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Sample records for retinoids arrest breast

  1. Consequences of the natural retinoid/retinoid X receptor ligands action in human breast cancer MDA-MB-231 cell line: Focus on functional proteomics

    Czech Academy of Sciences Publication Activity Database

    Flodrová, Dana; Toporová, L.; Laštovičková, Markéta; Macejová, D.; Hunaková, L.; Brtko, J.; Bobálová, Janette

    2017-01-01

    Roč. 281, NOV (2017), s. 26-34 ISSN 0378-4274 R&D Projects: GA ČR(CZ) GA15-15479S Grant - others:AV ČR(CZ) SAV-15-01 Program:Bilaterální spolupráce Institutional support: RVO:68081715 Keywords : breast cancer * MDA-MB-231 * biomarker * retinoids Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 3.858, year: 2016

  2. Retinoids, carotenoids, and tocopherols in breast adipose tissue and serum of benign breast disease and breast cancer patients

    Science.gov (United States)

    Various retinoic acid (RA) isomers (all-trans, 13-cis, 11-cis, and 9-cis) as well as retinol, carotenoids, and tocopherol concentrations were determined in both serum and breast adipose tissue of 22 benign breast disease patients and 52 breast cancer patients categorized into 4 stages by malignancy....

  3. Modulation of Breast Tumor Cell Response to Retinoids by Histone Deacetylase Inhibitors

    National Research Council Canada - National Science Library

    Sacchi, Nicoletta

    2003-01-01

    .... One form of RA-resistance in breast cancer can be traced to loss of expression of the tumor suppressor RAR beta, due to epigenetic changes including DNA methylation and histone deacetylation in one...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-02-08

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

  5. Sinularin Selectively Kills Breast Cancer Cells Showing G2/M Arrest, Apoptosis, and Oxidative DNA Damage

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    Hurng-Wern Huang

    2018-04-01

    Full Text Available The natural compound sinularin, isolated from marine soft corals, is antiproliferative against several cancers, but its possible selective killing effect has rarely been investigated. This study investigates the selective killing potential and mechanisms of sinularin-treated breast cancer cells. In 3-(4,5-dimethylthiazol-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H- tetrazolium, inner salt (MTS assay, sinularin dose-responsively decreased the cell viability of two breast cancer (SKBR3 and MDA-MB-231 cells, but showed less effect on breast normal (M10 cells after a 24 h treatment. According to 7-aminoactinomycin D (7AAD flow cytometry, sinularin dose-responsively induced the G2/M cycle arrest of SKBR3 cells. Sinularin dose-responsively induced apoptosis on SKBR3 cells in terms of a flow cytometry-based annexin V/7AAD assay and pancaspase activity, as well as Western blotting for cleaved forms of poly(ADP-ribose polymerase (PARP, caspases 3, 8, and 9. These caspases and PARP activations were suppressed by N-acetylcysteine (NAC pretreatment. Moreover, sinularin dose-responsively induced oxidative stress and DNA damage according to flow cytometry analyses of reactive oxygen species (ROS, mitochondrial membrane potential (MitoMP, mitochondrial superoxide, and 8-oxo-2′-deoxyguanosine (8-oxodG. In conclusion, sinularin induces selective killing, G2/M arrest, apoptosis, and oxidative DNA damage of breast cancer cells.

  6. Retinoid Signaling in Pancreatic Cancer, Injury and Regeneration

    Science.gov (United States)

    Colvin, Emily K.; Susanto, Johana M.; Kench, James G.; Ong, Vivienna N.; Mawson, Amanda; Pinese, Mark; Chang, David K.; Rooman, Ilse; O'Toole, Sandra A.; Segara, Davendra; Musgrove, Elizabeth A.; Sutherland, Robert L.; Apte, Minoti V.; Scarlett, Christopher J.; Biankin, Andrew V.

    2011-01-01

    Background Activation of embryonic signaling pathways quiescent in the adult pancreas is a feature of pancreatic cancer (PC). These discoveries have led to the development of novel inhibitors of pathways such as Notch and Hedgehog signaling that are currently in early phase clinical trials in the treatment of several cancer types. Retinoid signaling is also essential for pancreatic development, and retinoid therapy is used successfully in other malignancies such as leukemia, but little is known concerning retinoid signaling in PC. Methodology/Principal Findings We investigated the role of retinoid signaling in vitro and in vivo in normal pancreas, pancreatic injury, regeneration and cancer. Retinoid signaling is active in occasional cells in the adult pancreas but is markedly augmented throughout the parenchyma during injury and regeneration. Both chemically induced and genetically engineered mouse models of PC exhibit a lack of retinoid signaling activity compared to normal pancreas. As a consequence, we investigated Cellular Retinoid Binding Protein 1 (CRBP1), a key regulator of retinoid signaling known to play a role in breast cancer development, as a potential therapeutic target. Loss, or significant downregulation of CRBP1 was present in 70% of human PC, and was evident in the very earliest precursor lesions (PanIN-1A). However, in vitro gain and loss of function studies and CRBP1 knockout mice suggested that loss of CRBP1 expression alone was not sufficient to induce carcinogenesis or to alter PC sensitivity to retinoid based therapies. Conclusions/Significance In conclusion, retinoid signalling appears to play a role in pancreatic regeneration and carcinogenesis, but unlike breast cancer, it is not mediated directly by CRBP1. PMID:22220202

  7. Retinoid signaling in pancreatic cancer, injury and regeneration.

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    Emily K Colvin

    Full Text Available BACKGROUND: Activation of embryonic signaling pathways quiescent in the adult pancreas is a feature of pancreatic cancer (PC. These discoveries have led to the development of novel inhibitors of pathways such as Notch and Hedgehog signaling that are currently in early phase clinical trials in the treatment of several cancer types. Retinoid signaling is also essential for pancreatic development, and retinoid therapy is used successfully in other malignancies such as leukemia, but little is known concerning retinoid signaling in PC. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the role of retinoid signaling in vitro and in vivo in normal pancreas, pancreatic injury, regeneration and cancer. Retinoid signaling is active in occasional cells in the adult pancreas but is markedly augmented throughout the parenchyma during injury and regeneration. Both chemically induced and genetically engineered mouse models of PC exhibit a lack of retinoid signaling activity compared to normal pancreas. As a consequence, we investigated Cellular Retinoid Binding Protein 1 (CRBP1, a key regulator of retinoid signaling known to play a role in breast cancer development, as a potential therapeutic target. Loss, or significant downregulation of CRBP1 was present in 70% of human PC, and was evident in the very earliest precursor lesions (PanIN-1A. However, in vitro gain and loss of function studies and CRBP1 knockout mice suggested that loss of CRBP1 expression alone was not sufficient to induce carcinogenesis or to alter PC sensitivity to retinoid based therapies. CONCLUSIONS/SIGNIFICANCE: In conclusion, retinoid signalling appears to play a role in pancreatic regeneration and carcinogenesis, but unlike breast cancer, it is not mediated directly by CRBP1.

  8. Breastfeeding, retinoids, and postpartum depression: a new theory.

    Science.gov (United States)

    Mawson, Anthony R; Xueyuan, Wang

    2013-09-25

    Postpartum depression (PPD) is an international public health problem affecting at least 1 in 8 mothers. Known risk factors include: giving birth to a preterm or low birth weight infant, babies with greater symptoms of illness at age 4-6 weeks, formula feeding, younger maternal age, smoking, and fatigue. Prolonged breastfeeding is associated with a reduced risk of PPD but the mechanisms are not well understood. Interventions for PPD focusing on psychosocial risk factors have been largely unsuccessful, suggesting that the condition has a mainly biological basis. The hypothesis proposed for consideration is that breastfeeding protects against PPD by maintaining endogenous retinoids (vitamin A-related compounds) below a threshold concentration. In fact, breast milk is rich in retinoids; pregnant women accumulate retinoids in liver and breast in preparation for lactation; there is increasing evidence that retinoids in higher concentration are associated with cognitive disturbances and mood disorders, including depression and suicide; and prolonged lactation reduces maternal stores of retinoids. Consistent with this hypothesis, it is estimated that an amount of vitamin A is transferred from mother to infant during the first six months of exclusive breastfeeding equivalent to 76% of a dose known to cause acute vitamin A poisoning in an adult. Breastfeeding may thus have evolutionary-adaptive functions for both mother and infant, transferring vital nutrients to an infant unable to feed itself, yet at the same time providing a natural means of reducing potentially toxic concentrations of retinoids in the mother. © 2013 Elsevier B.V. All rights reserved.

  9. Alcohol and retinoids

    DEFF Research Database (Denmark)

    Crabb, D.W.; Pinairs, J.; Hasanadka, R.

    2001-01-01

    , M. Fang, and David W. Crabb; (2) Alcohol, vitamin A, and beta-carotene: Adverse interactions, by M. A. Leo and Charles S. Lieber; (3) Retinoic acid, hepatic stellate cells, and Kupffer cells, by Hidekazu Tsukamoto, K. Motomura, T. Miyahara, and M. Ohata; (4) Retinoid storage and metabolism in liver...

  10. Phytoestrogen bakuchiol exhibits in vitro and in vivo anti-breast cancer effects by inducing S phase arrest and apoptosis

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    Li eLi

    2016-05-01

    Full Text Available Phytoestrogen has been proposed as an alternative to hormone replacement therapy, which has been demonstrated to promote a high risk of breast cancer. However, the effect of phytoestrogen on breast cancer development has not been fully understood. Bakuchiol is an active ingredient of a traditional Chinese herbal medicine Fructus Psoraleae, the dried ripe fruit of Psoralea corylifolia L. (Fabaceae. The in vitro and in vivo estrogenic activities and anti-breast cancer effects of bakuchiol have not been well studied. We found that bakuchiol induced the GFP expression in transgenic medaka (Oryzias melastigma, Tg, Chg:GFP dose-dependently (0-1 µg/ml, demonstrating its in vivo estrogenic activity. Low dose of bakuchiol (1 µg/ml induced the cell proliferation and ERα expression in MCF-7 cells, which could be blocked by the antiestrogen ICI 182780, suggesting the in vitro estrogenic activity of bakuchiol. Our data indicated that high doses of bakuchiol (>2 µg/ml inhibited breast cancer cell growth, with a stronger antiproliferative effect than resveratrol, a widely studied analogue of bakuchiol. High doses of bakuchiol (4 µg/ml, 7 µg/ml and 10 µg/ml were used for the further in vitro anti-breast cancer studies. Bakuchiol induced ERβ expression and suppressed ERα expression in MCF-7 cells. It also induced S phase arrest in both MCF-7 and MDA-MB-231 cells, which could be rescued by caffeine. Knock-down of p21 also marginally rescued S phase arrest in MCF-7 cells. The S phase arrest was accompanied by the upregulation of ATM, P-Cdc2 (Tyr15, Myt1, P-Wee1 (Ser642, p21 and Cyclin B1, suggesting that blocking of Cdc2 activation may play an important role in bakuchiol-induced S phase arrest. Furthermore, bakuchiol induced cell apoptosis and disturbed mitochondrial membrane potential in MCF-7 cells. The bakuchiol-induced apoptosis was associated with increased expression of Caspase family and Bcl-2 family proteins, suggesting that bakuchiol may induce

  11. Photodecomposition and Phototoxicity of Natural Retinoids

    Directory of Open Access Journals (Sweden)

    Peter P. Fu

    2005-04-01

    Full Text Available Sunlight is a known human carcinogen. Many cosmetics contain retinoid-based compounds, such as retinyl palmitate (RP, either to protect the skin or to stimulate skin responses that will correct skin damaged by sunlight. However, little is known about the photodecomposition of some retinoids and the toxicity of these retinoids and their sunlight-induced photodecomposition products on skin. Thus, studies are required to test whether topical application of retinoids enhances the phototoxicity and photocarcinogenicity of sunlight and UV light. Mechanistic studies are needed to provide insight into the disposition of retinoids in vitro and on the skin, and to test thoroughly whether genotoxic damage by UV-induced radicals may participate in any toxicity of topically applied retinoids in the presence of UV light. This paper reports the update information and our experimental results on photostability, photoreactions, and phototoxicity of the natural retinoids including retinol (ROH, retinal, retinoid acid (RA, retinyl acetate, and RP (Figure 1.

  12. A Flavone Constituent from Myoporum bontioides Induces M-Phase Cell Cycle Arrest of MCF-7 Breast Cancer Cells

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    Jing-Ru Weng

    2017-03-01

    Full Text Available Abstract: Myoporum bontioides is a traditional medicinal plant in Asia with various biological activities, including anti-inflammatory and anti-bacterial characteristics. To identify the bioactive constituents from M. bontioides, a newly-identified flavone, 3,4′-dimethoxy-3′,5,7-trihydroxyflavone (compound 1, along with eight known compounds, were investigated in human MCF-7 breast cancer, SCC4 oral cancer, and THP-1 monocytic leukemia cells. Among these compounds, compound 1 exhibited the strongest antiproliferative activity with half-maximal inhibitory concentration (IC50 values ranging from 3.3 μM (MCF-7 to 8.6 μM (SCC4. Flow cytometric analysis indicated that compound 1 induced G2/M cell cycle arrest in MCF-7 cells. Mechanistic evidence suggests that the G2/M arrest could be attributable to compound 1’s modulatory effects on the phosphorylation and expression of numerous key signaling effectors, including cell division cycle 2 (CDC2, CDC25C, and p53. Notably, compound 1 downregulated the expression of histone deacetylase 2 (HDAC2 and HDAC4, leading to increased histone H3 acetylation and p21 upregulation. Together, these findings suggest the translational potential of compound 1 as a breast cancer treatment.

  13. Increased Susceptibility to Apoptosis and Growth Arrest of Human Breast Cancer Cells Treated by a Snake Venom-Loaded Silica Nanoparticles

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    Gamal Badr

    2014-11-01

    Full Text Available Background: The development of effective treatments against metastatic cancers, including breast cancer, is among the most important challenges in current experimental and clinical cancer research. We recently demonstrated that Walterinnesia aegyptia venom (WEV, either alone or in combination with silica nanoparticles (WEV+NP, resulted in the growth arrest and apoptosis of different cancer cell lines. Aims: In the present study, we evaluated the impact of WEV alone and WEV+NP on human breast cancer cells isolated from cancer biopsies. Methods: The potential effects of WEV alone and WEV+NP on the proliferation, induction of apoptosis and generation of free radicals in breast cancer cells isolated from 80 patients clinically diagnosed with breast cancer were evaluated by flow cytometry and ELISA. Results: WEV alone and WEV+NP inhibited the proliferation, altered the cell cycle and enhanced the induction of apoptosis of the breast cancer cells by increasing the activities of caspase-3, caspase-8 and caspase-9. In addition, the combination of WEV and NP robustly sensitized the breast cancer cells to growth arrest and apoptosis by increasing the generation of free radicals, including reactive oxygen species (ROS, hydroperoxide and nitric oxide. The combination of WEV with NP significantly enhanced the anti-tumor effect of WEV in breast cancer cells. Conclusion: Our data indicate the therapeutic potential of the nanoparticle-sustained delivery of snake venom for the treatment of breast cancer.

  14. Cellular effect of styrene substituted biscoumarin caused cellular apoptosis and cell cycle arrest in human breast cancer cells.

    Science.gov (United States)

    Perumalsamy, Haribalan; Sankarapandian, Karuppasamy; Kandaswamy, Narendran; Balusamy, Sri Renukadevi; Periyathambi, Dhaiveegan; Raveendiran, Nanthini

    2017-11-01

    Coumarins occurs naturally across plant kingdoms exhibits significant pharmacological properties and pharmacokinetic activity. The conventional, therapeutic agents are often associated with poor stability, absorption and increased side effects. Therefore, identification of a drug that has little or no-side effect on humans is consequential. Here, we investigated the antiproliferative activity of styrene substituted biscoumarin against various human breast cancer cell lines, such as MCF-7, (ER-) MDA-MB-231 and (AR+) MDA-MB-453. Styrene substituted biscoumarin induced cell death by apoptosis in MDA-MB-231 cell line was analyzed. Antiproliferative activity of Styrene substituted biscoumarin was performed by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Styrene substituted biscoumarin induced apoptosis was assessed by Hoechst staining, Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) staining and flow cytometric analysis. Migratory and proliferating characteristic of breast cancer cell line MDA-MB-231 was also analyzed by wound healing and colony formation assay. Furthermore, mRNA expression of BAX and BCL-2 were quantified using qRT-PCR and protein expression level analyzed by Western blot. The inhibition concentration (IC 50 ) of styrene substituted biscoumarin was assayed against three breast cancer cell lines. The inhibition concentration (IC 50 ) value of styrene substituted biscoumarin toward MDA-MB-231, MDA-MB-453 and MCF-7 cell lines was 5.63, 7.30 and 10.84μg/ml respectively. Styrene substituted biscoumarin induced apoptosis was detected by Hoechst staining, DAPI/PI analysis and flow-cytometric analysis. The migration and proliferative efficiency of MDA-MB-231 cells were completely arrested upon styrene substituted biscoumarin treatment. Also, mRNA gene expression and protein expression of pro-apoptotic (BAX) and anti-apoptotic (BCL-2) genes were analyzed by qRT-PCR and western blot analysis upon

  15. The ubiquitin peptidase UCHL1 induces G0/G1 cell cycle arrest and apoptosis through stabilizing p53 and is frequently silenced in breast cancer.

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    Tingxiu Xiang

    Full Text Available Breast cancer (BrCa is a complex disease driven by aberrant gene alterations and environmental factors. Recent studies reveal that abnormal epigenetic gene regulation also plays an important role in its pathogenesis. Ubiquitin carboxyl- terminal esterase L1 (UCHL1 is a tumor suppressor silenced by promoter methylation in multiple cancers, but its role and alterations in breast tumorigenesis remain unclear.We found that UCHL1 was frequently downregulated or silenced in breast cancer cell lines and tumor tissues, but readily expressed in normal breast tissues and mammary epithelial cells. Promoter methylation of UCHL1 was detected in 9 of 10 breast cancer cell lines (90% and 53 of 66 (80% primary tumors, but rarely in normal breast tissues, which was statistically correlated with advanced clinical stage and progesterone receptor status. Pharmacologic demethylation reactivated UCHL1 expression along with concomitant promoter demethylation. Ectopic expression of UCHL1 significantly suppressed the colony formation and proliferation of breast tumor cells, through inducing G0/G1 cell cycle arrest and apoptosis. Subcellular localization study showed that UCHL1 increased cytoplasmic abundance of p53. We further found that UCHL1 induced p53 accumulation and reduced MDM2 protein level, and subsequently upregulated the expression of p21, as well as cleavage of caspase3 and PARP, but not in catalytic mutant UCHL1 C90S-expressed cells.UCHL1 exerts its tumor suppressive functions by inducing G0/G1cell cycle arrest and apoptosis in breast tumorigenesis, requiring its deubiquitinase activity. Its frequent silencing by promoter CpG methylation may serve as a potential tumor marker for breast cancer.

  16. Selumetinib suppresses cell proliferation, migration and trigger apoptosis, G1 arrest in triple-negative breast cancer cells.

    Science.gov (United States)

    Zhou, Yan; Lin, Shuchen; Tseng, Kuo-Fu; Han, Kun; Wang, Yaling; Gan, Zhi-Hua; Min, Da-Liu; Hu, Hai-Yan

    2016-10-21

    Triple-negative breast cancer (TNBC) has aggressive progression with poor prognosis and ineffective treatments. Selumetinib is an allosteric, ATP-noncompetitive inhibitor of MEK1/2, which has benn known as effective antineoplastic drugs for several malignant tumors. We hypothesized that Selumetinib might be potential drug for TNBC and explore the mechanism. After treated with Selumetinib, the viability and mobility of HCC1937 and MDA-MB-231 were detected by MTT, tunnel, wound-healing assay, transwell assay and FCM methods. MiR array was used to analysis the change of miRs. We predicted and verified CUL1 is the target of miR-302a using Luciferase reporter assay. We also silenced the CUL1 by siRNA, to clarify whether CUL1 take part in the cell proliferation, migration and regulated its substrate TIMP1 and TRAF2. Moreover, after transfection, the antagomir of miR-302a and CUL1 over-expressed plasmid into HCC1937 and MDA-MB-231 cell accompanied with the Selumetinib treatment, we detected the proliferation and migration again. Selumetinib reduce the proliferation, migration, triggered apoptosis and G1 arrest in TNBC cell lines. In this process, the miR-302a was up-regulated and inhibited the CUL1 expression. The later negatively regulated the TIMP1 and TRAF2. As soon as we knockdown miR-302a and over-expression CUL1 in TNBC cells, the cytotoxicity of Selumetinib was reversed. MiR-302a targeted regulated the CUL1 expression and mediated the Selumetinib-induced cytotoxicity of triple-negative breast cancer.

  17. High-throughput screening (HTS) and modeling of the retinoid ...

    Science.gov (United States)

    Presentation at the Retinoids Review 2nd workshop in Brussels, Belgium on the application of high throughput screening and model to the retinoid system Presentation at the Retinoids Review 2nd workshop in Brussels, Belgium on the application of high throughput screening and model to the retinoid system

  18. Flavokawain derivative FLS induced G2/M arrest and apoptosis on breast cancer MCF-7 cell line

    Directory of Open Access Journals (Sweden)

    Ali NM

    2016-06-01

    Full Text Available Norlaily Mohd Ali,1 M Nadeem Akhtar,2 Huynh Ky,3 Kian Lam Lim,1 Nadiah Abu,4 Seema Zareen,2 Wan Yong Ho,5 Han Kiat Alan-Ong,1 Sheau Wei Tan,6 Noorjahan Banu Alitheen,4 Jamil bin Ismail,2 Swee Keong Yeap,6 Tunku Kamarul7 1Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Selangor, 2Department of Industrial Biotechnology, Faculty of Industrial Sciences & Technology, Universiti Malaysia Pahang, Pahang, Malaysia; 3Department of Agriculture Genetics and Breeding, College of Agriculture and Applied Biology, Cantho University, CanTho City, Vietnam; 4Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 5School of Biomedical Sciences, The University of Nottingham Malaysia Campus, 6Institute of Bioscience, Universiti Putra Malaysia, Selangor, 7Tissue Engineering Group, National Orthopaedic Centre of Excellence for Research and Learning, Department of Orthopaedic Surgery, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia Abstract: Known as naturally occurring biologically active compounds, flavokawain A and B are the leading chalcones that possess anticancer properties. Another flavokawain derivative, (E-1-(2'-Hydroxy-4',6'-dimethoxyphenyl-3-(4-methylthiophenylprop-2-ene-1-one (FLS was characterized with 1H-nuclear magnetic resonance, electron-impact mas spectrometry, infrared spectroscopy, and ultraviolet (1H NMR, EI-MS, IR, and UV spectroscopic techniques. FLS cytotoxic efficacy against human cancer cells (MCF-7, MDA-MB-231, and MCF-10A resulted in the reduction of IC50 values in a time- and dose-dependent mode with high specificity on MCF-7 (IC50 of 36 µM at 48 hours against normal breast cell MCF-10A (no IC50 detected up to 180 µM at 72 hours. Light, scanning electron, and fluorescent microscopic analysis of MCF-7 cell treated with 36 µM of FLS displayed cell shrinkage, apoptotic body, and DNA fragmentation. Additionally, induction of G2/M cell

  19. Cytotoxicity and Proapoptotic Effects of Allium atroviolaceum Flower Extract by Modulating Cell Cycle Arrest and Caspase-Dependent and p53-Independent Pathway in Breast Cancer Cell Lines

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    Somayeh Khazaei

    2017-01-01

    Full Text Available Breast cancer is the second leading cause of cancer death among women and despite significant advances in therapy, it remains a critical health problem worldwide. Allium atroviolaceum is an herbaceous plant, with limited information about the therapeutic capability. We aimed to study the anticancer effect of flower extract and the mechanisms of action in MCF-7 and MDA-MB-231. The extract inhibits the proliferation of the cells in a time- and dose-dependent manner. The underlying mechanism involved the stimulation of S and G2/M phase arrest in MCF-7 and S phase arrest in MDA-MB-231 associated with decreased level of Cdk1, in a p53-independent pathway. Furthermore, the extract induces apoptosis in both cell lines, as indicated by the percentage of sub-G0 population, the morphological changes observed by phase contrast and fluorescent microscopy, and increase in Annexin-V-positive cells. The apoptosis induction was related to downregulation of Bcl-2 and also likely to be caspase-dependent. Moreover, the combination of the extract and tamoxifen exhibits synergistic effect, suggesting that it can complement current chemotherapy. LC-MS analysis displayed 17 major compounds in the extract which might be responsible for the observed effects. Overall, this study demonstrates the potential applications of Allium atroviolaceum extract as an anticancer drug for breast cancer treatment.

  20. Long Term Exposure to Polyphenols of Artichoke (Cynara scolymus L.) Exerts Induction of Senescence Driven Growth Arrest in the MDA-MB231 Human Breast Cancer Cell Line.

    Science.gov (United States)

    Mileo, Anna Maria; Di Venere, Donato; Abbruzzese, Claudia; Miccadei, Stefania

    2015-01-01

    Polyphenolic extracts from the edible part of artichoke (Cynara scolymus L.) have been shown to be potential chemopreventive and anticancer dietary compounds. High doses of polyphenolic extracts (AEs) induce apoptosis and decrease the invasive potential of the human breast cancer cell line, MDA-MB231. However, the molecular mechanism underlying AEs antiproliferative effects is not completely understood. We demonstrate that chronic and low doses of AEs treatment at sublethal concentrations suppress human breast cancer cell growth via a caspases-independent mechanism. Furthermore, AEs exposure induces a significant increase of senescence-associated β-galactosidase (SA-β-gal) staining and upregulation of tumour suppressor genes, p16(INK4a) and p21(Cip1/Waf1) in MDA-MB231 cells. AEs treatment leads to epigenetic alterations in cancer cells, modulating DNA hypomethylation and lysine acetylation levels in total proteins. Cell growth arrest correlates with increased reactive oxygen species (ROS) production in AEs treated breast cancer cells. Inhibition of ROS generation by N-acetylcysteine (NAC) attenuates the antiproliferative effect. These findings demonstrate that chronic AEs treatment inhibits breast cancer cell growth via the induction of premature senescence through epigenetic and ROS-mediated mechanisms. Our results suggest that artichoke polyphenols could be a promising dietary tool either in cancer chemoprevention or/and in cancer treatment as a nonconventional, adjuvant therapy.

  1. Inhibition of estrogen-responsive gene activation by the retinoid X receptor beta: evidence for multiple inhibitory pathways.

    OpenAIRE

    Segars, J H; Marks, M S; Hirschfeld, S; Driggers, P H; Martinez, E; Grippo, J F; Brown, M; Wahli, W; Ozato, K

    1993-01-01

    The retinoid X receptor beta (RXR beta; H-2RIIBP) forms heterodimers with various nuclear hormone receptors and binds multiple hormone response elements, including the estrogen response element (ERE). In this report, we show that endogenous RXR beta contributes to ERE binding activity in nuclear extracts of the human breast cancer cell line MCF-7. To define a possible regulatory role of RXR beta regarding estrogen-responsive transcription in breast cancer cells, RXR beta and a reporter gene d...

  2. Quantitation of biological retinoids by high-pressure liquid chromatography: primary internal standardization using tritiated retinoids

    International Nuclear Information System (INIS)

    Cullum, M.E.; Zile, M.H.

    1986-01-01

    A single method is described for quantitation of 14 retinoids found in biological material. The method consists of reversed-phase HPLC, internal standardization, and carrier extraction procedures with three synthetic retinoids. Primary standardization of HPLC uv detector is achieved using tritiated all-trans-retinoic acid, all-trans-retinol, all-trans-retinyl palmitate, and all-trans-retinyl acetate. Extraction methods are standardized by correlating the uv absorbance of retinoids at 340 nm with radioactivity of tritiated retinoids of known specific activity. Quantitation of 10 pg of tritiated or 5 ng of nonradioactive retinoid per 0.1 g sample in a polarity range from 4-oxo-retinoic acid to retinyl stearate can be achieved in a single, 50-min chromatographic run. A single HPLC pump, a C 18 reversed-phased analytical column, a multistep three-solvent gradient, and inexpensive solvents based on methanol, water, and chloroform comprise this cost-effective chromatographic system. Our primary standardization method allows investigators employing different procedures to compare results between laboratories by standardizing the HPLC uv detector with commercially available tritiated retinoids. With this method we were able to quantitate nanomolar amounts of endogenous retinoic acids and retinyl esters, that HPLC uv only conditions usually would not detect in the circulation and liver of rats under physiological conditions

  3. Retinoid quantification by HPLC/MS(n)

    Science.gov (United States)

    McCaffery, Peter; Evans, James; Koul, Omanand; Volpert, Amy; Reid, Kevin; Ullman, M. David

    2002-01-01

    Retinoic acid (RA) mediates most of the biological effects of vitamin A that are essential for vertebrate survival. It acts through binding to receptors that belong to the nuclear receptor transcription factor superfamily (Mangelsdorf et al. 1994). It is also a highly potent vertebrate teratogen. To determine the function and effects of endogenous and exogenous RA, it is important to have a highly specific, sensitive, accurate, and precise analytical procedure. Current analyses of RA and other retinoids are labor intensive, of poor sensitivity, have limited specificity, or require compatibility with RA reporter cell lines (Chen et al. 1995. BIOCHEM: Pharmacol. 50: 1257-1264; Creech Kraft et al. 1994. BIOCHEM: J. 301: 111-119; Lanvers et al. 1996. J. Chromatogr. B Biomed. Appl. 685: 233-240; Maden et al. 1998. DEVELOPMENT: 125: 4133-4144; Wagner et al. 1992. DEVELOPMENT: 116: 55-66). This paper describes an HPLC/mass spectrometry/mass spectrometry product ion scan (HPLC/MS(n)) procedure for the analysis of retinoids that employs atmospheric pressure chemical ionization MS. The retinoids are separated by normal-phase column chromatography with a linear hexane-isopropanol-dioxane gradient. Each retinoid is detected by a unique series of MS(n) functions set at optimal collision-induced dissociation energy (30% to 32%) for all MS(n) steps. The scan events are divided into three segments, based on HPLC elution order, to maximize the mass spectrometer duty cycle. The all-trans, 9-cis, and 13-cis RA isomers are separated, if desired, by an isocratic hexane-dioxane-isopropanol mobile phase. This paper describes an HPLC/MS(n) procedure possessing high sensitivity and specificity for retinoids.

  4. Benzylidene derivatives of andrographolide inhibit growth of breast and colon cancer cells in vitro by inducing G1 arrest and apoptosis

    Science.gov (United States)

    Jada, S R; Matthews, C; Saad, M S; Hamzah, A S; Lajis, N H; Stevens, M F G; Stanslas, J

    2008-01-01

    Background and purpose: Andrographolide, the major phytoconstituent of Andrographis paniculata, was previously shown by us to have activity against breast cancer. This led to synthesis of new andrographolide analogues to find compounds with better activity than the parent compound. Selected benzylidene derivatives were investigated for their mechanisms of action by studying their effects on the cell cycle progression and cell death. Experimental approach: Microculture tetrazolium, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and sulphorhodamine B (SRB) assays were utilized in assessing the in vitro growth inhibition and cytotoxicity of compounds. Flow cytometry was used to analyse the cell cycle distribution of control and treated cells. CDK1 and CDK4 levels were determined by western blotting. Apoptotic cell death was assessed by fluorescence microscopy and flow cytometry. Key results: Compounds, in nanomolar to micromolar concentrations, exhibited growth inhibition and cytotoxicity in MCF-7 (breast) and HCT-116 (colon) cancer cells. In the NCI screen, 3,19-(2-bromobenzylidene) andrographolide (SRJ09) and 3,19-(3-chloro-4-fluorobenzylidene) andrographolide (SRJ23) showed greater cytotoxic potency and selectivity than andrographolide. SRJ09 and SRJ23 induced G1 arrest and apoptosis in MCF-7 and HCT-116 cells, respectively. SRJ09 downregulated CDK4 but not CDK1 level in MCF-7 cells. Apoptosis induced by SRJ09 and SRJ23 in HCT-116 cells was confirmed by annexin V-FITC/PI flow cytometry analysis. Conclusion and implications: The new benzylidene derivatives of andrographolide are potential anticancer agents. SRJ09 emerged as the lead compound in this study, exhibiting anticancer activity by downregulating CDK4 to promote a G1 phase cell cycle arrest, coupled with induction of apoptosis. PMID:18806812

  5. Alteronol induces cell cycle arrest and apoptosis via increased reactive oxygen species production in human breast cancer T47D cells.

    Science.gov (United States)

    Ren, Boxue; Li, Defang; Si, Lingling; Ding, Yangfang; Han, Jichun; Chen, Xiaoyu; Zheng, Qiusheng

    2018-04-01

    Emerging evidence showed that alteronol has a potential antitumour effect in several tumour cells. However, the antitumour effect of alteronol on breast cancer has not been reported. This study investigated the mechanisms of alteronol-induced cell proliferation inhibition in human breast cancer T47D cells. After treatment with alteronol, T47D cell proliferation was examined by MTT assay. The cell cycle distribution, cell apoptosis, reactive oxygen species level and mitochondrial membrane potential were evaluated via flow cytometry. Next, the protein levels of cyclin B1, cdc2, p21, p-cyclin B1, p-cdc2, p53, Bax, Bcl-2 and cytochrome c were analysed using Western blot analysis. Meanwhile, the mRNA levels of cyclin B1, cdc2, p21 and p53 were examined by qRT-PCR. Our data showed that alteronol inhibited the proliferation of T47D cells via inducing G2-phase arrest and cell apoptosis. Compared with control group, alteronol significantly increased ROS level and triggered mitochondrial dysfunction in alteronol-treated T47D cells. Further studies showed that the mRNA and protein levels of cdc2 and cyclin B1 were downregulated, while the mRNA and protein levels of p21, p53, p-cyclin B1, p-cdc2 and cytochrome c were upregulated. In addition, the expression level of Bax was increased, and the expression level of Bcl-2 was decreased. Alteronol induced T47D cell cycle arrest and cell apoptosis through increasing ROS production and triggering mitochondrial dysfunction, and subsequently inhibiting T47D cell proliferation. © 2018 Royal Pharmaceutical Society.

  6. Ajwa Date (Phoenix dactylifera L. Extract Inhibits Human Breast Adenocarcinoma (MCF7 Cells In Vitro by Inducing Apoptosis and Cell Cycle Arrest.

    Directory of Open Access Journals (Sweden)

    Fazal Khan

    Full Text Available Phoenix dactylifera L (Date palm is a native plant of the Kingdom of Saudi Arabia (KSA and other Middle Eastern countries. Ajwa date has been described in the traditional and alternative medicine to provide several health benefits including anticholesteremic, antioxidant, hepatoprotective and anticancer effects, but most remains to be scientifically validated. Herein, we evaluated the anticancer effects of the Methanolic Extract of Ajwa Date (MEAD on human breast adenocarcinoma (MCF7 cells in vitro.MCF7 cells were treated with various concentrations (5, 10, 15, 20 and 25 mg/ml of MEAD for 24, 48 and 72 h and changes in cell morphology, cell cycle, apoptosis related protein and gene expression were studied.Phase contrast microscopy showed various morphological changes such as cell shrinkage, vacuolation, blebbing and fragmentation. MTT (2-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay demonstrated statistically significant dose-dependent inhibitions of MCF7 cell proliferation from 35% to 95%. Annexin V-FITC and TUNEL assays showed positive staining for apoptosis of MCF7 cells treated with MEAD (15 mg and 25 mg for 48 h. Flow cytometric analyses of MCF7 cells with MEAD (15 mg/ml and 20 mg/ml for 24 h demonstrated cell cycle arrest at 'S' phase; increased p53, Bax protein expression; caspase 3activation and decreased the mitochondrial membrane potential (MMP. Quantitative real time PCR (qRT-PCR analysis showed up-regulation of p53, Bax, Fas, and FasL and down-regulation of Bcl-2.MEAD inhibited MCF7 cells in vitro by the inducing cell cycle arrest and apoptosis. Our results indicate the anticancer effects of Ajwa dates, which therefore may be used as an adjunct therapy with conventional chemotherapeutics to achieve a synergistic effect against breast cancer.

  7. TGF-β-Dependent Growth Arrest and Cell Migration in Benign and Malignant Breast Epithelial Cells Are Antagonistically Controlled by Rac1 and Rac1b.

    Science.gov (United States)

    Melzer, Catharina; von der Ohe, Juliane; Hass, Ralf; Ungefroren, Hendrik

    2017-07-20

    Despite improvements in diagnosis and treatment, breast cancer is still the most common cancer type among non-smoking females. TGF-β can inhibit breast cancer development by inducing cell cycle arrest in both, cancer cells and, as part of a senescence program in normal human mammary epithelial cells (HMEC). Moreover, TGF-β also drives cell migration and invasion, in part through the small GTPases Rac1 and Rac1b. Depletion of Rac1b or Rac1 and Rac1b in MDA-MB-231 or MDA-MB-435s breast cancer cells by RNA interference enhanced or suppressed, respectively, TGF-β1-induced migration/invasion. Rac1b depletion in MDA-MB-231 cells also increased TGF-β-induced p21 WAF1 expression and ERK1/2 phosphorylation. Senescent HMEC (P15/P16), when compared to their non-senescent counterparts (P11/P12), presented with dramatically increased migratory activity. These effects were paralleled by elevated expression of genes associated with TGF-β signaling and metastasis, downregulated Rac1b, and upregulated Rac1. Our data suggest that acquisition of a motile phenotype in HMEC resulted from enhanced autocrine TGF-β signaling, invasion/metastasis-associated gene expression, and a shift in the ratio of antimigratory Rac1b to promigratory Rac1. We conclude that although enhanced TGF-β signaling is considered antioncogenic in HMEC by suppressing oncogene-induced transformation, this occurs at the expense of a higher migration and invasion potential.

  8. Therapy of psoriasis with retinoid plus PUVA

    International Nuclear Information System (INIS)

    Heidbreder, G.; Christophers, E.

    1979-01-01

    In a group of 40 patients suffering from wide-spread psoriasis oral administration of a retinoid (Ro 10-9359) was followed by PUVA therapy. The clearance rate was increased by 30% as compared to PUVA alone. Except for cheilitis no side effects were seen. Histological analysis in 20 patients before, during and after therapy revealed an intensification of psoriatic tissue changes after retinoid treatment. Loss of corneal layers, massive exoserosis, and neutrophil migration were prominent features. Mitotic counts were not increased by the pretreatment. The increased susceptibility of diseased skin to PUVA as produced by this drug appears to be based on several factors related to the tissue changes revealed by histology. (orig.) [de

  9. Isolation of key retinoid signalling and metabolic modules in invertebrates

    Directory of Open Access Journals (Sweden)

    Ana André

    2014-05-01

    Full Text Available Retinoids are a class of molecules related to vitamin A (Retinol that are required for regulation of critical chordate ndocrine-mediated process, such as embryonic development, reproduction, and vision. To maintain such physiological process, chordates have a complex mechanism to regulate the spatial and temporal distribution of retinoids that includes metabolic and signalling modules. Initially, retinoid modules were seen as a chordate novelty. However, emerging biochemical and genomic evidences have challenged this view, clearly pointing to a more basal ancestry than previously thought. However, for the majority of non-chordate invertebrate lineages a clearly characterization of the main enzymatic/molecular players is still missing. Despite limited, the available evidence supports the presence of biologically active retinoid pathways in invertebrates. In order to enhance our insights on retinoid biology, evolution, and its putative disruption by environmental chemicals, the isolation and functional characterization of key retinoid metabolic players in marine invertebrates has been carried out.

  10. Cumulative irritation potential of topical retinoid formulations.

    Science.gov (United States)

    Leyden, James J; Grossman, Rachel; Nighland, Marge

    2008-08-01

    Localized irritation can limit treatment success with topical retinoids such as tretinoin and adapalene. The factors that influence irritant reactions have been shown to include individual skin sensitivity, the particular retinoid and concentration used, and the vehicle formulation. To compare the cutaneous tolerability of tretinoin 0.04% microsphere gel (TMG) with that of adapalene 0.3% gel and a standard tretinoin 0.025% cream. The results of 2 randomized, investigator-blinded studies of 2 to 3 weeks' duration, which utilized a split-face method to compare cumulative irritation scores induced by topical retinoids in subjects with healthy skin, were combined. Study 1 compared TMG 0.04% with adapalene 0.3% gel over 2 weeks, while study 2 compared TMG 0.04% with tretinoin 0.025% cream over 3 weeks. In study 1, TMG 0.04% was associated with significantly lower cumulative scores for erythema, dryness, and burning/stinging than adapalene 0.3% gel. However, in study 2, there were no significant differences in cumulative irritation scores between TMG 0.04% and tretinoin 0.025% cream. Measurements of erythema by a chromameter showed no significant differences between the test formulations in either study. Cutaneous tolerance of TMG 0.04% on the face was superior to that of adapalene 0.3% gel and similar to that of a standard tretinoin cream containing a lower concentration of the drug (0.025%).

  11. Daily Arrests

    Data.gov (United States)

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

  12. Cardiac arrest

    Science.gov (United States)

    ... magnesium. These minerals help your heart's electrical system work. Abnormally high or low levels can cause cardiac arrest. Severe physical stress. Anything that causes a severe stress on your ...

  13. An antioxidant extract of tropical lichen, Parmotrema reticulatum, induces cell cycle arrest and apoptosis in breast carcinoma cell line MCF-7.

    Directory of Open Access Journals (Sweden)

    Nikhil Baban Ghate

    Full Text Available This report highlights the phytochemical analysis, antioxidant potential and anticancer activity against breast carcinoma of 70% methanolic extract of lichen, Parmotrema reticulatum (PRME. Phytochemical analysis of PRME confirms the presence of various phytoconstituents like alkaloids, carbohydrates, flavonoids, glycosides, phenols, saponins, tannins, anthraquinones, and ascorbic acid; among which alkaloids, phenols and flavonoids are found in abundant amount. High performance liquid chromatography (HPLC analysis of PRME revealed the presence of catechin, purpurin, tannic acid and reserpine. Antioxidant activity was evaluated by nine separate methods. PRME showed excellent hydroxyl and hypochlorous radical scavenging as well as moderate DPPH, superoxide, singlet oxygen, nitric oxide and peroxynitrite scavenging activity. Cytotoxicity of PRME was tested against breast carcinoma (MCF-7, lung carcinoma (A549 and normal lung fibroblast (WI-38 using WST-1 method. PRME was found cytotoxic against MCF-7 cells with an IC50 value 130.03 ± 3.11 µg/ml while negligible cytotoxicity was observed on A549 and WI-38 cells. Further flow cytometric study showed that PRME halted the MCF-7 cells in S and G2/M phases and induces apoptosis in dose as well as time dependent manner. Cell cycle arrest was associated with downregulation of cyclin B1, Cdk-2 and Cdc25C as well as slight decrease in the expression of Cdk-1 and cyclin A1 with subsequent upregulation of p53 and p21. Moreover PRME induced Bax and inhibited Bcl-2 expression, which results in increasing Bax/Bcl-2 ratio and activation of caspase cascade. This ultimately leads to PARP degradation and induces apoptosis in MCF-7 cells. It can be hypothesised from the current study that the antioxidant and anticancer potential of the PRME may reside in the phytoconstitutents present in it and therefore, PRME may be used as a possible source of natural antioxidant that may be developed to an anticancer agent.

  14. Synthesis of an anthraquinone derivative (DHAQC) and its effect on induction of G2/M arrest and apoptosis in breast cancer MCF-7 cell line.

    Science.gov (United States)

    Yeap, SweeKeong; Akhtar, Muhammad Nadeem; Lim, Kian Lam; Abu, Nadiah; Ho, Wan Yong; Zareen, Seema; Roohani, Kiarash; Ky, Huynh; Tan, Sheau Wei; Lajis, Nordin; Alitheen, Noorjahan Banu

    2015-01-01

    Anthraquinones are an important class of naturally occurring biologically active compounds. In this study, anthraquinone derivative 1,3-dihydroxy-9,10-anthraquinone-2- carboxylic acid (DHAQC) (2) was synthesized with 32% yield through the Friedel-Crafts condensation reaction. The mechanisms of cytotoxicity of DHAQC (2) in human breast cancer MCF-7 cells were further investigated. Results from the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that DHAQC (2) exhibited potential cytotoxicity and selectivity in the MCF-7 cell line, comparable with the naturally occurring anthraquinone damnacanthal. DHAQC (2) showed a slightly higher IC50 (inhibitory concentration with 50% cell viability) value in the MCF-7 cell line compared to damnacanthal, but it is more selective in terms of the ratio of IC50 on MCF-7 cells and normal MCF-10A cells. (selective index for DHAQC (2) was 2.3 and 1.7 for damnacanthal). The flow cytometry cell cycle analysis on the MCF-7 cell line treated with the IC50 dose of DHAQC (2) for 48 hours showed that DHAQC (2) arrested MCF-7 cell line at the G2/M phase in association with an inhibited expression of PLK1 genes. Western blot analysis also indicated that the DHAQC (2) increased BAX, p53, and cytochrome c levels in MCF-7 cells, which subsequently activated apoptosis as observed in annexin V/propidium iodide and cell cycle analyses. These results indicate that DHAQC (2) is a synthetic, cytotoxic, and selective anthraquinone, which is less toxic than the natural product damnacanthal, and which demonstrates potential in the induction of apoptosis in the breast cancer MCF-7 cell line.

  15. Chromatographic analysis of endogenous retinoids in tissues and serum

    NARCIS (Netherlands)

    Schmidt, C.K.; Brouwer, A.; Nau, H.

    2003-01-01

    We present a reliable, highly sensitive, and versatile method for the simultaneous determination of endogenous polar (acidic) and apolar (retinol, retinal, and retinyl esters) retinoids in various biological matrices. Following a single liquid extraction of retinoids from tissues or plasma with

  16. Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN): could retinoids play a causative role?

    Science.gov (United States)

    Mawson, Anthony R; Eriator, Ike; Karre, Sridhar

    2015-01-12

    Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are overlapping manifestations on a spectrum of acute drug-induced conditions associated with severe blistering, skin peeling, and multi-organ damage. TEN is an eruption resembling severe scalding, with ≥30% skin detachment. SJS is a mild form of TEN, characterized histologically by epidermal keratinocyte apoptosis with dermo-epidermal separation and extensive small blisters with <10% body surface skin detachment. The syndrome can be induced by numerous medications and typically occurs 1-4 weeks after the initiation of therapy. Granulysin is found in the lesions of patients with SJS/TEN and plays a significant pathogenic role in the condition, but the overall mechanisms linking medications, granulysin, and disease manifestations remain obscure. This paper reviews evidence suggesting that the different medications implicated in SJS/TEN have the common property of interacting and synergizing with endogenous retinoids (vitamin A and its congeners), in many instances causing the latter to accumulate in and damage the liver, the main storage organ for vitamin A. It is hypothesized that liver damage leads to the spillage of toxic retinoid compounds into the circulation, resulting in an endogenous form of hypervitaminosis A and cytotoxicity with widespread apoptosis, mediated by granulysin and recognized as SJS/TEN. Subject to testing, the model suggests that symptom worsening could be arrested at onset by lowering the concentration of circulating retinoids and/or granulysin via phlebotomy or plasmapheresis or by pharmacological measures to limit their expression.

  17. Side effects of retinoid therapy on the quality of vision

    Directory of Open Access Journals (Sweden)

    Bergler-Czop Beata

    2016-12-01

    Full Text Available Retinoids are compounds chemically related to vitamin A, which are frequently used in dermatological practice (1. They are characterized by numerous mechanisms of action leading to normalization of keratinocyte proliferation and maturation. They have anti-seborrhoeic, immunomodulatory and anti-inflammatory effects (1, 2. A number of side effects to retinoid treatment have been recorded; one group of such side effects relates to eyes and vision. Dry eye syndrome and blepharoconjunctivitis are the most common side effects, appearing in 20-50 % of patients treated with retinoids. They often contribute to the occurrence of other side-effects such as eye discomfort and contact lens intolerance. Due to the widespread use in clinical practice, the adverse effects, including ocular side effects, should be studied. To confirm the variety of adverse effects of retinoids, several case reports of rare side-effects are presented.

  18. Identification of Novel Retinoid Targets in Prostate Cancer

    National Research Council Canada - National Science Library

    Piedrafita, F. J

    2006-01-01

    .... However except for the efficient treatment of acute promyelocytic leukemia and certain skin disorders most natural and synthetic retinoids have failed in clinical trials because of toxicity and limited activity...

  19. Retinoid receptor signaling and autophagy in acute promyelocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Orfali, Nina [Cork Cancer Research Center, University College Cork, Cork (Ireland); Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA. (United States); McKenna, Sharon L. [Cork Cancer Research Center, University College Cork, Cork (Ireland); Cahill, Mary R. [Department of Hematology, Cork University Hospital, Cork (Ireland); Gudas, Lorraine J., E-mail: ljgudas@med.cornell.edu [Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA. (United States); Mongan, Nigel P., E-mail: nigel.mongan@nottingham.ac.uk [Faculty of Medicine and Health Science, School of Veterinary Medicine and Science, University of Nottingham, LE12 5RD (United Kingdom); Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA. (United States)

    2014-05-15

    Retinoids are a family of signaling molecules derived from vitamin A with well established roles in cellular differentiation. Physiologically active retinoids mediate transcriptional effects on cells through interactions with retinoic acid (RARs) and retinoid-X (RXR) receptors. Chromosomal translocations involving the RARα gene, which lead to impaired retinoid signaling, are implicated in acute promyelocytic leukemia (APL). All-trans-retinoic acid (ATRA), alone and in combination with arsenic trioxide (ATO), restores differentiation in APL cells and promotes degradation of the abnormal oncogenic fusion protein through several proteolytic mechanisms. RARα fusion-protein elimination is emerging as critical to obtaining sustained remission and long-term cure in APL. Autophagy is a degradative cellular pathway involved in protein turnover. Both ATRA and ATO also induce autophagy in APL cells. Enhancing autophagy may therefore be of therapeutic benefit in resistant APL and could broaden the application of differentiation therapy to other cancers. Here we discuss retinoid signaling in hematopoiesis, leukemogenesis, and APL treatment. We highlight autophagy as a potential important regulator in anti-leukemic strategies. - Highlights: • Normal and aberrant retinoid signaling in hematopoiesis and leukemia is reviewed. • We suggest a novel role for RARα in the development of X-RARα gene fusions in APL. • ATRA therapy in APL activates transcription and promotes onco-protein degradation. • Autophagy may be involved in both onco-protein degradation and differentiation. • Pharmacologic autophagy induction may potentiate ATRA's therapeutic effects.

  20. Retinoid receptor signaling and autophagy in acute promyelocytic leukemia

    International Nuclear Information System (INIS)

    Orfali, Nina; McKenna, Sharon L.; Cahill, Mary R.; Gudas, Lorraine J.; Mongan, Nigel P.

    2014-01-01

    Retinoids are a family of signaling molecules derived from vitamin A with well established roles in cellular differentiation. Physiologically active retinoids mediate transcriptional effects on cells through interactions with retinoic acid (RARs) and retinoid-X (RXR) receptors. Chromosomal translocations involving the RARα gene, which lead to impaired retinoid signaling, are implicated in acute promyelocytic leukemia (APL). All-trans-retinoic acid (ATRA), alone and in combination with arsenic trioxide (ATO), restores differentiation in APL cells and promotes degradation of the abnormal oncogenic fusion protein through several proteolytic mechanisms. RARα fusion-protein elimination is emerging as critical to obtaining sustained remission and long-term cure in APL. Autophagy is a degradative cellular pathway involved in protein turnover. Both ATRA and ATO also induce autophagy in APL cells. Enhancing autophagy may therefore be of therapeutic benefit in resistant APL and could broaden the application of differentiation therapy to other cancers. Here we discuss retinoid signaling in hematopoiesis, leukemogenesis, and APL treatment. We highlight autophagy as a potential important regulator in anti-leukemic strategies. - Highlights: • Normal and aberrant retinoid signaling in hematopoiesis and leukemia is reviewed. • We suggest a novel role for RARα in the development of X-RARα gene fusions in APL. • ATRA therapy in APL activates transcription and promotes onco-protein degradation. • Autophagy may be involved in both onco-protein degradation and differentiation. • Pharmacologic autophagy induction may potentiate ATRA's therapeutic effects

  1. Mefloquine use, psychosis, and violence: a retinoid toxicity hypothesis.

    Science.gov (United States)

    Mawson, Anthony

    2013-07-15

    Mefloquine use has been linked to severe gastrointestinal and neuropsychiatric adverse effects, including cognitive disturbances, anxiety, depression, psychosis, and violence. The adverse effects of the drug are thought to result from the secondary consequences of hepatocellular injury; in fact, mefloquine is known to cause a transient, anicteric chemical hepatitis. However, the mechanism of mefloquine-associated liver damage and the associated neuropsychiatric and behavioral effects of the drug are not well understood. Mefloquine and other 8-amino-quinolines are the only antimalarial drugs that target the liver-stage malaria parasites, which selectively absorb vitamin A from the host. Vitamin A is also stored mainly in the liver, in potentially poisonous concentrations. These observations suggest that both the therapeutic effectiveness of mefloquine and its adverse effects are related to the ability of the 8-aminoquinolines to alter the metabolism of retinoids (vitamin A and its congeners). Several lines of evidence support the hypothesis that mefloquine neurotoxicity and other adverse effects reflect an endogenous form of hypervitaminosis A due to a process involving: mefloquine-induced dehydrogenase inhibition; the accumulation of retinoids in the liver; retinoid-induced hepatocellular damage; the spillage of stored retinoids into the circulation; and the transport of these compounds to the gut and brain in toxic concentrations. The retinoid hypothesis could be tested clinically by comparing cases of mefloquine toxicity and untreated controls in terms of retinoid profiles (retinol, retinyl esters, percent retinyl esters, and retinoic acid). Subject to such tests, retinoid profiling could provide an indicator for assessing mefloquine-associated adverse effects.

  2. Retinoid receptor signaling and autophagy in acute promyelocytic leukemia.

    LENUS (Irish Health Repository)

    Orfali, Nina

    2014-05-15

    Retinoids are a family of signaling molecules derived from vitamin A with well established roles in cellular differentiation. Physiologically active retinoids mediate transcriptional effects on cells through interactions with retinoic acid (RARs) and retinoid-X (RXR) receptors. Chromosomal translocations involving the RARα gene, which lead to impaired retinoid signaling, are implicated in acute promyelocytic leukemia (APL). All-trans-retinoic acid (ATRA), alone and in combination with arsenic trioxide (ATO), restores differentiation in APL cells and promotes degradation of the abnormal oncogenic fusion protein through several proteolytic mechanisms. RARα fusion-protein elimination is emerging as critical to obtaining sustained remission and long-term cure in APL. Autophagy is a degradative cellular pathway involved in protein turnover. Both ATRA and ATO also induce autophagy in APL cells. Enhancing autophagy may therefore be of therapeutic benefit in resistant APL and could broaden the application of differentiation therapy to other cancers. Here we discuss retinoid signaling in hematopoiesis, leukemogenesis, and APL treatment. We highlight autophagy as a potential important regulator in anti-leukemic strategies.

  3. Off-label uses of retinoids in dermatology

    Directory of Open Access Journals (Sweden)

    Wei Li

    2012-09-01

    Full Text Available Retinoids has been used widely in the topical and systemic treatments of various dermatoses: psoriasis, disorders of keratinization (DOK, keratotic genodermatosis, and severe acne. Moreover, it is also used in the treatment and/or chemoprevention of skin cancer and other neoplasms. Retinoids display key regulatory functions and most dermatologists are familiar with the FDA-approved indication of this medication. Retinoic acid is a potent signaling molecule that is essential for many biological processes, and its levels are tightly regulated by mechanisms that are only partially understood. This article will review these recent findings and attempt to synthesize their meaning to provide a view into the off-label uses of retinoids in dermatology with an emphasis on oral isotretinoin and acitrein.

  4. Liposomal Formulation of Retinoids Designed for Enzyme Triggered Release

    DEFF Research Database (Denmark)

    Pedersen, Palle Jacob; Adolph, Sidsel Kramshøj; Subramanian, Arun Kumar

    2010-01-01

    The design of retinoid phospholipid prodrugs is described based on molecular dynamics simulations and cytotoxicity studies of synthetic retinoid esters. The prodrugs are degradable by secretory phospholipase A(2) IIA and have potential in liposomal drug delivery targeting tumors. We have synthesi...... displayed IC50 values in the range of 3-19 mu M toward HT-29 and Colo205 colon cancer cells in the presence of phospholipase A(2), while no significant cell death was observed in the absence of the enzyme....

  5. Signalling with retinoids in the human lung: validation of new tools for the expression study of retinoid receptors

    International Nuclear Information System (INIS)

    Poulain, Stéphane; Lacomme, Stéphanie; Battaglia-Hsu, Shyue-Fang; Manoir, Stanislas du; Brochin, Lydia; Vignaud, Jean-Michel; Martinet, Nadine

    2009-01-01

    Retinoid Receptors are involved in development and cell homeostasis. Alterations of their expressions have been observed in lung cancer. However, retinoid chemoprevention trials in populations at risk to develop such tumors have failed. Therefore, the pertinence of new clinical trials using second generation retinoid requires prior better understanding of retinoid signalling. This is our aim when validating extensively research tools, focused on Retinoic Acid Receptor beta, whose major role in lung cancer is documented. Biocomputing was used to assess the genomic organization of RAR beta. Its putative RAR-beta1' promoter features were investigated experimentally. Specific measures realized, with qRT-PCR Syber Green assays and a triplex of Taqman probes, were extensively validated to establish Retinoid Receptors mRNAs reference values for in vivo normal human bronchial cells, lung tumors and cell lines. Finally, a pan-RAR-beta antibody was generated and extensively validated by western-blot and immunoprecipitation. No promoter-like activity was found for RAR-beta1'. RAR-beta2 mRNAs increase signs the normal differentiation of the human bronchial epithelium while a decrease is observed in most lung cancer cell lines. Accordingly, it is also, along with RXR beta, down-regulated in lung tumors. When using nuclear extracts of BEAS-2B and normal lung cells, only the RAR-beta2 long protein isoform was recognized by our antibody. Rigorous samples processing and extensive biocomputing, were the key factors for this study. mRNA reference values and validated tools can now be used to advance researches on retinoid signalling in the lung

  6. Circulatory Arrest, Brain Arrest and Death Determination

    Directory of Open Access Journals (Sweden)

    Sam David Shemie

    2018-03-01

    Full Text Available Technological advances, particularly in the capacity to support, replace or transplant failing organs, continue to challenge and refine our understanding of human death. Given the ability to reanimate organs before and after death, both inside and outside of the body, through reinstitution of oxygenated circulation, concepts related to death of organs (e.g. cardiac death are no longer valid. This paper advances the rationale for a single conceptual determination of death related to permanent brain arrest, resulting from primary brain injury or secondary to circulatory arrest. The clinical characteristics of brain arrest are the permanent loss of capacity for consciousness and loss of all brainstem functions. In the setting of circulatory arrest, death occurs after the arrest of circulation to the brain rather than death of the heart. Correspondingly, any intervention that resumes oxygenated circulation to the brain after circulatory arrest would invalidate the determination of death.

  7. Organochlorine contaminant and retinoid levels in blubber of common dolphins (Delphinus delphis) off northwestern Spain

    International Nuclear Information System (INIS)

    Tornero, Victoria; Borrell, Assumpcio; Aguilar, Alex; Forcada, Jaume; Lockyer, Christina

    2006-01-01

    The effect of age, sex, nutritive condition and organochlorine concentration on blubber retinoid concentrations was examined in 74 common dolphins incidentally caught off northwestern Spain. Age and blubber lipid content were strong determinants of the retinoid concentrations in males, while these variables did not account for the variation found in females. Retinoids were positively correlated with organochlorines in males and negatively in females. However, pollution levels were moderate and likely to be below threshold levels above that a toxicological response is to be expected. Thus, a cause-effect relationship between organochlorine and retinoid concentrations could not be properly established, and the observed correlation may be the result of an independent association of the two variables with age. Further research on the influence of the best predictor variables on retinoid dynamics is required to implement the use of retinoids as biomarkers of pollutant exposure in cetaceans. - Organochlorine contaminants and retinoids in common dolphins

  8. Ziyuglycoside I Inhibits the Proliferation of MDA-MB-231 Breast Carcinoma Cells through Inducing p53-Mediated G2/M Cell Cycle Arrest and Intrinsic/Extrinsic Apoptosis.

    Science.gov (United States)

    Zhu, Xue; Wang, Ke; Zhang, Kai; Zhang, Ting; Yin, Yongxiang; Xu, Fei

    2016-11-22

    Due to the aggressive clinical behavior, poor outcome, and lack of effective specific targeted therapies, triple-negative breast cancer (TNBC) has currently been recognized as one of the most malignant types of tumors. In the present study, we investigated the cytotoxic effect of ziyuglycoside I, one of the major components extracted from Chinese anti-tumor herbal Radix Sanguisorbae , on the TNBC cell line MDA-MB-231. The underlying molecular mechanism of the cytotoxic effect ziyuglycoside I on MDA-MB-231 cells was investigated with cell viability assay, flow cytometric analysis and Western blot. Compared to normal mammary gland Hs 578Bst cells, treatment of ziyuglycoside I resulted in a significant growth inhibitory effect on MDA-MB-231 cells. Ziyuglycoside I induced the G2/M phase arrest and apoptosis of MDA-MB-231 cells in a dose-dependent manner. These effects were found to be partially mediated through the up-regulation of p53 and p21 WAF1 , elevated Bax/Bcl-2 ratio, and the activation of both intrinsic (mitochondrial-initiated) and extrinsic (Fas/FasL-initiated) apoptotic pathways. Furthermore, the p53 specific siRNA attenuated these effects. Our study suggested that ziyuglycoside I-triggered MDA-MB-231 cell cycle arrest and apoptosis were probably mediated by p53. This suggests that ziyuglycoside I might be a potential drug candidate for treating TNBC.

  9. CASTING A BROAD NETWORK: FISHING FOR MECHANISMS OF RETINOID TERATOGENICITY

    Science.gov (United States)

    This is a short essay that serves to introduce a featured paper for an issue of Toxicological Sciences. The paper being introduced describes a study of mechanisms of retinoid induced abnormal limb development in mice. The paper was notable because the authors used gene expressi...

