to adapt to the many challenges put to them: family income, finding support in their community, the availability of hospitals, churches and professionals, family togetherness, family communication, family hardiness, commitment to the family, reframing crises

  12. Helping concerned family members of individuals with substance use and concurrent disorders: An evaluation of a family member-oriented treatment program.

    Science.gov (United States)

    Denomme, William James; Benhanoh, Orry

    2017-08-01

    There is a growing body of research demonstrating that families of individuals with substance use and concurrent disorders (SUCD) experience a wide range of biopsychosocial problems that significantly impedes their quality of life and health. However, there has been a relative lack of treatment programs primarily focused on improving the well-being and quality of life of these family members. The current study assessed the efficacy of such a program at reducing stress, increasing perceived social support from family and friends, and increasing general, dyadic, and self-rated family functioning within these concerned family members. A sample of 125 family members of individuals with SUCDs was recruited, of which 97 participated in the treatment program and 28 were used as the comparison group. Results indicated that the treatment program significantly reduced stress, increased perceived social support from family and friends, and increased general, dyadic and self-rated family functioning. A perceived personal benefits questionnaire demonstrated that participants had a better understanding of SUCDs, better coping capabilities in regard to emotional difficulties, adopted stronger coping methods, participated in more leisure activities, and improved their relationship with the individual with a SUCD. The results of the current study further demonstrate the need to implement more of these family-member oriented psycho-educational treatment programs. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Perception of family emotional climate by family members of persons with schizophrenia.

    Science.gov (United States)

    Gandhi, Sailaxmi; Pavalur, Rajitha; Thirthalli, Jagadisha; Phillip, Mariamma

    2016-08-01

    There is a dearth of instruments to assess schizophrenia persons' Family Emotional Climate (FEC). This study aims to explore the relation between family members' personality traits and FEC. We invited a convenience sample of 50 both gender family members who were accompanying the person with schizophrenia for out-patient department (OPD) consultation to provide data on a socio-demographic proforma and the researcher prepared 'Emotional climate assessment questionnaire - caregivers' version' (ECAQ-C) as well as the Eysenck personality questionnaire. Caregivers' extroversion traits (r = .427, p = .002) were positively correlated and neuroticism traits were negatively correlated (r = -.330, p = .019) with their positive perception of FEC. There was a higher perception of positive FEC (mean scores = 65.5 ± 10.5) while caregivers seemed to perceive less negative FEC (mean scores = 36.5 ± 10.2). Caregivers with education above 11th std perceived less (χ(2) = 8.6, p = .013) of negative FEC. The findings highlight that caregivers' personality traits seem to influence the FEC. While caregivers' perception of FEC is positive in this study, those in the higher education group seem to have a better perception of FEC indicating that education also may influence FEC. © The Author(s) 2016.

  14. RBP2 Promotes Adult Acute Lymphoblastic Leukemia by Upregulating BCL2.

    Directory of Open Access Journals (Sweden)

    Xiaoming Wang

    Full Text Available Despite recent increases in the cure rate of acute lymphoblastic leukemia (ALL, adult ALL remains a high-risk disease that exhibits a high relapse rate. In this study, we found that the histone demethylase retinoblastoma binding protein-2 (RBP2 was overexpressed in both on-going and relapse cases of adult ALL, which revealed that RBP2 overexpression was not only involved in the pathogenesis of ALL but that its overexpression might also be related to relapse of the disease. RBP2 knockdown induced apoptosis and attenuated leukemic cell viability. Our results demonstrated that BCL2 is a novel target of RBP2 and supported the notion of RBP2 being a regulator of BCL2 expression via directly binding to its promoter. As the role of RBP2 in regulating apoptosis was confirmed, RBP2 overexpression and activation of BCL2 might play important roles in ALL development and progression.

  15. Mechanism of effect of ionizing radiation on bcl-2 protein expression and apoptosis in mouse thymus

    International Nuclear Information System (INIS)

    Liu Jiamei; Chen Aijun; Chen Dong; Liu Shuzheng

    2002-01-01

    Objective: To study the mechanism of effect of ionizing radiation in varied doses of X-rays on bcl-2 express and apoptosis in mouse thymus. Methods: Immunohistochemistry, image analysis and transmission electron microscope were used in the study. Results: The expression of bcl-2 protein was limited within thymic medulla, decreased with 2 Gy, however, increased with 0.075 Gy after whole-body irradiation. Some typical apoptotic cells were found in thymic cortex after 2 Gy irradiation. The apoptotic cells decreased and mitotic metaphase increased after 0.075 Gy irradiation. Conclusion: The mechanism of effect of ionizing radiation on apoptosis of thymus was related with the expression of bcl-2 proteins

  16. Quinacrine induces apoptosis in human leukemia K562 cells via p38 MAPK-elicited BCL2 down-regulation and suppression of ERK/c-Jun-mediated BCL2L1 expression

    International Nuclear Information System (INIS)

    Changchien, Jung-Jung; Chen, Ying-Jung; Huang, Chia-Hui; Cheng, Tian-Lu; Lin, Shinne-Ren; Chang, Long-Sen

    2015-01-01

    Although previous studies have revealed the anti-cancer activity of quinacrine, its effect on leukemia is not clearly resolved. We sought to explore the cytotoxic effect and mechanism of quinacrine action in human leukemia K562 cells. Quinacrine induced K562 cell apoptosis accompanied with ROS generation, mitochondrial depolarization, and down-regulation of BCL2L1 and BCL2. Upon exposure to quinacrine, ROS-mediated p38 MAPK activation and ERK inactivation were observed in K562 cells. Quinacrine-induced cell death and mitochondrial depolarization were suppressed by the p38MAPK inhibitor SB202190 and constitutively active MEK1 over-expression. Activation of p38 MAPK was shown to promote BCL2 degradation. Further, ERK inactivation suppressed c-Jun-mediated transcriptional expression of BCL2L1. Over-expression of BCL2L1 and BCL2 attenuated quinacrine-evoked mitochondrial depolarization and rescued the viability of quinacrine-treated cells. Taken together, our data indicate that quinacrine-induced K562 cell apoptosis is mediated through mitochondrial alterations triggered by p38 MAPK-mediated BCL2 down-regulation and suppression of ERK/c-Jun-mediated BCL2L1 expression. - Highlights: • Quinacrine induces K562 cell apoptosis via down-regulation of BCL2 and BCL2L1. • Quinacrine induces p38 MAPK activation and ERK inactivation in K562 cells. • Quinacrine elicits p38 MAPK-mediated BCL2 down-regulation. • Quinacrine suppresses ERK/c-Jun-mediated BCL2L1 expression

  17. Family members' lived experience in the intensive care unit: a phemenological study.

    LENUS (Irish Health Repository)

    McKiernan, Margaret

    2012-01-31

    AIM: To describe the lived experience of family members of patients in the intensive care unit. BACKGROUND: Admission of a critically ill relative to an intensive care unit causes anxiety and stress to family members. Nursing care is initially focused on maintaining the physiological stability of the patient and less on the needs and concerns of family members. Understanding how families make sense of this experience may help nurses focus on the delivery of family centred care. METHODOLOGY: A phenomenological method was used to describe the lived experiences of family members of patients in an intensive care unit. In-depth interviews were conducted with six family members and analysed using qualitative thematic analysis. RESULTS: Four main themes emerged from the data: the need to know, making sense of it all, being there with them and caring and support. Family members needed honest information about the patient\\'s progress and outcome to make the situation more bearable for them. Making sense of the situation was a continuous process which involved tracking and evaluating care given. Being with their relative sustained their family bond and was a way to demonstrate love and support. Caring reassurance provided by the nurses enabled a sense of security. Support was needed by family members to assist them in coping. CONCLUSION: The research provided an insight into how family members viewed the impact of the admission and how they subsequently found ways of dealing with the situation. RELEVANCE TO CLINICAL PRACTICE: Using a holistic approach to nursing assessment and care delivery in intensive care necessitates that nurses interact with and care for family members of patients. Development of a philosophy of family centred care is necessary, with formal assessment of families to take place soon after admission and an appropriate plan of care drawn up at this time.

  18. Spouses/Family Members of Service Members at Risk for PTSD or Suicide

    Science.gov (United States)

    2016-09-01

    maintaining work / life balance . 4. Strong connection with extended family – both the partner’s (for support) and the soldier’s (for attempting to...the demands of the military, due to frequent moves. 2. Disruptions to family life , such as canceled vacations (due to changes in work demands...Some spouses noted that effective leaders could reduce the negative impact (e.g., by attempting to help soldiers achieve work / family balance with

  19. Understanding of advance care planning by family members of persons undergoing hemodialysis.

    Science.gov (United States)

    Calvin, Amy O; Engebretson, Joan C; Sardual, S Alexander

    2014-11-01

    The purpose of this qualitative descriptive study was to explore hemodialysis patients' family members' understanding of end-of-life decision-making processes. The project aimed to address (a) family members' constructions of advance care planning (ACP), including their roles and responsibilities, and (b) family members' perceptions of health care providers' roles and responsibilities in ACP. Eighteen family members of persons undergoing hemodialysis were recruited primarily from outpatient dialysis facilities and interviewed individually. Confirmed transcript data were analyzed, coded, and compared, and categories were established. Interpretations were validated throughout the interviews and peer debriefing sessions were used at a later stage in the analysis. The overarching construct identified was one of Protection. Family members protect patients by (a) Sharing Burdens, (b) Normalizing Life, and (c) Personalizing Care. Recommendations for future research include the need to explore ACP of persons undergoing hemodialysis who do not have a family support system. © The Author(s) 2013.

  20. Inhibition of Bcl-2 or IAP proteins does not provoke mutations in surviving cells

    International Nuclear Information System (INIS)

    Shekhar, Tanmay M.; Green, Maja M.; Rayner, David M.; Miles, Mark A.; Cutts, Suzanne M.; Hawkins, Christine J.

    2015-01-01

    Graphical abstract: - Highlights: • Mutagenicities of anti-cancer drugs were tested using HPRT, γH2AX and comet assays. • TRAIL, doxorubicin and etoposide were more mutagenic than BH3- or Smac-mimetics. • Physiologically achievable levels of the BH3-mimetic ABT-737 were not mutagenic. • High concentrations of ABT-737 provoked mutations via an off-target mechanism. • Even very high concentrations of IAP antagonists were not mutagenic. - Abstract: Chemotherapy and radiotherapy can cause permanent damage to the genomes of surviving cells, provoking severe side effects such as second malignancies in some cancer survivors. Drugs that mimic the activity of death ligands, or antagonise pro-survival proteins of the Bcl-2 or IAP families have yielded encouraging results in animal experiments and early phase clinical trials. Because these agents directly engage apoptosis pathways, rather than damaging DNA to indirectly provoke tumour cell death, we reasoned that they may offer another important advantage over conventional therapies: minimisation or elimination of side effects such as second cancers that result from mutation of surviving normal cells. Disappointingly, however, we previously found that concentrations of death receptor agonists like TRAIL that would be present in vivo in clinical settings provoked DNA damage in surviving cells. In this study, we used cell line model systems to investigate the mutagenic capacity of drugs from two other classes of direct apoptosis-inducing agents: the BH3-mimetic ABT-737 and the IAP antagonists LCL161 and AT-406. Encouragingly, our data suggest that IAP antagonists possess negligible genotoxic activity. Doses of ABT-737 that were required to damage DNA stimulated Bax/Bak-independent signalling and exceeded concentrations detected in the plasma of animals treated with this drug. These findings provide hope that cancer patients treated by BH3-mimetics or IAP antagonists may avoid mutation-related illnesses that afflict

  1. Inhibition of Bcl-2 or IAP proteins does not provoke mutations in surviving cells

    Energy Technology Data Exchange (ETDEWEB)

    Shekhar, Tanmay M. [Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora 3083 (Australia); Green, Maja M. [Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora 3083 (Australia); Department of Anatomy & Neuroscience, The University of Melbourne, Parkville 3010 (Australia); Rayner, David M.; Miles, Mark A.; Cutts, Suzanne M. [Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora 3083 (Australia); Hawkins, Christine J., E-mail: c.hawkins@latrobe.edu.au [Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora 3083 (Australia)

    2015-07-15

    Graphical abstract: - Highlights: • Mutagenicities of anti-cancer drugs were tested using HPRT, γH2AX and comet assays. • TRAIL, doxorubicin and etoposide were more mutagenic than BH3- or Smac-mimetics. • Physiologically achievable levels of the BH3-mimetic ABT-737 were not mutagenic. • High concentrations of ABT-737 provoked mutations via an off-target mechanism. • Even very high concentrations of IAP antagonists were not mutagenic. - Abstract: Chemotherapy and radiotherapy can cause permanent damage to the genomes of surviving cells, provoking severe side effects such as second malignancies in some cancer survivors. Drugs that mimic the activity of death ligands, or antagonise pro-survival proteins of the Bcl-2 or IAP families have yielded encouraging results in animal experiments and early phase clinical trials. Because these agents directly engage apoptosis pathways, rather than damaging DNA to indirectly provoke tumour cell death, we reasoned that they may offer another important advantage over conventional therapies: minimisation or elimination of side effects such as second cancers that result from mutation of surviving normal cells. Disappointingly, however, we previously found that concentrations of death receptor agonists like TRAIL that would be present in vivo in clinical settings provoked DNA damage in surviving cells. In this study, we used cell line model systems to investigate the mutagenic capacity of drugs from two other classes of direct apoptosis-inducing agents: the BH3-mimetic ABT-737 and the IAP antagonists LCL161 and AT-406. Encouragingly, our data suggest that IAP antagonists possess negligible genotoxic activity. Doses of ABT-737 that were required to damage DNA stimulated Bax/Bak-independent signalling and exceeded concentrations detected in the plasma of animals treated with this drug. These findings provide hope that cancer patients treated by BH3-mimetics or IAP antagonists may avoid mutation-related illnesses that afflict

  2. Is upregulation of BCL2 a determinant of tumor development driven by inactivation of CDH1/E-cadherin?

    Directory of Open Access Journals (Sweden)

    Inga Karch

    Full Text Available Inactivation of CDH1, encoding E-cadherin, promotes cancer initiation and progression. According to a newly proposed molecular mechanism, loss of E-cadherin triggers an upregulation of the anti-apoptotic oncoprotein BCL2. Conversely, reconstitution of E-cadherin counteracts overexpression of BCL2. This reciprocal regulation is thought to be critical for early tumor development. We determined the relevance of this new concept in human infiltrating lobular breast cancer (ILBC, the prime tumor entity associated with CDH1 inactivation. BCL2 expression was examined in human ILBC cell lines (IPH-926, MDA-MB-134, SUM-44 harboring deleterious CDH1 mutations. To test for an intact regulatory axis between E-cadherin and BCL2, wild-type E-cadherin was reconstituted in ILBC cells by ectopic expression. Moreover, BCL2 and E-cadherin were evaluated in primary invasive breast cancers and in synchronous lobular carcinomas in situ (LCIS. MDA-MB-134 and IPH-926 showed little or no BCL2 expression, while SUM-44 ILBC cells were BCL2-positive. Reconstitution of E-cadherin failed to impact on BCL2 expression in all cell lines tested. Primary ILBCs were almost uniformly E-cadherin-negative (97% and were frequently BCL2-negative (46%. When compared with an appropriate control group, ILBCs showed a trend towards an increased frequency of BCL2-negative cases (P = 0.064. In terminal duct-lobular units affected by LCIS, the E-cadherin-negative neoplastic component showed a similar or a reduced BCL2-immunoreactivity, when compared with the adjacent epithelium. In conclusion, upregulation of BCL2 is not involved in lobular breast carcinogenesis and is unlikely to represent an important determinant of tumor development driven by CDH1 inactivation.

  3. Osteochondritis Dissecans Lesions in Family Members: Does a Positive Family History Impact Phenotypic Potency?

    Science.gov (United States)

    Gornitzky, Alex L; Mistovich, R Justin; Atuahuene, Brittany; Storey, Eileen P; Ganley, Theodore J

    2017-06-01

    Although repetitive microtrauma and athletic overuse patterns are most commonly associated with osteochondritis dissecans (OCD), recent studies have identified a potential genetic predisposition for OCD. Several case series have documented family pedigrees that support autosomal-dominant inheritance, but the families in these studies were all selected as a result of unique histories that may not accurately represent OCD inheritance patterns at large. Because there has been little investigation beyond these case reports, we aimed to describe a broader, more representative pattern of OCD inheritance applicable to all affected patients. (1) What proportion of patients treated for OCD of the knee have one or more immediate and/or extended family members with a history of OCD lesions? (2) Do patients with more phenotypically potent lesions, which we defined as patients with bilateral OCD lesions or patients who have undergone multiple procedures for OCD, have a higher frequency of affected relatives than those with less potent lesions? This retrospective study queried patient databases, diagnosis codes (International Classification of Diseases, 9th Revision), and surgical logs at a regional, tertiary care children's hospital to identify all patients treated over a 10-year period (March 2004-March 2014) by the senior author for OCD of the knee. All patients aged 0-18 years at the time of diagnosis were included. At our institution, patients with intact lesions are treated with a trial of conservative therapy; conversely, patients with a break in the articular cartilage and/or loose fragments of bone/cartilage are treated surgically. There were no OCD-specific contraindications to surgery. This search identified 543 patients. After patient identification, a questionnaire was designed that asked for the number, age, and gender of all immediate family members and the history of OCD lesions in any family member (immediate or extended). For all positive family members

  4. FGFR Family Members Protein Expression as Prognostic Markers in Oral Cavity and Oropharyngeal Squamous Cell Carcinoma

    NARCIS (Netherlands)

    Koole, Koos; Clausen, Martijn J. A. M.; van Es, Robert J. J.; van Kempen, Pauline M. W.; Melchers, Lieuwe J.; Koole, Ron; Langendijk, Johannes A.; van Diest, Paul J.; Roodenburg, Jan L. N.; Schuuring, Ed; Willems, Stefan M.

    Introduction Fibroblast growth factor receptor family member proteins (FGFR1-4) have been identified as promising novel therapeutic targets and prognostic markers in a wide spectrum of solid tumors. The present study investigates the expression and prognostic value of four FGFR family member

  5. The needs of patient family members in the intensive care unit in ...

    African Journals Online (AJOL)

    Background. The admission of a relative to an intensive care unit (ICU) is a stressful experience for family members. There has been limited research addressing this issue in Kigali, Rwanda. Objective. To explore the needs of patient family members admitted into an ICU in Kigali, Rwanda. Methods. This study used a ...

  6. Stress and Depressive Symptoms in Cancer Survivors and Their Family Members: Korea Community Health Survey, 2012.

    Science.gov (United States)

    Han, Mi Ah

    2017-09-01

    This study examined the prevalence of perceived stress and depressive symptoms in cancer survivors and their family members compared with subjects without cancer and without family members with cancer. The subjects of this cross-sectional study were adults ≥19 years old who participated in the 2012 Korea Community Health Survey. Stress and depressive symptoms in cancer survivors and their family members were assessed and compared to symptoms in control groups by chi-square tests and multiple logistic regression analyses. Of the 6783 cancer survivors, 26.9% and 8.7% reported having stress and depressive symptoms, respectively, and 27.7% and 5.9% of family members of cancer survivors reported having stress and depressive symptoms, respectively. Cancer survivors showed higher adjusted odds ratio (aOR) for stress (aOR = 1.26, 95% confidence interval (CI) = 1.16-1.37) and depressive symptoms (aOR = 1.82, 95% CI = 1.57-2.11) than subjects without cancer history. Family members of cancer survivors showed a higher OR for stress and depressive symptoms than subjects without a family member who survived cancer. Cancer survivors and family members of cancer survivors had more stress and depressive symptoms than controls. Careful management for cancer patients and their family members should include screening for stress and depression to improve mental health associated with cancer survivorship.

  7. Caregiving for Dementia in Family Members: Caregiving Burden and Prospects for Effective Intervention.

    Science.gov (United States)

    Maiden, Robert J.; And Others

    Caring for a family member with dementia is a major source of stress for the caregiver. To assess the impact of caring for an impaired family member and to evaluate the effectiveness of intervention programs, 34 caregivers of relatives with dementia completed an amended form of the Philadelphia Geriatric Center's Caregiver Survey and two…

  8. Effective doses to family members of patients treated with radioiodine-131

    International Nuclear Information System (INIS)

    Kocovska, M Zdraveska; Vaskova, O; Majstorov, V; Kuzmanovska, S; Gjorceva, D Pop; Jokic, V Spasic

    2011-01-01

    The purpose of this study was to evaluate the effective dose to family members of thyroid cancer and hyperthyroid patients treated with radioiodine-131, and also to compare the results with dose constraints proposed by the International Commission of Radiological Protection (ICRP) and the Basic Safety Standards (BSS) of the International Atomic Energy Agency (IAEA). For the estimation of the effective doses, sixty family members of sixty patients, treated with radioiodine-131, and thermoluminiscent dosimeters (Model TLD 100) were used. Thyroid cancer patients were hospitalized for three days, while hyperthyroid patients were treated on out-patient basis. The family members wore TLD in front of the torso for seven days. The radiation doses to family members of thyroid cancer patients were well below the recommended dose constraint of 1 mSv. The mean value of effective dose was 0.21 mSv (min 0.02 - max 0.51 mSv). Effective doses, higher than 1 mSv, were detected for 11 family members of hyperthyroid patients. The mean value of effective dose of family members of hyperthyroid patients was 0.87 mSv (min 0.12 - max 6.79). The estimated effective doses to family members of hyperthyroid patients were higher than the effective doses to family members of thyroid carcinoma patients. These findings may be considered when establishing new national guidelines concerning radiation protection and release of patients after a treatment with radioiodine therapy.

  9. Familial idiopathic pulmonary fibrosis. Evidence of lung inflammation in unaffected family members

    International Nuclear Information System (INIS)

    Bitterman, P.B.; Rennard, S.I.; Keogh, B.A.; Wewers, M.D.; Adelberg, S.; Crystal, R.G.

    1986-01-01

    We evaluated 17 clinically unaffected members of three families with an autosomal dominant form of idiopathic pulmonary fibrosis for evidence of alveolar inflammation. Each person in the study was examined by gallium-67 scanning for a general estimate of pulmonary inflammation, and by bronchoalveolar lavage for characterization of the types of recovered cells and their state of activation. Eight of the 17 subjects had evidence of alveolar inflammation on the lavage studies. Supporting data included increased numbers of neutrophils and activated macrophages that released one or more neutrophil chemoattractants, and growth factors for lung fibroblasts--findings similar to those observed in patients with overt idiopathic pulmonary fibrosis. Four of these eight also had a positive gallium scan; in all the other clinically unaffected subjects the scan was normal. During a follow-up of two to four years in seven of the eight subjects who had evidence of inflammation, no clinical evidence of pulmonary fibrosis has appeared. These results indicate that alveolar inflammation occurs in approximately half the clinically unaffected family members at risk of inheriting autosomal dominant idiopathic pulmonary fibrosis. Whether these persons with evidence of pulmonary inflammation but no fibrosis will proceed to have clinically evident pulmonary fibrosis is not yet known

  10. Stress Hormone Cortisol Enhances Bcl2 Like-12 Expression to Inhibit p53 in Hepatocellular Carcinoma Cells.

    Science.gov (United States)

    Wu, Weizhong; Liu, Sanguang; Liang, Yunfei; Zhou, Zegao; Bian, Wei; Liu, Xueqing

    2017-12-01

    The pathogenesis of hepatocellular carcinoma (HC) is unclear. It is suggested that psychological stress associates with the pathogenesis of liver cancer. Bcl2-like protein 12 (Bcl2L12) suppresses p53 protein. This study tests a hypothesis that the major stress hormone, cortisol, inhibits the expression of p53 in HC cells (HCC) via up regulating the expression of Bcl2L12. Peripheral blood samples were collected from patients with HC to be analyzed for the levels of cortisol. HCC were cultured to assess the role of cortisol in the regulation of the expression of Bcl2L12 and p53 in HCC. We observed that the serum cortisol levels were higher in HC patients. Expression of Bcl2L12 in HCC was correlated with serum cortisol. Cortisol enhanced the Bcl2L12 expression in HCC. Bcl2L12 binding to the TP53 promoter was correlated with p53 expression in HCC. Cortisol increased the Bcl2L12 expression in HCC to inhibit p53 expression. Stress hormone cortisol suppresses p53 in HCC via enhancing Bcl2L12 expression in HCC. The results suggest that cortisol may be a therapeutic target for the treatment of HC.

  11. The impact of leader-member exchange (LMX) on work-family interference and work-family facilitation

    NARCIS (Netherlands)

    L.G. Tummers (Lars); B.A.C. Bronkhorst (Babette)

    2014-01-01

    markdownabstract__Abstract__ __Purpose__ – We analyze the effects of leadership on work-family spillovers. Specifically, we analyze the relationships between leadership (leader-member exchange, LMX) with one negative work-family spillover effect (work-family interference) and one positive

  12. Resilient family processes, personal reintegration, and subjective well-being outcomes for military personnel and their family members.

    Science.gov (United States)

    Clark, Malissa A; O'Neal, Catherine W; Conley, Kate M; Mancini, Jay A

    2018-01-01

    Deployment affects not just the service members, but also their family members back home. Accordingly, this study examined how resilient family processes during a deployment (i.e., frequency of communication and household management) were related to the personal reintegration of each family member (i.e., how well each family member begins to "feel like oneself again" after a deployment), as well as several indicators of subjective well-being. Drawing from the family attachment network model (Riggs & Riggs, 2011), the present study collected survey data from 273 service members, their partners, and their adolescent children. Resilient family processes during the deployment itself (i.e., frequency of communication, household management), postdeployment positive and negative personal reintegration, and several indicators of well-being were assessed. Frequency of communication was related to personal reintegration for service members, while household management was related to personal reintegration for nondeployed partners; both factors were related to personal reintegration for adolescents. Negative and positive personal reintegration related to a variety of subjective well-being outcomes for each individual family member. Interindividual (i.e., crossover) effects were also found, particularly between adolescents and nondeployed partners. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  13. Caring for a family member with intellectual disability and epilepsy: practical, social and emotional perspectives.

    Science.gov (United States)

    Thompson, Rose; Kerr, Mike; Glynn, Mike; Linehan, Christine

    2014-11-01

    To examine the caregiving impact of those who support a family member with intellectual disability and epilepsy. An online, qualitative international survey was conducted via the auspices of the International Bureau of Epilepsy with various stakeholders who support individuals who have intellectual disability and epilepsy. Qualitative comments were analyzed from respondents who identified themselves as family members (n=48; 36%) who referred specifically to the impact of supporting a family member with these combined disabilities. Four main domains, which were comprised of ten themes, were derived from the qualitative data using Braun and Clarke's qualitative framework. These domains comprised (1) practical concerns, (2) disrupted family dynamics, (3) emotional burden and (4) positive experiences. In combination these themes illustrate the pervasive impact on family life for those supporting an individual with complex needs. Financial concerns, coordination and responsibility of care, diverted attention from other family members and social isolation all contributed a significant burden of care for family members. Positive aspects were, however, also cited including the closeness of the family unit and a fostering of altruistic behavior. The study provides an insight into an under-researched area. The burden of caring for a family member across the lifespan has a largely negative and pervasive impact. Targeted service provision could contribute to an amelioration of the challenges faced by these families. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  14. Involvement of family members in life with type 2 diabetes

    DEFF Research Database (Denmark)

    Grabowski, Dan; Andersen, Tue Helms; Varming, Annemarie

    2017-01-01

    OBJECTIVES: Family involvement plays a key role in diabetes management. Problems and challenges related to type 2-diabetes often affect the whole family, and relatives are at increased risk of developing diabetes themselves. We highlight these issues in our objectives: (1) to uncover specific...... family problems associated with mutual involvement in life with type 2-diabetes and (2) to analytically look at ways of approaching these problems in healthcare settings. METHODS: Qualitative data were gathered in participatory problem assessment workshops. The data were analysed in three rounds using...... radical hermeneutics. RESULTS: Problems were categorized in six domains: knowledge, communication, support, everyday life, roles and worries. The final cross-analysis focusing on the link between family identity and healthcare authenticity provided information on how the six domains can be approached...

  15. Recovering from Opioid Overdose: Resources for Overdose Survivors & Family Members

    Science.gov (United States)

    ... and gratitude, all accompanied by the discomfort of opioid withdrawal. Most need the support of family and friends to take the next steps toward recovery. While many factors can contribute to opioid overdose, it is al most always an accident. ...

  16. Bcl-2 protein level in blood of patients with acute myeloid leukaemia ...

    African Journals Online (AJOL)

    (AML), bcl-2 being an anti-apoptotic protein incriminated in cancer. ... resistant to apoptosis, defining this protein as a factor of bad prognosis in AML. Moreover, the determination ..... of the molecular mechanisms of physiological ... long term survival in breast cancer, Am. J. Pathol. ... Burkitt subtype at presentation, and is not.

  17. Bax/Bcl-2 expression ratio in prediction of response to breast cancer radiotherapy

    Directory of Open Access Journals (Sweden)

    Hosein Azimian

    2018-03-01

    Full Text Available Objective(s: Radiotherapy is one of the most effective modalities of cancer therapy, but clinical responses of individual patients varies considerably. To enhance treatment efficiency it is essential to implement an individual-based treatment. The aim of present study was to identify the mechanism of intrinsic apoptosis pathway on radiosensitivity and normal tissue complications caused by the radiotherapy. Materials and Methods: Peripheral blood mononuclear cells from ten breast cancer patients were exposed to 6MV X-rays to deliver 1 and 2 Gy. Expression levels of Bax, Bcl-2, and Bax/Bcl-2 ratio were examined by relative quantitative RT-PCR. All the patients received similar tangential irradiation of the whole breast and conventional fractionation. Skin dosimetry was done by GAFChromic EBT-3 film and clinical radiosensitivity was determined using the acute reactions to radiotherapy of the skin according to Radiation Therapy Oncology Group score. All statistical analyses were performed using GraphPad Prism, version 7.01. Results: In the in-vitro experiment, Bax and Bax/Bcl-2 ratios were significantly increased with 1 and 2 Gy doses (PP0.05 for all patients. Conclusion: Significant correlation between Bax/Bcl-2 ratio determined before radiation therapy and clinical response in the patients, can be used as a biomarker to identify radiosensitive individuals. However, further studies are required to validate radiation-induced apoptotic biomarkers.

  18. Discovery and molecular characterization of a Bcl-2-regulated cell death pathway in schistosomes.

    Science.gov (United States)

    Lee, Erinna F; Clarke, Oliver B; Evangelista, Marco; Feng, Zhiping; Speed, Terence P; Tchoubrieva, Elissaveta B; Strasser, Andreas; Kalinna, Bernd H; Colman, Peter M; Fairlie, W Douglas

    2011-04-26

    Schistosomiasis is an infectious disease caused by parasites of the phylum platyhelminthe. Here, we describe the identification and characterization of a Bcl-2-regulated apoptosis pathway in Schistosoma japonicum and S. mansoni. Genomic, biochemical, and cell-based mechanistic studies provide evidence for a tripartite pathway, similar to that in humans including BH3-only proteins that are inhibited by prosurvival Bcl-2-like molecules, and Bax/Bak-like proteins that facilitate mitochondrial outer-membrane permeabilization. Because Bcl-2 proteins have been successfully targeted with "BH3 mimetic" drugs, particularly in the treatment of cancer, we investigated whether schistosome apoptosis pathways could provide targets for future antischistosomal drug discovery efforts. Accordingly, we showed that a schistosome prosurvival protein, sjA, binds ABT-737, a well-characterized BH3 mimetic. A crystal structure of sjA bound to a BH3 peptide provides direct evidence for the feasibility of developing BH3 mimetics to target Bcl-2 prosurvival proteins in schistosomes, suggesting an alternative application for this class of drugs beyond cancer treatment.

  19. Discovery and molecular characterization of a Bcl-2–regulated cell death pathway in schistosomes

    Science.gov (United States)

    Lee, Erinna F.; Clarke, Oliver B.; Evangelista, Marco; Feng, Zhiping; Speed, Terence P.; Tchoubrieva, Elissaveta B.; Strasser, Andreas; Kalinna, Bernd H.; Colman, Peter M.; Fairlie, W. Douglas

    2011-01-01

    Schistosomiasis is an infectious disease caused by parasites of the phylum platyhelminthe. Here, we describe the identification and characterization of a Bcl-2–regulated apoptosis pathway in Schistosoma japonicum and S. mansoni. Genomic, biochemical, and cell-based mechanistic studies provide evidence for a tripartite pathway, similar to that in humans including BH3-only proteins that are inhibited by prosurvival Bcl-2–like molecules, and Bax/Bak-like proteins that facilitate mitochondrial outer-membrane permeabilization. Because Bcl-2 proteins have been successfully targeted with “BH3 mimetic” drugs, particularly in the treatment of cancer, we investigated whether schistosome apoptosis pathways could provide targets for future antischistosomal drug discovery efforts. Accordingly, we showed that a schistosome prosurvival protein, sjA, binds ABT-737, a well-characterized BH3 mimetic. A crystal structure of sjA bound to a BH3 peptide provides direct evidence for the feasibility of developing BH3 mimetics to target Bcl-2 prosurvival proteins in schistosomes, suggesting an alternative application for this class of drugs beyond cancer treatment. PMID:21444803

  20. Mutational analysis of Bax and Bcl-2 in childhood acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Salomons, G. S.; Buitenhuis, C. K.; Martínez Muñoz, C.; Verwijs-Jassen, M.; Behrendt, H.; Zsiros, J.; Smets, L. A.

    1998-01-01

    In childhood acute lymphoblastic leukaemia there are large interpatient variations in levels of the apoptosis-regulating proteins Bax and Bcl-2, but the molecular basis for this variation is unknown. Point-mutations in bax have been reported in cell lines derived from haematological malignancies.

  1. Cannabinoids Regulate Bcl-2 and Cyclin D2 Expression in Pancreatic β Cells.

    Directory of Open Access Journals (Sweden)

    Jihye Kim

    Full Text Available Recent reports have shown that cannabinoid 1 receptors (CB1Rs are expressed in pancreatic β cells, where they induce cell death and cell cycle arrest by directly inhibiting insulin receptor activation. Here, we report that CB1Rs regulate the expression of the anti-apoptotic protein Bcl-2 and cell cycle regulator cyclin D2 in pancreatic β cells. Treatment of MIN6 and βTC6 cells with a synthetic CB1R agonist, WIN55,212-2, led to a decrease in the expression of Bcl-2 and cyclin D2, in turn inducing cell cycle arrest in G0/G1 phase and caspase-3-dependent apoptosis. Additionally, genetic deletion and pharmacological blockade of CB1Rs after injury in mice led to increased levels of Bcl-2 and cyclin D2 in pancreatic β cells. These findings provide evidence for the involvement of Bcl-2 and cyclin D2 mediated by CB1Rs in the regulation of β-cell survival and growth, and will serve as a basis for developing new therapeutic interventions to enhance β-cell function and growth in diabetes.

  2. Expression of Bcl-2, Melan A and HMB-45 in Dysplastic Nevi.

    Science.gov (United States)

    Patrascu, Oana Maria; Costache, Mariana; Dumitru, Adrian Vasile; Mehotin, Corina Nicoleta; Sajin, Maria; Lazaroiu, Anca Mihaela

    2016-03-01

    From the first recognition of dysplastic nevi as a pathology per se, many debates have been raised and many histological and immunohistological studies have been conducted in order to establish the true significance of these lesions. Therefore, the aim of this study was to establish if there is a correlation between HMB-45, Melan A and Bcl-2 expression and the grade of dysplasia, as well as between the marker's staining patterns. Ten dysplastic nevi from six female patients were selected and their histological features (size, dysplasia), as well as the immunohistological staining patterns, were studied (HMB-45, Melan A, Bcl-2). The Pearson correlation coefficient and regression was calculated with Windows Excel Data Analysis. We demonstrated that there was a notable correlation between the dysplasia and the size of the lesions (r(8)= 0.62 with p-value= 0.052), and also between Melan A and Bcl-2 (a r(6)= 0.73, p0.05). We can affirm, at least in our cases, there is a correlation between the grade of dysplasia and the size of the lesion, and also, that there is a correlation between Melan A and Bcl-2 staining, explained by MITF gene. These results were only partial concordant with those in other studies, therefore a larger number of cases is recommended to be further analyzed in order to clearly draw a conclusion.

  3. Withaferin A Suppresses Anti-apoptotic BCL2, Bcl-xL, XIAP and ...

    African Journals Online (AJOL)

    apoptotic genes, BCL2, Bcl-xL, XIAP and Survivin), in cervical carcinoma cells. Methods: Annexin V-FITC/propidium iodide (PI) staining was used for the investigation of cell apoptosis. RNA RNeasy Kits was used to isolate RNA and Omniscript ...

  4. The experiences of family members in the nursing home to hospital transfer decision

    Directory of Open Access Journals (Sweden)

    Kathleen Abrahamson

    2016-11-01

    Full Text Available Abstract Background The objective of this study was to better understand the experiences of family members in the nursing home to hospital transfer decision making process. Semi-structured interviews were conducted with 20 family members who had recently been involved in a nursing home to hospital transfer decision. Results Family members perceived themselves to play an advocacy role in their resident’s care and interview themes clustered within three over-arching categories: Family perception of the nursing home’s capacity to provide medical care: Resident and family choices; and issues at ‘hand-off’ and the hospital. Multiple sub-themes were also identified. Conclusions Findings from this study contribute to knowledge surrounding the nursing home transfer decision by illuminating the experiences of family members in the transfer decision process.

  5. Knowledge of Dementia: Do family members understand dementia as a terminal condition?

    Science.gov (United States)

    Andrews, Sharon; McInerney, Fran; Toye, Christine; Parkinson, Camillus-Anthony; Robinson, Andrew

    2017-07-01

    Current research identifies advanced dementia to be the terminal phase of this progressive and incurable condition. However, there has been relatively little investigation into how family members of people with advanced dementia understand their relative's condition. In this article, we report on semi-structured interviews with 10 family members of people with advanced dementia, in a residential aged care facility. Using a qualitative, descriptive design, we explored family members' understandings of dementia, whether they were aware that it was a terminal condition, and the ways they developed their understandings. Findings revealed that the majority of family members could not recognize the terminal nature of dementia. Relying on predominantly lay understandings, they had little access to formal information and most failed to conceptualize a connection between dementia and death. Moreover, family members engaged in limited dialogue with aged care staff about such issues, despite their relatives being in an advanced stage of the disease. Findings from our study suggest that how family members understand their relative's condition requires greater attention. The development of staff/family partnerships that promote shared communication about dementia and dying may enhance family members' understandings of the dementia trajectory and the types of decisions they may be faced with during the more advanced stages of the disease.