  10. Retinoids, race and the pathogenesis of dengue hemorrhagic fever.

    Science.gov (United States)

    Mawson, Anthony R

    2013-12-01

    Dengue hemorrhagic fever (DHF) is the most significant mosquito-borne viral disease worldwide in terms of illness, mortality and economic cost, but the pathogenesis of DHF is not well understood and there is no specific treatment or vaccine. Based on evidence of liver involvement, it is proposed that dengue virus and retinoids interact to cause cholestatic liver damage, resulting in the spillage of stored retinoids into the circulation and in an endogenous form of hypervitaminosisis A manifested by the signs and symptoms of the disease, including: fever, severe joint and bone pain, capillary leakage, thrombocytopenia, headache, and gastrointestinal symptoms. While retinoids in low concentration are essential for numerous biological functions, they are prooxidant, cytotoxic, mutagenic and teratogenic in higher concentration, especially when unbound to protein, and an endogenous form of vitamin A intoxication is recognized in cholestasis. The model tentatively explains the observations that 1) repeat infections are more severe than initial dengue virus infections; 2) the incidence of denue has increased dramatically worldwide in recent decades; 3) DHF is less prevalent in people of African ancestry than those of other racial backgrounds; and 4) infants are protected from dengue. The retinoid toxicity hypothesis of DHF predicts the co-existence of low serum concentrations of retinol coupled with high concentrations of retinoic acid and an increased percentage of retinyl esters to total vitamin A. Subject to such tests, it may be possible to treat DHF effectively using drugs that target the metabolism and expression of retinoids. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Retinoids in the treatment of glioma: a new perspective.

    Science.gov (United States)

    Mawson, Anthony R

    2012-01-01

    Primary brain tumors are among the top ten causes of cancer-related deaths in the US. Malignant gliomas account for approximately 70% of the 22,500 new cases of malignant primary brain tumors diagnosed in adults each year and are associated with high morbidity and mortality. Despite optimal treatment, the prognosis for patients with gliomas remains poor. The use of retinoids (vitamin A and its congeners) in the treatment of certain tumors was originally based on the assumption that these conditions were associated with an underlying deficiency of vitamin A and that supplementation with pharmacological doses would correct the deficiency. Yet the results of retinoid treatment have been only modestly beneficial and usually short-lived. Studies also indicate that vitamin A excess and supplementation have pro-oxidant effects and are associated with increased risks of mortality from cancer and other diseases. The therapeutic role of vitamin A in cancer thus remains uncertain and a new perspective on the facts is needed. The modest and temporary benefits of retinoid treatment could result from a process of feedback inhibition, whereby exogenous retinoid temporarily inhibits the endogenous synthesis of these compounds. In fact, repeated and/or excessive exposure of the tissues to endogenous retinoic acid may contribute to carcinogenesis. Gliomas, in particular, may result from an imbalance in retinoid receptor expression initiated by environmental factors that increase the endogenous production of retinoic acid in glia. At the receptor level, it is proposed that this imbalance is characterized by excessive expression of retinoic acid receptor-α (RARα) and reduced expression of retinoic acid receptor-β (RARβ). This suggests a potential new treatment strategy for gliomas, possibly even at a late stage of the disease, ie, to combine the use of a RARα antagonist and a RARβ agonist. According to this hypothesis, the RARα antagonist would be expected to inhibit RAR

  12. Retinoids in the treatment of glioma: a new perspective

    International Nuclear Information System (INIS)

    Mawson, Anthony R

    2012-01-01

    Primary brain tumors are among the top ten causes of cancer-related deaths in the US. Malignant gliomas account for approximately 70% of the 22,500 new cases of malignant primary brain tumors diagnosed in adults each year and are associated with high morbidity and mortality. Despite optimal treatment, the prognosis for patients with gliomas remains poor. The use of retinoids (vitamin A and its congeners) in the treatment of certain tumors was originally based on the assumption that these conditions were associated with an underlying deficiency of vitamin A and that supplementation with pharmacological doses would correct the deficiency. Yet the results of retinoid treatment have been only modestly beneficial and usually short-lived. Studies also indicate that vitamin A excess and supplementation have pro-oxidant effects and are associated with increased risks of mortality from cancer and other diseases. The therapeutic role of vitamin A in cancer thus remains uncertain and a new perspective on the facts is needed. The modest and temporary benefits of retinoid treatment could result from a process of feedback inhibition, whereby exogenous retinoid temporarily inhibits the endogenous synthesis of these compounds. In fact, repeated and/or excessive exposure of the tissues to endogenous retinoic acid may contribute to carcinogenesis. Gliomas, in particular, may result from an imbalance in retinoid receptor expression initiated by environmental factors that increase the endogenous production of retinoic acid in glia. At the receptor level, it is proposed that this imbalance is characterized by excessive expression of retinoic acid receptor-α (RARα) and reduced expression of retinoic acid receptor-β (RARβ). This suggests a potential new treatment strategy for gliomas, possibly even at a late stage of the disease, ie, to combine the use of a RARα antagonist and a RARβ agonist. According to this hypothesis, the RARα antagonist would be expected to inhibit RAR

  13. Acyclic retinoid in chemoprevention of hepatocellular carcinoma: Targeting phosphorylated retinoid X receptor-α for prevention of liver carcinogenesis

    Directory of Open Access Journals (Sweden)

    Masahito Shimizu

    2012-01-01

    Full Text Available One of the key features of hepatocellular carcinoma (HCC is the high rate of intrahepatic recurrence that correlates with poor prognosis. Therefore, in order to improve the clinical outcome for patients with HCC, development of a chemopreventive agent that can decrease or delay the incidence of recurrence is a critical issue for urgent investigation. Acyclic retinoid (ACR, a synthetic retinoid, successfully improves HCC patient survival by preventing recurrence and the formation of secondary tumors. A malfunction of the retinoid X receptor-α (RXRα due to phosphorylation by the Ras-MAPK signaling pathway plays a critical role in liver carcinogenesis, and ACR exerts chemopreventive effects on HCC development by inhibiting RXRα phosphorylation. Here, we review the relationship between retinoid signaling abnormalities and liver disease, the mechanisms of how RXRα phosphorylation contributes to liver carcinogenesis, and the detailed effects of ACR on preventing HCC development, especially based on the results of our basic and clinical research. We also outline the concept of "clonal deletion and inhibition" therapy, which is defined as the removal and inhibition of latent malignant clones from the liver before they expand into clinically detectable HCC, because ACR prevents the development of HCC by implementing this concept. Looking toward the future, we discuss "combination chemoprevention" using ACR as a key drug since it can generate a synergistic effect, and may thus be an effective new strategy for the prevention of HCC.

  14. Phenolic Fractions from Muscadine Grape "Noble" Pomace can Inhibit Breast Cancer Cell MDA-MB-231 Better than those from European Grape "Cabernet Sauvignon" and Induce S-Phase Arrest and Apoptosis.

    Science.gov (United States)

    Luo, Jianming; Wei, Zheng; Zhang, Shengyu; Peng, Xichun; Huang, Yu; Zhang, Yali; Lu, Jiang

    2017-05-01

    Tons of grape pomace which still contained a rich amount of plant polyphenols, is discarded after winemaking. Plant polyphenols have multi-functional activities for human body. In this study, polyphenols of pomaces from Muscadinia rotundifolia "Noble" and Vitis vinifera "Cabernet Sauvignon" were extracted and fractionated, and then they were analyzed with LC-MS and the inhibitory effects on breast cancer cells were compared. The inhibition on MDA-MB-231 cells of fractions from "Noble" was further evaluated. The results showed that polyphenols from 2 grape pomaces could be separated into 3 fractions, and ellagic acid and/or ellagitannins were only detected in fractions from "Noble" pomace. All 3 fractions from "Noble" pomace inhibited MDA-MB-231 better than MCF-7. But fraction 2 from "Cabernet Sauvignon" inhibited MCF-7 better while fraction 1 and fraction 3 inhibited both 2 cells similarly. Moreover, the fractions from "Noble" pomace rather than "Cabernet Sauvignon" can inhibit MDA-MB-231 better. Finally, fractions from "Noble" pomace can induce S-phase arrest and apoptosis on MDA-MB-231. These findings suggested the extracts from grape pomace especially those from "Noble," are potential to be utilized as health beneficial products or even anti-breast cancer agents. © 2017 Institute of Food Technologists®.

  15. RPF101, a new capsaicin-like analogue, disrupts the microtubule network accompanied by arrest in the G2/M phase, inducing apoptosis and mitotic catastrophe in the MCF-7 breast cancer cells

    International Nuclear Information System (INIS)

    Sá-Júnior, Paulo Luiz de; Pasqualoto, Kerly Fernanda Mesquita; Ferreira, Adilson Kleber; Tavares, Maurício Temotheo; Damião, Mariana Celestina Frojuello Costa Bernstorff; Azevedo, Ricardo Alexandre de; Câmara, Diana Aparecida Dias; Pereira, Alexandre; Madeiro de Souza, Dener; Parise Filho, Roberto

    2013-01-01

    Breast cancer is the world's leading cause of death among women. This situation imposes an urgent development of more selective and less toxic agents. The use of natural molecular fingerprints as sources for new bioactive chemical entities has proven to be a quite promising and efficient method. Capsaicin, which is the primary pungent compound in red peppers, was reported to selectively inhibit the growth of a variety tumor cell lines. Here, we report for the first time a novel synthetic capsaicin-like analogue, RPF101, which presents a high antitumor activity on MCF-7 cell line, inducing arrest of the cell cycle at the G2/M phase through a disruption of the microtubule network. Furthermore, it causes cellular morphologic changes characteristic of apoptosis and a decrease of Δψm. Molecular modeling studies corroborated the biological findings and suggested that RPF101, besides being a more reactive molecule towards its target, may also present a better pharmacokinetic profile than capsaicin. All these findings support the fact that RPF101 is a promising anticancer agent. -- Highlights: ► We report for the first time that RPF101 possesses anticancer properties. ► RPF101 induces apoptosis of human breast cancer cells. ► RPF 101 decreases mitochondrial potential and induces DNA fragmentation.

  16. Retinoid-binding proteins: similar protein architectures bind similar ligands via completely different ways.

    Directory of Open Access Journals (Sweden)

    Yu-Ru Zhang

    Full Text Available BACKGROUND: Retinoids are a class of compounds that are chemically related to vitamin A, which is an essential nutrient that plays a key role in vision, cell growth and differentiation. In vivo, retinoids must bind with specific proteins to perform their necessary functions. Plasma retinol-binding protein (RBP and epididymal retinoic acid binding protein (ERABP carry retinoids in bodily fluids, while cellular retinol-binding proteins (CRBPs and cellular retinoic acid-binding proteins (CRABPs carry retinoids within cells. Interestingly, although all of these transport proteins possess similar structures, the modes of binding for the different retinoid ligands with their carrier proteins are different. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we analyzed the various retinoid transport mechanisms using structure and sequence comparisons, binding site analyses and molecular dynamics simulations. Our results show that in the same family of proteins and subcellular location, the orientation of a retinoid molecule within a binding protein is same, whereas when different families of proteins are considered, the orientation of the bound retinoid is completely different. In addition, none of the amino acid residues involved in ligand binding is conserved between the transport proteins. However, for each specific binding protein, the amino acids involved in the ligand binding are conserved. The results of this study allow us to propose a possible transport model for retinoids. CONCLUSIONS/SIGNIFICANCE: Our results reveal the differences in the binding modes between the different retinoid-binding proteins.

  17. Retinoids in the treatment of glioma: a new perspective

    Directory of Open Access Journals (Sweden)

    Mawson AR

    2012-08-01

    Full Text Available Anthony R MawsonDepartment of Health Policy and Management, School of Health Sciences, College of Public Service, Jackson State University, Jackson, MS, USAAbstract: Primary brain tumors are among the top ten causes of cancer-related deaths in the US. Malignant gliomas account for approximately 70% of the 22,500 new cases of malignant primary brain tumors diagnosed in adults each year and are associated with high morbidity and mortality. Despite optimal treatment, the prognosis for patients with gliomas remains poor. The use of retinoids (vitamin A and its congeners in the treatment of certain tumors was originally based on the assumption that these conditions were associated with an underlying deficiency of vitamin A and that supplementation with pharmacological doses would correct the deficiency. Yet the results of retinoid treatment have been only modestly beneficial and usually short-lived. Studies also indicate that vitamin A excess and supplementation have pro-oxidant effects and are associated with increased risks of mortality from cancer and other diseases. The therapeutic role of vitamin A in cancer thus remains uncertain and a new perspective on the facts is needed. The modest and temporary benefits of retinoid treatment could result from a process of feedback inhibition, whereby exogenous retinoid temporarily inhibits the endogenous synthesis of these compounds. In fact, repeated and/or excessive exposure of the tissues to endogenous retinoic acid may contribute to carcinogenesis. Gliomas, in particular, may result from an imbalance in retinoid receptor expression initiated by environmental factors that increase the endogenous production of retinoic acid in glia. At the receptor level, it is proposed that this imbalance is characterized by excessive expression of retinoic acid receptor-α(RARα and reduced expression of retinoic acid receptor-β (RARβ. This suggests a potential new treatment strategy for gliomas, possibly even at a

  18. Cis-retinoids and the chemistry of vision.

    Science.gov (United States)

    Cascella, Michele; Bärfuss, Simon; Stocker, Achim

    2013-11-15

    We discuss here principal biochemical transformations of retinoid molecules in the visual cycle. We focus our analysis on the accumulating evidence of alternate pathways and functional redundancies in the cycle. The efficiency of the visual cycle depends, on one hand, on fast regeneration of the photo-bleached chromophores. On the other hand, it is crucial that the cyclic process should be highly selective to avoid accumulation of byproducts. The state-of-the-art knowledge indicates that single enzymatically active components of the cycle are not strictly selective and may require chaperones to enhance their rates. It appears that protein-protein interactions significantly improve the biological stability of the visual cycle. In particular, synthesis of thermodynamically less stable 11-cis-retinoid conformers is favored by physical interactions of the isomerases present in the retina with cellular retinaldehyde binding protein. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Potential role of retinoids in ovarian physiology and pathogenesis of polycystic ovary syndrome.

    Science.gov (United States)

    Jiang, Yanwen; Li, Chunjin; Chen, Lu; Wang, Fengge; Zhou, Xu

    2017-06-01

    Retinoids (retinol and its derivatives) are required for maintaining vision, immunity, barrier function, reproduction, embryogenesis, cell proliferation and differentiation. Furthermore, retinoid signaling plays a key role in initiating meiosis of germ cells of the mammalian fetal ovary. Recently, studies indicated that precise retinoid level regulation in the ovary provides a molecular control of ovarian development, steroidogenesis and oocyte maturation. Besides, abnormal retinoid signaling may be involved in the pathogenesis of polycystic ovary syndrome (PCOS), one of the most common ovarian endocrinopathies in reproductive-aged women worldwide. This review primarily summarizes recent advancements made in investigating the action of retinoid signaling in ovarian physiology as well as the abnormal retinoid signaling in PCOS. Copyright © 2017. Published by Elsevier B.V.

  20. Effects of retinoids on ultraviolet-induced carcinogenesis

    International Nuclear Information System (INIS)

    Epstein, J.H.

    1981-01-01

    The evidence for effects of the retinoids on UV-induced carcinogenesis is sparse. Clinical observations indicate that topical RA can cause significant regression of premalignant actinic keratoses. Also there is some evidence that this agent can cause dissolution of some basal cell epitheliomas. However this latter effect does not appear to be of therapeutic value. Systemic retinoids are of little value in the treatment of premalignant and malignant cutaneous lesions though 13-cis-retinoic acid might be of use in the basal cell nevus syndrome. Examination of the influence of the retinoids on photocarcinogenesis essentially has been confined to RA and animal experimentation. RA in nontoxic concentrations can both stimulate and inhibit photocarcinogenesis depending upon the circumstances of the study. The mechanisms of these responses are not clear. Influences on DNA synthesis directly and/or indirectly or on immune responses may be involved in both effects. Preliminary studies with oral 13-cis-retinoic acid have not demonstrated any effects to date on UV-induced skin cancer formation

  1. Metformin Induces Apoptosis and Cell Cycle Arrest Mediated by Oxidative Stress, AMPK and FOXO3a in MCF-7 Breast Cancer Cells

    Science.gov (United States)

    Queiroz, Eveline A. I. F.; Puukila, Stephanie; Eichler, Rosangela; Sampaio, Sandra C.; Forsyth, Heidi L.; Lees, Simon J.; Barbosa, Aneli M.; Dekker, Robert F. H.; Fortes, Zuleica B.; Khaper, Neelam

    2014-01-01

    Recent studies have demonstrated that the anti-diabetic drug, metformin, can exhibit direct antitumoral effects, or can indirectly decrease tumor proliferation by improving insulin sensitivity. Despite these recent advances, the underlying molecular mechanisms involved in decreasing tumor formation are not well understood. In this study, we examined the antiproliferative role and mechanism of action of metformin in MCF-7 cancer cells treated with 10 mM of metformin for 24, 48, and 72 hours. Using BrdU and the MTT assay, it was found that metformin demonstrated an antiproliferative effect in MCF-7 cells that occurred in a time- and concentration- dependent manner. Flow cytometry was used to analyze markers of cell cycle, apoptosis, necrosis and oxidative stress. Exposure to metformin induced cell cycle arrest in G0-G1 phase and increased cell apoptosis and necrosis, which were associated with increased oxidative stress. Gene and protein expression were determined in MCF-7 cells by real time RT-PCR and western blotting, respectively. In MCF-7 cells metformin decreased the activation of IRβ, Akt and ERK1/2, increased p-AMPK, FOXO3a, p27, Bax and cleaved caspase-3, and decreased phosphorylation of p70S6K and Bcl-2 protein expression. Co-treatment with metformin and H2O2 increased oxidative stress which was associated with reduced cell number. In the presence of metformin, treating with SOD and catalase improved cell viability. Treatment with metformin resulted in an increase in p-p38 MAPK, catalase, MnSOD and Cu/Zn SOD protein expression. These results show that metformin has an antiproliferative effect associated with cell cycle arrest and apoptosis, which is mediated by oxidative stress, as well as AMPK and FOXO3a activation. Our study further reinforces the potential benefit of metformin in cancer treatment and provides novel mechanistic insight into its antiproliferative role. PMID:24858012

  2. The Dietary Flavonoid Fisetin Causes Cell Cycle Arrest, Caspase-Dependent Apoptosis, and Enhanced Cytotoxicity of Chemotherapeutic Drugs in Triple-Negative Breast Cancer Cells.

    Science.gov (United States)

    Smith, Matthew L; Murphy, Kaylee; Doucette, Carolyn D; Greenshields, Anna L; Hoskin, David W

    2016-08-01

    Fisetin (3,3',4',7-tetrahydroxyflavone), a flavonoid found in a number of fruits and vegetables, has diverse biological activities, including cytotoxic effects on cancer cells. In this study, we investigated the effect of fisetin on triple-negative breast cancer (TNBC) cells. TNBC has a poorer prognosis than other types of breast cancer and treatment options for this disease are limited. Fisetin inhibited the growth of MDA-MB-468 and MDA-MB-231 TNBC cells, as well as their ability to form colonies, without substantially affecting the growth of non-malignant cells. In addition, fisetin inhibited the growth of estrogen receptor-bearing MCF-7 breast cancer cells and human epidermal growth factor receptor 2-overexpressing SK-BR-3 breast cancer cells. Fisetin inhibited TNBC cell division and induced apoptosis, which was associated with mitochondrial membrane permeabilization and the activation of caspase-9 and caspase-8, as well as the cleavage of poly(ADP-ribose) polymerase-1. Induction of caspase-dependent apoptosis by fisetin was confirmed by reduced killing of TNBC cells in the presence of the pan-caspase inhibitors Z-VAD-FMK and BOC-D-FMK. Decreased phosphorylation of histone H3 at serine 10 in fisetin-treated TNBC cells at G2/M phase of the cell cycle suggested that fisetin-induced apoptosis was the result of Aurora B kinase inhibition. Interestingly, the cytotoxic effect of cisplatin, 5-fluorouracil, and 4-hydroxycyclophosphamide metabolite of cyclophosphamide on TNBC cells was increased in the presence of fisetin. These findings suggest that further investigation of fisetin is warranted for possible use in the management of TNBC. J. Cell. Biochem. 117: 1913-1925, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. Cytotoxicity and cell cycle arrest induced by andrographolide lead to programmed cell death of MDA-MB-231 breast cancer cell line.

    Science.gov (United States)

    Banerjee, Malabika; Chattopadhyay, Subrata; Choudhuri, Tathagata; Bera, Rammohan; Kumar, Sanjay; Chakraborty, Biswajit; Mukherjee, Samir Kumar

    2016-04-16

    Breast cancer is considered as an increasing major life-threatening concern among the malignancies encountered globally in females. Traditional therapy is far from satisfactory due to drug resistance and various side effects, thus a search for complementary/alternative medicines from natural sources with lesser side effects is being emphasized. Andrographis paniculata, an oriental, traditional medicinal herb commonly available in Asian countries, has a long history of treating a variety of diseases, such as respiratory infection, fever, bacterial dysentery, diarrhea, inflammation etc. Extracts of this plant showed a wide spectrum of therapeutic effects, such as anti-bacterial, anti-malarial, anti-viral and anti-carcinogenic properties. Andrographolide, a diterpenoid lactone, is the major active component of this plant. This study reports on andrographolide induced apoptosis and its possible mechanism in highly proliferative, invasive breast cancer cells, MDA-MB-231 lacking a functional p53 and estrogen receptor (ER). Furthermore, the pharmacokinetic properties of andrographolide have also been studied in mice following intravenous and oral administration. Andrographolide showed a time- and concentration- dependent inhibitory effect on MDA-MB-231 breast cancer cell proliferation, but the treatment did not affect normal breast epithelial cells, MCF-10A (>80 %). The number of cells in S as well as G2/M phase was increased after 36 h of treatment. Elevated reactive oxygen species (ROS) production with concomitant decrease in Mitochondrial Membrane Potential (MMP) and externalization of phosphatidyl serine were observed. Flow cytometry with Annexin V revealed that the population of apoptotic cells increased with prolonged exposure to andrographolide. Activation of caspase-3 and caspase-9 were also noted. Bax and Apaf-1 expression were notably increased with decreased Bcl-2 and Bcl-xL expression in andrographolide-treated cells. Pharmacokinetic study with andrographolide

  4. Development of 68Ga-SCN-DOTA-Capsaicin as an Imaging Agent Targeting Apoptosis and Cell Cycle Arrest in Breast Cancer.

    Science.gov (United States)

    Lee, Jun Young; Lee, Sang-Yeun; Kim, Gun Gyun; Hur, Min Goo; Yang, Seung Dae; Park, Jeong-Hoon; Kim, Sang Wook

    2017-06-01

    68 Ga-labeled capsaicin using a DOTA (1,4,7,10-tetraazocyclododecane-N,N',N″,N'″-tetraacetic acid) derivative [ 68 Ga-SCN-Benzyl(Bn)-DOTA-capsaicin] was studied for the diagnosis of breast cancers, such as MCF-7 and SK-BR-3. The standard compound, 69 Ga-SCN-Bn-DOTA-capsaicin, was also prepared and characterized by spectroscopic analysis. The binding affinity of 68 Ga-SCN-Bn-DOTA-capsaicin was evaluated by using breast cancer cell lines (MCF-7, SK-BR-3) and colon cancer cell (CT-26); the biodistribution was carried out by using MCF-7-bearing nude mice, after which the positron emission tomography (PET) images were obtained at different time intervals (15-120 minutes). 68 Ga-SCN-Bn-DOTA-capsaicin showed a cellular uptake of 0.93% Injected Dose (ID) after 30 minutes of incubation, whereas 68 Ga-SCN-Bn-DOTA showed a lower uptake of 0.25% ID. The tumor-to-blood ID/g% ratios increased and were found to be 0.49, 0.22, and 0.77 for 15, 30, and 60 minutes, respectively. The small-animal PET study showed that the uptake of 68 Ga-SCN-Bn-DOTA-capsaicin was higher in the tumor regions even at 30 minutes after injection. These results suggest that 68 Ga-SCN-Bn-DOTA-capsaicin is a potential targeting agent for PET imaging of MCF-7.

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

    Directory of Open Access Journals (Sweden)

    Marisa Halpern

    2007-06-01

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

  6. Abnormal retinoid and TrkB signaling in the prefrontal cortex in mood disorders

    NARCIS (Netherlands)

    Qi, Xin-Rui; Zhao, Juan; Liu, Ji; Fang, Hui; Swaab, Dick F; Zhou, Jiang-Ning

    The prefrontal cortex shows structural and functional alterations in mood disorders. Retinoid signaling, brain-derived neurotrophic factor (BDNF), and its receptor TrkB are reported to be involved in depression. Here, we found that mRNA levels of key elements of retinoid signaling were significantly

  7. The neurobehavioral teratology of retinoids: a 50-year history.

    Science.gov (United States)

    Adams, Jane

    2010-10-01

    This review of the central nervous system (CNS) and behavioral teratology of the retinoids over the last 50 years is a commemorative retrospective organized by decade to show the prominent research focus within each period and the most salient findings. In the 1960s, research focused on the gross CNS malformations associated with exposure and the delineation of dose-response and stage-specific responses in rodent models. Relevant scientific events before and during the 1960s are also discussed to provide the zeitgeist in which the field of neurobehavioral teratology emerged in the 1970s. During this period, studies demonstrated that adverse effects on postnatal behavior could be produced in animals exposed to doses of vitamin A lower than those that were teratogenic or impacted growth. Work during the 1980s showed an overrepresentation of behavioral studies focused on the reliability of screening methods, while the marked effects of human exposure were illustrated in children born to women treated with isotretinoin during pregnancy. The human catastrophe invigorated research during the 1990s, a period when technological advances allowed more elegant examinations of the developing CNS, of biochemical, cellular, and molecular developmental events and regulatory actions, and of the effects of direct genetic manipulations. Likewise, research in the 1990s reflected a reinvigoration of research in neurobehavioral teratology evinced in studies that used animal models to try to better understand human vulnerability. These foci continued in the 2000-2010 period while examinations of the role of retinoids in brain development and lifelong functioning became increasingly sophisticated and broader in scope. This review of the work on retinoids also provides a lens on the more general ontogeny of the field of neurobehavioral teratology. Birth Defects Research (Part A), 2010. © 2010 Wiley-Liss, Inc.

  8. Breast

    International Nuclear Information System (INIS)

    Ribeiro, G.G.

    1985-01-01

    The treatment of malignant disease of the breast arouses more controversy and emotion than that of any other form of malignant disease. Many clinical trials have been carried out and others are still in progress. In addition, research work continues in regard to other aspects of the disease, such as epidemiology, population screening, and endocrine factors; yet little is really known about the true biological nature of carcinoma of the breast. A vast amount of literature has accumulated on the treatment of ''operable'' carcinoma of the breast, but it is not proposed to discuss here the merits or demerits of the various suggested treatments. Instead this chapter will be confined to the practical management of carcinoma of the breast as seen from the point of view of radiotherapist. For this reason greater attention will be paid to the radiotherapy techniques as practised at the Christie Hospital

  9. Synergistic Effects of PPARγ Ligands and Retinoids in Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Masahito Shimizu

    2008-01-01

    Full Text Available Peroxisome proliferator-activated receptors (PPARs are members of the nuclear receptor superfamily. The activation of PPARs by their specific ligands is regarded as one of the promising strategies to inhibit cancer cell growth. However, recent clinical trials targeting several common cancers showed no beneficial effect when PPAR ligands are used as a monotherapy. Retinoid X receptors (RXRs, which play a critical role in normal cell proliferation as a master regulator for nuclear receptors, preferentially form heterodimers with PPARs. A malfunction of RXRα due to phosphorylation by the Ras/MAPK signaling pathway is associated with the development of certain types of human malignancies. The activation of PPARγ/RXR heterodimer by their respective ligands synergistically inhibits cell growth, while inducing apoptosis in human colon cancer cells when the phosphorylation of RXRα was inhibited. We herein review the synergistic antitumor effects produced by the combination of the PPAR, especially PPARγ, ligands plus other agents, especially retinoids, in a variety of human cancers. We also focus on the phosphorylation of RXRα because the inhibition of RXRα phosphorylation and the restoration of its physiological function may activate PPAR/RXR heterodimer and, therefore, be a potentially effective and critical strategy for the inhibition of cancer cell growth.

  10. RETINOID RECEPTORS IN BONE AND THEIR ROLE IN BONE REMODELING

    Directory of Open Access Journals (Sweden)

    Petra eHenning

    2015-03-01

    Full Text Available Vitamin A (retinol is a necessary and important constituent of the body which is provided by food intake of retinyl esters and carotenoids. Vitamin A is known best for being important for vision, but in addition to the eye, vitamin A is necessary in numerous other organs in the body, including the skeleton. Vitamin A is converted to an active compound, all-trans-retinoic acid (ATRA, which is responsible for most of its biological actions. ATRA binds to intracellular nuclear receptors called retinoic acid receptors (RAR, RAR, RAR. RARs and closely related retinoid X receptors (RXR, RXR, RXR form heterodimers which bind to DNA and function as ligand activated transcription factors. It has been known for many years that hypervitaminosis A promotes skeleton fragility by increasing osteoclast formation and decreasing cortical bone mass. Some epidemiological studies have suggested that increased intake of vitamin A and increased serum levels of retinoids may decrease bone mineral density and increase fracture rate, but the literature on this is not conclusive. The current review summarizes how vitamin A is taken up by the intestine, metabolized, stored in the liver and processed to ATRA. ATRA’s effects on formation and activity of osteoclasts and osteoblasts are outlined, and a summary of clinical data pertaining to vitamin A and bone is presented.

  11. Pittsburgh Police Arrest Data

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — Arrest data contains information on people taken into custody by City of Pittsburgh police officers. More serious crimes such as felony offenses are more likely to...

  12. Uptake and processing of [3H]retinoids in rat liver studied by electron microscopic autoradiography

    International Nuclear Information System (INIS)

    Hendriks, H.F.; Elhanany, E.; Brouwer, A.; de Leeuw, A.M.; Knook, D.L.

    1988-01-01

    The role of rat liver cell organelles in retinoid uptake and processing was studied by electron microscopic autoradiography. [ 3 H]Retinoids were administered either orally, to make an inventory of the cell organelles involved, or intravenously as chylomicron remnant constituents to study retinoid processing by the liver with time. No qualitative differences were observed between the two routes of administration. Time-related changes in the distribution of grains were studied using chylomicron remnant [ 3 H]retinoids. The percentages of grains observed over cells and the space of Disse at 5 and 30 min after administration were, respectively: parenchymal cells, 72.6 and 70.4%; fat-storing cells, 5.0 and 18.1%, and the space of Disse, 14.4 and 8.9%. Low numbers of grains were observed over endothelial and Kupffer cells. The percentages of grains observed over parenchymal cell organelles were, respectively: sinusoidal area, 59.6 and 34.4%; smooth endoplasmic reticulum associated with glycogen, 13.8 and 13.4%; mitochondria, 5.4 and 13.6%; rough endoplasmic reticulum, 4.2 and 7.3%, and rough endoplasmic reticulum associated with mitochondria, 3.7 and 6.5%. It is concluded that chylomicron remnant [ 3 H]retinoids in combination with electron microscopic autoradiography provide a good system to study the liver processing of retinoids in vivo. These results, obtained in the intact liver under physiological conditions, further substantiate that retinoids are processed through parenchymal cells before storage occurs in fat-storing cell lipid droplets, that retinoid uptake is not mediated through lysosomes and that the endoplasmic reticulum is a major organelle in retinoid processing

  13. Retinoid Expression in Onchocercal Skin Disease: Pilot Study.

    Science.gov (United States)

    Mawson, Anthony R; Makunde, Williams H; Penman, Alan D; Hernandez Morales, Veronica de Los Angeles; Kalinga, Akili K; Francis, Filbert; Rubinchik, Semyon; Kibweja, Addow

    2017-01-01

    Based on the observation that the parasite Onchocerca volvulus selectively absorbs vitamin A from the host, and the known toxicity of vitamin A in higher concentration, it was hypothesized that dying microfilariae (mf) release their stores of vitamin A (retinoids) into the host circulation in toxic concentrations, inducing the signs and symptoms of onchocerciasis. We conducted a pilot study to test the hypothesis in Songea communities in Southern Tanzania, where mass drug administration with ivermectin had not been implemented by the time of the survey. The specific aim was to evaluate the correlation between the diagnosis of onchocerciasis and increased levels of retinoic acid at infection sites. The analysis was performed by determining copy numbers of a genome of O volvulus present in skin snip samples of persons with onchocerciacis, and correlating these numbers with expression levels of retinoic acid receptor-α (RAR-α), which is inducible by retinoic acid. Total DNA and RNA were extracted from each of 25 mf-positive and 25 mf-negative skin samples and evaluated using quantitative polymerase chain reaction with appropriate negative controls. Analysis of the samples, adjusted with glyceraldehyde 3-phosphate dehydrogenase gene levels, revealed that most samples with detectable RAR-α transcripts had higher levels of RAR-α expression than the assay control. However, the quality and number of samples were insufficient for statistical analysis. Fold data on the expression levels of both O volvulus DNA and RAR RNA suggested a possible trend toward higher relative RAR-α expression in samples with higher levels of O volvulus DNA ( r 2  = 0.25, P  = .079). Evidence of a contribution of vitamin A to the pathology of onchocerciasis thus remains elusive. Future studies on the role of retinoids in onchocerciasis will require larger groups of participants as well as careful monitoring of the cold chain and tissue storage procedures in view of the sensitivity of

  14. Carotenoids and retinoids in Finnish foods: dairy products and eggs.

    Science.gov (United States)

    Ollilainen, V; Heinonen, M; Linkola, E; Varo, P; Koivistoinen, P

    1989-09-01

    As part of an overall composition study of Finnish foods, the carotenoid and retinoid content of 20 dairy product samples and eggs were determined by HPLC. The total beta-carotene (all-trans beta-carotene plus 15-cis beta-carotene) was quantitated for dairy products. For egg and egg yolk, lutein content was also determined. Only traces of lycopene, cryptoxanthin, and alpha-carotene were present. All-trans retinol and 13-cis retinol were the major retinoids in dairy products. Small amounts of 9-cis, 11-cis, and 9,11-cis retinols were found. High values of both retinol and beta-carotene were found in full fat cheeses and whipping cream: from 179.0 (cheese, Edam-type) to 318.7 micrograms/100 g (whipping cream) and from 86.7 (cheese, Edam-type) to 186.5 micrograms/100 g (whipping cream) for all-trans retinol and total beta-carotene, respectively. The retinol content averaged 16.3, 32.6, and 52.2 and that of beta-carotene 9.6, 16.7, and 3.0 micrograms/100 g in milk (1.9% fat), milk (3.9% fat), and human milk, respectively. The major pigment in eggs and egg yolk was lutein, 619.5 micrograms/100 g in eggs and 1575.8 micrograms/100 g in egg yolk. According to this study, at the present level of consumption in Finland, milk, milk products (excluding butter), and eggs result in a daily intake of about 350 retinol equivalents, and consequently, are a major source of vitamin A.

  15. Dose-dependent pharmacokinetics and teratogenic activity of topical retinoids

    International Nuclear Information System (INIS)

    Sharma, R.P.; Willhite, C.C.; Berry, D.L.; Allen, P.V.

    1990-01-01

    Oral retinoid treatment can be teratogenic and topical applications are used to treat acne and smooth wrinkles. A single topical trace (2.5 μg; 191 μCi/kg) or high (1.3 mg; 195 μCi/kg) dose of all-trans-[10, 11- 3 H 2 ] retinoic acid (RA) dissolved in acetone was applied to 4 cm 2 shaved dorsal hamster skin. Peak plasma radioactivity (C max ) occurred at 12 and 36 hr and mean t1/2 values for parent PA absorption were 48 min and 2.8 hr, for trace and high dose, respectively. The dermal RA C max values were only 2% of that after an equivalent oral dose, but plasma AUC after dermal treatment was 63% of the oral value. The mean t1/2 for rapid elimination was shorter for the high (57 min) than for the trace (6.9 hr) dose, but t1/2 values for slow elimination were comparable (t1/2 high = 51.2 hr; t1/2 trace = 36.8 hr). Single topical application of 10-30 mg/kg RA or 5 mg/kg etretinate (Ro 10-9359) to pregnant hamsters (day 8) caused local hyperkeratosis, but failed to induce terata. Similar application of 10-1000 μg/kg arotinoid Ro 13-6298 caused dose-dependent terata, being twice as embryolethal by parenteral as enteric dosing. Skin toxicity and attenuated maternal blood levels limit the amount of retinoids that can reach the embryo

  16. Retinoid inhibition of in vitro invasion of human amnion basement membrane by human tumor cells

    International Nuclear Information System (INIS)

    Fazely, F.; Ledinko, N.; Smith, D.J.

    1986-01-01

    The biological activity of retinoids was assayed in an in vitro quantitative assay of human tumor cell invasion using human amnion basement membrane (BM). The effects measured were the inhibition of tumor cell migration through the BM and tumor cell degradative enzyme activity on 14 C-proline labeled collagenous and noncollagenous components of the BM. The human lung carcinoma A549 or the human Ewing's sarcoma TC-106 cell lines treated with retinoids for two days were incubated on the BM in the absence of retinoids. A dose-dependent inhibition of cell invasion was produced by retinoids. Among the retinoids tested, the most powerful was retinol acetate which inhibited invasion by 50% of A549 cells at a concentration of 0.009 μg/mL, and of TC-106 cells at 0.07 μg/mL. Retinol acetate inhibited A549 and TC-106 cell growth by approximately 50% at levels over 100-fold higher than those needed for antiinvasive activity. Retinol acetate was about 20 times more potent than retinoic acid and 30 times more potent than retinol palmitate. The model system will be useful for investigating antiinvasive activity of other retinoids as well as other compounds

  17. Runway Arrested Landing Site (RALS)

    Data.gov (United States)

    Federal Laboratory Consortium — The Runway Arrested Landing Site includes an underground complex located on a Mod 2, Mod 3, and Mod 3+ arresting gear and are located under the runway and accurately...

  18. Retinoid production using metabolically engineered Escherichia coli with a two-phase culture system.

    Science.gov (United States)

    Jang, Hui-Jeong; Yoon, Sang-Hwal; Ryu, Hee-Kyung; Kim, Jung-Hun; Wang, Chong-Long; Kim, Jae-Yean; Oh, Deok-Kun; Kim, Seon-Won

    2011-07-29

    Retinoids are lipophilic isoprenoids composed of a cyclic group and a linear chain with a hydrophilic end group. These compounds include retinol, retinal, retinoic acid, retinyl esters, and various derivatives of these structures. Retinoids are used as cosmetic agents and effective pharmaceuticals for skin diseases. Retinal, an immediate precursor of retinoids, is derived by β-carotene 15,15'-mono(di)oxygenase (BCM(D)O) from β-carotene, which is synthesized from the isoprenoid building blocks isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Retinoids are chemically unstable and biologically degraded via retinoic acid. Although extensive studies have been performed on the microbial production of carotenoids, retinoid production using microbial metabolic engineering has not been reported. Here, we report retinoid production using engineered Escherichia coli that express exogenous BCM(D)O and the mevalonate (MVA) pathway for the building blocks synthesis in combination with a two-phase culture system using a dodecane overlay. Among the BCM(D)O tested in E. coli, the synthetic retinoid synthesis protein (SR), based on bacteriorhodopsin-related protein-like homolog (Blh) of the uncultured marine bacteria 66A03, showed the highest β-carotene cleavage activity with no residual intracellular β-carotene. By introducing the exogenous MVA pathway, 8.7 mg/L of retinal was produced, which is 4-fold higher production than that of augmenting the MEP pathway (dxs overexpression). There was a large gap between retinal production and β-carotene consumption using the exogenous MVA pathway; therefore, the retinal derivatives were analyzed. The derivatives, except for retinoic acid, that formed were identified, and the levels of retinal, retinol, and retinyl acetate were measured. Amounts as high as 95 mg/L retinoids were obtained from engineered E. coli DH5α harboring the synthetic SR gene and the exogenous MVA pathway in addition to dxs overexpression, which

  19. Evolution of Retinoid and Steroid Signaling: Vertebrate Diversification from an Amphioxus Perspective

    Science.gov (United States)

    Albalat, Ricard; Brunet, Frédéric; Laudet, Vincent; Schubert, Michael

    2011-01-01

    Although the physiological relevance of retinoids and steroids in vertebrates is very well established, the origin and evolution of the genetic machineries implicated in their metabolic pathways is still very poorly understood. We investigated the evolution of these genetic networks by conducting an exhaustive survey of components of the retinoid and steroid pathways in the genome of the invertebrate chordate amphioxus (Branchiostoma floridae). Due to its phylogenetic position at the base of chordates, amphioxus is a very useful model to identify and study chordate versus vertebrate innovations, both on a morphological and a genomic level. We have characterized more than 220 amphioxus genes evolutionarily related to vertebrate components of the retinoid and steroid pathways and found that, globally, amphioxus has orthologs of most of the vertebrate components of these two pathways, with some very important exceptions. For example, we failed to identify a vertebrate-like machinery for retinoid storage, transport, and delivery in amphioxus and were also unable to characterize components of the adrenal steroid pathway in this invertebrate chordate. The absence of these genes from the amphioxus genome suggests that both an elaboration and a refinement of the retinoid and steroid pathways took place at the base of the vertebrate lineage. In stark contrast, we also identified massive amplifications in some amphioxus gene families, most extensively in the short-chain dehydrogenase/reductase superfamily, which, based on phylogenetic and genomic linkage analyses, were likely the result of duplications specific to the amphioxus lineage. In sum, this detailed characterization of genes implicated in retinoid and steroid signaling in amphioxus allows us not only to reconstruct an outline of these pathways in the ancestral chordate but also to discuss functional innovations in retinoid homeostasis and steroid-dependent regulation in both cephalochordate and vertebrate evolution

  20. Bovine cumulus-granulosa cells contain biologically active retinoid receptors that can respond to retinoic acid

    Directory of Open Access Journals (Sweden)

    Malayer Jerry

    2003-11-01

    Full Text Available Abstract Retinoids, a class of compounds that include retinol and its metabolite, retinoic acid, are absolutely essential for ovarian steroid production, oocyte maturation, and early embryogenesis. Previous studies have detected high concentrations of retinol in bovine large follicles. Further, administration of retinol in vivo and supplementation of retinoic acid during in vitro maturation results in enhanced embryonic development. In the present study, we hypothesized that retinoids administered either in vivo previously or in vitro can exert receptor-mediated effects in cumulus-granulosa cells. Total RNA extracted from in vitro cultured cumulus-granulosa cells was subjected to reverse transcription polymerase chain reaction (RT-PCR and mRNA expression for retinol binding protein (RBP, retinoic acid receptor alpha (RARalpha, retinoic acid receptor beta (RARbeta, retinoic acid receptor gamma (RARgamma, retinoid X receptor alpha (RXRalpha, retinoid X receptor beta (RXRbeta, retinaldehyde dehydrogenase-2 (RALDH-2, and peroxisome proliferator activated receptor gamma (PPARgamma. Transcripts were detected for RBP, RARalpha, RARgamma, RXRalpha, RXRbeta, RALDH-2, and PPARgamma. Expression of RARbeta was not detected in cumulus-granulosa cells. Using western blotting, immunoreactive RARalpha, and RXRbeta protein was also detected in bovine cumulus-granulosa cells. The biological activity of these endogenous retinoid receptors was tested using a transient reporter assay using the pAAV-MCS-betaRARE-Luc vector. Addition of 0.5 and 1 micro molar all-trans retinoic acid significantly (P trans retinol stimulated a mild increase in reporter activity, however, the increase was not statistically significant. Based on these results we conclude that cumulus cells contain endogenously active retinoid receptors and may also be competent to synthesize retinoic acid using the precursor, retinol. These results also indirectly provide evidence that retinoids

  1. Disposition and biotransformation of the acetylenic retinoid tazarotene in humans.

    Science.gov (United States)

    Attar, Mayssa; Yu, Dale; Ni, Jinsong; Yu, Zhiling; Ling, Kah-Hiing John; Tang-Liu, Diane D-S

    2005-10-01

    Oral tazarotene, an acetylenic retinoid, is in clinical development for the treatment of psoriasis. The disposition and biotransformation of tazarotene were investigated in six healthy male volunteers, following a single oral administration of a 6 mg (100 microCi) dose of [14C]tazarotene, in a gelatin capsule. Blood levels of radioactivity peaked 2 h postdose and then rapidly declined. Total recovery of radioactivity was 89.2+/-8.0% of the administered dose, with 26.1+/-4.2% in urine and 63.0+/-7.0% in feces, within 7 days of dosing. Only tazarotenic acid, the principle active metabolite formed via esterase hydrolysis of tazarotene, was detected in blood. One major urinary oxidative metabolite, tazarotenic acid sulfoxide, accounted for 19.2+/-3.0% of the dose. The majority of radioactivity recovered in the feces was attributed to tazarotenic acid representing 46.9+/-9.9% of the dose and only 5.82+/-3.84% of dose was excreted as unchanged tazarotene. Thus following oral administration, tazarotene was rapidly absorbed and underwent extensive hydrolysis to tazarotenic acid, the major circulating species in the blood that was then excreted unchanged in feces. A smaller fraction of tazarotenic acid was further metabolized to an inactive sulfoxide that was excreted in the urine. Copyright (c) 2005 Wiley-Liss, Inc. and the American Pharmacists Association

  2. Exploring (novel) gene expression during retinoid-induced maturation and cell death of acute promyelocytic leukemia.

    Science.gov (United States)

    Benoit, G R; Tong, J H; Balajthy, Z; Lanotte, M

    2001-01-01

    During recent years, reports have shown that biological responses of acute promyelocytic leukemia (APL) cells to retinoids are more complex than initially envisioned. PML-RARalpha chimeric protein disturbs various biological processes such as cell proliferation, differentiation, and apoptosis. The distinct biological programs that regulate these processes stem from specific transcriptional activation of distinct (but overlapping) sets of genes. These programs are sometimes mutually exclusive and depend on whether the signals are delivered by RAR or RXR agonists. Furthermore, evidence that retinoid nuclear signaling by retinoid, on its own, is not enough to trigger these cellular responses is rapidly accumulating. Indeed, work with NB4 cells show that the fate of APL cells treated by retinoid depends on complex signaling cross-talk. Elucidation of the sequence of events and cascades of transcriptional regulation necessary for APL cell maturation will be an additional tool with which to further improve therapy by retinoids. In this task, the classical techniques used to analyze gene expression have proved time consuming, and their yield has been limited. Global analyses of the APL cell transcriptome are needed. We review the technical approaches currently available (differential display, complementary DNA microarrays), to identify novel genes involved in the determination of cell fate.

  3. A possible contribution of retinoids to regulation of fetal B lymphopoiesis.

    Science.gov (United States)

    Chen, Xinrong; Welner, Robert S; Kincade, Paul W

    2009-09-01

    We recently found that all trans retinoic acid (ATRA) accelerated B lymphocyte formation. In the current study, we address the question whether retinoids account for the rapid lymphopoiesis that is characteristic of fetal progenitors. Surprisingly, addition of ATRA to fetal liver cultures actually reduced B lymphopoiesis. A pan-retinoid receptor antagonist selectively suppressed lymphocyte formation from fetal and adult progenitors, suggesting some normal contribution of retinoids to this process. Consistent with this role, B lymphopoiesis was compromised in the marrow of mice with prolonged vitamin A deficiency. Recently identified B1 progenitors from adult marrow were similar to adult B2 progenitors in that their differentiation was stimulated by ATRA. The inhibitory response observed with fetal cells was seen when adult progenitors were exposed to high doses in culture or when adult mice were treated with ATRA for 2 wk. In addition to explosive lymphocyte generation, fetal progenitors tend to be less IL-7 dependent than their adult counterparts, but ATRA did not make fetal progenitors IL-7 independent. We conclude that all known categories of B lineage progenitors are responsive to retinoids and probably regulated by these compounds under physiological conditions. Retinoids may account in part for rapid differentiation in fetal life, but not all unique features of fetal progenitors.

  4. Changes in the skeleton after long-term treatment with retinoids

    Energy Technology Data Exchange (ETDEWEB)

    Montag, M.; Reiser, M.; Hamm, H.; Traupe, H.; Vogt, H.J.

    1988-07-01

    The synthetic retinoids, the vitamin-A-derivatives ethretinate and isotretinoin, have substantially enlarged the therapeutic arsenal in dermatology. They are primarily used in severe cases of acne and cornification disorders. In the majority of cases, long-term treatment is necessary. Certain side effects in the skeletal system can occur, e.g., osteoporosis, premature epiphyseal closure, and changes similar to DISH (diffuse idiopathic skeletal hyperostosis). We discuss the reports in the literature and our own observations in 31 patients treated at the Westphalian Wilhelms University in Muenster, as well as at the Technical University in Munich. In 3 out of 31 patients treated by retinoids on a long-term basis, skeletal changes were found radiologically as a result of the retinoid medication.

  5. Identifying the receptor subtype selectivity of retinoid X and retinoic acid receptors via quantum mechanics.

    Science.gov (United States)

    Tsuji, Motonori; Shudo, Koichi; Kagechika, Hiroyuki

    2017-03-01

    Understanding and identifying the receptor subtype selectivity of a ligand is an important issue in the field of drug discovery. Using a combination of classical molecular mechanics and quantum mechanical calculations, this report assesses the receptor subtype selectivity for the human retinoid X receptor (hRXR) and retinoic acid receptor (hRAR) ligand-binding domains (LBDs) complexed with retinoid ligands. The calculated energies show good correlation with the experimentally reported binding affinities. The technique proposed here is a promising method as it reveals the origin of the receptor subtype selectivity of selective ligands.

  6. Effects of retinoic acid isomers on proteomic pattern in human breast cancer MCF-7 cell line

    Czech Academy of Sciences Publication Activity Database

    Flodrová, Dana; Benkovská, Dagmar; Macejová, D.; Bialešová, L.; Bobálová, Janette; Brtko, J.

    2013-01-01

    Roč. 47, č. 4 (2013), s. 205-209 ISSN 1210-0668 R&D Projects: GA MŠk(CZ) 7AMB12SK151 Institutional support: RVO:68081715 Keywords : retinoic acid isomers * retinoid * breast cancer * malignant cells * proteomic analysis Subject RIV: CB - Analytical Chemistry, Separation

  7. Inhibition of estrogen-responsive gene activation by the retinoid X receptor beta: evidence for multiple inhibitory pathways.

    Science.gov (United States)

    Segars, J H; Marks, M S; Hirschfeld, S; Driggers, P H; Martinez, E; Grippo, J F; Brown, M; Wahli, W; Ozato, K

    1993-04-01

    The retinoid X receptor beta (RXR beta; H-2RIIBP) forms heterodimers with various nuclear hormone receptors and binds multiple hormone response elements, including the estrogen response element (ERE). In this report, we show that endogenous RXR beta contributes to ERE binding activity in nuclear extracts of the human breast cancer cell line MCF-7. To define a possible regulatory role of RXR beta regarding estrogen-responsive transcription in breast cancer cells, RXR beta and a reporter gene driven by the vitellogenin A2 ERE were transfected into estrogen-treated MCF-7 cells. RXR beta inhibited ERE-driven reporter activity in a dose-dependent and element-specific fashion. This inhibition occurred in the absence of the RXR ligand 9-cis retinoic acid. The RXR beta-induced inhibition was specific for estrogen receptor (ER)-mediated ERE activation because inhibition was observed in ER-negative MDA-MB-231 cells only following transfection of the estrogen-activated ER. No inhibition of the basal reporter activity was observed. The inhibition was not caused by simple competition of RXR beta with the ER for ERE binding, since deletion mutants retaining DNA binding activity but lacking the N-terminal or C-terminal domain failed to inhibit reporter activity. In addition, cross-linking studies indicated the presence of an auxiliary nuclear factor present in MCF-7 cells that contributed to RXR beta binding of the ERE. Studies using known heterodimerization partners of RXR beta confirmed that RXR beta/triiodothyronine receptor alpha heterodimers avidly bind the ERE but revealed the existence of another triiodothyronine-independent pathway of ERE inhibition. These results indicate that estrogen-responsive genes may be negatively regulated by RXR beta through two distinct pathways.

  8. Retinoid inhibition of in vitro invasion of human amnion basement membrane by human tumor cells

    International Nuclear Information System (INIS)

    Fazely, F.

    1988-01-01

    The effects measured were the inhibition of tumor cell migration through the basement membrane (BM) and tumor cell degradative enzyme activity on 3 H-proline labeled collagenous and non collagenous components of the BM. The human lung carcinoma A549 or the human Ewing's sarcoma TC-106 cell lines treated with retinoids for two days were incubated on the BM in the absence of retinoids. A dose-dependent inhibition of cell invasion was produced by retinoids. Among the retinoids tested the most powerful was retinol acetate which inhibited invasion by 50% of A549 cells at a concentration of 0.09 μg/ml, and TC-106 cells at 0.08 μg/ml. Retinol acetate inhibited A549 and TC-106 cell growth by approximately 50% at levels almost 100-fold higher than those needed for antiinvasive activity. Retinol acetate was about 20 times more potent than retinoic acid and 30 times more than retinol palmitate. Furthermore, A549 cells treated with retinol acetate, under conditions whereby an anti-invasive state was induced,showed an increase in the number of cellular retinoic acid binding proteins (CRABP), a decrease in the activity of type IV collagenase and ectosialyltransferase, and no change in the activity of transglutaminase

  9. Cardiac arrest – cardiopulmonary resuscitation

    Directory of Open Access Journals (Sweden)

    Basri Lenjani

    2014-01-01

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

  10. Cardiac Arrest: MedlinePlus Health Topic

    Science.gov (United States)

    ... Handouts Cardiac arrest (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Cardiac Arrest updates ... this? GO MEDICAL ENCYCLOPEDIA Cardiac arrest Related Health Topics Arrhythmia CPR Pacemakers and Implantable Defibrillators National Institutes ...

  11. Retinoids induce integrin-independent lymphocyte adhesion through RAR-α nuclear receptor activity

    Energy Technology Data Exchange (ETDEWEB)

    Whelan, Jarrett T.; Wang, Lei; Chen, Jianming; Metts, Meagan E.; Nasser, Taj A.; McGoldrick, Liam J. [Department of Biochemistry and Molecular Biology, The Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States); Bridges, Lance C., E-mail: bridgesl@ecu.edu [Department of Biochemistry and Molecular Biology, The Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States); East Carolina Diabetes and Obesity Institute, The Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States)

    2014-11-28

    Highlights: • Transcription and translation are required for retinoid-induced lymphocyte adhesion. • RAR activation is sufficient to induced lymphocyte cell adhesion. • Vitamin D derivatives inhibit RAR-prompted lymphocyte adhesion. • Adhesion occurs through a novel binding site within ADAM disintegrin domains. • RARα is a key nuclear receptor for retinoid-dependent lymphocyte cell adhesion. - Abstract: Oxidative metabolites of vitamin A, in particular all-trans-retinoic acid (atRA), have emerged as key factors in immunity by specifying the localization of immune cells to the gut. Although it is appreciated that isomers of retinoic acid activate the retinoic acid receptor (RAR) and retinoid X receptor (RXR) family of nuclear receptors to elicit cellular changes, the molecular details of retinoic acid action remain poorly defined in immune processes. Here we employ a battery of agonists and antagonists to delineate the specific nuclear receptors utilized by retinoids to evoke lymphocyte cell adhesion to ADAM (adisintegrin and metalloprotease) protein family members. We report that RAR agonism is sufficient to promote immune cell adhesion in both immortal and primary immune cells. Interestingly, adhesion occurs independent of integrin function, and mutant studies demonstrate that atRA-induced adhesion to ADAM members required a distinct binding interface(s) as compared to integrin recognition. Anti-inflammatory corticosteroids as well as 1,25-(OH){sub 2}D{sub 3}, a vitamin D metabolite that prompts immune cell trafficking to the skin, potently inhibited the observed adhesion. Finally, our data establish that induced adhesion was specifically attributable to the RAR-α receptor isotype. The current study provides novel molecular resolution as to which nuclear receptors transduce retinoid exposure into immune cell adhesion.

  12. Retinoids induce integrin-independent lymphocyte adhesion through RAR-α nuclear receptor activity

    International Nuclear Information System (INIS)

    Whelan, Jarrett T.; Wang, Lei; Chen, Jianming; Metts, Meagan E.; Nasser, Taj A.; McGoldrick, Liam J.; Bridges, Lance C.

    2014-01-01

    Highlights: • Transcription and translation are required for retinoid-induced lymphocyte adhesion. • RAR activation is sufficient to induced lymphocyte cell adhesion. • Vitamin D derivatives inhibit RAR-prompted lymphocyte adhesion. • Adhesion occurs through a novel binding site within ADAM disintegrin domains. • RARα is a key nuclear receptor for retinoid-dependent lymphocyte cell adhesion. - Abstract: Oxidative metabolites of vitamin A, in particular all-trans-retinoic acid (atRA), have emerged as key factors in immunity by specifying the localization of immune cells to the gut. Although it is appreciated that isomers of retinoic acid activate the retinoic acid receptor (RAR) and retinoid X receptor (RXR) family of nuclear receptors to elicit cellular changes, the molecular details of retinoic acid action remain poorly defined in immune processes. Here we employ a battery of agonists and antagonists to delineate the specific nuclear receptors utilized by retinoids to evoke lymphocyte cell adhesion to ADAM (adisintegrin and metalloprotease) protein family members. We report that RAR agonism is sufficient to promote immune cell adhesion in both immortal and primary immune cells. Interestingly, adhesion occurs independent of integrin function, and mutant studies demonstrate that atRA-induced adhesion to ADAM members required a distinct binding interface(s) as compared to integrin recognition. Anti-inflammatory corticosteroids as well as 1,25-(OH) 2 D 3 , a vitamin D metabolite that prompts immune cell trafficking to the skin, potently inhibited the observed adhesion. Finally, our data establish that induced adhesion was specifically attributable to the RAR-α receptor isotype. The current study provides novel molecular resolution as to which nuclear receptors transduce retinoid exposure into immune cell adhesion

  13. "House Arrest" or "Developmental Arrest"? A Study of Youth Under House Arrest.

    Science.gov (United States)

    Chamiel, Elad; Walsh, Sophie D

    2018-06-01

    Studies have examined the potential benefits and risks of alternative forms of detention, such as house arrest, for adults but, despite its growing use, little research has examined the implications of house arrest for juveniles. The current research examined the experience of 14 adolescents under house arrest. Six main themes were identified in the narratives of the participants: the experience of detention, daily schedule and utilization of time, emotions and self-reflection, relationships with peers, relation to parents and supervisor(s), and contact with professionals. Findings emphasized the potential developmental dangers of house arrest at the critical stage of adolescence. Yet, analysis also showed that the period of house arrest has the potential to be a period of positive changes, and can be used for successful rehabilitation.

  14. Metoclopramide-induced cardiac arrest

    Directory of Open Access Journals (Sweden)

    Martha M. Rumore

    2011-11-01

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

  15. Cell-mediated immunity against human retinal extract, S-antigen, and interphotoreceptor retinoid binding protein in onchocercal chorioretinopathy

    NARCIS (Netherlands)

    van der Lelij, A.; Rothova, A.; Stilma, J. S.; Hoekzema, R.; Kijlstra, A.

    1990-01-01

    Autoimmune mechanisms are thought to be involved in the pathogenesis of onchocercal chorioretinopathy. Cell-mediated immune responses to human retinal S-antigen, interphotoreceptor retinoid binding protein (IRBP), and crude retinal extract were investigated in patients with onchocerciasis from

  16. highroad Is a Carboxypetidase Induced by Retinoids to Clear Mutant Rhodopsin-1 in Drosophila Retinitis Pigmentosa Models

    Directory of Open Access Journals (Sweden)

    Huai-Wei Huang

    2018-02-01

    Full Text Available Rhodopsins require retinoid chromophores for their function. In vertebrates, retinoids also serve as signaling molecules, but whether these molecules similarly regulate gene expression in Drosophila remains unclear. Here, we report the identification of a retinoid-inducible gene in Drosophila, highroad, which is required for photoreceptors to clear folding-defective mutant Rhodopsin-1 proteins. Specifically, knockdown or genetic deletion of highroad blocks the degradation of folding-defective Rhodopsin-1 mutant, ninaEG69D. Moreover, loss of highroad accelerates the age-related retinal degeneration phenotype of ninaEG69D mutants. Elevated highroad transcript levels are detected in ninaEG69D flies, and interestingly, deprivation of retinoids in the fly diet blocks this effect. Consistently, mutations in the retinoid transporter, santa maria, impairs the induction of highroad in ninaEG69D flies. In cultured S2 cells, highroad expression is induced by retinoic acid treatment. These results indicate that cellular quality-control mechanisms against misfolded Rhodopsin-1 involve regulation of gene expression by retinoids.

  17. Singlet Oxygen and Free Radical Reactions of Retinoids and Carotenoids—A Review

    Science.gov (United States)

    Truscott, T. George

    2018-01-01

    We report on studies of reactions of singlet oxygen with carotenoids and retinoids and a range of free radical studies on carotenoids and retinoids with emphasis on recent work, dietary carotenoids and the role of oxygen in biological processes. Many previous reviews are cited and updated together with new data not previously reviewed. The review does not deal with computational studies but the emphasis is on laboratory-based results. We contrast the ease of study of both singlet oxygen and polyene radical cations compared to neutral radicals. Of particular interest is the switch from anti- to pro-oxidant behavior of a carotenoid with change of oxygen concentration: results for lycopene in a cellular model system show total protection of the human cells studied at zero oxygen concentration, but zero protection at 100% oxygen concentration. PMID:29301252

  18. Prevention of UV irradiation induced suppression of monocyte functions by retinoids and carotenoids in vitro

    International Nuclear Information System (INIS)

    Schoen, D.J.; Watson, R.R.

    1988-01-01

    The effects of stimulation of human peripheral blood monocytes in vitro with retinoids and carotenoids, and subsequent exposure to ultraviolet light of the B wavelength were measured. The compounds were applied to the monocytes in culture for 24 h, and the washed cells were then exposed to UVB light up to 220 J/m 2 . The compounds tested protected the monocyte from UVB induced damage to phagocytic activity. This protection may be due to the antioxidant or UVB energy-quenching properties of these compounds. Monocyte cytotoxicity against a melanoma cell line was stimulated by exposure to the retinoids or carotenoids, but a protective effect in vitro against UVB damage was not seen for this cell function. (author)

  19. Lecithin:Retinol Acyltransferase: A Key Enzyme Involved in the Retinoid (visual) Cycle

    OpenAIRE

    Sears, Avery E.; Palczewski, Krzysztof

    2016-01-01

    Lecithin:retinol acyltransferase (LRAT) catalyzes the acyl transfer from the sn-1 position of phosphatidylcholine (PC) to all-trans-retinol, creating fatty acid retinyl esters (palmitoyl, stearoyl, and some unsaturated derivatives). In the eye, these retinyl esters are substrates for the 65 kDa retinoid isomerase (RPE65). LRAT is well characterized biochemically, and recent structural data from closely related family members of the NlpC/P60 superfamily and a chimeric protein have established ...

  20. HPMA copolymer-based polymer conjugates for the delivery and controlled release of retinoids

    Czech Academy of Sciences Publication Activity Database

    Lidický, Ondřej; Šírová, Milada; Etrych, Tomáš

    2016-01-01

    Roč. 65, Suppl. 2 (2016), S233-S241 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LQ1604 Institutional support: RVO:61389013 ; RVO:61388971 Keywords : polymer conjugate * retinoid * HPMA Subject RIV: EB - Genetics ; Molecular Biology; EA - Cell Biology (MBU-M) Impact factor: 1.461, year: 2016 http://www.biomed.cas.cz/physiolres/pdf/65%20Suppl%202/65_S233.pdf

  1. Peretinoin, an Acyclic Retinoid, Inhibits Hepatitis B Virus Replication by Suppressing Sphingosine Metabolic Pathway In Vitro

    Directory of Open Access Journals (Sweden)

    Kazuhisa Murai

    2018-01-01

    Full Text Available Hepatocellular carcinoma (HCC frequently develops from hepatitis C virus (HCV and hepatitis B virus (HBV infection. We previously reported that peretinoin, an acyclic retinoid, inhibits HCV replication. This study aimed to examine the influence of peretinoin on the HBV lifecycle. HBV-DNA and covalently closed circular DNA (cccDNA were evaluated by a qPCR method in HepG2.2.15 cells. Peretinoin significantly reduced the levels of intracellular HBV-DNA, nuclear cccDNA, and HBV transcript at a concentration that did not induce cytotoxicity. Conversely, other retinoids, such as 9-cis, 13-cis retinoic acid (RA, and all-trans-retinoic acid (ATRA, had no effect or rather increased HBV replication. Mechanistically, although peretinoin increased the expression of HBV-related transcription factors, as observed for other retinoids, peretinoin enhanced the binding of histone deacetylase 1 (HDAC1 to cccDNA in the nucleus and negatively regulated HBV transcription. Moreover, peretinoin significantly inhibited the expression of SPHK1, a potential inhibitor of HDAC activity, and might be involved in hepatic inflammation, fibrosis, and HCC. SPHK1 overexpression in cells cancelled the inhibition of HBV replication induced by peretinoin. This indicates that peretinoin activates HDAC1 and thereby suppresses HBV replication by inhibiting the sphingosine metabolic pathway. Therefore, peretinoin may be a novel therapeutic agent for HBV replication and chemoprevention against HCC.

  2. Retinoids: literature review and suggested algorithm for use prior to facial resurfacing procedures

    Directory of Open Access Journals (Sweden)

    Patrick J Buchanan

    2016-01-01

    Full Text Available Vitamin A-containing products have been used topically since the early 1940s to treat various skin conditions. To date, there are four generations of retinoids, a family of Vitamin A-containing compounds. Tretinoin, all-trans-retinoic acid, is a first-generation, naturally occurring, retinoid. It is available, commercially, as a gel or cream. The authors conducted a complete review of all studies, clinical- and basic science-based studies, within the literature involving tretinoin treatment recommendations for impending facial procedures. The literature currently lacks definitive recommendations for the use of tretinoin-containing products prior to undergoing facial procedures. Tretinoin pretreatment regimens vary greatly in terms of the strength of retinoid used, the length of the pre-procedure treatment, and the ideal time to stop treatment before the procedure. Based on the current literature and personal experience, the authors set forth a set of guidelines for the use of tretinoin prior to various facial procedures.

  3. Topical retinoids in the management of photodamaged skin: from theory to evidence-based practical approach.

    Science.gov (United States)

    Darlenski, R; Surber, C; Fluhr, J W

    2010-12-01

    Skin, being exposed directly to the environment, represents a unique model for demonstrating the synergistic effects of intrinsic and extrinsic factors on the ageing process. Ultraviolet radiation (UVR) is the major factor among exogenous stressors responsible for premature skin ageing. The problem of skin ageing has captured public attention and has an important social impact. Different therapeutic approaches have been developed to treat cutaneous ageing and to diminish or prevent the negative effects of UVR. Topical retinoids represent an important and powerful class of molecules in the dermatologist's hands for the treatment of photodamaged skin. Since their introduction more than 20 years ago, topical retinoids have shown beneficial efficacy and good safety profiles in the management of photodamaged skin, and as therapeutic anti-ageing agents. This review provides a brief retrospective of the development of topical retinoids in the treatment of photodamaged skin, elucidates their mechanism of action, delineates their use and addresses clinical, pharmaceutical and regulatory issues in connection with their intended use. © 2010 The Authors. BJD © 2010 British Association of Dermatologists.

  4. A new class of synthetic retinoid antibiotics effective against bacterial persisters.

    Science.gov (United States)

    Kim, Wooseong; Zhu, Wenpeng; Hendricks, Gabriel Lambert; Van Tyne, Daria; Steele, Andrew D; Keohane, Colleen E; Fricke, Nico; Conery, Annie L; Shen, Steven; Pan, Wen; Lee, Kiho; Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Vlahovska, Petia M; Wuest, William M; Gilmore, Michael S; Gao, Huajian; Ausubel, Frederick M; Mylonakis, Eleftherios

    2018-04-05

    A challenge in the treatment of Staphylococcus aureus infections is the high prevalence of methicillin-resistant S. aureus (MRSA) strains and the formation of non-growing, dormant 'persister' subpopulations that exhibit high levels of tolerance to antibiotics and have a role in chronic or recurrent infections. As conventional antibiotics are not effective in the treatment of infections caused by such bacteria, novel antibacterial therapeutics are urgently required. Here we used a Caenorhabditis elegans-MRSA infection screen to identify two synthetic retinoids, CD437 and CD1530, which kill both growing and persister MRSA cells by disrupting lipid bilayers. CD437 and CD1530 exhibit high killing rates, synergism with gentamicin, and a low probability of resistance selection. All-atom molecular dynamics simulations demonstrated that the ability of retinoids to penetrate and embed in lipid bilayers correlates with their bactericidal ability. An analogue of CD437 was found to retain anti-persister activity and show an improved cytotoxicity profile. Both CD437 and this analogue, alone or in combination with gentamicin, exhibit considerable efficacy in a mouse model of chronic MRSA infection. With further development and optimization, synthetic retinoids have the potential to become a new class of antimicrobials for the treatment of Gram-positive bacterial infections that are currently difficult to cure.

  5. A new class of synthetic retinoid antibiotics effective against bacterial persisters

    Science.gov (United States)

    Kim, Wooseong; Zhu, Wenpeng; Hendricks, Gabriel Lambert; van Tyne, Daria; Steele, Andrew D.; Keohane, Colleen E.; Fricke, Nico; Conery, Annie L.; Shen, Steven; Pan, Wen; Lee, Kiho; Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Vlahovska, Petia M.; Wuest, William M.; Gilmore, Michael S.; Gao, Huajian; Ausubel, Frederick M.; Mylonakis, Eleftherios

    2018-04-01

    A challenge in the treatment of Staphylococcus aureus infections is the high prevalence of methicillin-resistant S. aureus (MRSA) strains and the formation of non-growing, dormant ‘persister’ subpopulations that exhibit high levels of tolerance to antibiotics and have a role in chronic or recurrent infections. As conventional antibiotics are not effective in the treatment of infections caused by such bacteria, novel antibacterial therapeutics are urgently required. Here we used a Caenorhabditis elegans–MRSA infection screen to identify two synthetic retinoids, CD437 and CD1530, which kill both growing and persister MRSA cells by disrupting lipid bilayers. CD437 and CD1530 exhibit high killing rates, synergism with gentamicin, and a low probability of resistance selection. All-atom molecular dynamics simulations demonstrated that the ability of retinoids to penetrate and embed in lipid bilayers correlates with their bactericidal ability. An analogue of CD437 was found to retain anti-persister activity and show an improved cytotoxicity profile. Both CD437 and this analogue, alone or in combination with gentamicin, exhibit considerable efficacy in a mouse model of chronic MRSA infection. With further development and optimization, synthetic retinoids have the potential to become a new class of antimicrobials for the treatment of Gram-positive bacterial infections that are currently difficult to cure.

  6. Retinoid-induced expression and activity of an immediate early tumor suppressor gene in vascular smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Jeffrey W Streb

    2011-04-01

    Full Text Available Retinoids are used clinically to treat a number of hyper-proliferative disorders and have been shown in experimental animals to attenuate vascular occlusive diseases, presumably through nuclear receptors bound to retinoic acid response elements (RARE located in target genes. Here, we show that natural or synthetic retinoids rapidly induce mRNA and protein expression of a specific isoform of A-Kinase Anchoring Protein 12 (AKAP12β in cultured smooth muscle cells (SMC as well as the intact vessel wall. Expression kinetics and actinomycin D studies indicate Akap12β is a retinoid-induced, immediate-early gene. Akap12β promoter analyses reveal a conserved RARE mildly induced with atRA in a region that exhibits hyper-acetylation. Immunofluorescence microscopy and protein kinase A (PKA regulatory subunit overlay assays in SMC suggest a physical association between AKAP12β and PKA following retinoid treatment. Consistent with its designation as a tumor suppressor, inducible expression of AKAP12β attenuates SMC growth in vitro. Further, immunohistochemistry studies establish marked decreases in AKAP12 expression in experimentally-injured vessels of mice as well as atheromatous lesions in humans. Collectively, these results demonstrate a novel role for retinoids in the induction of an AKAP tumor suppressor that blocks vascular SMC growth thus providing new molecular insight into how retiniods may exert their anti-proliferative effects in the injured vessel wall.

  7. Sudden Cardiac Arrest (SCA) Risk Assessment

    Science.gov (United States)

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

  8. Targeted Therapy for Breast Cancer Prevention

    Science.gov (United States)

    den Hollander, Petra; Savage, Michelle I.; Brown, Powel H.

    2013-01-01

    With a better understanding of the etiology of breast cancer, molecularly targeted drugs have been developed and are being testing for the treatment and prevention of breast cancer. Targeted drugs that inhibit the estrogen receptor (ER) or estrogen-activated pathways include the selective ER modulators (tamoxifen, raloxifene, and lasofoxifene) and aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) have been tested in preclinical and clinical studies. Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer and promising results of AIs in breast cancer trials, suggest that AIs might be even more effective in the prevention of ER-positive breast cancer. However, these agents only prevent ER-positive breast cancer. Therefore, current research is focused on identifying preventive therapies for other forms of breast cancer such as human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer (TNBC, breast cancer that does express ER, progesterone receptor, or HER2). HER2-positive breast cancers are currently treated with anti-HER2 therapies including trastuzumab and lapatinib, and preclinical and clinical studies are now being conducted to test these drugs for the prevention of HER2-positive breast cancers. Several promising agents currently being tested in cancer prevention trials for the prevention of TNBC include poly(ADP-ribose) polymerase inhibitors, vitamin D, and rexinoids, both of which activate nuclear hormone receptors (the vitamin D and retinoid X receptors). This review discusses currently used breast cancer preventive drugs, and describes the progress of research striving to identify and develop more effective preventive agents for all forms of breast cancer. PMID:24069582

  9. Allergen-Induced Dermatitis Causes Alterations in Cutaneous Retinoid-Mediated Signaling in Mice

    Science.gov (United States)

    Gericke, Janine; Ittensohn, Jan; Mihály, Johanna; Dubrac, Sandrine; Rühl, Ralph

    2013-01-01

    Nuclear receptor-mediated signaling via RARs and PPARδ is involved in the regulation of skin homeostasis. Moreover, activation of both RAR and PPARδ was shown to alter skin inflammation. Endogenous all-trans retinoic acid (ATRA) can activate both receptors depending on specific transport proteins: Fabp5 initiates PPARδ signaling whereas Crabp2 promotes RAR signaling. Repetitive topical applications of ovalbumin (OVA) in combination with intraperitoneal injections of OVA or only intraperitoneal OVA applications were used to induce allergic dermatitis. In our mouse model, expression of IL-4, and Hbegf increased whereas expression of involucrin, Abca12 and Spink5 decreased in inflamed skin, demonstrating altered immune response and epidermal barrier homeostasis. Comprehensive gene expression analysis showed alterations of the cutaneous retinoid metabolism and retinoid-mediated signaling in allergic skin immune response. Notably, ATRA synthesis was increased as indicated by the elevated expression of retinaldehyde dehydrogenases and increased levels of ATRA. Consequently, the expression pattern of genes downstream to RAR was altered. Furthermore, the increased ratio of Fabp5 vs. Crabp2 may indicate an up-regulation of the PPARδ pathway in allergen-induced dermatitis in addition to the altered RAR signaling. Thus, our findings suggest that ATRA levels, RAR-mediated signaling and signaling involved in PPARδ pathways are mainly increased in allergen-induced dermatitis and may contribute to the development and/or maintenance of allergic skin diseases. PMID:23977003

  10. Keratoacanthoma centrifugum marginatum: unresponsive to oral retinoid and successfully treated with wide local excision.

    Directory of Open Access Journals (Sweden)

    Kapildev Das

    2010-01-01

    Full Text Available We describe a case of a 65-year-old male presenting with a large plaque with a rolled-out interrupted margin, atrophic center, and island of normal skin over the left arm. It grew peripherally with central healing, and there was a history of recurrence after inadequate excision. Investigations ruled out other clin­ical mimickers; namely, squamous cell carcinoma, lupus vulgaris, botryomycosis, and blastomycosis-like pyoderma. Histopathological sections showed irregularly shaped craters filled with keratin and epithelial pearl but no evidence of granuloma or cellular atypia. Clinico­pathological correlation proved the lesion to be keratoacanthoma centrifugum marginatum (KCM, a rare variant of keratoacanthoma, which spreads centrifugally, attains a huge size, and never involutes spontaneously. Treatment of KCM has been a problem always and, in our case, systemic retinoid (acitretin for three months proved ineffective. The patient also had a history of recurrence following surgical intervention previously, necessitating wide excision to achieve complete clearance of tumor cells. Hence, after failure of retinoid therapy, the decision of excision with a 1-centimeter margin was taken and the large defect was closed by a split thickness skin graft. The graft uptake was satisfactory, and the patient is being followed-up presently and shows no signs of recurrence after six months, highlighting wide local excision as a useful treatment option.

  11. Synthesis of retinoid vitamin A-vitamin B6 conjugate analogues for antiviral chemotherapy

    International Nuclear Information System (INIS)

    Kesel, Andreas J.

    2003-01-01

    The synthesis of retinoid vitamin A-vitamin B 6 conjugate analogues from a vitamin B 6 coenzyme analogue and putative HIV-1 trans-activating transcriptional regulatory protein Tat antagonist (Z)-5 ' -O-phosphono-pyridoxylidenerhodanine (B6PR) monosodium salt hemiheptadecahydrate [(Z)-B6PRNa8.5H 2 O] is discussed here. All-trans-retinoic acid (ATRA) is coupled to B6PR by a modified Stork enamine acylation. It results in a product library of more than eight compounds, each with at least one intact all-trans or 13-cis vitamin A double bond system. This yellow oily concentrate mixture was subjected to matrix-assisted laser desorption/ionization-time-of-flight (MALDI-ToF) mass spectrometry (MS), UV/VIS-spectrophotometry, and proton nuclear magnetic resonance spectroscopy ( 1 H-NMR). The chemical structures of six components of the concentrate mixture could be established by combination of these analytical methods. The two main components are 65% 2 ' C,3O-(all-trans-retinylidyne)B6PT (B6RA) and 25% 2 ' C-(all-trans-retinoyl)B6PT, chemically derived from (5RS)-5-(5 ' -O-phosphono-pyridoxyl)-2,4-thiazolidinedione (B6PT). This new retinoid selection could be of further interest in antiviral applications, especially treating conditions caused by RNA viruses like HIV

  12. Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity

    Science.gov (United States)

    van de Pavert, Serge A.; Ferreira, Manuela; Domingues, Rita G.; Ribeiro, Hélder; Molenaar, Rosalie; Moreira-Santos, Lara; Almeida, Francisca F.; Ibiza, Sales; Barbosa, Inês; Goverse, Gera; Labão-Almeida, Carlos; Godinho-Silva, Cristina; Konijn, Tanja; Schooneman, Dennis; O'Toole, Tom; Mizee, Mark R.; Habani, Yasmin; Haak, Esther; Santori, Fabio R.; Littman, Dan R.; Schulte-Merker, Stefan; Dzierzak, Elaine; Simas, J. Pedro; Mebius, Reina E.; Veiga-Fernandes, Henrique

    2014-04-01

    The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed. Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells. Here we show that mouse fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in utero, which pre-sets the immune fitness in adulthood. We found that embryonic lymphoid organs contain ILC progenitors that differentiate locally into mature LTi cells. Local LTi cell differentiation was controlled by maternal retinoid intake and fetal RA signalling acting in a haematopoietic cell-autonomous manner. RA controlled LTi cell maturation upstream of the transcription factor RORγt. Accordingly, enforced expression of Rorgt restored maturation of LTi cells with impaired RA signalling, whereas RA receptors directly regulated the Rorgt locus. Finally, we established that maternal levels of dietary retinoids control the size of secondary lymphoid organs and the efficiency of immune responses in the adult offspring. Our results reveal a molecular link between maternal nutrients and the formation of immune structures required for resistance to infection in the offspring.

  13. The real performance of radioactive lightning arrester

    International Nuclear Information System (INIS)

    Leite, D.M.

    1985-01-01

    The study of the performance of radioactive lightning arrester comparing to the performance of conventional one are presented. Measurements of currents between lightning arrester and an energyzed plate with wind simulation were done for radioactive and conventional lightning arresters, separately. The attraction range of radioactive and conventional lightning arresters using atmospheric pulses produced by a generator of 3MV were verified, separately and simultaneously. The influence of ionization produced by radioactive lightning arrester on critical disruptive tension of a spark plate, testing two lightning arresters for differents nominal attraction distances with applications of atmospheric pulses (positive and negative polarity) and tensions of 60 Hz was verified. The radiation emitted by a radioactive lightning had used in a building was retired and handled without special carefullness by a personnel without worthy of credence to evaluate the hazard in handling radioactive lightning arrester was measured. Critical disruptive tensions of radioactive and conventional lightning arrester using a suspensed electrode and external pulse generator of 6MV was measured. The effect of attraction of a radioactive and conventional lightning arresters disposed symmetrically regarding the same suspensed electrode was verified simultaneously. Seven cases on faults of radioactive lightning arrester in external areas are present. (M.C.K.) [pt

  14. An engineering interpretation of pop-in arrest and tearing arrest in terms of static crack arrest, Ksub(Ia)

    International Nuclear Information System (INIS)

    Witt, F.J.

    1983-01-01

    When fracture toughness specimens are tested under displacement controlled conditions, they are often observed to exhibit unstable cleavage fracture followed by arrest of the cleavage mode wherein a significant load remains on the specimen (pop-in arrest). This behavior carries over into the ductile tearing regime wherein tearing may occur rapidly identified by load reduction and then proceeds at a discernible less rate (tearing arrest). Both these behaviors represent an initiation condition followed by an arrest condition. In this paper it is demonstrated that from either of the arrest conditions an arrest value may be determined which, for available experimental data, is shown to be an engineering estimate for the static crack arrest toughness, Ksub(Ia). A data analysis procedure is outlined and Ksub(Ic) and Ksub(Ia) estimates from sixty-eight 1/2, 1 and 2 in. thick compact specimens from two steels (A533 Grade B Class 1 and AISI 1018) tested between -40 deg F and 200 deg F are summarized. The crack arrest estimates are seen to compare favorably with Ksub(Ia) results obtained by other investigators using 2 in. thick specimens. Also it is demonstrated that when failure is by fully ductile tearing, the crack arrest toughness is at least equal to the estimate for Ksub(Ic) for the specimen. (author)

  15. The retinoids. A review of their clinical pharmacology and therapeutic use.

    Science.gov (United States)

    Orfanos, C E; Ehlert, R; Gollnick, H

    1987-10-01

    With the introduction of the synthetic retinoids, oral therapy with an acceptable risk/benefit ratio became possible for a variety of skin diseases including severe acne, psoriasis and numerous genodermatoses. This article reviews the clinical pharmacology, mechanisms of action and therapeutic use of the retinoids, particularly isotretinoin (13-cis-retinoic acid) and etretinate. The free aromatic acid of etretinate, etretin, and the new polyaromatic retinoid compounds (arotinoids) are also discussed. Isotretinoin is used clinically for oral therapy of severe acne, but is also recommended for severe Gram-negative folliculitis and rosacea not responding to traditional therapy. The results of several studies have established that acne therapy should be started with 1.0 mg/kg/day for 2 to 3 months after which the daily dosage should be lowered to 0.2 to 0.5 mg/kg/day for another 2 to 3 months. This therapeutic regimen of isotretinoin has proven to be the most successful in preventing relapses. Etretinate is particularly useful for oral therapy of widespread plaque-like, pustular and erythrodermic psoriasis, and of generalised lichen planus, Darier's disease and severe congenital ichthyoses. Whereas pustular forms of psoriasis require a high daily dosage of 1.0 mg/kg/day, erythrodermic psoriasis should be treated with a lower dosage of 0.25 to 0.35 mg/kg/day. In chronic plaque-like psoriasis, a mean daily dosage of 0.5 mg/kg/day over several weeks to months, usually combined with photo(chemo)therapy, tar or dithranol, is recommended. Other indications for oral etretinate therapy are adequately treated with a moderate dosage of 0.4 to 0.75 mg/kg/day. Etretin differs from etretinate in having a much shorter elimination half-life of 2 to 3 days, in contrast to 80 to 100 days after long term administration of etretinate. Moreover, it has not been shown to increase serum cholesterol levels. However, its clinical efficacy is not yet clearly established. Among the arotinoids

  16. Dynamic photoelastic investigation of crack arrest

    International Nuclear Information System (INIS)

    Irwin, G.R.; Dally, J.W.; Kobayashi, T.; Fourney, W.L.

    1977-01-01

    Crack arrest and crack arrest toughness are of great interest, particularly for studies pertaining to safety of nuclear reactor pressure vessels. Investigations are needed in which the instantaneous values of stress intensity factor (K) can be observed during crack propagation and arrest. Such observations are possible if the test specimens are made from plates of a transparent photoelastic sensitive material. Values of K as a function of crack speed are shown for Homalite 100 and various epoxy blends. 9 figures

  17. Simulated Cardiopulmonary Arrests in a Hospital Setting.

    Science.gov (United States)

    Mishkin, Barbara H.; And Others

    1982-01-01

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

  18. Assessment of risks for employees of France Telecom regarding overvoltage arresters containing radio-elements

    International Nuclear Information System (INIS)

    Thomassin, A.; Metz, C.; Rannou, A.

    2010-01-01

    As a great number of overvoltage arresters used by France Telecom to protect its telecommunication network against disturbing voltages (notably lightning) contain radio-elements, this report aims at assessing dose levels and associated risks for employees exposed to radioactive overvoltage arrester when setting them up, exploiting installations containing such arresters, or when removing them. After a presentation of these devices, a modelling of activities and geometries is proposed, as well as computation tools. Different scenarios and exposure situations are considered. As far as risks are concerned, after a recall on cancers and ionizing radiation, and on the exposure of France Telecom employees, the report comments the knowledge on radio-induced cancers; notably breast cancer, skin cancer, and mouth and pharynx cancers

  19. Cheilitis in acne vulgaris patients with no previous use of systemic retinoid products.

    Science.gov (United States)

    Balighi, Kamran; Daneshpazhooh, Maryam; Lajevardi, Vahideh; Talebi, Shahin; Azizpour, Arghavan

    2017-08-01

    Isotretinoin is commonly used in the treatment of acne vulgaris. While one of the more common side-effects is cheilitis, we have observed an increased incidence of cheilitis prior to the commencement of systemic isotretinoin. The aim of this study was to assess the prevalence of cheilitis among acne vulgaris patients. A non-interventional cross-sectional study of patients with acne vulgaris. Patients with previous use of systemic retinoids were excluded. The patients were examined for signs and symptoms of cheilitis. Of a total of 400 patients, 134 (34%) had evidence of cheilitis at initial presentation. Two-thirds (63%) were female (P acne excorie, compared with only 8% of patients with no signs of cheilitis. Our findings suggest that cheilitis is quite common among acne vulgaris patients even before treatment with isotretinoin. © 2016 The Australasian College of Dermatologists.

  20. Independent Activation of Hepatitis B Virus Biosynthesis by Retinoids, Peroxisome Proliferators, and Bile Acids

    Science.gov (United States)

    Reese, Vanessa C.; Oropeza, Claudia E.

    2013-01-01

    In the human hepatoma cell line HepG2, retinoic acid, clofibric acid, and bile acid treatment can only modestly increase hepatitis B virus (HBV) biosynthesis. Utilizing the human embryonic kidney cell line 293T, it was possible to demonstrate that the retinoid X receptor α (RXRα) plus its ligand can support viral biosynthesis independently of additional nuclear receptors. In addition, RXRα/peroxisome proliferator-activated receptor α (PPARα) and RXRα/farnesoid X receptor α (FXRα) heterodimeric nuclear receptors can also mediate ligand-dependent HBV transcription and replication when activated by clofibric acid and bile acid, respectively, independently of a requirement for the ligand-dependent activation of RXRα. These observations indicate that there are at least three possible modes of ligand-mediated activation of HBV transcription and replication existing within hepatocytes, suggesting that multiple independent mechanisms control viral production in the livers of infected individuals. PMID:23135717

  1. [Immunosuppresive agents, retinoids and new trends in the therapy of psoriasis].

    Science.gov (United States)

    Svozil, M

    2002-11-01

    Some psoriasis forms can be successfully treated with topical medicaments; serious and extensive forms cannot be cured without systemic treatment with retinoids (etretinate, acitretin, tazarotene) or with immunosuppressives (methotrexate, cyclosporine A, tacrolimus, SDZ 281-240). Immunotherapy and nucleotide analogues are being newly introduced, a number of potentially effective substances interfering with pathogenetic mechanisms participating in the emergence and self-prolongation of psoriasis are in the stage of research and clinical trials, and gene therapy possibilities are being investigated. The development and testing of drugs serving therapy for psoriasis correlates with the development of knowledge about the origins of the disease and the mechanisms of how antipsoriatics in current use as well as the new potential ones work.

  2. NADPH-d activity in rat thymus after the application of retinoid acid

    Directory of Open Access Journals (Sweden)

    F. Dorko

    2012-02-01

    Full Text Available The aim of this work was to determine the localization of nicotinamide-adenine dinucleotide phosphate-diaphorase (NADPH-d activity as the marker for synthesis of nitric oxide synthase (NOS in the rat thymus after the application of retinoid acid (RA on 1st, 7th, 14th and 21st days of gestation. The given results can build the basis for understanding of the role of NOS in rat thymus. NADPH-d positive cells were represented with dark-blue color and were localized on corticomedullar junction of the thymus. These cells were of different intensity of coloring and were shaped in oval, circle or irregular forms. NADPH-d positive nerve fibers were observed in perivascular topography. They were marked more strongly in the case of control group. The result of application of RA to gravid rats was that the birth weights of newborn rats and their thymuses were smaller, but without statistically significance.

  3. Loss of function of the retinoid-related nuclear receptor (RORB) gene and epilepsy

    DEFF Research Database (Denmark)

    Rudolf, Gabrielle; Lesca, Gaetan; Mehrjouy, Mana M

    2016-01-01

    nuclear receptor (RORβ), in four affected family members. In addition, two de novo variants (c.218T>C/p.(Leu73Pro); c.1249_1251delACG/p.(Thr417del)) were identified in sporadic patients by trio-based exome sequencing. We also found two de novo deletions in patients with behavioral and cognitive impairment...... in various types of epilepsies in the past few years. In the present study, we performed whole-exome sequencing in a family with GGE consistent with the diagnosis of eyelid myoclonia with absences. We found a nonsense variant (c.196C>T/p.(Arg66*)) in RORB, which encodes the beta retinoid-related orphan...

  4. Vitamin D receptor–retinoid X receptor heterodimer signaling regulates oligodendrocyte progenitor cell differentiation

    Science.gov (United States)

    de la Fuente, Alerie Guzman; Errea, Oihana; van Wijngaarden, Peter; Gonzalez, Ginez A.; Kerninon, Christophe; Jarjour, Andrew A.; Lewis, Hilary J.; Jones, Clare A.; Nait-Oumesmar, Brahim; Zhao, Chao; Huang, Jeffrey K.; ffrench-Constant, Charles

    2015-01-01

    The mechanisms regulating differentiation of oligodendrocyte (OLG) progenitor cells (OPCs) into mature OLGs are key to understanding myelination and remyelination. Signaling via the retinoid X receptor γ (RXR-γ) has been shown to be a positive regulator of OPC differentiation. However, the nuclear receptor (NR) binding partner of RXR-γ has not been established. In this study we show that RXR-γ binds to several NRs in OPCs and OLGs, one of which is vitamin D receptor (VDR). Using pharmacological and knockdown approaches we show that RXR–VDR signaling induces OPC differentiation and that VDR agonist vitamin D enhances OPC differentiation. We also show expression of VDR in OLG lineage cells in multiple sclerosis. Our data reveal a role for vitamin D in the regenerative component of demyelinating disease and identify a new target for remyelination medicines. PMID:26644513

  5. Arresting relaxation in Pickering Emulsions

    Science.gov (United States)

    Atherton, Tim; Burke, Chris

    2015-03-01

    Pickering emulsions consist of droplets of one fluid dispersed in a host fluid and stabilized by colloidal particles absorbed at the fluid-fluid interface. Everyday materials such as crude oil and food products like salad dressing are examples of these materials. Particles can stabilize non spherical droplet shapes in these emulsions through the following sequence: first, an isolated droplet is deformed, e.g. by an electric field, increasing the surface area above the equilibrium value; additional particles are then adsorbed to the interface reducing the surface tension. The droplet is then allowed to relax toward a sphere. If more particles were adsorbed than can be accommodated by the surface area of the spherical ground state, relaxation of the droplet is arrested at some non-spherical shape. Because the energetic cost of removing adsorbed colloids exceeds the interfacial driving force, these configurations can remain stable over long timescales. In this presentation, we present a computational study of the ordering present in anisotropic droplets produced through the mechanism of arrested relaxation and discuss the interplay between the geometry of the droplet, the dynamical process that produced it, and the structure of the defects observed.

  6. Integrating protein structures and precomputed genealogies in the Magnum database: Examples with cellular retinoid binding proteins

    Directory of Open Access Journals (Sweden)

    Bradley Michael E

    2006-02-01

    Full Text Available Abstract Background When accurate models for the divergent evolution of protein sequences are integrated with complementary biological information, such as folded protein structures, analyses of the combined data often lead to new hypotheses about molecular physiology. This represents an excellent example of how bioinformatics can be used to guide experimental research. However, progress in this direction has been slowed by the lack of a publicly available resource suitable for general use. Results The precomputed Magnum database offers a solution to this problem for ca. 1,800 full-length protein families with at least one crystal structure. The Magnum deliverables include 1 multiple sequence alignments, 2 mapping of alignment sites to crystal structure sites, 3 phylogenetic trees, 4 inferred ancestral sequences at internal tree nodes, and 5 amino acid replacements along tree branches. Comprehensive evaluations revealed that the automated procedures used to construct Magnum produced accurate models of how proteins divergently evolve, or genealogies, and correctly integrated these with the structural data. To demonstrate Magnum's capabilities, we asked for amino acid replacements requiring three nucleotide substitutions, located at internal protein structure sites, and occurring on short phylogenetic tree branches. In the cellular retinoid binding protein family a site that potentially modulates ligand binding affinity was discovered. Recruitment of cellular retinol binding protein to function as a lens crystallin in the diurnal gecko afforded another opportunity to showcase the predictive value of a browsable database containing branch replacement patterns integrated with protein structures. Conclusion We integrated two areas of protein science, evolution and structure, on a large scale and created a precomputed database, known as Magnum, which is the first freely available resource of its kind. Magnum provides evolutionary and structural

  7. Fatty acid transport protein 1 regulates retinoid metabolism and photoreceptor development in mouse retina.

    Directory of Open Access Journals (Sweden)

    Aurélie Cubizolle

    Full Text Available In retinal pigment epithelium (RPE, RPE65 catalyzes the isomerization of all-trans-retinyl fatty acid esters to 11-cis-retinol in the visual cycle and controls the rhodopsin regeneration rate. However, the mechanisms by which these processes are regulated are still unclear. Fatty Acid Transport Protein 1 (FATP1 is involved in fatty acid uptake and lipid metabolism in a variety of cell types. FATP1 co-localizes with RPE65 in RPE and inhibits its isomerase activity in vitro. Here, we further investigated the role of FATP1 in the visual cycle using transgenic mice that overexpress human FATP1 specifically in the RPE (hFATP1TG mice. The mice displayed no delay in the kinetics of regeneration of the visual chromophore 11-cis-retinal after photobleaching and had no defects in light sensitivity. However, the total retinoid content was higher in the hFATP1TG mice than in wild type mice, and the transgenic mice also displayed an age-related accumulation (up to 40% of all-trans-retinal and retinyl esters that was not observed in control mice. Consistent with these results, hFATP1TG mice were more susceptible to light-induced photoreceptor degeneration. hFATP1 overexpression also induced an ~3.5-fold increase in retinosome autofluorescence, as measured by two-photon microscopy. Interestingly, hFATP1TG retina contained ~25% more photoreceptor cells and ~35% longer outer segments than wild type mice, revealing a non-cell-autonomous effect of hFATP1 expressed in the RPE. These data are the first to show that FATP1-mediated fatty acid uptake in the RPE controls both retinoid metabolism in the outer retina and photoreceptor development.

  8. Mechanical Entrapment Is Insufficient and Intercellular Adhesion Is Essential for Metastatic Cell Arrest in Distant Organs

    Directory of Open Access Journals (Sweden)

    Olga V. Glinskii

    2005-05-01

    Full Text Available In this report, we challenge a common perception that tumor embolism is a size-limited event of mechanical arrest, occurring in the first capillary bed encountered by blood-borne metastatic cells. We tested the hypothesis that mechanical entrapment alone, in the absence of tumor cell adhesion to blood vessel walls, is not sufficient for metastatic cell arrest in target organ microvasculature. The in vivo metastatic deposit formation assay was used to assess the number and location of fluorescently labeled tumor cells lodged in selected organs and tissues following intravenous inoculation. We report that a significant fraction of breast and prostate cancer cells escapes arrest in a lung capillary bed and lodges successfully in other organs and tissues. Monoclonal antibodies and carbohydrate-based compounds (anti-Thomsen-Friedenreich antigen antibody, anti-galectin-3 antibody, modified citrus pectin, and lactulosyl-L-leucine, targeting specifically β-galactoside-mediated tumor-endothelial cell adhesive interactions, inhibited by >90% the in vivo formation of breast and prostate carcinoma metastatic deposits in mouse lung and bones. Our results indicate that metastatic cell arrest in target organ microvessels is not a consequence of mechanical trapping, but is supported predominantly by intercellular adhesive interactions mediated by cancer-associated Thomsen-Friedenreich glycoantigen and β-galactoside-binding lectin galectin-3. Efficient blocking of β-galactoside-mediated adhesion precludes malignant cell lodging in target organs.

  9. Chromosomal locations and modes of action of genes of the retinoid (vitamin A) system support their involvement in the etiology of schizophrenia

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, A.B. [Columbia Univ. School of Public Health, New York, NY (United States)

    1995-08-14

    Vitamin A (retinoid), an essential nutrient for fetal and subsequent mammalian development, is involved in gene expression, cell differentiation, proliferation, migration, and death. Retinoic acid (RA) the morphogenic derivative of vitamin A is highly teratogenic. In humans retinoid excess or deficit can result in brain anomalies and psychosis. This review discusses chromosomal loci of genes that control the retinoid cascade in relation to some candidate genes in schizophrenia. The paper relates the knowledge about the transport, delivery, and action of retinoids to what is presently known about the pathology of schizophrenia, with particular reference to the dopamine hypothesis, neurotransmitters, the glutamate hypothesis, neurotransmitters, the glutamate hypothesis, retinitis pigmentosa, dermatologic disorders, and craniofacial anomalies. 201 refs., 1 tab.

  10. Breast Pain

    Science.gov (United States)

    ... result in the development of breast cysts. Breast trauma, prior breast surgery or other factors localized to the breast can lead to breast pain. Breast pain may also start outside the breast — in the chest wall, muscles, joints or heart, for example — and ...

  11. Ultrastructure and /sup 3/H-TdR autoradiography after topical application of aromatic retinoid in guinea pigs

    Energy Technology Data Exchange (ETDEWEB)

    Ueda, K.; Maruo, M.; Inoue, Y.; Wakabayashi, S. (Kyoto Prefectural Univ. of Medicine (Japan))

    1981-12-01

    Histological, autoradiographical and electron microscopical investigations were performed on the epidermis of guinea pigs after topical application of 0.1% aromatic retinoid ointment for 7 days. Histologically, the epidermis exhibited a thickening of granular layer and acanthosis, without a prolonged rete ridge. Labelling indices were 3 to 4 times higher than in the control epidermis. Electron microscopically, the nuclei in the spinous and the basal layer were large in size and nucleoli were increased in number. In the cytoplasm, tonofilaments were reduced in number and lots of vacuoles containing less dense amorphous material appeared. Amorphous material was present in the intercellular spaces of the epidermis. Differentiation and proliferation of the epidermis in guinea pigs after topical application of aromatic retinoid showed almost the same response in quantity to the epidermis after topical application of retinoic acid, while the epidermal alternation was slight in degree than in the epidermis after topical application of retinoic acid.

  12. Ultrastructure and 3H-TdR autoradiography after topical application of aromatic retinoid in guinea pigs

    International Nuclear Information System (INIS)

    Ueda, Keiichi; Maruo, Mitsuru; Inoue, Yuji; Wakabayashi, Shunji

    1981-01-01

    Histological, autoradiographical and electron microscopical investigations were performed on the epidermis of guinea pigs after topical application of 0.1% aromatic retinoid ointment for 7 days. Histologically, the epidermis exhibited a thickening of granular layer and acanthosis, without a prolonged rete ridge. Labelling indices were 3 to 4 times higher than in the control epidermis. Electron microscopically, the nuclei in the spinous and the basal layer were large in size and nucleoli were increased in number. In the cytoplasm, tonofilaments were reduced in number and lots of vacuoles containing less dense amorphous material appeared. Amorphous material was present in the intercellular spaces of the epidermis. Differentiation and proliferation of the epidermis in guinea pigs after topical application of aromatic retinoid showed almost the same response in quantity to the epidermis after topical application of retinoic acid, while the epidermal alternation was slight in degree than in the epidermis after topical application of retinoic acid. (author)

  13. N-retinylidene-phosphatidylethanolamine is the preferred retinoid substrate for the photoreceptor-specific ABC transporter ABCA4 (ABCR).

    Science.gov (United States)

    Beharry, Seelochan; Zhong, Ming; Molday, Robert S

    2004-12-24

    ABCA4, a member of the family of ATP binding cassette (ABC) proteins found in rod and cone photoreceptors, has been implicated in the transport of retinoid compounds across the outer segment disk membrane following the photoactivation of rhodopsin. Mutations in the ABCA4 gene are responsible for Stargardt macular dystrophy and related retinal degenerative diseases that cause a loss in vision. To identify the retinoid substrate that interacts with ABCA4, we have isolated ABCA4 from rod outer segment disk membranes on an immunoaffinity matrix and analyzed retinoid compounds that bind to ABCA4 using high performance liquid chromatography and radiolabeling methods. When all-trans-retinal was added to ABCA4 in the presence of phosphatidylethanolamine, approximately 0.9 mol of N-retinylidene-phosphatidylethanolamine and 0.3 mol of all-trans-retinal were bound per mol of ABCA4 with an apparent K(d) of 2-5 microm. ATP and GTP released these retinoids from ABCA4, whereas ADP, GDP, and nonhydrolyzable derivatives, adenosine 5'-(beta,gamma-imido)triphosphate and guanosine 5'-(beta,gamma-imido)triphosphate, were ineffective. One mole of N-retinyl-phosphatidylethanolamine, the reduced form of N-retinylidene-phosphatidylethanolamine, bound per mol of ABCA4, whereas 0.3 mol of all-trans-retinal were bound in the absence of phosphatidylethanolamine. No binding of all-trans-retinol to ABCA4 was observed. Our results indicate that ABCA4 preferentially binds N-retinylidene-phosphatidylethanolamine with high affinity in the absence of ATP. Our studies further suggest that ATP binding and hydrolysis induces a protein conformational change that causes N-retinylidene-phosphatidylethanolamine to dissociate from ABCA4.

  14. A comparison of carotenoids, retinoids, and tocopherols in the serum and buccal mucosa of chronic cigarette smokers versus nonsmokers.

    OpenAIRE

    Gabriel, Helen E.; Liu, Zhenhua; Crott, Jimmy W.; Choi, Sang-Woon; Song, Byeng Chun; Mason, Joel B.; Johnson, Elizabeth J.

    2006-01-01

    Biomarker: micronucleiDiet, food or substance: carotenoids, retinoids, and tocopherols. Study type: humans Study design: case-control studyStudy size: 35 smokers and 21 nonsmokers Tissue/biological material/sample size: Buccal Mucosa Cells (BMC); blood. Method of analysis: freshly prepared BMC suspension were smeared on a microscope slide and scored for the presence of micronuclei. Impact on outcome (including dose-response): General linear regression with adjustments for dietary intake showe...

  15. Distinct populations of hepatic stellate cells in the mouse liver have different capacities for retinoid and lipid storage.

    Directory of Open Access Journals (Sweden)

    Diana N D'Ambrosio

    Full Text Available Hepatic stellate cell (HSC lipid droplets are specialized organelles for the storage of retinoid, accounting for 50-60% of all retinoid present in the body. When HSCs activate, retinyl ester levels progressively decrease and the lipid droplets are lost. The objective of this study was to determine if the HSC population in a healthy, uninjured liver demonstrates heterogeneity in its capacity for retinoid and lipid storage in lipid droplets. To this end, we utilized two methods of HSC isolation, which leverage distinct properties of these cells, including their vitamin A content and collagen expression. HSCs were isolated either from wild type (WT mice in the C57BL/6 genetic background by flotation in a Nycodenz density gradient, followed by fluorescence activated cell sorting (FACS based on vitamin A autofluorescence, or from collagen-green fluorescent protein (GFP mice by FACS based on GFP expression from a GFP transgene driven by the collagen I promoter. We show that GFP-HSCs have: (i increased expression of typical markers of HSC activation; (ii decreased retinyl ester levels, accompanied by reduced expression of the enzyme needed for hepatic retinyl ester synthesis (LRAT; (iii decreased triglyceride levels; (iv increased expression of genes associated with lipid catabolism; and (v an increase in expression of the retinoid-catabolizing cytochrome, CYP2S1.Our observations suggest that the HSC population in a healthy, uninjured liver is heterogeneous. One subset of the total HSC population, which expresses early markers of HSC activation, may be "primed" and ready for rapid response to acute liver injury.

  16. Liver X receptors balance lipid stores in hepatic stellate cells through Rab18, a retinoid responsive lipid droplet protein.

    Science.gov (United States)

    O'Mahony, Fiona; Wroblewski, Kevin; O'Byrne, Sheila M; Jiang, Hongfeng; Clerkin, Kara; Benhammou, Jihane; Blaner, William S; Beaven, Simon W

    2015-08-01

    Liver X receptors (LXRs) are determinants of hepatic stellate cell (HSC) activation and liver fibrosis. Freshly isolated HSCs from Lxrαβ(-/-) mice have increased lipid droplet (LD) size, but the functional consequences of this are unknown. Our aim was to determine whether LXRs link cholesterol to retinoid storage in HSCs and how this impacts activation. Primary HSCs from Lxrαβ(-/-) and wild-type mice were profiled by gene array during in vitro activation. Lipid content was quantified by high-performance liquid chromatography and mass spectroscopy. Primary HSCs were treated with nuclear receptor ligands, transfected with small interfering RNA and plasmid constructs, and analyzed by immunocytochemistry. Lxrαβ(-/-) HSCs have increased cholesterol and retinyl esters. The retinoid increase drives intrinsic retinoic acid receptor signaling, and activation occurs more rapidly in Lxrαβ(-/-) HSCs. We identify Rab18 as a novel retinoic acid-responsive, LD-associated protein that helps mediate stellate cell activation. Rab18 mRNA, protein, and membrane insertion increase during activation. Both Rab18 guanosine triphosphatase activity and isoprenylation are required for stellate cell LD loss and induction of activation markers. These phenomena are accelerated in Lxrαβ(-/-) HSCs, where there is greater retinoic acid flux. Conversely, Rab18 knockdown retards LD loss in culture and blocks activation, just like the functional mutants. Rab18 is also induced with acute liver injury in vivo. Retinoid and cholesterol metabolism are linked in stellate cells by the LD-associated protein Rab18. Retinoid overload helps explain the profibrotic phenotype of Lxrαβ(-/-) mice, and we establish a pivotal role for Rab18 GTPase activity and membrane insertion in wild-type stellate cell activation. Interference with Rab18 may have significant therapeutic benefit in ameliorating liver fibrosis. © 2015 by the American Association for the Study of Liver Diseases.

  17. Liver X Receptors Balance Lipid Stores in Hepatic Stellate Cells via Rab18, a Retinoid Responsive Lipid Droplet Protein

    Science.gov (United States)

    O’Mahony, Fiona; Wroblewski, Kevin; O’Byrne, Sheila M.; Jiang, Hongfeng; Clerkin, Kara; Benhammou, Jihane; Blaner, William S.; Beaven, Simon W.

    2014-01-01

    Liver X receptors (LXRs) are determinants of hepatic stellate cell (HSC) activation and liver fibrosis. Freshly isolated HSCs from Lxrαβ−/− mice have increased lipid droplet (LD) size but the functional consequences of this are unknown. Our aim was to determine whether LXRs link cholesterol to retinoid storage in HSCs and how this impacts activation. Primary HSCs from Lxrαβ−/− and wild-type (WT) mice were profiled by gene array during in vitro activation. Lipid content was quantified by HPLC and mass spectroscopy. Primary HSCs were treated with nuclear receptor ligands, transfected with siRNA and plasmid constructs, and analyzed by immunocytochemistry. Lxrαβ−/− HSCs have increased cholesterol and retinyl esters (CEs & REs). The retinoid increase drives intrinsic retinoic acid receptor (RAR) signaling and activation occurs more rapidly in Lxrαβ−/− HSCs. We identify Rab18 as a novel retinoic acid responsive, lipid droplet associated protein that helps mediate stellate cell activation. Rab18 mRNA, protein, and membrane insertion increase during activation. Both Rab18 GTPase activity and isoprenylation are required for stellate cell lipid droplet loss and induction of activation markers. These phenomena are accelerated in the Lxrαβ−/− HSCs, where there is greater retinoic acid flux. Conversely, Rab18 knockdown retards lipid droplet loss in culture and blocks activation, just like the functional mutants. Rab18 is also induced with acute liver injury in vivo. Conclusion Retinoid and cholesterol metabolism are linked in stellate cells by the LD associated protein, Rab18. Retinoid overload helps explain the pro-fibrotic phenotype of Lxrαβ−/− mice and we establish a pivotal role for Rab18 GTPase activity and membrane insertion in wild-type stellate cell activation. Interference with Rab18 may have significant therapeutic benefit in ameliorating liver fibrosis. PMID:25482505

  18. Extracorporeal membrane oxygenation for refractory cardiac arrest

    Directory of Open Access Journals (Sweden)

    Steven A Conrad

    2017-01-01

    Full Text Available Extracorporeal cardiopulmonary resuscitation (ECPR is the use of rapid deployment venoarterial (VA extracorporeal membrane oxygenation to support systemic circulation and vital organ perfusion in patients in refractory cardiac arrest not responding to conventional cardiopulmonary resuscitation (CPR. Although prospective controlled studies are lacking, observational studies suggest improved outcomes compared with conventional CPR when ECPR is instituted within 30-60 min following cardiac arrest. Adult and pediatric patients with witnessed in-hospital and out-of-hospital cardiac arrest and good quality CPR, failure of at least 15 min of conventional resuscitation, and a potentially reversible cause for arrest are candidates. Percutaneous cannulation where feasible is rapid and can be performed by nonsurgeons (emergency physicians, intensivists, cardiologists, and interventional radiologists. Modern extracorporeal systems are easy to prime and manage and are technically easy to manage with proper training and experience. ECPR can be deployed in the emergency department for out-of-hospital arrest or in various inpatient units for in-hospital arrest. ECPR should be considered for patients with refractory cardiac arrest in hospitals with an existing extracorporeal life support program, able to provide rapid deployment of support, and with resources to provide postresuscitation evaluation and management.

  19. The action of a dietary retinoid on gene expression and cancer induction in electron-irradiated rat skin

    International Nuclear Information System (INIS)

    Burns, F.J.; Chen, S.; Xu, G.; Wu, F.; Tang, M.S.

    2002-01-01

    Current models of radiation carcinogenesis generally assume that the DNA is damaged in a variety of ways by the radiation and that subsequent cell divisions contribute to the conversion of the damage to heritable mutations. Cancer may seem complex and intractable, but its complexity provides multiple opportunities for preventive interventions. Mitotic inhibitors are among the strongest cancer preventive agents, not only slowing the growth rate of preneoplasias but also increasing the fidelity of DNA repair processes. Ionizing radiation, including electrons, is a strong inducer of cancer in rat skin, and dietary retinoids have shown potent cancer preventive activity in the same system. A non-toxic dietary dose of retinyl acetate altered gene expression levels 24 hours after electron irradiation of rat skin. Of the 8740 genes on an Affymetrix rat expression array, the radiation significantly (5 fold or higher) altered 188, while the retinoid altered 231, including 16 radiation-altered genes that were reversely altered. While radiation strongly affected the expression of stress response, immune/inflammation and nucleic acid metabolism genes, the retinoid most strongly affected proliferation-related genes, including some significant reversals, such as, keratin 14, retinol binding protein, and calcium binding proteins. These results point to reversal of proliferation-relevant genes as a likely basis for the anti-radiogenic effects of dietary retinyl acetate. (author)

  20. Waterborne cadmium and nickel impact oxidative stress responses and retinoid metabolism in yellow perch

    International Nuclear Information System (INIS)

    Defo, Michel A.; Bernatchez, Louis; Campbell, Peter G.C.; Couture, Patrice

    2014-01-01

    Highlights: • Cd and Ni affected indicators of retinoid metabolism and oxidative stress in fish. • Liver rdh-2 transcription levels increase in fish exposed to waterborne Cd. • Liver REH and LdRAT activities increase with increasing kidney Cd concentration. • Changes at molecular levels do not always mean changes at the functional levels. • Multi-level biological approaches are needed when assessing fish metal toxicology. - Abstract: In this experiment, we studied the transcriptional and functional (enzymatic) responses of yellow perch (Perca flavescens) to metal stress, with a focus on oxidative stress and vitamin A metabolism. Juvenile yellow perch were exposed to two environmentally relevant concentrations of waterborne cadmium (Cd) and nickel (Ni) for a period of 6 weeks. Kidney Cd and Ni bioaccumulation significantly increased with increasing metal exposure. The major retinoid metabolites analyzed in liver and muscle decreased with metal exposure except at high Cd exposure where no variation was reported in liver. A decrease in free plasma dehydroretinol was also observed with metal exposure. In the liver of Cd-exposed fish, both epidermal retinol dehydrogenase 2 transcription level and corresponding enzyme activities retinyl ester hydrolase and lecithin dehydroretinyl acyl transferase increased. In contrast, muscle epidermal retinol dehydrogenase 2 transcription level decreased with Cd exposure. Among antioxidant defences, liver transcription levels of catalase, microsomal glutathione-S-transferase-3 and glucose-6-phosphate dehydrogenase were generally enhanced in Cd-exposed fish and this up-regulation was accompanied by an increase in the activities of corresponding enzymes, except for microsomal glutathione-S-transferase. No consistent pattern in antioxidant defence responses was observed between molecular and biochemical response when fish were exposed to Ni, suggesting a non-synchronous response of antioxidant defence in fish exposed to

  1. Waterborne cadmium and nickel impact oxidative stress responses and retinoid metabolism in yellow perch

    Energy Technology Data Exchange (ETDEWEB)

    Defo, Michel A. [Institut national de la recherche scientifique (INRS), Centre Eau Terre Environnement, 490 de la Couronne, Québec, Québec G1K 9A9 (Canada); Bernatchez, Louis [Institut de Biologie Intégrative et des Systèmes (IBIS), Université Laval, Québec, Québec G1V 0A6 (Canada); Campbell, Peter G.C. [Institut national de la recherche scientifique (INRS), Centre Eau Terre Environnement, 490 de la Couronne, Québec, Québec G1K 9A9 (Canada); Couture, Patrice, E-mail: patrice.couture@ete.inrs.ca [Institut national de la recherche scientifique (INRS), Centre Eau Terre Environnement, 490 de la Couronne, Québec, Québec G1K 9A9 (Canada)

    2014-09-15

    Highlights: • Cd and Ni affected indicators of retinoid metabolism and oxidative stress in fish. • Liver rdh-2 transcription levels increase in fish exposed to waterborne Cd. • Liver REH and LdRAT activities increase with increasing kidney Cd concentration. • Changes at molecular levels do not always mean changes at the functional levels. • Multi-level biological approaches are needed when assessing fish metal toxicology. - Abstract: In this experiment, we studied the transcriptional and functional (enzymatic) responses of yellow perch (Perca flavescens) to metal stress, with a focus on oxidative stress and vitamin A metabolism. Juvenile yellow perch were exposed to two environmentally relevant concentrations of waterborne cadmium (Cd) and nickel (Ni) for a period of 6 weeks. Kidney Cd and Ni bioaccumulation significantly increased with increasing metal exposure. The major retinoid metabolites analyzed in liver and muscle decreased with metal exposure except at high Cd exposure where no variation was reported in liver. A decrease in free plasma dehydroretinol was also observed with metal exposure. In the liver of Cd-exposed fish, both epidermal retinol dehydrogenase 2 transcription level and corresponding enzyme activities retinyl ester hydrolase and lecithin dehydroretinyl acyl transferase increased. In contrast, muscle epidermal retinol dehydrogenase 2 transcription level decreased with Cd exposure. Among antioxidant defences, liver transcription levels of catalase, microsomal glutathione-S-transferase-3 and glucose-6-phosphate dehydrogenase were generally enhanced in Cd-exposed fish and this up-regulation was accompanied by an increase in the activities of corresponding enzymes, except for microsomal glutathione-S-transferase. No consistent pattern in antioxidant defence responses was observed between molecular and biochemical response when fish were exposed to Ni, suggesting a non-synchronous response of antioxidant defence in fish exposed to

  2. Combination Superficial Peels With Salicylic Acid and Post-Peel Retinoids.

    Science.gov (United States)

    Kligman, Douglas E; Draelos, Zoe D

    2016-04-01

    Salicylic acid (SA) and retinoids, tretinoin (all-trans retinoic acid [ATRA]), and retinol (all-trans retinol) are widely used as topical agents for the improvement of photodamage and acne vulgaris. They can be used in daily take-home products or as part of an in-office procedure, combining the benefits of a keratolytic (SA) and a retinoid. The objective of this research was to compare the efficacy for ameliorating photodamage of topical tretinoin (0.25%) and retinol (0.25%) to baseline and with each other when applied after a 30% salicylic acid peel on human facial skin. Twenty female subjects received a full face 30% SA peel followed by the overnight application of tretinoin to a 1 randomized half-face and retinol to the opposite side (split-face study). The identical procedure was repeated at week 2. Double-blinded subject and investigator assessments of the results were captured at weeks 2 and 4. By investigator evaluation, both peeling regimens were effective in improving photodamage parameters compared to baseline. (ATRA P-values at week 4 were: P=.00008 texture, P=.00013 roughness, P=.00221 pores, P=.00098 dryness, P=.02770 erythema, and P=.00008 overall appearance. Retinol P-values at week 4 were: P=.00019 texture, P=.00053 roughness, P=.00221 pores, P=.00147 dryness, P=.02770 erythema, and P=.0043 overall appearance.) By subject self-assessment compared with baseline, both tretinoin and retinol were effective in improving overall appearance (ATRA P=.0229 and retinol P=.0190). By investigator evaluation comparing tretinoin with retinol, tretinoin was slightly better than retinol at week 4 in improving texture P=.00506, roughness P=.01171, and overall appearance P=.00506. By subject self-assessment comparing tretinoin with retinol, there was no difference in overall appearance (ATRA P=.2367 and retinol P=.3613). Either topical tretinoin (0.25%) or retinol (0.25%) can be used safely and effectively when applied in office immediately after SA peeling to

  3. The Role of RB in the Therapeutic Response of Breast Cancer

    National Research Council Canada - National Science Library

    Bosco, Emily E

    2005-01-01

    The retinoblastoma tumor suppressor protein (RB) participates in the growth regulation of breast cancer cells by controlling G-S phase progression and mediating cell cycle arrest in response to anti-mitogenic signaling...

  4. Comparison of crack arrest methodologies

    International Nuclear Information System (INIS)

    Anon.

    1979-01-01

    The ASTM Cooperative Test Program Data were used to compare the static (K/sub Ia/) and dynamic (K/sud ID/, K/sub IDm/) approaches to crack arrest. K/sub Ia/ is not dependent on K/sub Q/. This is consistent with the requirements of the static approach, but not the dynamic one which requires that K/sub Ia/ decrease with K/sub Q/ if K/sub ID/ (= K/sub IDm/) is a constant. K/sub ID/ increases systematically with K/sub Q/ at a rate that is consistent with calculations based on the use of a constant value for K/sub Ia/ which is equal to its measured mean value. Only in the limiting case of very short crack jumps (associated with very low average crack speeds) can K/sub ID/ be identified as a minimum value at which K/sub ID/ = K/sub IDm/. In this case K/sub IDm/ approx. K/sub Ia/ approx. K/sub Im/. The latter is the idealized minimum value of K that will support the continued propagation of a running crack

  5. Retinoids repress Ah receptor CYP1A1 induction pathway through the SMRT corepressor

    International Nuclear Information System (INIS)

    Fallone, Frederique; Villard, Pierre-Henri; Seree, Eric; Rimet, Odile; Nguyen, Quock Binh; Bourgarel-Rey, Veronique; Fouchier, Francis; Barra, Yves; Durand, Alain; Lacarelle, Bruno

    2004-01-01

    CYP1A1 isoform is mainly regulated by the transcription factor AhR and to a lesser extent by the nuclear receptor RAR. The effect of a coexposure with 3MC, a AhR ligand, and RA, a RAR ligand, which are, respectively, strong and weak CYP1A1 inducers, is poorly known. We showed in Caco-2 cells that addition of RA significantly decreased 3MC-induced CYP1A1 expression by -55% for mRNA level and -30% for promoter and enzymatic activities. We further showed that RA decreased AhR protein level. Moreover, a physical interaction between AhR and the RAR-corepressor SMRT has been described in vitro. Using the corepressor inhibitor TSA, transfected-cells with SMRT cDNA, and coimmunoprecipitation experiments, we demonstrated that RA addition repressed AhR function through a marked AhR/SMRT physical interaction. This interaction explains the decrease of 3MC-induced CYP1A1 expression. This new mechanism involving the repression of AhR-induced CYP1A1 expression by retinoids allows better knowledge of the CYP1A1 regulation

  6. Abscisic-acid-induced cellular apoptosis and differentiation in glioma via the retinoid acid signaling pathway.

    Science.gov (United States)

    Zhou, Nan; Yao, Yu; Ye, Hongxing; Zhu, Wei; Chen, Liang; Mao, Ying

    2016-04-15

    Retinoid acid (RA) plays critical roles in regulating differentiation and apoptosis in a variety of cancer cells. Abscisic acid (ABA) and RA are direct derivatives of carotenoids and share structural similarities. Here we proposed that ABA may also play a role in cellular differentiation and apoptosis by sharing a similar signaling pathway with RA that may be involved in glioma pathogenesis. We reported for the first time that the ABA levels were twofold higher in low-grade gliomas compared with high-grade gliomas. In glioma tissues, there was a positive correlation between the ABA levels and the transcription of cellular retinoic acid-binding protein 2 (CRABP2) and a negative correlation between the ABA levels and transcription of fatty acid-binding protein 5 (FABP5). ABA treatment induced a significant increase in the expression of CRABP2 and a decrease in the expression of peroxisome proliferator-activated receptor (PPAR) in glioblastoma cells. Remarkably, both cellular apoptosis and differentiation were increased in the glioblastoma cells after ABA treatment. ABA-induced cellular apoptosis and differentiation were significantly reduced by selectively silencing RAR-α, while RAR-α overexpression exaggerated the ABA-induced effects. These results suggest that ABA may play a role in the pathogenesis of glioma by promoting cellular apoptosis and differentiation through the RA signaling pathway. © 2015 UICC.

  7. Retinoid X Receptor α-Dependent HBV Minichromosome Remodeling and Viral Replication.

    Science.gov (United States)

    Zhang, Yan; He, Song; Guo, Jin-Jun; Peng, Hong; Fan, Jia-Hao; Li, Qing-Ling

    2017-01-01

    The HBV covalently closed circular DNA (cccDNA) is organized into a minichromosome in the nuclei of infected hepatocytes through interactions with histone and nonhistone proteins. Retinoid X receptor α (RXRα), a liver-enriched nuclear receptor, participates in regulation of HBV replication and transcription through modulation of HBV enhancer 1 and core promoter activity. This study investigated RXRα involvement in HBV cccDNA epigenetic modifications. Quantitative cccDNA chromatin immunoprecipitation (ChIP) was applied to study the recruitment of RXRα, histones, and chromatin-modifying enzymes to HBV minichromosome in HepG2 cells after transfection of the linear HBV genome. RXRα Was found to directly bind to HBV cccDNA; recruitment of RXRα to HBV mini-chromosome paralleled HBV replication, histone recruitment, and histone acetylation in HBVcccDNA. Moreover, RXRα overexpression or knock-down significantly increased or impaired the recruitment of the p300 acetyltransferase to cccDNAminichromosome. Our results confirmed the regulation of RXRα on HBV replication in vitro and demonstrated the modulation of RXRα on HBV cccDNA epigenetics. These findings provide a profound theoretical and experimental basis for late-model antiviral treatment acting on the HBV cccDNA and minichromosome.