  6. Tissue factor/FVIIa activates Bcl-2 and prevents doxorubicin-induced apoptosis in neuroblastoma cells

    International Nuclear Information System (INIS)

    Fang, Jun; Gu, Lubing; Zhu, Ningxi; Tang, Hao; Alvarado, Carlos S; Zhou, Muxiang

    2008-01-01

    Tissue factor (TF) is a transmembrane protein that acts as a receptor for activated coagulation factor VII (FVIIa), initiating the coagulation cascade. Recent studies demonstrate that expression of tumor-derived TF also mediates intracellular signaling relevant to tumor growth and apoptosis. Our present study investigates the possible mechanism by which the interaction between TF and FVIIa regulates chemotherapy resistance in neuroblastoma cell lines. Gene and siRNA transfection was used to enforce TF expression in a TF-negative neuroblastoma cell line and to silence endogenous TF expression in a TF-overexpressing neuroblastoma line, respectively. The expression of TF, Bcl-2, STAT5, and Akt as well as the phosphorylation of STAT5 and Akt in gene transfected cells or cells treated with JAK inhibitor and LY294002 were determined by Western blot assay. Tumor cell growth was determined by a clonogenic assay. Cytotoxic and apoptotic effect of doxorubicin on neuroblastoma cell lines was analyzed by WST assay and annexin-V staining (by flow cytometry) respectively. Enforced expression of TF in a TF-negative neuroblastoma cell line in the presence of FVIIa induced upregulation of Bcl-2, leading to resistance to doxorubicin. Conversely, inhibition of endogenous TF expression in a TF-overexpressing neuroblastoma cell line using siRNA resulted in down-regulation of Bcl-2 and sensitization to doxorubicin-induced apoptosis. Additionally, neuroblastoma cells expressing high levels of either endogenous or transfected TF treated with FVIIa readily phosphorylated STAT5 and Akt. Using selective pharmacologic inhibitors, we demonstrated that JAK inhibitor I, but not the PI3K inhibitor LY294002, blocked the TF/FVIIa-induced upregulation of Bcl-2. This study shows that in neuroblastoma cell lines overexpressed TF ligated with FVIIa produced upregulation of Bcl-2 expression through the JAK/STAT5 signaling pathway, resulting in resistance to apoptosis. We surmise that this TF

  7. PPAR-γ Silencing Inhibits the Apoptosis of A549 Cells by Upregulating Bcl-2

    Directory of Open Access Journals (Sweden)

    Jingyu YANG

    2013-03-01

    Full Text Available Background and objective Drug resistance is the one of primary causes of death in patients with lung cancer, PPAR-γ could induce the apoptosis and reverse drug resistance. The aim of this study is to investigate the expression of PPAR-γ on cisplatin sensitivity and apoptosis response of human lung cancer cell line A549. Methods Reconstruction of PPAR-γ silencing A549 cells (A549/PPAR-γ(- by siRNA. MTT assay was employed to determine the effect of cisplatin on the proliferation of A549/PPAR-γ(-, flow cytometry to determine the effect of cisplatin on the cell apoptosis, Western blot to determine the change of phosphorylation of Akt, caspase-3 and expression of bcl-2/bax. Finally, RT-PCR was employed to determine the transcriptional level of bcl-2. Results Two PPAR-γ silencing A549 cell clones were established successfully, and the expression of PPAR-γ was downregulated significantly as confirmed by RT-PCR and Western blot. After PPAR-γ silencing, the resistance of these two A549 clones to cisplatin was increased by 1.29-fold and 1.60-fold respectively. Flow cytometry showed that the apoptosis rate was decreased, and Western Blot showed that the phosphorylation of Akt and expression of bcl-2/bax were upregulated, caspase-3 was downregulated. Finally, RT-PCR showed that the transcriptional level of bcl-2 was upregulated as well. Conclusion Downregulation of PPAR-γ in A549 cells led to increase of cisplatin resistance. One of the mechanisms was upregulatin of phosphorylation of Akt and expression of bcl-2, which inhibited the apoptosis of cells. The downregulation of PPAR-γ is a possible mechanism that leads to the clinical drug resistance of cancer.

  8. Effect of bcl-2 overexpression in mice on ovotoxicity caused by 4-vinylcyclohexene

    International Nuclear Information System (INIS)

    Flaws, Jodi A.; Marion, Samuel L.; Miller, Kimberly P.; Christian, Patricia J.; Babus, Janice K.; Hoyer, Patricia B.

    2006-01-01

    The occupational chemical 4-vinylcyclohexene (VCH) destroys small preantral ovarian follicles in mice following repeated daily dosing. The cell survival gene bcl-2 is thought to protect against follicular death during embryogenesis because primordial follicle numbers in newborn bcl-2 overexpressing (OE) mice are greater than in wild-type (WT) controls. Thus, this study was designed to determine if overexpression of bcl-2 protects against VCH-induced follicle loss during embryonic development. Pregnant bcl-2 OE or WT mice were dosed (p.o.) daily with VCH (500 mg/kg) or sesame oil (vehicle control) on days 8-18 of pregnancy. Ovaries were collected from moms and female pups on pup postnatal day (PND) 8. Nonpregnant OE and WT females were also treated with VCH (500 mg/kg p.o.) or vehicle and evaluated in the same manner. As previously reported, ovaries from PND8 OE female pups contained 50% more primordial follicles than WT pups (P < 0.05). Unlike WT pups, relative to vehicle controls, in utero exposure to VCH resulted in a reduction in primordial (25% of control), primary (38% of control), and secondary (33% of control) follicles in ovaries of OE pups (P < 0.05). VCH had no significant effect on follicle numbers in OE or WT moms. Conversely, in nonpregnant adults, VCH did not affect WT mice but caused loss of primordial (55% of control), primary (51% of control), and secondary (69% of control) follicles in OE mice (P < 0.05). These results demonstrate that bcl-2 overexpression does not protect against, but instead increases susceptibility to VCH-induced follicle loss in transplacentally exposed or in nonpregnant mice

  9. Support needs and experiences of family members of wounded, injured or sick UK service personnel.

    Science.gov (United States)

    Verey, Anna; Keeling, M; Thandi, G; Stevelink, S; Fear, N

    2017-12-01

    When a service person has been wounded, injured or sick (WIS), family members may provide care during their recovery in an unpaid capacity. This may occur in diverse environments including hospitals, inpatient rehabilitation centres, in the community and at home. Thirty-seven family members of WIS personnel were interviewed regarding their support needs, family relationships and use of UK support services. Semistructured, in-depth telephone interviews were used, with data analysis undertaken using a thematic approach. 'Family member involvement' was the main theme under which four subthemes were situated: 'continuity of support', 'proactive signposting and initiating contact', 'psychoeducation and counselling' and 'higher risk groups'. Family members felt they might benefit from direct, consistent and continuous care regardless of the WIS person's injury or engagement type, and whether the WIS person was being treated in a hospital, rehabilitative centre or at home. The findings of this study suggest that family members of WIS personnel value proactive, direct and sustained communication from support service providers. We suggest that families of UK service personnel may benefit from family care coordinators, who could provide continuous and consistent care to family members of WIS personnel. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. Nurses' views of forensic care in emergency departments and their attitudes, and involvement of family members.

    Science.gov (United States)

    Linnarsson, Josefin Rahmqvist; Benzein, Eva; Årestedt, Kristofer

    2015-01-01

    To describe Nurses' views of forensic care provided for victims of violence and their families in EDs, to identify factors associated with Nurses' attitudes towards families in care and to investigate if these attitudes were associated with the involvement of patients' families in care. Interpersonal violence has serious health consequences for individuals and family members. Emergency departments provide care for victims of violence, and nurses play a key role in forensic care. However, there is limited knowledge of their views and their involvement of family members. A cross-sectional design was used with a sample of all registered nurses (n = 867) in 28 emergency departments in Sweden. A self-report questionnaire, including the instrument Families' Importance in Nursing Care - Nurses' Attitudes, was used to collect data. Descriptive statistics, multiple linear regression and ordinal regression were used to analyse data. Four hundred and fifty-seven nurses completed the questionnaire (53%). Most nurses provided forensic care, but few had specific education for this task. Policy documents and routines existed for specific patient groups. Most nurses involved family members in care although education and policy documents rarely included them. Being a woman, policy documents and own experience of a critically ill family member were associated with a positive attitude towards family. A positive attitude towards family members was associated with involving patients' families in care. Many emergency department nurses provided forensic care without having specific education, and policy documents only concerned women and children. Nurses' positive attitude to family members was not reflected in policies or education. These results can inspire clinical forensic care interventions in emergency departments. Educational efforts for nurses and policies for all groups of victims of violence are needed. Emergency departments may need to rethink how family members are included

  11. High expression of BCL-2 predicts favorable outcome in non-small cell lung cancer patients with non squamous histology

    International Nuclear Information System (INIS)

    Anagnostou, Valsamo K; Boffa, Daniel; Gettinger, Scott; Detterbeck, Frank; Homer, Robert J; Dougenis, Dimitrios; Rimm, David L; Syrigos, Konstantinos N; Lowery, Frank J; Zolota, Vassiliki; Tzelepi, Vassiliki; Gopinath, Arun; Liceaga, Camil; Panagopoulos, Nikolaos; Frangia, Konstantina; Tanoue, Lynn

    2010-01-01

    Bcl-2 promotes cell survival by inhibiting adapters needed for the activation and cleavage of caspases thus blocking the proteolytic cascade that ultimately dismantles the cell. Bcl-2 has been investigated as a prognostic factor in non small cell lung cancer (NSCLC) patients with conflicting results. Here, we quantitatively assessed Bcl-2 expression in two large and independent cohorts to investigate the impact of Bcl-2 on survival. AQUA ® , a fluorescent-based method for analysis of in situ protein expression, was used to measure Bcl-2 protein levels and classify tumors by Bcl-2 expression in a cohort of 180 NSCLC patients. An independent cohort of 354 NSCLC patients was used to validate Bcl-2 classification and evaluate outcome. Fifty % and 52% of the cases were classified as high expressers in training and validation cohorts respectively. Squamous cell carcinomas were more likely to be high expressers compared to adenocarcinomas (63% vs. 45%, p = 0.002); Bcl-2 was not associated with other clinical or pathological characteristics. Survival analysis showed that patients with high BCL-2 expression had a longer median survival compared to low expressers (22 vs. 17.5 months, log rank p = 0.014) especially in the subset of non-squamous tumors (25 vs. 13.8 months, log rank p = 0.04). Multivariate analysis revealed an independent lower risk for all patients with Bcl-2 expressing tumors (HR = 0.53, 95% CI 0.37-0.75, p = 0.0003) and for patients with non-squamous tumors (HR = 0.5, 95% CI 0.31-0.81, p = 0.005). Bcl-2 expression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of NSCLC patients

  12. Being a close family member of a person with dementia living in a nursing home.

    Science.gov (United States)

    Seiger Cronfalk, Berit; Ternestedt, Britt-Marie; Norberg, Astrid

    2017-11-01

    To illuminate how family members of persons with dementia describe their own experiences, before and after placing their relative in a nursing home. In the Western world and with a growing population of older people, the number of persons with dementia increases. Family members often become carers in their own homes creating stressful and exhausting situation that eventually leads to relocating the person to a nursing home. This may lead to troubled conscience among family members. This is a qualitative study with descriptive design based on interviews with ten family members to residents with dementia at one small nursing home ward. Data were analysed using content analysis. Five categories were derived from data: relocating a person with dementia - a responsibility; visiting the resident - a relief or a burden; the participants taking part in and monitoring the residents' care needs; participants meeting their own needs; and thoughts about the future and resident's death. The result shows both positive and negative aspects of being a family member to persons with dementia. Family members described feeling relief as well as having a troubled conscience when placing a relative in a nursing home. They held themselves responsible for monitoring and evaluating the quality of the care. Family members expressed fearing a slow death for the person with dementia as well as for their own sake. Most felt well treated by the staff. Family members were responsible for relocating the residents to the nursing home. This in itself was found to cause feelings of moral concerns and generating troubled conscience. Staff at nursing homes needs to exercise family-centred care to benefit the persons with dementia, their family members and the staff themselves. © 2017 John Wiley & Sons Ltd.

  13. 76 FR 67363 - Extending Religious and Family Member FICA and FUTA Exceptions to Disregarded Entities

    Science.gov (United States)

    2011-11-01

    ... unless the requisite family relationship exists between the employee and each of the partners comprising... the exceptions from employment that apply because of the existence of a family relationship between...(c). The inability of these entities to benefit from the exceptions for family employees and members...

  14. Bcl-2 and Bcl-xL overexpression inhibits cytochrome c release, activation of multiple caspases, and virus release following coxsackievirus B3 infection

    International Nuclear Information System (INIS)

    Carthy, Christopher M.; Yanagawa, Bobby; Luo Honglin; Granville, David J.; Yang, Decheng; Cheung, Paul; Cheung, Caroline; Esfandiarei, Mitra; Rudin, Charles M.; Thompson, Craig B.; Hunt, David W.C.; McManus, Bruce M.

    2003-01-01

    Coxsackievirus B3, a cytopathic virus in the family Picornaviridae, induces degenerative changes in host cell morphology. Here we demonstrate cytochrome c release and caspases-2, -3, -6, -7, -8, and -9 processing. Enforced Bcl-2 and Bcl-xL expression markedly reduced release of cytochrome c, presentation of the mitochondrial epitope 7A6, and depressed caspase activation following infection. In comparison, cell death using TRAIL ligand caused caspase-8 processing prior to cytochrome c release and executioner caspases and cell death was only partially rescued by Bcl-2 and Bcl-xL overexpression. Disruption of the mitochondrial inner membrane potential following CVB3 infection was not inhibited by zVAD.fmk treatment. Bcl-2 or Bcl-xL overexpression or zVAD.fmk treatment delayed the loss of host cell viability and decreased progeny virus release following infection. Our data suggest that mitochondrial release of cytochrome c may be an important early event in caspase activation in CVB3 infection, and, as such, may contribute to the loss of host-cell viability and progeny virus release

  15. Family members' informal roles in end-of-life decision making in adult intensive care units.

    Science.gov (United States)

    Quinn, Jill R; Schmitt, Madeline; Baggs, Judith Gedney; Norton, Sally A; Dombeck, Mary T; Sellers, Craig R

    2012-01-01

    To support the process of effective family decision making, it is important to recognize and understand informal roles that various family members may play in the end-of-life decision-making process. To describe some informal roles consistently enacted by family members involved in the process of end-of-life decision making in intensive care units. Ethnographic study. Data were collected via participant observation with field notes and semistructured interviews on 4 intensive care units in an academic health center in the mid-Atlantic United States from 2001 to 2004. The units studied were a medical, a surgical, a burn and trauma, and a cardiovascular intensive care unit. Health care clinicians, patients, and family members. Informal roles for family members consistently observed were primary caregiver, primary decision maker, family spokesperson, out-of-towner, patient's wishes expert, protector, vulnerable member, and health care expert. The identified informal roles were part of families' decision-making processes, and each role was part of a potentially complicated family dynamic for end-of-life decision making within the family system and between the family and health care domains. These informal roles reflect the diverse responses to demands for family decision making in what is usually a novel and stressful situation. Identification and description of these informal roles of family members can help clinicians recognize and understand the functions of these roles in families' decision making at the end of life and guide development of strategies to support and facilitate increased effectiveness of family discussions and decision-making processes.

  16. Perceptions of Individual and Family Functioning Among Deployed Female National Guard Members.

    Science.gov (United States)

    Kelly, Patricia J; Cheng, An-Lin; Berkel, LaVerne A; Nilsson, Johanna

    2016-08-01

    Females currently make up 15% of U.S. military service members. Minimal attention has been paid to families of female National Guard members who have been deployed and their subsequent reintegration challenges. This cross-sectional Internet-based survey of female members of four National Guard units compared those who were and were not deployed. Instruments, guided by the variables of the Family Resilience Model, measured individual, family, and deployment-related factors. Bivariate analysis and ordinal logistic regression were done to assess differences between the groups. Of the 239 National Guard members surveyed, deployed women (n = 164) had significantly higher levels of posttraumatic stress disorder (PTSD; p family functioning were higher among deployed when compared with never deployed women. Results indicate community interventions that focus on strengthening coping skills of female Guard members would be useful for this population. © The Author(s) 2016.

  17. Use of augmentative and alternative communication strategies by family members in the intensive care unit.

    Science.gov (United States)

    Broyles, Lauren M; Tate, Judith A; Happ, Mary Beth

    2012-03-01

    Little is known about communication between patients and their family members during critical illness and mechanical ventilation in the intensive care unit, including use of augmentative and alternative communication tools and strategies. To identify (1) which augmentative and alternative communication tools families use with nonspeaking intensive care patients and how they are used, and (2) what families and nurses say about communication of family members with nonspeaking intensive care patients. A qualitative secondary analysis was conducted of existing data from a clinical trial testing interventions to improve communication between nurses and intensive care patients. Narrative study data (field notes, intervention logs, nurses' interviews) from 127 critically ill adults were reviewed for evidence of family involvement with augmentative and alternative communication tools. Qualitative content analysis was applied for thematic description of family members' and nurses' accounts of patient-family communication. Family involvement with augmentative and alternative communication tools was evident in 44% of the 93 patients who completed the parent study protocol. Spouses or significant others communicated with patients most often. Main themes describing patient-family communication included (1) families being unprepared and unaware, (2) families' perceptions of communication effectiveness, (3) nurses deferring to or guiding patient-family communication, (4) patients' communication characteristics, and (5) families' experience with and interest in augmentative and alternative communication tools. Assessment by skilled bedside clinicians can reveal patients' communication potential and facilitate useful augmentative and alternative communication tools and strategies for patients and their families.

  18. Effects of continued psychological care toward brain tumor patients and their family members' negative emotions.

    Science.gov (United States)

    Xiao, Ning; Zhu, Dan; Xiao, Shuiyuan

    2018-01-01

    Numerous studies have confirmed that brain tumor patients and their family members frequently exhibit negative emotional reactions, such as anxiety and depression, during diagnosis and treatment of the disease. Family members experience increasing pressure as the year of survival of patient progress. The aim of this study was to investigate the effects of the continued psychological care (CPC) toward the brain tumor patients and their family members' emotions. The asynchronous clinical control trial was performed, and 162 brain tumor patients and their family members were divided into the control group and the intervention group. The control group was only performed the telephone follow-up toward the patients. Beside this way, the intervention group was performed the CPC toward the patients and their family member. The self-rating anxiety scale (SAS) and the self-rating depression scale (SDS) were used to measure the negative emotions of the patients and their family members, and the patients' treatment compliance and the incidence of seizures were compared. The SAS and SDS scores of the intervention group on the 14 days, 28 days and 3 months of the CPC were significantly lower than the control group (P family members.

  19. Family Benefits In Member States Of The European Union: A Comparative Perspective

    Directory of Open Access Journals (Sweden)

    Stănescu Simona Maria

    2015-06-01

    Full Text Available The article intends to be a screening of family benefits in the 28 Member States of the European Union (EU and to contribute to the research of shared trends with respect to family approach in these countries. Four types of family benefits including eight distinctive categories are analysed: child-benefit, child care allowances, child-raising allowances, and other benefits (birth and adoption grants, allowance for single parents, special allowances for children with disabilities, advance payments for maintenance and other allowances. The paper is based on primary and secondary analysis of 28 sets of national data provided through the European Union's Mutual Information System on Social Protection (MISSOC. Three categories of member states are considered: founder member states of the EU, other “old” member states, and the new Central and Eastern ones. Chronological development of national regulations with impact on family benefits is analysed in connection with the moment of becoming a member state. Various forms of family benefits legislation and their main subjects of interest are further researched. The last part of the article looks at the coverage of family benefits. Seven member states operate in this respect based on regulations adopted before EU accession. Belgium, Finland, and Lithuania have the “most preserved” family regulations per category of member states. The first three topics of family regulations are: child, family, and allowance / benefit. The most frequently provided family benefits are: birth and adoption grants, and special allowance for children with disabilities. All eight family benefits are provided in France, Finland, Hungary, and Slovenia. Only two types of family benefits are available in Ireland, Spain, and Cyprus.

  20. ICU versus Non-ICU Hospital Death: Family Member Complicated Grief, Posttraumatic Stress, and Depressive Symptoms.

    Science.gov (United States)

    Probst, Danielle R; Gustin, Jillian L; Goodman, Lauren F; Lorenz, Amanda; Wells-Di Gregorio, Sharla M

    2016-04-01

    Family members of patients who die in an ICU are at increased risk of psychological sequelae compared to those who experience a death in hospice. This study explored differences in rates and levels of complicated grief (CG), posttraumatic stress disorder (PTSD), and depression between family members of patients who died in an ICU versus a non-ICU hospital setting. Differences in family members' most distressing experiences at the patient's end of life were also explored. The study was an observational cohort. Subjects were next of kin of 121 patients who died at a large, Midwestern academic hospital; 77 died in the ICU. Family members completed measures of CG, PTSD, depression, and end-of-life experiences. Participants were primarily Caucasian (93%, N = 111), female (81%, N = 98), spouses (60%, N = 73) of the decedent, and were an average of nine months post-bereavement. Forty percent of family members met the Inventory of Complicated Grief CG cut-off, 31% met the Impact of Events Scale-Revised PTSD cut-off, and 51% met the Center for Epidemiologic Studies Depression Scale depression cut-off. There were no significant differences in rates or levels of CG, PTSD, or depressive symptoms reported by family members between hospital settings. Several distressing experiences were ranked highly by both groups, but each setting presented unique distressing experiences for family members. Psychological distress of family members did not differ by hospital setting, but the most distressing experiences encountered at end of life in each setting highlight potentially unique interventions to reduce distress post-bereavement for family members.

  1. p53-Dependent radiation-induced apoptosis in vivo: relationship to Bcl-2 and Bax expression

    International Nuclear Information System (INIS)

    Hasegawa, Masatoshi; Suzuki, Yoshiyuki; Furuta, Masaya; Yamakawa, Michitaka; Maebayashi, Katsuya; Hayakawa, Kayoko; Saito, Yoshihiro; Mitsuhashi, Norio; Niibe, Hideo

    1997-01-01

    Purpose: A close correlation between p53 protein expression and radiation-induced apoptosis has already been reported, however, Bcl-2 and Bax expression and the ratio of Bcl-2 to Bax have been also suggested to play an important role in the regulation of apoptotic cell death. In this study, we investigated the relationship between p53-dependent radiation-induced apoptosis and expression of Bcl-2 and Bax by using human tumors transplanted into nude mice. Materials and Methods: Three human tumors (an ependymoblastoma, a glioblastoma, and a small cell lung cancer) were subcutaneously transplanted into nude mice and irradiated with single doses of 1, 2, 5, or 10 Gy. The tumors were excised 1, 3, 6, 12, 24, and 48 hours after irradiation, fixed in 10% formalin for 24 hours, and embedded in paraffin. Slides were stained with hematoxylin and eosin for morphologic examination. Immunohistochemical studies were performed with mouse monoclonal antibodies to demonstrate p53, p21 (WAF-1), Bcl-2, and Bax expression. TdT-mediated dUTP-biotin nick-end labeling (TUNEL) and electron microscopic studies were performed to identify apoptosis, and PCR-SSCP analysis was used to evaluate p53 gene mutation. Results: All of the tumors showed only a few cells undergoing apoptosis before irradiation. Beginning several hours after irradiation, only the ependymoblastoma showed a large increase in the number of cells undergoing apoptosis, peaking at 6 hours after irradiation, and there was a clear dose-effect relationship. In contrast, the other tumors showed much less change following irradiation, and the dose-effect relationship was not as clear as in the ependymoblastoma. Immunohistochemically, the non-irradiated ependymoblastoma was negative for p53, p21, Bcl-2, and Bax. Following irradiation, however, many of the tumor cells became positive for p53 and p21, and a few cells became positive for bcl-2. In contrast, the glioblastoma and the small cell lung cancer were positive for p53 and Bcl-2

  2. Emotional reactions and needs of family members of ICU patients.

    Science.gov (United States)

    Płaszewska-Żywko, Lucyna; Gazda, Dorota

    2012-01-01

    The aim of the study was to determine emotional reactions and needs of families of ICU patients. The study group included 60 relatives of ICU patients, aged 18-80 years. The diagnostic questionnaire-based survey was conducted. The questionnaire contained questions regarding demographic data, emotions and needs as well as the Courtauld Emotional Control Scale (CECS). The major emotions of patients' families on ICU admission were anxiety, uncertainty, fear, depression, and nervousness (particularly among parents and adult offsprings). On second-third day of hospitalisation, the emotions became less severe (P emotional reactions were better controlled by men (P emotions (P emotions of ICU patients' relatives were highly intense, especially amongst parents and adult children. Women were characterised by higher levels of emotions and needs compared to men.

  3. Forgotten family members: the importance of siblings in early psychosis.

    Science.gov (United States)

    Bowman, Siann; Alvarez-Jimenez, Mario; Wade, Darryl; McGorry, Patrick; Howie, Linsey

    2014-08-01

    This paper reviews the evidence on the significance of sibling inclusion in family interventions and support during early psychosis. This narrative review presents the current research related to the importance of family work during early psychosis, the needs and developmental significance of siblings during adolescence and early adulthood, the protective effects of sibling relationships, and the characteristics of early psychosis relevant to the sibling experience. It will also review the evidence of the sibling experience in chronic physical illness and disability, as well as long-term psychotic illness. Despite the evidence that working with families is important during early psychosis, siblings have been largely ignored. Siblings are an important reciprocal relationship of long duration. They play an important role in development during adolescence and early adulthood. These relationships may be an underutilized protective factor due to their inherent benefits and social support. Developmental theories imply that early psychosis could negatively impact the sibling relationship and their quality of life, effecting personality development and health outcomes. The evidence shows that adolescent physical illness or disability has a significantly negative impact on the sibling's quality of life and increases the risk for the onset of mental health issues. Long-term psychotic illness also results in negative experiences for siblings. Current evidence shows that siblings in early psychosis experience psychological distress and changes in functional performance. Further research using standard measures is required to understand the impact early psychosis has on the sibling relationship and their quality of life. © 2013 Wiley Publishing Asia Pty Ltd.

  4. Stigma by association and family burden among family members of people with mental illness: the mediating role of coping.

    Science.gov (United States)

    van der Sanden, Remko L M; Pryor, John B; Stutterheim, Sarah E; Kok, Gerjo; Bos, Arjan E R

    2016-09-01

    When someone has a mental illness, family members may share the experience of stigma. Past research has established that family members' experiences of stigma by association predict psychological distress and lower quality-of-life. The present study, conducted with 503 family members of people with mental illness examined the prevalence of 14 different coping strategies. Of greater importance, we examined the role of these coping strategies as mediators of the relationships between stigma by association and family burden, on the one hand, and outcomes, such as psychological distress and quality-of-life, on the other. The results showed that both perceived stigma by association and family burden are associated with greater psychological distress and lower quality-of-life, and that most coping strategies mediate these relationships. Adaptive coping strategies were related to reduced negative outcomes, while most maladaptive coping strategies were related to enhanced negative outcomes. Implications for intervention development are discussed.

  5. The effect of an anger management program for family members of patients with alcohol use disorders.

    Science.gov (United States)

    Son, Ju-Young; Choi, Yun-Jung

    2010-02-01

    This study was aimed to test the structured anger management nursing program for the family members of patients with alcohol use disorders (AUDs). Families with the AUDs suffer from the dysfunctional family dynamic caused by the patients' deteriorative disease processes of alcohol dependence. Family members of AUDs feel bitter and angry about the uncontrolled behaviors and relapses of the patients in spite of great effort for a long time. This chronic anger threatens the optimal function of the family as well as obstructs the family to help the patients who are suffering from AUDs. Sixty three subjects were participated who were referred from community mental health centers, alcohol consultation centers, and an alcohol hospital in Korea. Pre-post scores of the Korean Anger Expression Inventory were used to test the program. An anger management program was developed and implemented to promote anger expression and anger management for the family members of the patients with AUDs. The total anger expression score of the experimental group was significantly more reduced as compared with that of the control group. Subjects in the experimental group reported after the program that they felt more comfortable and their life was changed in a better way. The anger management program was effective to promote anger expression and anger management for family members of AUDs. Nurses need to include family members in their nursing process as well as to care of patients with AUDs to maximize nursing outcome and patient satisfaction. 2010 Elsevier Inc. All rights reserved.

  6. "Living with dying": the evolution of family members' experience of mechanical ventilation.

    Science.gov (United States)

    Sinuff, Tasnim; Giacomini, Mita; Shaw, Rhona; Swinton, Marilyn; Cook, Deborah J

    2009-01-01

    Communication with families about mechanical ventilation may be more effective once we gain a better understanding of what families experience and understand about this life support technology when their loved ones are admitted to the intensive care unit (ICU). We conducted in-depth interviews with family members of 27 critically ill patients who required mechanical ventilation for > or = 7 days and had an estimated ICU mortality of > or = 50%. Team members reviewed transcripts independently and used grounded theory analysis. The central theme of family members' experience with mechanical ventilation was "living with dying." Initial reactions to the ventilator were of shock and surprise. Family members perceived no option except mechanical ventilation. Although the ventilator kept the patient alive, it also symbolized proximity to death. In time, families became accustomed to images of the ICU as ventilation became more familiar and routine. Their shock and horror were replaced by hope that the ventilator would allow the body to rest, heal, and recover. However, ongoing exposure to their loved one's critical illness and the new role as family spokesperson were traumatizing. Family members' experiences and their understanding of mechanical ventilation change over time, influenced by their habituation to the ICU environment and its routines. They face uncertainty about death, but maintain hope. Understanding these experiences may engender more respectful, meaningful communication about life support with families.

  7. Family members' experience of the pre-diagnostic phase of dementia: a synthesis of qualitative evidence.

    Science.gov (United States)

    Rogers, Kirrily; Coleman, Honor; Brodtmann, Amy; Darby, David; Anderson, Vicki

    2017-09-01

    Most research on family members' experience of dementia has focused on the time after diagnosis. Yet, once people reach clinical attention, families have already been living with the changes for some time. These pre-diagnosis experiences can influence later caregiving. We aimed to synthesize qualitative research exploring family members' experiences of the pre-diagnostic phase of dementia to inform clinical practice. We conducted a thematic synthesis of 11 studies that met our inclusion criteria following a comprehensive literature search. An overarching theme, sense-making, captured the primary process that family members engage in throughout the pre-diagnostic period. Within this, four major analytic themes were extracted as central concepts in understanding family members' experiences of the pre-diagnostic phase of dementia: the nature of change; appraisals of change; reactions to change; and the influence of others. Relevant features of the family experience of dementia onset can be characterized within several major themes. These findings highlight the complex process of recognizing early symptoms of dementia for people living with this condition and their families. Our findings also provide the foundation for developing theoretical frameworks that will ultimately assist with improving recognition of dementia onset, clinical communication with family members, and interventions to reduce family burden.

  8. DNA rearrangement in human follicular lymphoma can involve the 5' or the 3' region of the bcl-2 gene

    International Nuclear Information System (INIS)

    Tsujimoto, Y.; Bashir, M.M.; Givol, I.; Cossman, J.; Jaffe, E.; Croce, C.M.

    1987-01-01

    In most human lymphomas, the chromosome translocation t(14;18) occurs within two breakpoint clustering regions on chromosome 18, the major one at the 3' untranslated region of the bcl-2 gene and the minor one at 3' of the gene. Analysis of a panel of follicular lymphoma DNAs using probes for the first exon of the bcl-2 gene indicates that DNA rearrangements may also occur 5' to the involved bcl-2 gene. In this case the IgH locus and the bcl-2 gene are found in an order suggesting that an inversion also occurred during the translocation process. The coding region of the bcl-2 gene, however, are left intact in all cases of follicular lymphoma studied to date

  9. Family members' expectations regarding nurses' competence in care homes: a qualitative interview study.

    Science.gov (United States)

    Kiljunen, Outi; Kankkunen, Päivi; Partanen, Pirjo; Välimäki, Tarja

    2017-11-22

    Structural and cultural changes in the care of older people have influenced nursing practice, creating a need to identify current competency requirements for nurses working in care homes. Family members have an important role in ensuring the well-being of older people living in care homes, and family members' can provide valuable information about competence requirements. To explore the expectations of the care home residents' family members regarding the competence of nurses in care homes for older people. A qualitative descriptive design was used. Semi-structured interviews were conducted with 18 care home residents' family members between March and September 2016. Participants were recruited with help from regional associations and member associations of The Central Association of Carers in Finland and from regional associations of The Alzheimer's Society of Finland. The snowball technique was also used. The data were analysed using inductive content analysis. Ethics committee approval was obtained from the university committee on research ethics, and written informed consent was obtained from participants. The care home residents' family members expected that nurses would be able to interact with and treat people respectfully. Reflective collaboration between the nurse and a family member was also emphasised. Family members expected nurses to provide high-quality basic care and nursing and support residents' well-being individually and holistically. Family members' expectations reflect the need for ethical and interactional competence in the care home. In addition, evidence-based practice competencies are required to provide high-quality care. Nurses' ability to provide person-centred, individual and holistic care is vital to ensure care home residents' well-being. © 2017 Nordic College of Caring Science.

  10. The Needs of Family Members of Cancer Patients

    Science.gov (United States)

    1988-01-01

    suffering in addition to feelings of powerlessness, guilt , anger, ambivalence, and fear for the patient and themselves. Another task for the family is...patients had breast cancer, five patients had lung cancer, five more had cancer of the gastrointestinal tract, three had cancer of the liver or pancreas ...the patient 3.03 1.07 E 14. To talk about feelings such as anger or guilt 3.03 1.07 E 15. To have comfortable furniture in the waiting room 2.82 0.90 P

  11. Perceived Intrafamilial Connectedness and Autonomy in Families with and without an Anxious Family Member: A Multiple Informant Approach

    Science.gov (United States)

    de Albuquerque, Jiske E. G.; Schneider, Silvia

    2012-01-01

    Perceived intrafamilial "emotional connectedness" and "autonomy" were investigated within families with and without an anxious family member using a multiple informant approach. The sample consisted of 32 mothers with a current anxiety disorder and 56 controls, their partners, and their anxious and nonanxious teenage children. No differences were…

  12. Quality of relationship between veterans with traumatic brain injury and their family members.

    Science.gov (United States)

    Winter, Laraine; Moriarty, Helene J

    2017-01-01

    The quality of the relationship between patients with many illnesses and their family members has been shown to affect the well-being of both. Yet, relationship quality has not been studied in traumatic brain injury (TBI), and giving and receiving aspects have not been distinguished. The present study of veterans with TBI examined associations between relationship quality and caregiver burden, satisfaction with caregiving, and veterans' competence in interpersonal functioning, rated by veterans and family members. In this cross-sectional study, 83 veterans and their family members were interviewed at home. Measures of quality of relationship, veterans' interpersonal competence and sociodemographics were collected for both, caregiver burden and satisfaction for family members only. As predicted, veteran-rated Q rel /Giving was associated with family-rated Q rel /Receiving, and veteran-rated Q rel /Receiving with family-rated Q rel /Giving. Lower caregiver burden and higher caregiving satisfaction were associated with higher Q rel /Receiving scores but not with Q rel /Giving scores. Veterans' interpersonal competence was associated with total Q rel as rated by either veterans or family members. Relationship quality should be included in family research in TBI, and giving and receiving aspects should be differentiated. Findings suggest that lower caregiver burden and greater satisfaction should be more achievable by increasing caregivers' sense of benefits received from the relationship.

  13. The needs of family members of intensive care unit patients: A ...

    African Journals Online (AJOL)

    ARTICLE. 44 SAJCC November 2016, Vol. 32, No. 2. The needs of family members of intensive care unit patients: A ... loved one will be survival, disability or death.[1] .... the participants of this study (the constructivist paradigm, which was.

  14. Factors affecting frequency of communication about family health history with family members and doctors in a medically underserved population.

    Science.gov (United States)

    Kaphingst, Kimberly A; Goodman, Melody; Pandya, Chintan; Garg, Priyanka; Stafford, Jewel; Lachance, Christina

    2012-08-01

    Family history contributes to risk for many common chronic diseases. Little research has investigated patient factors affecting communication of this information. 1061 adult community health center patients were surveyed. We examined factors related to frequency of discussions about family health history (FHH) with family members and doctors. Patients who talked frequently with family members about FHH were more likely to report a family history of cancer (p =.012) and heart disease (p history of heart disease (p = .011), meet physical activity recommendations (p = .022), seek health information frequently in newspapers (p history of some diseases, those not meeting physical activity recommendations, and those who do not frequently seek health information may not have ongoing FHH discussions. Interventions are needed to encourage providers to update patients' family histories systematically and assist patients in initiating FHH conversations in order to use this information for disease prevention and control. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  15. Hedgehog Signaling Regulates the Survival of Gastric Cancer Cells by Regulating the Expression of Bcl-2

    Science.gov (United States)

    Han, Myoung-Eun; Lee, Young-Suk; Baek, Sun-Yong; Kim, Bong-Seon; Kim, Jae-Bong; Oh, Sae-Ock

    2009-01-01

    Gastric cancer is the second most common cause of cancer deaths worldwide. The underlying molecular mechanisms of its carcinogenesis are relatively poorly characterized. Hedgehog (Hh) signaling, which is critical for development of various organs including the gastrointestinal tract, has been associated with gastric cancer. The present study was undertaken to reveal the underlying mechanism by which Hh signaling controls gastric cancer cell proliferation. Treatment of gastric cancer cells with cyclopamine, a specific inhibitor of Hh signaling pathway, reduced proliferation and induced apoptosis of gastric cancer cells. Cyclopamine treatment induced cytochrome c release from mitochondria and cleavage of caspase 9. Moreover, Bcl-2 expression was significantly reduced by cyclopamine treatment. These results suggest that Hh signaling regulates the survival of gastric cancer cells by regulating the expression of Bcl-2. PMID:19742123

  16. Perceptions of family members of palliative medicine and hospice patients who experienced music therapy.

    Science.gov (United States)

    Gallagher, Lisa M; Lagman, Ruth; Bates, Debbie; Edsall, Melissa; Eden, Patricia; Janaitis, Jessica; Rybicki, Lisa

    2017-06-01

    Evidence shows that music therapy aids in symptom management and improves quality of life for palliative medicine and hospice patients. The majority of previous studies have addressed patient needs, while only a few addressed the needs of family members. The primary purpose of this study was to understand family members' perceptions of music therapy experienced by a relative in palliative medicine or hospice. Patient self-reported scales and music therapist assessment of change were also investigated. Patients scored their symptoms (pain, anxiety, depression, shortness of breath, and mood) before and after music therapy sessions. One family member present during the session assessed perceived effect on the patient's pain, anxiety, depression, shortness of breath, stress level, restlessness, comfort level, mood, and quality of life. The effect on family member's stress level, quality of life, and mood and helpfulness of the music therapy session for the patient and self were studied. Recommendations about future patient participation in music therapy and qualitative comments were also solicited. Fifty family member/patient dyads participated in the study. Family member perceptions were positive, with 82% of responders indicating improvement for self and patient in stress, mood, and quality of life; 80% rating the session as extremely helpful; and 100% of 49 recommending further music therapy sessions for the patient. Patients reported statistically significant improvement in pain, depression, distress, and mood scores. Family members of patients in palliative medicine and hospice settings reported an immediate positive impact of music therapy on the patient and on themselves. More research needs to be conducted to better understand the benefits of music therapy for family members.

  17. Stress-coping morbidity among family members of addiction patients in Singapore.

    Science.gov (United States)

    Lee, Kae Meng Thomas; Manning, Victoria; Teoh, Hui Chin; Winslow, Munidasa; Lee, Arthur; Subramaniam, Mythily; Guo, Song; Wong, Kim Eng

    2011-07-01

    INTRODUCTIONS AND AIMS: Research from western countries indicates that family members of addiction patients report heightened stress and psychological morbidity. This current study aimed to examine stress, coping behaviours, related morbidity and subsequent resource utilisation among family members of patients attending a national treatment program in Singapore. The study used a matched case-control design. One hundred family members of addiction patients attending treatment and 100 matched controls completed a semi-structured interview with a researcher. This included the Beck Depression Inventory-II, Short-Form Health Survey-36, General Health Questionnaire-28, Perceived Stress Scale, Family Member Impact Scale and Coping Questionnaire, and also assessed service utilisation. T-tests revealed significantly greater depression, stress and psychiatric morbidity and poorer overall well-being (Short-Form Health Survey-36) among family members compared with controls. Despite the apparent negative impact on mental health, their physical morbidity did not differ from controls and services utilisation was low. Tolerant-inactive coping was found to be most strongly correlated with psychological well-being. Multivariate analysis indicated that perceived stress was the strongest predictor of overall strain (General Health Questionnaire), but this was not moderated by coping style. Subjective appraisal of stress and coping responses are essential factors affecting the morbidity of family members. Family members demonstrated a need and willingness to engage in formal treatment/counselling for their own problems that were attributed to living with an addiction patient. This provides an opportunity for stress management and brief interventions to modify coping styles, thereby minimizing the potential negative mental health impact on family members. © 2011 Australasian Professional Society on Alcohol and other Drugs.

  18. Influence of p53 and bcl-2 on chemosensitivity in benign and malignant prostatic cell lines.

    Science.gov (United States)

    Serafin, Antonio M; Bohm, Lothar

    2005-01-01

    The administration of cancer chemotherapeutic agents results in an increase in the apoptotic cells in the tumor: therefore, it has been assumed that anticancer drugs exhibit their cytotoxic effects via apoptotic signaling pathways. Characteristics that confer sensitivity to drug-induced apoptosis are, a functional p53 protein and expression of the apoptosis-promoting protein, bax. The role of p53 and bax/bcl-2 in drug-induced apoptosis was assessed in six prostate cell lines, 1532T, 1535T, 1542T, 1542N, BPH-1 and LNCaP using TD(50) concentrations of etoposide, vinblastine and estramustine. Cell death was monitored morphologically by fluorescent microscopy, and by flow cytometry (Annexin-V assay). Apoptotic morphology was rather low and ranged from 0.1% to 12.1%, 3.0% to 6.0% and 0.1% to 8.5% for etoposide, estramustine and vinblastine, respectively. Annexin-V binding and flow cytometry indicated apoptotic propensities of 0% to 4%, 0% to 3% and 0% to 5%, respectively. The percentage of cells responding to drug-induced apoptosis was, on average, higher in the tumor cell lines than in the normal cell lines, but showed no correlation with p53 status. The percentage of cells showing necrosis, assessed by Annexin binding and Propidium Iodide permeability in aqueous medium, tended to be much higher, and was found to be at the level of 5% to 30%. Immunoblotting demonstrated that bax and bcl-2 proteins were expressed at a basal level in all cell lines, but did not increase after exposure to TD(50) doses of the three drugs. The ratio of bax and bcl-2, measured by laser scanning densitometry, was not altered by the drug-induced DNA damage. The results suggest that apoptosis is not a major mechanism of drug-induced cell death in prostate cell lines and appears to be independent of p53 status and bax/bcl-2 expression.

  19. Psychiatric worker and family members: pathways towards co-operation networks within psychiatric assistance services

    Directory of Open Access Journals (Sweden)

    Silvia Carbone

    2014-03-01

    Full Text Available The family’s role in patient care was greatly altered by Law 180. This law, introduced in Italy in 1978, led to a gradual phasing out of custodial treatment for psychiatric patients. This different mindset, which views the family as an alternative to institutionalization, leads to it being seen as an essential entity in the setting up of community service dynamics. We interviewed health professionals in order to understand obstacles of collaboration between family members and mental health care workers. The goal was to uncover actions that promote collaboration and help build alliances between families and psychiatric workers. Results showed that health professionals view the family as a therapeutic resource. Despite this view, family members were rarely included in patient treatment. The reasons is: the structures have a theoretical orientation of collaboration with the family but, for nurses not are organized a few meeting spaces with family members. Services should create moments, such as multi-family groups or groups of information, managed by nurses and not only by doctors. These occasions it might facilitate the knowledge between professionals and family members.

  20. A qualitative study on communication between nursing students and the family members of patients.

    Science.gov (United States)

    Chan, Zenobia C Y

    2017-12-01

    When caring for a family as a unit, it is as crucial to communicate with the family members of a patient as it is with the patient. However, there is a lack of research on the views of nursing students on communicating with the family members of patients, and little has been mentioned in the nursing curriculum on this topic. The aim of this study was to explore nursing students' experiences of communicating with the family members of patients. A qualitative descriptive study. A total of 42 nursing students (21 undergraduate year-two students and 21 were master's year-one students) from one school of nursing in Hong Kong participated in in-depth individual interviews. Content analysis was adopted. The trustworthiness of this study was ensured by enhancing its credibility, confirmability, and dependability. Two main themes were discerned. The first, "inspirations gained from nursing student-family communication", included the following sub-themes: (a) responding to enquiries clearly, (b) avoiding sensitive topics, (c) listening to the patient's family, and (d) sharing one's own experiences. The second, "emotions aroused from nursing student-family communication", had the following sub-themes: (a) happiness, (b) anger, (c) sadness, and (d) anxiety. More studies on the perspectives of nursing students on communicating with family members should be conducted, to strengthen the contents and learning outcomes of nursing student-family communication in the existing nursing curriculum. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. A Comparative Study on the Meaning in Life of Patients with Cancer and Their Family Members.

    Science.gov (United States)

    Hassankhani, Hadi; Soheili, Amin; Hosseinpour, Issa; Eivazi Ziaei, Jamal; Nahamin, Mina

    2017-12-01

    Introduction: The overwhelming effects of cancer could be catastrophic for the patients and their family members, putting them at risk of experiencing uncertainty, loss, and an interruption in life. Also, it can influence their sense of meaning, a fundamental need equated with the purpose in life. Accordingly, this study aimed to compare the meaning in life (MiL) of patients with cancer and their family members. Methods: This descriptive comparative study was conducted on 400 patients with cancer and their family members admitted to university hospitals in Tabriz and Ardebil provinces, Iran. The participants were sampled conveniently and the Life Evaluation Questionnaire (LEQ) were used for collecting data analyzed through descriptive and inferential statistics in SPSS ver. 13 Software. Results: The mean score for the MiL of the patients with cancer and their family members was 119 (16.92) and 146.2 (17.07), respectively. There was a significant difference between patients with cancer and their family members in terms of MiL. Conclusion: The MiL of patients with cancer is lower than that of their family members, which indicates the need for further attention to the psychological processes and their modification in Iranian healthcare systems.

  2. A survey of family members' satisfaction with the services provided by hospice palliative care volunteers.

    Science.gov (United States)

    Claxton-Oldfield, Stephen; Gosselin, Natasha; Schmidt-Chamberlain, Kirsten; Claxton-Oldfield, Jane

    2010-05-01

    A total of 22 family members, whose deceased loved ones had used the services of a hospice palliative care volunteer, responded to a brief survey designed to assess the importance of the different kinds of support offered to them (family members) by the volunteer, their impressions of the volunteers' personal qualities/characteristics, their general experiences with the volunteer, and their overall satisfaction with the volunteer services. The kind of support that received the highest importance rating from family members was the opportunity to take a much-needed break from the demands of caring for their loved one, closely followed by emotional support, the volunteer spending time with them, and the volunteer providing them with information. Family members rated volunteers highly on a list of qualities/characteristics that exemplify individuals who are effective in this role. In all, 85% of the family members felt that their volunteer was well trained and 95% did not feel that their or their loved one's privacy had been invaded by having a volunteer. Overall, family members were very satisfied with the volunteer support they received. Some limitations of the study are discussed.

  3. BCL-2 inhibition targets oxidative phosphorylation and selectively eradicates quiescent human leukemia stem cells

    Science.gov (United States)

    Lagadinou, Eleni D.; Sach, Alexander; Callahan, Kevin; Rossi, Randall M.; Neering, Sarah J.; Minhajuddin, Mohammad; Ashton, John M.; Pei, Shanshan; Grose, Valerie; O’Dwyer, Kristen M.; Liesveld, Jane L.; Brookes, Paul S.; Becker, Michael W.; Jordan, Craig T.

    2013-01-01

    Summary Most forms of chemotherapy employ mechanisms involving induction of oxidative stress, a strategy that can be effective due to the elevated oxidative state commonly observed in cancer cells. However, recent studies have shown that relative redox levels in primary tumors can be heterogeneous, suggesting that regimens dependent on differential oxidative state may not be uniformly effective. To investigate this issue in hematological malignancies, we evaluated mechanisms controlling oxidative state in primary specimens derived from acute myelogenous leukemia (AML) patients. Our studies demonstrate three striking findings. First, the majority of functionally-defined leukemia stem cells (LSCs) are characterized by relatively low levels of reactive oxygen species (termed “ROS-low”). Second, ROS-low LSCs aberrantly over-express BCL-2. Third, BCL-2 inhibition reduced oxidative phosphorylation and selectively eradicated quiescent LSCs. Based on these findings, we propose a model wherein the unique physiology of ROS-low LSCs provides an opportunity for selective targeting via disruption of BCL-2-dependent oxidative phosphorylation. PMID:23333149

  4. Methamphetamine induces apoptosis in immortalized neural cells: protection by the proto-oncogene, bcl-2.

    Science.gov (United States)

    Cadet, J L; Ordonez, S V; Ordonez, J V

    1997-02-01

    Methamphetamine (METH) is an amphetamine analog that produces degeneration of the dopaminergic system in mammals. The neurotoxic effects of the drug are thought to be mediated by oxygen-based free radicals. In the present report, we have used immortalized neural cells obtained from rat mesencephalon in order to further assess the role of oxidative stress in METH-induced neurotoxicity. We thus tested if the anti-death proto-oncogene, bcl-2 could protect against METH-induced cytotoxicity. METH caused dose-dependent loss of cellular viability in control cells while bcl-2-expressing cells were protected against these deleterious effects. Using flow cytometry, immunofluorescent staining, and DNA electrophoresis, we also show that METH exposure can cause DNA strand breaks, chromatin condensation, nuclear fragmentation, and DNA laddering. All these changes were prevented by bcl-2 expression. These observations provide further support for the involvement of oxidative stress in the toxic effects of amphetamine analogs. They also document that METH-induced cytotoxicity is secondary to apoptosis. These findings may be of relevance to the cause(s) of Parkinson's disease which involves degeneration of the nigrostriatal dopaminergic pathway.

  5. HAMLET triggers apoptosis but tumor cell death is independent of caspases, Bcl-2 and p53.

    Science.gov (United States)

    Hallgren, O; Gustafsson, L; Irjala, H; Selivanova, G; Orrenius, S; Svanborg, C

    2006-02-01

    HAMLET (Human alpha-lactalbumin Made Lethal to Tumor cells) triggers selective tumor cell death in vitro and limits tumor progression in vivo. Dying cells show features of apoptosis but it is not clear if the apoptotic response explains tumor cell death. This study examined the contribution of apoptosis to cell death in response to HAMLET. Apoptotic changes like caspase activation, phosphatidyl serine externalization, chromatin condensation were detected in HAMLET-treated tumor cells, but caspase inhibition or Bcl-2 over-expression did not prolong cell survival and the caspase response was Bcl-2 independent. HAMLET translocates to the nuclei and binds directly to chromatin, but the death response was unrelated to the p53 status of the tumor cells. p53 deletions or gain of function mutations did not influence the HAMLET sensitivity of tumor cells. Chromatin condensation was partly caspase dependent, but apoptosis-like marginalization of chromatin was also observed. The results show that tumor cell death in response to HAMLET is independent of caspases, p53 and Bcl-2 even though HAMLET activates an apoptotic response. The use of other cell death pathways allows HAMLET to successfully circumvent fundamental anti-apoptotic strategies that are present in many tumor cells.

  6. CHIS - Information concerning the health insurance of frontalier workers who are family members of a CHIS main member

    CERN Multimedia

    2014-01-01

    We recently informed you that the Organization was still in discussions with the Host State authorities to clarify the situation regarding the health insurance of frontalier workers who are family members (as defined in the Staff Rules and Regulations) of a CHIS main member, and that we were hoping to arrive at a solution soon.   After extensive exchanges, we finally obtained a response a few days ago from the Swiss authorities, with which we are fully satisfied and which we can summarise as follows: 1) Frontalier workers who are currently using the CHIS as their basic health insurance can continue to do so. 2) Family members who become frontalier workers, or those who have not yet exercised their “right to choose” (droit d’option) can opt to use the CHIS as their basic health insurance. To this end, they must complete the form regarding the health insurance of frontaliers, ticking the LAMal box and submitting their certificate of CHIS membership (available from U...

  7. Routine HIV Testing of Family Members of Hospitalized Patients in Nigeria

    Directory of Open Access Journals (Sweden)

    Olusegun Busari

    2012-04-01

    Full Text Available Background: HIV testing for family members of HIV-positive patients may enhance disclosure of status of spouses, encourage family social support and improve access to HIV services. Objective was to employ the approach of routine HIV testing to determine the prevalence of HIV among family members of both HIV positive and negative patients on admission in a federal HIV treatment designated hospital in Western Nigeria Methodology: This prospective study was conducted between January 2006 and June 2009. Ethical clearance was obtained from the Research and Ethics committee of the hospital prior to the study. Informed consent was obtained from each participant. HIV testing was offered to consenting family members of HIV positive and negative patients on admission. The family members included spouses, children of patients, parents of paediatric patients and other family members. Analysis was done in frequencies and percentages Results: 162 family members of 184 patients were tested. Spouses were, 81 (50.0%; fathers, 14 (8.6%; mothers, 20 (12.3%; children, 19 (11.7% and others family members, 28 (17.3%. 151 (93.2% of testers were first timers. Majority of those tested (82.1% had post-test counseling. The overall HIV prevalence was 12.3% (20/162. HIV prevalence within different family members was 14.8% (12/81, 20% (4/20, 7.1% (1/14, 10.5% (2/19 and 3.6% (1/28 for spouses, mothers, fathers, children and others respectively.In addition, the prevalence of HIV among family members of HIV positive and negative patients was 15.6% (14/90 and 8.3% (6/72 respectively. Of 12 spouses that were positive, 7 (13.5% were HIV-discordant; and in 71.4% (5/7 of discordant couples, the spouse was positive while the patient on admission was negative. Conclusion: The results indicate that routine HIV testing of family members of patients on admission is a strategy for identification of vast number of HIV infected persons. This method is not only innovative, but also a novel

  8. The needs of patient family members in the intensive care unit in Kigali Rwanda

    Directory of Open Access Journals (Sweden)

    Petra Brysiewicz

    2014-07-01

    Full Text Available Background. The admission of a relative to an intensive care unit (ICU is a stressful experience for family members. There has been limited research addressing this issue in Kigali, Rwanda.Objective. To explore the needs of patient family members admitted into an ICU in Kigali, Rwanda.Methods. This study used a quantitative exploratory design focused on exploring the needs of patient family members in ICU at one hospital in Kigali, Rwanda. Family members (N=40 were recruited using the convenience sampling strategy. The Critical Care Family Needs Inventory was used to collect relevant data.Results. The participants identified various needs to be met for the family during the patient’s admission in ICU. The most important was the need for assurance, followed by the need for comfort, information, proximity and lastly support. Three additional needs specific to this sample group were also identified, related to resource constraints present in the hospital where the study was carried out.Conclusion. These results offer insight for nurses and other healthcare professionals as to what the important needs are that must be considered for the patient family members in ICUs within a resource-constrained environment.

  9. Experience and needs of family members of patients treated with extracorporeal membrane oxygenation.

    Science.gov (United States)

    Tramm, Ralph; Ilic, Dragan; Murphy, Kerry; Sheldrake, Jayne; Pellegrino, Vincent; Hodgson, Carol

    2017-06-01

    To explore the experiences of family members of patients treated with extracorporeal membrane oxygenation. Sudden onset of an unexpected and severe illness is associated with an increased stress experience of family members. Only one study to date has explored the experience of family members of patients who are at high risk of dying and treated with extracorporeal membrane oxygenation. A qualitative descriptive research design was used. A total of 10 family members of patients treated with extracorporeal membrane oxygenation were recruited through a convenient sampling approach. Data were collected using open-ended semi-structured interviews. A six-step process was applied to analyse the data thematically. Four criteria were employed to evaluate methodological rigour. Family members of extracorporeal membrane oxygenation patients experienced psychological distress and strain during and after admission. Five main themes (Going Downhill, Intensive Care Unit Stress and Stressors, Carousel of Roles, Today and Advice) were identified. These themes were explored from the four roles of the Carousel of Roles theme (decision-maker, carer, manager and recorder) that participants experienced. Nurses and other staff involved in the care of extracorporeal membrane oxygenation patients must pay attention to individual needs of the family and activate all available support systems to help them cope with stress and strain. An information and recommendation guide for families and staff caring for extracorporeal membrane oxygenation patients was developed and needs to be applied cautiously to the individual clinical setting. © 2016 John Wiley & Sons Ltd.

  10. Home support workers perceptions of family members of their older clients: a qualitative study.

    Science.gov (United States)

    Sims-Gould, Joanie; Byrne, Kerry; Tong, Catherine; Martin-Matthews, Anne

    2015-12-12

    Health care discourse is replete with references to building partnerships between formal and informal care systems of support, particularly in community and home based health care. Little work has been done to examine the relationship between home health care workers and family caregivers of older clients. The purpose of this study is to examine home support workers' (HSWs) perceptions of their interactions with their clients' family members. The goal of this research is to improve client care and better connect formal and informal care systems. A qualitative study, using in-depth interviews was conducted with 118 home support workers in British Columbia, Canada. Framework analysis was used and a number of strategies were employed to ensure rigor including: memo writing and analysis meetings. Interviews were transcribed verbatim and sent to a professional transcription agency. Nvivo 10 software was used to manage the data. Interactions between HSWs and family members are characterized in terms both of complementary labour (family members providing informational and instrumental support to HSWs), and disrupted labour (family members creating emotion work and additional instrumental work for HSWs). Two factors, the care plan and empathic awareness, further impact the relationship between HSWs and family caregivers. HSWs and family members work to support one another instrumentally and emotionally through interdependent interactions and empathic awareness. Organizational Care Plans that are too rigid or limited in their scope are key factors constraining interactions.

  11. Adaptive coping strategies of affected family members of a relative with substance misuse: A qualitative study.

    Science.gov (United States)

    McCann, Terence V; Lubman, Dan I

    2018-01-01

    To explore the coping strategies used by affected family members of a relative with substance misuse. Families play an important role in supporting a relative with substance misuse. However, the experience often has an adverse effect on their general well-being, the extent of which depends largely on their coping strategies. An interpretative phenomenological analysis study. Data were collected between January - December 2015. Semistructured, audio-recorded qualitative interviews were conducted with 31 affected family members. Three main themes and related subthemes were abstracted from the data illustrating how participants coped with their relative's substance misuse: (1) Seeking timely access to evidence-based information; (2) Enhancing personal coping strategies and (3) Accessing informal and formal support. Greater investment is needed in support services for affected family members, particularly in regional and rural areas. A wide range of accessible evidence-based information and informal and formal support, including telephone and online support, is needed to assist them to cope in this crucial support-giving role. Affected family members need to adopt a flexible set of coping strategies while supporting a relative with substance misuse. Family and friends, alcohol and other drug services, mental health nurses and other clinicians have a critical role providing emotional, instrumental and educational support to affected family members to enhance their adaptive coping strategies. © 2017 John Wiley & Sons Ltd.

  12. Family members' involvement in psychiatric care: experiences of the healthcare professionals' approach and feeling of alienation.

    Science.gov (United States)

    Ewertzon, M; Lützén, K; Svensson, E; Andershed, B

    2010-06-01

    The involvement of family members in psychiatric care is important for the recovery of persons with psychotic disorders and subsequently reduces the burden on the family. Earlier qualitative studies suggest that the participation of family members can be limited by how they experience the professionals' approach, which suggests a connection to the concept of alienation. Thus, the aim of this study was in a national sample investigate family members' experiences of the psychiatric health care professionals' approach. Data were collected by the Family Involvement and Alienation Questionnaire. The median level and quartiles were used to describe the distributions and data were analysed with non-parametric statistical methods. Seventy family members of persons receiving psychiatric care participated in the study. The results indicate that a majority of the participants respond that they have experiencing a negative approach from the professionals, indicating lack of confirmation and cooperation. The results also indicate that a majority of the participants felt powerlessness and social isolation in the care being provided, indicating feelings of alienation. A significant but weak association was found between the family members' experiences of the professionals' approach and their feelings of alienation.

  13. Caring for a family member with a traumatic brain injury.

    Science.gov (United States)

    Knight, R G; Devereux, R; Godfrey, H P

    1998-06-01

    The responses to a questionnaire on subjective burden are reported for 52 primary caregivers of a group of persons with traumatic brain injuries sustained an average of 6 years previously. The aim of the study was to examine satisfaction with social support, perception of coping skills, and appraisal of symptoms as predictors of strain in the carers. A range of responses, both positive and negative, to the work of caring for a relative with a head injury was reported. A high prevalence rate of emotional and behavioural changes in the persons with head injuries was found and the amount of distress caused by these symptoms was found to be predictive of burden. The other factor important in predicting burden was the carers' ratings of their satisfaction with their ability to cope with the work of caregiving. Social support, injury severity, and the demographic characteristics of the persons with head injury and their carers were not significant predictors. Depression in the carers was also investigated and the variable most predictive of elevated depression scores was coping satisfaction. These findings reinforce the importance of strengthening carers coping resources in rehabilitation work with head injured persons and their families.

  14. Leiomodins: larger members of the tropomodulin (Tmod) gene family

    Science.gov (United States)

    Conley, C. A.; Fritz-Six, K. L.; Almenar-Queralt, A.; Fowler, V. M.

    2001-01-01

    The 64-kDa autoantigen D1 or 1D, first identified as a potential autoantigen in Graves' disease, is similar to the tropomodulin (Tmod) family of actin filament pointed end-capping proteins. A novel gene with significant similarity to the 64-kDa human autoantigen D1 has been cloned from both humans and mice, and the genomic sequences of both genes have been identified. These genes form a subfamily closely related to the Tmods and are here named the Leiomodins (Lmods). Both Lmod genes display a conserved intron-exon structure, as do three Tmod genes, but the intron-exon structure of the Lmods and the Tmods is divergent. mRNA expression analysis indicates that the gene formerly known as the 64-kDa autoantigen D1 is most highly expressed in a variety of human tissues that contain smooth muscle, earning it the name smooth muscle Leiomodin (SM-Lmod; HGMW-approved symbol LMOD1). Transcripts encoding the novel Lmod gene are present exclusively in fetal and adult heart and adult skeletal muscle, and it is here named cardiac Leiomodin (C-Lmod; HGMW-approved symbol LMOD2). Human C-Lmod is located near the hypertrophic cardiomyopathy locus CMH6 on human chromosome 7q3, potentially implicating it in this disease. Our data demonstrate that the Lmods are evolutionarily related and display tissue-specific patterns of expression distinct from, but overlapping with, the expression of Tmod isoforms. Copyright 2001 Academic Press.

  15. Acute Physiologic Stress and Subsequent Anxiety Among Family Members of ICU Patients.

    Science.gov (United States)

    Beesley, Sarah J; Hopkins, Ramona O; Holt-Lunstad, Julianne; Wilson, Emily L; Butler, Jorie; Kuttler, Kathryn G; Orme, James; Brown, Samuel M; Hirshberg, Eliotte L

    2018-02-01

    The ICU is a complex and stressful environment and is associated with significant psychologic morbidity for patients and their families. We sought to determine whether salivary cortisol, a physiologic measure of acute stress, was associated with subsequent psychologic distress among family members of ICU patients. This is a prospective, observational study of family members of adult ICU patients. Adult medical and surgical ICU in a tertiary care center. Family members of ICU patients. Participants provided five salivary cortisol samples over 24 hours at the time of the patient ICU admission. The primary measure of cortisol was the area under the curve from ground; the secondary measure was the cortisol awakening response. Outcomes were obtained during a 3-month follow-up telephone call. The primary outcome was anxiety, measured by the Hospital Anxiety and Depression Scale-Anxiety. Secondary outcomes included depression and posttraumatic stress disorder. Among 100 participants, 92 completed follow-up. Twenty-nine participants (32%) reported symptoms of anxiety at 3 months, 15 participants (16%) reported depression symptoms, and 14 participants (15%) reported posttraumatic stress symptoms. In our primary analysis, cortisol level as measured by area under the curve from ground was not significantly associated with anxiety (odds ratio, 0.94; p = 0.70). In our secondary analysis, however, cortisol awakening response was significantly associated with anxiety (odds ratio, 1.08; p = 0.02). Roughly one third of family members experience anxiety after an ICU admission for their loved one, and many family members also experience depression and posttraumatic stress. Cortisol awakening response is associated with anxiety in family members of ICU patients 3 months following the ICU admission. Physiologic measurements of stress among ICU family members may help identify individuals at particular risk of adverse psychologic outcomes.

  16. Effect of polysaccharides from Angelica sinensis on Bcl-2 and Bax protein expression of irradiated liver cells

    International Nuclear Information System (INIS)

    Sun Yuanlin; Tang Jian; Gu Xiaohong; Li Deyuan

    2009-01-01

    Objective: To investigate the effect of polysaccharides from Angelica sinensis (ASP3) on Bcl-2 and Bax protein expression of irradiated liver cells from mice. Methods: Bcl-2 and Bax protein expression of liver cells in vitro exposed to 2.0 Gy rays were examined by using immunohistochemistry method. Results: The expression of apoptosis-accelerating protein Bax in the irradiation group was enhanced obviously (70.83%), while apoptosis inhibiting protein Bcl-2 tended to decline (55.60%), with the statistically significant difference (P <0.01) compared with that of the control. ASP3 pretreatment could regulate Bcl-2 and Bax protein expression of liver cells, inhibiting Bax protein expression(64.14/58.37%) and increasing Bcl-2 protein expression(59.21%/ 67.45%). The differences between the high dosage (100 mg/L of ASP3) and the irradiation group were statistically significant (P<0.05). Conclusions: ASP3 pretreatment could prohibit the apoptosis of radiation- damaged liver cells due to abnormal expression of Bcl-2 and Bax, and reduce the cell apoptosis by increasing Bcl-2/Bax protein expression so as to enhance the radiation endurance of liver cells. (authors)

  17. Inter- and intratumoral heterogeneity of BCL2 correlates with IgH expression and prognosis in follicular lymphoma

    International Nuclear Information System (INIS)

    Barreca, A; Martinengo, C; Annaratone, L; Righi, L; Chiappella, A; Ladetto, M; Demurtas, A; Chiusa, L; Stacchini, A; Crosetto, N; Oudenaarden, A van; Chiarle, R

    2014-01-01

    Most follicular lymphomas (FLs) are genetically defined by the t(14;18)(q32;q21) translocation that juxtaposes the BCL2 gene to the immunoglobulin heavy chain (IgH) 3' regulatory regions (IgH-3'RRs). Despite this recurrent translocation, FL cases are heterogeneous in terms of intratumoral clonal diversity for acquired mutations and variations in the tumor microenvironment. Here we describe an additional mechanism that contributes to inter- and intratumoral heterogeneity in FLs. By applying a novel single-molecule RNA fluorescence-based in situ hybridization (FISH) technique to detect mRNA molecules of BCL2 and IgH in single cells, we found marked heterogeneity in the number of BCL2 mRNA transcripts within individual lymphoma cells. Moreover, BCL2 mRNA molecules correlated with IgH mRNA molecules in individual cells both in t(14;18) lymphoma cell lines and in patient samples. Consistently, a strong correlation between BCL2 and IgH protein levels was found in a series of 205 primary FL cases by flow cytometry and immunohistochemistry. Inter- and intratumoral heterogeneity of BCL2 expression determined resistance to drugs commonly used in FL treatment and affected overall survival of FL patients. These data demonstrate that BCL2 and IgH expressions are heterogeneous and coregulated in t(14;18)-translocated cells, and determine the response to therapy in FL patients

  18. Impact of family history assessment on communication with family members and health care providers: A report from the Family Healthware™ Impact Trial (FHITr).

    Science.gov (United States)

    Wang, Catharine; Sen, Ananda; Plegue, Melissa; Ruffin, Mack T; O'Neill, Suzanne M; Rubinstein, Wendy S; Acheson, Louise S

    2015-08-01

    This study examines the impact of Family Healthware™ on communication behaviors; specifically, communication with family members and health care providers about family health history. A total of 3786 participants were enrolled in the Family Healthware™ Impact Trial (FHITr) in the United States from 2005-7. The trial employed a two-arm cluster-randomized design, with primary care practices serving as the unit of randomization. Using generalized estimating equations (GEE), analyses focused on communication behaviors at 6month follow-up, adjusting for age, site and practice clustering. A significant interaction was observed between study arm and baseline communication status for the family communication outcomes (p'scommunicating at baseline and those who were not. Among participants who were not communicating at baseline, intervention participants had higher odds of communicating with family members about family history risk (OR=1.24, p=0.042) and actively collecting family history information at follow-up (OR=2.67, p=0.026). Family Healthware™ did not have a significant effect on family communication among those already communicating at baseline, or on provider communication, regardless of baseline communication status. Greater communication was observed among those at increased familial risk for a greater number of diseases. Family Healthware™ prompted more communication about family history with family members, among those who were not previously communicating. Efforts are needed to identify approaches to encourage greater sharing of family history information, particularly with health care providers. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Family Members' Views on Seeking Placement in State-Supported Living Centers in Texas

    Science.gov (United States)

    Colvin, Alex D.; Larke, Patricia J.

    2013-01-01

    This study investigated the factors that influence family members' decisions to seek placement for relatives with intellectual and/or developmental disabilities (ID/DD) into state-supported living centers in Texas. The sample included 51 family caregivers between the ages of 26 and 95. Using descriptive statistics, correlation, and inferential…

  20. Parent Perspectives: Understanding Support Systems for Kindergarteners with Special Needs and Their Family Members

    Science.gov (United States)

    Okraski, Ronni

    2017-01-01

    Having a child with special needs can be overwhelming, emotionally draining and extremely stressful for parents and their family members. Research identifies the support systems families need in order to have quality-of-life. The current study uses mixed methods to evaluate the degree to which parents and other primary caregivers in Arizona view…

  1. A follow-up meeting post death is appreciated by family members of deceased patients.

    Science.gov (United States)

    Kock, M; Berntsson, C; Bengtsson, A

    2014-08-01

    A practice with a follow-up meeting post death (FUMPD) with physician and staff for family members of patients who died in the intensive care unit (ICU) was started as a quality project to improve the support of families in post-ICU bereavement. A quality improvement control was conducted after 4 years. The quality improvement control was made retrospectively as an anonymous non-coded questionnaire. Part A related to the FUMPD. Part B inquired if we could contact the family member again for a research project to evaluate family support post-ICU bereavement. The questionnaires were sent to 84 family members of 56 deceased patients. Part A: 46 out of 84 family members answered and had attended a FUMPD. Ninety-one percent of the family members thought that we should continue to offer FUMPD. Seventy-eight percent were satisfied with their meeting. Eighty percent felt that they understood the cause of death. The majority wanted the meeting to take place within 6 weeks of death. Ninety-one percent rated the physician as important to be present at the meeting. The social worker was rated more important to attend the meeting than the assistant nurse. Ninety-one percent wanted to discuss the cause of death.Part B: 54 out of 84 family members answered. Twenty out of 54 did not want us to contact them again. A routine with a Follow-Up Meeting Post Death with the ICU team for the families of the patients who die in the ICU is appreciated. The presence of the physician is important. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  2. The Relationship Between the Perceived Risk of Harm by a Family Member with Mental Illness and the Family Experience.

    Science.gov (United States)

    Katz, Judith; Medoff, Deborah; Fang, Li Juan; Dixon, Lisa B

    2015-10-01

    Family members of people with serious mental illness (SMI) at times report that they act to stop their ill relative from self harm or harming others. This study examines the relationship between the perception of risk of harm and family distress, burden, empowerment, coping, physical and mental health, appraisal of the caregiving experience, family communication, and family functioning. The study is a secondary analysis of baseline data collected for a randomized study of the family-to-family peer driven education program (FTF). Four hundred thirty-four enrolled individuals who were seeking to participate in FTF completed survey items that asked if they had tried to stop or prevent their ill family member from harming themselves or others in the last 30 days. Participants who perceived a recent risk of harm by their ill relative reported more negative appraisals of caregiving, greater psychological distress, poorer mental health and greater objective burden compared with those who did not perceive a recent risk of harm. The results suggest that families of persons with SMI should be asked about perceived risk of harm to self and others, and the presence of perceived risk of harm should serve as a red flag indicating the need for further evaluation of the family experience and additional support for the family.

  3. Difficult relationships--interactions between family members and staff in long-term care.

    Science.gov (United States)

    Norris, S

    2000-01-01

    Staff of long-term care facilities and family members have a common responsibility to ensure the best course of treatment and everyday care for residents who often cannot speak for themselves. Understanding the difference between instrumental and preservative care, and who the proper agent is to provide care in each category will not only improve staff/family interactions, but residential care in general. The Resident Enrichment and Activity Program improves the family/staff relationship obliquely by involving family in social activities; the Family Involvement in Care program, and the Patterns in Caregiving program directly target the relationship and involve the facility's administration to effect policy change.

  4. Complex Determinants in Specific Members of the Mannose Receptor Family Govern Collagen Endocytosis

    DEFF Research Database (Denmark)

    Jürgensen, Henrik J; Johansson, Kristina; Madsen, Daniel H

    2014-01-01

    Members of the well-conserved mannose receptor (MR) protein family have been functionally implicated in diverse biological and pathological processes. Importantly, a proposed common function is the internalization of collagen for intracellular degradation occurring during bone development, cancer...... invasion, and fibrosis protection. This functional relationship is suggested by a common endocytic capability and a candidate collagen-binding domain. Here we conducted a comparative investigation of each member's ability to facilitate intracellular collagen degradation. As expected, the family members u......PARAP/Endo180 and MR bound collagens in a purified system and internalized collagens for degradation in cellular settings. In contrast, the remaining family members, PLA2R and DEC-205, showed no collagen binding activity and were unable to mediate collagen internalization. To pinpoint the structural elements...

  5. NWHSS Implement Family Member Assessment Component in the Millennium Cohort Study

    Science.gov (United States)

    2012-10-01

    Response and Referral Rates (McMaster) Panel 4 Impact of Cognitive Dissonance Improvement Strategies *Open Discussion* Family Improvement... Cognitive Dissonance (Via Effort Justification) Study  This pilot study utilized a random selection of married Panel 4 Millennium Cohort members taking...Spousal and family  functioning  Determine service member  factors that are associated  with spouse reports of  marital  satisfaction  and  family

  6. Impact of prior ICU experience on ICU patient family members' psychological distress: A descriptive study.

    Science.gov (United States)

    Lewis, Chrystal L; Taylor, Jessica Z

    2017-12-01

    To determine if current levels of anxiety, depression and acute stress disorder symptoms differ significantly among family members of intensive-care-unit patients depending upon previous intensive-care experience. This study used a prospective, descriptive study design. Family members (N=127) from patients admitted within a 72-hour timeframe to the medical, surgical, cardiac and neurological intensive care units were recruited from waiting rooms at a medium-sized community hospital in the Southeastern United States. Participants completed the Hospital Anxiety and Depression Scale, the Impact of Events Scale-Revised, the Acute Stress Disorder Scale and a demographic questionnaire. A multivariate analysis revealed that family members of intensive-care-unit patients with a prior intensive-care experience within the past two years (n=56) were significantly more likely to report anxiety, depression and acute stress symptoms, Λ=0.92, F [4122]=2.70, p=0.034, partial η 2 =0.08, observed power=0.74. Results of this study show that family members' psychological distress is higher with previous familial or personal intensive-care experience. Nurses need to assess for psychological distress in ICU family members and identify those who could benefit from additional support services provided in collaboration with multidisciplinary support professionals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Development and Examination of a Family Triadic Measure to Examine Quality of Life Family Congruence in Nursing Home Residents and Two Family Members.