  8. Vitamin D Receptor, Retinoid X Receptor, Ki-67, Survivin, and Ezrin Expression in Canine Osteosarcoma

    Directory of Open Access Journals (Sweden)

    John Davies

    2012-01-01

    Full Text Available Canine osteosarcoma (OS is an aggressive malignant bone tumor. Prognosis is primarily determined by clinical parameters. Vitamin D has been postulated as a novel therapeutic option for many malignancies. Upon activation, vitamin D receptors (VDRs combine with retinoid receptor (RXR forming a heterodimer initiating a cascade of events. Vitamin D's antineoplastic activity and its mechanism of action in OS remain to be clearly established. Expression of VDR, RXR, Ki-67, survivin, and ezrin was studied in 33 archived, canine OS specimens. VDR, RXR, survivin, and ezrin were expressed in the majority of cases. There was no statistically significant difference in VDR expression in relationship with tumor grade, type, or locations or animal breed, age, and/or sex. No significant association (p=0.316 between tumor grade and Ki-67 expression was found; in particular, no difference in Ki-67 expression between grades 2 and 3 OSs was found, while a negative correlation was noted between Ki-67 and VDR expression (ρ=−0.466, a positive correlation between survivin and RXR expression was found (p=0.374. A significant relationship exists between VDR and RXR expression in OSs and proliferative/apoptosis markers. These results establish a foundation for elucidating mechanisms by which vitamin D induces antineoplastic activity in OS.

  9. Retinoid X receptor gene expression and protein content in tissues of the rock shell Thais clavigera

    Energy Technology Data Exchange (ETDEWEB)

    Horiguchi, Toshihiro [Research Center for Environmental Risk, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506 (Japan)], E-mail: thorigu@nies.go.jp; Nishikawa, Tomohiro [Research Center for Environmental Risk, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506 (Japan); Ohta, Yasuhiko [Department of Veterinary Science, Faculty of Agriculture, Tottori University, 4-101 Koyamacho-Minami, Tottori 680-8553 (Japan); Shiraishi, Hiroaki; Morita, Masatoshi [Research Center for Environmental Risk, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506 (Japan)

    2007-10-15

    To elucidate the role of retinoid X receptor (RXR) in the development of imposex caused by organotin compounds in gastropod molluscs, we investigated RXR gene expression and RXR protein content in various tissues of male and female wild rock shells (Thais clavigera). Quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry with a commercial antibody against human RXR {alpha} revealed that RXR gene expression was significantly higher in the penises of males and imposex-exhibiting females than in the penis-forming areas of normal females (P < 0.01 and P < 0.05, respectively). Western blotting demonstrated that the antibody could detect rock shell RXR and showed that the male penis had the highest content of RXR protein among the analyzed tissues of males and normal females. Immunohistochemical staining revealed nuclear localization of RXR protein in the epithelial and smooth muscle cells of the vas deferens and in the interstitial or connective tissues and epidermis of the penis in males and imposex-exhibiting females. RXR could be involved in the mechanism of induction of male-type genitalia (penis and vas deferens) by organotin compounds in female rock shells.

  10. Crisis management during anaesthesia: cardiac arrest.

    Science.gov (United States)

    Runciman, W B; Morris, R W; Watterson, L M; Williamson, J A; Paix, A D

    2005-06-01

    Cardiac arrest attributable to anaesthesia occurs at the rate of between 0.5 and 1 case per 10 000 cases, tends to have a different profile to that of cardiac arrest occurring elsewhere, and has an in-hospital mortality of 20%. However, as individual practitioners encounter cardiac arrest rarely, the rapidity with which the diagnosis is made and the consistency of appropriate management varies considerably. To examine the role of a previously described core algorithm "COVER ABCD-A SWIFT CHECK", supplemented by a sub-algorithm for cardiac arrest, in the management of cardiac arrest occurring in association with anaesthesia. The potential performance of this structured approach for each the relevant incidents among the first 4000 reported to the Australian Incident Monitoring Study (AIMS) was compared with the actual management as reported by the anaesthetists involved. There were 129 reports of cardiac arrest associated with anaesthesia among the first 4000 AIMS incident reports. Identified aetiological factors were grouped into five categories: (1) anaesthetic technique (11 cases with this category alone; 32 with this and one or more of the other categories, representing 25% of all 129 cardiac arrests); (2) drug related (16; 32, 25%); (3) associated with surgical procedure (9; 29, 22%); (4) associated with pre-existing medical or surgical disease (30; 82, 64%); (5) unknown (8; 14, 11%). The "real life" presentation and management of cardiac arrest in association with anaesthesia differs substantially from that detailed in general published guidelines. Cardiac rhythms at the time were sinus bradycardia (23%); asystole (22%); tachycardia/ventricular tachycardia/ventricular fibrillation (14%); and normal (7%), with a further third unknown. Details of treatment were recorded in 110 reports; modalities employed included cardiac compression (72%); adrenaline (61%); 100% oxygen (58%); atropine (38%); intravenous fluids (25%), and electrical defibrillation (17%). There

  11. Dental Calculus Arrest of Dental Caries

    OpenAIRE

    Keyes, Paul H.; Rams, Thomas E.

    2016-01-01

    Background An inverse relationship between dental calculus mineralization and dental caries demineralization on teeth has been noted in some studies. Dental calculus may even form superficial layers over existing dental caries and arrest their progression, but this phenomenon has been only rarely documented and infrequently considered in the field of Cariology. To further assess the occurrence of dental calculus arrest of dental caries, this study evaluated a large number of extracted human t...

  12. Tumor-suppressor activity of RRIG1 in breast cancer

    International Nuclear Information System (INIS)

    Zhang, Guihong; Brewster, Abenaa; Guan, Baoxiang; Fan, Zhen; Brown, Powel H; Xu, Xiao-Chun

    2011-01-01

    Retinoid receptor-induced gene-1 (RRIG1) is a novel gene that has been lost in several types of human cancers. The aim of this study was to determine whether RRIG1 plays a role in breast cancer, such as in the suppression of breast cancer cell growth and invasion. Immunohistochemistry was used to detect RRIG1 expression in breast tissue specimens. Gene transfection was used to restore or knock down RRIG1 expression in breast cancer cell lines for analysis of cell viability, colony formation, and migration/invasion potential. Reverse-transcription polymerase chain reaction and western blot assays were used to detect the changes in gene expression. The RhoA activation assay was used to assess RRIG1-induced inhibition of RhoA activity. The immunohistochemical data showed that RRIG1 expression was reduced in breast cancer tissues compared with normal and atypical hyperplastic breast tissues. RRIG1 expression was inversely correlated with lymph node metastasis of breast cancer but was not associated with the status of hormone receptors, such as estrogen receptor, progesterone receptor, or HER2. Furthermore, restoration of RRIG1 expression inhibited proliferation, colony formation, migration, and invasion of breast cancer cells. Expression of RRIG1 also reduced phosphorylated Erk1/2 and Akt levels; c-Jun, MMP9, and Akt expressions; and RhoA activity. In contrast, knockdown of RRIG1 expression promoted breast cancer cell proliferation, colony formation, migration, and invasion potential. The data from the current study indicated that RRIG1 expression was reduced or lost in breast cancer and that restoration of RRIG1 expression suppressed breast cancer cell growth and invasion capacity. Future studies will determine the underlying molecular mechanisms and define RRIG1 as a tumor-suppressor gene in breast cancer

  13. Sex Disparities in Arrest Outcomes for Domestic Violence

    Science.gov (United States)

    Hamilton, Melissa; Worthen, Meredith G. F.

    2011-01-01

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

  14. Hepatic retinoid levels in seven fish species (teleosts) from a tropical coastal lagoon receiving effluents from iron-ore mining and processing.

    Science.gov (United States)

    Pereira, Adriana A; van Hattum, Bert; Brouwer, Abraham

    2012-02-01

    The present study was undertaken to investigate the possible effects of Fe and trace element exposure on hepatic levels of retinoids in seven fish species. Concentrations of retinoids were measured in fish collected from a coastal lagoon in Brazil that receives effluents from an iron-ore mining and processing plant. Fish from nearby coastal lagoons were also included to assess possible differences related to chemical exposure. Results indicated considerable differences in hepatic retinoid composition among the various species investigated. The most striking differences were in retinol and derivative-specific profiles and in didehydro retinol and derivative-specific profiles. The Perciformes species Geophagus brasiliensis, Tilapia rendalli, Mugil liza, and Cichla ocellaris and the Characiforme Hoplias malabaricus were characterized as retinol and derivative-specific, while the Siluriformes species Hoplosternum littorale and Rhamdia quelen were didehydro retinol and derivative-specific fish species. A negative association was observed between Al, Pb, As, and Cd and hepatic didehydro retinoid levels. Fish with higher levels of hepatic Fe, Cu, and Zn showed unexpectedly significant positive correlations with increased hepatic retinol levels. This finding, associated with the positive relationships between retinol and retinyl palmitate with lipid peroxidation, may suggest that vitamin A is mobilized from other tissues to increase hepatic antioxidant levels for protection against oxidative damage. These data show significant but dissimilar associations between trace element exposure and hepatic retinoid levels in fish species exposed to iron-ore mining and processing effluents, without apparent major impacts on fish health and condition. Copyright © 2011 SETAC.

  15. Assessment of the efficacy and safety of a combination of 2 topical retinoids (RetinSphere) in maintaining post-treatment response of acne to oral isotretinoin.

    Science.gov (United States)

    Truchuelo, M T; Jiménez, N; Mavura, D; Jaén, P

    2015-03-01

    The high rate of relapse of acne lesions following oral isotretinoin treatment is a common problem which remains unsolved. To avoid or minimize relapses, topical retinoids have been used for many years as maintenance treatment. However, adverse effects frequently occur. To determine the efficacy and safety of a new retinoid combination (Retinsphere technology) in maintaining post-treatment response to oral isotretinoin. Prospective, randomized, double-blind and vehicle-controlled study of 30 patients with acne previously treated with isotretinoin. Treatment with the retinoid combination was applied to one side of the face and vehicle was applied to the other, once daily, for 3 months. Standardized photographs were taken using RBX technology at baseline, 1.5 months and 3 months. The primary efficacy endpoint was the appearance of relapse on the treated side compared to the vehicle-treated side. Other endpoints included lesion count, investigator-reported improvement, patient-reported improvement, impact on quality-of-life, and side effects. Although the majority of patients did not reach the total target dose of oral isotretinoin, the relapse rate was significantly lower on the retinoid-treated side compared to the vehicle-treated side. Likewise, improved lesion count and excellent tolerance were observed. This new retinoid combination (Retinsphere technology) were effective and safe as maintenance therapy after post-treatment response to oral isotretinoin in patients with acne. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

  16. The Effects of Fatty Acids on Retinoid Signaling in Human Mammary Epithelial Cells and Breast Cancer Cells

    National Research Council Canada - National Science Library

    Langton, Simne; Gudas, Lorraine J

    2005-01-01

    ...) and docosahexaenoic acid (DHA) are diet-derived fatty acids that bind to rexinoid X receptors (RXR). Therefore, we hypothesized that inhibitory effects on cell proliferation may be enhanced by the addition of PA and DHA to RA- treated cells...

  17. The Effects of Fatty Acids on Retinoid Signaling in Human Mammary Epithelial Cells and Breast Cancer Cells

    National Research Council Canada - National Science Library

    Langton, Simne; Gudas, Lorraine J

    2004-01-01

    ...) and docosahexaenoic acid (DHA) are diet-derived fatty acids that bind to rexinoid X receptors (RXR). Therefore, we hypothesized that inhibitory effects on cell proliferation may be enhanced by the addition of PA and DHA to RA-treated cells...

  18. Natural and synthetic retinoids afford therapeutic effects on intracerebral hemorrhage in mice.

    Science.gov (United States)

    Matsushita, Hideaki; Hijioka, Masanori; Hisatsune, Akinori; Isohama, Yoichiro; Shudo, Koichi; Katsuki, Hiroshi

    2012-05-15

    We have recently proposed that retinoic acid receptor (NR1B) is a promising target of neuroprotective therapy for intracerebral hemorrhage, since pretreatment of mice with an NR1B1/NR1B2 agonist Am80 attenuated various pathological and neurological abnormalities associated with the disease. In the present study we further addressed the effects of retinoids as potential therapeutic drugs, using a collagenase-induced model of intracerebral hemorrhage. Daily oral administration of all-trans retinoic acid (ATRA; 5 and 15 mg/kg), a naturally occurring NR1B agonist, from 1 day before collagenase injection significantly inhibited loss of neurons within the hematoma. ATRA in the same treatment regimen also decreased the number of activated microglia/macrophages around the hematoma but did not affect the hematoma volume. ATRA (15 mg/kg) as well as Am80 (5mg/kg) rescued neurons in the central region of hematoma, even when drug administration was started from 6h after induction of intracerebral hemorrhage. However, in this post-treatment regimen, only Am80 significantly decreased the number of activated microglia/macrophages. With regard to neurological deficits, both ATRA (15 mg/kg) and Am80 (5mg/kg) given in the post-treatment regimen improved performance of mice in the beam-walking test and the modified limb-placing test. ATRA and Am80 also significantly attenuated damage of axon tracts as revealed by amyloid precursor protein immunohistochemistry. These results underscore potential therapeutic values of NR1B agonists for intracerebral hemorrhage. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Arrested larval development in cattle nematodes.

    Science.gov (United States)

    Armour, J; Duncan, M

    1987-06-01

    Most economically important cattle nematodes are able to arrest their larval development within the host - entering a period of dormancy or hypobiosis. Arrested larvae have a low death rate, and large numbers can accumulate in infected cattle during the grazing season. Because of this, outbreaks of disease caused by such nematodes can occur at times when recent infection with the parasites could not have occurred, for example during winter in temperature northern climates when cattle are normally housed. The capacity to arrest is a heritable trait. It is seen as an adaptation by the parasite to avoid further development to its free-living stages during times when the climate is unsuitable for free-living survival. But levels of arrestment can vary markedly in different regions, in different cattle, and under different management regimes. Climatic factors, previous conditioning, host immune status, and farm management all seem to affect arrestment levels. In this article, James Armour and Mary Duncan review the biological basis of the phenomenon, and discuss the apparently conflicting views on how it is controlled.

  20. Putrescine treatment reverses α-tocopherol-induced desynchronization of polyamine and retinoid metabolism during rat liver regeneration

    Directory of Open Access Journals (Sweden)

    Lourdes Sánchez-Sevilla

    2016-10-01

    Full Text Available Abstract Background The pre-treatment with α-tocopherol inhibits progression of rat liver proliferation induced by partial hepatectomy (PH, by decreasing and/or desynchronizing cyclin D1 expression and activation into the nucleus, activation and nuclear translocation of STAT-1 and -3 proteins and altering retinoid metabolism. Interactions between retinoic acid and polyamines have been reported in the PH-induced rat liver regeneration. Therefore, we evaluated the effect of low dosage of α-tocopherol on PH-induced changes in polyamine metabolism. Methods This study evaluated the participation of polyamine synthesis and metabolism during α-tocopherol-induced inhibition of rat liver regeneration. In PH-rats (Wistar treated with α-tocopherol and putrescine, parameters indicative of cell proliferation, lipid peroxidation, ornithine decarboxylase expression (ODC, and polyamine levels, were determined. Results Pre-treatment with α-tocopherol to PH-animals exerted an antioxidant effect, shifting earlier the increased ODC activity and expression, temporally affecting polyamine synthesis and ornithine metabolism. Whereas administration of putrescine induced minor changes in PH-rats, the concomitant treatment actually counteracted most of adverse actions exerted by α-tocopherol on the remnant liver, restituting its proliferative potential, without changing its antioxidant effect. Putrescine administration to these rats was also associated with lower ODC expression and activity in the proliferating liver, but the temporally shifting in the amount of liver polyamines induced by α-tocopherol, was also “synchronized” by the putrescine administration. The latter is supported by the fact that a close relationship was observed between fluctuations of polyamines and retinoids. Conclusions Putrescine counteracted most adverse actions exerted by α-tocopherol on rat liver regeneration, restoring liver proliferative potential and restituting the decreased

  1. Breast Tomosynthesis

    Science.gov (United States)

    ... in distinguishing non-cancerous breast conditions from breast cancers. Breast implants may also impede accurate mammogram readings because both ... view as much as possible without rupturing the implant. top of ... discuss breast cancer screening options with their doctors: Breast Density and ...

  2. Breast infection

    Science.gov (United States)

    Mastitis; Infection - breast tissue; Breast abscess ... must continue to breastfeed or pump to relieve breast swelling from milk production. In case if the abscess does not go away, needle aspiration under ultrasound ...

  3. Breast lump

    Science.gov (United States)

    ... with milk). These cysts can occur with breastfeeding. Breast abscess . These typically occur if you are breastfeeding or ... Breast infections are treated with antibiotics. Sometimes a breast abscess needs to be drained with a needle or ...

  4. Breast Diseases

    Science.gov (United States)

    ... bumps, and discharges (fluids that are not breast milk). If you have a breast lump, pain, discharge or skin irritation, see your health care provider. Minor and serious breast problems have similar ...

  5. Breast lift

    Science.gov (United States)

    ... and areola may be moved. Sometimes, women have breast augmentation (enlargement with implants) when they have a breast lift. Why the ... MD, FACS, general surgery practice specializing in breast cancer, Virginia Mason Medical Center, Seattle, WA. Also reviewed ...

  6. Breast cancer

    Science.gov (United States)

    ... can help you know how to prevent breast cancer. Breast implants, using antiperspirants, and wearing underwire bras do not increase the risk for breast cancer. There is also no evidence of a direct ...

  7. Fibroadenoma - breast

    Science.gov (United States)

    Breast lump - fibroadenoma; Breast lump - noncancerous; Breast lump - benign ... The cause of fibroadenomas is not known. They may be related to hormones. Girls who are going through puberty and women who are ...

  8. Location of cardiac arrest and impact of pre-arrest chronic disease and medication use on survival

    DEFF Research Database (Denmark)

    Granfeldt, Asger; Wissenberg, Mads; Hansen, Steen Møller

    2017-01-01

    location and a higher mortality can be explained by differences in chronic diseases and medication. METHODS: We identified 27,771 out-of-hospital cardiac arrest patients ≥18 years old from the Danish Cardiac Arrest Registry (2001-2012). Using National Registries, we identified pre-arrest chronic disease......INTRODUCTION: Cardiac arrest in a private location is associated with a higher mortality when compared to public location. Past studies have not accounted for pre-arrest factors such as chronic disease and medication. AIM: To investigate whether the association between cardiac arrest in a private...

  9. Effect of Am-80, A Novel Retinoid Derivative, On Contact Hypersensitivity Caused by Repeated Applications of Hapten in Mice

    Directory of Open Access Journals (Sweden)

    Satoru Niwa

    2000-01-01

    Full Text Available Some retinoids show an anti-inflammatory action through regulation of transcription of various genes. In the present study, the inhibitory effect of 4-((5,6,7,8- tetrahydro-5,5,8,8-tetramethyl-2-naphthyl carbamoyl benzoic acid (Am-80, a synthetic retinoid, on mouse contact hypersensitivity provoked by repeated applications of 2,4-dinitrofluorobenzene (DNFB to the ear was investigated. Five-fold applications of DNFB on ears once per week elicited severe contact dermatitis with marked infiltration of inflammatory cells and elevation of anti-dinitrophenyl (DNP-IgE antibody in the serum. The Am-80 significantly inhibited ear swelling in a dose-dependent manner. In the histopathologic study, infiltration of inflammatory cells was clearly decreased by Am-80. However, Am-80 did not affect the production of DNP-specific IgE antibody both at the transcriptional and post-transcriptional levels. The effects of Am-80 on the transcriptional level of cytokines, interferon (IFN-γ, interleukin (IL-1 and IL-4 in cervical lymph nodes were investigated. Marked elevation of mRNA for all cytokines was observed and Am-80 potently inhibited the expression of IFN-γ mRNA, but not IL-1 and IL-4 mRNA. These findings indicated that Am-80 may inhibit the contact dermatitis at the post-sensitization phase by inhibiting IFN-γ production at the transcriptional level in mice.

  10. Breast reconstruction - implants

    Science.gov (United States)

    Breast implants surgery; Mastectomy - breast reconstruction with implants; Breast cancer - breast reconstruction with implants ... harder to find a tumor if your breast cancer comes back. Getting breast implants does not take as long as breast reconstruction ...

  11. Dietary Natural Products for Prevention and Treatment of Breast Cancer.

    Science.gov (United States)

    Li, Ya; Li, Sha; Meng, Xiao; Gan, Ren-You; Zhang, Jiao-Jiao; Li, Hua-Bin

    2017-07-08

    Breast cancer is the most common cancer among females worldwide. Several epidemiological studies suggested the inverse correlation between the intake of vegetables and fruits and the incidence of breast cancer. Substantial experimental studies indicated that many dietary natural products could affect the development and progression of breast cancer, such as soy, pomegranate, mangosteen, citrus fruits, apple, grape, mango, cruciferous vegetables, ginger, garlic, black cumin, edible macro-fungi, and cereals. Their anti-breast cancer effects involve various mechanisms of action, such as downregulating ER-α expression and activity, inhibiting proliferation, migration, metastasis and angiogenesis of breast tumor cells, inducing apoptosis and cell cycle arrest, and sensitizing breast tumor cells to radiotherapy and chemotherapy. This review summarizes the potential role of dietary natural products and their major bioactive components in prevention and treatment of breast cancer, and special attention was paid to the mechanisms of action.

  12. The effect of acyclic retinoid on the metabolomic profiles of hepatocytes and hepatocellular carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Xian-Yang Qin

    Full Text Available BACKGROUND/PURPOSE: Acyclic retinoid (ACR is a promising chemopreventive agent for hepatocellular carcinoma (HCC that selectively inhibits the growth of HCC cells (JHH7 but not normal hepatic cells (Hc. To better understand the molecular basis of the selective anti-cancer effect of ACR, we performed nuclear magnetic resonance (NMR-based and capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS-based metabolome analyses in JHH7 and Hc cells after treatment with ACR. METHODOLOGY/PRINCIPAL FINDINGS: NMR-based metabolomics revealed a distinct metabolomic profile of JHH7 cells at 18 h after ACR treatment but not at 4 h after ACR treatment. CE-TOFMS analysis identified 88 principal metabolites in JHH7 and Hc cells after 24 h of treatment with ethanol (EtOH or ACR. The abundance of 71 of these metabolites was significantly different between EtOH-treated control JHH7 and Hc cells, and 49 of these metabolites were significantly down-regulated in the ACR-treated JHH7 cells compared to the EtOH-treated JHH7 cells. Of particular interest, the increase in adenosine-5'-triphosphate (ATP, the main cellular energy source, that was observed in the EtOH-treated control JHH7 cells was almost completely suppressed in the ACR-treated JHH7 cells; treatment with ACR restored ATP to the basal levels observed in both EtOH-control and ACR-treated Hc cells (0.72-fold compared to the EtOH control-treated JHH7 cells. Moreover, real-time PCR analyses revealed that ACR significantly increased the expression of pyruvate dehydrogenase kinases 4 (PDK4, a key regulator of ATP production, in JHH7 cells but not in Hc cells (3.06-fold and 1.20-fold compared to the EtOH control, respectively. CONCLUSIONS/SIGNIFICANCE: The results of the present study suggest that ACR may suppress the enhanced energy metabolism of JHH7 cells but not Hc cells; this occurs at least in part via the cancer-selective enhancement of PDK4 expression. The cancer-selective metabolic pathways

  13. Thyroid hormone and retinoid X receptor function and expression during sea lamprey (Petromyzon marinus) metamorphosis.

    Science.gov (United States)

    Manzon, Lori A; Youson, John H; Holzer, Guillaume; Staiano, Leopoldo; Laudet, Vincent; Manzon, Richard G

    2014-08-01

    Sea lampreys (Petromyzon marinus) are members of the ancient class Agnatha and undergo a metamorphosis that transforms blind, sedentary, filter-feeding larvae into free-swimming, parasitic juveniles. Thyroid hormones (THs) appear to be important for lamprey metamorphosis, however, serum TH concentrations are elevated in the larval phase, decline rapidly during early metamorphosis and remain low until metamorphosis is complete; these TH fluctuations are contrary to those of other metamorphosing vertebrates. Moreover, thyroid hormone synthesis inhibitors (goitrogens) induce precocious metamorphosis and exogenous TH treatments disrupt natural metamorphosis in P. marinus. Given that THs exert their effects by binding to TH nuclear receptors (TRs) that often act as heterodimers with retinoid X receptors (RXRs), we cloned and characterized these receptors from P. marinus and examined their expression during metamorphosis. Two TRs (PmTR1 and PmTR2) and three RXRs (PmRXRs) were isolated from P. marinus cDNA. Phylogenetic analyses group the PmTRs together on a branch prior to the gnathostome TRα/β split. The three RXRs also group together, but our data indicated that these transcripts are most likely either allelic variants of the same gene locus, or the products of a lamprey-specific duplication event. Importantly, these P. marinus receptors more closely resemble vertebrate as opposed to invertebrate chordate receptors. Functional analysis revealed that PmTR1 and PmTR2 can activate transcription of TH-responsive genes when treated with nanomolar concentrations of TH and they have distinct pharmacological profiles reminiscent of vertebrate TRβ and TRα, respectively. Also similar to other metamorphosing vertebrates, expression patterns of the PmTRs during lamprey metamorphosis suggest that PmTR1 has a dynamic, tissue-specific expression pattern that correlates with tissue morphogenesis and biochemical changes and PmTR2 has a more uniform expression pattern. This TR

  14. Antagonist effect of triptolide on AKT activation by truncated retinoid X receptor-alpha.

    Directory of Open Access Journals (Sweden)

    Na Lu

    Full Text Available BACKGROUND: Retinoid X receptor-alpha (RXRα is a key member of the nuclear receptor superfamily. We recently demonstrated that proteolytic cleavage of RXRα resulted in production of a truncated product, tRXRα, which promotes cancer cell survival by activating phosphatidylinositol-3-OH kinase (PI3K/AKT pathway. However, how the tRXRα-mediated signaling pathway in cancer cells is regulated remains elusive. METHODOLOGY/PRINCIPAL FINDINGS: We screened a natural product library for tRXRα targeting leads and identified that triptolide, an active component isolated from traditional Chinese herb Trypterygium wilfordii Hook F, could modulate tRXRα-mediated cancer cell survival pathway in vitro and in animals. Our results reveal that triptolide strongly induces cancer cell apoptosis dependent on intracellular tRXRα expression levels, demonstrating that tRXRα serves as an important intracellular target of triptolide. We show that triptolide selectively induces tRXRα degradation and inhibits tRXRα-dependent AKT activity without affecting the full-length RXRα. Interestingly, such effects of triptolide are due to its activation of p38. Although triptolide also activates Erk1/2 and MAPK pathways, the effects of triptolide on tRXRα degradation and AKT activity are only reversed by p38 siRNA and p38 inhibitor. In addition, the p38 inhibitor potently inhibits tRXRα interaction with p85α leading to AKT inactivation. Our results demonstrate an interesting novel signaling interplay between p38 and AKT through tRXRα mediation. We finally show that targeting tRXRα by triptolide strongly activates TNFα death signaling and enhances the anticancer activity of other chemotherapies. CONCLUSIONS/SIGNIFICANCE: Our results identify triptolide as a new xenobiotic regulator of the tRXRα-dependent survival pathway and provide new insight into the mechanism by which triptolide acts to induce apoptosis of cancer cells. Triptolide represents one of the most

  15. Cell cycle arrest induced by radiation

    International Nuclear Information System (INIS)

    Okaichi, Yasuo; Matsumoto, Hideki; Ohnishi, Takeo

    1994-01-01

    It is known that various chemical reactions, such as cell cycle arrest, DNA repair and cell killing, can occur within the cells when exposed to ionizing radiation and ultraviolet radiation. Thus protein dynamics involved in such chemical reactions has received considerable attention. In this article, cell cycle regulation is first discussed in terms of the G2/M-phase and the G1/S-phase. Then, radiation-induced cell cycle arrest is reviewed. Cell cycle regulation mechanism involved in the G2 arrest, which is well known to occur when exposed to radiation, has recently been investigated using yeasts. In addition, recent study has yielded a noticeable finding that the G1 arrest can occur with intracellular accumulation of p53 product following ionization radiation. p53 is also shown to play an extremely important role in both DNA repair and cell killing due to DNA damage. Studies on the role of genes in protein groups induced by radiation will hold promise for the elucidation of cell cycle mechanism. (N.K.) 57 refs

  16. The 20-hydroxyecdysone-induced signalling pathway in G2/M arrest of Plodia interpunctella imaginal wing cells.

    Science.gov (United States)

    Siaussat, David; Bozzolan, Françoise; Porcheron, Patrick; Debernard, Stéphane

    2008-05-01

    The mechanisms involved in the control of cellular proliferation by the steroid hormone 20-hydroxyecdysone (20E) in insects are not known. We dissected the 20E signalling pathway responsible for G2/M arrest of imaginal cells from the IAL-PID2 cells of the Indian meal moth Plodia interpunctella. We first used a 5'-3' RACE-based strategy to clone a 4479bp cDNA encoding a putative P. interpunctella HR3 transcription factor named PiHR3. The deduced amino acid sequence of PiHR3 was highly similar to those of HR3 proteins from other lepidopterans, e.g. Manduca sexta and Bombyx mori. Using double-stranded RNA-mediated interference (dsRNAi), we then succeeded in blocking the ability of 20E to induce the expression of PiEcR-B1, PiUSP-2 and PiHR3 genes that encode the P. interpunctella ecdysone receptor B1-isoform, Ultraspiracle-2 isoform, the insect homologue of the vertebrate retinoid X receptor, and the HR3 transcription factor. We showed that inhibiting the 20E induction of PiEcR-B1, PiUSP-2 and PiHR3 mRNAs prevented the decreased expression of B cyclin and consequently the G2/M arrest of IAL-PID2 cells. Using this functional approach, we revealed the participation of EcR, USP and HR3 in a 20E signalling pathway that controls the proliferation of imaginal cells by regulating the expression of B cyclin.

  17. 32 CFR 935.125 - Citation in place of arrest.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Citation in place of arrest. 935.125 Section 935... INSULAR REGULATIONS WAKE ISLAND CODE Peace Officers § 935.125 Citation in place of arrest. In any case in which a peace officer may make an arrest without a warrant, he may issue and serve a citation if he...

  18. Transient Central Diabetes Insipidus and Marked Hypernatremia following Cardiorespiratory Arrest

    Directory of Open Access Journals (Sweden)

    Sahar H. Koubar

    2017-01-01

    Full Text Available Central Diabetes Insipidus is often an overlooked complication of cardiopulmonary arrest and anoxic brain injury. We report a case of transient Central Diabetes Insipidus (CDI following cardiopulmonary arrest. It developed 4 days after the arrest resulting in polyuria and marked hypernatremia of 199 mM. The latter was exacerbated by replacing the hypotonic urine by isotonic saline.

  19. An Audit Of Perioperative Cardiac Arrest At Lagos University ...

    African Journals Online (AJOL)

    Objective: Intraoperative cardiac arrests are not uncommon and are related to both surgical and anaesthetic factors. This study aimed to examine the factors which predispose to a periopeartive cardiac arrest, to assess the appropriateness of therapy and the outcome. Materials and Methods: All perioperative cardiac arrests ...

  20. Duration of oral tetracycline-class antibiotic therapy and use of topical retinoids for the treatment of acne among general practitioners (GP): A retrospective cohort study.

    Science.gov (United States)

    Barbieri, John S; Hoffstad, Ole; Margolis, David J

    2016-12-01

    Guidelines recommend limiting the duration of oral antibiotic therapy in acne to 3 to 6 months and prescribing concomitant topical retinoids for all patients. We sought to evaluate the duration of therapy with oral tetracyclines and the use of topical retinoids among patients with acne treated primarily by general practitioners in the United Kingdom. We conducted a retrospective cohort study using the Health Improvement Network database. The mean duration of therapy was 175.1 days. Of antibiotic courses, 62% were not associated with a topical retinoid; 29% exceeded 6 months in duration. If all regions were to achieve uses similar to the region with the shortest mean duration of therapy, approximately 3.3 million antibiotic days per year could be avoided in the United Kingdom. The Health Improvement Network does not include information on acne severity and clinical outcomes. Prescribing behavior for oral antibiotics in the treatment of acne among general practitioners is not aligned with current guideline recommendations. Increasing the use of topical retinoids and considering alternative agents to oral antibiotics when appropriate represent opportunities to reduce antibiotic exposure and associated complications such as antibiotic resistance and to improve outcomes in patients treated for acne. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  1. Witnessed arrest, but not delayed bystander cardiopulmonary resuscitation improves prehospital cardiac arrest survival.

    Science.gov (United States)

    Vukmir, R B

    2004-05-01

    This study correlated the effect of witnessing a cardiac arrest and instituting bystander CPR (ByCPR), as a secondary end point in a study evaluating the effect of bicarbonate on survival. This prospective, randomised, double blinded clinical intervention trial enrolled 874 prehospital cardiopulmonary arrest patients encountered in a prehospital urban, suburban, and rural regional emergency medical service (EMS) area. This group underwent conventional advanced cardiac life support intervention followed by empiric early administration of sodium bicarbonate (1 mEq/l), monitoring conventional resuscitation parameters. Survival was measured as presence of vital signs on emergency department (ED) arrival. Data were analysed using chi(2) with Pearson correlation and odds ratio where appropriate. The overall survival rate was 13.9% (110 of 792) of prehospital cardiac arrest patients. The mean (SD) time until provision of bystander cardiopulmonary resuscitation (ByCPR) by laymen was 2.08 (2.77) minutes, and basic life support (BLS) by emergency medical technicians was 6.62 (5.73) minutes. There was improved survival noted with witnessed cardiac arrest-a 2.2-fold increase in survival, 18.9% (76 of 402) versus 8.6% (27 of 315) compared with unwitnessed arrests (ptwo minutes (p = 0.3752). Survival after prehospital cardiac arrest is more likely when witnessed, but not necessarily when ByCPR was performed by laymen.

  2. Cloning retinoid and peroxisome proliferator-activated nuclear receptors of the Pacific oyster and in silico binding to environmental chemicals.

    Directory of Open Access Journals (Sweden)

    Susanne Vogeler

    Full Text Available Disruption of nuclear receptors, a transcription factor superfamily regulating gene expression in animals, is one proposed mechanism through which pollution causes effects in aquatic invertebrates. Environmental pollutants have the ability to interfere with the receptor's functions through direct binding and inducing incorrect signals. Limited knowledge of invertebrate endocrinology and molecular regulatory mechanisms, however, impede the understanding of endocrine disruptive effects in many aquatic invertebrate species. Here, we isolated three nuclear receptors of the Pacific oyster, Crassostrea gigas: two isoforms of the retinoid X receptor, CgRXR-1 and CgRXR-2, a retinoic acid receptor ortholog CgRAR, and a peroxisome proliferator-activated receptor ortholog CgPPAR. Computer modelling of the receptors based on 3D crystal structures of human proteins was used to predict each receptor's ability to bind to different ligands in silico. CgRXR showed high potential to bind and be activated by 9-cis retinoic acid and the organotin tributyltin (TBT. Computer modelling of CgRAR revealed six residues in the ligand binding domain, which prevent the successful interaction with natural and synthetic retinoid ligands. This supports an existing theory of loss of retinoid binding in molluscan RARs. Modelling of CgPPAR was less reliable due to high discrepancies in sequence to its human ortholog. Yet, there are suggestions of binding to TBT, but not to rosiglitazone. The effect of potential receptor ligands on early oyster development was assessed after 24h of chemical exposure. TBT oxide (0.2μg/l, all-trans retinoic acid (ATRA (0.06 mg/L and perfluorooctanoic acid (20 mg/L showed high effects on development (>74% abnormal developed D-shelled larvae, while rosiglitazone (40 mg/L showed no effect. The results are discussed in relation to a putative direct (TBT disruption effect on nuclear receptors. The inability of direct binding of ATRA to CgRAR suggests

  3. Out-of-hospital cardiac arrest

    DEFF Research Database (Denmark)

    Sondergaard, Kathrine B; Hansen, Steen Moller; Pallisgaard, Jannik L

    2018-01-01

    AIMS: Despite wide dissemination of automated external defibrillators (AEDs), bystander defibrillation rates remain low. We aimed to investigate how route distance to the nearest accessible AED was associated with probability of bystander defibrillation in public and residential locations. METHODS......: We used data from the nationwide Danish Cardiac Arrest Registry and the Danish AED Network to identify out-of-hospital cardiac arrests and route distances to nearest accessible registered AED during 2008-2013. The association between route distance and bystander defibrillation was described using...... in public locations, the probability of bystander defibrillation at 0, 100 and 200meters from the nearest AED was 35.7% (95% confidence interval 28.0%-43.5%), 21.3% (95% confidence interval 17.4%-25.2%), and 13.7% (95% confidence interval 10.1%-16.8%), respectively. The corresponding numbers for cardiac...

  4. HSST crack-arrest studies overview

    International Nuclear Information System (INIS)

    Pugh, C.E.; Whitman, G.D.

    1985-01-01

    An overview is given of the efforts underway in the Heavy-Section Steel Technology (HSST) Program to better understand and model crack-arrest behavior in reactor pressure vessel steels. The efforts are both experimental and analytical. The experimental work provides K/sub Ia/ data from laboratory-sized specimens, from thick-wall cylinders which exhibit essentially-full restraint and from nonisothermal wide-plate specimens. These data serve to define toughness-temperature trends and to provide validation data under prototypical reactor conditions. The analytical efforts interpret and correlate the data, plus provide LEFM, elastodynamic and viscoplastic methods for analyzing crack run-arrest behavior in reactor vessels. The analysis methods are incorporated into finite element computer programs which are under development at three separate laboratories. 22 refs., 10 figs

  5. Dental Calculus Arrest of Dental Caries.

    Science.gov (United States)

    Keyes, Paul H; Rams, Thomas E

    An inverse relationship between dental calculus mineralization and dental caries demineralization on teeth has been noted in some studies. Dental calculus may even form superficial layers over existing dental caries and arrest their progression, but this phenomenon has been only rarely documented and infrequently considered in the field of Cariology. To further assess the occurrence of dental calculus arrest of dental caries, this study evaluated a large number of extracted human teeth for the presence and location of dental caries, dental calculus, and dental plaque biofilms. A total of 1,200 teeth were preserved in 10% buffered formal saline, and viewed while moist by a single experienced examiner using a research stereomicroscope at 15-25× magnification. Representative teeth were sectioned and photographed, and their dental plaque biofilms subjected to gram-stain examination with light microscopy at 100× magnification. Dental calculus was observed on 1,140 (95%) of the extracted human teeth, and no dental carious lesions were found underlying dental calculus-covered surfaces on 1,139 of these teeth. However, dental calculus arrest of dental caries was found on one (0.54%) of 187 evaluated teeth that presented with unrestored proximal enamel caries. On the distal surface of a maxillary premolar tooth, dental calculus mineralization filled the outer surface cavitation of an incipient dental caries lesion. The dental calculus-covered carious lesion extended only slightly into enamel, and exhibited a brown pigmentation characteristic of inactive or arrested dental caries. In contrast, the tooth's mesial surface, without a superficial layer of dental calculus, had a large carious lesion going through enamel and deep into dentin. These observations further document the potential protective effects of dental calculus mineralization against dental caries.

  6. Dental Calculus Arrest of Dental Caries

    Science.gov (United States)

    Keyes, Paul H.; Rams, Thomas E.

    2016-01-01

    Background An inverse relationship between dental calculus mineralization and dental caries demineralization on teeth has been noted in some studies. Dental calculus may even form superficial layers over existing dental caries and arrest their progression, but this phenomenon has been only rarely documented and infrequently considered in the field of Cariology. To further assess the occurrence of dental calculus arrest of dental caries, this study evaluated a large number of extracted human teeth for the presence and location of dental caries, dental calculus, and dental plaque biofilms. Materials and methods A total of 1,200 teeth were preserved in 10% buffered formal saline, and viewed while moist by a single experienced examiner using a research stereomicroscope at 15-25× magnification. Representative teeth were sectioned and photographed, and their dental plaque biofilms subjected to gram-stain examination with light microscopy at 100× magnification. Results Dental calculus was observed on 1,140 (95%) of the extracted human teeth, and no dental carious lesions were found underlying dental calculus-covered surfaces on 1,139 of these teeth. However, dental calculus arrest of dental caries was found on one (0.54%) of 187 evaluated teeth that presented with unrestored proximal enamel caries. On the distal surface of a maxillary premolar tooth, dental calculus mineralization filled the outer surface cavitation of an incipient dental caries lesion. The dental calculus-covered carious lesion extended only slightly into enamel, and exhibited a brown pigmentation characteristic of inactive or arrested dental caries. In contrast, the tooth's mesial surface, without a superficial layer of dental calculus, had a large carious lesion going through enamel and deep into dentin. Conclusions These observations further document the potential protective effects of dental calculus mineralization against dental caries. PMID:27446993

  7. Roles of Retinoids and Retinoic Acid Receptors in the Regulation of Hematopoietic Stem Cell Self-Renewal and Differentiation

    Directory of Open Access Journals (Sweden)

    Louise E. Purton

    2007-01-01

    Full Text Available Multipotent hematopoietic stem cells (HSCs sustain blood cell production throughout an individual's lifespan through complex processes ultimately leading to fates of self-renewal, differentiation or cell death decisions. A fine balance between these decisions in vivo allows for the size of the HSC pool to be maintained. While many key factors involved in regulating HSC/progenitor cell differentiation and cell death are known, the critical regulators of HSC self-renewal are largely unknown. In recent years, however, a number of studies describing methods of increasing or decreasing the numbers of HSCs in a given population have emerged. Of major interest here are the emerging roles of retinoids in the regulation of HSCs.

  8. Peretinoin, an acyclic retinoid, improves the hepatic gene signature of chronic hepatitis C following curative therapy of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Honda, Masao; Yamashita, Taro; Yamashita, Tatsuya; Arai, Kuniaki; Sakai, Yoshio; Sakai, Akito; Nakamura, Mikiko; Mizukoshi, Eishiro; Kaneko, Shuichi

    2013-01-01

    The acyclic retinoid, peretinoin, has been shown to be effective for suppressing hepatocellular carcinoma (HCC) recurrence after definitive treatment in a small-scale randomized clinical trial. However, little has been documented about the mechanism by which peretinoin exerts its inhibitory effects against recurrent HCC in humans in vivo. Twelve hepatitis C virus-positive patients whose HCC had been eradicated through curative resection or ablation underwent liver biopsy at baseline and week 8 of treatment with either a daily dose of 300 or 600 mg peretinoin. RNA isolated from biopsy samples was subjected to gene expression profile analysis. Peretinoin treatment elevated the expression levels of IGFBP6, RBP1, PRB4, CEBPA, G0S2, TGM2, GPRC5A, CYP26B1, and many other retinoid target genes. Elevated expression was also observed for interferon-, Wnt-, and tumor suppressor-related genes. By contrast, decreased expression levels were found for mTOR- and tumor progression-related genes. Interestingly, gene expression profiles for week 8 of peretinoin treatment could be classified into two groups of recurrence and non-recurrence with a prediction accuracy rate of 79.6% (P<0.05). In the liver of patients with non-recurrence, expression of PDGFC and other angiogenesis genes, cancer stem cell marker genes, and genes related to tumor progression was down-regulated, while expression of genes related to hepatocyte differentiation, tumor suppression genes, and other genes related to apoptosis induction was up-regulated. Gene expression profiling at week 8 of peretinoin treatment could successfully predict HCC recurrence within 2 years. This study is the first to show the effect of peretinoin in suppressing HCC recurrence in vivo based on gene expression profiles and provides a molecular basis for understanding the efficacy of peretinoin

  9. Distinct mechanisms act in concert to mediate cell cycle arrest.

    Science.gov (United States)

    Toettcher, Jared E; Loewer, Alexander; Ostheimer, Gerard J; Yaffe, Michael B; Tidor, Bruce; Lahav, Galit

    2009-01-20

    In response to DNA damage, cells arrest at specific stages in the cell cycle. This arrest must fulfill at least 3 requirements: it must be activated promptly; it must be sustained as long as damage is present to prevent loss of genomic information; and after the arrest, cells must re-enter into the appropriate cell cycle phase to ensure proper ploidy. Multiple molecular mechanisms capable of arresting the cell cycle have been identified in mammalian cells; however, it is unknown whether each mechanism meets all 3 requirements or whether they act together to confer specific functions to the arrest. To address this question, we integrated mathematical models describing the cell cycle and the DNA damage signaling networks and tested the contributions of each mechanism to cell cycle arrest and re-entry. Predictions from this model were then tested with quantitative experiments to identify the combined action of arrest mechanisms in irradiated cells. We find that different arrest mechanisms serve indispensable roles in the proper cellular response to DNA damage over time: p53-independent cyclin inactivation confers immediate arrest, whereas p53-dependent cyclin downregulation allows this arrest to be sustained. Additionally, p21-mediated inhibition of cyclin-dependent kinase activity is indispensable for preventing improper cell cycle re-entry and endoreduplication. This work shows that in a complex signaling network, seemingly redundant mechanisms, acting in a concerted fashion, can achieve a specific cellular outcome.

  10. All-trans-retinoic Acid Modulates the Plasticity and Inhibits the Motility of Breast Cancer Cells: ROLE OF NOTCH1 AND TRANSFORMING GROWTH FACTOR (TGFβ).

    Science.gov (United States)

    Zanetti, Adriana; Affatato, Roberta; Centritto, Floriana; Fratelli, Maddalena; Kurosaki, Mami; Barzago, Maria Monica; Bolis, Marco; Terao, Mineko; Garattini, Enrico; Paroni, Gabriela

    2015-07-17

    All-trans-retinoic acid (ATRA) is a natural compound proposed for the treatment/chemoprevention of breast cancer. Increasing evidence indicates that aberrant regulation of epithelial-to-mesenchymal transition (EMT) is a determinant of the cancer cell invasive and metastatic behavior. The effects of ATRA on EMT are largely unknown. In HER2-positive SKBR3 and UACC812 cells, showing co-amplification of the ERBB2 and RARA genes, ATRA activates a RARα-dependent epithelial differentiation program. In SKBR3 cells, this causes the formation/reorganization of adherens and tight junctions. Epithelial differentiation and augmented cell-cell contacts underlie the anti-migratory action exerted by the retinoid in cells exposed to the EMT-inducing factors EGF and heregulin-β1. Down-regulation of NOTCH1, an emerging EMT modulator, is involved in the inhibition of motility by ATRA. Indeed, the retinoid blocks NOTCH1 up-regulation by EGF and/or heregulin-β1. Pharmacological inhibition of γ-secretase and NOTCH1 processing also abrogates SKBR3 cell migration. Stimulation of TGFβ contributes to the anti-migratory effect of ATRA. The retinoid switches TGFβ from an EMT-inducing and pro-migratory determinant to an anti-migratory mediator. Inhibition of the NOTCH1 pathway not only plays a role in the anti-migratory action of ATRA; it is relevant also for the anti-proliferative activity of the retinoid in HCC1599 breast cancer cells, which are addicted to NOTCH1 for growth/viability. This effect is enhanced by the combination of ATRA and the γ-secretase inhibitor N-(N-(3,5-difluorophenacetyl)-l-alanyl)-S-phenylglycine t-butyl ester, supporting the concept that the two compounds act at the transcriptional and post-translational levels along the NOTCH1 pathway. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Breast Gangrene

    Directory of Open Access Journals (Sweden)

    Husasin Irfan

    2011-08-01

    Full Text Available Abstract Background Breast gangrene is rare in surgical practice. Gangrene of breast can be idiopathic or secondary to some causative factor. Antibiotics and debridement are used for management. Acute inflammatory infiltrate, severe necrosis of breast tissue, necrotizing arteritis, and venous thrombosis is observed on histopathology. The aim of was to study patients who had breast gangrene. Methods A prospective study of 10 patients who had breast gangrene over a period of 6 years were analyzed Results All the patients in the study group were female. Total of 10 patients were encountered who had breast gangrene. Six patients presented with breast gangrene on the right breast whereas four had on left breast. Out of 10 patients, three had breast abscess after teeth bite followed by gangrene, one had iatrogenic trauma by needle aspiration of erythematous area of breast under septic conditions. Four had history of application of belladonna on cutaneous breast abscess and had then gangrene. All were lactating female. Amongst the rest two were elderly, one of which was a diabetic who had gangrene of breast and had no application of belladonna. All except one had debridement under cover of broad spectrum antibiotics. Three patients had grafting to cover the raw area. Conclusion Breast gangrene occurs rarely. Etiology is variable and mutifactorial. Teeth bite while lactation and the iatrogenic trauma by needle aspiration of breast abscess under unsterlised conditions could be causative. Uncontrolled diabetes can be one more causative factor for the breast gangrene. Belladonna application as a topical agent could be inciting factor. Sometimes gangrene of breast can be idiopathic. Treatment is antibiotics and debridement.

  12. Breast Exam

    Science.gov (United States)

    ... ends. What you can expect Begin with a visual examination of your breasts Sit or stand shirtless ... to the next section. If you have a disability that makes it difficult to examine your breasts ...

  13. Breast cancer

    African Journals Online (AJOL)

    A collaborative article gives an overview of breast cancer in LICs, ... approach to the problem; therefore they are published as two separate ... attached to the diagnosis of breast cancer. ... Their founding statement in its early form is included.

  14. A case of thyroid storm with cardiac arrest

    Directory of Open Access Journals (Sweden)

    Nakashima Y

    2014-05-01

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

  15. Hydroxylated PBDEs induce developmental arrest in zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Usenko, Crystal Y., E-mail: Crystal_usenko@baylor.edu; Hopkins, David C.; Trumble, Stephen J., E-mail: Stephen_trumble@baylor.edu; Bruce, Erica D., E-mail: Erica_bruce@baylor.edu

    2012-07-01

    The ubiquitous spread of polybrominated diphenyl ethers (PBDEs) has led to concerns regarding the metabolites of these congeners, in particular hydroxylated PBDEs. There are limited studies regarding the biological interactions of these chemicals, yet there is some concern they may be more toxic than their parent compounds. In this study three hydroxylated PBDEs were assessed for toxicity in embryonic zebrafish: 3-OH-BDE 47, 5-OH-BDE 47, and 6-OH-BDE 47. All three congeners induced developmental arrest in a concentration-dependent manner; however, 6-OH-BDE 47 induced adverse effects at lower concentrations than the other congeners. Furthermore, all three induced cell death; however apoptosis was not observed. In short-term exposures (24–28 hours post fertilization), all hydroxylated PBDEs generated oxidative stress in the region corresponding to the cell death at 5 and 10 ppm. To further investigate the short-term effects that may be responsible for the developmental arrest observed in this study, gene regulation was assessed for embryos exposed to 0.625 ppm 6-OH-BDE 47 from 24 to 28 hpf. Genes involved in stress response, thyroid hormone regulation, and neurodevelopment were significantly upregulated compared to controls; however, genes related to oxidative stress were either unaffected or downregulated. This study suggests that hydroxylated PBDEs disrupt development, and may induce oxidative stress and potentially disrupt the cholinergic system and thyroid hormone homeostasis. -- Highlights: ► OH-PBDEs induce developmental arrest in a concentration-dependent manner. ► Hydroxyl group location influences biological interaction. ► OH-PBDEs induce oxidative stress. ► Thyroid hormone gene regulation was disrupted following exposure. ► To our knowledge, this is the first whole organism study of OH-PBDE toxicity.

  16. Breast Cancer

    Science.gov (United States)

    Breast cancer affects one in eight women during their lives. No one knows why some women get breast cancer, but there are many risk factors. Risks that ... who have family members with breast or ovarian cancer may wish to be tested for the genes. ...

  17. Crack arrest concepts for failure prevention and life extension. Proceedings

    International Nuclear Information System (INIS)

    Wiesner, C.S.

    1996-01-01

    These proceedings contain the thirteen papers presented at a seminar on crack arrest concepts for failure prevention and life extension. They provide a picture of the current position of crack arrest testing, models and applications, discussion of the relevance of recent research to industrial problems, and an assessment of whether the application of crack arrest models provides additional safety. Separate abstracts have been prepared for seven papers of relevance to the nuclear industry and, in particular, reactor pressure vessels. (UK)

  18. Gestational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters retinoid homeostasis in maternal and perinatal tissues of the Holtzman rat

    International Nuclear Information System (INIS)

    Kransler, Kevin M.; Tonucci, David A.; McGarrigle, Barbara P.; Napoli, Joseph L.; Olson, James R.

    2007-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), one of the most widely studied environmental contaminants, causes a variety of adverse health effects including teratogenesis and altered development which may be related to disruptions in retinoid homeostasis. The purpose of this study was to determine the effect that gestational administration of TCDD has on retinoid homeostasis in both pregnant Holtzman rats and developing fetuses and neonates. A single oral dose of TCDD (0, 1.5, 3, or 6 μg/kg) was administered to pregnant rats on gestation day 10, with fetuses analyzed on gestation days 17 and 20, and neonates analyzed on post natal day 7. Exposure to TCDD generally produced decreases in the concentrations of retinyl esters, such as retinyl palmitate, and retinol in maternal and perinatal liver and lung, while increasing levels in the maternal kidney. Additionally, perinatal hepatic retinol binding protein 1-dependent retinyl ester hydrolysis was also decrease by TCDD. Sensitivity of the developing perinates to TCDD appeared to have an age-related component demonstrated by an increased rate of mortality and significant alterations to body weight and length on post natal day 7 relative to that observed at gestation day 20. A unique observation made in this study was a significant decrease in lung weight observed in the perinates exposed to TCDD. Taken together, these data demonstrate that TCDD significantly alters retinoid homeostasis in tissues of the developing fetus and neonate, suggesting that their unique sensitivity to TCDD may at least be in part the result of altered retinoid homeostasis

  19. Pathological links between stroke and cardiac arrest

    Institute of Scientific and Technical Information of China (English)

    Shaila Ghanekar; Sydney Corey; Trenton Lippert; Cesar V.Borlongan

    2017-01-01

    There may be a pathological connection between cardiac failure and ischemic stroke.In this article we describe pertinent research that demonstrates subsequent death of cardiac and neural myocytes in the post ischemic stroke brain.Current stroke therapy overlooks the connection between cardiac and cerebrovascular events and fails to address the shared risk factors.Current pre-clinical stroke investigations have provided evidence that suggests the presence of an indirect cell death pathway in which toxic molecules emanate from the stroke brain and trigger cardiac cell death.On the other hand,other studies highlight the presence of a reverse cell death cascade in which toxic molecules from the heart,following cardiac arrest,travel to the brain and induce ischemic cell death.Further examination of these putative cell death pathways between ischemic stroke and cardiac arrest will prompt the advancement of innovative treatments specifically targeting both diseases,leading to ameliorated clinical results of patients diagnosed with heart failure and ischemic stroke.

  20. Cerebral intolerance during flow arrested carotid angioplasty.

    Science.gov (United States)

    St Louis, Myron; Park, Brian D; Dahn, Michael; Bozeman, Patricia

    2012-01-01

    The use of flow arrest as a means of providing cerebral protection during carotid angioplasty offers the advantages of improved efficiency of debris removal and the ability to provide protection under unfavorable (tortuous) anatomic circumstances. However, in contrast to the filtration methods of cerebral protection, this modality requires complete interruption of antegrade carotid artery flow during balloon angioplasty and stent deployment. We report our experience with 9 patients undergoing carotid angioplasty with the Mo.Ma device, which utilizes common and external carotid artery balloon occlusion during the angioplasty procedure. We assessed the clinical outcomes and intraprocedural hemodynamic data. The average duration of carotid occlusion was 8.3 minutes. Of the 9 patients, 2 patients (22%) experienced cerebral intolerance. No stroke occurred in this patient cohort. There appeared to be a poor relationship between procedure intolerance and the presence of significant contralateral stenosis or low carotid back pressure. Furthermore, the incidence of postangioplasty hypotension was not clearly related to cerebral intolerance. Carotid angioplasty with stenting can be safely conducted with flow arrest as an alternative to filter-type cerebral protection devices. However, because cerebral intolerance is not an infrequent occurrence with this approach, clinicians must be cognizant of management strategies for transient cerebral intolerance.

  1. Ultrastructure and /sup 3/H-TdR autoradiogram in the skin of guinea pigs after topical application of aromatic retinoid (Ro 10-9359)

    Energy Technology Data Exchange (ETDEWEB)

    Ueda, K.; Inoue, Y.; Wakabayashi, S.; Kitamura, T. (Kyoto Prefectural Univ. of Medicine (Japan))

    1982-01-01

    The effect of topical application with 0.1% aromatic retinoid ointment for 7 days on quinea pig epidermis were investigated histologically, electron microscopically and autoradiographically. 1. Histological changes of the epidermis after topical application of aromatic retinoid were characterized by acanthosis and thickening of epidermal layer without prolonged rete ridge. Epidermal cells were stained slightly positive with alcian blue. 2. Labelling index in epidermis was 18% high in average rate, and labelled cells distributed in basal layer and 2 to 3 upper basal layers. Labelling index was 3 to 4 times higher than in control skin. 3. Ultrastructural changes were observed in nuclei and cytoplasm of epidermal cells. Nuclei were large in size and irregular in shape, and nucleoli were large in size and increased in number. In the cytoplasm, tonofilament was reduced in number and lots of vacuoles containing less dense material appeared. Mitochondria, endoplasmic reticulum and ribosomes were rich in number. In the intercellular spaces, amorphous less dense materials were seen. Desmosomes were kept in figure and were floating in the wide intercellular spaces. 4. Differentiation and proliferation of the epidermis in guinea pig after topical application of aromatic retinoid and retinoic acid were almost same in quality of the reaction, but the reaction was different in quantity between both agents.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-06-03

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

  3. Breast Reconstruction After Mastectomy

    Science.gov (United States)

    ... Cancer Prevention Genetics of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Reconstruction After Mastectomy On This Page What is breast reconstruction? How do surgeons use implants to reconstruct a woman’s breast? How do surgeons ...

  4. Breast cancer screening

    Science.gov (United States)

    Mammogram - breast cancer screening; Breast exam - breast cancer screening; MRI - breast cancer screening ... is performed to screen women to detect early breast cancer when it is more likely to be cured. ...

  5. Stages of Breast Cancer

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Treatment (PDQ®)–Patient Version General Information About Breast Cancer Go to Health Professional Version Key Points Breast ...

  6. Breast Cancer Prevention

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Prevention (PDQ®)–Patient Version What is prevention? Go ... from starting. Risk-reducing surgery . General Information About Breast Cancer Key Points Breast cancer is a disease in ...

  7. Breast Cancer Treatment

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Treatment (PDQ®)–Patient Version General Information About Breast Cancer Go to Health Professional Version Key Points Breast ...

  8. Evaluation of retinoids for induction of the redundant gene ABCD2 as an alternative treatment option in X-linked adrenoleukodystrophy.

    Directory of Open Access Journals (Sweden)

    Franziska D Weber

    Full Text Available X-linked adrenoleukodystrophy (X-ALD, the most common peroxisomal disorder, is a clinically heterogeneous disease that can manifest as devastating inflammatory cerebral demyelination (CALD leading to death of affected males. Currently, the only curative treatment is allogeneic hematopoietic stem cell transplantation (HSCT. However, HSCT is only effective when performed at an early stage because the inflammation may progress for eighteen months after HSCT. Thus, alternative treatment options able to immediately halt the progression are urgently needed. X-ALD is caused by mutations in the ABCD1 gene, encoding the peroxisomal membrane protein ABCD1, resulting in impaired very long-chain fatty acid metabolism. The related ABCD2 protein is able to functionally compensate for ABCD1-deficiency both in vitro and in vivo. Recently, we demonstrated that of the cell types derived from CD34+ stem cells, predominantly monocytes but not lymphocytes are metabolically impaired in X-ALD. As ABCD2 is virtually not expressed in these cells, we hypothesize that a pharmacological up-regulation of ABCD2 should compensate metabolically and halt the inflammation in CALD. Retinoids are anti-inflammatory compounds known to act on ABCD2. Here, we investigated the capacity of selected retinoids for ABCD2 induction in human monocytes/macrophages. In THP-1 cells, 13-cis-retinoic acid reached the highest, fivefold, increase in ABCD2 expression. To test the efficacy of retinoids in vivo, we analyzed ABCD2 mRNA levels in blood cells isolated from acne patients receiving 13-cis-retinoic acid therapy. In treated acne patients, ABCD2 mRNA levels were comparable to pre-treatment levels in monocytes and lymphocytes. Nevertheless, when primary monocytes were in vitro differentiated into macrophages and treated with 13-cis-retinoic acid, we observed a fourfold induction of ABCD2. However, the level of ABCD2 induction obtained by retinoids alone is probably not of therapeutic relevance

  9. Association of National Initiatives to Improve Cardiac Arrest Management With Rates of Bystander Intervention and Patient Survival After Out-of-Hospital Cardiac Arrest

    DEFF Research Database (Denmark)

    Wissenberg, Mads; Lippert, Freddy K; Folke, Fredrik

    2013-01-01

    resuscitation was attempted were identified between 2001 and 2010 in the nationwide Danish Cardiac Arrest Registry. Of 29 111 patients with cardiac arrest, we excluded those with presumed noncardiac cause of arrest (n = 7390) and those with cardiac arrests witnessed by emergency medical services personnel (n...

  10. Performance of Surge Arrester Installation to Enhance Protection

    Directory of Open Access Journals (Sweden)

    Mbunwe Muncho Josephine

    2017-01-01

    Full Text Available The effects of abnormal voltages on power system equipment and appliances in the home have raise concern as most of the equipments are very expensive. Each piece of electrical equipment in an electrical system needs to be protected from surges. To prevent damage to electrical equipment, surge protection considerations are paramount to a well designed electrical system. Lightning discharges are able to damage electric and electronic devices that usually have a low protection level and these are influenced by current or voltage pulses with a relatively low energy, which are induced by lightning currents. This calls for proper designed and configuration of surge arresters for protection on the particular appliances. A more efficient non-linear surge arrester, metal oxide varistor (MOV, should be introduced to handle these surges. This paper shows the selection of arresters laying more emphasis on the arresters for residential areas. In addition, application and installation of the arrester will be determined by the selected arrester. This paper selects the lowest rated surge arrester as it provides insulation when the system is under stress. It also selected station class and distribution class of arresters as they act as an open circuit under normal system operation and to bring the system back to its normal operation mode as the transient voltage is suppressed. Thus, reduces the risk of damage, which the protection measures can be characterized, by the reduction value of the economic loss to an acceptable level.

  11. Cardiac arrest during anesthesia at a University Hospital in Nigeria ...

    African Journals Online (AJOL)

    Background: We assessed the incidence and outcomes of cardiac arrest during anesthesia in the operating room at our university hospital. A previous study on intraoperative cardiac arrests covered a period from 1994-1998 and since then; anesthetic personnel, equipment, and workload have increased remarkably.

  12. Efficacy of silver diamine fluoride for Arresting Caries Treatment.

    NARCIS (Netherlands)

    Yee, R.T.F.; Holmgren, C.J.; Mulder, J.; Lama, D.; Walker, D.; Palenstein Helderman, W.H. van

    2009-01-01

    Arresting Caries Treatment (ACT) has been proposed to manage untreated dental caries in children. This prospective randomized clinical trial investigated the caries-arresting effectiveness of a single spot application of: (1) 38% silver diamine fluoride (SDF) with tannic acid as a reducing agent;

  13. Cooling the crisis: Therapeutic hypothermia after sickle cardiac arrest

    NARCIS (Netherlands)

    Metske, Hennie A.; Postema, Pieter G.; Biemond, Bart J.; Bouman, Catherine S. C.

    2012-01-01

    Objective: The management of patients with sickle-cell disease and cardiac arrest presents special challenges. Mild therapeutic hypothermia may improve survival and neurologic outcome after cardiac arrest, however, it may also precipitate sickling in patients with sickle-cell disease. Rigorous

  14. 29 CFR 1915.159 - Personal fall arrest systems (PFAS).

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Personal fall arrest systems (PFAS). 1915.159 Section 1915... Protective Equipment (PPE) § 1915.159 Personal fall arrest systems (PFAS). The criteria of this section apply to PFAS and their use. Effective January 1, 1998, body belts and non-locking snaphooks are not...

  15. Jojoba Oil Soft Colloidal Nanocarrier of a Synthetic Retinoid: Preparation, Characterization and Clinical Efficacy in Psoriatic Patients.

    Science.gov (United States)

    Nasr, Maha; Abdel-Hamid, Sameh; Moftah, Noha H; Fadel, Maha; Alyoussef, Abdullah A

    2017-01-01

    Nanotechnology has provided substantial benefits in drug delivery, especially in the treatment of dermatological diseases. Psoriasis is a chronic inflammatory skin disease in which topical delivery of antipsoriatic agents is considered the first line treatment. To investigate whether the encapsulation of the synthetic retinoid tazarotene in a nanocarrier based on jojoba oil would decrease its irritation potential and clinically improve its therapeutic outcome in psoriatic patients. A microemulsion system based on jojoba wax and labrasol/plurol isostearique was prepared and characterized. The selected formula displayed spherical morphology, particle size of 15.49±2.41 nm, polydispersity index of 0.20 ±0.08, negative charge and low viscosity. The microemulsion provided two folds increase in skin deposition of tazarotene, correlating with higher reduction in psoriatic patients PASI scores after treatment (68% reduction in PASI scores versus 8.96% reduction with the marketed gel). No irritation was encountered in patients using microemulsion, with redness and inflammation reported with the marketed gel-treated patients. Jojoba oil microemulsion proved to be advantageous in reducing the irritancy of tazarotene, enhancing its skin deposition and achieving better therapeutic outcome in psoriatic patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Development of real-time quantitative polymerase chain reaction assays to track treatment response in retinoid resistant acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    Jelena V Jovanovic

    2011-10-01

    Full Text Available Molecular detection of minimal residual disease (MRD has become established to assess remission status and guide therapy in patients with PML-RARA+ acute promyelocytic leukemia (APL. However, there are few data on tracking disease response in patients with rarer retinoid resistant subtypes of APL, characterized by PLZF-RARA and STAT5b-RARA. Despite their relative rarity (<1% of APL we identified 6 cases (PLZF-RARA, n=5; STAT5b-RARA, n=1, established the respective breakpoint junction regions and designed real-time quantitative polymerase chain reaction (RQ-PCR assays to detect leukemic transcripts. The relative level of fusion gene expression in diagnostic samples was comparable to that observed in t(15;17-associated APL, affording assay sensitivities of ~1 in 104-105. Serial samples were available from 2 PLZF-RARA APL patients. One showed persistent PCR positivity, predicting subsequent relapse, and remains in CR2, ~11 years post-autograft. The other, achieved molecular remission (CRm with combination chemotherapy, remaining in CR1 at 6 years. The STAT5b-RARA patient failed to achieve CRm following frontline combination chemotherapy and ultimately proceeded to allogeneic transplant on the basis of a steadily rising fusion transcript level. These data highlight the potential of RQ-PCR detection of MRD to facilitate development of more individualized approaches to the management of rarer molecularly-defined subsets of acute leukemia.

  17. Retinoid X receptor signaling pathway in leukemia%维A酸X受体信号通路与白血病

    Institute of Scientific and Technical Information of China (English)

    陆晓茜(综述); 马志贵; 高举; 朱易萍(审校)

    2014-01-01

    Retinoid X receptor (RXR) acts as ligand-dependent transcription factors playing an important role in regulating a serial of physiological processes,such as embryo development and organ homeostasis.At the molecular level,RXRs exert their functions by inter-activating with multiple signal pathways to regulate target gene expression which control cell growth,differentiation,survival and death.The interference in the network of RXR and other signal pathways has turned RXR into an attractive drug target.%维 A 酸 X 受体(RXR)是配体依赖的核转录因子,在调节一系列生理病理过程中起重要作用。在分子水平上,RXR 与多个信号通路相互作用,调控细胞生长、分化、生存与死亡等靶基因的表达。RXR 信号通路网络与其他信号通路之间的相互作用使 RXR 成为抗肿瘤药物作用的新靶点。本文就 RXR 信号通路在白血病发生发展中的作用进行简要综述。

  18. Suppressive effects of a novel compound on interphotoreceptor retinoid-binding protein-induced experimental autoimmune uveoretinitis in rats

    Directory of Open Access Journals (Sweden)

    Jun-ichi Sakai

    1999-01-01

    Full Text Available The immunosuppressive effect of ethyl O-(N-(pcarboxyphenyl-carbamoyl-mycophenolate(CAM was examined in interphotoreceptor retinoid-binding protein (IRBP-induced experimental autoimmune uveoretinitis (EAU in rats. Lewis rats immunized with bovine IRBP were treated with various oral doses of CAM postimmunization. The degree of inflammation was assessed clinically each day and histologically on day 14 or day 20. Production of various cytokines and IRBP-specific antibody, as well as IRBP-specific proliferation response, was assessed. Complete inhibition of EAU in rats, both by clinical and histologic criteria, was achieved with 50 mg/kg CAM when administered daily for 14 days following IRBP immunization. Partial inhibition was observed at lesser doses of CAM. This CAM-mediated response was accompanied by diminished production of cytokines interleukin-2, interferon-γ and tumor necrosis factor-α, as well as a reduction in IRBP-specific antibody production. Furthermore, administration of CAM either in the induction phase only (days 0–7 or in the effector phase only (days 9 or 11 to day 20 was also capable of suppressing EAU, as assessed histopathologically on day 20. We conclude that CAM is effective in suppressing EAU in rats and its mechanism of action appears to involve modulation of T cell function.

  19. Identification of interacting proteins of retinoid-related orphan nuclear receptor gamma in HepG2 cells

    Directory of Open Access Journals (Sweden)

    Ze-Min Huang1,#, Jun Wu2,#, Zheng-Cai Jia1, Yi Tian1, Jun Tang3, Yan Tang1, Ying Wang2, Yu-Zhang Wu1,* & Bing Ni1,*

    2012-06-01

    Full Text Available The retinoid-related orphan nuclear receptor gamma (RORγplays critical roles in regulation of development, immunity andmetabolism. As transcription factor usually forms a proteincomplex to function, thus capturing and dissecting of theRORγ protein complex will be helpful for exploring themechanisms underlying those functions. After construction ofthe recombinant tandem affinity purification (TAP plasmid,pMSCVpuro RORγ-CTAP(SG, the nuclear localization ofRORγ-CTAP(SG fusion protein was verified. Followingisolation of RORγ protein complex by TAP strategy, sevencandidate interacting proteins were identified. Finally, the heatshock protein 90 (HSP90 and receptor-interacting protein 140(RIP140 were confirmed to interplay with RORγ byco-immunoprecipitation. Interference of HSP90 or/and RIP140genes resulted in dramatically decreased expression ofCYP2C8 gene, the RORγ target gene. Data from this studydemonstrate that HSP90 and RIP140 proteins interact withRORγ protein in a complex format and function asco-activators in the RORγ-mediated regulatory processes ofHepG2 cells.

  20. Development of Real-Time Quantitative Polymerase Chain Reaction Assays to Track Treatment Response in Retinoid Resistant Acute Promyelocytic Leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Jovanovic, Jelena V. [Cancer Genetics Laboratory, Department of Medical and Molecular Genetics, King’s College London School of Medicine, London (United Kingdom); Rennie, Kristian [GSTS Pathology, Guy’s Hospital, London (United Kingdom); Culligan, Dominic [Department of Haematology, Aberdeen Royal Infirmary, Aberdeen (United Kingdom); Peniket, Andrew [Department of Haematology, John Radcliffe Hospital, Oxford (United Kingdom); Lennard, Anne [Department of Haematology, Royal Victoria Infirmary, Newcastle (United Kingdom); Harrison, Justin [Department of Haematology, Hemel Hempstead Hospital, Hemel Hempstead (United Kingdom); Vyas, Paresh [Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford (United Kingdom); Grimwade, David, E-mail: david.grimwade@genetics.kcl.ac.uk [Cancer Genetics Laboratory, Department of Medical and Molecular Genetics, King’s College London School of Medicine, London (United Kingdom)

    2011-10-25

    Molecular detection of minimal residual disease (MRD) has become established to assess remission status and guide therapy in patients with ProMyelocytic Leukemia–RARA+ acute promyelocytic leukemia (APL). However, there are few data on tracking disease response in patients with rarer retinoid resistant subtypes of APL, characterized by PLZF–RARA and STAT5b–RARA. Despite their rarity (<1% of APL) we identified 6 cases (PLZF–RARA, n = 5; STAT5b–RARA, n = 1), established the respective breakpoint junction regions and designed reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) assays to detect leukemic transcripts. The relative level of fusion gene expression in diagnostic samples was comparable to that observed in t(15;17) – associated APL, affording assay sensitivities of ∼1 in 10{sup 4}−10{sup 5}. Serial samples were available from two PLZF–RARA APL patients. One showed persistent polymerase chain reaction positivity, predicting subsequent relapse, and remains in CR2, ∼11 years post-autograft. The other, achieved molecular remission (CRm) with combination chemotherapy, remaining in CR1 at 6 years. The STAT5b–RARA patient failed to achieve CRm following frontline combination chemotherapy and ultimately proceeded to allogeneic transplant on the basis of a steadily rising fusion transcript level. These data highlight the potential of RT-qPCR detection of MRD to facilitate development of more individualized approaches to the management of rarer molecularly defined subsets of acute leukemia.

  1. Development of Real-Time Quantitative Polymerase Chain Reaction Assays to Track Treatment Response in Retinoid Resistant Acute Promyelocytic Leukemia

    International Nuclear Information System (INIS)

    Jovanovic, Jelena V.; Rennie, Kristian; Culligan, Dominic; Peniket, Andrew; Lennard, Anne; Harrison, Justin; Vyas, Paresh; Grimwade, David

    2011-01-01

    Molecular detection of minimal residual disease (MRD) has become established to assess remission status and guide therapy in patients with ProMyelocytic Leukemia–RARA+ acute promyelocytic leukemia (APL). However, there are few data on tracking disease response in patients with rarer retinoid resistant subtypes of APL, characterized by PLZF–RARA and STAT5b–RARA. Despite their rarity (<1% of APL) we identified 6 cases (PLZF–RARA, n = 5; STAT5b–RARA, n = 1), established the respective breakpoint junction regions and designed reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) assays to detect leukemic transcripts. The relative level of fusion gene expression in diagnostic samples was comparable to that observed in t(15;17) – associated APL, affording assay sensitivities of ∼1 in 10 4 −10 5 . Serial samples were available from two PLZF–RARA APL patients. One showed persistent polymerase chain reaction positivity, predicting subsequent relapse, and remains in CR2, ∼11 years post-autograft. The other, achieved molecular remission (CRm) with combination chemotherapy, remaining in CR1 at 6 years. The STAT5b–RARA patient failed to achieve CRm following frontline combination chemotherapy and ultimately proceeded to allogeneic transplant on the basis of a steadily rising fusion transcript level. These data highlight the potential of RT-qPCR detection of MRD to facilitate development of more individualized approaches to the management of rarer molecularly defined subsets of acute leukemia.

  2. Maturation arrest of human oocytes at germinal vesicle stage

    Directory of Open Access Journals (Sweden)

    Zhi Qin Chen

    2010-01-01

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

  3. Growth arrest specific protein (GAS) 6

    DEFF Research Database (Denmark)

    Haase, T N; Rasmussen, Morten; Jaksch, C A M

    2013-01-01

    using RNA microarray and quantitative PCR. The role of a differentially expressed gene, growth arrest specific protein 6 (GAS6), was evaluated in vitro using neonatal rat islets. Results The mRNA level of Gas6, known to be mitogenic in other tissues, was reduced in LP offspring. The mRNA content of Mafa...... was increased in LP offspring suggesting an early maturation of beta cells. When applied in vitro, GAS6 increased proliferation of neonatal pancreatic beta cells, while reducing glucose-stimulated insulin secretion without changing the total insulin content of the islets. In addition, GAS6 decreased the m......RNA content of Mafa. Conclusions/interpretation We propose a role for GAS6 in the regulation of pancreatic beta cells in the critical period around the time of birth. Our results support the hypothesis that the reduced beta cell mass seen in LP offspring is caused by a change in the intra-uterine environment...

  4. Structural arrest in an ideal gas.

    Science.gov (United States)

    van Ketel, Willem; Das, Chinmay; Frenkel, Daan

    2005-04-08

    We report a molecular dynamics study of a simple model system that has the static properties of an ideal gas, yet exhibits nontrivial "glassy" dynamics behavior at high densities. The constituent molecules of this system are constructs of three infinitely thin hard rods of length L, rigidly joined at their midpoints. The crosses have random but fixed orientation. The static properties of this system are those of an ideal gas, and its collision frequency can be computed analytically. For number densities NL(3)/V>1, the single-particle diffusivity goes to zero. As the system is completely structureless, standard mode-coupling theory cannot describe the observed structural arrest. Nevertheless, the system exhibits many dynamical features that appear to be mode-coupling-like. All high-density incoherent intermediate scattering functions collapse onto master curves that depend only on the wave vector.

  5. ERC initiatives to reduce the burden of cardiac arrest: the European Cardiac Arrest Awareness Day.

    Science.gov (United States)

    Georgiou, Marios; Lockey, Andrew S

    2013-09-01

    The rate of survival from out-of-hospital cardiac arrest in Europe remains unacceptably low and could be increased by better bystander cardiopulmonary resuscitation (CPR) rates. The European Resuscitation Council has announced that there will be a European Cardiac Arrest Awareness Day every year on the 16th of October. This is to coincide with the goals of the Written Declaration passed by the European Parliament in June 2012 that emphasised the importance of equal access to CPR and automated external defibrillator (AED) training. The topic of this year's Awareness Day is 'Children Saving Lives' and it is hoped that all national resuscitation councils will promote awareness of the benefits of training all children in CPR and AED use and lobby for legislative change to ensure that all children receive this training. Children are not just the adults of tomorrow - they are the lifesavers of today and tomorrow. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Prehospital cardiac arrest survival and neurologic recovery.

    Science.gov (United States)

    Hillis, M; Sinclair, D; Butler, G; Cain, E

    1993-01-01

    Many studies of prehospital defibrillation have been conducted but the effects of airway intervention are unknown and neurologic follow-up has been incomplete. A non-randomized cohort prospective study was conducted to determine the effectiveness of defibrillation in prehospital cardiac arrest. Two ambulance companies in the study area developed a defibrillation protocol and they formed the experimental group. A subgroup of these patients received airway management with an esophageal obturator airway (EOA) or endotracheal intubation (ETT). The control group was composed of patients who suffered a prehospital cardiac arrest and did not receive prehospital defibrillation. All survivors were assessed for residual deficits using the Sickness Impact Profile (SIP) and the Dementia Rating Scale (DRS). A total of 221 patients were studied over a 32-month period. Both the experimental group (N = 161) and the control group (N = 60) were comparable with respect to age, sex distribution, and ambulance response time. Survival to hospital discharge was 2/60 (3.3%) in the control group and 12/161 (6.3%) in the experimental group. This difference is not statistically significant. Survival in the experimental group by airway management technique was basic airway support (3/76 3.9%), EOA (3/67 4.5%), and ETT (6/48 12.5%). The improved effect on survival by ETT management was statistically significant. Survivors had minor differences in memory, work, and recreation as compared to ischemic heart disease patients as measured by the SIP and DRS. No effect of defibrillation was found on survival to hospital discharge. However, endotracheal intubation improved survival in defibrillated patients. Survivors had a good functional outcome.

  7. Polydimethylsiloxane (PDMS) modulates CD38 expression, absorbs retinoic acid and may perturb retinoid signalling.

    Science.gov (United States)

    Futrega, Kathryn; Yu, Jianshi; Jones, Jace W; Kane, Maureen A; Lott, William B; Atkinson, Kerry; Doran, Michael R

    2016-04-21

    Polydimethylsiloxane (PDMS) is the most commonly used material in the manufacture of customized cell culture devices. While there is concern that uncured PDMS oligomers may leach into culture medium and/or hydrophobic molecules may be absorbed into PDMS structures, there is no consensus on how or if PDMS influences cell behaviour. We observed that human umbilical cord blood (CB)-derived CD34(+) cells expanded in standard culture medium on PDMS exhibit reduced CD38 surface expression, relative to cells cultured on tissue culture polystyrene (TCP). All-trans retinoic acid (ATRA) induces CD38 expression, and we reasoned that this hydrophobic molecule might be absorbed by PDMS. Through a series of experiments we demonstrated that ATRA-mediated CD38 expression was attenuated when cultures were maintained on PDMS. Medium pre-incubated on PDMS for extended durations resulted in a time-dependant reduction of ATRA in the medium and increasingly attenuated CD38 expression. This indicated a time-dependent absorption of ATRA into the PDMS. To better understand how PDMS might generally influence cell behaviour, Ingenuity Pathway Analysis (IPA) was used to identify potential upstream regulators. This analysis was performed for differentially expressed genes in primary cells including CD34(+) haematopoietic progenitor cells, mesenchymal stromal cells (MSC), and keratinocytes, and cell lines including prostate cancer epithelial cells (LNCaP), breast cancer epithelial cells (MCF-7), and myeloid leukaemia cells (KG1a). IPA predicted that the most likely common upstream regulator of perturbed pathways was ATRA. We demonstrate here that ATRA is absorbed by PDMS in a time-dependent manner and results in the concomitant reduced expression of CD38 on the cell surface of CB-derived CD34(+) cells.

  8. Sevoflurane suppresses proliferation by upregulating microRNA-203 in breast cancer cells.

    Science.gov (United States)

    Liu, Jiaying; Yang, Longqiu; Guo, Xia; Jin, Guangli; Wang, Qimin; Lv, Dongdong; Liu, Junli; Chen, Qiu; Song, Qiong; Li, Baolin

    2018-05-03

    Rapid proliferation is one of the critical characteristics of breast cancer. However, the underlying regulatory mechanism of breast cancer cell proliferation is largely unclear. The present study indicated that sevoflurane, one of inhalational anesthetics, could significantly suppress breast cancer cell proliferation by arresting cell cycle at G1 phase. Notably, the rescue experiment indicated that miR-203 was upregulated by sevoflurane and mediated the function of sevoflurane on suppressing the breast cancer cell proliferation. The present study indicated the function of the sevoflurane/miR-203 signaling pathway on regulating breast cancer cell proliferation. These results provide mechanistic insight into how the sevoflurane/miR-203 signaling pathway supresses proliferation of breast cancer cells, suggesting the sevoflurane/miR-203 pathway may be a potential target in the treatment of breast cancer.

  9. Breast cancer

    OpenAIRE

    Gablerová, Pavlína

    2010-01-01

    In this work the topic of breast cancer treated more generally and mainly focused on risk factors for the development. The theoretical part describes the general knowledge about breast cancer as a stage or treatment. The practical part is to have clarified the risk factors that have some bearing on the diagnosis of breast cancer. What level are involved in the probability of occurrence? Can we eliminate them? As a comparison of risk factors examined in the Czech Republic, England, Australia a...

  10. Sudden Cardiac Arrest during Participation in Competitive Sports.

    Science.gov (United States)

    Landry, Cameron H; Allan, Katherine S; Connelly, Kim A; Cunningham, Kris; Morrison, Laurie J; Dorian, Paul

    2017-11-16

    The incidence of sudden cardiac arrest during participation in sports activities remains unknown. Preparticipation screening programs aimed at preventing sudden cardiac arrest during sports activities are thought to be able to identify at-risk athletes; however, the efficacy of these programs remains controversial. We sought to identify all sudden cardiac arrests that occurred during participation in sports activities within a specific region of Canada and to determine their causes. In this retrospective study, we used the Rescu Epistry cardiac arrest database (which contains records of every cardiac arrest attended by paramedics in the network region) to identify all out-of-hospital cardiac arrests that occurred from 2009 through 2014 in persons 12 to 45 years of age during participation in a sport. Cases were adjudicated as sudden cardiac arrest (i.e., having a cardiac cause) or as an event resulting from a noncardiac cause, on the basis of records from multiple sources, including ambulance call reports, autopsy reports, in-hospital data, and records of direct interviews with patients or family members. Over the course of 18.5 million person-years of observation, 74 sudden cardiac arrests occurred during participation in a sport; of these, 16 occurred during competitive sports and 58 occurred during noncompetitive sports. The incidence of sudden cardiac arrest during competitive sports was 0.76 cases per 100,000 athlete-years, with 43.8% of the athletes surviving until they were discharged from the hospital. Among the competitive athletes, two deaths were attributed to hypertrophic cardiomyopathy and none to arrhythmogenic right ventricular cardiomyopathy. Three cases of sudden cardiac arrest that occurred during participation in competitive sports were determined to have been potentially identifiable if the athletes had undergone preparticipation screening. In our study involving persons who had out-of-hospital cardiac arrest, the incidence of sudden cardiac

  11. Retinoides (RARβ y CRBP1 en carcinoma de pulmón a células no pequeñas Retinoid expression (RARβ and CRBP1 in non-small-cell lung carcinoma

    Directory of Open Access Journals (Sweden)

    Laura V. Mauro

    2008-06-01

    Full Text Available Aunque los pacientes con cáncer de pulmón a células no pequeñas en estadios tempranos (NSCLC tienen buen pronóstico, el 20-30% recae, siendo relevante la identificación de biomarcadores pronósticos. Los retinoides regulan crecimiento y diferenciación, y pueden antagonizar la progresión tumoral. Su efecto depende del transporte citosólico mediado por moléculas como CRBP1, y de la unión a receptores específicos (RARβ. Alteraciones en esta vía se asociaron con cáncer. Nuestro objetivo fue estudiar la expresión, mediante inmunohistoquímica, de RARβ y CRBP1 en el tejido tumoral de 49 pacientes NSCLC Estadio I/II, obtenido durante la cirugía. La supervivencia se analizó mediante los test Log Rank y multivariado de Cox. El 44.9% de los tumores fueron positivos para RARβ con expresión a nivel citoplasmático, mientras que el 34.7% lo expresó a nivel nuclear. La tinción para CRBP1 se observó en el 61.2% de los tumores. No se encontró asociación entre la expresión de ambas moléculas y las características clinicopatológicas (sexo, tamaño tumoral, nódulos línfáticos comprometidos, histopatología y p53. Tampoco se encontró asociación con el hábito de fu-mar. La presencia de células tumorales en el lavado pleural se asoció significativamente con la expresión de CRBP1. Por otro lado, se demostró asociación entre la expresión elevada de RARβ citoplasmático y menor supervivencia global (LR 4.17, p=0.0412. El análisis multivariado no mostró asociación con otras variables de pronóstico en NSCLC. En conclusión, en este grupo de pacientes NSCLC Estadio I/II, RARβ pareciera predecir la supervivencia global en forma independiente.Although early-stage non-small-cell lung carcinoma (NSCLC patients have a relative by favorable prognosis, the risk of a bad outcome remains substantial. Identification of reliable prognostic markers for disease recurrence and death has meaningful clinical application. Retinoids are

  12. Post-resuscitation care for survivors of cardiac arrest

    Directory of Open Access Journals (Sweden)

    Ashvarya Mangla

    2014-01-01

    Full Text Available Cardiac arrest can occur following a myriad of clinical conditions. With advancement of medical science and improvements in Emergency Medical Services systems, the rate of return of spontaneous circulation for patients who suffer an out-of-hospital cardiac arrest (OHCA continues to increase. Managing these patients is challenging and requires a structured approach including stabilization of cardiopulmonary status, early consideration of neuroprotective strategies, identifying and managing the etiology of arrest and initiating treatment to prevent recurrence. This requires a closely coordinated multidisciplinary team effort. In this article, we will review the initial management of survivors of OHCA, highlighting advances and ongoing controversies.

  13. Breast asymmetry and predisposition to breast cancer

    OpenAIRE

    Scutt, Diane; Lancaster, Gillian A; Manning, John T

    2006-01-01

    INTRODUCTION: It has been shown in our previous work that breast asymmetry is related to several of the known risk factors for breast cancer, and that patients with diagnosed breast cancer have more breast volume asymmetry, as measured from mammograms, than age-matched healthy women. METHODS: In the present study, we compared the breast asymmetry of women who were free of breast disease at time of mammography, but who had subsequently developed breast cancer, with that of age-matched healthy ...

  14. Efficacy of the dietary histone deacetylase inhibitor butyrate alone or in combination with vitamin A against proliferation of MCF-7 human breast cancer cells

    International Nuclear Information System (INIS)

    Andrade, F.O.; Nagamine, M.K.; De Conti, A.; Chaible, L.M.; Fontelles, C.C.; Jordão Junior, A.A.; Vannucchi, H.; Dagli, M.L.Z.; Bassoli, B.K.; Moreno, F.S.; Ong, T.P.

    2012-01-01

    The combined treatment with histone deacetylase inhibitors (HDACi) and retinoids has been suggested as a potential epigenetic strategy for the control of cancer. In the present study, we investigated the effects of treatment with butyrate, a dietary HDACi, combined with vitamin A on MCF-7 human breast cancer cells. Cell proliferation was evaluated by the crystal violet staining method. MCF-7 cells were plated at 5 x 10 4 cells/mL and treated with butyrate (1 mM) alone or combined with vitamin A (10 µM) for 24 to 120 h. Cell proliferation inhibition was 34, 10 and 46% following treatment with butyrate, vitamin A and their combination, respectively, suggesting that vitamin A potentiated the inhibitory activities of butyrate. Furthermore, exposure to this short-chain fatty acid increased the level of histone H3K9 acetylation by 9.5-fold (Western blot), but not of H4K16, and increased the expression levels of p21 WAF1 by 2.7-fold (Western blot) and of RARβ by 2.0-fold (quantitative real-time PCR). Our data show that RARβ may represent a molecular target for butyrate in breast cancer cells. Due to its effectiveness as a dietary HDACi, butyrate should be considered for use in combinatorial strategies with more active retinoids, especially in breast cancers in which RARβ is epigenetically altered

  15. Efficacy of the dietary histone deacetylase inhibitor butyrate alone or in combination with vitamin A against proliferation of MCF-7 human breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, F.O. [Laboratório de Dieta, Nutrição e Câncer, Departamento de Alimentos e Nutrição Experimental, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP (Brazil); Nagamine, M.K. [Laboratório de Oncologia Experimental, Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP (Brazil); De Conti, A. [Laboratório de Dieta, Nutrição e Câncer, Departamento de Alimentos e Nutrição Experimental, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP (Brazil); Chaible, L.M. [Laboratório de Oncologia Experimental, Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP (Brazil); Fontelles, C.C. [Laboratório de Dieta, Nutrição e Câncer, Departamento de Alimentos e Nutrição Experimental, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP (Brazil); Jordão Junior, A.A.; Vannucchi, H. [Divisão de Nutrição, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Dagli, M.L.Z. [Laboratório de Oncologia Experimental, Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP (Brazil); Bassoli, B.K.; Moreno, F.S.; Ong, T.P. [Laboratório de Dieta, Nutrição e Câncer, Departamento de Alimentos e Nutrição Experimental, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP (Brazil)

    2012-06-22

    The combined treatment with histone deacetylase inhibitors (HDACi) and retinoids has been suggested as a potential epigenetic strategy for the control of cancer. In the present study, we investigated the effects of treatment with butyrate, a dietary HDACi, combined with vitamin A on MCF-7 human breast cancer cells. Cell proliferation was evaluated by the crystal violet staining method. MCF-7 cells were plated at 5 x 10{sup 4} cells/mL and treated with butyrate (1 mM) alone or combined with vitamin A (10 µM) for 24 to 120 h. Cell proliferation inhibition was 34, 10 and 46% following treatment with butyrate, vitamin A and their combination, respectively, suggesting that vitamin A potentiated the inhibitory activities of butyrate. Furthermore, exposure to this short-chain fatty acid increased the level of histone H3K9 acetylation by 9.5-fold (Western blot), but not of H4K16, and increased the expression levels of p21{sup WAF1} by 2.7-fold (Western blot) and of RARβ by 2.0-fold (quantitative real-time PCR). Our data show that RARβ may represent a molecular target for butyrate in breast cancer cells. Due to its effectiveness as a dietary HDACi, butyrate should be considered for use in combinatorial strategies with more active retinoids, especially in breast cancers in which RARβ is epigenetically altered.

  16. Determination and occurrence of retinoids in a eutrophic lake (Taihu Lake, China): cyanobacteria blooms produce teratogenic retinal.

    Science.gov (United States)

    Wu, Xiaoqin; Jiang, Jieqiong; Hu, Jianying

    2013-01-15

    Besides retinoic acids (RAs), some retinoids such as retinal (RAL) and retinol (ROH), which are considered as RA precursors in vertebrates, are also reported to be teratogenic agents. In this study we investigated four RA precursors including RAL, ROH, retinyl palmitate, and β-carotene in the eutrophic Taihu Lake, China, by developing a sensitive analytical method. RAL and β-carotene were widely detected in natural cyanobacteria blooms and lake water. Intracellular concentrations of RAL and β-carotene in blooms were 9.4 to 6.9 × 10(3) and 3.4 to 1.8 × 10(5) ng L(-1), respectively, and their concentrations in lake water were up to 1.4 × 10 ng L(-1) (RAL) and 9.8 × 10(2) ng L(-1) (β-carotene). The good correlation between intracellular concentrations of RAL and RAs implied that RAL was involved in the production of RAs by cyanobacteria blooms. Further examination of 39 cyanobacteria and algae species revealed that most species could produce RAL and β-carotene. The greatest amount of RAL was found in Chlamydomonas sp. (FACHB-715; 1.9 × 10(3) ng g(-1) dry weight). As the main cyanobacteria in Taihu Lake, many Microcystis species could produce high amounts of RAL and were thought to greatly contribute to the production of RAL measured in the blooms. Productions of RAL and β-carotene by cyanobacteria were associated with species, origin location, and growth stage. The results in this study present the existence of a potential risk to aquatic animals living in a eutrophic environment from a high concentration of RAL in cyanobacteria blooms and also provide a clue for further investigating the mechanism underlying the biosynthetic pathway of RAs in cyanobacteria and algae.

  17. A comparison of carotenoids, retinoids, and tocopherols in the serum and buccal mucosa of chronic cigarette smokers versus nonsmokers.

    Science.gov (United States)

    Gabriel, Helen E; Liu, Zhenhua; Crott, Jimmy W; Choi, Sang-Woon; Song, Byeng Chun; Mason, Joel B; Johnson, Elizabeth J

    2006-05-01

    Cigarette smoking, a major risk factor for oropharyngeal cancer, is reported to alter oral levels of carotenoids and tocopherols. Such effects may be important because these nutrients, as well as retinoids, are putative chemoprotective agents. To determine whether chronic smoking is associated with altered concentrations of these nutrients in serum and buccal mucosa; to distinguish whether such effects are ascribable to diet; and to determine whether oral concentrations of these nutrients correlate with a putative biomarker of oral cancer risk. Serum and buccal mucosal cells (BMC) were analyzed for these nutrients and for BMC micronuclei in smokers (n = 35) and nonsmokers (n = 21). General linear regression with adjustments for dietary intake showed that smokers possess lower serum concentrations of beta- and alpha-carotene, cryptoxanthin, lutein, and zeaxanthin (P

  18. Retinoid X receptor and peroxisome proliferator-activated receptor activate an estrogen responsive gene independent of the estrogen receptor.

    Science.gov (United States)

    Nuñez, S B; Medin, J A; Braissant, O; Kemp, L; Wahli, W; Ozato, K; Segars, J H

    1997-03-14

    Estrogen receptors regulate transcription of genes essential for sexual development and reproductive function. Since the retinoid X receptor (RXR) is able to modulate estrogen responsive genes and both 9-cis RA and fatty acids influenced development of estrogen responsive tumors, we hypothesized that estrogen responsive genes might be modulated by RXR and the fatty acid receptor (peroxisome proliferator-activated receptor, PPAR). To test this hypothesis, transfection assays in CV-1 cells were performed with an estrogen response element (ERE) coupled to a luciferase reporter construct. Addition of expression vectors for RXR and PPAR resulted in an 11-fold increase in luciferase activity in the presence of 9-cis RA. Furthermore, mobility shift assays demonstrated binding of RXR and PPAR to the vitellogenin A2-ERE and an ERE in the oxytocin promoter. Methylation interference assays demonstrated that specific guanine residues required for RXR/PPAR binding to the ERE were similar to residues required for ER binding. Moreover, RXR domain-deleted constructs in transfection assays showed that activation required RXR since an RXR delta AF-2 mutant completely abrogated reporter activity. Oligoprecipitation binding studies with biotinylated ERE and (35)S-labeled in vitro translated RXR constructs confirmed binding of delta AF-2 RXR mutant to the ERE in the presence of baculovirus-expressed PPAR. Finally, in situ hybridization confirmed RXR and PPAR mRNA expression in estrogen responsive tissues. Collectively, these data suggest that RXR and PPAR are present in reproductive tissues, are capable of activating estrogen responsive genes and suggest that the mechanism of activation may involve direct binding of the receptors to estrogen response elements.

  19. Breast cancer

    International Nuclear Information System (INIS)

    Tokunaga, Masayoshi

    1992-01-01

    More than 20-year follow-up of A-bomb survivors in Hiroshima and Nagasaki has a crucial role in determining the relationship of radiation to the occurrence of breast cancer. In 1967, Wanebo et al have first reported 27 cases of breast cancer during the period 1950-1966 among the Adult Health Study population of A-bomb survivors. Since then, follow-up surveys for breast cancer have been made using the Life Span Study (LSS) cohort, and the incidence of breast cancer has increased year by year; that is breast cancer was identified in 231 cases by the first LSS series (1950-1969), 360 cases by the second LSS series (1950-1974), 564 cases by the third LSS series (1950-1980), and 816 cases in the fourth LSS series (1950-1085). The third LSS series have revealed a high risk for radiation-induced breast cancer in women aged 10 or less at the time of exposure (ATE). Both relative and absolute risks are found to be decreased with increasing ages ATE. Based on the above-mentioned findings and other studies on persons exposed medical radiation, radiation-induced breast cancer is characterized by the following: (1) the incidence of breast cancer is linearly increased with increasing radiation doses; (2) both relative and absolute risks for breast cancer are high in younger persons ATE; (3) age distribution of breast cancer in proximally exposed A-bomb survivors is the same as that in both distally A-bomb survivors and non-exposed persons, and there is no difference in histology between the former and latter groups. Thus, immature mammary gland cells before the age of puberty are found to be most radiosensitive. (N.K.)

  20. Genome-Wide Profiling of Liver X Receptor, Retinoid X Receptor, and Peroxisome Proliferator-Activated Receptor α in Mouse Liver Reveals Extensive Sharing of Binding Sites

    DEFF Research Database (Denmark)

    Boergesen, Michael; Pedersen, Thomas Åskov; Gross, Barbara

    2012-01-01

    and correlate with an LXR-dependent hepatic induction of lipogenic genes. To further investigate the roles of RXR and LXR in the regulation of hepatic gene expression, we have mapped the ligand-regulated genome-wide binding of these factors in mouse liver. We find that the RXR agonist bexarotene primarily......The liver X receptors (LXRs) are nuclear receptors that form permissive heterodimers with retinoid X receptor (RXR) and are important regulators of lipid metabolism in the liver. We have recently shown that RXR agonist-induced hypertriglyceridemia and hepatic steatosis in mice are dependent on LXRs...

  1. Prediction of cardiac arrest recurrence using ensemble classifiers

    Indian Academy of Sciences (India)

    Nachiket Tapas

    ECG dataset from PhysioNet, Pima Indian Diabetes dataset from UCI Machine Learning Repository and gene expression ... electrical activity, medically the condition is known as cardiac arrest ... ing, (5) lack of physical exercise, etc. [9]. Using ...

  2. Arrest of cytoplasmic streaming induces algal proliferation in green paramecia.

    Directory of Open Access Journals (Sweden)

    Toshiyuki Takahashi

    Full Text Available A green ciliate Paramecium bursaria, bearing several hundreds of endosymbiotic algae, demonstrates rotational microtubule-based cytoplasmic streaming, in which cytoplasmic granules and endosymbiotic algae flow in a constant direction. However, its physiological significance is still unknown. We investigated physiological roles of cytoplasmic streaming in P. bursaria through host cell cycle using video-microscopy. Here, we found that cytoplasmic streaming was arrested in dividing green paramecia and the endosymbiotic algae proliferated only during the arrest of cytoplasmic streaming. Interestingly, arrest of cytoplasmic streaming with pressure or a microtubule drug also induced proliferation of endosymbiotic algae independently of host cell cycle. Thus, cytoplasmic streaming may control the algal proliferation in P. bursaria. Furthermore, confocal microscopic observation revealed that a division septum was formed in the constricted area of a dividing paramecium, producing arrest of cytoplasmic streaming. This is a first report to suggest that cytoplasmic streaming controls proliferation of eukaryotic cells.

  3. The outcome of anaesthesia related cardiac arrest in a

    Directory of Open Access Journals (Sweden)

    O.O. Adekola

    2016-07-01

    Conclusion: Anaesthesia related cardiac arrest and mortality were linked to cardiovascular depression from halothane overdose in our institution. The burden can be reduced by improving on establishing standard monitoring in the perioperative period, and a team approach to patients care.

  4. Role of ornithine decarboxylase in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Wensheng Deng; Xian Jiang; Yu Mei; Jingzhong Sun; Rong Ma; Xianxi Liu; Hui Sun; Hui Tian; Xueying Sun

    2008-01-01

    Ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis that decarboxylates ornithine to putrescine, has become a promising target for cancer research. The aim of this study is to investigate the role of ODC in breast cancer. We detected expression of ODC in breast cancer tissues and four breast cancer cell lines, and transfected breast cancer cells with an adenoviral vector carrying antisense ODC (rAd-ODC/Ex3as) and examined their growth and migration.ODC was overexpressed in breast cancer tissues and cell lines compared with non-tumor tissues and normal breast epithelial celis,and there was a positive correlation between the level of ODC mRNA and the staging of tumors.The expression of ODC correlated with cyclin D1,a cell cycle protein,in synchronized breast cancer MDA-MB-231 cells.Gene transfection of rAd-ODC/Ex3as markedly down-regulated expression Of ODC and cyclin D1,resulting in suppression of proliferation and cell cycle arrest at G0-G1 phase,and the inhibifion of colony formation,an anchorage-independent growth pattern,and the migratory ability of MDA-MB-231 cells.rAd-ODC/Ex3as also markedly reduced the concentration of putrescine,but not spermidine or spermine,in MDA-MB-231 cells.The results suggested that the ODC gene might act as aprognostic factor for breast cancer and it could be a promising therapeutic target.

  5. Dynamic propagation and cleavage crack arrest in bainitic steel

    International Nuclear Information System (INIS)

    Hajjaj, M.

    2006-06-01

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

  6. Al-Qaeda arrest casts shadow over the LHC

    CERN Multimedia

    Dacey, James

    2010-01-01

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

  7. Breast reconstruction - natural tissue

    Science.gov (United States)

    ... flap; TRAM; Latissimus muscle flap with a breast implant; DIEP flap; DIEAP flap; Gluteal free flap; Transverse upper gracilis flap; TUG; Mastectomy - breast reconstruction with natural tissue; Breast cancer - breast reconstruction with natural tissue

  8. Breast Cancer: Treatment Options

    Science.gov (United States)

    ... Breast Cancer > Breast Cancer: Treatment Options Request Permissions Breast Cancer: Treatment Options Approved by the Cancer.Net Editorial ... can be addressed as quickly as possible. Recurrent breast cancer If the cancer does return after treatment for ...

  9. Associates of Cardiopulmonary Arrest in the Perihemodialytic Period

    Science.gov (United States)

    Flythe, Jennifer E.; Li, Nien-Chen; Brunelli, Steven M.; Lacson, Eduardo

    2014-01-01

    Cardiopulmonary arrest during and proximate to hemodialysis is rare but highly fatal. Studies have examined peridialytic sudden cardiac event risk factors, but no study has considered associates of cardiopulmonary arrests (fatal and nonfatal events including cardiac and respiratory causes). This study was designed to elucidate patient and procedural factors associated with peridialytic cardiopulmonary arrest. Data for this case-control study were taken from the hemodialysis population at Fresenius Medical Care, North America. 924 in-center cardiopulmonary events (cases) and 75,538 controls were identified. Cases and controls were 1 : 5 matched on age, sex, race, and diabetes. Predictors of cardiopulmonary arrest were considered for logistic model inclusion. Missed treatments due to hospitalization, lower body mass, coronary artery disease, heart failure, lower albumin and hemoglobin, lower dialysate potassium, higher serum calcium, greater erythropoietin stimulating agent dose, and normalized protein catabolic rate (J-shaped) were associated with peridialytic cardiopulmonary arrest. Of these, lower albumin, hemoglobin, and body mass index; higher erythropoietin stimulating agent dose; and greater missed sessions had the strongest associations with outcome. Patient health markers and procedural factors are associated with peridialytic cardiopulmonary arrest. In addition to optimizing nutritional status, it may be prudent to limit exposure to low dialysate potassium (<2 K bath) and to use the lowest effective erythropoietin stimulating agent dose. PMID:25530881

  10. Associates of Cardiopulmonary Arrest in the Perihemodialytic Period

    Directory of Open Access Journals (Sweden)

    Jennifer E. Flythe

    2014-01-01

    Full Text Available Cardiopulmonary arrest during and proximate to hemodialysis is rare but highly fatal. Studies have examined peridialytic sudden cardiac event risk factors, but no study has considered associates of cardiopulmonary arrests (fatal and nonfatal events including cardiac and respiratory causes. This study was designed to elucidate patient and procedural factors associated with peridialytic cardiopulmonary arrest. Data for this case-control study were taken from the hemodialysis population at Fresenius Medical Care, North America. 924 in-center cardiopulmonary events (cases and 75,538 controls were identified. Cases and controls were 1 : 5 matched on age, sex, race, and diabetes. Predictors of cardiopulmonary arrest were considered for logistic model inclusion. Missed treatments due to hospitalization, lower body mass, coronary artery disease, heart failure, lower albumin and hemoglobin, lower dialysate potassium, higher serum calcium, greater erythropoietin stimulating agent dose, and normalized protein catabolic rate (J-shaped were associated with peridialytic cardiopulmonary arrest. Of these, lower albumin, hemoglobin, and body mass index; higher erythropoietin stimulating agent dose; and greater missed sessions had the strongest associations with outcome. Patient health markers and procedural factors are associated with peridialytic cardiopulmonary arrest. In addition to optimizing nutritional status, it may be prudent to limit exposure to low dialysate potassium (<2 K bath and to use the lowest effective erythropoietin stimulating agent dose.

  11. Cardiac arrest due to lymphocytic colitis: a case report

    Directory of Open Access Journals (Sweden)

    Groth Kristian A

    2012-03-01

    Full Text Available Abstract Introduction We present a case of cardiac arrest due to hypokalemia caused by lymphocytic colitis. Case presentation A 69-year-old Caucasian man presented four months prior to a cardiac arrest with watery diarrhea and was diagnosed with lymphocytic colitis. Our patient experienced a witnessed cardiac arrest at his general practitioner's surgery. Two physicians and the emergency medical services resuscitated our patient for one hour and four minutes before arriving at our university hospital. Our patient was defibrillated 16 times due to the recurrence of ventricular tachyarrhythmias. An arterial blood sample revealed a potassium level of 2.0 mmol/L (reference range: 3.5 to 4.6 mmol/L and pH 6.86 (reference range: pH 7.37 to 7.45. As the potassium level was corrected, the propensity for ventricular tachyarrhythmias ceased. Our patient recovered from his cardiac arrest without any neurological deficit. Further tests and examinations revealed no other reason for the cardiac arrest. Conclusion Diarrhea can cause life-threatening situations due to the excretion of potassium, ultimately causing cardiac arrest due to hypokalemia. Physicians treating patients with severe diarrhea should consider monitoring their electrolyte levels.

  12. The neighborhood context of racial and ethnic disparities in arrest.

    Science.gov (United States)

    Kirk, David S

    2008-02-01

    This study assesses the role of social context in explaining racial and ethnic disparities in arrest, with afocus on how distinct neighborhood contexts in which different racial and ethnic groups reside explain variations in criminal outcomes. To do so, I utilize a multilevel, longitudinal research design, combining individual-level data with contextual data from the Project on Human Development in Chicago Neighborhoods (PHDCN). Findings reveal that black youths face multiple layers of disadvantage relative to other racial and ethnic groups, and these layers work to create differences in arrest. At the family level, results show that disadvantages in the form of unstable family structures explain much of the disparities in arrest across race and ethnicity. At the neighborhood level, black youths tend to reside in areas with both significantly higher levels of concentrated poverty than other youths as well as lower levels of collective efficacy than white youths. Variations in neighborhood tolerance of deviance across groups explain little of the arrest disparities, yet tolerance of deviance does influence the frequency with which a crime ultimately ends in an arrest. Even after accounting for relevant demographic, family, and neighborhood-level predictors, substantial residual arrest differences remain between black youths and youths of other racial and ethnic groups.

  13. Human breast tissue disposition and bioactivity of limonene in women with early stage breast cancer

    Science.gov (United States)

    Miller, Jessica A.; Lang, Julie E.; Ley, Michele; Nagle, Ray; Hsu, Chiu-Hsieh; Thompson, Patricia A; Cordova, Catherine; Waer, Amy; Chow, H.-H. Sherry

    2013-01-01

    Limonene is a bioactive food component found in citrus peel oil that has demonstrated chemopreventive and chemotherapeutic activities in preclinical studies. We conducted an open label pilot clinical study to determine the human breast tissue disposition of limonene and its associated bioactivity. We recruited forty-three women with newly diagnosed operable breast cancer electing to undergo surgical excision to take 2 grams of limonene daily for 2 – 6 weeks before surgery. Blood and breast tissue were collected to determine drug/metabolite concentrations and limonene-induced changes in systemic and tissue biomarkers of breast cancer risk or carcinogenesis. Limonene was found to preferentially concentrate in the breast tissue, reaching high tissue concentration (mean=41.3 μg/g tissue) while the major active circulating metabolite, perillic acid, did not concentrate in the breast tissue. Limonene intervention resulted in a 22% reduction in cyclin D1 expression (P=0.002) in tumor tissue but minimal changes in tissue Ki67 and cleaved caspase 3 expression. No significant changes in serum leptin, adiponectin, TGF-β1, IGFBP-3 and IL-6 levels were observed following limonene intervention. There was a small but statistically significant post-intervention increase in IGF-1 levels. We conclude that limonene distributed extensively to human breast tissue and reduced breast tumor cyclin D1 expression that may lead to cell cycle arrest and reduced cell proliferation. Further placebo-controlled clinical trials and translational research are warranted to establish limonene’s role for breast cancer prevention or treatment. PMID:23554130

  14. Human breast tissue disposition and bioactivity of limonene in women with early-stage breast cancer.

    Science.gov (United States)

    Miller, Jessica A; Lang, Julie E; Ley, Michele; Nagle, Ray; Hsu, Chiu-Hsieh; Thompson, Patricia A; Cordova, Catherine; Waer, Amy; Chow, H-H Sherry

    2013-06-01

    Limonene is a bioactive food component found in citrus peel oil that has shown chemopreventive and chemotherapeutic activities in preclinical studies. We conducted an open-label pilot clinical study to determine the human breast tissue disposition of limonene and its associated bioactivity. We recruited 43 women with newly diagnosed operable breast cancer electing to undergo surgical excision to take 2 grams of limonene daily for two to six weeks before surgery. Blood and breast tissue were collected to determine drug/metabolite concentrations and limonene-induced changes in systemic and tissue biomarkers of breast cancer risk or carcinogenesis. Limonene was found to preferentially concentrate in the breast tissue, reaching high tissue concentration (mean = 41.3 μg/g tissue), whereas the major active circulating metabolite, perillic acid, did not concentrate in the breast tissue. Limonene intervention resulted in a 22% reduction in cyclin D1 expression (P = 0.002) in tumor tissue but minimal changes in tissue Ki67 and cleaved caspase-3 expression. No significant changes in serum leptin, adiponectin, TGF-β1, insulin-like growth factor binding protein-3 (IGFBP-3), and interleukin-6 (IL-6) levels were observed following limonene intervention. There was a small but statistically significant postintervention increase in insulin-like growth factor I (IGF-I) levels. We conclude that limonene distributed extensively to human breast tissue and reduced breast tumor cyclin D1 expression that may lead to cell-cycle arrest and reduced cell proliferation. Furthermore, placebo-controlled clinical trials and translational research are warranted to establish limonene's role for breast cancer prevention or treatment.

  15. Lymphatic vessel assessment by podoplanin (D2-40 immunohistochemistry in breast cancer

    Directory of Open Access Journals (Sweden)

    Shailja Puri Wahal

    2015-01-01

    Conclusion: Taking into account our small sample size, we conclude that a further large-sized study should be carried out to further prove the role of lymphatics in tumor dissemination. New therapeutic options can be developed targeting the lymphatic channels to arrest the lymphatic spread of the breast cancer.

  16. Interfacial crack arrest in sandwich beams subjected to fatigue loading using a novel crack arresting device – Numerical modelling

    DEFF Research Database (Denmark)

    Martakos, G.; Andreasen, J.H.; Berggreen, Christian

    2017-01-01

    A novel crack arresting device is implemented in foam-cored composite sandwich beams and tested using the Sandwich Tear Test (STT) configuration. A finite element model of the setup is developed, and the predictions are correlated with observations and results from a recently conducted experiment...... concept, as well as a design tool that can be used for the implementation of crack arresting devises in engineering applications of sandwich components and structures....

  17. A model of survival following pre-hospital cardiac arrest based on the Victorian Ambulance Cardiac Arrest Register.

    Science.gov (United States)

    Fridman, Masha; Barnes, Vanessa; Whyman, Andrew; Currell, Alex; Bernard, Stephen; Walker, Tony; Smith, Karen L

    2007-11-01

    This study describes the epidemiology of sudden cardiac arrest patients in Victoria, Australia, as captured via the Victorian Ambulance Cardiac Arrest Register (VACAR). We used the VACAR data to construct a new model of out-of-hospital cardiac arrest (OHCA), which was specified in accordance with observed trends. All cases of cardiac arrest in Victoria that were attended by Victorian ambulance services during the period of 2002-2005. Overall survival to hospital discharge was 3.8% among 18,827 cases of OHCA. Survival was 15.7% among 1726 bystander witnessed, adult cardiac arrests of presumed cardiac aetiology, presenting in ventricular fibrillation or ventricular tachycardia (VF/VT), where resuscitation was attempted. In multivariate logistic regression analysis, bystander CPR, cardiac arrest (CA) location, response time, age and sex were predictors of VF/VT, which, in turn, was a strong predictor of survival. The same factors that affected VF/VT made an additional contribution to survival. However, for bystander CPR, CA location and response time this additional contribution was limited to VF/VT patients only. There was no detectable association between survival and age younger than 60 years or response time over 15min. The new model accounts for relationships among predictors of survival. These relationships indicate that interventions such as reduced response times and bystander CPR act in multiple ways to improve survival.

  18. Characterization of Mitochondrial Injury after Cardiac Arrest (COMICA)

    Science.gov (United States)

    Donnino, Michael W.; Liu, Xiaowen; Andersen, Lars W.; Rittenberger, Jon C.; Abella, Benjamin S.; Gaieski, David F.; Ornato, Joseph P.; Gazmuri, Raúl J.; Grossestreur, Anne V.; Cocchi, Michaen N.; Abbate, Antonio; Uber, Amy; Clore, John; Peberdy, Mary Anne; Callaway, Clifton

    2017-01-01

    Introduction Mitochondrial injury post-cardiac arrest has been described in pre-clinical settings but the extent to which this injury occurs in humans remains largely unknown. We hypothesized that increased levels of mitochondrial biomarkers would be associated with mortality and neurological morbidity in post-cardiac arrest subjects. Methods We performed a prospective multicenter study of post-cardiac arrest subjects. Inclusion criteria were comatose adults who suffered an out-of-hospital cardiac arrest. Mitochondrial biomarkers were measured at 0, 12, 24, 36 and 48 hours after return of spontaneous circulation as well as in healthy controls. Results Out of 111 subjects enrolled, 102 had evaluable samples at 0 hours. Cardiac arrest subjects had higher baseline cytochrome c levels compared to controls (2.18 ng/mL [0.74, 7.74] vs. 0.16 ng/mL [0.03, 0.91], p<0.001), and subjects who died had higher 0 hours cytochrome c levels compared to survivors (3.66 ng/mL [1.40, 14.9] vs. 1.27 ng/mL [0.16, 2.37], p<0.001). There were significantly higher RNAase P (3.3 [1.2, 5.7] vs. 1.2 [0.8, 1.2], p<0.001) and B2M (12.0 [1.0, 22.9], vs. 0.6 [0.6, 1.3], p<0.001) levels in cardiac arrest subjects at baseline compared to the control subjects. There were no differences between survivors and non-survivors for mitochondrial DNA, nuclear DNA, or cell free DNA. Conclusions Cytochrome C was increased in post-cardiac arrest subjects compared to controls, and in post-cardiac arrest non-survivors compared to survivors. Nuclear DNA and cell free DNA was increased in plasma of post-cardiac arrest subjects. There were no differences in mitochondrial DNA, nuclear DNA, or cell free DNA between survivors and non-survivors. Mitochondrial injury markers showed mixed results in post-arrest period. Future research needs to investigate these differences. PMID:28126408

  19. Characterization of mitochondrial injury after cardiac arrest (COMICA).

    Science.gov (United States)

    Donnino, Michael W; Liu, Xiaowen; Andersen, Lars W; Rittenberger, Jon C; Abella, Benjamin S; Gaieski, David F; Ornato, Joseph P; Gazmuri, Raúl J; Grossestreuer, Anne V; Cocchi, Michael N; Abbate, Antonio; Uber, Amy; Clore, John; Peberdy, Mary Anne; Callaway, Clifton W

    2017-04-01

    Mitochondrial injury post-cardiac arrest has been described in pre-clinical settings but the extent to which this injury occurs in humans remains largely unknown. We hypothesized that increased levels of mitochondrial biomarkers would be associated with mortality and neurological morbidity in post-cardiac arrest subjects. We performed a prospective multicenter study of post-cardiac arrest subjects. Inclusion criteria were comatose adults who suffered an out-of-hospital cardiac arrest. Mitochondrial biomarkers were measured at 0, 12, 24, 36 and 48h after return of spontaneous circulation as well as in healthy controls. Out of 111 subjects enrolled, 102 had evaluable samples at 0h. Cardiac arrest subjects had higher baseline cytochrome c levels compared to controls (2.18ng/mL [0.74, 7.74] vs. 0.16ng/mL [0.03, 0.91], p<0.001), and subjects who died had higher 0h cytochrome c levels compared to survivors (3.66ng/mL [1.40, 14.9] vs. 1.27ng/mL [0.16, 2.37], p<0.001). There were significantly higher Ribonuclease P (RNaseP) (3.3 [1.2, 5.7] vs. 1.2 [0.8, 1.2], p<0.001) and Beta-2microglobulin (B2M) (12.0 [1.0, 22.9], vs. 0.6 [0.6, 1.3], p<0.001) levels in cardiac arrest subjects at baseline compared to the control subjects. There were no differences between survivors and non-survivors for mitochondrial DNA, nuclear DNA, or cell free DNA. Cytochrome c was increased in post- cardiac arrest subjects compared to controls, and in post-cardiac arrest non-survivors compared to survivors. Nuclear DNA and cell free DNA was increased in plasma of post-cardiac arrest subjects. There were no differences in mitochondrial DNA, nuclear DNA, or cell free DNA between survivors and non-survivors. Mitochondrial injury markers showed mixed results in the post-cardiac arrest period. Future research needs to investigate these differences. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Breast cancer

    International Nuclear Information System (INIS)

    Delgado, L.; Krygier, G.; Castillo, C.

    2009-01-01

    This article is about the diagnosis, treatment and monitoring of breast cancer. Positive diagnosis is based on clinical mammary exam, mammography, mammary ultrasonography, and histological study. Before the chemotherapy and radiotherapy treatment are evaluated the risks

  1. Breast Augmentation

    Science.gov (United States)

    ... Administration (FDA) has identified a possible association between breast implants and the development of anaplastic large cell lymphoma (ALCL), a rare cancer of the immune system. The FDA believes that ...

  2. Breast Augmentation

    African Journals Online (AJOL)

    1974-04-13

    Apr 13, 1974 ... Complications encountered after breast augmentation are dealt with in .... in Phisohex or other suitable preparation for a few days before surgery ... In all cases, the prosthesis causes a fibrous tissue capsule to form around it.

  3. Breast Cancer

    Science.gov (United States)

    ... modulators and aromatase inhibitors, reduce the risk of breast cancer in women with a high risk of the disease. These medications carry a risk of side effects, so doctors reserve these medications for women who ...

  4. Focal epithelial hyperplasia by human papillomavirus (HPV)-32 misdiagnosed as HPV-16 and treated with combination of retinoids, imiquimod and quadrivalent HPV vaccine.

    Science.gov (United States)

    Gemigniani, Franco; Hernández-Losa, Javier; Ferrer, Berta; García-Patos, Vicente

    2015-12-01

    Focal epithelial hyperplasia (FEH) or Heck's disease is a rare, benign and asymptomatic mucosal proliferation associated with human papillomavirus (HPV) infection, mainly with genotypes 13 and 32. We report a florid case of FEH in an 11-year-old Haitian girl with systemic lupus erythematosus receiving immunosuppressive therapy. Cryotherapy was previously performed on numerous occasions with no results. We decided to prescribe a non-invasive and more comfortable treatment. A combination of topical retinoid and imiquimod cream was well tolerated and led to an important improvement. The evidence of infection by HPV-16 detected by polymerase chain reaction (PCR) technique, prompted us to prescribe the quadrivalent HPV vaccine (types 6, 11,16 and 18). Subsequent PCR sequencing with generic primers GP5-GP6 and further BLAST comparative analysis confirmed that genomic viral sequence in our case truly corresponded with HPV-32. This molecular misdiagnosis can be explained by the similarity between genomic sequences of both HPV-16 and -32 genotypes. At the 1-year follow up, we observed total clinical improvement and no recurrences of the disease. Complete healing in this case may correspond to a potential action of topical retinoid, imiquimod and the cross-protection mechanism of the quadrivalent HPV vaccine. © 2015 Japanese Dermatological Association.

  5. Effects of a synthetic retinoid on skin structure, matrix metalloproteinases, and procollagen in healthy and high-risk subjects with diabetes.

    Science.gov (United States)

    Zeng, Wei; Tahrani, Abd; Shakher, Jayadave; Varani, James; Hughes, Sharon; Dubb, Kiran; Stevens, Martin J

    2011-01-01

    In diabetes, foot ulceration may result from increased skin fragility. Retinoids can reverse some diabetes-induced deficits of skin structure and function, but their clinical utility is limited by skin irritation. The effects of diabetes and MDI 301, a nonirritating synthetic retinoid, and retinoic acid have been evaluated on matrix metalloproteinases (MMPs), procollagen expression, and skin structure in skin biopsies from nondiabetic volunteers and diabetic subjects at risk of foot ulceration using organ culture techniques. Zymography and enzyme-linked immunosorbent assay were utilized for analysis of MMP-1, -2, and -9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) and immunohistochemistry for type I procollagen protein abundance. Collagen structure parameters were assessed in formalin-fixed, paraffin-embedded tissue sections. The % of active MMP-1 and -9 was higher and TIMP-1 abundance was lower in subjects with diabetes. Type 1 procollagen abundance was reduced and skin structural deficits were increased in diabetes. Three μM MDI 301 reduced active MMP-1 and -9 abundance by 29% (P structural deficit scores. Two μM retinoic acid reduced MMP-1 but did not significantly affect skin structure. These data indicate that diabetic patients at risk of foot ulceration have deficits of skin structure and function. MDI 301 offers potential for repairing this skin damage complicating diabetes. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Selective ligand activity at Nur/retinoid X receptor complexes revealed by dimer-specific bioluminescence resonance energy transfer-based sensors

    Science.gov (United States)

    Giner, Xavier C; Cotnoir-White, David; Mader, Sylvie; Lévesque, Daniel

    2017-01-01

    Retinoid X receptors (RXR) play a role as master regulators due to their capacity to form heterodimers with other nuclear receptors. Accordingly, retinoid signaling is involved in multiple biological processes, including development, cell differentiation, metabolism and cell death. However, the role and functions of RXR in different heterodimer complexes remain unsolved, mainly because most RXR drugs (called rexinoids) are not selective to specific heterodimer complexes. This also strongly limits the use of rexinoids for specific therapeutic approaches. In order to better characterize rexinoids at specific nuclear receptor complexes, we have developed and optimized luciferase protein complementation-based Bioluminescence Resonance Energy Transfer (BRET) assays, which can directly measure recruitment of a co-activator motif fused to yellow fluorescent protein (YFP) by specific nuclear receptor dimers. To validate the assays, we compared rexinoid modulation of co-activator recruitment by RXR homodimer, and heterodimers Nur77/RXR and Nurr1/RXR. Results reveal that some rexinoids display selective co-activator recruitment activities with homo- or hetero-dimer complexes. In particular, SR11237 (BMS649) has increased potency for recruitment of co-activator motif and transcriptional activity with the Nur77/RXR heterodimer compared to other complexes. This technology should prove useful to identify new compounds with specificity for individual dimeric species formed by nuclear receptors. PMID:26148973

  7. Interaction between retinoid acid receptor-related orphan receptor alpha (RORA and neuropeptide S receptor 1 (NPSR1 in asthma.