    Science.gov (United States)

    Aalgaard Kelly, Gina

    2015-01-01

    Objective: The overall purpose of this study was to propose and test a conceptual model and apply family analyses methods to understand quality of life family congruence in the nursing home setting. Method: Secondary data for this study were from a larger study, titled Measurement, Indicators and Improvement of the Quality of Life (QOL) in Nursing Homes . Research literature, family systems theory and human ecological assumptions, fostered the conceptual model empirically testing quality of life family congruence. Results: The study results supported a model examining nursing home residents and two family members on quality of life family congruence. Specifically, family intergenerational dynamic factors, resident personal and social-psychological factors, and nursing home family input factors were examined to identify differences in quality of life family congruence among triad families. Discussion: Formal family involvement and resident cognitive functioning were found as the two most influential factors to quality of life family congruence (QOLFC).

  8. Impact of Family History Assessment on Communication with Family Members and Health Care Providers: A report from the Family Healthware™ Impact Trial (FHITr)

    Science.gov (United States)

    Wang, Catharine; Sen, Ananda; Plegue, Melissa; Ruffin, Mack T.; O'Neill, Suzanne M.; Rubinstein, Wendy S.; Acheson, Louise S.

    2015-01-01

    Objective This study examines the impact of Family Healthware™ on communication behaviors; specifically, communication with family members and health care providers about family health history. Methods A total of 3786 participants were enrolled in the Family Healthware™ Impact Trial (FHITr) in the United States from 2005-7. The trial employed a two-arm cluster-randomized design, with primary care practices serving as the unit of randomization. Using generalized estimating equations (GEE), analyses focused on communication behaviors at 6 month follow-up, adjusting for age, site and practice clustering. Results A significant interaction was observed between study arm and baseline communication status for the family communication outcomes (psfamily members about family history risk (OR=1.24, p=0.042) and actively collecting family history information at follow-up (OR=2.67, p=0.026). Family Healthware™ did not have a significant effect on family communication among those already communicating at baseline, or on provider communication, regardless of baseline communication status. Greater communication was observed among those at increased familial risk for a greater number of diseases. Conclusion Family Healthware™ prompted more communication about family history with family members, among those who were not previously communicating. Efforts are needed to identify approaches to encourage greater sharing of family history information, particularly with health care providers. PMID:25901453

  9. Quotidian of accompanying family members in an environment of care: the emergence of hospital tribes

    Directory of Open Access Journals (Sweden)

    Silvia da Silva Santos Passos

    2016-06-01

    Full Text Available ABSTRACT OBJECTIVE Understand the quotidian relationships of accompanying family members in an environment of care, which are close to the metaphor of a tribe in hospital environment. METHODQualitative study with data gathered from semi-structured interviews and observations with 16 family members accompanying hospitalized individuals with dependence on self-care. Data were submitted to thematic analysis, and analyzed through the metaphor of "tribe" proposed by comprehensive sociology. RESULTS Family members build up social clusters around caring, where we find traits typical of tribes: emotional ambience; solidarity based on links of sympathy and mutual assistance; an affectual nebula in the process of interaction; a logic of fusion in tactile relations; and communion/religiosity in the process of connecting in a collective identity. CONCLUSION In the presence of tragedy, families build social clusters similar to tribes having care as a totem.

  10. Effective doses to family members of patients treated with radioiodine 131

    International Nuclear Information System (INIS)

    Kocovska, Marina Zdravevska; Ristevska, Svetlana Micevska; Nikolovski, Sasho; Jokic, Vesna Spasic

    2010-01-01

    The purpose of this study was to evaluate the effective dose to family members of thyroid cancer and hyperthyroid patients treated with radioiodine 131; also to compare the results with dose constraints proposed by International Commission of Radiological Protection (ICRP) and Basic Safety Standards (BSS) of the International Atomic Energy Agency (IAEA). Material and methods: for estimation of effective doses at sixty family members of thirty thyroid cancer and thirty hyperthyroid patients treated with radioiodine 131, the thermoluminescent dosimeters, Model TLD 100, were used. Thyroid cancer patients were hospitalized for three days, while hyperthyroid patients were treated on out-patient basis. The family members wore thermoluminescent dosimeter in front of the torso for seven days. Results: The radiation doses to family members of thyroid cancer patients were well below recommended dose constraint of 1 mSv. The mean value of effective dose was 0.21 mSv (min 0.02 - max 0.51 mSv). Effective doses, higher than 1 mSv, were detected at 11 family members of hyperthyroid patients.. The mean value of effective dose at family members of hyperthyroid patients was 0.87 mSv (min 0.12 - max 6.79) Conclusion: After three days of hospitalization and detailed given oral and written instruction, thyroid carcinoma patients maintain not to exceed the proposed dose limits. Hyperthyroid patients present a greater radiation hazard than thyroid carcinoma patients. The estimated effective doses were higher than the effective doses at family members of thyroid carcinoma patients. These findings may be considered when establishing new national guidelines concerning radiation protection and release of patients after a treatment with radioiodine therapy.(Author)

  11. The impact of disease on family members: a critical aspect of medical care.

    Science.gov (United States)

    Golics, Catherine Jane; Basra, Mohammad Khurshid Azam; Finlay, Andrew Yule; Salek, Sam

    2013-10-01

    Most existing health-related quality of life research concerns the impact of disease on patients. However, in several medical specialties including dermatology, oncology, and physical and mental disability, studies have been carried out investigating the impact of disease on the lives of families of patients. The aim of this paper is to review the literature which relates to the impact of disease on family members of patients. The OVIDSP Medline was selected as the primary database, Searches were limited to sources published in English. 158 papers were identified for review. The definition of "family" varied across the literature, and a broad definition was accepted in this review. This review shows that a wide variety of aspects of family members' lives can be affected, including emotional, financial, family relationships, education and work, leisure time, and social activities. Many of these themes are linked to one another, with themes including financial impact and social impact being linked to emotional impact. Some positive aspects were also identified from the literature, including family relationships growing stronger. Several instruments exist to measure the impact of illness on the family, and most are disease or specialty- specific. The impact of disease on families of patients is often unrecognised and underestimated. Taking into account the quality of life of families as well as patients can offer the clinician a unique insight into issues such as family relationships and the effect of treatment decisions on the patient's close social group of partner and family.

  12. PI3K and Bcl-2 inhibition primes glioblastoma cells to apoptosis through downregulation of Mcl-1 and Phospho-BAD.

    Science.gov (United States)

    Pareja, Fresia; Macleod, David; Shu, Chang; Crary, John F; Canoll, Peter D; Ross, Alonzo H; Siegelin, Markus D

    2014-07-01

    Glioblastoma multiforme (GBM) is a highly malignant human brain neoplasm with limited therapeutic options. GBMs display a deregulated apoptotic pathway with high levels of the antiapoptotic Bcl-2 family of proteins and overt activity of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Therefore, combined interference of the PI3K pathway and the Bcl-2 family of proteins is a reasonable therapeutic strategy. ABT-263 (Navitoclax), an orally available small-molecule Bcl-2 inhibitor, and GDC-0941, a PI3K inhibitor, were used to treat established glioblastoma and glioblastoma neurosphere cells, alone or in combination. Although GDC-0941 alone had a modest effect on cell viability, treatment with ABT-263 displayed a marked reduction of cell viability and induction of apoptotic cell death. Moreover, combinatorial therapy using ABT-263 and GDC-0941 showed an enhanced effect, with a further decrease in cellular viability. Furthermore, combination treatment abrogated the ability of stem cell-like glioma cells to form neurospheres. ABT-263 and GDC-0941, in combination, resulted in a consistent and significant increase of Annexin V positive cells and loss of mitochondrial membrane potential compared with either monotherapy. The combination treatment led to enhanced cleavage of both initiator and effector caspases. Mechanistically, GDC-0941 depleted pAKT (Serine 473) levels and suppressed Mcl-1 protein levels, lowering the threshold for the cytotoxic actions of ABT-263. GDC-0941 decreased Mcl-1 in a posttranslational manner and significantly decreased the half-life of Mcl-1 protein. Ectopic expression of human Mcl-1 mitigated apoptotic cell death induced by the drug combination. Furthermore, GDC-0941 modulated the phosphorylation status of BAD, thereby further enhancing ABT-263-mediated cell death. Combination therapy with ABT-263 and GDC-0941 has novel therapeutic potential by specifically targeting aberrantly active, deregulated pathways in GBM, overcoming

  13. Radiation dose to family members of hyperthyroidism and thyroid cancer patients treated with 131I

    International Nuclear Information System (INIS)

    Pant, G. S.; Sharma, S. K.; Bal, C. S.; Kumar, R.; Rath, G. K.

    2006-01-01

    The thermoluminescence dosemeter (TLD) was used for measuring radiation dose to family members of thyrotoxicosis and thyroid cancer patients treated with 131 I using CaSO 4 :Dy discs. There were 45 family members of thyrotoxicosis patients, who were divided into two groups with 22 in the first and 23 in the second group. Radiation safety instructions were the same for both the groups except in the second group where the patients were advised to use a separate bed at home for the first 3 d of dose administration. An activity ranging from 185 to 500 MBq was administered to these patients. The whole-body dose to family members ranged from 0.4 to 2.4 mSv (mean 1.1 mSv) in the first group and 0-1.9 mSv (mean 0.6 mSv) in the second group. A total of 297 family members of thyroid cancer patients were studied for whole-body dose estimation. An activity ranging from 0.925 to 7.4 GBq was administered to the thyroid cancer patients. The family members were divided into three groups depending upon the mode of transport and facilities available at home to avoid close proximity with the patient. Group A with 25 family members received a dose ranging from 0 to 0.9 mSv (mean 0.4 mSv), group B with 96 family members received a dose ranging from 0 to 8.5 mSv (mean 0.8 mSv) and group C with 176 family members received a dose ranging from 0 to 5.0 mSv (mean 0.8 mSv). The thyroid monitoring was also done in 103 family members who attended the patients in isolation wards for >2 d. Thyroid dose in them ranged from 0 to 2.5 mGy (mean 0.1 mGy). (authors)

  14. The spiritual struggle of anger toward God: a study with family members of hospice patients.

    Science.gov (United States)

    Exline, Julie J; Prince-Paul, Maryjo; Root, Briana L; Peereboom, Karen S

    2013-04-01

    Anger toward God is a common form of spiritual struggle, one that people often experience when they see God as responsible for severe harm or suffering. The aim of this study was to assess the prevalence, correlates, and preferred coping strategies associated with anger toward God among family members of hospice patients. Teams from a large hospice in the midwestern United States distributed surveys, one per household, to family members of home-care patients. The survey assessed feelings toward God (anger/disappointment and positive feelings), depressive symptoms, religiosity, and perceived meaning. Participants also rated their interest in various strategies for coping with conflicts with God. Surveys (n=134) indicated that 43% of participants reported anger/disappointment toward God, albeit usually at low levels of intensity. Anger toward God was associated with more depressive symptoms, lower religiosity, more difficulty finding meaning, and belief that the patient was experiencing greater pain. Prayer was the most highly endorsed strategy for managing conflicts with God. Other commonly endorsed strategies included reading sacred texts; handling the feelings on one's own; and conversations with friends, family, clergy, or hospice staff. Self-help resources and therapy were less popular options. Anger toward God is an important spiritual issue among family members of hospice patients, one that is commonly experienced and linked with depressive symptoms. It is valuable for hospice staff to be informed about the issue of anger toward God, especially because many family members reported interest in talking with hospice team members about such conflicts.

  15. Patients' and family members' views on patient-centered communication during cancer care.

    Science.gov (United States)

    Mazor, Kathleen M; Beard, Reneé L; Alexander, Gwen L; Arora, Neeraj K; Firneno, Cassandra; Gaglio, Bridget; Greene, Sarah M; Lemay, Celeste A; Robinson, Brandi E; Roblin, Douglas W; Walsh, Kathleen; Street, Richard L; Gallagher, Thomas H

    2013-11-01

    To explore patients' and family members' views on communication during cancer care and to identify those aspects of clinician-patient communication which were most important to patients and family members. We conducted a secondary data analysis of qualitative data from 137 patients with cancer and family members of patients with cancer. We used a modified version of the constant comparative method and coding paradigm of grounded theory. Patients want sensitive, caring clinicians who provide information that they need, when they need it, in a way that they can understand; who listen and respond to questions and concerns, and who attempt to understand the patient's experience. Effective information exchange and a positive interpersonal relationship with the clinician were of fundamental importance to patients and family members. These were interrelated; for instance, failure to provide information a patient needed could damage the relationship, whereas excellent listening could foster the relationship. Information exchange and relationship were also integral to decision-making, managing uncertainty, responding to emotions, and self-management. Clinicians who were responsive to patients' needs beyond the immediate medical encounter were valued. The complexity of cancer care today suggests that efforts to improve communication must be multilevel, acknowledging and addressing patient, clinician, organizational and policy barriers, and facilitators. Measurement tools are needed to assess cancer patients' and family members' experiences with communication over the course of cancer care to provide meaningful, actionable feedback to those seeking to optimize their effectiveness in communicating with patients with cancer. Copyright © 2013 John Wiley & Sons, Ltd.

  16. Resilience in family members of persons with autism spectrum disorder: a review of the literature.

    Science.gov (United States)

    Bekhet, Abir K; Johnson, Norah L; Zauszniewski, Jaclene A

    2012-10-01

    Worldwide, caregivers find caring for children with Autism Spectrum Disorder (ASD) challenging. Family members must manage many aspects of care giving, which is demanding, overwhelming, and can affect the family members' mental health. However learning how to be resilient may help family members overcome the stress and burden associated with caring for a person with ASD. A search was completed in Medline, PsycINFO, Proquest, Web of Science, and CINAHL using the key words "autism," "caregivers," "mothers," and "fathers," alone and in combination. Inclusion criteria were English language articles reporting studies with samples of children with ASD, as distinct from children with other intellectual or developmental disabilities. Fifty-eight articles that met these inclusion criteria were summarized and, from those, the authors selected 22 articles that included indicators of resilience. This integrative review highlights current research on resilience in adult family members of persons with ASD. Indicators of resilience, risk factors, protective factors, and outcomes of resilience were identified. The review indicates that parents of children with ASD who possess indicators of resilience are better able to manage the adversity associated with caring for children with ASD. Thus, enhancing resilience among family members of persons with autism may be beneficial to both the caregivers and care recipients.

  17. In our own voice-family companion: reducing self-stigma of family members of persons with serious mental illness.

    Science.gov (United States)

    Perlick, Deborah A; Nelson, Ann H; Mattias, Kate; Selzer, James; Kalvin, Carla; Wilber, Charles H; Huntington, Brittney; Holman, Caroline S; Corrigan, Patrick W

    2011-12-01

    This article reports preliminary findings from a novel, family peer-based intervention designed to reduce self-stigma among family members of people with serious mental illness. A total of 158 primary caregivers of patients with schizophrenia were recruited from a large urban mental health facility (93 caregivers) or from a family and consumer advocacy organization (65 caregivers). Caregivers (N=122) who reported they perceived at least a moderate level of mental illness-related stigma were evaluated on measures of self-stigma, withdrawal, secrecy, anxiety, and social comparison and randomly assigned to receive one of two, one-session group interventions: a peer-led intervention (In Our Own Voice-Family Companion [IOOV-FC]) designed to stimulate group discussion or a clinician-led family education session, which delivered information about mental illness in a structured, didactic format. IOOV-FC consisted of playing a videotape of family members who describe their experiences coping with stigma, which was followed by a discussion led by two family peers who modeled sharing their own experiences and facilitated group sharing. Of 24 family members and ten consumers, 96% rated the videotape above a predetermined acceptability threshold on a 19-item scale assessing cultural sensitivity, respect for different stakeholders, relevance of content, and technical quality (α=.92). Caregivers receiving IOOV-FC with low to moderate pretreatment anxiety reported a substantial reduction in self-stigma (effect size=.50) relative to those receiving clinician-led family education (p=.017) as well as significant reductions in secrecy (p=.031). Peer-led group interventions may be more effective in reducing family self-stigma than clinician-led education, at least for persons reporting experiencing low to moderate anxiety levels on a standard questionnaire

  18. Effects of cognitive-behavioral treatment for weight loss in family members.

    Science.gov (United States)

    Rossini, Raffaella; Moscatiello, Simona; Tarrini, Giulietta; Di Domizio, Silvia; Soverini, Valentina; Romano, Andreina; Mazzotti, Arianna; Dalle Grave, Riccardo; Marchesini, Giulio

    2011-11-01

    The possibility that lifestyle changes may be shared by the family members of subjects with obesity attending cognitive-behavioral treatment (CBT) for weight loss has been scarcely evaluated. The purpose of this study was to measure the changes in body weight, lifestyle habits, and stage of change toward physical activity in the family members of 149 subjects with overweight/obesity enrolled into a weekly group CBT for weight management in the years 2007-2008. 230 adult (aged >18 years) family members (129 spouses, 72 children (43 female, 29 male), 29 with a different family relationship) completed a self-administered questionnaire at baseline and soon after the end of the completion of their relatives' program (approximately 6 months later). The questionnaire consisted of qualitative information regarding food choices, estimation of energy and food intake, self-report of height and weight, and motivation toward physical activity. At baseline, self-reported body mass index was normal in 115 cases, in the range 25 to 29.9 in 80 and ≥30 in 35. Following CBT of their relatives, the family members significantly reduced their average daily energy intake (-232 kcal/day; Pfood choices revealed a reduced average daily amount of energy from dressings (-40 kcal, Pbread (-58 kcal, P<0.001), breakfast biscuits (-23 kcal, P=0.005), chocolate (-7 kcal, P=0.024), and nonalcoholic beverages (fruit juices and carbonated drinks; -10 kcal; P=0.013), whereas fruit consumption was increased (+10 kcal; P=0.023). There was also a shift in the stage of change toward exercising. Body mass index changes of family members and CBT subjects were significantly correlated, mainly within spouses. In conclusion, CBT for weight loss positively influences the lifestyle habits of family members of participants, reducing energy intake and promoting a more favorable attitude toward physical activity. Copyright © 2011 American Dietetic Association. Published by Elsevier Inc. All rights reserved.

  19. Targeting of BCL2 Family Proteins with ABT-199 and Homoharringtonine Reveals BCL2- and MCL1-Dependent Subgroups of Diffuse Large B-Cell Lymphoma

    Czech Academy of Sciences Publication Activity Database

    Klanova, M.; Anděra, Ladislav; Bražina, Jan; Švadlenka, Jan; Benešová, Simona; Soukup, J.; Průková, D.; Vejmelkova, D.; Jaksa, R.; Helman, K.; Vockova, P.; Lateckova, L.; Molinsky, J.; Maswabi, B.C.; Alam, M.; Kodet, R.; Pytlik, R.; Trneny, M.; Klener, P.

    2016-01-01

    Roč. 22, č. 5 (2016), s. 1138-1149 ISSN 1078-0432 R&D Projects: GA ČR GA14-19590S Institutional support: RVO:68378050 Keywords : NON-HODGKINS-LYMPHOMA * PROGNOSTIC-SIGNIFICANCE * OMACETAXINE MEPESUCCINATE * GENE-EXPRESSION * APOPTOSIS * REARRANGEMENT * SURVIVAL * LEUKEMIA * CANCER * AGENTS Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Genetics and heredity (medical genetics to be 3) Impact factor: 9.619, year: 2016

  20. Understanding Response Rates to Surveys About Family Members' Psychological Symptoms After Patients' Critical Illness.

    Science.gov (United States)

    Long, Ann C; Downey, Lois; Engelberg, Ruth A; Nielsen, Elizabeth; Ciechanowski, Paul; Curtis, J Randall

    2017-07-01

    Achieving adequate response rates from family members of critically ill patients can be challenging, especially when assessing psychological symptoms. To identify factors associated with completion of surveys about psychological symptoms among family members of critically ill patients. Using data from a randomized trial of an intervention to improve communication between clinicians and families of critically ill patients, we examined patient-level and family-level predictors of the return of usable surveys at baseline, three months, and six months (n = 181, 171, and 155, respectively). Family-level predictors included baseline symptoms of psychological distress, decisional independence preference, and attachment style. We hypothesized that family with fewer symptoms of psychological distress, a preference for less decisional independence, and secure attachment style would be more likely to return questionnaires. We identified several predictors of the return of usable questionnaires. Better self-assessed family member health status was associated with a higher likelihood and stronger agreement with a support-seeking attachment style with a lower likelihood, of obtaining usable baseline surveys. At three months, family-level predictors of return of usable surveys included having usable baseline surveys, status as the patient's legal next of kin, and stronger agreement with a secure attachment style. The only predictor of receipt of surveys at six months was the presence of usable surveys at three months. We identified several predictors of the receipt of surveys assessing psychological symptoms in family of critically ill patients, including family member health status and attachment style. Using these characteristics to inform follow-up mailings and reminders may enhance response rates. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  1. The small-molecule Bcl-2 inhibitor HA14-1 sensitizes cervical cancer cells, but not normal fibroblasts, to heavy-ion radiation

    International Nuclear Information System (INIS)

    Hamada, Nobuyuki; Kataoka, Keiko; Sora, Sakura; Hara, Takamitsu; Omura-Minamisawa, Motoko; Funayama, Tomoo; Sakashita, Tetsuya; Nakano, Takashi; Kobayashi, Yasuhiko

    2008-01-01

    This is the first study to demonstrate that the small-molecule Bcl-2 inhibitor HA14-1 renders human cervical cancer cells and their Bcl-2 overexpressing radioresistant counterparts, but not normal fibroblasts, more susceptible to heavy ions. Thus, Bcl-2 may be an attractive target for improving the efficacy of heavy-ion therapy

  2. Psychological Support for Families During Crises (as exemplified by families members of Ukrainian war veterans

    Directory of Open Access Journals (Sweden)

    Yablonska Tetiana

    2017-06-01

    Full Text Available The goal of the article is to describe the theoretical and empirical research of characteristics of families under non-normative crises, having as an example the families of combatants participated in the anti-terrorist operation in Ukraine. The following family crises are discussed: normative crises, as period of transition from one stage of the family life cycle to another and non-normative crises caused by traumatic life events.

  3. Stress Reduction in Postcardiac Surgery Family Members: Implementation of a Postcardiac Surgery Tool Kit.

    Science.gov (United States)

    Breisinger, Lauren; Macci Bires, Angela; Cline, Thomas W

    The intensive care unit (ICU) can be a place of stress, anxiety, and emotional instability for both patients and families. Medical and nursing care during this acute time is patient focused, and family members are often left in the dark. Unintentional exclusion from information results in high levels of stress, anxiety, and uncertainty for families. Due to the acuity of illness, family members of cardiac surgery patients experience the highest levels of stress. Spouses may experience intense psychosomatic symptoms such as depression, anxiety, and fear for several months after the surgery. The purpose of this study was aimed at decreasing those feelings of anxiety in family members with postcardiac surgery through the use of a cardiac surgery tool kit. The study was a quality improvement project utilizing a convenience sample of 83 participants 18 years and older. Participants were asked to use the State Trait Anxiety Inventory (STAI) Form Y-1 (state anxiety) to rate their anxiety level preintervention and then again postintervention. Data were collected over a 6-month period. Descriptive data including age, education level, ethnicity, relationship, experience in the ICU, and active diagnoses of mental disorders did not affect the changes in the pre- and posttest data. A paired t test was conducted on the sample to assess changes in state anxiety, using the STAI Form Y-1. The results were statistically significant (t = 11.97, df = 81, P family members of postcardiac surgery patients.

  4. Predicting the number and sizes of IBD regions among family members and evaluating the family size requirement for linkage studies.

    Science.gov (United States)

    Yang, Wanling; Wang, Zhanyong; Wang, Lusheng; Sham, Pak-Chung; Huang, Peng; Lau, Yu Lung

    2008-12-01

    With genotyping of high-density single nucleotide polymorphisms (SNPs) replacing that of microsatellite markers in linkage studies, it becomes possible to accurately determine the genomic regions shared identity by descent (IBD) by family members. In addition to evaluating the likelihood of linkage for a region with the underlining disease (the LOD score approach), an appropriate question to ask is what would be the expected number and sizes of IBD regions among the affecteds, as there could be more than one region reaching the maximum achievable LOD score for a given family. Here, we introduce a computer program to allow the prediction of the total number of IBD regions among family members and their sizes. Reversely, it can be used to predict the portion of the genome that can be excluded from consideration according to the family size and user-defined inheritance mode and penetrance. Such information has implications on the feasibility of conducting linkage analysis on a given family of certain size and structure or on a few small families when interfamily homogeneity can be assumed. It can also help determine the most relevant members to be genotyped for such a study. Simulation results showed that the IBD regions containing true mutations are usually larger than regions IBD due to random chance. We have made use of this feature in our program to allow evaluation of the identified IBD regions based on Bayesian probability calculation and simulation results.

  5. MRP- and BCL-2-mediated drug resistance in human SCLC: effects of apoptotic sphingolipids in vitro.

    Science.gov (United States)

    Khodadadian, M; Leroux, M E; Auzenne, E; Ghosh, S C; Farquhar, D; Evans, R; Spohn, W; Zou, Y; Klostergaard, J

    2009-10-01

    Multidrug-resistance-associated protein (MRP) and BCL-2 contribute to drug resistance expressed in SCLC. To establish whether MRP-mediated drug resistance affects sphingolipid (SL)-induced apoptosis in SCLC, we first examined the human SCLC cell line, UMCC-1, and its MRP over-expressing, drug-resistant subline, UMCC-1/VP. Despite significantly decreased sensitivity to doxorubicin (Dox) and to the etoposide, VP-16, the drug-selected line was essentially equally as sensitive to treatment with exogenous ceramide (Cer), sphingosine (Sp) or dimethyl-sphingosine (DMSP) as the parental line. Next, we observed that high BCL-2-expressing human H69 SCLC cells, that were approximately 160-fold more sensitive to Dox than their combined BCL-2 and MRP-over-expressing (H69AR) counterparts, were only approximately 5-fold more resistant to DMSP. Time-lapse fluorescence microscopy of either UMCC cell line treated with DMSP-Coumarin revealed comparable extents and kinetics of SL uptake, further ruling out MRP-mediated effects on drug uptake. DMSP potentiated the cytotoxic activity of VP-16 and Taxol, but not Dox, in drug-resistant UMCC-1/VP cells. However, this sensitization did not appear to involve DMSP-mediated effects on the function of MRP in drug export; nor did DMSP strongly shift the balance of pro-apoptotic Sps and anti-apoptotic Sp-1-Ps in these cells. We conclude that SL-induced apoptosis markedly overcomes or bypasses MRP-mediated drug resistance relevant to SCLC and may suggest a novel therapeutic approach to chemotherapy for these tumors.

  6. Zerumbone induced apoptosis in liver cancer cells via modulation of Bax/Bcl-2 ratio

    Directory of Open Access Journals (Sweden)

    Azimahtol Hawariah LP

    2007-04-01

    Full Text Available Abstract Background Zerumbone is a cytotoxic component isolated from Zingiber zerumbet Smith, a herbal plant which is also known as lempoyang. This new anticancer bioactive compound from Z. zerumbet was investigated for its activity and mechanism in human liver cancer cell lines. Results Zerumbone significantly showed an antiproliferative activity upon HepG2 cells with an IC50 of 3.45 ± 0.026 μg/ml. Zerumbone was also found to inhibit the proliferation of non-malignant Chang Liver and MDBK cell lines. However the IC50 obtained was higher compared to the IC50 for HepG2 cells (> 10 μg/ml. The extent of DNA fragmentation was evaluated by the Tdt-mediated dUTP nick end labelling assay which showed that, zerumbone significantly increased apoptosis in HepG2 cells in a time-course manner. In detail, the apoptotic process triggered by zerumbone involved the up-regulation of pro-apoptotic Bax protein and the suppression of anti-apoptotic Bcl-2 protein expression. The changes that occurred in the levels of this antagonistic proteins Bax/Bcl-2, was independent of p53 since zerumbone did not affect the levels of p53 although this protein exists in a functional form. Western blotting analysis for Bax protein was further confirmed qualitatively with an immunoassay that showed the distribution of Bax protein in zerumbone-treated cells. Conclusion Therefore, zerumbone was found to induce the apoptotic process in HepG2 cells through the up and down regulation of Bax/Bcl-2 protein independently of functional p53 activity.

  7. Associations of Bcl-2 rs956572 genotype groups in the structural covariance network in early-stage Alzheimer's disease.

    Science.gov (United States)

    Chang, Chiung-Chih; Chang, Ya-Ting; Huang, Chi-Wei; Tsai, Shih-Jen; Hsu, Shih-Wei; Huang, Shu-Hua; Lee, Chen-Chang; Chang, Wen-Neng; Lui, Chun-Chung; Lien, Chia-Yi

    2018-02-08

    Alzheimer's disease (AD) is a complex neurodegenerative disease, and genetic differences may mediate neuronal degeneration. In humans, a single-nucleotide polymorphism in the B-cell chronic lymphocytic leukemia/lymphoma-2 (Bcl-2) gene, rs956572, has been found to significantly modulate Bcl-2 protein expression in the brain. The Bcl-2 AA genotype has been associated with reduced Bcl-2 levels and lower gray matter volume in healthy populations. We hypothesized that different Bcl-2 genotype groups may modulate large-scale brain networks that determine neurobehavioral test scores. Gray matter structural covariance networks (SCNs) were constructed in 104 patients with AD using T1-weighted magnetic resonance imaging with seed-based correlation analysis. The patients were stratified into two genotype groups on the basis of Bcl-2 expression (G carriers, n = 76; A homozygotes, n = 28). Four SCNs characteristic of AD were constructed from seeds in the default mode network, salience network, and executive control network, and cognitive test scores served as the major outcome factor. For the G carriers, influences of the SCNs were observed mostly in the default mode network, of which the peak clusters anchored by the posterior cingulate cortex seed determined the cognitive test scores. In contrast, genetic influences in the A homozygotes were found mainly in the executive control network, and both the dorsolateral prefrontal cortex seed and the interconnected peak clusters were correlated with the clinical scores. Despite a small number of cases, the A homozygotes showed greater covariance strength than the G carriers among all four SCNs. Our results suggest that the Bcl-2 rs956572 polymorphism is associated with different strengths of structural covariance in AD that determine clinical outcomes. The greater covariance strength in the four SCNs shown in the A homozygotes suggests that different Bcl-2 polymorphisms play different modulatory roles.

  8. An audit of clinical service examining the uptake of genetic testing by at-risk family members.

    Science.gov (United States)

    Forrest, Laura; Delatycki, Martin; Curnow, Lisette; Gen Couns, M; Skene, Loane; Aitken, Maryanne

    2012-01-01

    The aim of this study was to investigate the uptake of genetic testing by at-risk family members for four genetic conditions: chromosomal translocations, fragile X syndrome, Huntington disease, and spinal muscular atrophy. A clinical audit was undertaken using genetics files from Genetic Health Services Victoria. Data were extracted from the files regarding the number of at-risk family members and the proportion tested. Information was also collected about whether discussion of at-risk family members and family communication during the genetic consultation was recorded. The proportion of at-risk family members who had genetic testing ranged from 11% to 18%. First-degree family members were most frequently tested and the proportion of testing decreased by degree of relatedness to the proband. Smaller families were significantly more likely to have genetic testing for all conditions except Huntington disease. Female at-risk family members were significantly more likely to have testing for fragile X syndrome. The majority of at-risk family members do not have genetic testing. Family communication is likely to influence the uptake of genetic testing by at-risk family members and therefore it is important that families are supported while communicating to ensure that at-risk family members are able to make informed decisions about genetic testing.

  9. In Asian americans, is having a family member diagnosed with cancer associated with fatalistic beliefs?

    Directory of Open Access Journals (Sweden)

    Carolee Polek

    2016-01-01

    Full Text Available Objective: Cancer can evoke long-held cultural beliefs which either facilitate or impede efforts to expand the health literacy of families. Among these beliefs is fatalism which holds that controlling ones′ outcome is not possible, and that ones′ outcome is predestined. Some fatalistic beliefs are broadly held within the Asian American (AA community and may be challenged or reinforced by the experience of having a family member diagnosed with cancer. This study evaluated the relationship between having a family member diagnosed with cancer and selected demographics in AAs on fatalistic beliefs. Methods: Data from 519 AA subjects from the Centers for Disease Control and Prevention Health Information Trends Survey were used to complete a secondary analysis. Descriptive statistics characterize fatalistic beliefs. Four models using four questions assessed fatalistic beliefs as dependent variables and independent variables of having or not having a family member diagnosed with cancer, completing college or not, sex, and age were assessed using ordinal regression. Results: All of the fatalistic beliefs examined were endorsed by large portions of the subjects. When considering the role of being exposed to having a family member with cancer, it was associated with an increase in the likelihood in a belief that one is likely to get cancer, and everything can cause cancer. Being exposed to a family member diagnosed with cancer was not significantly associated with believing, there was little one could do to control their cancer risk. This belief was broadly rejected. While the belief that there are so many different recommendations about preventing cancer, it is hard to know what to do, was broadly endorsed and not associated with having a family member diagnosed with cancer. Conclusions: The major practice implications within oncology nursing suggest the importance in assessing cancer health literacy and providing corrective knowledge in families

  10. Bcl-2–associated athanogene 3 protects the heart from ischemia/reperfusion injury

    OpenAIRE

    Su, Feifei; Myers, Valerie D.; Knezevic, Tijana; Wang, JuFang; Gao, Erhe; Madesh, Muniswamy; Tahrir, Farzaneh G.; Gupta, Manish K.; Gordon, Jennifer; Rabinowitz, Joseph; Ramsey, Frederick V.; Tilley, Douglas G.; Khalili, Kamel; Cheung, Joseph Y.; Feldman, Arthur M.

    2016-01-01

    Bcl-2–associated athanogene 3 (BAG3) is an evolutionarily conserved protein expressed at high levels in the heart and the vasculature and in many cancers. While altered BAG3 expression has been associated with cardiac dysfunction, its role in ischemia/reperfusion (I/R) is unknown. To test the hypothesis that BAG3 protects the heart from reperfusion injury, in vivo cardiac function was measured in hearts infected with either recombinant adeno-associated virus serotype 9–expressing (rAAV9-expre...

  11. Payment or reimbursement for certain medical expenses for Camp Lejeune family members. Interim final rule.

    Science.gov (United States)

    2014-09-24

    The Department of Veterans Affairs (VA) is promulgating regulations to implement statutory authority to provide payment or reimbursement for hospital care and medical services provided to certain veterans' family members who resided at Camp Lejeune, North Carolina, for at least 30 days during the period beginning on January 1, 1957, and ending on December 31, 1987. Under this rule, VA will reimburse family members, or pay providers, for medical expenses incurred as a result of certain illnesses and conditions that may be attributed to exposure to contaminated drinking water at Camp Lejeune during this time period. Payment or reimbursement will be made within the limitations set forth in statute and Camp Lejeune family members will receive hospital care and medical services that are consistent with the manner in which we provide hospital care and medical services to Camp Lejeune veterans.

  12. Caregiver burden in Danish family members of patients with severe brain injury

    DEFF Research Database (Denmark)

    Doser, Karoline; Norup, Anne

    2016-01-01

    OBJECTIVE: To investigate caregiver burden and factors associated with caregiver burden among family members of patients with severe brain injury in the chronic phase. Additionally, the study aimed at investigating differences in burden between parents and spouses. METHODS: Forty-four Danish...... caregivers of patients with severe brain injury were contacted 3-6 years post-injury and asked to complete a measure of caregiver burden. RESULTS: Medium, high and low levels of burden were observed in 45%, 16% and 39% of family members, respectively. Higher burden was seen in caregivers of patients...... with more severe injuries, who spent more time on caregiving and reported more unmet needs. Overall, spouses spent significantly more time taking care of their family member than parents and reported higher levels of burden. CONCLUSIONS: The findings emphasized the continuing consequences of brain injury...

  13. Bcl-2 and N-Myc Coexpression Increases IGF-IR and Features of Malignant Growth in Neuroblastoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Rama Jasty

    2001-01-01

    Full Text Available The bcl-2 and c-myc oncogenes cooperate to transform multiple cell types. In the pediatric malignancy NB2, Bcl2 is highly expressed. In tumors with a poor prognosis, N-Myc, a protein homologous to c-Myc, is overexpressed as a result of gene amplification. The present study was designed to determine whether Bcl-2 cooperates with N-Myc to bestow a tumorigenic phenotype to neuroblastoma (NB cells. NB cell lines that at baseline express neither Bcl-2 nor N-Myc were stably transfected to express these gene products. In this model, we found Bcl-2 rescues N-Myc-expressing cells from apoptosis induced by serum withdrawal. Coexpression of Bcl-2 and N-Myc supports growth in low serum conditions and anchorage-independent growth in soft agar. Similarly, in vivo tumorigenic and angiogenic activity was dependent on coexpression. Our data further suggests that the mechanism underlying these changes involves the receptor for insulin growth factor type I (IGF-IR.

  14. Immunohistochemical study of p21 and Bcl-2 in leukoplakia, oral submucous fibrosis and oral squamous cell carcinoma.

    Science.gov (United States)

    Sutariya, Rakesh V; Manjunatha, Bhari Sharanesha

    2016-11-01

    Oral Squamous cell carcinoma (OSCC) results from genetic damage, leading to uncontrolled cell proliferation of damaged cells and the cell death. In the course of its progression, visible changes are taking place at the cellular level (atypical) and the resultant at the tissue level (epithelial dysplasia). The Aim of the present study was to evaluate and compare the expressions of intensity of p21 and Bcl-2 in Leukoplakia, oralsubmucous fibrosis (OSMF) and oral squamous cell carcinoma. Total 60 cases, 30 cases of oral squamous cell carcinoma, 15 cases of oral submucous fibrosis and 15 cases of Leukoplakia were evaluated immunohistochemically for p21 and Bcl-2 expression. p21 showed positive expression in 13 (86.67%) cases out of 15 cases of OSMF, 12 (80%) cases of leukoplakia out of 15 cases and 24 (80%) cases out of 30 cases of OSCC. The Bcl-2 expression was positive in 13 (86.67%) cases of OSMF, all cases of Leukoplakia and 25 (83.33%) cases of OSCC. No statistical significance was noted in the expression of p21 and Bcl-2 positive expression between OSMF, Leukoplakia and OSCC. Statistical analysis for comparison of intensity of p21 expression in different grades of OSCC showed no significance. Statistical significance difference was found between the expressions of Bcl-2 in moderately and poorly differentiated SCC. The intensity of p21 and Bcl-2 expressions in different grades of OSCC indicates a key role in progression of oral neoplasia.

  15. Radiation exposure to family members of patients with thyrotoxicosis treated with iodine-131

    International Nuclear Information System (INIS)

    Cappelen, Tone; Amundsen, Anne Lise; Kravdal, Gunnhild; Unhjem, Jan Frede; Foelling, Ivar

    2006-01-01

    The purpose of this study was twofold: (1) to measure the radiation exposure to family members of out-patients with thyrotoxicosis treated with radioiodine, 131 I, using the recommendations from the European Commission (EC) guidance and age-specific periods for behaviour restrictions; (2) to use the results to identify necessary restrictions to ensure recommended dose constraints. The study population comprised 76 family members (46 adults and 30 children below the age of 18) of 42 patients. The patients were treated with an average activity of 417 MBq (range 260-600 MBq). They received oral and written EC recommendations about behaviour restrictions (translated into Norwegian). On the day of treatment we repeated the oral instructions to the patient and an adult family member. The time periods for restrictions were 14 days for children aged 0-10 years, 7 days for persons aged 11-59 years and 3 days for persons aged 60 years and older. Family members wore a thermoluminescent dosimeter (TLD) on each wrist day and night for 2 weeks. The doses received were adjusted to give an estimate of the expected values if the TLDs had been worn indefinitely. Radiation doses well below the recommended dose constraints were measured for all adult family members and children, except one 2-year-old child; in the latter case the mother probably did not comply with the instructions given. The radiation dose to family members of thyrotoxic patients treated with up to 600 MBq of radioiodine is well below recommended dose constraints if EC instructions are given and compliance is adequate. The duration of restrictions for various age groups used in this study may be considered when establishing guidelines in Norway. (orig.)

  16. Assessing the place of neurobiological explanations in accounts of a family member's addiction.

    Science.gov (United States)

    Meurk, Carla; Fraser, Doug; Weier, Megan; Lucke, Jayne; Carter, Adrian; Hall, Wayne

    2016-07-01

    The brain disease model of addiction posits that addiction is a persistent form of neural dysfunction produced by chronic drug use, which makes it difficult for addicted persons to become and remain abstinent. As part of an anticipatory policy analysis of addiction neuroscience, we engaged family members of addicted individuals to assess their views on the place and utility of brain-based accounts of addiction. Fifteen in-depth qualitative interviews were conducted and used to develop a quantitative online survey that was completed by 55 family members. This article reports responses on what addiction is and how it is caused and responses to explanations of the brain disease model of addiction. Participants gave multiple reasons for their family members developing an addiction and there was no single dominant belief about the best way to describe addiction. Participants emphasised the importance of both scientific and non-scientific perspectives on addiction by providing multifactorial explanations of their family members' addictions. Most family members acknowledged that repeated drug use can cause changes to the brain, but they varied in their reactions to labelling addiction a 'brain disease'. They believed that understanding addiction, and how it is caused, could help them support their addicted relative. Participants' beliefs about neurobiological information and the brain disease model of addiction appeared to be driven by empathetic, utilitarian considerations rather than rationalist ones. We discuss the importance of providing information about the nature and causes of addiction. [Meurk C, Fraser D, Weier M, Lucke J, Carter A, Hall W. Assessing the place of neurobiological explanations in accounts of a family member's addiction. Drug Alcohol Rev 2016;35:461-469]. © 2015 Australasian Professional Society on Alcohol and other Drugs.

  17. Family matters : The experiences and opinions of family members of persons with (severe) or profound intellectual disabilities

    NARCIS (Netherlands)

    Luijkx, Jorien

    2016-01-01

    “I love my sister, but sometimes I don’t”. This is one of the statements made in the study focused on the experiences of family members of people with (profound) intellectual (and multiple) disabilities (both of individuals living in a residential facility as persons living at home). In recent

  18. Marriage & Family Therapy Faculty Memberâ s Balance of Work and Personal Life

    OpenAIRE

    Matheson, Jennifer L.

    2002-01-01

    This mixed-method study examines the work and personal life balance of Marriage & Family Therapy faculty members across the U.S., 16 of whom were interviewed to gain a deeper understanding of their work and personal life balance issues. Of those, six felt they had good balance, six felt they had poor balance, and four were â middle of the road.â More men than women felt they had good balance. Faculty members indicated external and internal indicators such as family and workplace message...

  19. COMBINING WORK WITH CARING FOR ELDERLY FAMILY MEMBER IN POLAND (CHOSEN ISSUES

    Directory of Open Access Journals (Sweden)

    Lukasz Jurek

    2016-07-01

    Full Text Available The problem of combining work with caring for elderly family members is becoming an increasingly important matter due to demographic (population ageing and social (increasing economic activity of women changes that are currently in progress. The aim of the article is to present selected issues related to the professional situation of people taking care for their elderly family members. The primary focus of the study is reasons for not working of non-working caregivers, and professional problems of working caregivers

  20. Protecting the privacy of family members in survey and pedigree research.

    Science.gov (United States)

    Botkin, J

    2001-01-10

    The recent controversy at Virginia Commonwealth University involving research ethics raises important and complex issues in survey and pedigree research. The primary questions are whether family members of survey respondents themselves become subjects of the project and if they are subjects whether informed consent must be obtained for investigators to retain private information on these individuals. This article provides an analysis of the ethical issues and regulatory standards involved in this debate for consideration by investigators and institutional review boards. The analysis suggests that strong protections for the rights and welfare of subjects and their family members can be incorporated into survey and pedigree research protocols without hindering projects with extensive consent requirements.

  1. Perspectives of Family Members on Using Technology in Youth Mental Health Care: A Qualitative Study.

    Science.gov (United States)

    Lal, Shalini; Daniel, Winnie; Rivard, Lysanne

    2017-06-23

    Information and communication technologies (ICTs) are increasingly recognized as having an important role in the delivery of mental health services for youth. Recent studies have evaluated young people's access and use of technology, as well as their perspectives on using technology to receive mental health information, services, and support; however, limited attention has been given to the perspectives of family members in this regard. The aim of this study was to explore the perspectives of family members on the use of ICTs to deliver mental health services to youth within the context of specialized early intervention for a first-episode psychosis (FEP). Six focus groups were conducted with family members recruited from an early intervention program for psychosis. Twelve family members participated in the study (target sample was 12-18, and recruitment efforts took place over the duration of 1 year). A 12-item semistructured focus group guide was developed to explore past experiences of technology and recommendations for the use of technology in youth mental health service delivery. A qualitative thematic analysis guided the identification and organization of common themes and patterns identified across the dataset. Findings were organized by the following themes: access and use of technology, potential negative impacts of technology on youth in recovery, potential benefits of using technology to deliver mental health services to youth, and recommendations to use technology for (1) providing quality information in a manner that is accessible to individuals of diverse socioeconomic backgrounds, (2) facilitating communication with health care professionals and services, and (3) increasing access to peer support. To our knowledge, this is among the first (or the first) to explore the perspectives of family members of youth being treated for FEP on the use of technology for mental health care. Our results highlight the importance of considering diverse experiences

  2. Determining the satisfaction levels of the family members of patients with advanced-stage cancer.

    Science.gov (United States)

    Ozcelik, Hanife; Cakmak, Deniz Ezgi; Fadiloglu, Cicek; Yildirim, Yasemin; Uslu, Ruchan

    2015-06-01

    The objective of our study was to determine the satisfaction levels of family members of patients with advanced-stage cancer. This descriptive study was conducted in the palliative care and medical oncology clinics of a university hospital in the province of Izmir between April of 2011 and January of 2012. The study sample consisted of a total of 145 family members, who were selected from among the family members of patients with advanced-stage cancer receiving palliative treatment. The study data were obtained using the Patient Description Form and Family Satisfaction Scale during face-to-face interviews with patients. Some 67% of patients were female and 33% male, 70% were married, 35% were high school graduates, and 34.5% were housewives. The average total family satisfaction score was 76.87 ± 1.14, and the average scores for the component variables were as follows: information giving 74.37 ± 1.28, availability of care 78.40 ± 1.17, physical care 78.99 ± 1.09, and psychosocial care 74.52 ± 1.30. We found a relationship between the level of satisfaction of family members and (1) gender, (2) occupation, (3) presence of someone supporting the care, and (4) possession of sufficient information about the patient (p Satisfaction levels of participants were determined to be high. We found that family member satisfaction levels were affected by gender and occupation, the existence of someone supporting the care, and possession of sufficient information about the patient.

  3. Most important needs of family members of critical patients in light of the critical care family needs inventory.

    Science.gov (United States)

    Padilla Fortunatti, Cristóbal Felipe

    2014-01-01

    This work sought to identify the most important needs for family members of adult critical patients as described in the literature pursuant to the dimensions established in the "Critical Care Family Needs Inventory" (CCFNI) by Molter and Leske. A literature review was carried out by using the CCFNI instrument. The databases used were: Pubmed, CINAHL, Proquest Nursing & Allied Health Source, Proquest Psychology Journals, LILACS, Science Direct, Ovid SP, PsyicINFO, and SciELO. The following limitations for the search were identified: adult patients, articles in English and Spanish, with abstract and complete text available and which had been published from 2003 to June 2013; 15 articles were included. The family's hope on desired results and sincere communication with the healthcare staff turned out to be the most relevant needs, while the least important were related to comfort and having support structures or systems. Most of the studies were conducted in Asia and North America revealing differences in the order of importance assigned to each necessity. Certain sociodemographic and cultural characteristics impact upon how family members rank their needs; this also occurs with the nature of the most important needs for the family and the factors determining their prioritization. The articles included in this review mention the frequent interaction with the family and their holistic view of the person beyond the illness, determine that nurses are the most appropriate professionals to know and satisfy the family needs of critical patients.

  4. Most Important Needs of Family Members of Critical Patients in Light of the Critical Care Family Needs Inventory

    Directory of Open Access Journals (Sweden)

    Cristóbal Felipe Padilla Fortunatti

    2014-07-01

    Full Text Available Objective. This work sought to identify the most important needs for family members of adult critical patients as described in the literature pursuant to the dimensions established in the "Critical Care Family Needs Inventory" (CCFNI by Molter and Leske. Methodology. A literature review was carried out by using the CCFNI instrument. The databases used were: Pubmed, CINAHL, Proquest Nursing & Allied Health Source, Proquest Psychology Journals, LILACS, Science Direct, Ovid SP, PsyicINFO, and SciELO. The following limitations for the search were identified: adult patients, articles in English and Spanish, with abstract and complete text available and which had been published from 2003 to June 2013; 15 articles were included. Results. The family's hope on desired results and sincere communication with the healthcare staff turned out to be the most relevant needs, while the least important were related to comfort and having support structures or systems. Most of the studies were conducted in Asia and North America revealing differences in the order of importance assigned to each necessity. Certain sociodemographic and cultural characteristics impact upon how family members rank their needs; this also occurs with the nature of the most important needs for the family and the factors determining their prioritization. Conclusion. The articles included in this review mention the frequent interaction with the family and their holistic view of the person beyond the illness, determine that nurses are the most appropriate professionals to know and satisfy the family needs of critical patients.

  5. Family members' experiences with intensive care unit diaries when the patient does not survive.

    Science.gov (United States)

    Johansson, Maria; Wåhlin, Ingrid; Magnusson, Lennart; Runeson, Ingrid; Hanson, Elizabeth

    2018-03-01

    The aim of the study was to explore how family members experienced the use of a diary when a relative does not survive the stay in the intensive care unit (ICU). A qualitative method with a hermeneutic approach was used. Nine participants who read/wrote eight diaries in total were interviewed. The collected data were analysed using a hermeneutic technique inspired by Geanellos. The analysis revealed an overall theme 'the diary was experienced as a bridge connecting the past with the future', which was a metaphor referring to the temporal aspect where there was the period with the diary up until the patient's death and then the postbereavement period. The diary contributed to both a rational and emotional understanding of the death of the patient and disclosed glimmers of light that still existed before the illness deteriorated. Further, the diary bridged the space between family members themselves and between family and nursing staff. It helped to maintain a feeling of togetherness and engagement in the care of the patient which family members found comforting. Family members of nonsurvivors had a need to have the ICU time explained and expressed. The diary might work as a form of 'survival kit' to gain coherence and understanding; to meet their needs during the hospital stay; and, finally, to act as a bereavement support by processing the death of the patient. © 2017 Nordic College of Caring Science.

  6. Patient and family member perspectives on searching for cancer clinical trials: A qualitative interview study.

    Science.gov (United States)

    Ridgeway, Jennifer L; Asiedu, Gladys B; Carroll, Katherine; Tenney, Meaghan; Jatoi, Aminah; Radecki Breitkopf, Carmen

    2017-02-01

    Clinical trials are vital in the context of ovarian cancer and may offer further treatment options during disease recurrence, yet enrollment remains low. Understanding patient and family member experiences with identifying trials can inform engagement and education efforts. Interviews were conducted with 33 patients who had experience with clinical trial conversations and 39 nominated family members. Thematic analysis examined experiences and generated findings for clinical practice. Trial conversations with providers at diagnosis were uncommon and often overwhelming. Most participants delayed engagement until later in the disease course. With hindsight, though, some wished they considered trials earlier. Difficulty identifying appropriate trials led some to defer searching to providers, but then they worried about missed opportunities. Most family members felt unqualified to search. Trial conversations during clinical encounters should start early and include specifying search responsibilities of providers, patients, and family. Patients and family members can be engaged in searches but need guidance. Trials should be discussed throughout the disease course, even if patients are not ready to participate or are not making a treatment decision. Education should focus on identifying trials that meet search criteria. Transparency regarding each individual's role in identifying trials is critical. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Hope: A further dimension for engaging family members of people with ABI.

    Science.gov (United States)

    Kuipers, Pim; Doig, Emmah; Kendall, Melissa; Turner, Ben; Mitchell, Marion; Fleming, Jennifer

    2014-01-01

    Family member engagement is increasingly recognised as an influential factor in the rehabilitation continuum following Acquired Brain Injury, including the inpatient setting and longer-term community integration phases. To explore the experiences of patients and family members about their involvement in brain injury rehabilitation. This study comprised individual and group interviews with 14 ex-patients and family members. Interviews explored effects of inpatient rehabilitation on family relationships. Interview audio recordings were analysed using an interpretive approach by two independent researchers. Findings clearly confirmed the significance of engaging family members in inpatient rehabilitation, and specifically reinforced the importance of informational, emotional, practical and peer support. However, the key finding of the study was the importance of hope, and the need for rehabilitation professionals to foster hope. Despite not having included any questions on this topic, all interviewees noted the importance of hope, some saw it as fundamental to positive outcomes, and many were unconvinced of rehabilitation professionals' concern to avoid false hope. Various dimensions of hope are explored. The study notes that hope has been identified as highly important in many areas beyond brain injury rehabilitation. Based on this small preliminary study, the issue of hope is seen as a key focus for future research.

  8. The process of death imminence awareness by family members of patients in adult critical care.

    Science.gov (United States)

    Baumhover, Nancy C

    2015-01-01

    A focus on cost-effective quality end-of-life care remains a high priority in adult critical care given an aging population, high prevalence of death, and aggressive technologies used to extend or sustain life in this setting. A Glaserian grounded theory design was used to conduct this retrospective study to yield a substantive middle-range theory. The data source was semistructured interviews with 14 family members of decedents who died 6 to 60 months prior to the study. The purpose of this study was to generate a theory on how family members of patients in adult critical care come to realize that their loved one is dying. The Process of Death Imminence Awareness by Family Members of Patients in Adult Critical Care middle-range theory contained 6 phases: (1) patient's near-death awareness, (2) dying right in front of me, (3) turning points in the patient's condition, (4) no longer the person I once knew, (5) doing right by them, and (6) time to let go. Patient's near-death awareness preceded all other phases, if communicated by the decedent with their family. Then, family members iteratively moved through all the other key phases in the process until a time to let go became evident. This substantive middle-range theory will guide nursing education, practice, and research aimed at providing quality and cost-effective end-of-life care in adult critical care.

  9. Post-Traumatic Stress Symptoms in Post-ICU Family Members: Review and Methodological Challenges.

    Science.gov (United States)

    Petrinec, Amy B; Daly, Barbara J

    2016-01-01

    Family members of intensive care unit (ICU) patients are at risk for symptoms of post-traumatic stress disorder (PTSD) following ICU discharge. The aim of this systematic review is to examine the current literature regarding post-ICU family PTSD symptoms with an emphasis on methodological issues in conducting research on this challenging phenomenon. An extensive review of the literature was performed confining the search to English language studies reporting PTSD symptoms in adult family members of adult ICU patients. Ten studies were identified for review published from 2004 to 2012. Findings demonstrate a significant prevalence of family PTSD symptoms in the months following ICU hospitalization. However, there are several methodological challenges to the interpretation of existing studies and to the conduct of future research including differences in sampling, identification of risk factors and covariates of PTSD, and lack of consensus regarding the most appropriate PTSD symptom measurement tools and timing. © The Author(s) 2014.

  10. BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion.

    Science.gov (United States)

    Cekanova, Maria; Fernando, Romaine I; Siriwardhana, Nalin; Sukhthankar, Mugdha; De la Parra, Columba; Woraratphoka, Jirayus; Malone, Christine; Ström, Anders; Baek, Seung J; Wade, Paul A; Saxton, Arnold M; Donnell, Robert M; Pestell, Richard G; Dharmawardhane, Suranganie; Wimalasena, Jay

    2015-02-01

    We have previously demonstrated that the anti-apoptotic protein BAD is expressed in normal human breast tissue and shown that BAD inhibits expression of cyclin D1 to delay cell-cycle progression in breast cancer cells. Herein, expression of proteins in breast tissues was studied by immunohistochemistry and results were analyzed statistically to obtain semi-quantitative data. Biochemical and functional changes in BAD-overexpressing MCF7 breast cancer cells were evaluated using PCR, reporter assays, western blotting, ELISA and extracellular matrix invasion assays. Compared to normal tissues, Grade II breast cancers expressed low total/phosphorylated forms of BAD in both cytoplasmic and nuclear compartments. BAD overexpression decreased the expression of β-catenin, Sp1, and phosphorylation of STATs. BAD inhibited Ras/MEK/ERK and JNK signaling pathways, without affecting the p38 signaling pathway. Expression of the metastasis-related proteins, MMP10, VEGF, SNAIL, CXCR4, E-cadherin and TlMP2 was regulated by BAD with concomitant inhibition of extracellular matrix invasion. Inhibition of BAD by siRNA increased invasion and Akt/p-Akt levels. Clinical data and the results herein suggest that in addition to the effect on apoptosis, BAD conveys anti-metastatic effects and is a valuable prognostic marker in breast cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion

    Energy Technology Data Exchange (ETDEWEB)

    Cekanova, Maria, E-mail: mcekanov@utk.edu [Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States); Fernando, Romaine I. [Department of Obstetrics and Gynecology, Graduate School of Medicine, Medical Center, The University of Tennessee, Knoxville, TN (United States); Siriwardhana, Nalin [Department of Animal Science, The University of Tennessee, Knoxville, TN (United States); Sukhthankar, Mugdha [Department of Biomedical and Diagnostics Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States); Parra, Columba de la [Department of Biochemistry, School of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan, PR (United States); Woraratphoka, Jirayus [Department of Obstetrics and Gynecology, Graduate School of Medicine, Medical Center, The University of Tennessee, Knoxville, TN (United States); Malone, Christine [Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); Ström, Anders [Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX (United States); Baek, Seung J. [Department of Biomedical and Diagnostics Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States); Wade, Paul A. [Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); Saxton, Arnold M. [Department of Animal Science, The University of Tennessee, Knoxville, TN (United States); Donnell, Robert M. [Department of Biomedical and Diagnostics Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States); Pestell, Richard G. [Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); and others

    2015-02-01

    We have previously demonstrated that the anti-apoptotic protein BAD is expressed in normal human breast tissue and shown that BAD inhibits expression of cyclin D1 to delay cell-cycle progression in breast cancer cells. Herein, expression of proteins in breast tissues was studied by immunohistochemistry and results were analyzed statistically to obtain semi-quantitative data. Biochemical and functional changes in BAD-overexpressing MCF7 breast cancer cells were evaluated using PCR, reporter assays, western blotting, ELISA and extracellular matrix invasion assays. Compared to normal tissues, Grade II breast cancers expressed low total/phosphorylated forms of BAD in both cytoplasmic and nuclear compartments. BAD overexpression decreased the expression of β-catenin, Sp1, and phosphorylation of STATs. BAD inhibited Ras/MEK/ERK and JNK signaling pathways, without affecting the p38 signaling pathway. Expression of the metastasis-related proteins, MMP10, VEGF, SNAIL, CXCR4, E-cadherin and TlMP2 was regulated by BAD with concomitant inhibition of extracellular matrix invasion. Inhibition of BAD by siRNA increased invasion and Akt/p-Akt levels. Clinical data and the results herein suggest that in addition to the effect on apoptosis, BAD conveys anti-metastatic effects and is a valuable prognostic marker in breast cancer. - Highlights: • BAD and p-BAD expressions are decreased in breast cancer compared with normal breast tissue. • BAD impedes breast cancer invasion and migration. • BAD inhibits the EMT and transcription factors that promote cancer cell migration. • Invasion and migration functions of BAD are distinct from the BAD's role in apoptosis.

  12. BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion

    International Nuclear Information System (INIS)

    Cekanova, Maria; Fernando, Romaine I.; Siriwardhana, Nalin; Sukhthankar, Mugdha; Parra, Columba de la; Woraratphoka, Jirayus; Malone, Christine; Ström, Anders; Baek, Seung J.; Wade, Paul A.; Saxton, Arnold M.; Donnell, Robert M.; Pestell, Richard G.

    2015-01-01

    We have previously demonstrated that the anti-apoptotic protein BAD is expressed in normal human breast tissue and shown that BAD inhibits expression of cyclin D1 to delay cell-cycle progression in breast cancer cells. Herein, expression of proteins in breast tissues was studied by immunohistochemistry and results were analyzed statistically to obtain semi-quantitative data. Biochemical and functional changes in BAD-overexpressing MCF7 breast cancer cells were evaluated using PCR, reporter assays, western blotting, ELISA and extracellular matrix invasion assays. Compared to normal tissues, Grade II breast cancers expressed low total/phosphorylated forms of BAD in both cytoplasmic and nuclear compartments. BAD overexpression decreased the expression of β-catenin, Sp1, and phosphorylation of STATs. BAD inhibited Ras/MEK/ERK and JNK signaling pathways, without affecting the p38 signaling pathway. Expression of the metastasis-related proteins, MMP10, VEGF, SNAIL, CXCR4, E-cadherin and TlMP2 was regulated by BAD with concomitant inhibition of extracellular matrix invasion. Inhibition of BAD by siRNA increased invasion and Akt/p-Akt levels. Clinical data and the results herein suggest that in addition to the effect on apoptosis, BAD conveys anti-metastatic effects and is a valuable prognostic marker in breast cancer. - Highlights: • BAD and p-BAD expressions are decreased in breast cancer compared with normal breast tissue. • BAD impedes breast cancer invasion and migration. • BAD inhibits the EMT and transcription factors that promote cancer cell migration. • Invasion and migration functions of BAD are distinct from the BAD's role in apoptosis

  13. A New Approach for Assessing the Needs of Service Members and Their Families

    Science.gov (United States)

    2011-01-01

    their families. Nothing that I do as the Secretary of the Army is more important than this [emphasis added] ( Harvey , 2009). According to the Army...to address the physical, material, mental and spiritual needs of each member of the Total Army Family [emphasis added] ( Harvey and Schoomaker, 2006...Laurie Weinstein and Christie C. White, eds., Wives and Warriors: Women and the Military in the United States and Canada, Westport, Conn.: Greenwood

  14. [Meanings attributed by family members in pediatrics regarding their interactions with nursing professionals].

    Science.gov (United States)

    Gomes, Giovana Calcagno; Xavier, Daiani Modernel; Pintanel, Aline Campelo; Farias, Dóris Helena Ribeiro; Lunardi, Valéria Lerch; Aquino, Deise Ribeiro

    2015-12-01

    Understanding the meanings attributed by family caregivers of children in hospital environments about their interactions with nursing professionals. This qualitative study used Symbolic Interactionism as a theoretical reference and Grounded Theory as the methodological framework. It was carried out in a Pediatrics Center in southern Brazil, in the first half of 2013. Participants were 15 family caregivers of hospitalized children. Data were collected through interviews and submitted to open and axial analysis. Interactions with the nursing team enable family to trust or distrust in the provided child care and to positively evaluate the care received. Interactions between family members and the nursing team contribute to the significance attributed by the family to the nursing care received by the child. Nurses should be aware of the attitudes of the nursing team regarding the child and their family, prioritizing humanized care.

  15. Meanings attributed by family members in pediatrics regarding their interactions with nursing professionals

    Directory of Open Access Journals (Sweden)

    Giovana Calcagno Gomes

    2015-12-01

    Full Text Available Abstract OBJECTIVE Understanding the meanings attributed by family caregivers of children in hospital environments about their interactions with nursing professionals. METHODS This qualitative study used Symbolic Interactionism as a theoretical reference and Grounded Theory as the methodological framework. It was carried out in a Pediatrics Center in southern Brazil, in the first half of 2013. Participants were 15 family caregivers of hospitalized children. Data were collected through interviews and submitted to open and axial analysis. RESULTS Interactions with the nursing team enable family to trust or distrust in the provided child care and to positively evaluate the care received. CONCLUSION Interactions between family members and the nursing team contribute to the significance attributed by the family to the nursing care received by the child. Nurses should be aware of the attitudes of the nursing team regarding the child and their family, prioritizing humanized care.

  16. Relationship between bcl-2, bax, beclin-1, and cathepsin-D proteins during postovulatory follicular regression in fish ovary.

    Science.gov (United States)

    Morais, Roberto D V S; Thomé, Ralph G; Santos, Hélio B; Bazzoli, Nilo; Rizzo, Elizete

    2016-04-01

    In fish ovaries, postovulatory follicles (POFs) are key biomarkers of breeding and provide an interesting model for studying the relationship between autophagy and apoptosis. In this study, we investigated the immunohistochemical expression of autophagic and apoptotic proteins to improve the knowledge on the mechanisms regulating ovarian remodeling after spawning. Females from three neotropical fish species kept in captivity were submitted to hormonal induction. After ova stripping, ovarian sections were sampled daily until 5 days postspawning (dps). Similar events of POF regression were detected by histology, terminal transferase-mediated dUTP nick-end labeling (TUNEL), and electron microscopy in the three species: follicular cells hypertrophy, progressive disintegration of the basement membrane, gradual closing of the follicular lumen, theca thickening, and formation of large autophagic vacuoles preceding apoptosis of the follicular cells. Autophagic and apoptotic proteins were assessed by immunohistochemistry. Morphometric analysis of the immunolabeling revealed a more intense reaction for bcl-2 and beclin-1 (BECN1) in POFs at 0 to 1 dps and for bax at 2 to 3 dps (P family, BECN1, and cathepsin-D can be involved in the regulation of ovarian remodeling in teleost fish. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Deregulated expression of A1, Bcl-2, Bcl-xL, and Mcl-1 antiapoptotic proteins and Bid, Bad, and Bax proapoptotic genes in polycythemia vera patients

    Directory of Open Access Journals (Sweden)

    Elainy Patricia Lino Gasparotto

    2011-12-01

    Full Text Available Apoptosis deregulation might have a role in the pathophysiology of polycythemia vera (PV. This study evaluated Bcl-2 molecule expression in CD34+ cells and leukocytes in 12 PV patients. Gene expression was investigated by real time PCR using SybrGreen Quantitect kit and protein expression was evaluated by western-blotting. JAK2 V617F mutation was detected according to Baxter et al (2005. CD34+ cells from PV patients presented higher levels of A1 and Mcl-1 expression (median: 22.6 and 5.2, respectively in comparison with controls (0.9 and 0.5, p=0.004 and p=0.020; while Bcl-2 and Bcl-xL expression decreased in PV patients (0.18 and 1.19 compared with controls (1.39 and 2.01, p=0.006 and p=0.020. CD34+ cells in PV patients showed an elevated Bid expression (14.4 in comparison with healthy subjects (1.0; p=0.002. Patients' leukocytes showed an A1 augmentation (7.41, p=0.001 and a reduced expression of Bax (0.19; p=0.040 and Bad (0.2; p=0.030. There was no correlation between JAK2 V617F allele burden and molecular expression. PV patients showed alterations in Bcl-2 members' expression, which may interfere with control of apoptotic machinery and contribute to disease pathogenesis.A desregulação da apoptose parece participar da fisiopatologia da policitemia vera (PV. Este estudo avaliou a expressão das moléculas da família Bcl-2 em células hematopoéticas CD34 + e leucócitos de 12 pacientes com PV. Foram realizados: a quantificação da expressão gênica por PCR em tempo real utilizando kit Sybrgreen Quantitect, avaliação da expressão de proteínas por western-blot e detecção da mutação JAK2 V617F segundo Baxter et al. (2005. Células CD34 + dos pacientes com PV apresentaram maior expressão de A1 e Mcl-1 (mediana: 22,6 e 5,2, respectivamente em comparação com controles (0,9 e 0,5, p = 0,004 e p = 0,020 e expressão de Bcl-2 e Bcl-xL diminuída nestes pacientes (0,18 e 1,19 em relação aos controles (1,39 e 2,01, p = 0,006 e p = 0

  18. Dual targeting of MDM2 and BCL2 as a therapeutic strategy in neuroblastoma.

    Science.gov (United States)

    Van Goethem, Alan; Yigit, Nurten; Moreno-Smith, Myrthala; Vasudevan, Sanjeev A; Barbieri, Eveline; Speleman, Frank; Shohet, Jason; Vandesompele, Jo; Van Maerken, Tom

    2017-08-22

    Wild-type p53 tumor suppressor activity in neuroblastoma tumors is hampered by increased MDM2 activity, making selective MDM2 antagonists an attractive therapeutic strategy for this childhood malignancy. Since monotherapy in cancer is generally not providing long-lasting clinical responses, we here aimed to identify small molecule drugs that synergize with idasanutlin (RG7388). To this purpose we evaluated 15 targeted drugs in combination with idasanutlin in three p53 wild type neuroblastoma cell lines and identified the BCL2 inhibitor venetoclax (ABT-199) as a promising interaction partner. The venetoclax/idasanutlin combination was consistently found to be highly synergistic in a diverse panel of neuroblastoma cell lines, including cells with high MCL1 expression levels. A more pronounced induction of apoptosis was found to underlie the synergistic interaction, as evidenced by caspase-3/7 and cleaved PARP measurements. Mice carrying orthotopic xenografts of neuroblastoma cells treated with both idasanutlin and venetoclax had drastically lower tumor weights than mice treated with either treatment alone. In conclusion, these data strongly support the further evaluation of dual BCL2/MDM2 targeting as a therapeutic strategy in neuroblastoma.

  19. The prognostic significance of the immunohistochemical expression of P53 and BCL-2 in endometrial cancer

    Directory of Open Access Journals (Sweden)

    Lech Chyczewski

    2012-01-01

    Full Text Available The objective of this study was to verify the frequency of P53 and BCL-2 immunohistochemical expression in 98 patients with endometrial carcinoma, and to correlate it with clinical stage and patient survival. A significant difference was found regarding the frequency of P53 expression when comparing type I and II tumors (23.7% and 54.5%, respectively; p = 0.006. A positive correlation was observed between P53 immunoexpression and patient survival in type I and II tumors (p = 0.009 and p = 0.036, respectively. BCL-2 expression was significantly more frequent in early clinical stages in both types of endometrial cancer (p < 0.001 and 0.002 and correlated with a decrease in overall survival in type I endometrial cancer (p = 0.014. Thus, the prognostic value of these biomarkers in endometrial cancer needs to be further investigated. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 4, pp. 631–635

  20. Influence of Posttraumatic Stress Disorder of the Fathers on other Family MembersInfluence of Posttraumatic Stress Disorder of the Fathers on other Family Members

    Directory of Open Access Journals (Sweden)

    Amra Zalihić

    2008-02-01

    Full Text Available The purpose of this work is to analyze the frequency of depression and anxiety and children behaviour in families whose heads of the family (father suffer from post-traumatic stress disorder (PTSD. The study was conducted from September 2005 until July 2006, with patients living in Mostar. The frequency of depression and anxiety in family members older than 18 years, and changes of the behaviour in children younger than 18 years of age were measured. The data were collected from 60 men and their families who had been diagnosed with PTSD by their psychiatrist. The control group was formed using matching criteria (age of the head of the family, his education, religion, family income and number of children. In this study, three questionnaires were used: one specially designed for this study, covering general information about family members, and a personal opinion of each family member about the family situation and relations within the family; Hopkins symptoms checklist - 25 (HSCL-25 for evaluation of depression and anxiety for subjects older than 18; and General Health Questionnaire (GHQ for children 5 to 18 years of age, which was completed by their mothers.More wives from the PTSD families had depression than wives from the controlled group (χ2=21,099; df=1; P<0,050. There was no difference between groups in frequency of depression and anxiety (χ2=0,003; df=1; P=0,959 for children older than 18 years. No difference in answers between groups of children younger than 18 years were found in the General Health Questionnaire. However, we found significant differences in separate questions. Mothers, who filled the questionnaire form, reported that children from fathers who had PTSD experienced stomach pain more often (χ2=10,474;df=2; P=0,005, eating problems (χ2=14,204;df=2; P=0,001 and breathing problems (χ2=9,748;df=2; P=0,008, than children from fathers who did not have PTSD. Children from fathers with PTSD were more easily upset (χ2

  1. Family Members of Cancer Patients in Korea Are at an Increased Risk of Medically Diagnosed Depression

    Directory of Open Access Journals (Sweden)

    Youngdae Cho

    2018-03-01

    Full Text Available Objectives Family members are often cancer patients’ primary source of social and emotional support and make a major contribution to how well patients manage their illness. We compared the prevalence of depression in the family members of cancer patients and the general population. Methods This study used the data from the fourth, fifth, and sixth rounds of the Korea National Health and Nutrition Examination Survey. The variable of interest was the presence of a cohabitating cancer patient in the family and the dependent variable was the presence of diagnosed depression. Results The odds of having medically diagnosed depression in those with a cohabitating cancer patient in the family were significantly higher than among those who did not have cancer patients in their families (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.12 to 2.17; p=0.009. The OR for females was 1.59, and this increase was statistically significant (95% CI, 1.09 to 2.31; p=0.02. Conclusions We need to invest more effort into diagnosing and managing depression in the family members of cancer patients. This will have an impact both on their quality of life and on the well-being of patients, as supporters and caregivers play an instrumental role in helping patients manage their illness.

  2. Low-income families' perceptions on the use of drugs by one of their members.

    Science.gov (United States)

    Martins, Mayra; Santos, Manoel Antonio Dos; Pillon, Sandra Cristina

    2008-01-01

    Families who are socially excluded are vulnerable to problems related to the use of psychoactive substances. This study aimed to identify the perception regarding drugs use among families that lived in extreme poverty and participated in a social-educational group in the suburbs of a city in the interior of São Paulo State. A survey-like quantitative study was conducted involving 70 members of families who participated in the social-educational groups of the Program for Integral Assistance to the Family. Results indicated that 67 (95.7%) of the subjects were married, at an average age of 37, most of them had not completed grade school, and were unemployed. Fifty five (78.6%) had a family member who used alcohol, fifty two (74,3%) smoked, and twenty three (32.9%) used some kind of illicit drug. The results also showed that living with a relative who was a drug user was perceived as problem that elicited feelings resentment, but also conformism on the part of other family members.

  3. Social worker involvement in identifying problems and needs of families with mentally ill members

    Directory of Open Access Journals (Sweden)

    Kovalčíková N.

    2016-01-01

    Full Text Available The aim of the current study was to explore the impact of schizophrenia on the life of the patient and his family, in particular, which problems people with schizophrenia and their families face. We applied a qualitative research strategy and method of semi-structured interview. Qualitative analysis of the data demonstrated barriers in the working and financial areas of life of people with schizophrenia. In addition, schizophrenia negatively affects social interactions of patients which lead to their social isolation which is also derived from barriers at work. Families with this kind of patient suffer mainly in the economic sphere of life with the necessity to leave the job and take care of an ill member. These families also suffer from isolation, restriction of social contacts, reduction of free-time activities, and many other problems included within the barriers in social interactions. Family members suffer psychological stress and they badly cope with the situation if the ill member is hospitalized. In addition, the family meets with the structural discrimination in the form of lack of information about the disease, lack of day care centres network and similar barriers in communication with physicians and the other professionals.

  4. An Uncharacterized Member of the Ribokinase Family in Thermococcus kodakarensis Exhibits myo-Inositol Kinase Activity*

    Science.gov (United States)

    Sato, Takaaki; Fujihashi, Masahiro; Miyamoto, Yukika; Kuwata, Keiko; Kusaka, Eriko; Fujita, Haruo; Miki, Kunio; Atomi, Haruyuki

    2013-01-01

    Here we performed structural and biochemical analyses on the TK2285 gene product, an uncharacterized protein annotated as a member of the ribokinase family, from the hyperthermophilic archaeon Thermococcus kodakarensis. The three-dimensional structure of the TK2285 protein resembled those of previously characterized members of the ribokinase family including ribokinase, adenosine kinase, and phosphofructokinase. Conserved residues characteristic of this protein family were located in a cleft of the TK2285 protein as in other members whose structures have been determined. We thus examined the kinase activity of the TK2285 protein toward various sugars recognized by well characterized ribokinase family members. Although activity with sugar phosphates and nucleosides was not detected, kinase activity was observed toward d-allose, d-lyxose, d-tagatose, d-talose, d-xylose, and d-xylulose. Kinetic analyses with the six sugar substrates revealed high Km values, suggesting that they were not the true physiological substrates. By examining activity toward amino sugars, sugar alcohols, and disaccharides, we found that the TK2285 protein exhibited prominent kinase activity toward myo-inositol. Kinetic analyses with myo-inositol revealed a greater kcat and much lower Km value than those obtained with the monosaccharides, resulting in over a 2,000-fold increase in kcat/Km values. TK2285 homologs are distributed among members of Thermococcales, and in most species, the gene is positioned close to a myo-inositol monophosphate synthase gene. Our results suggest the presence of a novel subfamily of the ribokinase family whose members are present in Archaea and recognize myo-inositol as a substrate. PMID:23737529

  5. 78 FR 76529 - Members of a Family for Purpose of Filing CBP Family Declaration

    Science.gov (United States)

    2013-12-18

    .... Finally, the NPRM proposed to remove the phrase ``regardless of age'' where it currently appears in the... phrase is used in 19 CFR 148.34(b) and 148.103(b), which relate to the family grouping of exemptions for... duty exemption of $800 for articles acquired abroad (and not the family grouping of duty aggregation of...