    Directory of Open Access Journals (Sweden)

    Nathalie Acevedo

    Full Text Available Retinoid acid receptor-related Orphan Receptor Alpha (RORA was recently identified as a susceptibility gene for asthma in a genome-wide association study. To investigate the impact of RORA on asthma susceptibility, we performed a genetic association study between RORA single nucleotide polymorphisms (SNPs in the vicinity of the asthma-associated SNP (rs11071559 and asthma-related traits. Because the regulatory region of a previously implicated asthma susceptibility gene, Neuropeptide S receptor 1 (NPSR1, has predicted elements for RORA binding, we hypothesized that RORA may interact biologically and genetically with NPSR1. 37 RORA SNPs and eight NPSR1 SNPs were genotyped in the Swedish birth cohort BAMSE (2033 children and the European cross-sectional PARSIFAL study (1120 children. Seven RORA SNPs confined into a 49 kb region were significantly associated with physician-diagnosed childhood asthma. The most significant association with rs7164773 (T/C was driven by the CC genotype in asthma cases (OR = 2.0, 95%CI 1.36-2.93, p = 0.0003 in BAMSE; and 1.61, 1.18-2.19, p = 0.002 in the combined BAMSE-PARSIFAL datasets, respectively, and strikingly, the risk effect was dependent on the Gln344Arg mutation in NPSR1. In cell models, stimulation of NPSR1 activated a pathway including RORA and other circadian clock genes. Over-expression of RORA decreased NPSR1 promoter activity further suggesting a regulatory loop between these genes. In addition, Rora mRNA expression was lower in the lung tissue of Npsr1 deficient mice compared to wildtype littermates during the early hours of the light period. We conclude that RORA SNPs are associated with childhood asthma and show epistasis with NPSR1, and the interaction between RORA and NPSR1 may be of biological relevance. Combinations of common susceptibility alleles and less common functional polymorphisms may modify the joint risk effects on asthma susceptibility.

  8. Visualizing Vpr-induced G2 arrest and apoptosis.

    Directory of Open Access Journals (Sweden)

    Tomoyuki Murakami

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

  9. Serum tau and neurological outcome in cardiac arrest

    DEFF Research Database (Denmark)

    Mattsson, Niklas; Zetterberg, Henrik; Nielsen, Niklas

    2017-01-01

    OBJECTIVE: To test serum tau as a predictor of neurological outcome after cardiac arrest. METHODS: We measured the neuronal protein tau in serum at 24, 48, and 72 hours after cardiac arrest in 689 patients in the prospective international Target Temperature Management trial. The main outcome...... was poor neurological outcome, defined as Cerebral Performance Categories 3-5 at 6 months. RESULTS: Increased tau was associated with poor outcome at 6 months after cardiac arrest (median = 38.5, interquartile range [IQR] = 5.7-245ng/l in poor vs median = 1.5, IQR = 0.7-2.4ng/l in good outcome, for tau....... The accuracy in predicting outcome by serum tau was equally high for patients randomized to 33 °C and 36 °C targeted temperature after cardiac arrest. INTERPRETATION: Serum tau is a promising novel biomarker for prediction of neurological outcome in patients with cardiac arrest. It may be significantly better...

  10. Major life events as potential triggers of sudden cardiac arrest.

    Science.gov (United States)

    Wicks, April F; Lumley, Thomas; Lemaitre, Rozenn N; Sotoodehnia, Nona; Rea, Thomas D; McKnight, Barbara; Strogatz, David S; Bovbjerg, Viktor E; Siscovick, David S

    2012-05-01

    We investigated the risk of sudden cardiac arrest in association with the recent loss of, or separation from, a family member or friend. Our case-crossover study included 490 apparently healthy married residents of King County, Washington, who suffered sudden cardiac arrest between 1988 and 2005. We compared exposure to spouse-reported family/friend events occurring ≤ 1 month before sudden cardiac arrest with events occurring in the previous 5 months. We evaluated potential effect modification by habitual vigorous physical activity. Recent family/friend events were associated with a higher risk of sudden cardiac arrest (odds ratio [OR] = 1.6; 95% confidence interval [CI] = 1.1-2.4). ORs for cases with and without habitual vigorous physical activity were 1.1 (0.6-2.2) and 2.0 (1.2-3.1), respectively (interaction P = 0.02). These results suggest family/friend events may trigger sudden cardiac arrest and raise the hypothesis that habitual vigorous physical activity may lower susceptibility to these potential triggers.

  11. Current Pharmacological Advances in the Treatment of Cardiac Arrest

    Directory of Open Access Journals (Sweden)

    Andry Papastylianou

    2012-01-01

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

  12. The effectiveness of silver diamine fluoride in arresting caries.

    Science.gov (United States)

    Richards, Derek

    2017-10-27

    Data sourcesPubMed, Embase, Scopus, China National Knowledge Infrastructure (CNKI), Ichushi-web, Biblioteca Virtual en Salud Espana (BVSE) and Biblioteca Virtual em Saude (BVS) databases. There were no limits on language or publication dates.Study selectionTwo reviewers selected prospective clinical studies investigating SDF treatment for caries prevention in children.Data extraction and synthesisData was abstracted independently by two reviewers and risk of bias assessed. Meta-analysis was performed on studies in which the caries-arresting rate using 38% SDF solution on primary teeth could be obtained or calculated.ResultsNineteen studies were included; 16 were conducted in the primary dentition and three in permanent dentition. Fourteen studies used 38% SDF, three 30% SDF, and two 10% SDF. Eight studies using 38% SDF contributed to a meta-analysis and the overall proportion of arrested caries was 81% (95% CI; 68-89%). Percentage reductions were also calculated for 6,12,18,24 and >30 months. Arrested carious lesions stained black but no other adverse effects were reported.ConclusionsSDF commonly used at a high concentration (38%, 44,800ppm fluoride) is effective in arresting caries among children. There is no consensus on its number and frequency of application to arrest caries. Further studies are necessary to develop evidence-based guidelines on its use in children.

  13. Pattern of perioperative cardiac arrests at University of Maiduguri Teaching Hospital.

    Science.gov (United States)

    Kwari, Y D; Bello, M R; Eni, U E

    2010-01-01

    Perioperative cardiac arrests and death on the table represent the most serious complications of surgery and anaesthesia. This paper was designed to study their pattern, causes and outcomes following cardiopulmonary resuscitation (CPR) and intensive care unit (ICU) management in our institution. Three year retrospective review of perioperative cardiac arrests and death on operating table following surgical procedure under anaesthesia. For each cardiac arrest or death on the table the sequence of events leading to the arrest was evaluated using case notes, anaesthetic chart and ICU records. Study variables which include demographic data, ASA score, anaesthetic technique, causes and outcome were analysed and discussed. Fourteen perioperative cardiac arrests were encountered following 4051 anaesthetics administered over the three year study period. Twelve out of the fourteen cardiac arrests occurred following general anaesthesia, while the remaining two occurred following spinal anaesthesia. There was no cardiac arrest following local anaesthesia. Children suffered more cardiac arrest than adults. ASA class III and IV risk status suffered more arrests than ASA I and II. Hypoxia from airway problems was the commonest cause of cardiac arrest followed by septic shock. Monitoring with pulse oximeter was done in only 4 out of the 14 cardiac arrests. Only 2 (14%) out of 14 cardiac arrests recovered to home discharge, one of them with significant neurological deficit. Majority of arrests were due to hypoxia from airway problems that were not detected early There is need to improve on patient monitoring, knowledge of CPR and intensive care so as to improve the outcome of perioperative cardiac arrest.

  14. Arrester Resistive Current Measuring System Based on Heterogeneous Network

    Science.gov (United States)

    Zhang, Yun Hua; Li, Zai Lin; Yuan, Feng; Hou Pan, Feng; Guo, Zhan Nan; Han, Yue

    2018-03-01

    Metal Oxide Arrester (MOA) suffers from aging and poor insulation due to long-term impulse voltage and environmental impact, and the value and variation tendency of resistive current can reflect the health conditions of MOA. The common wired MOA detection need to use long cables, which is complicated to operate, and that wireless measurement methods are facing the problems of poor data synchronization and instability. Therefore a novel synchronous measurement system of arrester current resistive based on heterogeneous network is proposed, which simplifies the calculation process and improves synchronization, accuracy and stability and of the measuring system. This system combines LoRa wireless network, high speed wireless personal area network and the process layer communication, and realizes the detection of arrester working condition. Field test data shows that the system has the characteristics of high accuracy, strong anti-interference ability and good synchronization, which plays an important role in ensuring the stable operation of the power grid.

  15. Cardiac arrest following ventilator fire: A rare cause

    Directory of Open Access Journals (Sweden)

    K Nazeer Ahmed

    2012-01-01

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

  16. Crack arrest toughness measurements with A533B steel

    International Nuclear Information System (INIS)

    Salonen, Seppo.

    1979-11-01

    This work covers crack arrest toughness measurements on A533B steel done at the Technical Research Centre of Finland. These measurements are one part of a multinational effort, involving 30 laboratories. The aim of the cooperative test program is to examine two test procedures for measuring the crack arrest toughness, to give information about their reproducibility, and to identify the factors affecting the interpretation. The principles given for the testing were easy to apply in general and the results were satisfactory. Some factors in the test runs and in the specimen's behaviour are indicated which can cause error in the results or make implementation of the test more difficult. By comparing the results from our laboratory with average values from the test program a good agreement can be seen. Crack arrest toughness values derived from the compared procedures with a static analysis agree closely, but values calculated using a dynamic analysis differ considerably. (author)

  17. A crack arrest test using a toughness gradient steel plate

    International Nuclear Information System (INIS)

    Okamura, H.; Yagawa, G.; Urabe, Y.; Satoh, M.; Sano, J.

    1995-01-01

    Pressurized thermal shock (PTS) is a phenomenon that can occur in the reactor pressure vessels (RPVs) with internal pressure and is one of the most severe stress conditions that can be applied to the vessel. Preliminary research has shown that no PTS concern is likely to exist on Japanese RPVs during their design service lives. However, public acceptance of vessel integrity requires analyses and experiment in order to establish an analytical method and a database for life extension of Japanese RPVs. The Japanese PTS integrity study was carried out from FY 1983 to FY 1991 as a national project by Japan Power Engineering and Inspection Corporation (JAPEIC) under contract with Ministry of International Trade and Industry (MITI) in cooperation with LWR utilities and vendors. Here, a crack arrest test was carried out using a toughness gradient steel plate with three layers to study the concept of crack arrest toughness. Four-point bending load with thermal shock was applied to the large flat plate specimen with a surface crack. Five crack initiations and arrests were observed during the test and the propagated crack bifurcated. Finally, cracks were arrested at the boundary of the first and the second layer, except for a small segment of the crack. The first crack initiation took place slightly higher than the lower bound of K Ic data obtained by ITCT specimens. That is, the K IC concept for brittle crack initiation was verified for heavy section steel plates. The first crack arrest took place within the scatter band of K Ia and K Id data for the first layer. That is, the K Ia concept appears applicable for crack arrest of a short crack jump

  18. Complete maternal and fetal recovery after prolonged cardiac arrest.

    Science.gov (United States)

    Selden, B S; Burke, T J

    1988-04-01

    A case of complete maternal and fetal recovery after prolonged cardiac arrest from massive lidocaine overdose is presented. A 27-year-old woman at 15 weeks gestation had a complete neurologic recovery after 22 minutes of CPR, including 19 minutes of electromechanical dissociation and asystole, with normal fetal heart function and fetal motion confirmed by ultrasound immediately after resuscitation. The patient delivered a healthy and neurologically normal infant at 40 weeks gestation. This is the longest cardiac arrest in early pregnancy reported in the medical literature with normal maternal and fetal outcome.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  20. Out-of-Hospital Cardiac Arrest in Denmark

    DEFF Research Database (Denmark)

    Wissenberg Jørgensen, Mads

    challenges, due to the victim’s physical location, which brings an inherent risk of delay (or altogether absence) of recognition and treatment of cardiac arrest. A low frequency of bystander cardiopulmonary resuscitation and low 30-day survival after out-of-hospital cardiac arrest were identified nearly ten...... years ago in Denmark. These findings led to several national initiatives to strengthen bystander resuscitation attempts and advance care. Despite these nationwide efforts, it was unknown prior to this project whether these efforts resulted in changes in resuscitation attempts by bystanders and changes...

  1. Breast MRI scan

    Science.gov (United States)

    ... or breast ultrasound Evaluate for possible rupture of breast implants Find any cancer that remains after surgery or chemotherapy Show blood ... Mean Abnormal results may be due to: Breast cancer Cysts Leaking or ruptured breast implants Abnormal breast tissue that is not cancer Scar ...

  2. Breast Cancer Surgery

    Science.gov (United States)

    FACTS FOR LIFE Breast Cancer Surgery The goal of breast cancer surgery is to remove the whole tumor from the breast. Some lymph nodes ... might still be in the body. Types of breast cancer surgery There are two types of breast cancer ...

  3. Increasing human Th17 differentiation through activation of orphan nuclear receptor retinoid acid-related orphan receptor γ (RORγ) by a class of aryl amide compounds.

    Science.gov (United States)

    Zhang, Wei; Zhang, Jing; Fang, Leiping; Zhou, Ling; Wang, Shuai; Xiang, Zhijun; Li, Yuan; Wisely, Bruce; Zhang, Guifeng; An, Gang; Wang, Yonghui; Leung, Stewart; Zhong, Zhong

    2012-10-01

    In a screen for small-molecule inhibitors of retinoid acid-related orphan receptor γ (RORγ), we fortuitously discovered that a class of aryl amide compounds behaved as functional activators of the interleukin 17 (IL-17) reporter in Jurkat cells. Three of these compounds were selected for further analysis and found to activate the IL-17 reporter with potencies of ∼0.1 μM measured by EC₅₀. These compounds were shown to directly bind to RORγ by circular dichroism-based thermal stability experiments. Furthermore, they can enhance an in vitro Th17 differentiation process in human primary T cells. As RORγ remains an orphan nuclear receptor, discovery of these aryl amide compounds as functional agonists will now provide pharmacological tools for us to dissect functions of RORγ and facilitate drug discovery efforts for immune-modulating therapies.

  4. BREAST RECONSTRUCTIONS AFTER BREAST CANCER TREATING

    Directory of Open Access Journals (Sweden)

    Erik Vrabič

    2018-02-01

    Full Text Available Background. Breasts are an important symbol of physical beauty, feminity, mothering and sexual desire through the entire history of mankind. Lost of the whole or part of the breast is functional and aesthetic disturbance for woman. It is understandable, that the woman, who is concerned over breast loss, is as appropriate as another person´s concern over the loss of a limb or other body part. Before the 1960, breast reconstruction was considered as a dangerous procedure and it was almost prohibited. Considering the psychological importance of the breast in modern society, the possibility of breast reconstruction for the woman about to undergo a mastectomy is a comforting alternative. We can perform breast reconstruction with autologous tissue (autologous reconstruction, with breast implants and combination of both methods. For autologous reconstruction we can use local tissue (local flaps, or tissue from distant parts of the body (free vascular tissue transfer. Tissue expansion must be performed first, in many cases of breast reconstructions with breast implants. Conclusions. Possibility of breast reconstruction made a big progress last 3 decades. Today we are able to reconstruct almost every defect of the breast and the entire breast. Breast reconstruction rise the quality of life for breast cancer patients. Breast reconstruction is a team work of experts from many medicine specialites. In Slovenia we can offer breast reconstruction for breast cancer patients in Ljubljana, where plastic surgeons from Clinical Department for Plastic Surgery and Burns cooperate with oncologic surgeons. Ten years ago a similar cooperation between plastic surgeons and surgeons of the Centre for Breast Diseases was established in Maribor.

  5. Breast pain

    Science.gov (United States)

    ... that reducing the amount of fat, caffeine, or chocolate in your diet helps reduce breast pain. Vitamin ... harmful, but most studies have not shown any benefit. Talk to your provider before starting any medicine or ... Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA. Review provided by ...

  6. Breast Cancer

    Science.gov (United States)

    ... right away. He or she will do a physical exam. They will ask you about your health history and your family’s history of breast cancer. ... and Wellness Staying Healthy Healthy Living Travel Occupational Health First Aid and ... Pets and Animals myhealthfinder Food and Nutrition Healthy Food ...

  7. Breast lymphoma

    African Journals Online (AJOL)

    To fulfil the criteria for primary breast lymphoma, the following characteristics were reqUired: (I) technically adequate specimens; (iI) mammary tissue and lymphomatous infiltrate in close association; (iil) no evidence of concurrent widespread disease; and (iv) no previous. Haematology/Oncology Division, Department of ...

  8. Breast cancer

    CERN Multimedia

    2002-01-01

    "Cancer specialists will soon be able to compare mammograms with computerized images of breast cancer from across Europe, in a bid to improve diagnosis and treatment....The new project, known as MammoGrid, brings together computer and medical imaging experts, cancer specialists, radiologists and epidemiologists from Bristol, Oxford, Cambridge, France and Italy" (1 page).

  9. Standardized EEG interpretation accurately predicts prognosis after cardiac arrest

    NARCIS (Netherlands)

    Westhall, Erik; Rossetti, Andrea O.; van Rootselaar, Anne-Fleur; Wesenberg Kjaer, Troels; Horn, Janneke; Ullén, Susann; Friberg, Hans; Nielsen, Niklas; Rosén, Ingmar; Åneman, Anders; Erlinge, David; Gasche, Yvan; Hassager, Christian; Hovdenes, Jan; Kjaergaard, Jesper; Kuiper, Michael; Pellis, Tommaso; Stammet, Pascal; Wanscher, Michael; Wetterslev, Jørn; Wise, Matt P.; Cronberg, Tobias; Saxena, Manoj; Miller, Jennene; Inskip, Deborah; Macken, Lewis; Finfer, Simon; Eatough, Noel; Hammond, Naomi; Bass, Frances; Yarad, Elizabeth; O'Connor, Anne; Bird, Simon; Jewell, Timothy; Davies, Gareth; Ng, Karl; Coward, Sharon; Stewart, Antony; Micallef, Sharon; Parker, Sharyn; Cortado, Dennis; Gould, Ann; Harward, Meg; Thompson, Kelly; Glass, Parisa; Myburgh, John; Smid, Ondrej; Belholavek, Jan; Juffermans, Nicole P.; Boerma, EC

    2016-01-01

    To identify reliable predictors of outcome in comatose patients after cardiac arrest using a single routine EEG and standardized interpretation according to the terminology proposed by the American Clinical Neurophysiology Society. In this cohort study, 4 EEG specialists, blinded to outcome,

  10. Ventilation and gas exchange management after cardiac arrest.

    Science.gov (United States)

    Sutherasan, Yuda; Raimondo, Pasquale; Pelosi, Paolo

    2015-12-01

    For several decades, physicians had integrated several interventions aiming to improve the outcomes in post-cardiac arrest patients. However, the mortality rate after cardiac arrest is still as high as 50%. Post-cardiac arrest syndrome is associated with high morbidity and mortality due to not only poor neurological outcome and cardiovascular failure but also respiratory dysfunction. To minimize ventilator-associated lung injury, protective mechanical ventilation by using low tidal volume ventilation and driving pressure may decrease pulmonary complications and improve survival. Low level of positive end-expiratory pressure (PEEP) can be initiated and titrated with careful cardiac output and respiratory mechanics monitoring. Furthermore, optimizing gas exchange by avoiding hypoxia and hyperoxia as well as maintaining normocarbia may improve neurological and survival outcome. Early multidisciplinary cardiac rehabilitation intervention is recommended. Minimally invasive monitoring techniques, that is, echocardiography, transpulmonary thermodilution method measuring extravascular lung water, as well as transcranial Doppler ultrasound, might be useful to improve appropriate management of post-cardiac arrest patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Endothelial Dysfunction in Resuscitated Cardiac Arrest (ENDO-RCA)

    DEFF Research Database (Denmark)

    Meyer, Anna Sina P; Ostrowski, Sisse Rye; Kjærgaard, Jesper

    2016-01-01

    BACKGROUND: Morbidity and mortality following initial survival of cardiac arrest remain high despite great efforts to improve resuscitation techniques and post-resuscitation care, in part due to the ischemia-reperfusion injury secondary to the restoration of the blood circulation. Patients resusc...

  12. 19 CFR 162.63 - Arrests and seizures.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Arrests and seizures. 162.63 Section 162.63 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) INSPECTION, SEARCH, AND SEIZURE Controlled Substances, Narcotics, and Marihuana § 162...

  13. Crack arrest toughness of structural steels evaluated by compact test

    International Nuclear Information System (INIS)

    Nakano, Yoshifumi; Tanaka, Michihiro

    1982-01-01

    Crack arrest tests such as compact, ESSO and DCB tests were made on SA533B Cl. 1, HT80 and KD32 steels to evaluate the crack arrest toughness. The main results obtained are as follows: (1) The crack arrest toughness could be evaluated by K sub(Ia) which was obtained by the static analysis of compact test. (2) K sub(ID) determined by the dynamic analysis of compact test was greater than K sub(Ia), though K sub(ID) became close to K sub(Ia)/K sub(Q) became a unity where K sub(Q) is the stress intensity factor at the crack initiation. (3) No significant difference was observed between K sub(Ia) and K sub(ca) obtained by ESSO and DCB tests, though K sub(ca) obtained by DCB test tended to be smaller than K sub(Ia) at lower temperatures. (4) K sub(Ia) was smaller than K sub(Ic) in the transition temperature range, while it was greater than K sub(Id). In the temperature range where K sub(Ic), which was determined from J sub(Ic), decreased with temperature increase, however, it was smaller than K sub(Ia). (5) The fracture appearance transition temperature and the absorbed energy obtained by 2 mm V-notch Charpy test were appropriate parameters for representing the crack arrest toughness, while the NDT temperature was not. (author)

  14. Growth arrest despite growth hormone replacement, post-craniopharyngioma surgery.

    Science.gov (United States)

    DeVile, C J; Hayward, R D; Neville, B G; Grant, D B; Stanhope, R

    1995-01-01

    Children with growth failure, whether secondary to an endocrinopathy such as growth hormone deficiency or secondary to neurological handicap with poor nutrient intake, grow at a subnormal rate but it is most unusual for a child to have complete growth arrest. PMID:7745571

  15. Carbamazepine induces mitotic arrest in mammalian Vero cells

    International Nuclear Information System (INIS)

    Perez Martin, J.M.; Fernandez Freire, P.; Labrador, V.; Hazen, M.J.

    2008-01-01

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

  16. Cdc20 control of cell fate during prolonged mitotic arrest

    DEFF Research Database (Denmark)

    Nilsson, Jakob

    2011-01-01

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

  17. Outcomes After Cardiac Arrest in an Adult Burn Center

    Science.gov (United States)

    2013-12-07

    of in-hospital CA are likely to report widely varying survival rates as a result of study populations with characteristic but distinct demo- graphics ...Rehabil 1997;18:S119. [2] Sandroni C, Nolan J. In-hospital cardiac arrest: incidence, prognosis and possible measures to improve survival. Intens Care Med

  18. Trichostrongylus colubriformis rDNA polymorphism associated with arrested development

    Czech Academy of Sciences Publication Activity Database

    Langrová, I.; Zouhar, M.; Vadlejch, J.; Borovský, M.; Jankovská, I.; Lytvynets, Andrej

    2008-01-01

    Roč. 103, č. 2 (2008), s. 401-403 ISSN 0932-0113 Institutional research plan: CEZ:AV0Z50110509 Keywords : arrested development * polymorphism * rDNA Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.473, year: 2008

  19. Carbamazepine induces mitotic arrest in mammalian Vero cells

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-01-01

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

  20. Anaphylactic shock and cardiac arrest caused by thiamine infusion

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  1. Lupeol induces S-phase arrest and mitochondria-mediated ...

    Indian Academy of Sciences (India)

    48

    Lupeol induces S-phase arrest and mitochondria-mediated apoptosis in cervical cancer cells. Nupoor Prasad1, Akash Sabarwal2, Umesh C. S. Yadav1, Rana P. Singh2,*. 1School of Life Sciences, Central University of Gujarat, Gandhinagar, Gujarat, India. 2Cancer Biology Laboratory, School of Life Sciences, Jawaharlal ...

  2. Cardiac Arrest after Local Anaesthetic Toxicity in a Paediatric Patient

    Directory of Open Access Journals (Sweden)

    Liana Maria Torres de Araújo Azi

    2016-01-01

    Full Text Available We report a case of a paediatric patient undergoing urological procedure in which a possible inadvertent intravascular or intraosseous injection of bupivacaine with adrenaline in usual doses caused subsequent cardiac arrest, completely reversed after administration of 20% intravenous lipid emulsion. Early diagnosis of local anaesthetics toxicity and adequate cardiovascular resuscitation manoeuvres contribute to the favourable outcome.

  3. Offenders' Perceptions of House Arrest and Electronic Monitoring

    Science.gov (United States)

    Martin, Jamie S.; Hanrahan, Kate; Bowers, James H., Jr.

    2009-01-01

    This article reports on a study designed to examine the perceptions of house arrest (HA) and electronic monitoring (EM) among offenders who have recently experienced this criminal sentence. Data were gathered via a self-administered questionnaire and follow-up interviews with a sample of offenders. Our primary areas of interest were to assess (a)…

  4. Is Ward Experience in Resuscitation Effort Related to the Prognosis of Unexpected Cardiac Arrest?

    Directory of Open Access Journals (Sweden)

    Sen-Kuang Hou

    2007-09-01

    Conclusion: Hospital wards with more than 5 cardiac arrests per year have a better patient survival rate than those with fewer arrests. This is despite all ward staff receiving the same level of training.

  5. Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children.

    Science.gov (United States)

    Moler, Frank W; Silverstein, Faye S; Holubkov, Richard; Slomine, Beth S; Christensen, James R; Nadkarni, Vinay M; Meert, Kathleen L; Browning, Brittan; Pemberton, Victoria L; Page, Kent; Gildea, Marianne R; Scholefield, Barnaby R; Shankaran, Seetha; Hutchison, Jamie S; Berger, John T; Ofori-Amanfo, George; Newth, Christopher J L; Topjian, Alexis; Bennett, Kimberly S; Koch, Joshua D; Pham, Nga; Chanani, Nikhil K; Pineda, Jose A; Harrison, Rick; Dalton, Heidi J; Alten, Jeffrey; Schleien, Charles L; Goodman, Denise M; Zimmerman, Jerry J; Bhalala, Utpal S; Schwarz, Adam J; Porter, Melissa B; Shah, Samir; Fink, Ericka L; McQuillen, Patrick; Wu, Theodore; Skellett, Sophie; Thomas, Neal J; Nowak, Jeffrey E; Baines, Paul B; Pappachan, John; Mathur, Mudit; Lloyd, Eric; van der Jagt, Elise W; Dobyns, Emily L; Meyer, Michael T; Sanders, Ronald C; Clark, Amy E; Dean, J Michael

    2017-01-26

    Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after in-hospital cardiac arrest are limited. In a trial conducted at 37 children's hospitals, we compared two temperature interventions in children who had had in-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition (VABS-II, on which scores range from 20 to 160, with higher scores indicating better function), was evaluated among patients who had had a VABS-II score of at least 70 before the cardiac arrest. The trial was terminated because of futility after 329 patients had undergone randomization. Among the 257 patients who had a VABS-II score of at least 70 before cardiac arrest and who could be evaluated, the rate of the primary efficacy outcome did not differ significantly between the hypothermia group and the normothermia group (36% [48 of 133 patients] and 39% [48 of 124 patients], respectively; relative risk, 0.92; 95% confidence interval [CI], 0.67 to 1.27; P=0.63). Among 317 patients who could be evaluated for change in neurobehavioral function, the change in VABS-II score from baseline to 12 months did not differ significantly between the groups (P=0.70). Among 327 patients who could be evaluated for 1-year survival, the rate of 1-year survival did not differ significantly between the hypothermia group and the normothermia group (49% [81 of 166 patients] and 46% [74 of 161 patients], respectively; relative risk, 1.07; 95% CI, 0.85 to 1.34; P=0.56). The incidences of blood-product use, infection, and serious adverse

  6. Male Breast Cancer

    Science.gov (United States)

    Although breast cancer is much more common in women, men can get it too. It happens most often to men between ... 60 and 70. Breast lumps usually aren't cancer. However, most men with breast cancer have lumps. ...

  7. Breast biopsy -- stereotactic

    Science.gov (United States)

    ... org/-/media/ACR/Files/Practice-Parameters/stereo-breast.pdf . Updated 2016. Accessed March 14, 2017. Parker C, Umphrey H, Bland K. The role of stereotactic breast biopsy in the management of breast disease. In: Cameron ...

  8. Breast Cancer in Men

    Science.gov (United States)

    ... ultrasound or a breast MRI cannot rule out breast cancer then you will need a biopsy to confirm diagnosis. If diagnosed When first diagnosed with breast cancer, many men are in shock. After all, ...

  9. MRI of the Breast

    Science.gov (United States)

    ... in evaluating women at high risk for breast cancer. MRI can successfully image the dense breast tissue common in younger women, and it can successfully image breast implants. Both of these are difficult to image using ...

  10. Male Breast Cancer

    Science.gov (United States)

    ... types of breast cancer that can occur in men include Paget's disease of the nipple and inflammatory breast cancer. Inherited genes that increase breast cancer risk Some men inherit abnormal (mutated) genes from their parents that ...

  11. Plasmacytoma of the Breast

    African Journals Online (AJOL)

    GB

    2015-10-04

    Oct 4, 2015 ... The clinical diagnosis of a breast plasmacytoma is ... lead to a diagnosis of breast plasmacytoma (1-3). Bone marrow ... breast cancer cases present at an advanced stage, ... pelvic ultrasonography, were normal, Bence Jones.

  12. Breast Cancer Disparities

    Science.gov (United States)

    ... 2.65 MB] Read the MMWR Science Clips Breast Cancer Black Women Have Higher Death Rates from Breast ... of Page U.S. State Info Number of Additional Breast Cancer Deaths Among Black Women, By State SOURCE: National ...

  13. Epidemiology and Outcomes After In-Hospital Cardiac Arrest After Pediatric Cardiac Surgery

    Science.gov (United States)

    Gupta, Punkaj; Jacobs, Jeffrey P.; Pasquali, Sara K.; Hill, Kevin D.; Gaynor, J. William; O’Brien, Sean M.; He, Max; Sheng, Shubin; Schexnayder, Stephen M.; Berg, Robert A.; Nadkarni, Vinay M.; Imamura, Michiaki; Jacobs, Marshall L.

    2014-01-01

    Background Multicenter data regarding cardiac arrest in children undergoing heart operations are limited. We describe epidemiology and outcomes associated with postoperative cardiac arrest in a large multiinstitutional cohort. Methods Patients younger than 18 years in the Society of Thoracic Surgeons Congenital Heart Surgery Database (2007 through 2012) were included. Patient factors, operative characteristics, and outcomes were described for patients with and without postoperative cardiac arrest. Multivariable models were used to evaluate the association of center volume with cardiac arrest rate and mortality after cardiac arrest, adjusting for patient and procedural factors. Results Of 70,270 patients (97 centers), 1,843 (2.6%) had postoperative cardiac arrest. Younger age, lower weight, and presence of preoperative morbidities (all p < 0.0001) were associated with cardiac arrest. Arrest rate increased with procedural complexity across common benchmark operations, ranging from 0.7% (ventricular septal defect repair) to 12.7% (Norwood operation). Cardiac arrest was associated with significant mortality risk across procedures, ranging from 15.4% to 62.3% (all p < 0.0001). In multivariable analysis, arrest rate was not associated with center volume (odds ratio, 1.06; 95% confidence interval, 0.71 to 1.57 in low- versus high-volume centers). However, mortality after cardiac arrest was higher in low-volume centers (odds ratio, 2.00; 95% confidence interval, 1.52 to 2.63). This association was present for both high- and low-complexity operations. Conclusions Cardiac arrest carries a significant mortality risk across the stratum of procedural complexity. Although arrest rates are not associated with center volume, lower-volume centers have increased mortality after cardiac arrest. Further study of mechanisms to prevent cardiac arrest and to reduce mortality in those with an arrest is warranted. PMID:25443018

  14. The geometry of empty space is the key to arresting dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Lawlor, Aonghus; De Gregorio, Paolo; Dawson, K A [Department of Chemistry, University College Dublin, Irish Centre for Colloid Science and Biomaterials, Belfield, Dublin 4 (Ireland)

    2004-10-27

    We present the concept of dynamically available volume as a suitable order parameter for dynamical arrest. We show that dynamical arrest can be understood as a de-percolation transition of a vacancy network or available space. Beyond the arrest transition we find that droplets of available space are disconnected and the dynamics is frozen. This connection of the dynamics to the underlying geometrical structure of empty space provides us with a rich framework for studying the arrest transition.

  15. Crack propagation and arrest simulation of X90 gas pipe

    International Nuclear Information System (INIS)

    Yang, Fengping; Huo, Chunyong; Luo, Jinheng; Li, He; Li, Yang

    2017-01-01

    To determine whether X90 steel pipe has enough crack arrest toughness or not, a damage model was suggested as crack arrest criterion with material parameters of plastic uniform percentage elongation and damage strain energy per volume. Fracture characteristic length which characterizes fracture zone size was suggested to be the largest mesh size on expected cracking path. Plastic uniform percentage elongation, damage strain energy per volume and fracture characteristic length of X90 were obtained by five kinds of tensile tests. Based on this criterion, a length of 24 m, Φ1219 × 16.3 mm pipe segment model with 12 MPa internal gas pressure was built and computed with fluid-structure coupling method in ABAQUS. Ideal gas state equation was used to describe lean gas behavior. Euler grid was used to mesh gas zone inside the pipe while Lagrangian shell element was used to mesh pipe. Crack propagation speed and gas decompression speed were got after computation. The result shows that, when plastic uniform percentage elongation is equal to 0.054 and damage strain energy per volume is equal to 0.64 J/mm"3, crack propagation speed is less than gas decompression speed, which means the simulated X90 gas pipe with 12 MPa internal pressure can arrest cracking itself. - Highlights: • A damage model was suggested as crack arrest criterion. • Plastic uniform elongation and damage strain energy density are material parameters. • Fracture characteristic length is suggested to be largest mesh size in cracking path. • Crack propagating simulation with coupling of pipe and gas was realized in ABAQUS. • A Chinese X90 steel pipe with 12 MPa internal pressure can arrest cracking itself.

  16. Pseudomonal breast infection

    Science.gov (United States)

    Rastall, S; Catchpole, C; Bright-Thomas, R; Thrush, S

    2010-01-01

    Breast infection and breast sepsis secondary to Pseudomonas aeruginosa is uncommon. We report two cases of pseudomonal breast infection leading to septic shock and abscess formation in women with non-responding breast infection. The management of breast infection is broad-spectrum antibiotics and ultrasound with aspiration of any collection. To treat breast infection effectively, the causative organism must be isolated to enable appropriate antibiotic therapy. PMID:20412664

  17. Altered serotonin physiology in human breast cancers favors paradoxical growth and cell survival.

    Science.gov (United States)

    Pai, Vaibhav P; Marshall, Aaron M; Hernandez, Laura L; Buckley, Arthur R; Horseman, Nelson D

    2009-01-01

    The breast microenvironment can either retard or accelerate the events associated with progression of latent cancers. However, the actions of local physiological mediators in the context of breast cancers are poorly understood. Serotonin (5-HT) is a critical local regulator of epithelial homeostasis in the breast and other organs. Herein, we report complex alterations in the intrinsic mammary gland serotonin system of human breast cancers. Serotonin biosynthetic capacity was analyzed in human breast tumor tissue microarrays using immunohistochemistry for tryptophan hydroxylase 1 (TPH1). Serotonin receptors (5-HT1-7) were analyzed in human breast tumors using the Oncomine database. Serotonin receptor expression, signal transduction, and 5-HT effects on breast cancer cell phenotype were compared in non-transformed and transformed human breast cells. In the context of the normal mammary gland, 5-HT acts as a physiological regulator of lactation and involution, in part by favoring growth arrest and cell death. This tightly regulated 5-HT system is subverted in multiple ways in human breast cancers. Specifically, TPH1 expression undergoes a non-linear change during progression, with increased expression during malignant progression. Correspondingly, the tightly regulated pattern of 5-HT receptors becomes dysregulated in human breast cancer cells, resulting in both ectopic expression of some isoforms and suppression of others. The receptor expression change is accompanied by altered downstream signaling of 5-HT receptors in human breast cancer cells, resulting in resistance to 5-HT-induced apoptosis, and stimulated proliferation. Our data constitutes the first report of direct involvement of 5-HT in human breast cancer. Increased 5-HT biosynthetic capacity accompanied by multiple changes in 5-HT receptor expression and signaling favor malignant progression of human breast cancer cells (for example, stimulated proliferation, inappropriate cell survival). This occurs

  18. Experimental investigation of interfacial crack arrest in sandwich beams subjected to fatigue loading using a novel crack arresting device

    DEFF Research Database (Denmark)

    Martakos, G.; Andreasen, J.H.; Berggreen, Christian

    2017-01-01

    A recently proposed face-sheet–core interface crack arresting device is implemented in sandwich beams and tested using the Sandwich Tear Test configuration. Fatigue loading conditions are applied to propagate the crack and determine the effect of the crack stopper on the fatigue growth rate and a...

  19. 30 CFR 75.521 - Lightning arresters; ungrounded and exposed power conductors and telephone wires.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Lightning arresters; ungrounded and exposed... Electrical Equipment-General § 75.521 Lightning arresters; ungrounded and exposed power conductors and... leads underground shall be equipped with suitable lightning arresters of approved type within 100 feet...

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

    Science.gov (United States)

    Lally, William; DeMaris, Alfred

    2012-01-01

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

  1. Breast Reduction Surgery

    Science.gov (United States)

    ... considering breast reduction surgery, consult a board-certified plastic surgeon. It's important to understand what breast reduction surgery entails — including possible risks and complications — as ...

  2. Polycomb Group Protein PHF1 Regulates p53-dependent Cell Growth Arrest and Apoptosis*

    Science.gov (United States)

    Yang, Yang; Wang, Chenji; Zhang, Pingzhao; Gao, Kun; Wang, Dejie; Yu, Hongxiu; Zhang, Ting; Jiang, Sirui; Hexige, Saiyin; Hong, Zehui; Yasui, Akira; Liu, Jun O.; Huang, Haojie; Yu, Long

    2013-01-01

    Polycomb group protein PHF1 is well known as a component of a novel EED-EZH2·Polycomb repressive complex 2 complex and plays important roles in H3K27 methylation and Hox gene silencing. PHF1 is also involved in the response to DNA double-strand breaks in human cells, promotes nonhomologous end-joining processes through interaction with Ku70/Ku80. Here, we identified another function of PHF1 as a potential p53 pathway activator in a pathway screen using luminescence reporter assay. Subsequent studies showed PHF1 directly interacts with p53 proteins both in vivo and in vitro and co-localized in nucleus. PHF1 binds to the C-terminal regulatory domain of p53. Overexpression of PHF1 elevated p53 protein level and prolonged its turnover. Knockdown of PHF1 reduced p53 protein level and its target gene expression both in normal state and DNA damage response. Mechanically, PHF1 protects p53 proteins from MDM2-mediated ubiquitination and degradation. Furthermore, we showed that PHF1 regulates cell growth arrest and etoposide-induced apoptosis in a p53-dependent manner. Finally, PHF1 expression was significantly down-regulated in human breast cancer samples. Taken together, we establish PHF1 as a novel positive regulator of the p53 pathway. These data shed light on the potential roles of PHF1 in tumorigenesis and/or tumor progression. PMID:23150668

  3. Community involvement in out of hospital cardiac arrest

    Science.gov (United States)

    Shams, Ali; Raad, Mohamad; Chams, Nour; Chams, Sana; Bachir, Rana; El Sayed, Mazen J.

    2016-01-01

    Abstract Out of hospital cardiac arrest (OHCA) is a leading cause of death worldwide. Developing countries including Lebanon report low survival rates and poor neurologic outcomes in affected victims. Community involvement through early recognition and bystander cardiopulmonary resuscitation (CPR) can improve OHCA survival. This study assesses knowledge and attitude of university students in Lebanon and identifies potential barriers and facilitators to learning and performing CPR. A cross-sectional survey was administered to university students. The questionnaire included questions regarding the following data elements: demographics, knowledge, and awareness about sudden cardiac arrest, CPR, automated external defibrillator (AED) use, prior CPR and AED training, ability to perform CPR or use AED, barriers to performing/learning CPR/AED, and preferred location for attending CPR/AED courses. Descriptive analysis followed by multivariate analysis was carried out to identify predictors and barriers to learning and performing CPR. A total of 948 students completed the survey. Participants’ mean age was 20.1 (±2.1) years with 53.1% women. Less than half of participants (42.9%) were able to identify all the presenting signs of cardiac arrest. Only 33.7% of participants felt able to perform CPR when witnessing a cardiac arrest. Fewer participants (20.3%) reported receiving previous CPR training. Several perceived barriers to learning and performing CPR were also reported. Significant predictors of willingness to perform CPR when faced with a cardiac arrest were: earning higher income, previous CPR training and feeling confident in one's ability to apply an AED, or perform CPR. Lacking enough expertise in performing CPR was a significant barrier to willingness to perform CPR. University students in Lebanon are familiar with the symptoms of cardiac arrest, however, they are not well trained in CPR and lack confidence to perform it. The attitude towards the importance of

  4. [Fibrocystic breast disease--breast cancer sequence].

    Science.gov (United States)

    Habor, V; Habor, A; Copotoiu, C; Panţîru, A

    2010-01-01

    Fibrocystic breast disease has developed a major issue: the breast cancer sequence. Its involvement regarding the increse of breast cancer risk has 2 aspects: it may be either the marker of a prone tissue or a premalignant hystological deffect. Difficult differential diagnosis of benign proliferative breast lession and carcinoma led to the idea of sequency between the two: cancer does not initiate on normal mammary epithelia; it takes several proliferative stages for it to occur. In our series we analized a number of 677 breast surgical procedures where the pathologic examination reveals 115 cases (17%) of coexistence between cancer and fibrocystic breast disease. This aspect has proved to be related to earlier debut of breast cancer, suggesting that epithelial hyperplasia is a risk factor for breast cancer.

  5. The clinical impact of vehicle technology using a patented formulation of benzoyl peroxide 5%/clindamycin 1% gel: comparative assessments of skin tolerability and evaluation of combination use with a topical retinoid.

    Science.gov (United States)

    Del Rosso, James Q; Tanghetti, Emil

    2006-02-01

    A major challenge encountered in clinical practice in patients with acne vulgaris is irritation related to topical medications used for treatment. Advances in vehicle technology have improved formulations containing active ingredients known to produce irritation in some patients, such as benzoyl peroxide (BP) and topical retinoids. Clinical studies, including combination therapy studies have demonstrated that certain additives, such as silicates and specific humectants, reduce irritation by maintaining barrier integrity. A patented gel formulation of BP 5%/clindamycin phosphate 1% (clindamycin) containing dimethicone and glycerin has been studied both as a monotherapy and in combination with topical retinoid use. This article evaluates specific vehicle additives included in this gel formulation and explains their role in reducing irritation. Data from clinical trials utilizing this technology in acne management are also reviewed.

  6. Disabled-2 Mediation of Retinoic Acid Cell Growth Arrest Signal in Breast Cancer

    Science.gov (United States)

    2002-08-01

    C. Cohen, L. E. Mendez , I. R. Horowitz, ylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. A. I Godwin, and X X. Xu, submitted for publication. T...trans., 9-cis-retinoic acid) and P- caro - forming units of adenovirus were added to the cells in medium with low tene were purchased from Sigma

  7. Cell Growth Arrest Mediated by STAT Proteins in Breast Cancer Cells

    Science.gov (United States)

    1998-07-01

    Wei, S., Matsusaka, T., Yoshida, K., Sudo, T., Naruto , M., and Kishimoto, T. (1994) Cellll{\\), 63-71 34. David, M., and Larner, A. C. e. a. (1992...T., Naruto , M., and Kishimoto, T. (1994) Cell 77, 63-71 34. David, M., and Lamer, A. C. (1992) Science 257, 813-815 35. Sadowski, H. B., and Gilman

  8. Brassinosteroids cause cell cycle arrest and apoptosis of human breast cancer cells

    Czech Academy of Sciences Publication Activity Database

    Steigerová, J.; Oklešťková, Jana; Levková, M.; Rárová, Lucie; Kolář, Z.; Strnad, Miroslav

    2010-01-01

    Roč. 188, č. 3 (2010), s. 487-496 ISSN 0009-2797 R&D Projects: GA ČR GA301/08/1649 Institutional research plan: CEZ:AV0Z50380511 Keywords : Brassinosteroids * cause * cell Subject RIV: FD - Oncology ; Hematology Impact factor: 2.832, year: 2010

  9. Arrested of coalescence of emulsion droplets of arbitrary size

    Science.gov (United States)

    Mbanga, Badel L.; Burke, Christopher; Blair, Donald W.; Atherton, Timothy J.

    2013-03-01

    With applications ranging from food products to cosmetics via targeted drug delivery systems, structured anisotropic colloids provide an efficient way to control the structure, properties and functions of emulsions. When two fluid emulsion droplets are brought in contact, a reduction of the interfacial tension drives their coalescence into a larger droplet of the same total volume and reduced exposed area. This coalescence can be partially or totally hindered by the presence of nano or micron-size particles that coat the interface as in Pickering emulsions. We investigate numerically the dependance of the mechanical stability of these arrested shapes on the particles size, their shape anisotropy, their polydispersity, their interaction with the solvent, and the particle-particle interactions. We discuss structural shape changes that can be induced by tuning the particles interactions after arrest occurs, and provide design parameters for the relevant experiments.

  10. Interrater variability of EEG interpretation in comatose cardiac arrest patients

    DEFF Research Database (Denmark)

    Westhall, Erik; Rosén, Ingmar; Rossetti, Andrea O

    2015-01-01

    OBJECTIVE: EEG is widely used to predict outcome in comatose cardiac arrest patients, but its value has been limited by lack of a uniform classification. We used the EEG terminology proposed by the American Clinical Neurophysiology Society (ACNS) to assess interrater variability in a cohort...... who were blinded for patient outcome. Percent agreement and kappa (κ) for the categories in the ACNS EEG terminology and for prespecified malignant EEG-patterns were calculated. RESULTS: There was substantial interrater agreement (κ 0.71) for highly malignant patterns and moderate agreement (κ 0.......42) for malignant patterns. Substantial agreement was found for malignant periodic or rhythmic patterns (κ 0.72) while agreement for identifying an unreactive EEG was fair (κ 0.26). CONCLUSIONS: The ACNS EEG terminology can be used to identify highly malignant EEG-patterns in post cardiac arrest patients...

  11. Metazoan operons accelerate recovery from growth arrested states

    Science.gov (United States)

    Zaslaver, Alon; Baugh, L. Ryan; Sternberg, Paul W.

    2011-01-01

    Summary Existing theories explain why operons are advantageous in prokaryotes, but their occurrence in metazoans is an enigma. Nematode operon genes, typically consisting of growth genes, are significantly up-regulated during recovery from growth-arrested states. This expression pattern is anti-correlated to non-operon genes consistent with a competition for transcriptional resources. We find that transcriptional resources are initially limiting during recovery, and that recovering animals are highly sensitive to any additional decrease in transcriptional resources. Operons become advantageous because by clustering growth genes into operons, fewer promoters compete for the limited transcriptional machinery, effectively increasing the concentration of transcriptional resources, and accelerating recovery. Mathematical modeling reveals how a moderate increase in transcriptional resources can substantially enhance transcription rate and recovery. This design principle occurs in different nematodes and the chordate C. intestinalis. As transition from arrest to rapid growth is shared by many metazoans, operons could have evolved to facilitate these processes. PMID:21663799

  12. Cardiac arrest during a twin birth caesarean delivery.

    Science.gov (United States)

    Pampín-Huerta, F R; Moreira-Gómez, D; Lozano-Requelme, M L; Molina-Nieto, F; Fontán-García-Boente, L; Moreira-Pacheco, M

    2016-04-01

    The case of a 35 year-old pregnant woman with a right ovarian vein thrombosis complicated with a floating thrombus in the inferior vena cava reaching the right atrium, is presented. The patient had a cardiac arrest due to a pulmonary embolism during a twin-birth caesarean delivery. Discussion includes the pathophysiology of this condition and management options in a cardiac arrest secondary to this aetiology, recovered with stable blood pressure, highlighting the role of thrombolytic therapy in the Postoperative Care Unit in this situation. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Breast cancer in men

    Science.gov (United States)

    ... in situ - male; Intraductal carcinoma - male; Inflammatory breast cancer - male; Paget disease of the nipple - male; Breast cancer - male ... The cause of breast cancer in men is not clear. But there are risk factors that make breast cancer more likely in men: Exposure to ...

  14. Breast Cancer Overview

    Science.gov (United States)

    ... are here Home > Types of Cancer > Breast Cancer Breast Cancer This is Cancer.Net’s Guide to Breast Cancer. Use the menu below to choose the Overview/ ... social workers, and patient advocates. Cancer.Net Guide Breast Cancer Introduction Statistics Medical Illustrations Risk Factors and Prevention ...

  15. Breast Cancer -- Male

    Science.gov (United States)

    ... Home > Types of Cancer > Breast Cancer in Men Breast Cancer in Men This is Cancer.Net’s Guide to Breast Cancer in Men. Use the menu below to choose ... social workers, and patient advocates. Cancer.Net Guide Breast Cancer in Men Introduction Statistics Risk Factors and Prevention ...

  16. Relationship between chest compression rates and outcomes from cardiac arrest.

    Science.gov (United States)

    Idris, Ahamed H; Guffey, Danielle; Aufderheide, Tom P; Brown, Siobhan; Morrison, Laurie J; Nichols, Patrick; Powell, Judy; Daya, Mohamud; Bigham, Blair L; Atkins, Dianne L; Berg, Robert; Davis, Dan; Stiell, Ian; Sopko, George; Nichol, Graham

    2012-06-19

    Guidelines for cardiopulmonary resuscitation recommend a chest compression rate of at least 100 compressions per minute. Animal and human studies have reported that blood flow is greatest with chest compression rates near 120/min, but few have reported rates used during out-of-hospital (OOH) cardiopulmonary resuscitation or the relationship between rate and outcome. The purpose of this study was to describe chest compression rates used by emergency medical services providers to resuscitate patients with OOH cardiac arrest and to determine the relationship between chest compression rate and outcome. Included were patients aged ≥ 20 years with OOH cardiac arrest treated by emergency medical services providers participating in the Resuscitation Outcomes Consortium. Data were abstracted from monitor-defibrillator recordings during cardiopulmonary resuscitation. Multiple logistic regression analysis assessed the association between chest compression rate and outcome. From December 2005 to May 2007, 3098 patients with OOH cardiac arrest were included in this study. Mean age was 67 ± 16 years, and 8.6% survived to hospital discharge. Mean compression rate was 112 ± 19/min. A curvilinear association between chest compression rate and return of spontaneous circulation was found in cubic spline models after multivariable adjustment (P=0.012). Return of spontaneous circulation rates peaked at a compression rate of ≈ 125/min and then declined. Chest compression rate was not significantly associated with survival to hospital discharge in multivariable categorical or cubic spline models. Chest compression rate was associated with return of spontaneous circulation but not with survival to hospital discharge in OOH cardiac arrest.

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

    Directory of Open Access Journals (Sweden)

    Junqing Yuan

    2013-01-01

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

  18. Circulatory Arrest: A Surgical Option for Adult Window Ductus Closure

    Directory of Open Access Journals (Sweden)

    Vithalkumar Malleshi Betigeri

    2012-03-01

    Full Text Available The window ductus , an atypical type of patent ductus arteriosus(PDA is a characteristically large in size(>2cm with no recognizable length, characteristic continuation of main pulmonary artery with aortic arch and absence of internal ductal tissue. Surgical safety and effectiveness of its closure can be increased by using cardiopulmonary bypass (CPB and hypothermic total circulatory arrest (HTCA via median sternotomy.

  19. The Neighborhood Context of Racial and Ethnic Disparities in Arrest

    OpenAIRE

    KIRK, DAVID S.

    2008-01-01

    This study assesses the role of social context in explaining racial and ethnic disparities in arrest, with a focus on how distinct neighborhood contexts in which different racial and ethnic groups reside explain variations in criminal outcomes. To do so, I utilize a multilevel, longitudinal research design, combining individual-level data with contextual data from the Project on Human Development in Chicago Neighborhoods (PHDCN). Findings reveal that black youths face multiple layers of disad...

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

    International Nuclear Information System (INIS)

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

    1988-01-01

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

  1. Initiation and arrest - two approaches to pressure vessel safety

    International Nuclear Information System (INIS)

    Brumovsky, M.; Filip, R.; Stepanek, S.

    1976-01-01

    The safety analysis is described of the reactor pressure vessel related to brittle fracture based on the fracture mechanics theory using two different approximations, i.e., the Crack Arrest Temperature (CAT) or Nil Ductility Temperature (NDT), and fracture toughness. The variation of CAT with stress was determined for different steel specimens of 120 to 200 mm in thickness. A diagram is shown of CAT variation with stress allowing the determination of crack arrest temperature for all types of commonly used steels independently of the NDT initial value. The diagram also shows that the difference between fracture transition elastic (FTE) and NDT depends on the type of material and determines the value of the ΔTsub(sigma) factor typical of the safety coefficient. The so-called fracture toughness reference value Ksub(IR) is recommended for the computation of pressure vessel criticality. Also shown is a defect analysis diagram which may be used for the calculation of pressure vessel safety prior to and during operation and which may also be used in making the decision on what crack sizes are critical, what cracks may be arrested and what cracks are likely to expand. The diagram is also important for the fact that it is material-independent and may be employed for the estimates of pre-operational and operational inspections and for pressure vessel life prediction. It is generally applicable to materials of greater thickness in the region where the validity of linear elastic fracture mechanics is guaranteed. (J.P.)

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

    Science.gov (United States)

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

    2016-05-15

    Advanced cardiovascular life support guidelines exist, yet there are variations in clinical practice. Our study aims to describe the utilization of medications during resuscitation from in-hospital cardiopulmonary arrest. A retrospective review of patients who suffered a cardiopulmonary arrest from May 2008 to June 2014 was performed. Clinical and resuscitation data, including timing and dose of medications used, were extracted from the electronic medical record and comparisons made. A total of 94 patients were included in the study. Patients were divided into different groups based on the medication combination used during resuscitation: (1) epinephrine; (2) epinephrine and bicarbonate; (3) epinephrine, bicarbonate, and calcium; (4) epinephrine, bicarbonate, and epinephrine drip; and (5) epinephrine, bicarbonate, calcium, and epinephrine drip. No difference in baseline demographics or clinical data was present, apart from history of dementia and the use of calcium channel blockers. The number of medications given was correlated with resuscitation duration (Spearman's rank correlation = 0.50, p resuscitation durations compared to that of the other groups (p resuscitation efforts for in-hospital cardiopulmonary arrests. Increased duration and mortality rates were found in those resuscitations compared with epinephrine alone, likely due to the longer resuscitation duration in the former groups. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Genistein induces G2/M cell cycle arrest and apoptosis via ATM/p53-dependent pathway in human colon cancer cells.

    Science.gov (United States)

    Zhang, Zhiyu; Wang, Chong-Zhi; Du, Guang-Jian; Qi, Lian-Wen; Calway, Tyler; He, Tong-Chuan; Du, Wei; Yuan, Chun-Su

    2013-07-01

    Soybean isoflavones have been used as a potential preventive agent in anticancer research for many years. Genistein is one of the most active flavonoids in soybeans. Accumulating evidence suggests that genistein alters a variety of biological processes in estrogen-related malignancies, such as breast and prostate cancers. However, the molecular mechanism of genistein in the prevention of human colon cancer remains unclear. Here we attempted to elucidate the anticarcinogenic mechanism of genistein in human colon cancer cells. First we evaluated the growth inhibitory effect of genistein and two other isoflavones, daidzein and biochanin A, on HCT-116 and SW-480 human colon cancer cells. In addition, flow cyto-metry was performed to observe the morphological changes in HCT-116/SW-480 cells undergoing apoptosis or cell cycle arrest, which had been visualized using Annexin V-FITC and/or propidium iodide staining. Real-time PCR and western blot analyses were also employed to study the changes in expression of several important genes associated with cell cycle regulation. Our data showed that genistein, daidzein and biochanin A exhibited growth inhibitory effects on HCT-116/SW-480 colon cancer cells and promoted apoptosis. Genistein showed a significantly greater effect than the other two compounds, in a time- and dose-dependent manner. In addition, genistein caused cell cycle arrest in the G2/M phase, which was accompanied by activation of ATM/p53, p21waf1/cip1 and GADD45α as well as downregulation of cdc2 and cdc25A demonstrated by q-PCR and immunoblotting assay. Interestingly, genistein induced G2/M cell cycle arrest in a p53-dependent manner. These findings exemplify that isoflavones, especially genistein, could promote colon cancer cell growth inhibition and facilitate apoptosis and cell cycle arrest in the G2/M phase. The ATM/p53-p21 cross-regulatory network may play a crucial role in mediating the anticarcinogenic activities of genistein in colon cancer.

  4. Breast Reconstruction with Flap Surgery

    Science.gov (United States)

    ... augmented with a breast implant to achieve the desired breast size. Surgical methods Autologous tissue breast reconstruction ... as long as a year or two before feeling completely healed and back to normal. Future breast ...

  5. Stages of Male Breast Cancer

    Science.gov (United States)

    ... Breast & Gynecologic Cancers Breast Cancer Screening Research Male Breast Cancer Treatment (PDQ®)–Patient Version General Information about Male Breast Cancer Go to Health Professional Version Key Points Male ...

  6. The stepwise evolution of the exome during acquisition of docetaxel resistance in breast cancer cells

    DEFF Research Database (Denmark)

    Hansen, Stine Ninel; Ehlers, Natasja Spring; Zhu, Shida

    2016-01-01

    Background: Resistance to taxane-based therapy in breast cancer patients is a major clinical problem that may be addressed through insight of the genomic alterations leading to taxane resistance in breast cancer cells. In the current study we used whole exome sequencing to discover somatic genomic...... alterations, evolving across evolutionary stages during the acquisition of docetaxel resistance in breast cancer cell lines. Results: Two human breast cancer in vitro models (MCF-7 and MDA-MB-231) of the step-wise acquisition of docetaxel resistance were developed by exposing cells to 18 gradually increasing...... resistance relevant genomic variation appeared to arise midway towards fully resistant cells corresponding to passage 31 (5 nM docetaxel) for MDA-MB-231 and passage 16 (1.2 nM docetaxel) for MCF-7, and where the cells also exhibited a period of reduced growth rate or arrest, respectively. MCF-7 cell acquired...

  7. A novel imidazopyridine analogue as a phosphatidylinositol 3-kinase inhibitor against human breast cancer.

    Science.gov (United States)

    Lee, Hyunseung; Li, Guang-Yong; Jeong, Yujeong; Jung, Kyung Hee; Lee, Ju-Hee; Ham, Kyungrok; Hong, Sungwoo; Hong, Soon-Sun

    2012-05-01

    Potentiation of anti-breast cancer activity of an imidazopyridine-based PI3Kα inhibitor, HS-104, was investigated in human breast cancer cells. HS-104 shows strong inhibitory activity against recombinant PI3Kα isoform and the PI3K signaling pathway, resulting in anti-proliferative activity in breast cancer cells. It also induced cell cycle arrest at the G(2)/M phase as well as apoptosis. Furthermore, oral administration of HS-104 significantly inhibited the growth of tumor in SkBr3 mouse xenograft models. Therefore, HS-104 could be considered as a potential candidate for the treatment of human breast cancer. Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

  8. C.A.U.S.E.: Cardiac arrest ultra-sound exam--a better approach to managing patients in primary non-arrhythmogenic cardiac arrest.

    Science.gov (United States)

    Hernandez, Caleb; Shuler, Klaus; Hannan, Hashibul; Sonyika, Chionesu; Likourezos, Antonios; Marshall, John

    2008-02-01

    Cardiac arrest is a condition frequently encountered by physicians in the hospital setting including the Emergency Department, Intensive Care Unit and medical/surgical wards. This paper reviews the current literature involving the use of ultrasound in resuscitation and proposes an algorithmic approach for the use of ultrasound during cardiac arrest. At present there is the need for a means of differentiating between various causes of cardiac arrest, which are not a direct result of a primary ventricular arrhythmia. Identifying the cause of pulseless electrical activity or asystole is important as the underlying cause is what guides management in such cases. This approach, incorporating ultrasound to manage cardiac arrest aids in the diagnosis of the most common and easily reversible causes of cardiac arrest not caused by primary ventricular arrhythmia, namely; severe hypovolemia, tension pneumothorax, cardiac tamponade, and massive pulmonary embolus. These four conditions are addressed in this paper using four accepted emergency ultrasound applications to be performed during resuscitation of a cardiac arrest patient with the aim of determining the underlying cause of a cardiac arrest. Identifying the underlying cause of cardiac arrest represents the one of the greatest challenges of managing patients with asystole or PEA and accurate determination has the potential to improve management by guiding therapeutic decisions. We include several clinical images demonstrating examples of cardiac tamponade, massive pulmonary embolus, and severe hypovolemia secondary to abdominal aortic aneurysm. In conclusion, this protocol has the potential to reduce the time required to determine the etiology of a cardiac arrest and thus decrease the time between arrest and appropriate therapy.

  9. Breast development and anatomy.

    Science.gov (United States)

    Pandya, Sonali; Moore, Richard G

    2011-03-01

    In this article, the development of the female breast, as well as the functional anatomy, blood supply, innervation and lymphatic drainage are described. A thorough understanding of the breast anatomy is an important adjunct to a meticulous clinical breast examination. Breast examination is a complex skill involving key maneuvers, including careful inspection and palpation. Clinical breast examination can provide an opportunity for the clinician to educate patients about their breast and about breast cancer, its symptoms, risk factors, early detection, and normal breast composition, and specifically variability. Clinical breast examination can help to detect some cancers not found by mammography, and clinicians should not override their examination findings if imaging is not supportive of the physical findings.

  10. Effects of biosurfactants on the viability and proliferation of human breast cancer cells.

    Science.gov (United States)

    Duarte, Cristina; Gudiña, Eduardo J; Lima, Cristovao F; Rodrigues, Ligia R

    2014-01-01

    Biosurfactants are molecules with surface activity produced by microorganisms that can be used in many biomedical applications. The anti-tumour potential of these molecules is being studied, although results are still scarce and few data are available regarding the mechanisms underlying such activity. In this work, the anti-tumour activity of a surfactin produced by Bacillus subtilis 573 and a glycoprotein (BioEG) produced by Lactobacillus paracasei subsp. paracasei A20 was evaluated. Both biosurfactants were tested against two breast cancer cell lines, T47D and MDA-MB-231, and a non-tumour fibroblast cell line (MC-3 T3-E1), specifically regarding cell viability and proliferation. Surfactin was found to decrease viability of both breast cancer cell lines studied. A 24 h exposure to 0.05 g l(-1) surfactin led to inhibition of cell proliferation as shown by cell cycle arrest at G1 phase. Similarly, exposure of cells to 0.15 g l(-1) BioEG for 48 h decreased cancer cells' viability, without affecting normal fibroblasts. Moreover, BioEG induced the cell cycle arrest at G1 for both breast cancer cell lines. The biosurfactant BioEG was shown to be more active than surfactin against the studied breast cancer cells. The results gathered in this work are very promising regarding the biosurfactants potential for breast cancer treatment and encourage further work with the BioEG glycoprotein.