  6. Inclusion Complex of Zerumbone with Hydroxypropyl-β-Cyclodextrin Induces Apoptosis in Liver Hepatocellular HepG2 Cells via Caspase 8/BID Cleavage Switch and Modulating Bcl2/Bax Ratio

    Directory of Open Access Journals (Sweden)

    Nabilah Muhammad Nadzri

    2013-01-01

    Full Text Available Zerumbone (ZER isolated from Zingiber zerumbet was previously encapsulated with hydroxypropyl-β-cyclodextrin (HPβCD to enhance ZER’s solubility in water, thus making it highly tolerable in the human body. The anticancer effects of this new ZER-HPβCD inclusion complex via apoptosis cell death were assessed in this study for the first time in liver hepatocellular cells, HepG2. Apoptosis was ascertained by morphological study, nuclear stain, and sub-G1 cell population accumulation with G2/M arrest. Further investigations showed the release of cytochrome c and loss of mitochondrial membrane potential, proving mitochondrial dysfunction upon the ZER-HPβCD treatment as well as modulating proapoptotic and anti-apototic Bcl-2 family members. A significant increase in caspase 3/7, caspase 9, and caspase 8 was detected with the depletion of BID cleaved by caspase 8. Collectively, these results prove that a highly soluble inclusion complex of ZER-HPβCD could be a promising anticancer agent for the treatment of hepatocellular carcinoma in humans.

  7. Persea declinata (Bl. Kosterm Bark Crude Extract Induces Apoptosis in MCF-7 Cells via G0/G1 Cell Cycle Arrest, Bcl-2/Bax/Bcl-xl Signaling Pathways, and ROS Generation

    Directory of Open Access Journals (Sweden)

    Putri Narrima

    2014-01-01

    Full Text Available Persea declinata (Bl. Kosterm is a member of the Lauraceae family, widely distributed in Southeast Asia. It is from the same genus with avocado (Persea americana Mill, which is widely consumed as food and for medicinal purposes. In the present study, we examined the anticancer properties of Persea declinata (Bl. Kosterm bark methanolic crude extract (PDM. PDM exhibited a potent antiproliferative effect in MCF-7 human breast cancer cells, with an IC50 value of 16.68 µg/mL after 48 h of treatment. We observed that PDM caused cell cycle arrest and subsequent apoptosis in MCF-7 cells, as exhibited by increased population at G0/G1 phase, higher lactate dehydrogenase (LDH release, and DNA fragmentation. Mechanistic studies showed that PDM caused significant elevation in ROS production, leading to perturbation of mitochondrial membrane potential, cell permeability, and activation of caspases-3/7. On the other hand, real-time PCR and Western blot analysis showed that PDM treatment increased the expression of the proapoptotic molecule, Bax, but decreased the expression of prosurvival proteins, Bcl-2 and Bcl-xL, in a dose-dependent manner. These findings imply that PDM could inhibit proliferation in MCF-7 cells via cell cycle arrest and apoptosis induction, indicating its potential as a therapeutic agent worthy of further development.

  8. Payment or Reimbursement for Certain Medical Expenses for Camp Lejeune Family Members. Final rule.

    Science.gov (United States)

    2017-05-05

    The Department of Veterans Affairs (VA) adopts as final an interim final rule addressing payment or reimbursement of certain medical expenses for family members of Camp Lejeune veterans. Under this rule, VA reimburses family members, or pays providers, for medical expenses incurred as a result of certain illnesses and conditions that may be associated with contaminants present in the base water supply at U.S. Marine Corps Base Camp Lejeune (Camp Lejeune), North Carolina, from August 1, 1953, to December 31, 1987. Payment or reimbursement is made within the limitations set forth in statute and Camp Lejeune family members receive hospital care and medical services that are consistent with the manner in which we provide hospital care and medical services to Camp Lejeune veterans. The statutory authority has since been amended to also include certain veterans' family members who resided at Camp Lejeune, North Carolina, for no less than 30 days (consecutive or nonconsecutive) between August 1, 1953, and December 31, 1987. This final rule will reflect that statutory change and will address public comments received in response to the interim final rule.

  9. Personality Disorder Traits During Adolescence and Relationships with Family Members During the Transition to Adulthood

    Science.gov (United States)

    Johnson, Jeffrey G.; Chen, Henian; Cohen, Patricia

    2004-01-01

    Data from the Children in the Community Transitions Study, a prospective longitudinal investigation, were used to examine the association between adolescent personality disorder (PD) traits and conflict with family members during the transition to adulthood. PD traits at mean age 16 years were associated with elevated contact and conflict with…

  10. 5 CFR 3201.106 - Employment of family members outside the Corporation.

    Science.gov (United States)

    2010-01-01

    ... Employment of family members outside the Corporation. (a) Disqualification of employees. An employee shall... relationships. A covered employee shall make a written report to an agency designee within 30 days of the... relationship; or (3) A firm or business which, to the employee's knowledge, is seeking a business or...

  11. Self-Concept and Depression among Children Who Experienced the Death of a Family Member

    Science.gov (United States)

    Nguyen, Hong T.; Scott, Amy N.

    2013-01-01

    The present study investigates the moderating effects of physical and academic self-concept on depression among children who experienced the death of a family member. Data from Phase III of the National Institute of Child Health and Human Development Study of Early Child Care was used in the present study. Having a higher physical self-concept…

  12. The Role of Interleukin-1 Family Members in the Host Defence Against Aspergillus fumigatus

    NARCIS (Netherlands)

    Gresnigt, M.S.; Veerdonk, F.L. van de

    2014-01-01

    The interleukin (IL)-1 family consists of 11 members, which all play significant roles in regulating inflammatory responses in the host. IL-1alpha and IL-1beta exert potent pro-inflammatory effects and are key players in the recruitment of neutrophils to the site of inflammation. Protective

  13. Lipase H, a new member of the triglyceride lipase family synthesized by the intestine

    NARCIS (Netherlands)

    Jin, Weijun; Broedl, Uli C.; Monajemi, Houshang; Glick, Jane M.; Rader, Daniel J.

    2002-01-01

    We report here the molecular cloning of a novel member of the triglyceride lipase family, a 2.4-kb cDNA encoding human lipase H (LIPH) and the mouse ortholog (Liph). The human LIPH cDNA encodes a 451-amino-acid protein with a lipase domain. Mouse Liph shows 85% amino acid identity and 75% nucleotide

  14. Resident and family member perceptions of cultural diversity in aged care homes.

    Science.gov (United States)

    Xiao, Lily Dongxia; Willis, Eileen; Harrington, Ann; Gillham, David; De Bellis, Anita; Morey, Wendy; Jeffers, Lesley

    2017-03-01

    Similar to many developed nations, older people living in residential aged care homes in Australia and the staff who care for them have become increasingly multicultural. This cultural diversity adds challenges for residents in adapting to the care home. This study explores: (i) residents' and family members' perceptions about staff and cultural diversity, and (ii) culturally and linguistically diverse residents' and family members' experiences. An interpretive study design employing a thematic analysis was applied. Twenty-three residents and seven family members participated in interviews. Four themes were identified from interpreting residents and family members' perceptions of the impact of cultural diversity on their adaptation to aged care homes: (i) perceiving diversity as an attraction; (ii) adapting to cross-cultural communication; (iii) adjusting to diet in the residential care home; and (iv) anticipating individualized psychosocial interactions. The findings have implications for identifying strategies to support staff from all cultural backgrounds in order to create a caring environment that facilitates positive relationships with residents and supports residents to adjust to the care home. © 2016 John Wiley & Sons Australia, Ltd.

  15. Posttraumatic Symptoms in Japanese Bereaved Family Members with Special Regard to Suicide and Homicide Cases

    Science.gov (United States)

    Ogata, Kohske; Ishikawa, Takaki; Michiue, Tomomi; Nishi, Yuko; Maeda, Hitoshi

    2011-01-01

    The authors investigated posttraumatic stress disorder (PTSD) symptoms in Japanese bereaved family members using a questionnaire. Participants were bereaved as a result of suicide and homicide (n = 51 and 49, respectively), with natural death (n = 56) as a control; and their relationships to the deceased were parent-child (n = 79), conjugal (n =…

  16. Inhibition of Bcl-2 potentiates AZD-2014-induced anti-head and neck squamous cell carcinoma cell activity

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yi; Cui, Jiang-Tao, E-mail: cuijingtaopaper@126.com

    2016-09-02

    Mammalian target of rapamycin (mTOR) is a therapeutic target for head and neck squamous cell carcinoma (HNSCC). Here, we evaluated the activity of AZD-2014, a potent mTOR complex 1/2 (mTORC1/2) dual inhibitor, against HNSCC cells. We showed that AZD-2014 blocked mTORC1/2 activation in established and primary human HNSCC cells, where it was anti-proliferative and pro-apoptotic. Yet, AZD-2014 was non-cytotoxic to the human oral epithelial cells with low basal mTORC1/2 activation. In an effect to identify possible AZD-2014 resistance factors, we showed that the anti-apoptosis protein Bcl-2 was upregulated in AZD-2014-resistant SQ20B HNSCC cells. Inhibition of Bcl-2 by ABT-737 (a known Bcl-2 inhibitor) or Bcl-2 shRNA dramatically potentiated AZD-2014 lethality against HNSCC cells. On the other hand, exogenous overexpression of Bcl-2 largely attenuated AZD-2014’s activity against HNSCC cells. For the in vivo studies, we showed that oral gavage of AZD-2014 suppressed SQ20B xenograft growth in severe combined immunodeficient (SCID) mice. It also significantly improved mice survival. Importantly, AZD-2014’s anti-HNSCC activity in vivo was potentiated with co-administration of ABT-737. The preclinical results of this study suggest that AZD-2014 could be further tested as a valuable anti-HNSCC agent, either alone or in combination with Bcl-2 inhibitors. - Highlights: • AZD-2014 blocks mTORC1/2 activation in HNSCC cells. • AZD-2014 suppresses HNSCC cell proliferation. • AZD-2014 activates caspase-3 and apoptosis in HNSCC cells. • Bcl-2 is the key resistance factor of AZD-2014 in HNSCC cells. • ABT-737 sensitizes AZD-2014-induced anti-HNSCC activity in vivo.

  17. Inhibition of Bcl-2 potentiates AZD-2014-induced anti-head and neck squamous cell carcinoma cell activity

    International Nuclear Information System (INIS)

    Li, Yi; Cui, Jiang-Tao

    2016-01-01

    Mammalian target of rapamycin (mTOR) is a therapeutic target for head and neck squamous cell carcinoma (HNSCC). Here, we evaluated the activity of AZD-2014, a potent mTOR complex 1/2 (mTORC1/2) dual inhibitor, against HNSCC cells. We showed that AZD-2014 blocked mTORC1/2 activation in established and primary human HNSCC cells, where it was anti-proliferative and pro-apoptotic. Yet, AZD-2014 was non-cytotoxic to the human oral epithelial cells with low basal mTORC1/2 activation. In an effect to identify possible AZD-2014 resistance factors, we showed that the anti-apoptosis protein Bcl-2 was upregulated in AZD-2014-resistant SQ20B HNSCC cells. Inhibition of Bcl-2 by ABT-737 (a known Bcl-2 inhibitor) or Bcl-2 shRNA dramatically potentiated AZD-2014 lethality against HNSCC cells. On the other hand, exogenous overexpression of Bcl-2 largely attenuated AZD-2014’s activity against HNSCC cells. For the in vivo studies, we showed that oral gavage of AZD-2014 suppressed SQ20B xenograft growth in severe combined immunodeficient (SCID) mice. It also significantly improved mice survival. Importantly, AZD-2014’s anti-HNSCC activity in vivo was potentiated with co-administration of ABT-737. The preclinical results of this study suggest that AZD-2014 could be further tested as a valuable anti-HNSCC agent, either alone or in combination with Bcl-2 inhibitors. - Highlights: • AZD-2014 blocks mTORC1/2 activation in HNSCC cells. • AZD-2014 suppresses HNSCC cell proliferation. • AZD-2014 activates caspase-3 and apoptosis in HNSCC cells. • Bcl-2 is the key resistance factor of AZD-2014 in HNSCC cells. • ABT-737 sensitizes AZD-2014-induced anti-HNSCC activity in vivo.

  18. Opposite role of Bax and BCL-2 in the anti-tumoral responses of the immune system

    International Nuclear Information System (INIS)

    Bougras, Gwenola; Cartron, Pierre-François; Gautier, Fabien; Martin, Stéphane; LeCabellec, Marité; Meflah, Khaled; Gregoire, Marc; Vallette, François M

    2004-01-01

    The relative role of anti apoptotic (i.e. Bcl-2) or pro-apoptotic (e.g. Bax) proteins in tumor progression is still not completely understood. The rat glioma cell line A15A5 was stably transfected with human Bcl-2 and Bax transgenes and the viability of theses cell lines was analyzed in vitro and in vivo. In vitro, the transfected cell lines (huBax A15A5 and huBcl-2 A15A5) exhibited different sensitivities toward apoptotic stimuli. huBax A15A5 cells were more sensitive and huBcl-2 A15A5 cells more resistant to apoptosis than mock-transfected A15A5 cells (pCMV A15A5). However, in vivo, in syngenic rat BDIX, these cell lines behaved differently, as no tumor growth was observed with huBax A15A5 cells while huBcl-2 A15A5 cells formed large tumors. The immune system appeared to be involved in the rejection of huBax A15A5 cells since i) huBax A15A5 cells were tumorogenic in nude mice, ii) an accumulation of CD8+ T-lymphocytes was observed at the site of injection of huBax A15A5 cells and iii) BDIX rats, which had received huBax A15A5 cells developed an immune protection against pCMV A15A5 and huBcl-2 A15A5 cells. We show that the expression of Bax and Bcl-2 controls the sensitivity of the cancer cells toward the immune system. This sensitization is most likely to be due to an increase in immune induced cell death and/or the amplification of an anti tumour immune response

  19. ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2 and TRAF5.

    Science.gov (United States)

    Hsu, H; Solovyev, I; Colombero, A; Elliott, R; Kelley, M; Boyle, W J

    1997-05-23

    Members of tumor necrosis factor receptor (TNFR) family signal largely through interactions with death domain proteins and TRAF proteins. Here we report the identification of a novel TNFR family member ATAR. Human and mouse ATAR contain 283 and 276 amino acids, respectively, making them the shortest known members of the TNFR superfamily. The receptor is expressed mainly in spleen, thymus, bone marrow, lung, and small intestine. The intracellular domains of human and mouse ATAR share only 25% identity, yet both interact with TRAF5 and TRAF2. This TRAF interaction domain resides at the C-terminal 20 amino acids. Like most other TRAF-interacting receptors, overexpression of ATAR activates the transcription factor NF-kappaB. Co-expression of ATAR with TRAF5, but not TRAF2, results in synergistic activation of NF-kappaB, suggesting potentially different roles for TRAF2 and TRAF5 in post-receptor signaling.

  20. Chipmunk parvovirus is distinct from members in the genus Erythrovirus of the family Parvoviridae.

    Directory of Open Access Journals (Sweden)

    Zhaojun Chen

    2010-12-01

    Full Text Available The transcription profile of chipmunk parvovirus (ChpPV, a tentative member of the genus Erythrovirus in the subfamily Parvovirinae of the family Parvoviridae, was characterized by transfecting a nearly full-length genome. We found that it is unique from the profiles of human parvovirus B19 and simian parvovirus, the members in the genus Erythrovirus so far characterized, in that the small RNA transcripts were not processed for encoding small non-structural proteins. However, like the large non-structural protein NS1 of the human parvovirus B19, the ChpPV NS1 is a potent inducer of apoptosis. Further phylogenetic analysis of ChpPV with other parvoviruses in the subfamily Parvovirinae indicates that ChpPV is distinct from the members in genus Erythrovirus. Thus, we conclude that ChpPV may represent a new genus in the family Parvoviridae.

  1. Experiences of family members of patients with colostomies and expectations about professional intervention

    Directory of Open Access Journals (Sweden)

    Augusto Ferreira-Umpiérrez

    2014-04-01

    Full Text Available OBJECTIVE: the objective was to understand the experience of a group of family members of patients with colostomies, revealing their expectations regarding the intervention of health professionals.METHOD: qualitative research, with the social phenomenological approach of Alfred Schütz, conducted in Montevideo in 2012; twelve family members of patients with colostomies participated, from an ostomy service of a health institution.RESULTS: the following categories were identified: family ties, trust in the health care team, the nurse as the articulator of the process, the desire to humanize care, and adaptation to new family life.CONCLUSIONS: knowing the experience and expectations of the families of colostomy patients was achieved, emphasizing the previous family relationships to build upon them, and the trust in the health team, emphasizing the nurse as articulator of the process. Expectations focused on the desire for humanized care, enhancing adaptation of the nuclear family to the new way of life, restoring and enhancing its strengths, and collaborating in overcoming its weaknesses.

  2. Family members facilitating community re-integration and return to productivity following traumatic brain injury - motivations, roles and challenges.

    Science.gov (United States)

    Gagnon, Alicia; Lin, Jenny; Stergiou-Kita, Mary

    2016-01-01

    This study explores the experiences of family members in supporting community re-integration and return to productive occupations of the traumatic brain injury (TBI) survivor in order to: (i) describe family members' supportive roles, (ii) determine challenges family members experience in supporting the TBI survivor; and (iii) identify supports that family members require to maintain and enhance their roles. This qualitative descriptive study involved 14 interviews with immediate family members of TBI survivors. Data was analyzed using thematic analysis. Family members expressed strong motivation and engaged in six key roles to support TBI survivors: researcher, case manager, advocate, coach, activities of daily living (ADL)/instrumental ADLs and emotional supporter. Personal and family stressors and challenges navigating the health care system were perceived as challenges in meeting demands of their supportive roles. Stigma also presented a barrier to successful community and vocational re-integration. Subsequently, family members desired more education related to the functional implications of TBI, to be connected to health care and community resources, and sought a greater family-centred care approach. Family members require on-going counseling and community supports to prevent burnout and allow for their continued engagement in their supportive roles. Further education on how to navigate the health care system, access community programs and rights to workplace accommodation is also warranted. Family members are strongly motivated to support survivors' return to productive occupation following a traumatic brain injury, but require counseling and community support to enable their on-going engagement and prevent burnout. Family members can be further empowered through the implementation of family-centred care. Family members requested further education on the long-term functional implications of TBI, how to navigate the health care system, how to access community

  3. Psychoeducational Intervention for Sexuality with the Aged, Family Members of the Aged, and People Who Work with the Aged.

    Science.gov (United States)

    White, Charles B.; Catania, Joseph A.

    1982-01-01

    Conducted and evaluated a sexual psychoeducational intervention with older persons, adult family members of older persons, and staff members of nursing homes. Results indicated significant changes in attitudes toward and knowledge about sexuality and aging and sexual behavior. (Author)

  4. [Need for the role of the patient's family members at the intensive care unit].

    Science.gov (United States)

    Aliberch Raurell, A M; Miquel Aymar, I M

    2015-01-01

    To know the current status for the role of family members in the intensive care unit and its evolution, analyzing areas for improvement and learning about the nursing role. This work is a literature review. The selected articles included two of the key words in their title. Articles before year 2000 were excluded, except some work of great interest. Family members lose their role and suffer a crisis when one of them is at the intensive care unit. Their normal role into the family changes or disappears. Obtaining a participation role increases satisfaction and decreases anxiety in relatives. Nursing professionals are essential in addressing this need. Solving the need for this role decreases anxiety and stress on relatives and patients. Their implication on the patient process enhances and helps professionals to know the patient's background. Copyright © 2014 Elsevier España, S.L.U. y SEEIUC. All rights reserved.

  5. Obatoclax, a Pan-BCL-2 Inhibitor, Targets Cyclin D1 for Degradation to Induce Antiproliferation in Human Colorectal Carcinoma Cells.

    Science.gov (United States)

    Or, Chi-Hung R; Chang, Yachu; Lin, Wei-Cheng; Lee, Wee-Chyan; Su, Hong-Lin; Cheung, Muk-Wing; Huang, Chang-Po; Ho, Cheesang; Chang, Chia-Che

    2016-12-27

    Colorectal cancer is the third most common cancer worldwide. Aberrant overexpression of antiapoptotic BCL-2 (B-cell lymphoma 2) family proteins is closely linked to tumorigenesis and poor prognosis in colorectal cancer. Obatoclax is an inhibitor targeting all antiapoptotic BCL-2 proteins. A previous study has described the antiproliferative action of obatoclax in one human colorectal cancer cell line without elucidating the underlying mechanisms. We herein reported that, in a panel of human colorectal cancer cell lines, obatoclax inhibits cell proliferation, suppresses clonogenicity, and induces G₁-phase cell cycle arrest, along with cyclin D1 downregulation. Notably, ectopic cyclin D1 overexpression abrogated clonogenicity suppression but also G₁-phase arrest elicited by obatoclax. Mechanistically, pre-treatment with the proteasome inhibitor MG-132 restored cyclin D1 levels in all obatoclax-treated cell lines. Cycloheximide chase analyses further revealed an evident reduction in the half-life of cyclin D1 protein by obatoclax, confirming that obatoclax downregulates cyclin D1 through induction of cyclin D1 proteasomal degradation. Lastly, threonine 286 phosphorylation of cyclin D1, which is essential for initiating cyclin D1 proteasomal degradation, was induced by obatoclax in one cell line but not others. Collectively, we reveal a novel anticancer mechanism of obatoclax by validating that obatoclax targets cyclin D1 for proteasomal degradation to downregulate cyclin D1 for inducing antiproliferation.

  6. Hypoxic human cancer cells are sensitized to BH-3 mimetic–induced apoptosis via downregulation of the Bcl-2 protein Mcl-1

    Science.gov (United States)

    Harrison, Luke R.E.; Micha, Dimitra; Brandenburg, Martin; Simpson, Kathryn L.; Morrow, Christopher J.; Denneny, Olive; Hodgkinson, Cassandra; Yunus, Zaira; Dempsey, Clare; Roberts, Darren; Blackhall, Fiona; Makin, Guy; Dive, Caroline

    2011-01-01

    Solid tumors contain hypoxic regions in which cancer cells are often resistant to chemotherapy-induced apoptotic cell death. Therapeutic strategies that specifically target hypoxic cells and promote apoptosis are particularly appealing, as few normal tissues experience hypoxia. We have found that the compound ABT-737, a Bcl-2 homology domain 3 (BH-3) mimetic, promotes apoptotic cell death in human colorectal carcinoma and small cell lung cancer cell lines exposed to hypoxia. This hypoxic induction of apoptosis was mediated through downregulation of myeloid cell leukemia sequence 1 (Mcl-1), a Bcl-2 family protein that serves as a biomarker for ABT-737 resistance. Downregulation of Mcl-1 in hypoxia was independent of hypoxia-inducible factor 1 (HIF-1) activity and was consistent with decreased global protein translation. In addition, ABT-737 induced apoptosis deep within tumor spheroids, consistent with an optimal hypoxic oxygen tension being necessary to promote ABT-737–induced cell death. Tumor xenografts in ABT-737–treated mice also displayed significantly more apoptotic cells within hypoxic regions relative to normoxic regions. Synergies between ABT-737 and other cytotoxic drugs were maintained in hypoxia, suggesting that this drug may be useful in combination with chemotherapeutic agents. Taken together, these findings suggest that Mcl-1–sparing BH-3 mimetics may induce apoptosis in hypoxic tumor cells that are resistant to other chemotherapeutic agents and may have a role in combinatorial chemotherapeutic regimens for treatment of solid tumors. PMID:21393866

  7. Combination of erlotinib and EGCG induces apoptosis of head and neck cancers through posttranscriptional regulation of Bim and Bcl-2.

    Science.gov (United States)

    Haque, Abedul; Rahman, Mohammad Aminur; Chen, Zhuo Georgia; Saba, Nabil F; Khuri, Fadlo R; Shin, Dong M; Ruhul Amin, A R M

    2015-07-01

    Combinatorial approaches using two or more compounds are gaining increasing attention for cancer therapy. We have previously reported that the combination of the EGFR-TKI erlotinib and epigallocatechin-3-gallate (EGCG) exhibited synergistic chemopreventive effects in head and neck cancers by inducing the expression of Bim, p21, p27, and by inhibiting the phosphorylation of ERK and AKT and expression of Bcl-2. In the current study, we further investigated the mechanism of regulation of Bim, Bcl-2, p21 and p27, and their role in apoptosis. shRNA-mediated silencing of Bim significantly inhibited apoptosis induced by the combination of erlotinib and EGCG (p = 0.005). On the other hand, overexpression of Bcl-2 markedly protected cells from apoptosis (p = 0.003), whereas overexpression of constitutively active AKT only minimally protected cells from apoptosis induced by the combination of the two compounds. Analysis of mRNA expression by RT-PCR revealed that erlotinib, EGCG and their combination had no significant effects on the mRNA expression of Bim, p21, p27 or Bcl-2 suggesting the post-transcriptional regulation of these molecules. Furthermore, we found that erlotinib or the combination of EGCG and erlotinib inhibited the phosphorylation of Bim and stabilized Bim after inhibition of protein translation by cycloheximide. Taken together, our results strongly suggest that the combination of erlotinib and EGCG induces apoptosis of SCCHN cells by regulating Bim and Bcl-2 at the posttranscriptional level.

  8. Detection of bcl-2 translocation in patients with chronic hepatitis C and its possible relation to antiviral therapy: preliminary study

    International Nuclear Information System (INIS)

    Ibrahim, N.S.; Hanna, M.O.F.; Farid, R.J.; Zayed, N.A.; Hunter, S.S.; Esmat, J.

    2007-01-01

    It has been suggested that t(14; 18) translocation of bcl-2 to the immunoglobulin heavy chain (IgH) locus may contribute to the pathogenesis of lymphoproliferative disorders (LPD) related to hepatitis C virus (HCV) infection. The present study aimed to assess the prevalence of bcl-2 translocation in Egyptian chronic HCV patients and to investigate the effect of combination antiviral therapy of interferon a and ribavirin on t(14;18). Fifty five chronic HCV patients were studied for the prevalence of t(l4; 18). These patients were classified into 2 groups, 33 non treated HCV patients and 22 treated HCV patients with antiviral therapy as well as control group of age and sex matched individuals. The bcl-2/IgH rearrangement was detected in peripheral blood mononuclear cells (PBMCs) by nested polymerase chain reaction. All patients have undergone HCV viral determination by real time PCR. Bcl-2/IgH translocation was detected in 21 (38.2%) of all 55 chronically infected HCV patients. Considering all patients with chronic HCV-infection, bcl-2 rearrangement was slightly more frequent in the non treated group than in those who underwent treatment with interferon plus ribavirin but the difference was not statistically significant, although treated patients showed biochemical and virologic response at the end of 6 months of antiviral therapy. In conclusion, t(l4;18) in PBMCs is a frequent finding in chronic HCV infection

  9. Correlation of mammographical imaging signs with the expression of bcl-2 and bax proteins in breast cancer

    International Nuclear Information System (INIS)

    Zhang Yili; Du Hongwen; Zhang Yun; Zhang Yuelang; Kuang Fangjun; Guo Zuomin

    2004-01-01

    Objective: To discuss the correlation of mammographical imaging signs with the expression of bcl-2 and bax proteins in breast cancer for early diagnosis and forecast of its prognoses. Methods: Fifty-four breast cancers and 26 benign diseases were proved by pathologic methods and all cases underwent mammography. Immunohistochemical technique was used to measure the expression of bcl-2 and bax proteins in these tissues. The correlation of imaging signs with the expression of bcl-2 and bax proteins in breast cancer and benign lesion was analyzed. Results: The expression of bcl-2 or bax protein in the breast cancer was higher than that in breast benign diseases (χ 2 =15.116, 11.361, P 2 =10.358, 12.818, P 2 =10.996, 10.667, P 2 =10.405, P 2 =6.841, P<0.05). Conclusion: Some imaging signs of breast cancer were closely related to the expression of bcl-2 and bax proteins and these signs could reflect the biological behavior of tumor cells and prognoses. Therefore it could be helpful to the early diagnosis and treatment of breast cancer. (authors)

  10. Combined Targeting of BCL-2 and BCR-ABL Tyrosine Kinase Eradicates Chronic Myeloid Leukemia Stem Cells

    Science.gov (United States)

    Mak, Po Yee; Mu, Hong; Zhou, Hongsheng; Mak, Duncan H.; Schober, Wendy; Leverson, Joel D.; Zhang, Bin; Bhatia, Ravi; Huang, Xuelin; Cortes, Jorge; Kantarjian, Hagop; Konopleva, Marina

    2016-01-01

    BCR-ABL tyrosine kinase inhibitors (TKIs) are effective against chronic myeloid leukemia (CML), but they rarely eliminate CML stem cells. Disease relapse is common upon therapy cessation, even in patients with complete molecular responses. Furthermore, once CML progresses to blast crisis (BC), treatment outcomes are dismal. We hypothesized that concomitant targeting of BCL-2 and BCR-ABL tyrosine kinase could overcome these limitations. We demonstrate increased BCL-2 expression at the protein level in bone marrow cells, particularly in Lin−Sca-1+cKit+ cells of inducible CML in mice as determined by CyTOF mass cytometry. Further, selective inhibition of BCL-2, aided by TKI-mediated MCL-1 and BCL-XL inhibition, markedly decreased leukemic Lin−Sca-1+cKit+ cell numbers and long-term stem cell frequency, and prolonged survival in a murine CML model. Additionally, this combination effectively eradicated CD34+CD38−, CD34+CD38+, and quiescent stem/progenitor CD34+ cells from BC CML patient samples. Our results suggest that BCL-2 is a key survival factor for CML stem/progenitor cells and that combined inhibition of BCL-2 and BCR-ABL tyrosine kinase has the potential to significantly improve depth of response and cure rates of chronic phase and BC CML. PMID:27605552

  11. Family medical leave. An employee benefit for working caregivers of elderly family members.

    Science.gov (United States)

    Carruth, A K; Booth, D

    1991-09-01

    Future trends include a decrease in the number of adult children, an increase in the number of individuals over age 65, single parent families, working women, and individuals with no health care insurance. As more women with multiple roles and responsibilities enter and continue as part of the work force, employers recognize the need for support of family issues. Currently many employers lack initiative to make these needed changes. The occupational health nurses' role in relation to future policy for working caregivers includes assessment of how employment and caregiving impact work performance, job satisfaction, and health; and participation in defining public policy issues.

  12. Family matters: The experiences and opinions of family members of persons with (severe) or profound intellectual disabilities

    OpenAIRE

    Luijkx, Jorien

    2016-01-01

    “I love my sister, but sometimes I don’t”. This is one of the statements made in the study focused on the experiences of family members of people with (profound) intellectual (and multiple) disabilities (both of individuals living in a residential facility as persons living at home). In recent years, there has been greater recognition of the important position of parents and siblings of people with (profound) intellectual (and multiple) disabilities and the importance of the wellbeing of all ...

  13. Proposed regulations could limit access to affordable health coverage for workers' children and family members.

    Science.gov (United States)

    Jacobs, Ken; Graham-Squire, Dave; Roby, Dylan H; Kominski, Gerald F; Kinane, Christina M; Needleman, Jack; Watson, Greg; Gans, Daphna

    2011-12-01

    Key Findings. The Patient Protection and Affordable Care Act (ACA) is designed to offer premium subsidies to help eligible individuals and their families purchase insurance coverage when affordable job-based coverage is not available. However, the law is unclear on how this affordability protection is applied in those instances where self-only coverage offered by an employer is affordable but family coverage is not. Regulations recently proposed by the Department of the Treasury would make family members ineligible for subsidized coverage in the exchange if an employee is offered affordable self-only coverage by an employer, even if family coverage is unaffordable. This could have significant financial consequences for low- and moderate-income families that fall in this gap. Using an alternative interpretation of the law could allow the entire family to enter the exchange when family coverage is unaffordable, which would broaden access to coverage. However, this option has been cited as cost prohibitive. In this brief we consider a middle ground alternative that would base eligibility for the individual worker on the cost of self-only coverage, but would use the additional cost to the employee for family coverage as the basis for determining affordability and eligibility for subsidies for the remaining family members. We find that: Under the middle ground alternative scenario an additional 144,000 Californians would qualify for and use premium subsidies in the California Health Benefit Exchange, half of whom are children. Less than 1 percent of those with employer-based coverage would move to subsidized coverage in the California Health Benefit Exchange as a result of having unaffordable coverage on the job.

  14. Double-hit lymphoma demonstrating t(6;14;18)(p25;q32;q21), suggesting two independent dual-hit translocations, MYC/BCL-2 and IRF4/BCL-2.

    Science.gov (United States)

    Tabata, Rie; Yasumizu, Ryoji; Tabata, Chiharu; Kojima, Masaru

    2013-01-01

    Here, we report a rare case of double-hit lymphoma, demonstrating t(6;14;18)(p25;q32;q21), suggesting two independent dual-translocations, c-MYC/BCL-2 and IRF4/BCL-2. The present case had a rare abnormal chromosome, t(6;14;18)(p25;q32;q21), independently, in addition to known dual-hit chromosomal abnormalities, t(14;18)(q32;q21) and t(8;22)(q24;q11.2). Lymph node was characterized by a follicular and diffuse growth pattern with variously sized neoplastic follicles. The intrafollicular area was composed of centrocytes with a few centroblasts and the interfollicular area was occupied by uniformly spread medium- to large-sized lymphocytes. CD23 immunostaining demonstrated a disrupted follicular dendritic cell meshwork. The intrafollicular tumor cells had a germinal center phenotype with the expression of surface IgM, CD10, Bcl-2, Bcl-6, and MUM1/IRF4. However, the interfollicular larger cells showed plasmacytic differentiation with diminished CD20, Bcl-2, Bcl-6, and positive intracytoplasmic IgM, and co-expression of MUM1/IRF4 and CD138 with increased Ki-67-positive cells (> 90%). MUM1/IRF4 has been found to induce c-MYC expression, and in turn, MYC transactivates MUM1/IRF4, creating a positive autoregulatory feedback loop. On the other hand, MUM1/IRF4 functions as a tumor suppressor in c-MYC-induced B-cell leukemia. The present rare case arouses interest in view of the possible "dual" activation of both c-MYC and MUM1/IRF4 through two independent dual-translocations, c-MYC/BCL-2 and IRF4/BCL-2.

  15. 77 FR 18143 - Members of a Family for Purpose of Filing a CBP Family Declaration

    Science.gov (United States)

    2012-03-27

    ..., stepchildren, half-siblings, legal wards, other dependents, and individuals with an in loco parentis or... collected under 19 CFR part 148 is included under OMB control number 1651-0009. There are no new collections... in the family grouping.''; and b. By revising paragraph (b) and adding a new paragraph (c). The...

  16. Perceived timeliness of referral to hospice palliative care among bereaved family members in Korea.

    Science.gov (United States)

    Jho, Hyun Jung; Chang, Yoon Jung; Song, Hye Young; Choi, Jin Young; Kim, Yeol; Park, Eun Jung; Paek, Soo Jin; Choi, Hee Jae

    2015-09-01

    We aimed to explore the perceived timeliness of referral to hospice palliative care unit (HPCU) among bereaved family members in Korea and factors associated therewith. Cross-sectional questionnaire survey was performed for bereaved family members of patients who utilized 40 designated HPCUs across Korea. The questionnaire assessed whether admission to the HPCU was "too late" or "appropriate" and the Good Death Inventory (GDI). A total of 383 questionnaires were analyzed. Of participants, 25.8 % replied that admission to HPCU was too late. Patients with hepatobiliary cancer, poor performance status, abnormal consciousness level, and unawareness of terminal status were significantly related with the too late perception. Family members with younger age and being a child of the patient were more frequently noted in the too late group. Ten out of 18 GDI scores were significantly lower in the too late group. Multiple logistic regression analysis revealed patients' unawareness of terminal status, shorter stay in the HPCU, younger age of bereaved family, and lower scores for two GDI items (staying in a favored place, living without concerning death or disease) were significantly associated with the too late group. To promote timely HPCU utilization and better quality of end of life care, patients need to be informed of the terminal status and their preference should be respected.

  17. Stress regulated members of the plant organic cation transporter family are localized to the vacuolar membrane

    Directory of Open Access Journals (Sweden)

    Koch Wolfgang

    2008-07-01

    Full Text Available Abstract Background In Arabidopsis six genes group into the gene family of the organic cation transporters (OCTs. In animals the members of the OCT-family are mostly characterized as polyspecific transporters involved in the homeostasis of solutes, the transport of monoamine neurotransmitters and the transport of choline and carnitine. In plants little is known about function, localisation and regulation of this gene family. Only one protein has been characterized as a carnitine transporter at the plasma membrane so far. Findings We localized the five uncharacterized members of the Arabidopsis OCT family, designated OCT2-OCT6, via GFP fusions and protoplast transformation to the tonoplast. Expression analysis with RNA Gel Blots showed a distinct, organ-specific expression pattern of the individual genes. With reporter gene fusion of four members we analyzed the tissue specific distribution of OCT2, 3, 4, and 6. In experiments with salt, drought and cold stress, we could show that AtOCT4, 5 and 6 are up-regulated during drought stress, AtOCT3 and 5 during cold stress and AtOCT 5 and 6 during salt stress treatments. Conclusion Localisation of the proteins at the tonoplast and regulation of the gene expression under stress conditions suggests a specific role for the transporters in plant adaptation to environmental stress.

  18. Still Searching: A Meta-Synthesis of a Good Death from the Bereaved Family Member Perspective

    Directory of Open Access Journals (Sweden)

    Kelly E. Tenzek

    2017-04-01

    Full Text Available The concept of a good death continues to receive attention in end-of-life (EOL scholarship. We sought to continue this line of inquiry related to a good death by conducting a meta-synthesis of published qualitative research studies that examined a good death from the bereaved family member’s perspective. Results of the meta-synthesis included 14 articles with 368 participants. Based on analysis, we present a conceptual model called The Opportunity Model for Presence during the EOL Process. The model is framed in socio-cultural factors, and major themes include EOL process engagement with categories of healthcare participants, communication and practical issues. The second theme, (discontinuity of care, includes categories of place of care, knowledge of family member dying and moment of death. Both of these themes lead to perceptions of either a good or bad death, which influences the bereavement process. We argue the main contribution of the model is the ability to identify moments throughout the interaction where family members can be present to the EOL process. Recommendations for healthcare participants, including patients, family members and clinical care providers are offered to improve the quality of experience throughout the EOL process and limitations of the study are discussed.

  19. The role of the expression of bcl-2, p53 gene in tamoxifen-induced apoptosis of breast cancer cells and its relationship with hormone receptor status

    Energy Technology Data Exchange (ETDEWEB)

    Noh, Woo Chul; Ham, Yong Ho [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1998-01-01

    To investigate the relationship of bcl-2, p53, ER and tamoxifen-induced apoptosis of breast cancer cells, MCF-7 (ER+/bcl-2+/p53-) and MB MDA 468 (ER-/bcl-2-/p53+) cell line were cultured in estrogen-free condition. E2(10`-`9M) and tamoxifen (10`-`5M) were added to the media. The changes of bcl-2 and mutant p53 protein were checked by Western blot and apoptosis were measured by flowcytometry. In MCF-7 cells, we found that treatment with tamoxifen resulted in a decrease in bcl-2 protein level, but produced no change in mutant p53. In MB MDA 468 cell however, there were no changes of bcl-2 and mutant p53 protein level when E2 or tamoxifen were added. Apoptotic cells increased with time-dependent pattern when tamoxifen was added to MCF-7 cells. According to these result, ER+/blc-2+/mutant p53- cells, when treated with tamoxifen, were converted into bcl-2/mutant p53- cells which were more prone to apoptosis than bcl-2-/mutant p53+ cells. The paradoxical correlation of bcl-2 and ER which had been observed in clinical studies might be explained with this results and bcl-2 protein seems to be one of important factors that can predict the effect of hormone therapy. (author). 26 refs., 5 figs

  20. Loss in MCL-1 function sensitizes non-Hodgkin's lymphoma cell lines to the BCL-2-selective inhibitor venetoclax (ABT-199)

    International Nuclear Information System (INIS)

    Phillips, D C; Xiao, Y; Lam, L T; Litvinovich, E; Roberts-Rapp, L; Souers, A J; Leverson, J D

    2015-01-01

    As a population, non-Hodgkin's lymphoma (NHL) cell lines positive for the t(14;18) translocation and/or possessing elevated BCL2 copy number (CN; BCL2 High ) are exquisitely sensitive to navitoclax or the B-cell lymphoma protein-2 (BCL-2)-selective inhibitor venetoclax. Despite this, some BCL2 High cell lines remain resistant to either agent. Here we show that the MCL-1-specific inhibitor A-1210477 sensitizes these cell lines to navitoclax. Chemical segregation of this synergy with the BCL-2-selective inhibitor venetoclax or BCL-X L -selective inhibitor A-1155463 indicated that MCL-1 and BCL-2 are the two key anti-apoptotic targets for sensitization. Similarly, the CDK inhibitor flavopiridol downregulated MCL-1 expression and synergized with venetoclax in BCL2 High NHL cell lines to a similar extent as A-1210477. A-1210477 also synergized with navitoclax in the majority of BCL2 Low NHL cell lines. However, chemical segregation with venetoclax or A-1155463 revealed that synergy was driven by BCL-X L inhibition in this population. Collectively these data emphasize that BCL2 status is predictive of venetoclax potency in NHL not only as a single agent, but also in the adjuvant setting with anti-tumorigenic agents that inhibit MCL-1 function. These studies also potentially identify a patient population (BCL2 Low ) that could benefit from BCL-X L (navitoclax)-driven combination therapy

  1. The role of the expression of bcl-2, p53 gene in tamoxifen-induced apoptosis of breast cancer cells and its relationship with hormone receptor status

    International Nuclear Information System (INIS)

    Noh, Woo Chul; Ham, Yong Ho

    1998-01-01

    To investigate the relationship of bcl-2, p53, ER and tamoxifen-induced apoptosis of breast cancer cells, MCF-7 (ER+/bcl-2+/p53-) and MB MDA 468 (ER-/bcl-2-/p53+) cell line were cultured in estrogen-free condition. E2(10'-'9M) and tamoxifen (10'-'5M) were added to the media. The changes of bcl-2 and mutant p53 protein were checked by Western blot and apoptosis were measured by flowcytometry. In MCF-7 cells, we found that treatment with tamoxifen resulted in a decrease in bcl-2 protein level, but produced no change in mutant p53. In MB MDA 468 cell however, there were no changes of bcl-2 and mutant p53 protein level when E2 or tamoxifen were added. Apoptotic cells increased with time-dependent pattern when tamoxifen was added to MCF-7 cells. According to these result, ER+/blc-2+/mutant p53- cells, when treated with tamoxifen, were converted into bcl-2/mutant p53- cells which were more prone to apoptosis than bcl-2-/mutant p53+ cells. The paradoxical correlation of bcl-2 and ER which had been observed in clinical studies might be explained with this results and bcl-2 protein seems to be one of important factors that can predict the effect of hormone therapy. (author). 26 refs., 5 figs

  2. Study of American and Chinese family members' evaluations on institutionalized care for their older parents: potential development in the future.

    Science.gov (United States)

    Li, Yushi; Buechel, Annie

    2007-01-01

    The evaluations on institutionalized care facilities from family members, after their loved ones moved into such services, are very different from culture to culture, family to family and person to person. According to a recent survey in the United States and China, it is found that different cultures and the different health conditions of the residents strongly influence family member's viewpoints on institutionalized care services. It is also found that the availability of the institutionalized care facilities plays a significant role, which strongly affects family members' evaluations on nursing home services.

  3. Psychological crisis intervention for the family members of patients in a vegetative state

    Directory of Open Access Journals (Sweden)

    Ya-Hong Li

    2012-01-01

    Full Text Available OBJECTIVES: Family members of patients in a vegetative state have relatively high rates of anxiety and distress. It is important to recognize the problems faced by this population and apply psychological interventions to help them. This exploratory study describes the psychological stress experienced by family members of patients in a vegetative state. We discuss the effectiveness of a psychological crisis intervention directed at this population and offer suggestions for future clinical work. METHODS: A total of 107 family members of patients in a vegetative state were included in the study. The intervention included four steps: acquisition of facts about each family, sharing their first thoughts concerning the event, assessment of their emotional reactions and developing their coping abilities. The Symptom Check List-90 was used to evaluate the psychological distress of the participants at baseline and one month after the psychological intervention. Differences between the Symptom Check List-90 scores at the baseline and follow-up evaluations were analyzed. RESULTS: All participants in the study had significantly higher Symptom Check List-90 factor scores than the national norms at baseline. There were no significant differences between the intervention group and the control group at baseline. Most of the Symptom Check List-90 factor scores at the one-month follow-up evaluation were significantly lower than those at baseline for both groups; however, the intervention group improved significantly more than the control group on most subscales, including somatization, obsessive-compulsive behavior, depression, and anxiety. CONCLUSION: The results of this study indicate that the four-step intervention method effectively improves the mental health of the family members who received this treatment and lessens the psychological symptoms of somatization, obsessive-compulsive behavior, depression and anxiety.

  4. Exhaustive Training Increases Uncoupling Protein 2 Expression and Decreases Bcl-2/Bax Ratio in Rat Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    W. Y. Liu

    2013-01-01

    Full Text Available This work investigates the effects of oxidative stress due to exhaustive training on uncoupling protein 2 (UCP2 and Bcl-2/Bax in rat skeletal muscles. A total of 18 Sprague-Dawley female rats were randomly divided into three groups: the control group (CON, the trained control group (TC, and the exhaustive trained group (ET. Malondialdehyde (MDA, superoxide dismutase (SOD, xanthine oxidase (XOD, ATPase, UCP2, and Bcl-2/Bax ratio in red gastrocnemius muscles were measured. Exhaustive training induced ROS increase in red gastrocnemius muscles, which led to a decrease in the cell antiapoptotic ability (Bcl-2/Bax ratio. An increase in UCP2 expression can reduce ROS production and affect mitochondrial energy production. Thus, oxidative stress plays a significant role in overtraining.

  5. Evaluation of Bcl-2, Bcl-x and Cleaved Caspase-3 in Malignant Peripheral Nerve Sheath Tumors and Neurofibromas

    Directory of Open Access Journals (Sweden)

    KARIN S. CUNHA

    2013-11-01

    Full Text Available AIMS: To study the expression of Bcl-2, Bcl-x, as well the presence of cleaved caspase-3 in neurofibromas and malignant peripheral nerve sheath tumors. The expression of Bcl-2 and Bcl-x and the presence of cleaved caspase 3 were compared to clinicopathological features of malignant peripheral nerve sheath tumors and their impact on survival rates were also investigated. MATERIALS AND METHODS: The evaluation of Bcl-2, Bcl-x and cleaved caspase-3 was performed by immunohistochemistry using tissue microarrays in 28 malignant peripheral nerve sheath tumors and 38 neurofibromas. Immunoquantification was performed by computerized digital image analysis. CONCLUSIONS: Apoptosis is altered in neurofibromas and mainly in malignant peripheral nerve sheath tumors. High levels of cleaved caspase-3 are more common in tumors with more aggressive histological features and it is associated with lower disease free survival of patients with malignant peripheral nerve sheath tumors.

  6. Perspectives of family members on planning end-of-life care for terminally ill and frail older people.

    Science.gov (United States)

    van Eechoud, Ineke J; Piers, Ruth D; Van Camp, Sigrid; Grypdonck, Mieke; Van Den Noortgate, Nele J; Deveugele, Myriam; Verbeke, Natacha C; Verhaeghe, Sofie

    2014-05-01

    Advance care planning (ACP) is the process by which patients, together with their physician and loved ones, establish preferences for future care. Because previous research has shown that relatives play a considerable role in end-of-life care decisions, it is important to understand how family members are involved in this process. To gain understanding of the involvement of family members in ACP for older people near the end of life by exploring their views and experiences concerning this process. This was a qualitative research study, done with semistructured interviews. Twenty-one family members were recruited from three geriatric settings in Flanders, Belgium. The data were analyzed using the constant comparative method as proposed by the grounded theory. Family members took different positions in the ACP process depending on how much responsibility the family member wanted to take and to what extent the family member felt the patient expected him/her to play a part. The position of family members on these two dimensions was influenced by several factors, namely acknowledgment of the imminent death, experiences with death and dying, opinion about the benefits of ACP, burden of initiating conversations about death and dying, and trust in health care providers. Furthermore, the role of family members in ACP was embedded in the existing relationship patterns. This study provides insight into the different positions of family members in the end-of-life care planning of older patients with a short life expectancy. It is important for health care providers to understand the position of a family member in the ACP of the patient, take into account that family members may experience an active role in ACP as burdensome, and consider existing relationship patterns. Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

  7. Family members' needs and experiences of driving disruption over time following an acquired brain injury: an evolving issue.

    Science.gov (United States)

    Liang, Phyllis; Gustafsson, Louise; Liddle, Jacki; Fleming, Jennifer

    2017-07-01

    Family members often assume the role of driver for individuals who are not driving post-acquired brain injury (ABI). Given that return to driving can be unpredictable and uncertain, the impact of driving disruption on family members may vary at different stages post-injury. This study aims to understand the needs and experiences of family members over time during driving disruption following an ABI. A qualitative prospective longitudinal research design was used with semi-structured interviews at recruitment to study, 3 and 6 months later. Fourteen family members completed 41 interviews. The longitudinal data revealed four phases of driving disruption: (1) Wait and see, (2) Holding onto a quick fix, (3) No way out, and (4) Resolution and adjustment. The phases described a process of building tension and a need for support and resolution over time. Holding onto a quick fix is a pivotal phase whereby supports, such as engagement in realistic goal setting, are essential to facilitate family members' resolution of driving disruption issues. Family members who see no way out might not actively seek help and these points to a need for long-term and regular follow-ups. Future research can explore ways to support family members at these key times. Implications for rehabilitation Health professionals need to facilitate the process of fostering hope in family members to set realistic expectations of return to driving and the duration of driving disruption. It is necessary to follow-up with family members even years after ABI as the issue of driving disruption could escalate to be a crisis and family members might not actively seek help. Health professionals can consider both practical support for facilitating transport and emotional support when addressing the issue of driving disruption with family members.

  8. The incidence of tuberculosis transmission among family members and outside households.

    Science.gov (United States)

    Kozińska, Monika; Augustynowicz-Kopeć, Ewa

    2016-01-01

    The risk of Mycobacterium tuberculosis complex (MTBC) infection is correlated with the concentration of infectious particles and exposure time. In closed populations, healthy people staying in very frequent, close and prolonged contact with a smear-positive person, become infected and represent another link in the chain of transmission of the disease. Therefore, in the fight against tuberculosis, an important element is quick identification of the patient and potentially infected people from his environment. In epidemiological investigation of tuberculosis (TB), family members are brought under special control as they are particularly exposed to transmission of infectious diseases. The study included 150 patients with bacteriologically confirmed tuberculosis who were members of 59 families. In the years 2003-2013 this population represented all TB cases detected in Poland in a family environment.Three PCR-based genotyping methods: spoligotyping, IS6110-Mtb1-Mtb2 PCR and MIRU-VNTR typing were used. Of 150 patients, 138 could be assigned to intra-household transmission on the basis of identical DNA fingerprints upon a combined typing approach. For 12 patients in 6 households, the M. tuberculosis isolates were clearly distinct in individual analysis - IS6110-Mtb1-Mtb2 PCR, spoligotyping or MIRU-VNTR typing or in three genotyping methods, suggesting that these patients were infected by the sources in the community. The analysis confirmed the transmission of tuberculosis among members of 53 families. In the remaining 6 families the source of infection were people outside the households. In all families with young children, strains isolated from them have identical DNA patterns as strains obtained from their adult caregivers. To confirm the transmission of TB in the study population of patients, epidemiological analysis required the addition of a genotyping methods characterised by high discriminatory power.

  9. Narratives of family members on the suicide of older adults in an Amazonian metropolis.

    Science.gov (United States)

    Costa, André Luis Sales da; Souza, Maximiliano Loiola Ponte de

    2017-12-11

    To analyze the narratives of family members on the suicide of older adults in Manaus, State of Amazonas, Brazil. This is a qualitative study of the narratives of eight older adults, who committed suicide in the period of 2001-2012. In the analytic-interpretative process, we have tried to perform the hermeneutic double exercise: to interpret the interpretation of narrators. We have used as theoretical references authors who have investigated suicide from the perspective of gender and its correlations with the sociofamiliar context and with mental disorders. The family members would conceive the suicide of the older adults as related to losses, which would occur in a strained sociofamiliar scenario, leading to the appearance of psychopathological situations that, if not properly followed, would result in death. There would also be something inexorable in this sequence of events. The older adults, by the very time of their life, would tend to accumulate losses of different aspects in their trajectory. Their rigor and other relational limitations would simultaneously stress family relationships, favoring conflicts, and hinder adherence to treatment. This model of understanding, which has a wide support in the hegemonic medical-psychological discourse, in a sense minimizes possible self- or heteroaccusations directed at family members. Special attention should be given to identify the older adults who present losses, family conflicts, and signs of psychopathology and who do not follow-up psychosocial care services. Strategies to help older adults handle family conflicts and losses, empowering them, should be developed and made available by intersectoral actions. The adequate treatment of psychopathological conditions should be implanted in a context in which active search mechanisms also existed for older adults who abandoned follow-up. The implementation of these actions is a challenge to be faced in Manaus, State of Amazonas, Brazil, where there is a low availability

  10. Few opportunities to influence decisions regarding the care and treatment of an older hospitalized family member: a qualitative study among family members.

    Science.gov (United States)

    Nyborg, Ingrid; Danbolt, Lars Johan; Kirkevold, Marit

    2017-08-31

    The drive towards patient involvement in health services has been increasingly promoted. The World Health Organisation emphasizes the family's perspective in comprehensive care. Internationally there is an increased emphasis on what patients and their family tell about the hospital experiences. However, current literature does not adequately address the question of participation experiences among relatives of older hospitalized family members. There is a paucity of research with a generational perspective on relatives' opportunities to exert influence. The aim of the study was to explore relatives' experiences of opportunities to participate in decisions about the care and treatment of older hospitalized family members and whether there are different experiences of influence to the relatives' age. This was an explorative study applying individual qualitative interviews. The interviews were analysed following hermeneutic methodological principles. Two Norwegian geriatric wards participated: one at a university hospital and one at a local hospital. Twelve participants, six women and six men, were purposively selected. The relatives were aged from 36 to 88 (mean age 62) and were spouses, children and/or children-in-law of patients. The relatives' experienced opportunities to exert influence were distributed along a continuum ranging from older relatives being reactive waiting for an initiative from health professionals, to younger adults being proactive securing influence. Older "invisible" carers appeared to go unnoticed by the health professionals, establishing few opportunities to influence decisions. The middle-aged relatives also experienced limited influence, but participated when the hospital needed it. However, limited participation seemed to have less impact on their lives than in the older relatives. Middle-aged relatives and younger adults identified strategies in which visibility was the key to increasing the odds of gaining participation. The exceptional

  11. Guilt, censure, and concealment of active smoking status among cancer patients and family members after diagnosis: a nationwide study.

    Science.gov (United States)

    Shin, Dong Wook; Park, Jong Hyock; Kim, So Young; Park, Eal Whan; Yang, Hyung Kook; Ahn, Eunmi; Park, Seon Mee; Lee, Young Joon; Lim, Myong Cheol; Seo, Hong Gwan

    2014-05-01

    We aimed to identify the prevalence of feelings of guilt, censure, and concealment of smoking status among cancer patients and their family members who continued to smoke after the patient's diagnosis. Among 990 patient-family member dyads, 45 patients and 173 family members who continued to smoke for at least 1 month after the patients' diagnoses were administered questions examining feelings of guilt, censure, and smoking concealment. Most patients who continued to smoke reported experiencing feelings of guilt toward their families (75.6%) and censure from their family members (77.8%), and many concealed their smoking from their family members (44.4%) or healthcare professionals (46.7%). Family members who continued to smoke also reported feelings of guilt with respect to the patient (63.6%) and that the patient was critical of them (68.9%), and many concealed their smoking from the patient (28.5%) or healthcare professionals (9.3%). Patients' feeling of guilt was associated with concealment of smoking from family members (55.9% vs. 10.0%) or health care professionals (55.9% vs. 20.0%). Family members who reported feeling guilty (36.5% vs. 16.3%) or censured (34.5% vs. 16.7%) were more likely to conceal smoking from patients. Many patients and family members continue to smoke following cancer diagnosis, and the majority of them experience feelings of guilt and censure, which can lead to the concealment of smoking status from families or health care professionals. Feelings of guilt, censure, and concealment of smoking should be considered in the development and implementation of smoking cessation programs for cancer patients and family members. Copyright © 2013 John Wiley & Sons, Ltd.

  12. Apoptosis and BCL-2 expression as predictors of survival in radiation-treated non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Hwang, Jun-Hwa; Lim, Sung-Chul; Kim, Young-Chul; Park, Kyung-Ok; Ahn, Sung-Ja; Chung, Woong-Ki

    2001-01-01

    Objectives: We assessed the role of apoptosis and the expression of bcl-2, p53, and c-myc oncoproteins in pretreatment histologic specimens as a predictor of response to radiation therapy and survival in non-small-cell lung cancer (NSCLC) patients. Methods: Pretreatment biopsy specimens of 68 patients with NSCLC (62 squamous cell carcinoma, 6 adenocarcinoma) were stained with hematoxylin and eosin. From 5 high-powered fields, the apoptotic index (AI) was calculated as the ratio of apoptotic tumor cells to the total number of tumor cells. Bcl-2, p53, and c-myc oncoprotein expression was detected by immunohistochemical staining. Results: Twenty-nine cases showed partial or complete remission, whereas 39 showed no response. AI ranged from 0.2 to 12.0% (mean ± SD; 4.3±2.6%, median 4.0%). There was no difference in AI between responders (4.0±2.3) and nonresponders (4.5±2.8, p>0.05). However, in the responders, AI was correlated with the degree of change in tumor volume (r=0.41, p<0.05). In an analysis of 53 subjects who survived more than 1 month after the completion of radiation therapy, the patients with a higher AI (n=27, MST=22.8 m) survived longer than those with a lower AI (n=26, MST=9.2, log-rank, p=0.03). Patients expressing bcl-2 had poorer survival (n=22, MST=6.0 m) than patients without bcl-2 (n=31, 22.8 m, p<0.003). According to multivariate analysis, three variables, bcl-2 expression, AI, and response to radiation, were independent prognostic factors for survival. Conclusion: A low level of spontaneous apoptosis and expression of apoptosis blocking bcl-2 protein in pretreatment histology predict a poor prognosis for radiation-treated NSCLC patients

  13. Evaluation of multiple bio-pathological factors in colorectal adenocarcinomas: independent prognostic role of p53 and bcl-2.

    Science.gov (United States)

    Buglioni, S; D'Agnano, I; Cosimelli, M; Vasselli, S; D'Angelo, C; Tedesco, M; Zupi, G; Mottolese, M

    1999-12-22

    About 40% of patients with colorectal carcinoma will develop local or distant tumour recurrences. Integrated analyses of bio-pathological markers, predictive of tumour aggressiveness, may offer a more rational approach to planning adjuvant therapy. To this end, we analysed the correlation between p53 accumulation, Bcl-2 expression, DNA ploidy, cell proliferation and conventional clinico-pathological parameters by testing the prognostic significance of these variables in a series of 171 colorectal carcinoma patients with long-term follow-up. The relationships among the various bio-pathological parameters, analysed by multiple correspondence analysis, showed 2 different clinico-biological profiles. The first, characterised by p53 negativity, Bcl-2 positivity, diploidy, low percentage of cells in S-phase (%S-phase), a low Ki-67 score, is associated with Dukes' A-B stage, well differentiated tumours and lack of relapse. The second, defined by p53 positivity, Bcl-2 negativity, aneuploidy, high %S-phase and elevated Ki-67 score, correlates with Dukes' C-D stage, poorly differentiated tumours and presence of relapse. When these parameters were examined according to Kaplan-Meier's method, significantly shorter disease-free (DFS) and overall survival (OS) were also observed in patients bearing p53 positive and Bcl-2 negative tumours, in Dukes' B stage. In multivariate analysis, p53 accumulation and Bcl-2 expression emerged as independent predictors of a worse and better clinical outcome, respectively. Our results indicate that, in colorectal adenocarcinomas, a biological profile, based on the combined evaluation of p53 and Bcl-2, may be useful for identifying high risk patients to be enrolled in an adjuvant setting, mainly in an early stage of the disease. Int. J. Cancer (Pred. Oncol.) 84:545-552, 1999. Copyright 1999 Wiley-Liss, Inc.

  14. The importance of older family members in providing social resources and promoting cancer screening in families with a hereditary cancer syndrome.

    Science.gov (United States)

    Ashida, Sato; Hadley, Donald W; Goergen, Andrea F; Skapinsky, Kaley F; Devlin, Hillary C; Koehly, Laura M

    2011-12-01

    This study evaluates the role of older family members as providers of social resources within familial network systems affected by an inherited cancer susceptibility syndrome.  Respondents who previously participated in a study that involved genetic counseling and testing for Lynch syndrome and their family network members were invited to participate in a onetime telephone interview about family communication. A total of 206 respondents from 33 families identified 2,051 social relationships (dyads). Nineteen percent of the respondents and 25% of the network members were older (≥60 years). Younger respondents (≤59 years) were more likely to nominate older network members as providers of social resources than younger members: instrumental support (odds ratio [OR] = 1.68), emotional support (OR = 1.71), help in crisis situation (OR = 2.04), and dependability when needed (OR = 2.15). Compared with younger network members, older members were more likely to be listed as encouragers of colon cancer screening by both younger (OR = 3.40) and older respondents (OR = 1.90) independent of whether support exchange occurred in the relationship. Engaging older network members in health interventions to facilitate screening behaviors and emotional well-being of younger members within families affected by inherited conditions may be beneficial. Findings can be used to empower older individuals about their important social roles in enhancing the well-being of their family members and to inform younger individuals about their older relatives' resourcefulness to facilitate positive social interactions.

  15. Women service members, veterans, and their families: What we know now.

    Science.gov (United States)

    Mankowski, Mariann; Everett, Joyce E

    2016-12-01

    The purpose of this paper is to highlight what we know now about female service members, veterans, and their families. The experiences of U.S. female service members and veterans are more complex than previous eras and significant demographic changes have taken place. U.S. female veterans are more likely to be younger, come from ethnic and racial minority groups, have children, and combat exposure. U.S. female service members report high rates of sexual violence and they are more vulnerable to homelessness and unemployment when compared to previous female military cohorts. U.S. female service members and veterans are also at higher risk for significant mental and health issues. Children and adolescents of women service members and veterans may also carry a heavy burden as a result of lengthy deployments. A majority of female service members and veterans will utilize community based healthcare and social services, therefore, it is essential that all healthcare providers understand the unique needs of this cohort of women. Practice implications at the micro, mezzo, and macro levels are discussed. Qualitative and quantitative studies that expand our understanding of women's experience in the military and as veterans are encouraged. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. E2F family members are differentially regulated by reversible acetylation

    DEFF Research Database (Denmark)

    Marzio, G; Wagener, C; Gutierrez, M I

    2000-01-01

    of the other E2F family members. Here we report that E2F-1, -2, and -3, but not E2F-4, -5, and -6, associate with and are acetylated by p300 and cAMP-response element-binding protein acetyltransferases. Acetylation occurs at three conserved lysine residues located at the N-terminal boundary of their DNA......The six members of the E2F family of transcription factors play a key role in the control of cell cycle progression by regulating the expression of genes involved in DNA replication and cell proliferation. E2F-1, -2, and -3 belong to a structural and functional subfamily distinct from those...

  17. The role of interleukin-1 family members in the host defence against Aspergillus fumigatus.

    Science.gov (United States)

    Gresnigt, Mark S; van de Veerdonk, Frank L

    2014-12-01

    The interleukin (IL)-1 family consists of 11 members, which all play significant roles in regulating inflammatory responses in the host. IL-1α and IL-1β exert potent pro-inflammatory effects and are key players in the recruitment of neutrophils to the site of inflammation. Protective anti-Aspergillus host responses during the early stages of invasive aspergillosis are critically dependent on neutrophil recruitment, and several lines of evidence support that there is an important role for IL-1 in this process. However, IL-1-mediated inflammation needs to be tightly regulated, since uncontrolled inflammation can result in inflammatory pathology and thereby be detrimental for the host. Aspergillus-induced IL-1-mediated inflammation could therefore be amendable for IL-1 blockade under specific circumstances. This review describes the current understanding of the role of IL-1 family members in the host response against Aspergillus fumigatus and highlights the importance of balanced IL-1 responses in aspergillosis.

  18. Identification of the PDI-family member ERp90 as an interaction partner of ERFAD.

    Directory of Open Access Journals (Sweden)

    Jan Riemer

    Full Text Available In the endoplasmic reticulum (ER, members of the protein disulfide isomerase (PDI family perform critical functions during protein maturation. Herein, we identify the previously uncharacterized PDI-family member ERp90. In cultured human cells, we find ERp90 to be a soluble ER-luminal glycoprotein that comprises five potential thioredoxin (Trx-like domains. Mature ERp90 contains 10 cysteine residues, of which at least some form intramolecular disulfides. While none of the Trx domains contain a canonical Cys-Xaa-Xaa-Cys active-site motif, other conserved cysteines could endow the protein with redox activity. Importantly, we show that ERp90 co-immunoprecipitates with ERFAD, a flavoprotein involved in ER-associated degradation (ERAD, through what is most likely a direct interaction. We propose that the function of ERp90 is related to substrate recruitment or delivery to the ERAD retrotranslocation machinery by ERFAD.

  19. Expression of activator protein-1 (AP-1) family members in breast cancer

    International Nuclear Information System (INIS)

    Kharman-Biz, Amirhossein; Gao, Hui; Ghiasvand, Reza; Zhao, Chunyan; Zendehdel, Kazem; Dahlman-Wright, Karin

    2013-01-01

    The activator protein-1 (AP-1) transcription factor is believed to be important in tumorigenesis and altered AP-1 activity was associated with cell transformation. We aimed to assess the potential role of AP-1 family members as novel biomarkers in breast cancer. We studied the expression of AP-1 members at the mRNA level in 72 primary breast tumors and 37 adjacent non-tumor tissues and evaluated its correlation with clinicopathological parameters including estrogen receptor (ER), progesterone receptor (PR) and HER2/neu status. Expression levels of Ubiquitin C (UBC) were used for normalization. Protein expression of AP-1 members was assessed using Western blot analysis in a subset of tumors. We used student’s t-test, one-way ANOVA, logistic regression and Pearson’s correlation coefficient for statistical analyses. We found significant differences in the expression of AP-1 family members between tumor and adjacent non-tumor tissues for all AP-1 family members except Fos B. Fra-1, Fra-2, Jun-B and Jun-D mRNA levels were significantly higher in tumors compared to adjacent non-tumor tissues (p < 0.001), whilst c-Fos and c-Jun mRNA levels were significantly lower in tumors compared with adjacent non-tumor tissues (p < 0.001). In addition, Jun-B overexpression had outstanding discrimination ability to differentiate tumor tissues from adjacent non-tumor tissues as determined by ROC curve analysis. Moreover, Fra-1 was significantly overexpressed in the tumors biochemically classified as ERα negative (p = 0.012) and PR negative (p = 0.037). Interestingly, Fra-1 expression was significantly higher in triple-negative tumors compared with luminal carcinomas (p = 0.01). Expression levels of Fra-1 and Jun-B might be possible biomarkers for prognosis of breast cancer

  20. Al-Anon family groups' newcomers and members: Concerns about the drinkers in their lives.

    Science.gov (United States)

    Timko, Christine; Cronkite, Ruth; Laudet, Alexandre; Kaskutas, Lee Ann; Roth, Jeffrey; Moos, Rudolf H

    2014-01-01

    Despite Al-Anon's widespread availability and use, knowledge is lacking about the drinkers in attendees' lives. We filled this gap by describing and comparing Al-Anon newcomers' and members' reports about their "main drinker" (main person prompting initial attendance). Al-Anon's World Service Office mailed a random sample of groups, yielding completed surveys from newcomers (N = 362) and stable members (N = 265). Newcomers' and members' drinkers generally were comparable. They had known their drinker for an average of 22 years and been concerned about his or her's drinking for 9 years; about 50% had daily contact with the drinker. Most reported negative relationship aspects (drinker gets on your nerves; you disagree about important things). Newcomers had more concern about the drinker's alcohol use than members did, and were more likely to report their drinkers' driving under the influence. Drinkers' most frequent problem due to drinking was family arguments, and most common source of help was 12-step groups, with lower rates among drinkers of newcomers. Concerns spurring initial Al-Anon attendance were the drinker's poor quality of life, relationships, and psychological status; goals for initial attendance reflected these concerns. The drinker's alcohol use was of less concern in prompting initial Al-Anon attendance, and, accordingly, the drinker's reduced drinking was a less frequently endorsed goal of attendance. Family treatments for substance use problems might expand interventions and outcome domains beyond abstinence and relationship satisfaction to include the drinker's quality of life and psychological symptoms and in turn relieve concerns of family members. © American Academy of Addiction Psychiatry.

  1. A review of issues and concerns of family members of adult burn survivors.

    Science.gov (United States)

    Sundara, Diana C

    2011-01-01

    The purpose of this review is to synthesize what is known about the issues and concerns of families of adult burn survivors from research and clinical articles written between 1973 and 2009. Electronic database searching, ancestry searching, and electronic hand searching were performed to identify relevant articles. Seventeen research studies and 14 clinical articles were identified. Families are often in crisis immediately after the injury. This crisis involves strong emotions, some of which may persist over time. Throughout the course of hospitalization, family issues include worries about their loved one's physical appearance, logistical concerns, and the transition to home. For partners, role changes and sexual concerns may be of particular importance. Extended family, friends, the burn team, and other families affected by a burn injury are important sources of support for family members. Few studies have been conducted beyond the time of hospitalization. Clinical articles have identified issues not present in the research literature. Further research is needed that focuses more closely on families and their experiences both in and out of the hospital. Implications for burn care providers based on the findings of this review are discussed.

  2. Niakha virus: A novel member of the family Rhabdoviridae isolated from phlebotomine sandflies in Senegal

    OpenAIRE

    Vasilakis, Nikos; Widen, Steven; Mayer, Sandra V.; Seymour, Robert; Wood, Thomas G.; Popov, Vsevolov; Guzman, Hilda; Travassos da Rosa, Amelia P.A.; Ghedin, Elodie; Holmes, Edward C.; Walker, Peter J.; Tesh, Robert B.

    2013-01-01

    Members of the family Rhabdoviridae have been assigned to eight genera but many remain unassigned. Rhabdoviruses have a remarkably diverse host range that includes terrestrial and marine animals, invertebrates and plants. Transmission of some rhabdoviruses often requires an arthropod vector, such as mosquitoes, midges, sandflies, ticks, aphids and leafhoppers, in which they replicate. Herein we characterize Niakha virus (NIAV), a previously uncharacterized rhabdovirus isolated from phebotomin...

  3. Expression of Hepatoma-derived growth factor family members in the adult central nervous system

    Directory of Open Access Journals (Sweden)

    Abouzied Mekky M

    2006-01-01

    Full Text Available Abstract Background Hepatoma-derived growth factor (HDGF belongs to a polypeptide family containing five additional members called HDGF related proteins 1–4 (HRP-1 to -4 and Lens epithelial derived growth factor. Whereas some family members such as HDGF and HRP-2 are expressed in a wide range of tissues, the expression of others is very restricted. HRP-1 and -4 are only expressed in testis, HRP-3 only in the nervous system. Here we investigated the expression of HDGF, HRP-2 and HRP-3 in the central nervous system of adult mice on the cellular level by immunohistochemistry. In addition we performed Western blot analysis of various brain regions as well as neuronal and glial cell cultures. Results HDGF was rather evenly expressed throughout all brain regions tested with the lowest expression in the substantia nigra. HRP-2 was strongly expressed in the thalamus, prefrontal and parietal cortex, neurohypophysis, and the cerebellum, HRP-3 in the bulbus olfactorius, piriform cortex and amygdala complex. HDGF and HRP-2 were found to be expressed by neurons, astrocytes and oligodendrocytes. In contrast, strong expression of HRP-3 in the adult nervous system is restricted to neurons, except for very weak expression in oligodendrocytes in the brain stem. Although the majority of neurons are HRP-3 positive, some like cerebellar granule cells are negative. Conclusion The coexpression of HDGF and HRP-2 in glia and neurons as well as the coexpression of all three proteins in many neurons suggests different functions of members of the HDGF protein family in cells of the central nervous system that might include proliferation as well as cell survival. In addition the restricted expression of HRP-3 point to a special function of this family member for neuronal cells.

  4. MicroRNA-125 family members exert a similar role in the regulation of murine hematopoiesis.

    Science.gov (United States)

    Wojtowicz, Edyta E; Walasek, Marta A; Broekhuis, Mathilde J C; Weersing, Ellen; Ritsema, Martha; Ausema, Albertina; Bystrykh, Leonid V; de Haan, Gerald

    2014-10-01

    MicroRNAs (miRNAs) are crucial for proper functioning of hematopoietic stem and progenitor cells (HSPCs). Members of the miRNA-125 family (consisting of miR-125a, miR-125b1, and miR-125b2) are known to confer a proliferative advantage on cells upon overexpression, to decrease the rate of apoptosis by targeting proapoptotic genes, and to promote differentiation toward the myeloid lineage in mice. However, many distinct biological effects of the three miR-125 species have been reported as well. In the current study, we set out to assess whether the three miRNA-125s that carry identical seed sequences could be functionally different. Our data show that overexpression of each of the three miR-125 family members preserves HSPCs in a primitive state in vitro, results in a competitive advantage upon serial transplantation, and promotes skewing toward the myeloid lineage. All miR-125 family members decreased the pool of phenotypically defined Lin(-)Sca(+)Kit(+)CD48(-)CD150(+) long-term hematopoietic stem cells, simultaneously increasing the self-renewal activity upon secondary transplantation. The downregulation of miR-125s in hematopoietic stem cells abolishes these effects and impairs long-term contribution to blood cell production. The introduction of a point mutation within the miRNA-125 seed sequence abolishes all abovementioned effects and leads to the restoration of normal hematopoiesis. Our results show that all miR-125 family members are similar in function, they likely operate in a seed-sequence-dependent manner, and they induce a highly comparable hematopoietic phenotype. Copyright © 2014 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  5. The Unforgettables: a chorus for people with dementia with their family members and friends.

    Science.gov (United States)

    Mittelman, Mary Sherman; Papayannopoulou, Panayiota Maria

    2018-01-29

    Summary/Abstract Our experience evaluating a museum program for people with dementia together with their family members demonstrated benefits for all participants. We hypothesized that participation in a chorus would also have positive effects, giving them an opportunity to share a stimulating and social activity that could improve their quality of life. We inaugurated a chorus for people with dementia and their family caregivers in 2011, which rehearses and performs regularly. Each person with dementia must be accompanied by a friend or family member and must commit to attending all rehearsals and the concert that ensues. A pilot study included a structured assessment, take home questionnaires and focus groups. Analyses of pre-post scores were conducted; effect size was quantified using Cohen's d. Results showed that quality of life and communication with the other member of the dyad improved (Effect size: Cohen's d between 0.32 and 0.72) for people with dementia; quality of life, social support, communication and self-esteem improved (d between 0.29 and 0.68) for caregivers. Most participants stated that benefits included belonging to a group, having a normal activity together and learning new skills. Participants attended rehearsals in spite of harsh weather conditions. The chorus has been rehearsing and performing together for more than 6 years and contributing to its costs. Results of this pilot study suggest that people in the early to middle stage of dementia and their family members and friends can enjoy and learn from rehearsing and performing in concerts that also engage the wider community. It is essential to conduct additional larger studies of the benefits of participating in a chorus, which may include improved quality of life and social support for all, and reduced cognitive decline among people with dementia.