  11. New castanospermine glycoside analogues inhibit breast cancer cell proliferation and induce apoptosis without affecting normal cells.

    Directory of Open Access Journals (Sweden)

    Ghada Allan

    Full Text Available sp²-Iminosugar-type castanospermine analogues have been shown to exhibit anti-tumor activity. However, their effects on cell proliferation and apoptosis and the molecular mechanism at play are not fully understood. Here, we investigated the effect of two representatives, namely the pseudo-S- and C-octyl glycoside 2-oxa-3-oxocastanospermine derivatives SO-OCS and CO-OCS, on MCF-7 and MDA-MB-231 breast cancer and MCF-10A mammary normal cell lines. We found that SO-OCS and CO-OCS inhibited breast cancer cell viability in a concentration- and time-dependent manner. This effect is specific to breast cancer cells as both molecules had no impact on normal MCF-10A cell proliferation. Both drugs induced a cell cycle arrest. CO-OCS arrested cell cycle at G1 and G2/M in MCF-7 and MDA-MB-231 cells respectively. In MCF-7 cells, the G1 arrest is associated with a reduction of CDK4 (cyclin-dependent kinase 4, cyclin D1 and cyclin E expression, pRb phosphorylation, and an overexpression of p21(Waf1/Cip1. In MDA-MB-231 cells, CO-OCS reduced CDK1 but not cyclin B1 expression. SO-OCS accumulated cells in G2/M in both cell lines and this blockade was accompanied by a decrease of CDK1, but not cyclin B1 expression. Furthermore, both drugs induced apoptosis as demonstrated by the increased percentage of annexin V positive cells and Bax/Bcl-2 ratio. Interestingly, in normal MCF-10A cells the two drugs failed to modify cell proliferation, cell cycle progression, cyclins, or CDKs expression. These results demonstrate that the effect of CO-OCS and SO-OCS is triggered by both cell cycle arrest and apoptosis, suggesting that these castanospermine analogues may constitute potential anti-cancer agents against breast cancer.

  12. Involvement of the Retinoid X Receptor Ligand in the Anti-Inflammatory Effect Induced by Peroxisome Proliferator-Activated Receptor Agonist In Vivo

    Directory of Open Access Journals (Sweden)

    Atsuki Yamamoto

    2011-01-01

    Full Text Available Peroxisome proliferator-activated receptor γ (PPARγ forms a heterodimeric DNA-binding complex with retinoid X receptors (RXRs. It has been reported that the effect of the PPAR agonist is reduced in hepatocyte RXR-deficient mice. Therefore, it is suggested that the endogenous RXR ligand is involved in the PPARγ agonist-induced anti-inflammatory effect. However, the participation of the RXR ligand in the PPARγ-induced anti-inflammatory effect is unknown. Here, we investigated the influence of RXR antagonist on the anti-inflammatory effect of PPARγ agonist pioglitazone in carrageenan test. In addition, we also examined the influence of PPAR antagonist on the anti-inflammatory effect induced by RXR agonist NEt-3IP. The RXR antagonist suppressed the antiedema effect of PPARγ agonist. In addition, the anti-inflammatory effect of RXR agonist was suppressed by PPARγ antagonist. PPARγ agonist-induced anti-inflammatory effects were reversed by the RXR antagonist. Thus, we showed that the endogenous RXR ligand might contribute to the PPARγ agonist-induced anti-inflammatory effect.

  13. Dense Breasts: Answers to Commonly Asked Questions

    Science.gov (United States)

    ... Cancer Prevention Genetics of Breast & Gynecologic Cancers Breast Cancer Screening Research Dense Breasts: Answers to Commonly Asked Questions What are dense breasts? Breasts contain glandular, connective, and fat tissue. Breast density is a term that describes the ...

  14. Dendrobium candidum inhibits MCF-7 cells proliferation by inducing cell cycle arrest at G2/M phase and regulating key biomarkers

    Directory of Open Access Journals (Sweden)

    Sun J

    2015-12-01

    <0.05. The general apoptosis biomarker, Bcl-2, was significantly decreased and the Bax was significantly increased compared to the control group (P<0.05. In contrast to that in MCF-7, D. candidum does not affect cell proliferation at any concentration and any time points in normal breast epithelial cells, MCF10A cells. Conclusion: D. candidum could decrease the cell viability of MCF-7 cells by inducing cell cycle arrest at the G2/M phase and regulating the key biomarkers in breast cancer cells. Keywords: breast cancer, D. candidum, proliferation, biomarker, inhibition

  15. Fulvestrant radiosensitizes human estrogen receptor-positive breast cancer cells

    International Nuclear Information System (INIS)

    Wang, Jing; Yang, Qifeng; Haffty, Bruce G.; Li, Xiaoyan; Moran, Meena S.

    2013-01-01

    Highlights: ► Fulvestrant radiosensitizes MCF-7 cells. ► Fulvestrant increases G1 arrest and decreases S phase in MCF-7 cells. ► Fulvestrant down-regulates DNA-PKcs and RAD51 in MCF-7 cells. -- Abstract: The optimal sequencing for hormonal therapy and radiation are yet to be determined. We utilized fulvestrant, which is showing promise as an alternative to other agents in the clinical setting of hormonal therapy, to assess the cellular effects of concomitant anti-estrogen therapy (fulvestrant) with radiation (F + RT). This study was conducted to assess the effects of fulvestrant alone vs. F + RT on hormone-receptor positive breast cancer to determine if any positive or negative combined effects exist. The effects of F + RT on human breast cancer cells were assessed using MCF-7 clonogenic and tetrazolium salt colorimetric (MTT) assays. The assays were irradiated with a dose of 0, 2, 4, 6 Gy ± fulvestrant. The effects of F + RT vs. single adjuvant treatment alone on cell-cycle distribution were assessed using flow cytometry; relative expression of repair proteins (Ku70, Ku80, DNA-PKcs, Rad51) was assessed using Western Blot analysis. Cell growth for radiation alone vs. F + RT was 0.885 ± 0.013 vs. 0.622 ± 0.029 @2 Gy, 0.599 ± 0.045 vs. 0.475 ± 0.054 @4 Gy, and 0.472 ± 0.021 vs. 0.380 ± 0.018 @6 Gy RT (p = 0.003). While irradiation alone induced G2/M cell cycle arrest, the combination of F + RT induced cell redistribution in the G1 phase and produced a significant decrease in the proportion of cells in G2 phase arrest and in the S phase in breast cancer cells (p < 0.01). Furthermore, levels of repair proteins DNA-PKcs and Rad51 were significantly decreased in the cells treated with F + RT compared with irradiation alone. F + RT leads to a decrease in the surviving fraction, increased cell cycle arrest, down regulating of nonhomologous repair protein DNA-PKcs and homologous recombination repair protein RAD51. Thus, our findings suggest that F + RT

  16. Breast metastases from rectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    LI Jia; FANG Yu; LI Ang; LI Fei

    2011-01-01

    Metastases to the breast from extramammary neoplasms are very rare, constituting 2.7% of all malignant breast tumours. The most common primary tumor metastatic to the breast is primary breast cancer. Rectal cancer metastasizing to the breast is extremely rare. We report a case of aggressive rectal carcinoma with metastasis to the breast.

  17. Accelerated partial breast irradiation

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    @@ Whole breast radiotherapy afier tumor lumpectomy is based on the premise that that the breast cancer recurrence rate is reduced through the elimination of residual cancer foci in the remaining tissue immediately adjacent to the lumpectomy site and occult multicentric areas of in situ or infiltrating cancer in remote areas of the breast. The relevance of remote foci to ipsilateral breast failure rates after breast conserving treatment is debatable, because 65%~100% of recurrences develop in the same quadrant as the initial tumor. This has led several investigators to question whether radiotherapy must be administered to the entire breast.

  18. Biomechanics of fall arrest using the upper extremity: age differences.

    Science.gov (United States)

    Kim, Kyu-Jung; Ashton-Miller, James A

    2003-05-01

    This study tried to isolate critical biomechanical factors in fall arrests using the upper extremity during simulated forward falls. This study also attempted to find the differences in those factors between young and old age groups. The role of the upper extremity is not well defined despite its primary usage as a local shock absorber during fall impact. Comparative study in which two age groups underwent motion analysis.Methods. Ten healthy older males (mean age, 66.4 years) and 10 young males (mean age, 24.1 years) volunteered to perform self-initiated and cable-released falls at selected falling distances, while the joint motion and impact forces at the hand were recorded. Significant age differences were demonstrated in joint kinematics and impact force parameters at close distances. Excessive reflexive responses of the upper extremity in cable-released falls for the older adults resulted in 10-15 times higher peak impact forces and 2-3 times shorter body braking time than in self-initiated falls. Pre-impact activities of the upper extremity predispose the post-impact response during fall arrests. Suppressing excessive pre-impact reflexive activation of the arms could efficiently decrease the risk of fall-related injuries, which calls for securing sufficient arm movement time. Any fall prevention strategy that can increase arm movement time would be effective against injuries of the upper extremity during falling in the older adults. The findings will help to understand underlying mechanisms of fall arrest using the upper extremity for prevention of fall-related fractures.

  19. Calmodulin Mutations Associated with Recurrent Cardiac Arrest in Infants

    Science.gov (United States)

    Crotti, Lia; Johnson, Christopher N.; Graf, Elisabeth; De Ferrari, Gaetano M.; Cuneo, Bettina F.; Ovadia, Marc; Papagiannis, John; Feldkamp, Michael D.; Rathi, Subodh G.; Kunic, Jennifer D.; Pedrazzini, Matteo; Wieland, Thomas; Lichtner, Peter; Beckmann, Britt-Maria; Clark, Travis; Shaffer, Christian; Benson, D. Woodrow; Kääb, Stefan; Meitinger, Thomas; Strom, Tim M.; Chazin, Walter J.; Schwartz, Peter J.; George, Alfred L.

    2013-01-01

    Background Life-threatening disorders of heart rhythm may arise during infancy and can result in the sudden and tragic death of a child. We performed exome sequencing on two unrelated infants presenting with recurrent cardiac arrest to discover a genetic cause. Methods and Results We ascertained two unrelated infants (probands) with recurrent cardiac arrest and dramatically prolonged QTc interval who were both born to healthy parents. The two parent-child trios were investigated using exome sequencing to search for de novo genetic variants. We then performed follow-up candidate gene screening on an independent cohort of 82 subjects with congenital long-QT syndrome without an identified genetic cause. Biochemical studies were performed to determine the functional consequences of mutations discovered in two genes encoding calmodulin. We discovered three heterozygous de novo mutations in either CALM1 or CALM2, two of the three human genes encoding calmodulin, in the two probands and in two additional subjects with recurrent cardiac arrest. All mutation carriers were infants who exhibited life-threatening ventricular arrhythmias combined variably with epilepsy and delayed neurodevelopment. Mutations altered residues in or adjacent to critical calcium binding loops in the calmodulin carboxyl-terminal domain. Recombinant mutant calmodulins exhibited several fold reductions in calcium binding affinity. Conclusions Human calmodulin mutations disrupt calcium ion binding to the protein and are associated with a life-threatening condition in early infancy. Defects in calmodulin function will disrupt important calcium signaling events in heart affecting membrane ion channels, a plausible molecular mechanism for potentially deadly disturbances in heart rhythm during infancy. PMID:23388215

  20. Survey on current practices for neurological prognostication after cardiac arrest.

    Science.gov (United States)

    Friberg, Hans; Cronberg, Tobias; Dünser, Martin W; Duranteau, Jacques; Horn, Janneke; Oddo, Mauro

    2015-05-01

    To investigate current practices and timing of neurological prognostication in comatose cardiac arrest patients. An anonymous questionnaire was distributed to the 8000 members of the European Society of Intensive Care Medicine during September and October 2012. The survey had 27 questions divided into three categories: background data, clinical data, decision-making and consequences. A total of 1025 respondents (13%) answered the survey with complete forms in more than 90%. Twenty per cent of respondents practiced outside of Europe. Overall, 22% answered that they had national recommendations, with the highest percentage in the Netherlands (>80%). Eighty-nine per cent used induced hypothermia (32-34 °C) for comatose cardiac arrest patients, while 11% did not. Twenty per cent had separate prognostication protocols for hypothermia patients. Seventy-nine per cent recognized that neurological examination alone is not enough to predict outcome and a similar number (76%) used additional methods. Intermittent electroencephalography (EEG), brain computed tomography (CT) scan and evoked potentials (EP) were considered most useful. Poor prognosis was defined as cerebral performance category (CPC) 3-5 (58%) or CPC 4-5 (39%) or other (3%). When prognosis was considered poor, 73% would actively withdraw intensive care while 20% would not and 7% were uncertain. National recommendations for neurological prognostication after cardiac arrest are uncommon and only one physician out of five uses a separate protocol for hypothermia treated patients. A neurological examination alone was considered insufficient to predict outcome in comatose patients and most respondents advocated a multimodal approach: EEG, brain CT and EP were considered most useful. Uncertainty regarding neurological prognostication and decisions on level of care was substantial. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Multiple contacts with diversion at the point of arrest.

    Science.gov (United States)

    Riordan, Sharon; Wix, Stuart; Haque, M Sayeed; Humphreys, Martin

    2003-04-01

    A diversion at the point of arrest (DAPA) scheme was set up in five police stations in South Birmingham in 1992. In a study of all referrals made over a four-year period a sub group of multiple contact individuals was identified. During that time four hundred and ninety-two contacts were recorded in total, of which 130 were made by 58 individuals. The latter group was generally no different from the single contact group but did have a tendency to be younger. This research highlights the need for a re-evaluation of service provision and associated education of police officers and relevant mental health care professionals.

  2. ADULTHOOD ANIMAL ABUSE AMONG MEN ARRESTED FOR DOMESTIC VIOLENCE

    Science.gov (United States)

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

    2014-01-01

    Learning more about intimate partner violence (IPV) perpetrators could aid the development of more effective treatments. The prevalence of adulthood animal abuse (AAA) perpetration and its association with IPV perpetration, antisociality, and alcohol use in 307 men arrested for domestic violence was examined. 41% (n = 125) of the men committed at least one act of animal abuse since the age of 18, in contrast to the 3.0% prevalence rate reported by men in the general population. Controlling for antisociality and alcohol use, AAA showed a trend towards a significant association with physical and severe psychological IPV perpetration. PMID:25324474

  3. Elastodynamic fracture analyses of large crack-arrest experiments

    International Nuclear Information System (INIS)

    Bass, B.R.; Pugh, C.E.; Walker, J.K.

    1985-01-01

    Results obtained to date show that the essence of the run-arrest events, including dynamic behavior, is being modeled. Refined meshes and optimum solution algorithms are important parameters in elastodynamic analysis programs to give sufficient resolution to the geometric and time-dependent aspects of fracture analyses. Further refinements in quantitative representation of material parameters and the inclusion of rate dependence through viscoplastic modeling is expected to give an even more accurate basis for assessing the fracture behavior of reactor pressure vessels under PTS and other off-normal loading conditions

  4. A CASE OF GRANISETRON ASSOCIATED INTRAOPERATIVE CARDIAC ARREST.

    Science.gov (United States)

    Al Harbi, Mohammed; Al Rifai, Derar; Al Habeeb, Hassan; Wambi, Freddie; Geldhof, Georges; Dimitriou, Vassilios

    2016-02-01

    We report a case of intraoperative severe bradycardia that resulted in asystole and cardiac arrest shortly after (granisetron 1mg for postoperative nausea and vomiting prophylaxis, that occurred in a female patient who underwent an elective total thyroidectomy. After two cycles of cardiopulmonary resuscitation and defibrillation, spontaneous circulation and sinus rhythm returned successfully. Postoperatively, the patient was diagnosed with a drug-induced long QT syndrome. At the time of the event, granisetron was the only medication administered. Furthermore, there was no reason to suspect electrolyte abnormalities. We explore the association of the onset of severe sinus bradycardia with the intravenous administration of granisetron.

  5. Advanced life support for cardiac arrest beyond the algorithm

    DEFF Research Database (Denmark)

    Rudolph, Søren Steemann; Isbye, Dan Lou; Pfeiffer, Peter

    2018-01-01

    In an advanced emergency medical service all parts of the advanced life support (ALS) algorithm can be provided. This evidence-based algorithm outlines resuscitative efforts for the first 10-15 minutes after cardiac arrest, whereafter the algorithm repeats itself. Restoration of spontaneous...... circulation fails in most cases, but in some circumstances the patient may benefit from additional interventional approaches, in which case transport to hospital with ongoing cardiopulmonary resuscitation is indicated. This paper has summarized treatments outside the ALS algorithm, which may be beneficial...

  6. [Cerebral oximetry in pulmonary thromboendarterectomy with circulatory arrest].

    Science.gov (United States)

    Catalán Escudero, P; González Román, A; Serra Ruiz, C N; Barbero Mielgo, M; García Fernández, J

    2014-02-01

    Pulmonary thromboendarterectomy is an uncommon procedure and should be performed with circulatory arrest. One of the major concerns is the postoperative central neurological injuries. Perioperative brain oxygen monitoring is advisable in this surgical procedure for the early detection of brain hypoperfusion episodes and their intensity as well as any other postoperative episodes that can deteriorate the neurological outcome. Copyright © 2012 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  7. Dynamical arrest in dense short-ranged attractive colloids

    International Nuclear Information System (INIS)

    Foffi, G; Sciortino, F; Zaccarelli, E; Tartaglia, P

    2004-01-01

    We study thermodynamic and dynamic properties of model colloidal systems interacting with a hard core repulsion and a short-range attraction, and provide an overall picture of their phase diagrams which shows a very rich phenomenology. We focus on the slow dynamic properties of this model, investigating in detail the glass transition lines (both repulsive and attractive), the glass-glass transitions and the location of the higher order singularities. We discuss the relative location of the glass lines and of the metastable liquid-gas binodal, an issue relevant for the understanding of low density arrested states of matter

  8. Adulthood animal abuse among men arrested for domestic violence.

    Science.gov (United States)

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

    2014-09-01

    Learning more about intimate partner violence (IPV), perpetrators could aid the development of more effective treatments. The prevalence of adulthood animal abuse (AAA) perpetration and its association with IPV perpetration, antisociality, and alcohol use in 307 men arrested for domestic violence were examined. Forty-one percent (n = 125) of the men committed at least one act of animal abuse since the age of 18, in contrast to the 1.5% prevalence rate reported by men in the general population. Controlling for antisociality and alcohol use, AAA showed a trend toward a significant association with physical and severe psychological IPV perpetration. © The Author(s) 2014.

  9. Breast cancer screening in Korean woman with dense breast tissue

    International Nuclear Information System (INIS)

    Shin, Hee Jung; Ko, Eun Sook; Yi, Ann

    2015-01-01

    Asian women, including Korean, have a relatively higher incidence of dense breast tissue, compared with western women. Dense breast tissue has a lower sensitivity for the detection of breast cancer and a higher relative risk for breast cancer, compared with fatty breast tissue. Thus, there were limitations in the mammographic screening for women with dense breast tissue, and many studies for the supplemental screening methods. This review included appropriate screening methods for Korean women with dense breasts. We also reviewed the application and limitation of supplemental screening methods, including breast ultrasound, digital breast tomosynthesis, and breast magnetic resonance imaging; and furthermore investigated the guidelines, as well as the study results

  10. Breast cancer screening in Korean woman with dense breast tissue

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Hee Jung [Dept. of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Ko, Eun Sook [Dept. of Radiology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul (Korea, Republic of); Yi, Ann [Dept. of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul (Korea, Republic of)

    2015-11-15

    Asian women, including Korean, have a relatively higher incidence of dense breast tissue, compared with western women. Dense breast tissue has a lower sensitivity for the detection of breast cancer and a higher relative risk for breast cancer, compared with fatty breast tissue. Thus, there were limitations in the mammographic screening for women with dense breast tissue, and many studies for the supplemental screening methods. This review included appropriate screening methods for Korean women with dense breasts. We also reviewed the application and limitation of supplemental screening methods, including breast ultrasound, digital breast tomosynthesis, and breast magnetic resonance imaging; and furthermore investigated the guidelines, as well as the study results.

  11. Characteristics and possibilities of software tool for metal-oxide surge arresters selection

    Directory of Open Access Journals (Sweden)

    Đorđević Dragan

    2012-01-01

    Full Text Available This paper presents a procedure for the selection of metal-oxide surge arresters based on the instructions given in the Siemens and ABB catalogues, respecting their differences and the characteristics and possibilities of the software tool. The software tool was developed during the preparation of a Master's thesis titled, 'Automation of Metal-Oxide Surge Arresters Selection'. An example is presented of the selection of metal-oxide surge arresters using the developed software tool.

  12. Analysis of the G1 arrest position of senescent WI38 cells by quinacrine dihydrochloride nuclear fluorescence: evidence for a late G1 arrest

    International Nuclear Information System (INIS)

    Gorman, S.D.; Cristofalo, V.J.

    1986-01-01

    Senescence of the human diploid fibroblast-like cell line, W138, is characterized by a loss of proliferative activity and an arrest of cells with a 2C DNA content (G1 or G0). To examine the specific region within G1 in which senescent cells arrest, senescent cells were stained with quinacrine dihydrochloride (QDH) and their nuclear fluorescence was compared with that of young cultures arrested in early and late G1 by serum deprivation and hydroxyurea exposure, respectively. Release of these G1-arrested young cultures from their blocking conditions and timing the kinetics of their entry into the S phase by autoradiographic detection of [ 3 H]thymidine incorporation revealed that serum-deprived cells entered the S phase within 15-18h, whereas hydroxyurea-exposed cells entered the S phase within 1.5h, thus confirming their relative G1-arrest positions. QDH-stained, serum-deprived and hydroxyurea-exposed young cells exhibited relative nuclear fluorescence intensities of 51.7 and 23.9, respectively. Senescent cells exhibited a relative nuclear fluorescence intensity of 17.4, closely resembling the fluorescence of young cultures arrested in late G1 by hydroxyurea exposure. These data support the concept that senescent cells are arrested from further progression in the cell cycle in late G1

  13. G2 phase arrest of cell cycle induced by ionizing radiation

    International Nuclear Information System (INIS)

    Liu Guangwei; Gong Shouliang

    2002-01-01

    The exposure of mammalian cells to X rays results in the prolongation of the cell cycle, including the delay or the arrest in G 1 , S and G 2 phase. The major function of G 1 arrest may be to eliminate the cells containing DNA damage and only occurs in the cells with wild type p53 function whereas G 2 arrest following ionizing radiation has been shown to be important in protecting the cells from death and occurs in all cells regardless of p53 status. So the study on G 2 phase arrest of the cell cycle induced by ionizing radiation has currently become a focus at radiobiological fields

  14. An Exploratory Study of Functional Status in Post Cardiac Arrest Survivors Discharged To Home

    National Research Council Canada - National Science Library

    Whitcomb, John J

    2005-01-01

    .... Aims of the project were to describe perceived functional capacity, physical functional performance, mental health, symptom distress, and demographic factors in survivors of cardiopulmonary arrest...

  15. Breast Abscess Mimicking Breast Carcinoma in Male.

    Science.gov (United States)

    Gochhait, Debasis; Dehuri, Priyadarshini; Umamahesweran, Sandyya; Kamat, Rohan

    2018-01-01

    Male breast can show almost all pathological entities described in female breast. Inflammatory conditions of the breast in male are not common; however, occasionally, it can be encountered in the form of an abscess. Clinically, gynecomastia always presents as a symmetric unilateral or bilateral lump in the retroareolar region, and any irregular asymmetric lump raises a possibility of malignancy. Radiology should be used as a part of the triple assessment protocol for breast lump along with fine-needle aspiration cytology for definite diagnosis and proper management.

  16. Breast Abscess Mimicking Breast Carcinoma in Male

    Directory of Open Access Journals (Sweden)

    Debasis Gochhait

    2018-01-01

    Full Text Available Male breast can show almost all pathological entities described in female breast. Inflammatory conditions of the breast in male are not common; however, occasionally, it can be encountered in the form of an abscess. Clinically, gynecomastia always presents as a symmetric unilateral or bilateral lump in the retroareolar region, and any irregular asymmetric lump raises a possibility of malignancy. Radiology should be used as a part of the triple assessment protocol for breast lump along with fine-needle aspiration cytology for definite diagnosis and proper management.

  17. BREAST RECONSTRUCTIONS AFTER BREAST CANCER TREATING

    OpenAIRE

    Erik Vrabič

    2018-01-01

    Background. Breasts are an important symbol of physical beauty, feminity, mothering and sexual desire through the entire history of mankind. Lost of the whole or part of the breast is functional and aesthetic disturbance for woman. It is understandable, that the woman, who is concerned over breast loss, is as appropriate as another person´s concern over the loss of a limb or other body part. Before the 1960, breast reconstruction was considered as a dangerous procedure and it was almost prohi...

  18. ED breast cases and other breast emergencies.

    Science.gov (United States)

    Khadem, Nasim; Reddy, Sravanthi; Lee, Sandy; Larsen, Linda; Walker, Daphne

    2016-02-01

    Patients with pathologic processes of the breast commonly present in the Emergency Department (ED). Familiarity with the imaging and management of the most common entities is essential for the radiologist. Additionally, it is important to understand the limitations of ED imaging and management in the acute setting and to recognize when referrals to a specialty breast center are necessary. The goal of this article is to review the clinical presentations, pathophysiology, imaging, and management of emergency breast cases and common breast pathology seen in the ED.

  19. Optical Imaging of the Breast

    International Nuclear Information System (INIS)

    Kim, Min Jung; Kim, Eun Kyung

    2011-01-01

    As the increased prevalence of breast cancer and the advances in breast evaluation awareness have resulted in an increased number of breast examinations and benign breast biopsies, several investigations have been performed to improve the diagnostic accuracy for breast lesions. Optical imaging of the breast that uses nearinfrared light to assess the optical properties of breast tissue is a novel non-invasive imaging technique to characterize breast lesions in clinical practice. This review provides a summary of the current state of optical breast imaging and it describes the basic concepts of optical imaging, the potential clinical applications for breast cancer imaging and its potential incorporation with other imaging modalities

  20. Living Beyond Breast Cancer

    Science.gov (United States)

    ... ACTH CAF CMF FAC TAC TC TCH TH THP Radiation Therapy Whole Breast Radiation Partial Breast Radiation ... Basics Treatments and Your Bone Health Bone Health Tests Improving Bone Health Medicines To Protect Bones Diet, ...

  1. Breast cancer imaging

    International Nuclear Information System (INIS)

    Funke, M.; Villena, C.

    2008-01-01

    Advances in female breast imaging have substantially influenced the diagnosis, therapy, and prognosis of breast cancer in the past few years. Mammography using conventional or digital technique is considered the gold standard for the early detection of breast cancer. Other modalities such as breast ultrasound and contrast-enhanced magnetic resonance imaging of the breast play an important role in diagnostic imaging, staging, and follow-up of breast cancer. Percutaneous needle biopsy is a faster, less invasive, and more cost-effective method than surgical biopsy for verifying the histological diagnosis. New methods such as breast tomosynthesis, contrast-enhanced mammography, and positron emission tomography promise to further improve breast imaging. Further studies are mandatory to adapt these new methods to clinical needs and to evaluate their performance in clinical practice. (orig.) [de

  2. Inflammatory Breast Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... white women. Inflammatory breast tumors are frequently hormone receptor negative, which means they cannot be treated with ...

  3. Cosmetic breast surgery - discharge

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000273.htm Cosmetic breast surgery - discharge To use the sharing features on this page, please enable JavaScript. You had cosmetic breast surgery to change the size or shape ...

  4. Breast cancer staging

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000911.htm Breast cancer staging To use the sharing features on this ... Once your health care team knows you have breast cancer , they will do more tests to stage it. ...

  5. Perioperative cardiac arrest: an evolutionary analysis of the intra-operative cardiac arrest incidence in tertiary centers in Brazil

    Directory of Open Access Journals (Sweden)

    Matheus Fachini Vane

    2016-03-01

    Full Text Available Background: Great changes in medicine have taken place over the last 25 years worldwide. These changes in technologies, patient risks, patient profile, and laws regulating the medicine have impacted the incidence of cardiac arrest. It has been postulated that the incidence of intraoperative cardiac arrest has decreased over the years, especially in developed countries. The authors hypothesized that, as in the rest of the world, the incidence of intraoperative cardiac arrest is decreasing in Brazil, a developing country. Objectives: The aim of this study was to search the literature to evaluate the publications that relate the incidence of intraoperative cardiac arrest in Brazil and analyze the trend in the incidence of intraoperative cardiac arrest. Contents: There were 4 articles that met our inclusion criteria, resulting in 204,072 patients undergoing regional or general anesthesia in two tertiary and academic hospitals, totalizing 627 cases of intraoperative cardiac arrest. The mean intraoperative cardiac arrest incidence for the 25 years period was 30.72:10,000 anesthesias. There was a decrease from 39:10,000 anesthesias to 13:10,000 anesthesias in the analyzed period, with the related lethality from 48.3% to 30.8%. Also, the main causes of anesthesia-related cause of mortality changed from machine malfunction and drug overdose to hypovolemia and respiratory causes. Conclusions: There was a clear reduction in the incidence of intraoperative cardiac arrest in the last 25 years in Brazil. This reduction is seen worldwide and might be a result of multiple factors, including new laws regulating the medicine in Brazil, incorporation of technologies, better human development level of the country, and better patient care. Resumo: Justificativa: Nos últimos 25 anos ocorreram grandes mudanças na medicina em todo o mundo. Essas mudanças de tecnologias, riscos do paciente, perfil do paciente e leis que regulam medicamentos tiveram impacto na incid

  6. Electrophysiological Monitoring of Brain Injury and Recovery after Cardiac Arrest

    Directory of Open Access Journals (Sweden)

    Ruoxian Deng

    2015-10-01

    Full Text Available Reliable prognostic methods for cerebral functional outcome of post cardiac-arrest (CA patients are necessary, especially since therapeutic hypothermia (TH as a standard treatment. Traditional neurophysiological prognostic indicators, such as clinical examination and chemical biomarkers, may result in indecisive outcome predictions and do not directly reflect neuronal activity, though they have remained the mainstay of clinical prognosis. The most recent advances in electrophysiological methods—electroencephalography (EEG pattern, evoked potential (EP and cellular electrophysiological measurement—were developed to complement these deficiencies, and will be examined in this review article. EEG pattern (reactivity and continuity provides real-time and accurate information for early-stage (particularly in the first 24 h hypoxic-ischemic (HI brain injury patients with high sensitivity. However, the signal is easily affected by external stimuli, thus the measurements of EP should be combined with EEG background to validate the predicted neurologic functional result. Cellular electrophysiology, such as multi-unit activity (MUA and local field potentials (LFP, has strong potential for improving prognostication and therapy by offering additional neurophysiologic information to understand the underlying mechanisms of therapeutic methods. Electrophysiology provides reliable and precise prognostication on both global and cellular levels secondary to cerebral injury in cardiac arrest patients treated with TH.

  7. Archaeal RNA polymerase arrests transcription at DNA lesions.

    Science.gov (United States)

    Gehring, Alexandra M; Santangelo, Thomas J

    2017-01-01

    Transcription elongation is not uniform and transcription is often hindered by protein-bound factors or DNA lesions that limit translocation and impair catalysis. Despite the high degree of sequence and structural homology of the multi-subunit RNA polymerases (RNAP), substantial differences in response to DNA lesions have been reported. Archaea encode only a single RNAP with striking structural conservation with eukaryotic RNAP II (Pol II). Here, we demonstrate that the archaeal RNAP from Thermococcus kodakarensis is sensitive to a variety of DNA lesions that pause and arrest RNAP at or adjacent to the site of DNA damage. DNA damage only halts elongation when present in the template strand, and the damage often results in RNAP arresting such that the lesion would be encapsulated with the transcription elongation complex. The strand-specific halt to archaeal transcription elongation on modified templates is supportive of RNAP recognizing DNA damage and potentially initiating DNA repair through a process akin to the well-described transcription-coupled DNA repair (TCR) pathways in Bacteria and Eukarya.

  8. In-hospital pediatric cardiac arrest in Honduras.

    Science.gov (United States)

    Matamoros, Martha; Rodriguez, Roger; Callejas, Allison; Carranza, Douglas; Zeron, Hilda; Sánchez, Carlos; Del Castillo, Jimena; López-Herce, Jesús

    2015-01-01

    The objective of this study was to analyze the characteristic and the prognostic factors of in-hospital pediatric cardiac arrest (CA) in a public hospital Honduras. A prospective observational study was performed on pediatric in-hospital CA as a part of a multicenter international study. One hundred forty-six children were studied. The primary end point was survival at hospital discharge. Univariate and multivariate logistic regression analyses were performed to assess the influence of each factor on mortality. Cardiac arrest occurred in the emergency department in 66.9%. Respiratory diseases and sepsis were predominant causes of CA. Return of spontaneous circulation was achieved in 60% of patients, and 22.6% survived to hospital discharge. The factors related with mortality were nonrespiratory cause of CA (odds ratio [OR], 2.55; P = 0.045), adrenaline administration (OR, 4.96; P = 0.008), and a duration of cardiopulmonary resuscitation more than 10 minutes (OR, 3.40; P = 0.012). In-hospital CA in children in a developing country has low survival. Patients with nonrespiratory causes and those who need adrenaline administration and prolonged resuscitation had worse prognosis.

  9. Usefulness of emergency ultrasound in nontraumatic cardiac arrest.

    Science.gov (United States)

    Volpicelli, Giovanni

    2011-02-01

    Treatment of nontraumatic cardiac arrest in the hospital setting depends on the recognition of heart rhythm and differential diagnosis of the underlying condition while maintaining a constant oxygenated blood flow by ventilation and chest compression. Diagnostic process relies only on patient's history, physical findings, and active electrocardiography. Ultrasound is not currently scheduled in the resuscitation guidelines. Nevertheless, the use of real-time ultrasonography during resuscitation has the potential to improve diagnostic accuracy and allows the physician a greater confidence in deciding aggressive life-saving therapeutic procedures. This article reviews the current opinions and literature about the use of emergency ultrasound during resuscitation of nontraumatic cardiac arrest. Cardiac and lung ultrasound have a great potential in identifying the reversible mechanical causes of pulseless electrical activity or asystole. Brief examination of the heart can even detect a real cardiac standstill regardless of electrical activity displayed on the monitor, which is a crucial prognostic indicator. Moreover, ultrasound can be useful to verify and monitor the tracheal tube placement. Limitation to the use of ultrasound is the need to minimize the no-flow intervals during mechanical cardiopulmonary resuscitation. However, real-time ultrasound can be successfully applied during brief pausing of chest compression and first pulse-check. Finally, lung sonographic examination targeted to the detection of signs of pulmonary congestion has the potential to allow hemodynamic noninvasive monitoring before and after mechanical cardiopulmonary maneuvers. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Non-equilibrium theory of arrested spinodal decomposition

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-11-07

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

  11. Breast Self- Examination Contradiction

    OpenAIRE

    Ayla Akkas Gursoy

    2008-01-01

    Breast cancer is very important health problem among women in the World and Turkey. Although treatment chance is very rising and survival is getting longer thanks to early diagnosis in breast cancer. Some discussion is making related to breast self examination which is one of the early detection methods in recent years. This article consider the discussions about breast self examination under the historical development light. [TAF Prev Med Bull 2008; 7(3.000): 257-260

  12. Breast Self- Examination Contradiction

    Directory of Open Access Journals (Sweden)

    Ayla Akkas Gursoy

    2008-06-01

    Full Text Available Breast cancer is very important health problem among women in the World and Turkey. Although treatment chance is very rising and survival is getting longer thanks to early diagnosis in breast cancer. Some discussion is making related to breast self examination which is one of the early detection methods in recent years. This article consider the discussions about breast self examination under the historical development light. [TAF Prev Med Bull 2008; 7(3.000: 257-260

  13. Broccoli Sprout Extract in Treating Patients With Breast Cancer

    Science.gov (United States)

    2018-06-04

    Ductal Breast Carcinoma; Ductal Breast Carcinoma In Situ; Estrogen Receptor Negative; Estrogen Receptor Positive; Invasive Breast Carcinoma; Lobular Breast Carcinoma; Postmenopausal; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

  14. Tubercular breast abscess

    Directory of Open Access Journals (Sweden)

    Pradeep S Jadhav

    2013-01-01

    Full Text Available Tubercular breast abscess is a rare clinical entity and affects women from mainly the Indian subcontinent. It often mimics breast carcinoma and pyogenic breast abscess clinically. Routine laboratory investigations are not helpful in the diagnosis. Fine needle aspiration cytology (FNAC or biopsy is essential for diagnosis, and tuberculous culture when positive may be very useful to start antitubercular treatment.

  15. Breast sarcomas. Literature review

    Directory of Open Access Journals (Sweden)

    D. A. Ryabchikov

    2014-01-01

    Full Text Available The article presents an overview of the literature about breast sarcomas (nonepithelial malignances. Primary sarcomas are extremely rare, with less than 1 % of all malignant tumors of the breast. Breast carcinomas cause an increased interest of the scientists due to their unique clinical and pathological features and unpredictable prognosis.

  16. Risks of Breast Implants

    Science.gov (United States)

    ... have a risk of developing a type of cancer called breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) in the breast tissue surrounding the implant. BIA-ALCL is not breast cancer. Women diagnosed with BIA-ALCL may need to ...

  17. Breast Cancer (For Kids)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Breast Cancer KidsHealth / For Kids / Breast Cancer What's in this ... for it when they are older. What Is Breast Cancer? The human body is made of tiny building ...

  18. Prescription Monitoring Program Trends Among Individuals Arrested in Maine for Trafficking Prescription Drugs in 2014.

    Science.gov (United States)

    McCall, Kenneth; Nichols, Stephanie D; Holt, Christina; Ochs, Leslie; Cattabriga, Gary; Tu, Chunhao

    2016-06-01

    To evaluate controlled substance prescribing trends available in the Maine Prescription Monitoring Program (PMP) among individuals arrested for prescription drug "trafficking." The demographic characteristics of the individuals who had matching prescription records in the PMP within 90 days of the arrest were identified. A population-based, retrospective cohort study using data from the Maine Diversion Alert Program (DAP) and the Maine PMP. The study population consisted of persons arrested for trafficking prescription drugs in Maine during the 2014 calendar year from January 1 to December 31. There were 594 trafficking arrests reported by the Maine DAP in 2014. The study population consisted of the 235 persons (40%) with arrests involving controlled prescription medications. The mean age of these persons was 33 years (range 18-77 yrs), and 156 (66%) were male. Arrests involved 154 prescription opioids (65%), seven stimulants (3%), seven benzodiazepines (3%), and 77 unspecified controlled prescription drugs (33%). A minority of individuals (n=57, 24%) had a prescription record in the PMP that matched the substance involved in the arrest. Only one person with matching PMP and arrest records utilized ≥ 5 prescribers, while none used ≥ 5 pharmacies within 90 days before the arrest. Payment methods for matching prescriptions were commercial insurance (n=28, 49%), Medicaid (n=19, 33%), Medicare (n=5, 9%), and cash (n=5, 9%). The majority (76%) of persons arrested for prescription drug trafficking did not have PMP records and did not directly obtain the diverted medication from a licensed pharmacy. Traditional red flags, like cash payment and using multiple prescribers or pharmacies, were uncommon. Therefore, arrest records for diversion and PMPs are distinct and complementary tools for identifying individuals at risk for substance misuse. © 2016 Pharmacotherapy Publications, Inc.

  19. The retinoid X receptor agonist, 9-cis UAB30, inhibits cutaneous T-cell lymphoma proliferation through the SKP2-p27kip1 axis.

    Science.gov (United States)

    Chou, Chu-Fang; Hsieh, Yu-Hua; Grubbs, Clinton J; Atigadda, Venkatram R; Mobley, James A; Dummer, Reinhard; Muccio, Donald D; Eto, Isao; Elmets, Craig A; Garvey, W Timothy; Chang, Pi-Ling

    2018-06-01

    Bexarotene (Targretin ® ) is currently the only FDA approved retinoid X receptor (RXR) -selective agonist for the treatment of cutaneous T-cell lymphomas (CTCLs). The main side effects of bexarotene are hypothyroidism and elevation of serum triglycerides (TGs). The novel RXR ligand, 9-cis UAB30 (UAB30) does not elevate serum TGs or induce hypothyroidism in normal subjects. To assess preclinical efficacy and mechanism of action of UAB30 in the treatment of CTCLs and compare its action with bexarotene. With patient-derived CTCL cell lines, we evaluated UAB30 function in regulating growth, apoptosis, cell cycle check points, and cell cycle-related markers. Compared to bexarotene, UAB30 had lower half maximal inhibitory concentration (IC 50 ) values and was more effective in inhibiting the G1 cell cycle checkpoint. Both rexinoids increased the stability of the cell cycle inhibitor, p27kip1 protein, in part, through targeting components involved in the ubiquitination-proteasome system: 1) decreasing SKP2, a F-box protein that binds and targets p27kip1 for degradation by 26S proteasome and 2) suppressing 20S proteasome activity (cell line-dependent) through downregulation of PSMA7, a component of the 20S proteolytic complex in 26S proteasome. UAB30 and bexarotene induce both early cell apoptosis and suppress cell proliferation. Inhibition of the G1 to S cell cycle transition by rexinoids is mediated, in part, through downregulation of SKP2 and/or 20S proteasome activity, leading to increased p27kip1 protein stability. Because UAB30 has minimal effect in elevating serum TGs and inducing hypothyroidism, it is potentially a better alternative to bexarotene for the treatment of CTCLs. Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  20. Inhibition of type I NKT cells by retinoids or following sulfatide-mediated activation of type II NKT cells attenuates alcoholic liver disease

    Science.gov (United States)

    Maricic, Igor; Sheng, Huiming; Marrero, Idania; Seki, Ehikiro; Kisseleva, Tatiana; Chaturvedi, Som; Molle, Natasha; Mathews, K. Stephanie; Gao, Bin; Kumar, Vipin

    2015-01-01

    Innate immune mechanisms leading to liver injury following chronic alcohol ingestion are poorly understood. Natural killer T (NKT) cells, enriched in the liver and comprised of at least two distinct subsets, type I and type II, recognize different lipid antigens presented by CD1d molecules. We have investigated whether differential activation of NKT cell subsets orchestrates inflammatory events leading to alcoholic liver disease (ALD). We found that following chronic plus binge feeding of Lieber-DeCarli liquid diet in male C57BL/6 mice, type I but not type II NKT cells are activated leading to recruitment of inflammatory Gr-1highCD11b+ cells into liver. A central finding is that liver injury following alcohol feeding is dependent upon type I NKT cells. Thus liver injury is significantly inhibited in Jα18−/− mice deficient in type I NKT cells as well as following their inactivation by sulfatide-mediated activation of type II NKT cells. Furthermore we have identified a novel pathway involving all-trans retinoic acid (ATRA) and its receptor RARγ signaling that inhibits type I NKT cells and consequently ALD. A semi-quantitative PCR analysis of hepatic gene expression of some of the key proinflammatory molecules shared in human disease indicated that their upregulation in ALD is dependent upon type I NKT cells. Conclusion Type I but not type II NKT cells become activated following alcohol feeding. Type I NKT cells-induced inflammation and neutrophil recruitment results in liver tissue damage while type II NKT cells protect from injury in ALD. Inhibition of type I NKT cells by retinoids or by sulfatide prevents ALD. Since the CD1d pathway is highly conserved between mice and humans, NKT cell subsets might be targeted for potential therapeutic intervention in ALD. PMID:25477000

  1. Vitamin D receptor displays DNA binding and transactivation as a heterodimer with the retinoid X receptor, but not with the thyroid hormone receptor.

    Science.gov (United States)

    Thompson, P D; Hsieh, J C; Whitfield, G K; Haussler, C A; Jurutka, P W; Galligan, M A; Tillman, J B; Spindler, S R; Haussler, M R

    1999-12-01

    The vitamin D receptor (VDR) is a transcription factor believed to function as a heterodimer with the retinoid X receptor (RXR). However, it was reported [Schräder et al., 1994] that, on putative vitamin D response elements (VDREs) within the rat 9k and mouse 28k calcium binding protein genes (rCaBP 9k and mCaBP 28k), VDR and thyroid hormone receptor (TR) form heterodimers that transactivate in response to both 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) and triiodothyronine (T(3)). We, therefore, examined associations of these receptors on the putative rCaBP 9k and mCaBP 28k VDREs, as well as on established VDREs from the rat osteocalcin (rOC) and mouse osteopontin (mOP) genes, plus the thyroid hormone response element (TRE) from the rat myosin heavy chain (rMHC) gene. In gel mobility shift assays, we found no evidence for VDR-TR heterodimer interaction with any tested element. Further, employing these hormone response elements linked to reporter genes in transfected cells, VDR and TR mediated responses to their cognate ligands only from the rOC/mOP and rMHC elements, respectively, while the CaBP elements were unresponsive to any combination of ligand(s). Utilizing the rOC and mOP VDREs, two distinct repressive actions of TR on VDR-mediated signaling were demonstrated: a T(3)-independent action, presumably via direct TR-RXR competition for DNA binding, and a T(3)-dependent repression, likely by diversion of limiting RXR from VDR-RXR toward the formation of TR-RXR heterodimers. The relative importance of these two mechanisms differed in a response element-specific manner. These results may provide a partial explanation for the observed association between hyperthyroidism and bone demineralization/osteoporosis. Copyright 1999 Wiley-Liss, Inc.

  2. Signaling cross-talk between peroxisome proliferator-activated receptor/retinoid X receptor and estrogen receptor through estrogen response elements.

    Science.gov (United States)

    Keller, H; Givel, F; Perroud, M; Wahli, W

    1995-07-01

    Peroxisome proliferator-activated receptors (PPARs) and retinoid X receptors (RXRs) are nuclear hormone receptors that are activated by fatty acids and 9-cis-retinoic acid, respectively. PPARs and RXRs form heterodimers that activate transcription by binding to PPAR response elements (PPREs) in the promoter of target genes. The PPREs described thus far consist of a direct tandem repeat of the AGGTCA core element with one intervening nucleotide. We show here that the vitellogenin A2 estrogen response element (ERE) can also function as a PPRE and is bound by a PPAR/RXR heterodimer. Although this heterodimer can bind to several other ERE-related palindromic response elements containing AGGTCA half-sites, only the ERE is able to confer transactivation of test reporter plasmids, when the ERE is placed either close to or at a distance from the transcription initiation site. Examination of natural ERE-containing promoters, including the pS2, very-low-density apolipoprotein II and vitellogenin A2 genes, revealed considerable differences in the binding of PPAR/RXR heterodimers to these EREs. In their natural promoter context, these EREs did not allow transcriptional activation by PPARs/RXRs. Analysis of this lack of stimulation of the vitellogenin A2 promoter demonstrated that PPARs/RXRs bind to the ERE but cannot transactivate due to a nonpermissive promoter structure. As a consequence, PPARs/RXRs inhibit transactivation by the estrogen receptor through competition for ERE binding. This is the first example of signaling cross-talk between PPAR/RXR and estrogen receptor.

  3. Mental health court outcomes: a comparison of re-arrest and re-arrest severity between mental health court and traditional court participants.

    Science.gov (United States)

    Moore, Marlee E; Hiday, Virginia Aldigé

    2006-12-01

    Mental health courts have been proliferating across the country since their establishment in the late 1990's. Although numerous advocates have proclaimed their merit, only few empirical studies have evaluated their outcomes. This paper evaluates the effect of one mental health court on criminal justice outcomes by examining arrests and offense severity from one year before to one year after entry into the court, and by comparing mental health court participants to comparable traditional criminal court defendants on these measures. Multivariate models support the prediction that mental health courts reduce the number of new arrests and the severity of such re-arrests among mentally ill offenders. Similar analysis of mental health court completers and non-completers supports the prediction that a "full dose" of mental health treatment and court monitoring produce even fewer re-arrests.

  4. Inheritance of proliferative breast disease in breast cancer kindreds

    International Nuclear Information System (INIS)

    Skolnick, M.H.; Cannon-Albright, L.A.; Goldgar, D.E.; Ward, J.H.; Marshall, C.J.; Schumann, G.B.; Hogle, H.; McWhorter, W.P.; Wright, E.C.; Tran, T.D.; Bishop, D.T.; Kushner, J.P.; Eyre, H.J.

    1990-01-01

    Previous studies have emphasized that genetic susceptibility to breast cancer is rare and is expressed primarily as premenopausal breast cancer, bilateral breast cancer, or both. Proliferative breast disease (PBD) is a significant risk factor for the development of breast cancer and appears to be a precursor lesion. PBD and breast cancer were studied in 103 women from 20 kindreds that were selected for the presence of two first degree relatives with breast cancer and in 31 control women. Physical examination, screening mammography, and four-quadrant fine-needle breast aspirates were performed. Cytologic analysis of breast aspirates revealed PBD in 35% of clinically normal female first degree relatives of breast cancer cases and in 13% of controls. Genetic analysis suggests that genetic susceptibility causes both PBD and breast cancer in these kindreds. This study supports the hypothesis that this susceptibility is responsible for a considerable portion of breast cancer, including unilateral and postmenopausal breast cancer

  5. Quantitative proteomics reveals middle infrared radiation-interfered networks in breast cancer cells.

    Science.gov (United States)

    Chang, Hsin-Yi; Li, Ming-Hua; Huang, Tsui-Chin; Hsu, Chia-Lang; Tsai, Shang-Ru; Lee, Si-Chen; Huang, Hsuan-Cheng; Juan, Hsueh-Fen

    2015-02-06

    Breast cancer is one of the leading cancer-related causes of death worldwide. Treatment of triple-negative breast cancer (TNBC) is complex and challenging, especially when metastasis has developed. In this study, we applied infrared radiation as an alternative approach for the treatment of TNBC. We used middle infrared (MIR) with a wavelength range of 3-5 μm to irradiate breast cancer cells. MIR significantly inhibited cell proliferation in several breast cancer cells but did not affect the growth of normal breast epithelial cells. We performed iTRAQ-coupled LC-MS/MS analysis to investigate the MIR-triggered molecular mechanisms in breast cancer cells. A total of 1749 proteins were identified, quantified, and subjected to functional enrichment analysis. From the constructed functionally enriched network, we confirmed that MIR caused G2/M cell cycle arrest, remodeled the microtubule network to an astral pole arrangement, altered the actin filament formation and focal adhesion molecule localization, and reduced cell migration activity and invasion ability. Our results reveal the coordinative effects of MIR-regulated physiological responses in concentrated networks, demonstrating the potential implementation of infrared radiation in breast cancer therapy.

  6. Breast-Conserving Surgery Followed by Radiation Therapy With MRI-Detected Stage I or Stage II Breast Cancer

    Science.gov (United States)

    2011-12-07

    Ductal Breast Carcinoma in Situ; Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Male Breast Cancer; Medullary Ductal Breast Carcinoma With Lymphocytic Infiltrate; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Tubular Ductal Breast Carcinoma

  7. Docosahexaenoic Acid in Preventing Recurrence in Breast Cancer Survivors

    Science.gov (United States)

    2016-06-20

    Benign Breast Neoplasm; Ductal Breast Carcinoma In Situ; Invasive Breast Carcinoma; Lobular Breast Carcinoma In Situ; Paget Disease of the Breast; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  8. Cell cycle age dependence for radiation-induced G2 arrest: evidence for time-dependent repair

    International Nuclear Information System (INIS)

    Rowley, R.

    1985-01-01

    Exponentially growing eucaryotic cells, irradiated in interphase, are delayed in progression to mitosis chiefly by arrest in G 2 . The sensitivity of Chinese hamster ovary cells to G 2 arrest induction by X rays increases through the cell cycle, up to the X-ray transition point (TP) in G 2 . This age response can be explained by cell cycle age-dependent changes in susceptibility of the target(s) for G 2 arrest and/or by changes in capability for postirradiation recovery from G 2 arrest damage. Discrimination between sensitivity changes and repair phenomena is possible only if the level of G 2 arrest-causing damage sustained by a cell at the time of irradiation and the level ultimately expressed as arrest can be determined. The ability of caffeine to ameliorate radiation-induced G 2 arrest, while inhibiting repair of G 2 arrest-causing damage makes such an analysis possible. In the presence of caffeine, progression of irradiated cells was relatively unperturbed, but on caffeine removal, G 2 arrest was expressed. The duration of G 2 arrest was independent of the length of the prior caffeine exposure. This finding indicates that the target for G 2 arrest induction is present throughout the cell cycle and that the level of G 2 arrest damage incurred is initially constant for all cell cycle phases. The data are consistent with the existence of a time-dependent recovery mechanism to explain the age dependence for radiation induction of G 2 arrest

  9. EU Citizenship and European Arrest Warrant: The Same Rights for All?

    NARCIS (Netherlands)

    Marguery, T.P.

    2011-01-01

    In the case Wolzenburg, the principle of non-discrimination of European Union citizens is applied to the European arrest warrant. The implementation of the European arrest warrant by the Member States cannot escape a control of proportional- ity made by the Court. Member States may impose a period

  10. Return to Work in Out-of-Hospital Cardiac Arrest Survivors

    DEFF Research Database (Denmark)

    Kragholm, Kristian; Wissenberg, Mads; Mortensen, Rikke Normark

    2015-01-01

    BACKGROUND: Data on long-term function of out-of-hospital cardiac arrest survivors are sparse. We examined return to work as a proxy of preserved function without major neurologic deficits in survivors. METHODS AND RESULTS: In Denmark, out-of-hospital cardiac arrests have been systematically repo...

  11. 30 CFR 77.508 - Lightning arresters, ungrounded and exposed power conductors and telephone wires.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Lightning arresters, ungrounded and exposed... AND SURFACE WORK AREAS OF UNDERGROUND COAL MINES Electrical Equipment-General § 77.508 Lightning... conductors and telephone wires shall be equipped with suitable lightning arresters which are adequately...

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

    Science.gov (United States)

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

    2016-01-01

    This study tests a liberation hypothesis for statutory rape incidents, specifically that there may be same-sex and race/ethnicity arrest disparities among statutory rape incidents and that these will be greater among statutory rape than among forcible sex crime incidents. 26,726 reported incidents of statutory rape as defined under state statutes and 96,474 forcible sex crime incidents were extracted from National Incident-Based Reporting System data sets. Arrest outcomes were tested using multilevel modeling. Same-sex statutory rape pairings were rare but had much higher arrest odds. A victim-offender romantic relationship amplified arrest odds for same-sex pairings, but damped arrest odds for male-on-female pairings. Same-sex disparities were larger among statutory than among forcible incidents. Female-on-male incidents had uniformly lower arrest odds. Race/ethnicity effects were smaller than gender effects and more complexly patterned. The findings support the liberation hypothesis for same-sex statutory rape arrest disparities, particularly among same-sex romantic pairings. Support for race/ethnicity-based arrest disparities was limited and mixed. © The Author(s) 2014.

  13. 8 CFR 287.3 - Disposition of cases of aliens arrested without warrant.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Disposition of cases of aliens arrested without warrant. 287.3 Section 287.3 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS FIELD OFFICERS; POWERS AND DUTIES § 287.3 Disposition of cases of aliens arrested without warrant...

  14. The Tendency to Arrest Victims of Domestic Violence: A Preliminary Analysis of Officer Characteristics.

    Science.gov (United States)

    Saunders, Daniel G.

    1995-01-01

    Studied 111 police officers. Predicted that those inclined to arrest victims of domestic violence would have more negative stereotypes and attitudes toward victims and women. Results showed that those with an inclination to arrest victims believed domestic violence is justified situationally and that women stay in violent relationships for…

  15. The Influence of Peer and Educational Variables on Arrest Status among At-Risk Males.

    Science.gov (United States)

    Bullis, Michael; Walker, Hill M.; Stieber, Steve

    1998-01-01

    A study examined the predictive power of selected social and academic variables regarding the arrest frequency for 11th-grade boys who seven years earlier had been judged to be at risk of developing antisocial behavior patterns. Antisocial measures on which participants scored higher were associated with more frequent arrests. (Author/CR)

  16. Mental Disorders, Comorbidity, and Postrunaway Arrests among Homeless and Runaway Adolescents

    Science.gov (United States)

    Chen, Xiaojin; Thrane, Lisa; Whitbeck, Les B.; Johnson, Kurt

    2006-01-01

    This study examined the associations between lifetime mental disorder, comorbidity, and self-reported postrunaway arrests among 428 (187 males, 241 females) homeless and runaway youth. The analysis examined the pattern of arrests across five lifetime mental disorders (alcohol abuse, drug abuse, conduct disorder, major depressive episode, and…

  17. Interfacial Crack Arrest in Sandwich Panels with Embedded Crack Stoppers Subjected to Fatigue Loading

    DEFF Research Database (Denmark)

    Martakos, G.; Andreasen, J. H.; Berggreen, Christian

    2017-01-01

    A novel crack arresting device has been implemented in sandwich panels and tested using a special rig to apply out-of-plane loading on the sandwich panel face-sheets. Fatigue crack propagation was induced in the face-core interface of the sandwich panels which met the crack arrester. The effect o...

  18. 39 CFR 230.4 - Arrest and investigative powers of criminal investigators.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Arrest and investigative powers of criminal... OFFICE OF INSPECTOR GENERAL General Policy and Authority § 230.4 Arrest and investigative powers of criminal investigators. (a) Under the authority of 18 U.S.C. 3061, criminal investigators employed by the...

  19. Mental Condition and Ventricular Size in Arrested Hydrocephalus: an Analysis of 29 Shunt‐independent Children

    NARCIS (Netherlands)

    HOLTZER, G.J.; de LANGE, S.A.; ORBAAN, I.J.C.; GELSEMA, R.

    1971-01-01

    textabstractMeasurement of the diameter of the ventricular system, in a series of 29 patients with arrested hydrocephalus who had become shunt‐independent, showed that enlargement of the ventricles does not necessarily play a part in the arrest of hydrocephalus, for in many of these cases the

  20. Outcome of out-of-hospital cardiac arrest--why do physicians withhold resuscitation attempts?

    DEFF Research Database (Denmark)

    Horsted, Tina I; Rasmussen, Lars S; Lippert, Freddy K

    2004-01-01

    To describe the outcome of out-of-hospital cardiac arrest (OHCA) with a focus on why physicians withhold resuscitation attempts.......To describe the outcome of out-of-hospital cardiac arrest (OHCA) with a focus on why physicians withhold resuscitation attempts....

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

    Science.gov (United States)

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

    2011-01-01

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

  2. Comparison of analysis and experimental data for a unique crack arrest specimen

    International Nuclear Information System (INIS)

    Ayres, D.J.; Fabi, R.J.; Schonenberg, R.Y.; Norris, D.M.

    1988-01-01

    A new fracture test specimen has been developed to study crack extension and arrest in nuclear reactor vessel steels subject to stress-intensity factor and toughness gradients similar to those in postulated pressurized thermal shock situations. A summary of the results of all the tests performed is presented to illustrate the range of crack arrest and crack reinitiation conditions observed. One test of this specimen with the corresponding stress analysis is described in detail. During this test the crack initiated, extended, arrested, reinitiated, extended again, and reached a final arrest. Comparison of detailed dynamic elastic-plastic finite-element analyses and dynamic strain and displacement measurements of the crack extension, arrest, and reinitiation events, combined with topographic analysis of the future surfaces, has led to a new understanding of the crack extension and arrest process. The results of the tests demonstrate crack arrest in rising stress-intensity field at near-upper-shelf temperature conditions and show that the toughness required for arrest is lower than would be predicted by the analysis procedures usually employed for pressurized thermal shock evaluations

  3. Low cerebral blood flow after cardiac arrest is not associated with anaerobic cerebral metabolism

    NARCIS (Netherlands)

    Hoedemaekers, C.W.E.; Ainslie, Philip N.; Hinssen, S.; Aries, M.J.; Bisschops, Laurens L.; Hofmeijer, Jeannette; van der Hoeven, J.G.

    2017-01-01

    Aim of the study Estimation of cerebral anaerobic metabolism in survivors and non-survivors after cardiac arrest. Methods We performed an observational study in twenty comatose patients after cardiac arrest and 19 healthy control subjects. We measured mean flow velocity in the middle cerebral artery

  4. The effect of ultraviolet light on arrested human diploid cell populations

    International Nuclear Information System (INIS)

    Kantor, G.J.; Warner, C.; Hull, D.R.

    1977-01-01

    The results of the experiments to determine an effect of UV (254 nm) on human diploid fibroblasts (HDF) arrested with respect to division by using 0.5% fetal calf serum in the culture medium are reported. A fraction of cells from irradiated arrested populations, maintained in the arrested state post-irradiation, was lost from the populations. The extent of cell loss was fluence-dependent and cell strain specific. A Xeroderma pigmentosum cell strain was more sensitive to UV than were normal HDF. No difference in sensitivity were observed when arrested populations established from normal HDF populations of various in vitro ages were used. The length of the pre-irradiation arrested period affected the sensitivity of normal HDF, which appeared more resistant at longer arrested periods, but not the sensitivity of arrested Xeroderma populations. These results suggest that DNA repair processes play a role in maintaining irradiated cells in the arrested state. The suggestion is made that the lethal event caused by UV is an effect on transcription leading to an inhibition of required protein synthesis. (author)

  5. A seed treatment to prevent shoot apical meristem arrest in Brassica oleracea

    NARCIS (Netherlands)

    Jonge, de J.; Goffman, Fernando D.; Kodde, J.; Angenent, G.C.; Groot, S.P.C.

    2018-01-01

    Brassica oleracea plants can suffer from shoot apical meristem arrest, when sown at cold temperatures, giving rise to so-called blind seedlings that stop development and the formation of new leaves. We developed a seed treatment that strongly reduces the occurrence of this meristem arrest in

  6. 38 CFR 3.375 - Determination of inactivity (complete arrest) in tuberculosis.

    Science.gov (United States)

    2010-07-01

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

  7. Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer: A Nested Case-Control Study.

    Directory of Open Access Journals (Sweden)

    Tess V Clendenen

    Full Text Available Genetic polymorphisms in vitamin D metabolism and signaling genes have been inconsistently associated with risk of breast cancer, though few studies have examined SNPs in vitamin D-related genes other than the vitamin D receptor (VDR gene and particularly have not examined the association with the retinoid X receptor alpha (RXRA gene which may be a key vitamin D pathway gene. We conducted a nested case-control study of 734 cases and 1435 individually matched controls from a population-based prospective cohort study, the Northern Sweden Mammary Screening Cohort. Tag and functional SNPs were genotyped for the VDR, cytochrome p450 24A1 (CYP24A1, and RXRA genes. We also genotyped specific SNPs in four other genes related to vitamin D metabolism and signaling (GC/VDBP, CYP2R1, DHCR7, and CYP27B1. SNPs in the CYP2R1, DHCR7, and VDBP gene regions that were associated with circulating 25(OHD concentration in GWAS were also associated with plasma 25(OHD in our study (p-trend <0.005. After taking into account the false discovery rate, these SNPs were not significantly associated with breast cancer risk, nor were any of the other SNPs or haplotypes in VDR, RXRA, and CYP24A1. We observed no statistically significant associations between polymorphisms or haplotypes in key vitamin D-related genes and risk of breast cancer. These results, combined with the observation in this cohort and most other prospective studies of no association of circulating 25(OHD with breast cancer risk, do not support an association between vitamin D and breast cancer risk.