  6. Importance of dimer formation of myocardin family members in the regulation of their nuclear export.

    Science.gov (United States)

    Hayashi, Ken'ichiro; Morita, Tsuyoshi

    2013-01-01

    Myocardin (Mycd) family members function as a transcriptional cofactor for serum response factor (SRF). Dimer formation is necessary to exhibit their function, and the coiled-coil domain (CC) plays a critical role in their dimerization. We have recently revealed a detailed molecular mechanism for their Crm1 (exportin1)-mediated nuclear export. Here, we found other unique significances of the dimerization of Mycd family members. Introduction of mutations in the CC of myocardin-related transcription factor A (MRTF-A) and truncated Mycd resulted in significant decreases in their cytoplasmic localization and increases in their nuclear localization. In accordance with such subcellular localization changes, their binding to Crm1 were reduced. These results indicate that the dimerization of Mycd family members is necessary for their Crm1-mediated nuclear export. We have recently found that the N-terminal region of Mycd consisting of 128 amino acids (Mycd N128) self-associates to Mycd via the central basic domain (CB), resulting in masking the Crm1-binding site. Such self-association of MRTF-A would be unlikely. In this study, we also revealed that the dimerization of Mycd was also necessary for this self-association. Wild-type Mycd activated SRF-mediated transcription more potently than Mycd lacking the Mycd N128 (Mycd ΔN128) did. These results suggest two possible functions of the Mycd N128: 1) stabilization of Mycd dimer to enhance SRF-mediated transcription and 2) positive regulation of the transactivation ability of Mycd. These findings provide a new insight into the functional regulation of Mycd family members.

  7. The features of family relationship experience, style of parental bonding and relationship with family members of convicts

    Directory of Open Access Journals (Sweden)

    Daiva Karkockienė

    2016-01-01

    Full Text Available The aim of this article is to reveal the features of family relationship, style of parental bonding and relationship with family members of convicts. The tasks of the research: 1 to analyse the relationships experienced in families of convicts and the subjectively perceived style of parental bonding in their childhood; 2 to assess the relationships of convicts (men and women with their families; 3 to compare the attachment styles of convicts analysing different close relationships (with parents, relatives, partner or a close friend. The research was carried out in Panevėžys Correctional Facility and Lukiškės Remand Prison – Closed Prison. In total, the research involved 63 subjects, out of whom 33 were men and 30 women. The female subjects were 18–64 years old, males – 18–45 years old. The following tools were used: Parental Bonding Instrument (Parker G. et al., 1997, Familial Relationship Quality Measure (Ryan & Willits, 2007, Experiences in Close Relationships-Revised (ECR – RS; Fraley, Waller, & Brennan, 2000 and demographic questionnaire. The findings have showed that were no statistically significant differences with regard to gender were established assessing the subjectively perceived style of parental bonding, satisfaction with familial relationships and the attachment style in different close relationships. Both male and female subjects attributed the subjectively perceived upbringing style of a father to “overprotection”, that of a mother – to “care”. The attachment style of males characterised as “avoidance” is insignificantly higher than females, whereas the “anxiety” style of attachment in samples of males and females showed almost no differences. A positive relationship was established between the satisfaction with experienced familial relationships and the “caring” style of upbringing of both parents. Satisfaction with familial relationships positively correlates with the importance of

  8. Involvement of Family Members and Professionals in Older Women's Post-Fall Decision Making.

    Science.gov (United States)

    Bergeron, Caroline D; Hilfinger Messias, DeAnne K; Friedman, Daniela B; Spencer, S Melinda; Miller, Susan C

    2018-03-01

    This exploratory, descriptive study examined involvement of family members and professionals in older women's post-fall decision making. We conducted semistructured interviews with 17 older women who had recently fallen and 11 individuals these women identified as being engaged in their post-fall decision-making processes. Qualitative data analysis involved open and axial coding and development of themes. After experiencing a fall, these older women's openness to others' opinions and advice; their assessments of types and credibility of potential information sources; and the communication practices they established with these sources influenced how they accessed, accepted, or rejected information from family members and professionals. Increased awareness of the involvement of others in post-fall decision making could enhance communication with older women who fall. Developing and implementing practical strategies to help family members and professionals initiate and engage in conversations about falls and their consequences could lead to more open decision making and improved post-fall quality of life among older women.

  9. Evolutionary Pattern and Regulation Analysis to Support Why Diversity Functions Existed within PPAR Gene Family Members

    Directory of Open Access Journals (Sweden)

    Tianyu Zhou

    2015-01-01

    Full Text Available Peroxisome proliferators-activated receptor (PPAR gene family members exhibit distinct patterns of distribution in tissues and differ in functions. The purpose of this study is to investigate the evolutionary impacts on diversity functions of PPAR members and the regulatory differences on gene expression patterns. 63 homology sequences of PPAR genes from 31 species were collected and analyzed. The results showed that three isolated types of PPAR gene family may emerge from twice times of gene duplication events. The conserved domains of HOLI (ligand binding domain of hormone receptors domain and ZnF_C4 (C4 zinc finger in nuclear in hormone receptors are essential for keeping basic roles of PPAR gene family, and the variant domains of LCRs may be responsible for their divergence in functions. The positive selection sites in HOLI domain are benefit for PPARs to evolve towards diversity functions. The evolutionary variants in the promoter regions and 3′ UTR regions of PPARs result into differential transcription factors and miRNAs involved in regulating PPAR members, which may eventually affect their expressions and tissues distributions. These results indicate that gene duplication event, selection pressure on HOLI domain, and the variants on promoter and 3′ UTR are essential for PPARs evolution and diversity functions acquired.

  10. Evolutionary Pattern and Regulation Analysis to Support Why Diversity Functions Existed within PPAR Gene Family Members.

    Science.gov (United States)

    Zhou, Tianyu; Yan, Xiping; Wang, Guosong; Liu, Hehe; Gan, Xiang; Zhang, Tao; Wang, Jiwen; Li, Liang

    2015-01-01

    Peroxisome proliferators-activated receptor (PPAR) gene family members exhibit distinct patterns of distribution in tissues and differ in functions. The purpose of this study is to investigate the evolutionary impacts on diversity functions of PPAR members and the regulatory differences on gene expression patterns. 63 homology sequences of PPAR genes from 31 species were collected and analyzed. The results showed that three isolated types of PPAR gene family may emerge from twice times of gene duplication events. The conserved domains of HOLI (ligand binding domain of hormone receptors) domain and ZnF_C4 (C4 zinc finger in nuclear in hormone receptors) are essential for keeping basic roles of PPAR gene family, and the variant domains of LCRs may be responsible for their divergence in functions. The positive selection sites in HOLI domain are benefit for PPARs to evolve towards diversity functions. The evolutionary variants in the promoter regions and 3' UTR regions of PPARs result into differential transcription factors and miRNAs involved in regulating PPAR members, which may eventually affect their expressions and tissues distributions. These results indicate that gene duplication event, selection pressure on HOLI domain, and the variants on promoter and 3' UTR are essential for PPARs evolution and diversity functions acquired.

  11. Identification of a novel IL-1 cytokine family member in teleost fish.

    Science.gov (United States)

    Wang, Tiehui; Bird, Steve; Koussounadis, Antonis; Holland, Jason W; Carrington, Allison; Zou, Jun; Secombes, Christopher J

    2009-07-15

    A novel IL-1 family member (nIL-1F) has been discovered in fish, adding a further member to this cytokine family. The unique gene organization of nIL-1F, together with its location in the genome and low homology to known family members, suggests that this molecule is not homologous to known IL-1F. Nevertheless, it contains a predicted C-terminal beta-trefoil structure, an IL-1F signature region within the final exon, a potential IL-1 converting enzyme cut site, and its expression level is clearly increased following infection, or stimulation of macrophages with LPS or IL-1beta. A thrombin cut site is also present and may have functional relevance. The C-terminal recombinant protein antagonized the effects of rainbow trout rIL-1beta on inflammatory gene expression in a trout macrophage cell line, suggesting it is an IL-1beta antagonist. Modeling studies confirmed that nIL-1F has the potential to bind to the trout IL-1RI receptor protein, and may be a novel IL-1 receptor antagonist.

  12. Three members of the 6-cys protein family of Plasmodium play a role in gamete fertility.

    Directory of Open Access Journals (Sweden)

    Melissa R van Dijk

    2010-04-01

    Full Text Available The process of fertilization is critically dependent on the mutual recognition of gametes and in Plasmodium, the male gamete surface protein P48/45 is vital to this process. This protein belongs to a family of 10 structurally related proteins, the so called 6-cys family. To identify the role of additional members of this family in Plasmodium fertilisation, we performed genetic and functional analysis on the five members of the 6-cys family that are transcribed during the gametocyte stage of P. berghei. This analysis revealed that in addition to P48/45, two members (P230 and P47 also play an essential role in the process of parasite fertilization. Mating studies between parasites lacking P230, P48/45 or P47 demonstrate that P230, like P48/45, is a male fertility factor, consistent with the previous demonstration of a protein complex containing both P48/45 and P230. In contrast, disruption of P47 results in a strong reduction of female fertility, while males remain unaffected. Further analysis revealed that gametes of mutants lacking expression of p48/45 or p230 or p47 are unable to either recognise or attach to each other. Disruption of the paralog of p230, p230p, also specifically expressed in gametocytes, had no observable effect on fertilization. These results indicate that the P. berghei 6-cys family contains a number of proteins that are either male or female specific ligands that play an important role in gamete recognition and/or attachment. The implications of low levels of fertilisation that exist even in the absence of these proteins, indicating alternative pathways of fertilisation, as well as positive selection acting on these proteins, are discussed in the context of targeting these proteins as transmission blocking vaccine candidates.

  13. Reconstitution of the anti-apoptotic Bcl-2 protein into lipid membranes and biophysical evidence for its detergent-driven association with the pro-apoptotic Bax protein.

    Directory of Open Access Journals (Sweden)

    Marcus Wallgren

    Full Text Available The anti-apoptotic B-cell CLL/lymphoma-2 (Bcl-2 protein and its counterpart, the pro-apoptotic Bcl-2-associated X protein (Bax, are key players in the regulation of the mitochondrial pathway of apoptosis. However, how they interact at the mitochondrial outer membrane (MOM and there determine whether the cell will live or be sentenced to death remains unknown. Competing models have been presented that describe how Bcl-2 inhibits the cell-killing activity of Bax, which is common in treatment-resistant tumors where Bcl-2 is overexpressed. Some studies suggest that Bcl-2 binds directly to and sequesters Bax, while others suggest an indirect process whereby Bcl-2 blocks BH3-only proteins and prevents them from activating Bax. Here we present the results of a biophysical study in which we investigated the putative interaction of solubilized full-length human Bcl-2 with Bax and the scope for incorporating the former into a native-like lipid environment. Far-UV circular dichroism (CD spectroscopy was used to detect direct Bcl-2-Bax-interactions in the presence of polyoxyethylene-(23-lauryl-ether (Brij-35 detergent at a level below its critical micelle concentration (CMC. Additional surface plasmon resonance (SPR measurements confirmed this observation and revealed a high affinity between the Bax and Bcl-2 proteins. Upon formation of this protein-protein complex, Bax also prevented the binding of antimycin A2 (a known inhibitory ligand of Bcl-2 to the Bcl-2 protein, as fluorescence spectroscopy experiments showed. In addition, Bcl-2 was able to form mixed micelles with Triton X-100 solubilized neutral phospholipids in the presence of high concentrations of Brij-35 (above its CMC. Following detergent removal, the integral membrane protein was found to have been fully reconstituted into a native-like membrane environment, as confirmed by ultracentrifugation and subsequent SDS-PAGE experiments.

  14. The effect of family member migration on education and work among nonmigrant youth in Mexico.

    Science.gov (United States)

    Halpern-Manners, Andrew

    2011-02-01

    While academic and policy circles have given much attention to the assimilatory experiences of Mexican immigrants in the United States, less is known about those who stay behind-an especially unfortunate oversight given the increasing number of Mexican youth with migrant family members. Of the studies on this topic, most have sought to identify the effect that migration has on youths' migratory and educational aspirations, often using qualitative methods in individual sending communities. The present article supplements this research in two ways: (1) in addition to assessing educational outcomes, the scope of the analysis is expanded to include nonmigrant' interaction with another homeland institution of upward mobility: the labor market; and (2) using a large demographic data set, statistical techniques are employed to adjust for unobserved selectivity into the migrant family-member population, thus accounting for a potentially serious source of bias. The results suggest that youth in migrant-sending families are less likely to complete the educational transitions leading up to postsecondary school and have a lower probability of participating in the local economy. The results also indicate that unobserved factors play a "nonignorable" role in sorting youth into migrant and nonmigrant families.

  15. Perspective of Family Members of Transitions to Alternative Levels of Care in Anglo-Saxon Countries.

    Science.gov (United States)

    Merla, C; Wickson-Griffiths, A; Kaasalainen, S; Dal Bello-Haas, V; Banfield, L; Hadjistavropoulos, T; Di Sante, E

    2018-01-01

    This scoping review explores circumstances surrounding the decision about, and eventual experience of, transitioning older adults into alternative levels of housing (ALH), such as long-term care. This topic is examined from a family member perspective, given their exposure and involvement in the care of older adult relatives during this transitional period. The scoping review methodology is based on the framework of Arksey and O'Malley and subsequent recommendations from Levac, Colquhoun, and O'Brien. Approximately 470 articles were reviewed covering the period between 2000 and November 2014; 37 articles met inclusion criteria. A temporal organization of themes was used to describe the experiences of family members in the pretransition, active transition, and posttransition periods of moving older adult relatives into ALH. This paper highlights the transitional period as a time of crisis, with a lack of planning, support, and transparent discussion. This study identifies a need for future research on the potential benefits of family support groups, interim transitional housing options, different models of ALH, changing roles in the posttransition period, and the need for a comprehensive list of housing options for older adults. Results have the potential to inform policy/practice and improve the lives of older adults and their family.

  16. Combined Occurrence of Autosomal Dominant Aniridia and Autosomal Recessive Albinism in Several Members of a Family.

    Science.gov (United States)

    Yahalom, Claudia; Sharon, Dror; Dalia, Eli; Simhon, Shiran Ben; Shemesh, Efrat; Blumenfeld, Anat

    2015-06-01

    To characterize clinical and genetic aspects of a family with a unique combination of two hereditary blinding eye diseases. Comprehensive eye examination of proband and family members. Molecular analyses of the TYR and PAX6 genes. A young couple, both legally blind, requested genetic counselling regarding their ocular condition. The female was previously diagnosed with oculocutaneous albinism (OCA1A) and her spouse was diagnosed with Peters anomaly. A comprehensive clinical examination revealed that the female had OCA1A combined with signs of another ocular disease, showing some similarity to aniridia. A complete ocular examination of her family members revealed that her brother also suffered from the same combined phenotype, her father had typical OCA1A signs, and her mother and sister had aniridia-like phenotype, without clinical diagnosis until the time of presentation. Molecular analysis identified two compound heterozygous TYR mutations known to cause OCAIA and cosegregate with oculocutaneous albinism. In addition, we identified a novel heterozygous PAX6 mutation confirming the atypical aniridia phenotype. We report here a unique and rare clinical phenotype that is explained by the segregation of two severe inherited eye diseases. The clinical and genetic analysis in this family allowed them to receive accurate genetic counseling.

  17. Boron neutron capture therapy induces apoptosis of glioma cells through Bcl-2/Bax

    International Nuclear Information System (INIS)

    Wang, Peng; Zhen, Haining; Jiang, Xinbiao; Zhang, Wei; Cheng, Xin; Guo, Geng; Mao, Xinggang; Zhang, Xiang

    2010-01-01

    Boron neutron capture therapy (BNCT) is an alternative treatment modality for patients with glioma. The aim of this study was to determine whether induction of apoptosis contributes to the main therapeutic efficacy of BNCT and to compare the relative biological effect (RBE) of BNCT, γ-ray and reactor neutron irradiation. The neutron beam was obtained from the Xi'an Pulsed Reactor (XAPR) and γ-rays were obtained from [ 60 Co] γ source of the Fourth Military Medical University (FMMU) in China. Human glioma cells (the U87, U251, and SHG44 cell lines) were irradiated by neutron beams at the XAPR or [ 60 Co] γ-rays at the FMMU with different protocols: Group A included control nonirradiated cells; Group B included cells treated with 4 Gy of [ 60 Co] γ-rays; Group C included cells treated with 8 Gy of [ 60 Co] γ-rays; Group D included cells treated with 4 Gy BPA (p-borono-phenylalanine)-BNCT; Group E included cells treated with 8 Gy BPA-BNCT; Group F included cells irradiated in the reactor for the same treatment period as used for Group D; Group G included cells irradiated in the reactor for the same treatment period as used for Group E; Group H included cells irradiated with 4 Gy in the reactor; and Group I included cells irradiated with 8 Gy in the reactor. Cell survival was determined using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium (MTT) cytotoxicity assay. The morphology of cells was detected by Hoechst33342 staining and transmission electron microscope (TEM). The apoptosis rate was detected by flow cytometer (FCM). The level of Bcl-2 and Bax protein was measured by western blot analysis. Proliferation of U87, U251, and SHG44 cells was much more strongly inhibited by BPA-BNCT than by irradiation with [ 60 Co] γ-rays (P < 0.01). Nuclear condensation was determined using both a fluorescence technique and electron microscopy in all cell lines treated with BPA-BNCT. Furthermore, the cellular apoptotic rates in Group D and Group E treated with

  18. Patients' experiences of care and support at home after a family member's participation in an intervention during palliative care.

    Science.gov (United States)

    Norinder, Maria; Goliath, Ida; Alvariza, Anette

    2017-06-01

    Patients who receive palliative home care are in need of support from family members, who take on great responsibility related to caregiving but who often feel unprepared for this task. Increasing numbers of interventions aimed at supporting family members in palliative care have been described and evaluated. It is not known whether and how these interventions actually affect the care or support provided to a patient, even though it has been suggested that family members would be likely to provide better care and support and thus allow for positive experiences for patients. However, this has not been studied from the perspective of the patients themselves. The objective of our study was to explore patients' experiences of care and support at home after family members' participation in a psychoeducational intervention during palliative care. Our study took a qualitative approach, and interviews were conducted with 11 patients whose family members had participated in a psychoeducational intervention during palliative home care. The interviews were analyzed employing interpretive description. Patients' experiences were represented by three themes: "safe at home," "facilitated and more honest communication," and "feeling like a unit of care." Patients felt that their needs were better met and that family members became more confident at home without risking their own health. Patients felt relieved when family members were given the opportunity to talk and reflect with others and hoped that the intervention would contribute to more honest communications between themselves and their family members. Further, it was of great importance to patients that family members receive attention from and be confirmed and supported by healthcare professionals. Our findings show how an intervention targeted at family members during palliative home care also benefits the patients.

  19. The family’s experience of having a mentally ill family member

    Directory of Open Access Journals (Sweden)

    Margaret Ngqoboka

    1998-11-01

    Full Text Available The purpose of this study was firstly to explore and describe the experience of families with a mentally ill family member and secondly to describe guidelines (based on the results obtained for the advanced psychiatric nurse practitioner to assist families in mobilising their resources to facilitate the promotion, maintenance and restoration of their mental health as an integral part of health. Opsomming Die doel van hierdie studie was eerstens om die belewenis van gesinne wat 'n geestesongestelde gesinslid het, te verken en beskryfen in die tweede piek om riglyne te beskryfvir die gevorderde psigiatriese verpleegpraktisyn om hierdie gesinne the help in die mobilise ring van hulpbronne om hul geestes gesondheid as integrate deel van gesondheid te bevorder, te handhaaf en te herstel. *Please note: This is a reduced version of the abstract. Please refer to PDF for full text.

  20. Survival in common cancers defined by risk and survival of family members

    Directory of Open Access Journals (Sweden)

    Jianguang Ji

    2011-10-01

    Full Text Available Studies on survival between familial and sporadic cancers have been inconclusive and only recent data on a limited number of cancers are available on the concordance of survival between family members. In this review, we address these questions by evaluating the published and unpublished data from the nation-wide Swedish Family-Cancer Database and a total of 13 cancer sites were assessed. Using sporadic cancer as reference, HRs were close to 1.0 for most of the familial cancers in both the offspring and parental generations, which suggested that survival in patients with familial and sporadic cancers was equal, with an exception for ovarian cancer with a worse prognosis. Compared to offspring whose parents had a poor survival, those with a good parental survival had a decreased risk of death for most cancers and HR was significantly decreased for cancers in the breast, prostate, bladder, and kidney. For colorectal and nervous system cancers, favorable survival between the generations showed a borderline significance. These data are consistent in showing that both good and poor survival in certain cancers aggregate in families. Genetic factors are likely to contribute to the results. These observations call for intensified efforts to consider heritability in survival as one mechanism regulating prognosis in cancer patients.

  1. Deletion of AU-rich elements within the Bcl2 3'UTR reduces protein expression and B cell survival in vivo.

    Directory of Open Access Journals (Sweden)

    Manuel D Díaz-Muñoz

    Full Text Available Post-transcriptional mRNA regulation by RNA binding proteins (RBPs associated with AU-rich elements (AREs present in the 3' untranslated region (3'UTR of specific mRNAs modulates transcript stability and translation in eukaryotic cells. Here we have functionally characterised the importance of the AREs present within the Bcl2 3'UTR in order to maintain Bcl2 expression. Gene targeting deletion of 300 nucleotides of the Bcl2 3'UTR rich in AREs diminishes Bcl2 mRNA stability and protein levels in primary B cells, decreasing cell lifespan. Generation of chimeric mice indicates that Bcl2-ARE∆/∆ B cells have an intrinsic competitive disadvantage compared to wild type cells. Biochemical assays and predictions using a bioinformatics approach show that several RBPs bind to the Bcl2 AREs, including AUF1 and HuR proteins. Altogether, association of RBPs to Bcl2 AREs contributes to Bcl2 protein expression by stabilizing Bcl2 mRNA and promotes B cell maintenance.

  2. Overexpression of the human BCL-2 gene product results in growth enhancement of Epstein-Barr virus-immortalized B cells

    International Nuclear Information System (INIS)

    Tsujimoto, Yoshihide

    1989-01-01

    The biological activity of the human BCL-2 gene product was analyzed in an Epstein-Barr virus (EBV)-infected human lymphoblastoid B-cell line transfected with BCL-2 sequences driven by the simian virus 40 promoter and enhancer. Overproduction of the BCL-2 protein conferred a selective growth advantage to the EBV-infected B cells as compared with control transfectants in low-serum medium and also after seeding at limiting dilution but did not render the cells tumorigenic in athymic nude mice. This growth enhancement was also seen in cells transfected with the BCL-2 gene with its own promoter juxtaposed to the immunoglobulin heavy chain gene enhancer, which represents the translocated form of the BCL-2 gene observed in follicular lymphomas with the t(14;18) translocation. The growth advantage of EBV-infected B cells overproducing the BCL-2 protein is neither due to the enhanced growth factor production nor due to an enhanced sensitivity of the BCL-2 transfectants to interleukins 1 or 6, although both lymphokines are known to stimulate proliferation of EBV-infected B-cell lines. The growth advantage of EBV-infected B-cell lines. The growth advantage of EBV-infected B cells by overproduction of the BCL-2 protein suggests the direct involvement of the BCL-2 gene product in the pathogenesis of follicular lymphoma

  3. Caregiving to persons living with HIV/AIDS: experiences of Vietnamese family members.

    Science.gov (United States)

    Lundberg, Pranee C; Doan, Thoa Thi Kim; Dinh, Thu Thi Xuan; Oach, Nhung Kim; Le, Phong Hoang

    2016-03-01

    To examine the experiences of caregiving among Vietnamese family members of persons living with HIV/AIDS. As the number of persons living with HIV/AIDS increases, the need of family caregivers who can take responsibility for the home care of these persons increases. Vietnam has one of the fastest growing HIV epidemics in Asia. A descriptive cross-sectional study with quantitative and qualitative methods was used. A purposive sample of 104 family caregivers, both male and female, participated voluntarily by answering a questionnaire of caregiver burden, and 20 of them participated in in-depth interview. Female caregivers were mainly mothers and wives while male caregivers were mainly husbands, fathers and siblings. The largest group of family caregivers reported moderate to severe burden. There was no difference between genders in total caregiver burden, but there were several differences between older and younger caregivers in some items of caregiver burden. Five categories of experiences emerged: Different types of caregiving to persons living with HIV/AIDS, cultural and religious issues associated with caregiving, keeping secret to avoid stigma and discrimination, lack of knowledge about disease and provision of care, and fear, anxiety and frustration. Stigma and discrimination should be decreased by providing knowledge to the general public about HIV/AIDS, in particular about ways of transmission and protection. Special knowledge should be given to family caregivers to enable them to give care to persons living with HIV/AIDS at home. This could be done through culturally appropriate training/intervention programmes in which coping methods should be included. Support group interventions should also be carried through. The results obtained can be used as baseline information. Health care providers should consider gender, age and culture of family members of persons living with HIV/AIDS. Knowledge about HIV/AIDS, provision of care at home and in hospital, and

  4. Boron neutron capture therapy induces apoptosis of glioma cells through Bcl-2/Bax

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    Mao Xinggang

    2010-12-01

    Full Text Available Abstract Background Boron neutron capture therapy (BNCT is an alternative treatment modality for patients with glioma. The aim of this study was to determine whether induction of apoptosis contributes to the main therapeutic efficacy of BNCT and to compare the relative biological effect (RBE of BNCT, γ-ray and reactor neutron irradiation. Methods The neutron beam was obtained from the Xi'an Pulsed Reactor (XAPR and γ-rays were obtained from [60Co] γ source of the Fourth Military Medical University (FMMU in China. Human glioma cells (the U87, U251, and SHG44 cell lines were irradiated by neutron beams at the XAPR or [60Co] γ-rays at the FMMU with different protocols: Group A included control nonirradiated cells; Group B included cells treated with 4 Gy of [60Co] γ-rays; Group C included cells treated with 8 Gy of [60Co] γ-rays; Group D included cells treated with 4 Gy BPA (p-borono-phenylalanine-BNCT; Group E included cells treated with 8 Gy BPA-BNCT; Group F included cells irradiated in the reactor for the same treatment period as used for Group D; Group G included cells irradiated in the reactor for the same treatment period as used for Group E; Group H included cells irradiated with 4 Gy in the reactor; and Group I included cells irradiated with 8 Gy in the reactor. Cell survival was determined using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium (MTT cytotoxicity assay. The morphology of cells was detected by Hoechst33342 staining and transmission electron microscope (TEM. The apoptosis rate was detected by flow cytometer (FCM. The level of Bcl-2 and Bax protein was measured by western blot analysis. Results Proliferation of U87, U251, and SHG44 cells was much more strongly inhibited by BPA-BNCT than by irradiation with [60Co] γ-rays (P 60Co] γ-rays (P P Conclusions Compared with ��-ray and reactor neutron irradiation, a higher RBE can be achieved upon treatment of glioma cells with BNCT. Glioma cell apoptosis induced by

  5. Magnitude of the smoking problem, knowledge, attitude and practice, among family members of primary school students

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    Babak Nakhostin-Roohi

    2013-06-01

    Full Text Available Background: smoking is a very important public health problem, urgently requiring immediate and effective measures due to its harmful effect on health. The purpose of this study was to collect baseline information about the magnitude of smoking problem, knowledge, attitude, and practice among family members of primary school students in the northwest region of Iran.Methods: of 55 680 primary school students (the 3th, 4th and 5th grades, 7.1% (n=3 954 were selected using randomized multi-stage cluster sampling. Data collection was conducted in April, May, and June 2011, by means of a self-administered two-page questionnaire.Results: a total of 3 954 students (57.6% boys and 42.3% girls with the mean age of 10.46±1.09 years were evaluated. According to our data, the prevalence of cigarette smoking among fathers was more than other family members (27.1% versus 17.8% whereas the prevalence of water pipe smoking among fathers and other family members was almost similar (9.2% and 9.7% respectively. None of the smoking type was prevalent among mothers (cigarette: 1% and water pipe: 1.1%. Considerable numbers of all students under study had been exposed to secondhand smoke at home (cigarette: 19.8% and water pipe: 7.7%.Conclusions: considering our findings, two procedures recommended to prevail the problem are to provide greater education about hazards of tobacco consumption among students and their family; and to legislate new laws by officials to ban tobacco use at home.

  6. Metabolic Syndrome in Korean Cancer Survivors and Family Members: A Study in a Health Promotion Center.

    Science.gov (United States)

    Shin, Jin Young; Choi, Yoon Ho; Song, Yun Mi

    2015-01-01

    This cross-sectional study evaluated the risk of metabolic syndrome (MetS) in cancer survivors and family members. Subjects were 48,934 adults (24,786 men, 24,148 women) aged ≥40yr who receive a routine health examination at 1 hospital from January 2010 to December 2012. There were 2468 cancer survivors, 18,211 with cancer patients in the family, and 28,255 noncancer subjects, who never experienced cancer and whose family members either. Associations between MetS and cancer experience were assessed using multiple logistic regression analysis. The odds ratio (OR) of MetS in female cancer survivors was significantly higher than noncancer subjects after adjusting for age, smoking, physical activity, and alcohol intake (OR = 1.22, 95% confidence intervals: 1.02-1.47]. However, the OR of MetS for male survivors did not differ from that of noncancer subjects. Gastric cancer survivors had a lower OR of MetS than noncancer subjects (0.37, 0.27-0.50). ORs of breast cancer (1.49, 1.00-2.23) and prostate cancer survivors (1.46, 1.07-1.99) were higher than the OR of MetS for noncancer subjects. There was no difference in the OR of MetS between the family members of cancer patients and non-cancer subjects. These findings suggest that the odds of MetS for cancer survivors may differ by cancer type and by sex.

  7. Turnover of amyloid precursor protein family members determines their nuclear signaling capability.

    Science.gov (United States)

    Gersbacher, Manuel T; Goodger, Zoë V; Trutzel, Annette; Bundschuh, Diana; Nitsch, Roger M; Konietzko, Uwe

    2013-01-01

    The amyloid precursor protein (APP) as well as its homologues, APP-like protein 1 and 2 (APLP1 and APLP2), are cleaved by α-, β-, and γ-secretases, resulting in the release of their intracellular domains (ICDs). We have shown that the APP intracellular domain (AICD) is transported to the nucleus by Fe65 where they jointly bind the histone acetyltransferase Tip60 and localize to spherical nuclear complexes (AFT complexes), which are thought to be sites of transcription. We have now analyzed the subcellular localization and turnover of the APP family members. Similarly to AICD, the ICD of APLP2 localizes to spherical nuclear complexes together with Fe65 and Tip60. In contrast, the ICD of APLP1, despite binding to Fe65, does not translocate to the nucleus. In addition, APLP1 predominantly localizes to the plasma membrane, whereas APP and APLP2 are detected in vesicular structures. APLP1 also demonstrates a much slower turnover of the full-length protein compared to APP and APLP2. We further show that the ICDs of all APP family members are degraded by the proteasome and that the N-terminal amino acids of ICDs determine ICD degradation rate. Together, our results suggest that different nuclear signaling capabilities of APP family members are due to different rates of full-length protein processing and ICD proteasomal degradation. Our results provide evidence in support of a common nuclear signaling function for APP and APLP2 that is absent in APLP1, but suggest that APLP1 has a regulatory role in the nuclear translocation of APP family ICDs due to the sequestration of Fe65.

  8. Coenzyme Q10 Protects Hippocampal Neurons against Ischemia/ Reperfusion Injury via Modulation of BAX/Bcl-2 Expression

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    Mohammad Zamani

    2012-09-01

    Full Text Available Introduction: Preliminary studies have con.rmed reduction in cell death following treatment with antioxidants. According to this .nding we study the relationship between consumption of CoQ10 and expression of Bax and Bcl2 in hippocampus following ischemia/reperfusion as proteins involved in cell programmed death or apoptosis. Methods: We studied the protective role of CoQ10 against ischemia-reperfusion. Experimental design includes four groups:  intact, ischemic control, sham control and treatment group with CoQ10. The mice were pre-treated with CoQ10 for a week, then ischemia was induced by common carotid artery ligation and following the reduction in in.ammation (a week the mice was treated with CoQ10.  Nissl staining was applied for counting the necrotic cells of hippocampus and the western blot was performed to measure the Bax and Bcl2 expression.Results: Cell death was signi.cantly lower when mice were treated with CoQ10. Bax expression was signi.cantly high in the ischemic group but low in the treatment group, and the bcl2 expression was lower in the ischemic group than the treatment and the vehicle groups.Discussion: Ischemia for 15 minutes induced cell death in hippocampus with more potent effect on CA1. CoQ10 intake signi.cantly reduced cell death and prevented the expression of Bax while inducing an increase in expression of bcl2.

  9. Coenzyme Q10 Protects Hippocampal Neurons Against Ischemia/Reperfusion Injury via Modulation of BAX/Bcl-2 Expression

    Directory of Open Access Journals (Sweden)

    M Zamani

    2012-12-01

    Full Text Available Introduction : Preliminary studies confirmed reduction in cell death following treatment with antioxidants. According to this finding we study the relationship between consumption of CoQ10 and expression of bax and bcl2 in hippocampus following ischemia/reperfusion as proteins involved in cell programmed death or apoptosis.Material & methods : We studied the protective role of CoQ10 against Ischemia-Reperfusion. Experimental design includes four groups: intact, ischemic control, sham control and treatment groups with CoQ10. The mice treated with CoQ10 as Pre - Treatment for a week. Then, ischemia induced by common carotid artery ligation and following the reduction in inflammation (a week the mice post-treated with CoQ10.Nissl staining applied to counting necrotic cells of hippocampus and the western blotting performed to measurement the bax and bcl2 expression.Results :. Cell death was significantly lower when mice treated with CoQ10. Bax expression was significantly high in ischemic group but in treatment group was less and reversely the bcl2 expression in ischemic group was lower than treatment and vehicle groups.Conclusion : Ischemia for 15 minutes induced cell death in hippocampus with more potent effect on CA1. CoQ10 intake significantly reduced cell death and prevented the expression of bax while inducing an increase in expression of bcl2.

  10. Bcl-2 protects against apoptosis induced by antimycin A and bongkrekic acid without restoring cellular ATP levels.

    NARCIS (Netherlands)

    Graaf, A.O. de; Meijerink, J.P.P.; Heuvel, L.P.W.J. van den; Abreu, R.A. de; Witte, T.J.M. de; Jansen, J.H.; Smeitink, J.A.M.

    2002-01-01

    Several studies indicate that mitochondrial ATP production as well as ADP/ATP exchange across mitochondrial membranes are impaired during apoptosis. We investigated whether Bcl-2 could protect against cell death under conditions in which ATP metabolism is inhibited. Inhibition of ATP production

  11. Effect of Bcl-2/Bax gene expression on apoptosis of spermatogenic cells of mouse testes induced by low dose radiation

    International Nuclear Information System (INIS)

    Liu Guangwei; Wang Chunyan; Lu Zhe; Liu Shunchun; Gong Shouliang

    2003-01-01

    The different kinds of spermatogenic cells were separated using density gradient centrifugation and their apoptosis and Bcl-2 and Bax protein expression were measured with flow cytometry and immunohistochemical method, respectively. The results showed the apoptosis in all kinds of spermatogenic cells induced by low dose radiation (LDR) had a obvious regularity. When the doses were 0.025 and 0.05 Gy, spermatogonia apoptosis was dominant. With the increase of irradiation dose (0.075-0.2 Gy), spermatocytes also showed an apoptotic change, but the apoptotic percentage of spermatogonia was significantly higher than that of spermatocytes. Moreover, the apoptosis of spermatids and spermatozoa scarcely occurred after LDR. Bax protein was primarily expressed in spermatogonia and spermatocytes, and the former was significantly higher than that of the latter after LDR. With the increase of irradiation dose, Bax protein expression showed a upgrading tendency, but that of spermatids and spermatozoa scarcely occurred. Bcl-2 protein was primarily expressed in spermatids and spermatozoa, but the Bcl-2 protein expressions of spermatogonia and spermatocytes scarcely occurred after LDR. These results imply that the interacting regulation of Bcl-2 and Bax gene expression might be involved in selective apoptosis of spermatogenic cells induced by LDR, which provided an experimental evidence for further exploring the apoptotic mechanism of adaptive response of spermatogenic cells by LDR

  12. The role of apoptosis in the development of AGM hematopoietic stem cells revealed by Bcl-2 overexpression

    NARCIS (Netherlands)

    C. Orelio; K.N. Harvey; C. Miles; R.A. Oostendorp (Robert); K. van der Horn; E.A. Dzierzak (Elaine)

    2004-01-01

    textabstractApoptosis is an essential process in embryonic tissue remodeling and adult tissue homeostasis. Within the adult hematopoietic system, it allows for tight regulation of hematopoietic cell subsets. Previously, it was shown that B-cell leukemia 2 (Bcl-2) overexpression in

  13. Atherosclerosis-Associated Endothelial Cell Apoptosis by MiR-429-Mediated Down Regulation of Bcl-2

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    Tao Zhang

    2015-10-01

    Full Text Available Background/Aims: Endothelial cell injury and subsequent apoptosis play a key role in the development and pathogenesis of atherosclerosis, which is hallmarked by dysregulated lipid homeostasis, aberrant immunity and inflammation, and plaque-instability-associated coronary occlusion. Nevertheless, our understanding of the mechanisms underlying endothelial cell apoptosis is still limited. MicroRNA-429 (miR-29 is a known cancer suppressor that promotes cancer cell apoptosis. However, it is unknown whether miR-429 may be involved in the development of atherosclerosis through similar mechanisms. We addressed these questions in the current study. Methods: We examined the levels of endothelial cell apoptosis in ApoE (-/- mice suppled with high-fat diet (HFD, a mouse model for atherosclerosis (simplified as HFD mice. We analyzed the levels of anti-apoptotic protein Bcl-2 and the levels of miR-429 in the purified CD31+ endothelial cells from mouse aorta. Prediction of the binding between miR-429 and 3'-UTR of Bcl-2 mRNA was performed by bioinformatics analyses and confirmed by a dual luciferase