  8. The relevance of crack arrest phenomena for pressure vessel structural integrity assessment

    International Nuclear Information System (INIS)

    Connors, D.C.; Dowling, A.R.; Flewitt, P.E.J.

    1996-01-01

    The potential role of a crack arrest argument for the structural integrity assessments of steel pressure vessels and the relationship between crack initiation and crack arrest philosophies are described. A typical structural integrity assessment using crack initiation fracture mechanics is illustrated by means of a case study based on assessment of the steel pressure vessels for Magnox power stations. Evidence of the occurrence of crack arrest in structures is presented and reviewed, and the applications to pressure vessels which are subjected to similar conditions are considered. An outline is given of the material characterisation that would be required to undertake a crack arrest integrity assessment. It is concluded that crack arrest arguments could be significant in the structural integrity assessment of PWR reactor pressure vessels under thermal shock conditions, whereas for Magnox steel pressure vessels it would be limited in its potential to supporting existing arguments. (author)

  9. Proteomic analysis of the response to cell cycle arrests in human myeloid leukemia cells.

    Science.gov (United States)

    Ly, Tony; Endo, Aki; Lamond, Angus I

    2015-01-02

    Previously, we analyzed protein abundance changes across a 'minimally perturbed' cell cycle by using centrifugal elutriation to differentially enrich distinct cell cycle phases in human NB4 cells (Ly et al., 2014). In this study, we compare data from elutriated cells with NB4 cells arrested at comparable phases using serum starvation, hydroxyurea, or RO-3306. While elutriated and arrested cells have similar patterns of DNA content and cyclin expression, a large fraction of the proteome changes detected in arrested cells are found to reflect arrest-specific responses (i.e., starvation, DNA damage, CDK1 inhibition), rather than physiological cell cycle regulation. For example, we show most cells arrested in G2 by CDK1 inhibition express abnormally high levels of replication and origin licensing factors and are likely poised for genome re-replication. The protein data are available in the Encyclopedia of Proteome Dynamics (

  10. Application of Powell's optimization method to surge arrester circuit models' parameters

    Energy Technology Data Exchange (ETDEWEB)

    Christodoulou, C.A.; Stathopulos, I.A. [National Technical University of Athens, School of Electrical and Computer Engineering, 9 Iroon Politechniou St., Zografou Campus, 157 80 Athens (Greece); Vita, V.; Ekonomou, L.; Chatzarakis, G.E. [A.S.PE.T.E. - School of Pedagogical and Technological Education, Department of Electrical Engineering Educators, N. Heraklion, 141 21 Athens (Greece)

    2010-08-15

    Powell's optimization method has been used for the evaluation of the surge arrester models parameters. The proper modelling of metal-oxide surge arresters and the right selection of equivalent circuit parameters are very significant issues, since quality and reliability of lightning performance studies can be improved with the more efficient representation of the arresters' dynamic behavior. The proposed approach selects optimum arrester model equivalent circuit parameter values, minimizing the error between the simulated peak residual voltage value and this given by the manufacturer. Application of the method in performed on a 120 kV metal oxide arrester. The use of the obtained optimum parameter values reduces significantly the relative error between the simulated and manufacturer's peak residual voltage value, presenting the effectiveness of the method. (author)

  11. Condition Assessment of Metal Oxide Surge Arrester Based on Multi-Layer SVM Classifier

    Directory of Open Access Journals (Sweden)

    M Khodsuz

    2015-12-01

    Full Text Available This paper introduces the indicators for surge arrester condition assessment based on the leakage current analysis. Maximum amplitude of fundamental harmonic of the resistive leakage current, maximum amplitude of third harmonic of the resistive leakage current and maximum amplitude of fundamental harmonic of the capacitive leakage current were used as indicators for surge arrester condition monitoring. Also, the effects of operating voltage fluctuation, third harmonic of voltage, overvoltage and surge arrester aging on these indicators were studied. Then, obtained data are applied to the multi-layer support vector machine for recognizing of surge arrester conditions. Obtained results show that introduced indicators have the high ability for evaluation of surge arrester conditions.

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  13. Out-of-hospital cardiac arrests in children and adolescents

    DEFF Research Database (Denmark)

    Rajan, Shahzleen; Wissenberg, Mads; Folke, Fredrik

    2015-01-01

    BACKGROUND: There is insufficient knowledge of out-of-hospital cardiac arrest (OHCA) in the very young. OBJECTIVES: This nationwide study sought to examine age-stratified OHCA characteristics and the role of parental socioeconomic differences and its contribution to mortality in the young...... population. METHODS: All OHCA patients in Denmark, ≤21 years of age, were identified from 2001 to 2010. The population was divided into infants (adolescents/young adults (16-21 years). Multivariate logistic regression......-school children, school children and high school adolescents were 11.5, 3.5, 1.3 and 5.3 per 100,000 inhabitants. Overall bystander CPR rate was 48.8%, and for age groups: 55.4%, 41.2%, 44.9% and 63.0%, respectively. Overall 30-day survival rate was 8.1%, and for age groups: 1.4%, 4.5%, 16.1% and 9...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    BACKGROUND: We aimed to determine whether (1) patients with obstructive pulmonary disease (OPD) have an increased risk of sudden cardiac arrest (SCA) due to ventricular tachycardia or fibrillation (VT/VF), and (2) the SCA risk is mediated by cardiovascular risk-profile and/or respiratory drug use...... with electrocardiographic documentation of VT/VF were included. Conditional logistic regression analysis was used to assess the association between SCA and OPD. Pre-specified subgroup analyses were performed regarding age, sex, cardiovascular risk-profile, disease severity, and current use of respiratory drugs. RESULTS...... is associated with an increased observed risk of SCA. The most increased risk was observed in patients with a high cardiovascular risk-profile, and in those who received SABA and, possibly, those who received AC at the time of SCA....

  15. Current practice in out-of-hospital cardiac arrest management

    DEFF Research Database (Denmark)

    Proclemer, Alessandro; Dobreanu, Dan; Pison, Laurent

    2012-01-01

    AIMS: The purpose of this EP wire is to examine clinical practice in the field of out-of-hospital cardiac arrest (OHCA) management, with special focus on in-hospital diagnostic and therapeutic strategies. METHODS AND RESULTS: Fifty-three European centres, all members of the EHRA-EP Research network......, completed the questions of the survey. A dedicated strategy for OHCA management is active in 85% of the centres. Shockable tachyarrhythmias such as initial OHCA rhythm are reported in >70% of the patients in 64% of the centres. In-hospital therapeutic hypothermia was applied in >50% of the patients in 53...... management strategy, including coronary angiography/PCI and implantable cardioverter defibrillator therapy, while therapeutic hypothermia appears to be underused....

  16. A Unique Case of Cardiac Arrest following K2 Abuse

    Directory of Open Access Journals (Sweden)

    Saif Ibrahim

    2014-01-01

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

  17. Central diabetes insipidus following cardiopulmonary arrest in a dog.

    Science.gov (United States)

    Bellis, Tara; Daly, Meredith; Davidson, Benjamin

    2015-01-01

    To describe a clinical case of transient central diabetes insipidus (CDI) occurring post cardiopulmonary arrest (CPA) in a dog. An 8-week-old dog presented for intensive care after successful resuscitation following CPA. The patient exhibited neurologic deficits at initial presentation and over the following days developed marked polyuria, isosthenuria, and low urine osmolality. Treatment with synthetic vasopressin resulted in a reduction in urine output, increase in urine specific gravity (>50%), and increase in urine osmolality, suggesting a diagnosis of partial CDI. Clinical signs resolved over the following weeks and treatment was discontinued. CPA has been described as a cause of ischemic injury to the pituitary gland resulting in CDI in people. To the authors' knowledge, this is the first report of a dog developing transient partial CDI following CPA and successful resuscitation. © Veterinary Emergency and Critical Care Society 2015.

  18. Opiate Withdrawal Complicated by Tetany and Cardiac Arrest

    Directory of Open Access Journals (Sweden)

    Irfanali R. Kugasia

    2014-01-01

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

  19. Cellular Senescence in Postmitotic Cells: Beyond Growth Arrest.

    Science.gov (United States)

    Sapieha, Przemyslaw; Mallette, Frédérick A

    2018-04-25

    In mitotic cells, cellular senescence is a permanent state of G1 arrest, that may have evolved in parallel to apoptosis, to limit proliferation of damaged cells and oncogenesis. Recent studies have suggested that postmitotic cells are also capable of entering a state of senescence, although the repercussions of postmitotic cellular senescence (PoMiCS) on tissue health and function are currently ill-defined. In tissues made largely of post-mitotic cells, it is evolutionary advantageous to preserve cellular integrity and cellular senescence of post-mitotic cells may prevent stressor-induced tissue degeneration and promote tissue repair. Paradoxically, PoMiCS may also contribute to disease progression through the generation of inflammatory mediators, termed the senescence-associated secretory phenotype. Here, we discuss the potential roles of PoMiCS and propose to enlarge the current definition of cellular senescence to postmitotic terminally differentiated cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Massive Neurofibroma of the Breast

    African Journals Online (AJOL)

    Valued eMachines Customer

    Neurofibromas are benign nerve sheath tumors that are extremely rare in the breast. We report a massive ... plexiform breast neurofibromas may transform into a malignant peripheral nerve sheath tumor1. We present a case .... Breast neurofibroma. http://www.breast-cancer.ca/type/breast-neurofibroma.htm. August 2011. 2.

  1. Lobaplatin arrests cell cycle progression in human hepatocellular carcinoma cells

    Directory of Open Access Journals (Sweden)

    Chen Chang-Jie

    2010-10-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC still is a big burden for China. In recent years, the third-generation platinum compounds have been proposed as potential active agents for HCC. However, more experimental and clinical data are warranted to support the proposal. In the present study, the effect of lobaplatin was assessed in five HCC cell lines and the underlying molecular mechanisms in terms of cell cycle kinetics were explored. Methods Cytotoxicity of lobaplatin to human HCC cell lines was examined using MTT cell proliferation assay. Cell cycle distribution was determined by flow cytometry. Expression of cell cycle-regulated genes was examined at both the mRNA (RT-PCR and protein (Western blot levels. The phosphorylation status of cyclin-dependent kinases (CDKs and retinoblastoma (Rb protein was also examined using Western blot analysis. Results Lobaplatin inhibited proliferation of human HCC cells in a dose-dependent manner. For the most sensitive SMMC-7721 cells, lobaplatin arrested cell cycle progression in G1 and G2/M phases time-dependently which might be associated with the down-regulation of cyclin B, CDK1, CDC25C, phosphorylated CDK1 (pCDK1, pCDK4, Rb, E2F, and pRb, and the up-regulation of p53, p21, and p27. Conclusion Cytotoxicity of lobaplatin in human HCC cells might be due to its ability to arrest cell cycle progression which would contribute to the potential use of lobaplatin for the management of HCC.

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

    Directory of Open Access Journals (Sweden)

    Yuya Makiguchi

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

  3. Breast abscesses after breast conserving therapy for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, Kazuhisa [National Kyoto Hospital (Japan)

    2001-09-01

    Breast abscess after breast conserving therapy is a rare complication and the study of this cause has not been reported. A retrospective review of 190 patients undergoing breast conserving therapy in our institution revealed 4 patients with breast abscess (mean age, 50.6 years; range, 47-57 years and median follow up 4 months; 1-11 months). Risk factors which were common to all patients were: fine needle aspiration (FNA), surgical treatment; wide excision, adjuvant therapy; oral administration of tamoxifen (TAM), radiation therapy (RT) to ipsilateral whole breast; total dose of 50 Gy and skin desquamation by RT; level I or II. Other important risk factors in 3 patients were repeated aspirations of seroma post operatively and 2 patients received chemotherapy; CAF. Cultures from one abscess grew staphylococcus aureus, one grew staphylococcus epidermidis, and two were sterile. Breast abscess may be caused by a variety of factors and it is often difficult to specify the cause. This suggests that careful observation will be necessary to determine the cause. (author)

  4. Breast abscesses after breast conserving therapy for breast cancer

    International Nuclear Information System (INIS)

    Fujiwara, Kazuhisa

    2001-01-01

    Breast abscess after breast conserving therapy is a rare complication and the study of this cause has not been reported. A retrospective review of 190 patients undergoing breast conserving therapy in our institution revealed 4 patients with breast abscess (mean age, 50.6 years; range, 47-57 years and median follow up 4 months; 1-11 months). Risk factors which were common to all patients were: fine needle aspiration (FNA), surgical treatment; wide excision, adjuvant therapy; oral administration of tamoxifen (TAM), radiation therapy (RT) to ipsilateral whole breast; total dose of 50 Gy and skin desquamation by RT; level I or II. Other important risk factors in 3 patients were repeated aspirations of seroma post operatively and 2 patients received chemotherapy; CAF. Cultures from one abscess grew staphylococcus aureus, one grew staphylococcus epidermidis, and two were sterile. Breast abscess may be caused by a variety of factors and it is often difficult to specify the cause. This suggests that careful observation will be necessary to determine the cause. (author)

  5. Breast cancer screening with digital breast tomosynthesis.

    Science.gov (United States)

    Skaane, Per

    2017-01-01

    To give an overview of studies comparing full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) in breast cancer screening. The implementation of tomosynthesis in breast imaging is rapidly increasing world-wide. Experimental clinical studies of relevance for DBT screening have shown that tomosynthesis might have a great potential in breast cancer screening, although most of these retrospective reading studies are based on small populations, so that final conclusions are difficult to draw from individual reports. Several retrospective studies and three prospective trials on tomosynthesis in breast cancer screening have been published so far, confirming the great potential of DBT in mammography screening. The main results of these screening studies are presented. The retrospective screening studies from USA have all shown a significant decrease in the recall rate using DBT as adjunct to mammography. Most of these studies have also shown an increase in the cancer detection rate, and the non-significant results in some studies might be explained by a lack of statistical power. All the three prospective European trials have shown a significant increase in the cancer detection rate. The retrospective and the prospective screening studies comparing FFDM and DBT have all demonstrated that tomosynthesis has a great potential for improving breast cancer screening. DBT should be regarded as a better mammogram that could improve or overcome limitations of the conventional mammography, and tomosynthesis might be considered as the new technique in the next future of breast cancer screening.

  6. Increasing Breast Cancer Surveillance among African American Breast Cancer Survivors

    National Research Council Canada - National Science Library

    Thompson, Hayley

    2005-01-01

    ...; they also are at considerable risk for breast cancer recurrence. According to the American Society of Clinical Oncology, survivors should undergo careful breast cancer surveillance, including annual mammography and breast self-exam...

  7. Epigenetic reprogramming of breast cancer cells with oocyte extracts

    Directory of Open Access Journals (Sweden)

    Kumari Rajendra

    2011-01-01

    Full Text Available Abstract Background Breast cancer is a disease characterised by both genetic and epigenetic alterations. Epigenetic silencing of tumour suppressor genes is an early event in breast carcinogenesis and reversion of gene silencing by epigenetic reprogramming can provide clues to the mechanisms responsible for tumour initiation and progression. In this study we apply the reprogramming capacity of oocytes to cancer cells in order to study breast oncogenesis. Results We show that breast cancer cells can be directly reprogrammed by amphibian oocyte extracts. The reprogramming effect, after six hours of treatment, in the absence of DNA replication, includes DNA demethylation and removal of repressive histone marks at the promoters of tumour suppressor genes; also, expression of the silenced genes is re-activated in response to treatment. This activity is specific to oocytes as it is not elicited by extracts from ovulated eggs, and is present at very limited levels in extracts from mouse embryonic stem cells. Epigenetic reprogramming in oocyte extracts results in reduction of cancer cell growth under anchorage independent conditions and a reduction in tumour growth in mouse xenografts. Conclusions This study presents a new method to investigate tumour reversion by epigenetic reprogramming. After testing extracts from different sources, we found that axolotl oocyte extracts possess superior reprogramming ability, which reverses epigenetic silencing of tumour suppressor genes and tumorigenicity of breast cancer cells in a mouse xenograft model. Therefore this system can be extremely valuable for dissecting the mechanisms involved in tumour suppressor gene silencing and identifying molecular activities capable of arresting tumour growth. These applications can ultimately shed light on the contribution of epigenetic alterations in breast cancer and advance the development of epigenetic therapies.

  8. Breast Cancer Risk in American Women

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Risk in American Women On This Page What ... risk of developing the disease. Personal history of breast cancer : Women who have had breast cancer are more ...

  9. Ionic and Wigner Glasses, Superionic Conductors, and Spinodal Electrostatic Gels: Dynamically Arrested Phases of the Primitive Model

    International Nuclear Information System (INIS)

    Sanchez-Diaz, L. E.; Juarez-Maldonado, R.; Vizcarra-Rendon, A.

    2009-01-01

    Based on the recently proposed self-consistent generalized Langevin equation theory of dynamic arrest, in this letter we show that the ergodic-nonergodic phase diagram of a classical mixture of charged hard spheres (the so-called 'primitive model' of ionic solutions and molten salts) includes arrested phases corresponding to nonconducting ionic glasses, partially arrested states that represent solid electrolytes (or 'superionic' conductors), low-density colloidal Wigner glasses, and low-density electrostatic gels associated with arrested spinodal decomposition.

  10. Breast Prothesis Leakage and Malignant Changes of the Breast

    OpenAIRE

    Al-Lawati, Taha; Kutty, Rajyashree

    2009-01-01

    A breast implant is a prosthesis used to enhance the size of a woman’s breasts. Silicon implants are most commonly used, but as with all surgical implants it has some complications. The question is whether it can induce breast cancer? During the last year, a case of reconstructed breast with prosthesis which leaked was presented. The aim of this report is to review current literature to evaluate whether there are reported correlations between breast cancer and breast implants. The conclusion ...

  11. Defining the steps that lead to cancer: replicative telomere erosion, aneuploidy and an epigenetic maturation arrest of tissue stem cells.

    Science.gov (United States)

    Stindl, Reinhard

    2008-01-01

    Recently, an influential sequencing study found that more than 1700 genes had non-silent mutations in either a breast or colorectal cancer, out of just 11 breast and 11 colorectal tumor samples. This is not surprising given the fact that genomic instability is the hallmark of cancer cells. The plethora of genomic alterations found in every carcinoma does not obey the 'law of genotype-phenotype correlation', since the same histological subtype of cancer harbors different gene mutations and chromosomal aberrations in every patient. In an attempt to make sense out of the observed genetic and chromosomal chaos in cancer, I propose a cascade model. According to this model, tissue regeneration depends on the proliferation and serial activation of stem cells. Replicative telomere erosion limits the proliferative life span of adult stem cells and results in the Hayflick limit (M1). However, local tissue exhaustion or old age might promote the activation of M1-deficient tissue stem cells. Extended proliferation of these cells leads to telomere-driven chromosomal instability and aneuploidy (abnormal balance of chromosomes and/or chromosome material). Several of the aforementioned steps have been already described in the literature. However, in contrast to common theories, it is proposed here that the genomic damage blocks the epigenetic differentiation switch. As a result of aneuploidy, differentiation-specific genes cannot be activated by modification of methylation patterns. Consequently, the phenotype of cancer tissue is largely determined by the epigenetic maturation arrest of tissue stem cells, which in addition enables a fraction of cancer cells to proliferate, invade and metastasize, as normal adult stem cells do. The new model combines genetic and epigenetic alterations of cancer cells in one causative cascade and offers an explanation for why identical histologic cancer types harbor a confusing variety of chromosomal and gene aberrations. The Viennese Cascade, as

  12. Contralateral breast cancer risk

    International Nuclear Information System (INIS)

    Unnithan, Jaya; Macklis, Roger M.

    2001-01-01

    The use of breast-conserving treatment approaches for breast cancer has now become a standard option for early stage disease. Numerous randomized studies have shown medical equivalence when mastectomy is compared to lumpectomy followed by radiotherapy for the local management of this common problem. With an increased emphasis on patient involvement in the therapeutic decision making process, it is important to identify and quantify any unforeseen risks of the conservation approach. One concern that has been raised is the question of radiation- related contralateral breast cancer after breast radiotherapy. Although most studies do not show statistically significant evidence that patients treated with breast radiotherapy are at increased risk of developing contralateral breast cancer when compared to control groups treated with mastectomy alone, there are clear data showing the amount of scattered radiation absorbed by the contralateral breast during a routine course of breast radiotherapy is considerable (several Gy) and is therefore within the range where one might be concerned about radiogenic contralateral tumors. While radiation related risks of contralateral breast cancer appear to be small enough to be statistically insignificant for the majority of patients, there may exist a smaller subset which, for genetic or environmental reasons, is at special risk for scatter related second tumors. If such a group could be predicted, it would seem appropriate to offer either special counselling or special prevention procedures aimed at mitigating this second tumor risk. The use of genetic testing, detailed analysis of breast cancer family history, and the identification of patients who acquired their first breast cancer at a very early age may all be candidate screening procedures useful in identifying such at- risk groups. Since some risk mitigation strategies are convenient and easy to utilize, it makes sense to follow the classic 'ALARA' (as low as reasonably

  13. Breast Cancer Rates by State

    Science.gov (United States)

    ... Associated Lung Ovarian Prostate Skin Uterine Cancer Home Breast Cancer Rates by State Language: English (US) Español (Spanish) ... from breast cancer each year. Rates of Getting Breast Cancer by State The number of people who get ...

  14. Breast Cancer—Patient Version

    Science.gov (United States)

    Breast cancer is the second most common cancer in women after skin cancer. Mammograms can detect breast cancer early, possibly before it has spread. Start here to find information on breast cancer treatment, causes and prevention, screening, research, and statistics.

  15. CDC Vital Signs: Breast Cancer

    Science.gov (United States)

    ... 2.65 MB] Read the MMWR Science Clips Breast Cancer Black Women Have Higher Death Rates from Breast ... of Page U.S. State Info Number of Additional Breast Cancer Deaths Among Black Women, By State SOURCE: National ...

  16. Genetics Home Reference: breast cancer

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Breast cancer Breast cancer Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Breast cancer is a disease in which certain cells in ...

  17. Breast Cancer and Bone Loss

    Science.gov (United States)

    ... Menopause Map Featured Resource Find an Endocrinologist Search Breast Cancer and Bone Loss July 2010 Download PDFs English ... G. Komen Foundation What is the link between breast cancer and bone loss? Certain treatments for breast cancer ...

  18. 6 Common Cancers - Breast Cancer

    Science.gov (United States)

    ... Home Current Issue Past Issues 6 Common Cancers - Breast Cancer Past Issues / Spring 2007 Table of Contents For ... slow her down. Photo: AP Photo/Brett Flashnick Breast Cancer Breast cancer is a malignant (cancerous) growth that ...

  19. Accelerated Radiation Therapy After Surgery in Treating Patients With Breast Cancer

    Science.gov (United States)

    2017-11-15

    Inflammatory Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Tubular Ductal Breast Carcinoma

  20. Re-expression of ARHI (DIRAS3) induces autophagy in breast cancer cells and enhances the inhibitory effect of paclitaxel

    International Nuclear Information System (INIS)

    Zou, Chun-Fang; Yu, Yinhua; Jia, Luoqi; Jin, Hongyan; Yao, Ming; Zhao, Naiqing; Huan, Jin; Lu, Zhen; Bast, Robert C Jr; Feng, Youji

    2011-01-01

    ARHI is a Ras-related imprinted gene that inhibits cancer cell growth and motility. ARHI is downregulated in the majority of breast cancers, and loss of its expression is associated with its progression from ductal carcinoma in situ (DCIS) to invasive disease. In ovarian cancer, re-expression of ARHI induces autophagy and leads to autophagic death in cell culture; however, ARHI re-expression enables ovarian cancer cells to remain dormant when they are grown in mice as xenografts. The purpose of this study is to examine whether ARHI induces autophagy in breast cancer cells and to evaluate the effects of ARHI gene re-expression in combination with paclitaxel. Re-expression of ARHI was achieved by transfection, by treatment with trichostatin A (TSA) or by a combination of TSA and 5-aza-2'-deoxycytidine (DAC) in breast cancer cell cultures and by liposomal delivery of ARHI in breast tumor xenografts. ARHI re-expression induces autophagy in breast cancer cells, and ARHI is essential for the induction of autophagy. When ARHI was re-expressed in breast cancer cells treated with paclitaxel, the growth inhibitory effect of paclitaxel was enhanced in both the cell culture and the xenografts. Although paclitaxel alone did not induce autophagy in breast cancer cells, it enhanced ARHI-induced autophagy. Conversely, ARHI re-expression promoted paclitaxel-induced apoptosis and G2/M cell cycle arrest. ARHI re-expression induces autophagic cell death in breast cancer cells and enhances the inhibitory effects of paclitaxel by promoting autophagy, apoptosis, and G2/M cell cycle arrest

  1. A Case of AML Characterized by a Novel t(4;15(q31;q22 Translocation That Confers a Growth-Stimulatory Response to Retinoid-Based Therapy

    Directory of Open Access Journals (Sweden)

    Justin M. Watts

    2017-07-01

    Full Text Available Here we report the case of a 30-year-old woman with relapsed acute myeloid leukemia (AML who was treated with all-trans retinoic acid (ATRA as part of investigational therapy (NCT02273102. The patient died from rapid disease progression following eight days of continuous treatment with ATRA. Karyotype analysis and RNA-Seq revealed the presence of a novel t(4;15(q31;q22 reciprocal translocation involving the TMEM154 and RASGRF1 genes. Analysis of primary cells from the patient revealed the expression of TMEM154-RASGRF1 mRNA and the resulting fusion protein, but no expression of the reciprocal RASGRF1-TMEM154 fusion. Consistent with the response of the patient to ATRA therapy, we observed a rapid proliferation of t(4;15 primary cells following ATRA treatment ex vivo. Preliminary characterization of the retinoid response of t(4;15 AML revealed that in stark contrast to non-t(4;15 AML, these cells proliferate in response to specific agonists of RARα and RARγ. Furthermore, we observed an increase in the levels of nuclear RARγ upon ATRA treatment. In summary, the identification of the novel t(4;15(q31;q22 reciprocal translocation opens new avenues in the study of retinoid resistance and provides potential for a new biomarker for therapy of AML.

  2. DIAGNOSIS OF MUCINOUS BREAST CANCER

    Directory of Open Access Journals (Sweden)

    E. К. Saribekyan

    2014-01-01

    Full Text Available The paper presents the diagnostic results of 27 patients with mucinous breast cancer, which is a rare type of invasive ductal breast cancer accounting for less than 2% of all breast cancers. The role of radiological, histological and cytological examination in the diagnosis of mucinous breast cancer is evaluated. In cases with large tumors, it was difficult to differentiate mucinous breast cancer from fibrocystic and other benign breast lesions.

  3. Communication between members of the cardiac arrest team--a postal survey.

    Science.gov (United States)

    Pittman, J; Turner, B; Gabbott, D A

    2001-05-01

    Effective communication enhances team building and is perceived to improve the quality of team performance. A recent publication from the Resuscitation Council (UK) has highlighted this fact and recommended that cardiac arrest team members make contact daily. We wished to identify how often members of this team communicate prior to a cardiopulmonary arrest. A questionnaire on cardiac arrest team composition, leadership, communication and debriefing was distributed nationally to Resuscitation Training Officers (RTOs) and their responses analysed. One hundred and thirty (55%) RTOs replied. Physicians and anaesthetists were the most prominent members of the team. The Medical Senior House Officer is usually nominated as the team leader. Eighty-seven centres (67%) have no communication between team members prior to attending a cardiopulmonary arrest. In 33%, communication occurs but is either informal or fortuitous. The RTOs felt that communication is important to enhance team dynamics and optimise task allocation. Only 7% achieve a formal debrief following a cardiac arrest. Communication between members of the cardiac arrest team before and after a cardiac arrest is poor. Training and development of these skills may improve performance and should be prioritised. Team leadership does not necessarily reflect experience or training.

  4. Discrimination, arrest history, and major depressive disorder in the U.S. Black population.

    Science.gov (United States)

    Anglin, Deidre M; Lighty, Quenesha; Yang, Lawrence H; Greenspoon, Michelle; Miles, Rashun J; Slonim, Tzachi; Isaac, Kathleen; Brown, Monique J

    2014-09-30

    Everyday discrimination contributes negatively to depressive symptomatology among Blacks in the US and being arrested could add to this depression. Using data from the National Survey on American Life, the present study determined the association between an arrest history and major depressive disorder (MDD), while accounting for discrimination among African Americans, US-born Afro-Caribbeans and first-generation Black immigrants. Findings from logistic regression analyses adjusted for discrimination suggested an arrest history is associated with 12-month MDD (Adjusted OR=1.47; 95% CI=1.02-2.10) and lifetime MDD (Adjusted OR=1.56 CI=1.17-2.09). Accounting for drug and alcohol dependence attenuated the association between arrest history and 12-month MDD, but not lifetime MDD. The associations between arrest history and both 12-month and lifetime MDD, and discrimination and lifetime MDD varied by ethnic/immigrant group. Specifically, while the association between arrest history and MDD (both 12-month and lifetime) was strongest among US-born Afro-Caribbeans, evidence consistent with the immigrant paradox, the association between discrimination and lifetime MDD was particularly relevant for first-generation Black immigrants, suggesting discrimination may hinder the protection of first-generation status. Mental health prevention and treatment programs should target the stress associated with being arrested and experiencing discrimination among US Blacks. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Early Recognition of Foreign Body Aspiration as the Cause of Cardiac Arrest

    Directory of Open Access Journals (Sweden)

    Muhammad Kashif

    2016-01-01

    Full Text Available Foreign body aspiration (FBA is uncommon in the adult population but can be a life-threatening condition. Clinical manifestations vary according to the degree of airway obstruction, and, in some cases, making the correct diagnosis requires a high level of clinical suspicion combined with a detailed history and exam. Sudden cardiac arrest after FBA may occur secondary to asphyxiation. We present a 48-year-old male with no history of cardiac disease brought to the emergency department after an out-of-hospital cardiac arrest (OHCA. The patient was resuscitated after 15 minutes of cardiac arrest. He was initially managed with therapeutic hypothermia (TH. Subsequent history suggested FBA as a possible etiology of the cardiac arrest, and fiberoptic bronchoscopy demonstrated a piece of meat and bone lodged in the left main stem bronchus. The foreign body was removed with the bronchoscope and the patient clinically improved with full neurological recovery. Therapeutic hypothermia following cardiac arrest due to asphyxia has been reported to have high mortality and poor neurological outcomes. This case highlights the importance of early identification of FBA causing cardiac arrest, and we report a positive neurological outcome for postresuscitation therapeutic hypothermia following cardiac arrest due to asphyxia.

  6. Cardiopulmonary resuscitation duration and survival in out-of-hospital cardiac arrest patients.

    Science.gov (United States)

    Adnet, Frederic; Triba, Mohamed N; Borron, Stephen W; Lapostolle, Frederic; Hubert, Hervé; Gueugniaud, Pierre-Yves; Escutnaire, Josephine; Guenin, Aurelien; Hoogvorst, Astrid; Marbeuf-Gueye, Carol; Reuter, Paul-Georges; Javaud, Nicolas; Vicaut, Eric; Chevret, Sylvie

    2017-02-01

    Relationship between cardiopulmonary arrest and resuscitation (CPR) durations and survival after out-of-hospital cardiac arrest (OHCA) remain unclear. Our primary aim was to determine the association between survival without neurologic sequelae and cardiac arrest intervals in the setting of witnessed OHCA. We analyzed 27,301 non-traumatic, witnessed OHCA patients in France included in the national registry from June 1, 2011 through December 1, 2015. We analyzed cardiac arrest intervals, designated as no-flow (NF; from collapse to start of CPR) and low-flow (LF; from start of CPR to cessation of resuscitation) in relation to 30-day survival without sequelae. We determined the influence of recognized prognostic factors (age, gender, initial rhythm, location of cardiac arrest) on this relation. For the entire cohort, the area delimited by a value of NF greater than 12min (95% confidence interval: 11-13min) and LF greater than 33min (95% confidence interval: 29-45min), yielded a probability of 30-day survival of less than 1%. These sets of values were greatly influenced by initial cardiac arrest rhythm, age, sex and location of cardiac arrest. Extended CPR duration (greater than 40min) in the setting of initial shockable cardiac rhythm is associated with greater than 1% survival with NF less than 18min. The NF interval was highly influential on the LF interval regardless of outcome, whether return of spontaneous circulation (padvanced techniques. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Use of forces from instrumented Charpy V-notch testing to determine crack-arrest toughness

    International Nuclear Information System (INIS)

    Iskander, S.K.; Nanstad, R.K.; Sokolov, M.A.; McCabe, D.E.; Hutton, J.T.

    1996-06-01

    The objective of this investigation is an estimation of the crack-arrest toughness, particularly of irradiated materials, from voltage versus time output of an instrumented setup during a test on a Charpy V-notch (CVN) specimen. This voltage versus time trace (which can be converted to force versus displacement) displays events during fracture of the specimen. Various stages of the fracture process can be identified on the trace, including an arrest point indicating arrest of brittle fracture. The force at arrest, F a , versus test temperature, T, relationship is examined to explore possible relationships to other experimental measures of crack-arrest toughness such as the drop-weight nil-ductility temperature (NDT), or crack-arrest toughness, K a . For a wide range of weld and plate materials, the temperature at which F a = 2.45 kN correlates with NDT with a standard deviation, sigma, of about 11 K. Excluding the so-called low upper-shelf energy (USE) welds from the analysis resulted in F a = 4.12 kN and σ = 6.6 K. The estimates of the correlation of the temperature for F a = 7.4 kN with the temperature at 100-MPa√m level for a mean American Society of Mechanical Engineers (ASME) type K Ia curve through crack-arrest toughness values show that prediction of conservative values of K a are possible

  8. Induction of discrete apoptotic pathways by bromo-substituted indirubin derivatives in invasive breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Nicolaou, Katerina A. [Department of Biological Sciences, University of Cyprus, Nicosia (Cyprus); Liapis, Vasilis; Evdokiou, Andreas [Department of Surgery, Basil Hetzel Institute, Adelaide University, Adelaide (Australia); Constantinou, Constantina [St. George' s University of London Medical School at the University of Nicosia, Nicosia (Cyprus); Magiatis, Prokopios; Skaltsounis, Alex L. [Faculty of Pharmacy, University of Athens, Athens (Greece); Koumas, Laura; Costeas, Paul A. [Center for Study of Hematological Malignancies, Nicosia (Cyprus); Constantinou, Andreas I., E-mail: andreasc@ucy.ac.cy [Department of Biological Sciences, University of Cyprus, Nicosia (Cyprus)

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer The effects of 6BIO and 7BIO are evaluated against five breast cancer cell lines. Black-Right-Pointing-Pointer 6BIO induces a caspase dependent apoptotic effect via the intrinsic pathway. Black-Right-Pointing-Pointer 7BIO promotes G{sub 2}/M cells cycle arrest. Black-Right-Pointing-Pointer 7BIO triggers a caspase-8 mediated apoptotic pathway. Black-Right-Pointing-Pointer 7BIO triggers and a caspase independent pathway. -- Abstract: Indirubin derivatives gained interest in recent years for their anticancer and antimetastatic properties. The objective of the present study was to evaluate and compare the anticancer properties of the two novel bromo-substituted derivatives 6-bromoindirubin-3 Prime -oxime (6BIO) and 7-bromoindirubin-3 Prime -oxime (7BIO) in five different breast cancer cell lines. Cell viability assays identified that 6BIO and 7BIO are most effective in preventing the proliferation of the MDA-MB-231-TXSA breast cancer cell line from a total of five breast cancer cell lined examined. In addition it was found that the two compounds induce apoptosis via different mechanisms. 6BIO induces caspase-dependent programmed cell death through the intrinsic (mitochondrial) caspase-9 pathway. 7BIO up-regulates p21 and promotes G{sub 2}/M cell cycle arrest which is subsequently followed by the activation of two different apoptotic pathways: (a) a pathway that involves the upregulation of DR4/DR5 and activation of caspase-8 and (b) a caspase independent pathway. In conclusion, this study provides important insights regarding the molecular pathways leading to cell cycle arrest and apoptosis by two indirubin derivatives that can find clinical applications in targeted cancer therapeutics.

  9. Breast reconstruction after mastectomy

    Directory of Open Access Journals (Sweden)

    Daniel eSchmauss

    2016-01-01

    Full Text Available Breast cancer is the leading cause of cancer death in women worldwide. Its surgical approach has become less and less mutilating in the last decades. However, the overall number of breast reconstructions has significantly increased lately. Nowadays breast reconstruction should be individualized at its best, first of all taking into consideration oncological aspects of the tumor, neo-/adjuvant treatment and genetic predisposition, but also its timing (immediate versus delayed breast reconstruction, as well as the patient’s condition and wish. This article gives an overview over the various possibilities of breast reconstruction, including implant- and expander-based reconstruction, flap-based reconstruction (vascularized autologous tissue, the combination of implant and flap, reconstruction using non-vascularized autologous fat, as well as refinement surgery after breast reconstruction.

  10. Breast Cancer Screening

    International Nuclear Information System (INIS)

    Altaf, Fadwa J.

    2004-01-01

    Breast cancer is a very common health problem in Saudi females that can be reduced by early detection through introducing breast cancer screening. Literature review reveals significant reduction in breast cancer incidence and outcome after the beginning of breast cancer screening. The objectives of this article are to highlight the significance of breast cancer screening in different international societies and to write the major guidelines of breast cancer screening in relation to other departments involved with more emphasis on the Pathology Department guidelines in tissue handling, diagnostic criteria and significance of the diagnosis. This article summaries and acknowledges major work carried out before, and recommends similar modified work in order to meet the requirement for the Saudi society. (author)

  11. Secondary Breast Augmentation.

    Science.gov (United States)

    Brown, Mitchell H; Somogyi, Ron B; Aggarwal, Shagun

    2016-07-01

    After studying this article, the participant should be able to: 1. Assess common clinical problems in the secondary breast augmentation patient. 2. Describe a treatment plan to correct the most common complications of breast augmentation. 3. Provide surgical and nonsurgical options for managing complications of breast augmentation. 4. Decrease the incidence of future complications through accurate assessment, preoperative planning, and precise surgical technique. Breast augmentation has been increasing steadily in popularity over the past three decades. Many of these patients present with secondary problems or complications following their primary breast augmentation. Two of the most common complications are capsular contracture and implant malposition. Familiarity and comfort with the assessment and management of these complications is necessary for all plastic surgeons. An up-to-date understanding of current devices and techniques may decrease the need to manage future complications from the current cohort of breast augmentation patients.

  12. Module structure of interphotoreceptor retinoid-binding protein (IRBP may provide bases for its complex role in the visual cycle – structure/function study of Xenopus IRBP

    Directory of Open Access Journals (Sweden)

    Ghosh Debashis

    2007-08-01

    Full Text Available Abstract Background Interphotoreceptor retinoid-binding protein's (IRBP remarkable module structure may be critical to its role in mediating the transport of all-trans and 11-cis retinol, and 11-cis retinal between rods, cones, RPE and Müller cells during the visual cycle. We isolated cDNAs for Xenopus IRBP, and expressed and purified its individual modules, module combinations, and the full-length polypeptide. Binding of all-trans retinol, 11-cis retinal and 9-(9-anthroyloxy stearic acid were characterized by fluorescence spectroscopy monitoring ligand-fluorescence enhancement, quenching of endogenous protein fluorescence, and energy transfer. Finally, the X-ray crystal structure of module-2 was used to predict the location of the ligand-binding sites, and compare their structures among modules using homology modeling. Results The full-length Xenopus IRBP cDNA codes for a polypeptide of 1,197 amino acid residues beginning with a signal peptide followed by four homologous modules each ~300 amino acid residues in length. Modules 1 and 3 are more closely related to each other than either is to modules 2 and 4. Modules 1 and 4 are most similar to the N- and C-terminal modules of the two module IRBP of teleosts. Our data are consistent with the model that vertebrate IRBPs arose through two genetic duplication events, but that the middle two modules were lost during the evolution of the ray finned fish. The sequence of the expressed full-length IRBP was confirmed by liquid chromatography-tandem mass spectrometry. The recombinant full-length Xenopus IRBP bound all-trans retinol and 11-cis retinaldehyde at 3 to 4 sites with Kd's of 0.2 to 0.3 μM, and was active in protecting all-trans retinol from degradation. Module 2 showed selectivity for all-trans retinol over 11-cis retinaldehyde. The binding data are correlated to the results of docking of all-trans-retinol to the crystal structure of Xenopus module 2 suggesting two ligand-binding sites

  13. Scoulerine affects microtubule structure, inhibits proliferation, arrests cell cycle and thus culminates in the apoptotic death of cancer cells.

    Science.gov (United States)

    Habartova, Klara; Havelek, Radim; Seifrtova, Martina; Kralovec, Karel; Cahlikova, Lucie; Chlebek, Jakub; Cermakova, Eva; Mazankova, Nadezda; Marikova, Jana; Kunes, Jiri; Novakova, Lucie; Rezacova, Martina

    2018-03-19

    Scoulerine is an isoquinoline alkaloid, which indicated promising suppression of cancer cells growth. However, the mode of action (MOA) remained unclear. Cytotoxic and antiproliferative properties were determined in this study. Scoulerine reduces the mitochondrial dehydrogenases activity of the evaluated leukemic cells with IC 50 values ranging from 2.7 to 6.5 µM. The xCELLigence system revealed that scoulerine exerted potent antiproliferative activity in lung, ovarian and breast carcinoma cell lines. Jurkat and MOLT-4 leukemic cells treated with scoulerine were decreased in proliferation and viability. Scoulerine acted to inhibit proliferation through inducing G2 or M-phase cell cycle arrest, which correlates well with the observed breakdown of the microtubule network, increased Chk1 Ser345, Chk2 Thr68 and mitotic H3 Ser10 phosphorylation. Scoulerine was able to activate apoptosis, as determined by p53 upregulation, increase caspase activity, Annexin V and TUNEL labeling. Results highlight the potent antiproliferative and proapoptotic function of scoulerine in cancer cells caused by its ability to interfere with the microtubule elements of the cytoskeleton, checkpoint kinase signaling and p53 proteins. This is the first study of the mechanism of scoulerine at cellular and molecular level. Scoulerine is a potent antimitotic compound and that it merits further investigation as an anticancer drug.

  14. Oocyte transport: Developmental competence of bovine oocytes arrested at germinal vesicle stage by cycloheximide under air.

    Science.gov (United States)

    Hashimoto, Shu; Kimura, Kouji; Iwata, Hisataka; Takakura, Ryo

    2003-02-01

    The effects of the medium (TCM 199 or SOFaa) and temperature (20 or 39 C) during meiotic arrest by cycloheximide (CHX) under air on the developmental competence of bovine oocytes after in vitro maturation (IVM) and fertilization (IVF) were investigated. Oocytes were maintained in meiotic arrest by 10 microg/ml CHX in a 50-microl droplet of 25-mM HEPES-buffered TCM 199 (H199) at 39 C or synthetic oviduct fluid (HSOFaa) at 20 or 39 C in air for 24 h. After release from the arrest, the oocytes was matured and fertilized in vitro and their developmental competence was examined. The developmental rate of oocytes arrested in HSOFaa at 20 C to the blastocyst stage was similar to that of non-arrested oocytes but was significantly higher (Ptransport conditions, we also investigated the meiotic arrest of oocytes maintained in a 0.25-ml straw by CHX individually with 10 microl HSOFaa or as a group (40-50 oocytes) with 170-200 microl HSOFaa at 20 C in air for 24 h. After release from meiotic arrest, the developmental competence of these oocytes was assessed similarly. The developmental rate of oocytes treated with CHX individually was similar to that of those treated with CHX in 50-microl droplet of HSOFaa at 20 C. However, the developmental rate of oocytes treated with CHX as a group was lower than that of oocytes treated with CHX in a 50-microl droplet. Five blastocysts developed from oocytes maintained in meiotic arrest in a plastic straw were transferred to five recipient heifers. Consequently, three recipients became pregnant and 2 calves were delivered. The results of the present study indicate that bovine oocytes treated with CHX in HSOFaa at 20 C under air retain the same developmental competence as non-arrested oocytes.

  15. Mechanical versus manual chest compressions for cardiac arrest.

    Science.gov (United States)

    Brooks, Steven C; Hassan, Nizar; Bigham, Blair L; Morrison, Laurie J

    2014-02-27

    This is the first update of the Cochrane review on mechanical chest compression devices published in 2011 (Brooks 2011). Mechanical chest compression devices have been proposed to improve the effectiveness of cardiopulmonary resuscitation (CPR). To assess the effectiveness of mechanical chest compressions versus standard manual chest compressions with respect to neurologically intact survival in patients who suffer cardiac arrest. We searched the Cochrane Central Register of Controlled Studies (CENTRAL; 2013, Issue 12), MEDLINE Ovid (1946 to 2013 January Week 1), EMBASE (1980 to 2013 January Week 2), Science Citation abstracts (1960 to 18 November 2009), Science Citation Index-Expanded (SCI-EXPANDED) (1970 to 11 January 2013) on Thomson Reuters Web of Science, biotechnology and bioengineering abstracts (1982 to 18 November 2009), conference proceedings Citation Index-Science (CPCI-S) (1990 to 11 January 2013) and clinicaltrials.gov (2 August 2013). We applied no language restrictions. Experts in the field of mechanical chest compression devices and manufacturers were contacted. We included randomised controlled trials (RCTs), cluster RCTs and quasi-randomised studies comparing mechanical chest compressions versus manual chest compressions during CPR for patients with atraumatic cardiac arrest. Two review authors abstracted data independently; disagreement between review authors was resolved by consensus and by a third review author if consensus could not be reached. The methodologies of selected studies were evaluated by a single author for risk of bias. The primary outcome was survival to hospital discharge with good neurological outcome. We planned to use RevMan 5 (Version 5.2. The Nordic Cochrane Centre) and the DerSimonian & Laird method (random-effects model) to provide a pooled estimate for risk ratio (RR) with 95% confidence intervals (95% CIs), if data allowed. Two new studies were included in this update. Six trials in total, including data from 1166

  16. Identifying Breast Cancer Oncogenes

    Science.gov (United States)

    2011-10-01

    cells we observed that it promoted transformation of HMLE cells, suggesting a tumor suppressive role of Merlin in breast cancer (Figure 4B). A...08-1-0767 TITLE: Identifying Breast Cancer Oncogenes PRINCIPAL INVESTIGATOR: Yashaswi Shrestha...Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 W81XWH-08-1-0767 Identifying Breast Cancer Oncogenes Yashaswi Shrestha Dana-Farber

  17. Male breast lesions

    International Nuclear Information System (INIS)

    Matushita, J.P.K.; Andrade, L.G. de; Carregal, E.; Marimatsu, R.I.; Matushita, J.S.

    1989-01-01

    Roentgenographic examination of the male breast is an important aspect of the continued, intensive investigation of the radiologic morphology of the normal and diseased breast conducted in 17 cases examined at the Instituto Nacional do Cancer - RJ. It is purpose of this report to present the Roentgen appearance of various lesions of the male breast as they have been found in our practice and also to stress some of the difficulties in the differential diagnosis of these lesions. (author) [pt

  18. Herpesviruses and breast milk

    OpenAIRE

    C. Pietrasanta; B. Ghirardi; M.F. Manca; S. Uccella; C. Gualdi; E. Tota; L. Pugni; F. Mosca

    2014-01-01

    Breast milk has always been the best source of nourishment for newborns. However, breast milk can carry a risk of infection, as it can be contaminated with bacterial or viral pathogens. This paper reviews the risk of acquisition of varicella-zoster virus (VZV) and cytomegalovirus (CMV), herpesviruses frequently detected in breastfeeding mothers, via breast milk, focusing on the clinical consequences of this transmission and the possible strategies for preventing it. Maternal VZV infections ar...

  19. Xeroradiography of the breast

    International Nuclear Information System (INIS)

    Kalaf, J.M.

    1977-01-01

    Xeroradiography is a simple method of radiographic examination of the breast, it is readily interpreted, and with good technic xeroradiography can afford a more accurate identification of tumor calcifications and the periphery of the tumors. Xeroradiography of the breast must be faced as a complemental method and when associated with the informations of the medical history, the clinical examination and informations of other complemental methods will afford an effective evaluation of women with breast disease. (Author) [pt

  20. Poisson cluster analysis of cardiac arrest incidence in Columbus, Ohio.

    Science.gov (United States)

    Warden, Craig; Cudnik, Michael T; Sasson, Comilla; Schwartz, Greg; Semple, Hugh

    2012-01-01

    Scarce resources in disease prevention and emergency medical services (EMS) need to be focused on high-risk areas of out-of-hospital cardiac arrest (OHCA). Cluster analysis using geographic information systems (GISs) was used to find these high-risk areas and test potential predictive variables. This was a retrospective cohort analysis of EMS-treated adults with OHCAs occurring in Columbus, Ohio, from April 1, 2004, through March 31, 2009. The OHCAs were aggregated to census tracts and incidence rates were calculated based on their adult populations. Poisson cluster analysis determined significant clusters of high-risk census tracts. Both census tract-level and case-level characteristics were tested for association with high-risk areas by multivariate logistic regression. A total of 2,037 eligible OHCAs occurred within the city limits during the study period. The mean incidence rate was 0.85 OHCAs/1,000 population/year. There were five significant geographic clusters with 76 high-risk census tracts out of the total of 245 census tracts. In the case-level analysis, being in a high-risk cluster was associated with a slightly younger age (-3 years, adjusted odds ratio [OR] 0.99, 95% confidence interval [CI] 0.99-1.00), not being white, non-Hispanic (OR 0.54, 95% CI 0.45-0.64), cardiac arrest occurring at home (OR 1.53, 95% CI 1.23-1.71), and not receiving bystander cardiopulmonary resuscitation (CPR) (OR 0.77, 95% CI 0.62-0.96), but with higher survival to hospital discharge (OR 1.78, 95% CI 1.30-2.46). In the census tract-level analysis, high-risk census tracts were also associated with a slightly lower average age (-0.1 years, OR 1.14, 95% CI 1.06-1.22) and a lower proportion of white, non-Hispanic patients (-0.298, OR 0.04, 95% CI 0.01-0.19), but also a lower proportion of high-school graduates (-0.184, OR 0.00, 95% CI 0.00-0.00). This analysis identified high-risk census tracts and associated census tract-level and case-level characteristics that can be used to

  1. Breast cancer prevention.

    Science.gov (United States)

    Euhus, David M; Diaz, Jennifer

    2015-01-01

    Breast cancer is the most common cancer in women with 232,670 new cases estimated in the USA for 2014. Approaches for reducing breast cancer risk include lifestyle modification, chemoprevention, and prophylactic surgery. Lifestyle modification has a variety of health benefits with few associated risks and is appropriate for all women regardless of breast cancer risk. Chemoprevention options have expanded rapidly, but most are directed at estrogen receptor positive breast cancer and uptake is low. Prophylactic surgery introduces significant additional risks of its own and is generally reserved for the highest risk women. © 2014 Wiley Periodicals, Inc.

  2. Prevention of breast cancer.

    Science.gov (United States)

    Olver, Ian N

    2016-11-21

    Modifiable lifestyle factors may reduce the risk of developing breast cancer. Obesity is associated particularly with post-menopausal breast cancer. Diet is important, and exercise equivalent to running for up to 8 hours each week reduces the risk of breast cancer, both in its own right and through reducing obesity. Alcohol consumption may be responsible for 5.8% of breast cancers in Australia and it is recommended to reduce this to two standard drinks per day. Drinking alcohol and smoking increases the risk for breast cancer and, therefore, it is important to quit tobacco smoking. Prolonged use of combined oestrogen and progesterone hormone replacement therapy and oral contraceptives may increase breast cancer risk and this must be factored into individual decisions about their use. Ionising radiation, either from diagnostic or therapeutic radiation or through occupational exposure, is associated with a high incidence of breast cancer and exposure may be reduced in some cases. Tamoxifen chemoprevention may reduce the incidence of oestrogen receptor positive cancer in 51% of women with high risk of breast cancer. Uncommon but serious side effects include thromboembolism and uterine cancer. Raloxifene, which can also reduce osteoporosis, can be used in post-menopausal women and is not associated with the development of uterine cancer. Surgical prophylaxis with bilateral mastectomy and salpingo-oophorectomy can reduce the risk of breast cancer in patients carrying BRCA1 or BRCA2 mutations. For preventive treatments, mammographic screening can identify other women at high risk.

  3. Bilateral breast carcinoma

    International Nuclear Information System (INIS)

    Kim, Eung Jo; Oh, Ki Keun

    1990-01-01

    We evaluate 311 breast cancer patients admitted to Yong Dong Severance Hospital Between October 1st 1985 and July 31th 1989, and were able to obtain the following conclusions. 1) There were 14(4.5%) bilateral breast cancers among the 311 confirmed breast cancers. 2) Among the bilateral breast cancers, 5(31%) were synchronous and 9(69%) metachronous. 3) Average interval between the first and the second breast cancer in metachronous cancers was 3.8 year(1-15 years). 4) Bilateral breast cancer was most prevalent in the fifth decade (6/14) with the mean age of 47 years. 5) Film mammogram and sonomammogram showed findings of typical breast malignancies. There was no additional specific findings for each cancer in bilateral breast cancers which was different from unilateral cancers. Therefor, in the patients with unilateral breast cancer, possibility of the second lesion in the contralateral side must be considered and a close follow up observation should be done for at least 3 years

  4. Common ataxia telangiectasia mutated haplotypes and risk of breast cancer: a nested case–control study

    International Nuclear Information System (INIS)

    Tamimi, Rulla M; Hankinson, Susan E; Spiegelman, Donna; Kraft, Peter; Colditz, Graham A; Hunter, David J

    2004-01-01

    The ataxia telangiectasia mutated (ATM) gene is a tumor suppressor gene with functions in cell cycle arrest, apoptosis, and repair of DNA double-strand breaks. Based on family studies, women heterozygous for mutations in the ATM gene are reported to have a fourfold to fivefold increased risk of breast cancer compared with noncarriers of the mutations, although not all studies have confirmed this association. Haplotype analysis has been suggested as an efficient method for investigating the role of common variation in the ATM gene and breast cancer. Five biallelic haplotype tagging single nucleotide polymorphisms are estimated to capture 99% of the haplotype diversity in Caucasian populations. We conducted a nested case–control study of breast cancer within the Nurses' Health Study cohort to address the role of common ATM haplotypes and breast cancer. Cases and controls were genotyped for five haplotype tagging single nucleotide polymorphisms. Haplotypes were predicted for 1309 cases and 1761 controls for which genotype information was available. Six unique haplotypes were predicted in this study, five of which occur at a frequency of 5% or greater. The overall distribution of haplotypes was not significantly different between cases and controls (χ 2 = 3.43, five degrees of freedom, P = 0.63). There was no evidence that common haplotypes of ATM are associated with breast cancer risk. Extensive single nucleotide polymorphism detection using the entire genomic sequence of ATM will be necessary to rule out less common variation in ATM and sporadic breast cancer risk

  5. Molecular Modification of Metadherin/MTDH Impacts the Sensitivity of Breast Cancer to Doxorubicin.

    Directory of Open Access Journals (Sweden)

    Zhenchuan Song

    Full Text Available Breast cancer is a leading cause of death in women and with an increasing worldwide incidence. Doxorubicin, as a first-line anthracycline-based drug is conventional used on breast cancer clinical chemotherapy. However, the drug resistances limited the curative effect of the doxorubicin therapy in breast cancer patients, but the molecular mechanism determinants of breast cancer resistance to doxorubicin chemotherapy are not fully understood. In order to explore the association between metadherin (MTDH and doxorubicin sensitivity, the differential expressions of MTDH in breast cancer cell lines and the sensitivity to doxorubicin of breast cancer cell lines were investigated.The mRNA and protein expression of MTDH were determined by real-time PCR and Western blot in breast cancer cells such as MDA-MB-231, MCF-7, MDA-MB-435S, MCF-7/ADR cells. Once MTDH gene was knocked down by siRNA in MCF-7/ADR cells and overexpressed by MTDH plasmid transfection in MDA-MB-231 cells, the cell growth and therapeutic sensitivity of doxorubicin were evaluated using MTT and the Cell cycle assay and apoptosis rate was determined by flow cytometry.MCF-7/ADR cells revealed highly expressed MTDH and MDA-MB-231 cells had the lowest expression of MTDH. After MTDH gene was knocked down, the cell proliferation was inhibited, and the inhibitory rate of cell growth and apoptosis rate were enhanced, and the cell cycle arrest during the G0/G1 phase in the presence of doxorubicin treatment. On the other hand, the opposite results were observed in MDA-MB-231 cells with overexpressed MTDH gene.MTDH gene plays a promoting role in the proliferation of breast cancer cells and its high expression may be associated with doxorubicin sensitivity of breast cancer.

  6. Knockdown of Ran GTPase expression inhibits the proliferation and migration of breast cancer cells.

    Science.gov (United States)

    Sheng, Chenyi; Qiu, Jian; Wang, Yingying; He, Zhixian; Wang, Hua; Wang, Qingqing; Huang, Yeqing; Zhu, Lianxin; Shi, Feng; Chen, Yingying; Xiong, Shiyao; Xu, Zhen; Ni, Qichao

    2018-05-03

    Breast cancer is the second leading cause of cancer‑associated mortality in women worldwide. Strong evidence has suggested that Ran, which is a small GTP binding protein involved in the transport of RNA and protein across the nucleus, may be a key cellular protein involved in the metastatic progression of cancer. The present study investigated Ran gene expression in breast cancer tissue samples obtained from 140 patients who had undergone surgical resection for breast cancer. Western blot analysis of Ran in breast cancer tissues and paired adjacent normal tissues showed that expression of Ran was significantly increased in breast cancer tissues. Immunohistochemistry analyses conducted on formalin‑fixed paraffin‑embedded breast cancer tissue sections revealed that Ran expression was associated with tumor histological grade, nerve invasion and metastasis, vascular metastasis and Ki‑67 expression (a marker of cell proliferation). Kaplan‑Meier survival analysis showed that increased Ran expression in patients with breast cancer was positively associated with a poor survival prognosis. Furthermore, in vitro experiments demonstrated that highly migratory MDA‑MB‑231 cancer cells treated with Ran‑si‑RNA (si‑Ran), which knocked down expression of Ran, exhibited decreased motility in trans‑well migration and wound healing assays. Cell cycle analysis of Ran knocked down MDA‑MB‑231 cells implicated Ran in cell cycle arrest and the inhibition of proliferation. Furthermore, a starvation and re‑feeding (CCK‑8) assay was performed, which indicated that Ran regulated breast cancer cell proliferation. Taken together, the results provide strong in vitro evidence of the involvement of Ran in the progression of breast cancer and suggest that it could have high potential as a therapeutic target and/or marker of disease.

  7. Can vitamin A modify the activity of docetaxel in MCF-7 breast cancer cells?

    Directory of Open Access Journals (Sweden)

    Dorota Lemancewicz

    2008-04-01

    Full Text Available Docetaxel is one of the most effective chemotherapeutic agents in the treatment of breast cancer. On the other hand, the vitamin A family compounds play the essential roles in many biological processes in mammary gland. The aim of our study was to investigate the effect of all-trans retinol, carotenoids (beta-carotene, lycopene and retinoids (9-cis, 13-cis and all-trans retinoic acid on the activity of docetaxel and to compare these effects with the estradiol and tamoxifen actions on human ER(+ MCF-7 breast cancer cell line. The evaluation was based on [3H] thymidine incorporation and the proliferative activity of PCNA and Ki 67 positive cells. In our study, the incorporation of [3H] thymidine into cancer cells was inhibited to 50% by 0.2, 0.5 and 1 microM of docetaxel in the 24-hour culture and addition of estradiol (0.001 microM didn't influence the results. However, addition of tamoxifen caused a statistically significant decrease of the percentage of the proliferating cells in the culture medium with 0.2 and 0.5 microM of docetaxel (38.99 +/- 2.84%, p<0.01 and 40.67 +/- 5.62%, p<0.01 in comparison to the docetaxel only group. The above-mentioned observations were also confirmed with the use of the immunohistochemical investigations. Among the examined vitamin A family compounds, the simultaneous application of beta-carotene (0.1 microM and docetaxel (0.2 microM resulted in a statistically significant reduction in the percentage of proliferating cells (40.25 +/- 14.62%, p<0.01. Lycopene (0.1 microM, which stimulates the growth of breast cancer cells in a 24-hour culture, had an inhibitory effect (42.97 +/- 9.58%, p<0.01 when combined with docetaxel (0.2 microM. Although, beta-carotene and lycopene belong to the different chemical groups, they surprisingly had a similar inhibitory influence on both growth and proliferation of MCF-7 breast cancer cells when combined with docetaxel. The application of docetaxel either with beta-carotene or

  8. Potentiation of radiosensitivity by tetrandrine in human breast cancer cells and its mechanism

    International Nuclear Information System (INIS)

    Sun Xinchen; Zhen Yongsu; Shao Rongguang; Wang Junjie

    2003-01-01

    Objective: To investigate the potentiation of radiosensitivity and mechanism by tetrandrine (Tet) in human breast cancer p53-mutant MCF-7/ADR and p53-wt MCF-7 cells. Methods: Clonogenic assay, flow cytometry, Western blotting were preformed in this experiment. Results: The data of clonogenic assay showed that Tet markedly sensitized MCF-7/ADR cell to X-rays, and the sensitization enhancement ratio (SER) of Tet was 1.51. Flow cytometry assay showed that exposure of MCF-7/ADR cells to X-rays caused cells to arrest in G 2 phase, whereas Tet was able to lower the number of cells arrested in G 2 phase. However, in MCF-7 cells, the potentiation effect of Tet was lower, and its SER was 1.10. MCF-7 cells were induced to arrest in G 1 and G 2 phases by X-rays, and the number of cells arrested in G 2 phase abrogated by Tet was less than that in MCF-7/ADR cells. Furthermore, the results showed that the levels of Cyclin B1 and Cdc2 expression decreased after X-irradiation, and the mitotic index was lower too. Tet could reverse this decrease and induce X-ray-irradiated cells to enter mitosis. Conclusion: Tet is a potent G 2 checkpoint abrogator and markedly enhances the cytotoxicity of X irradiation in the p53-mutant cancer cells

  9. MicroRNA-139 suppresses proliferation in luminal type breast cancer cells by targeting Topoisomerase II alpha

    Energy Technology Data Exchange (ETDEWEB)

    Hua, Wei [Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Sa, Ke-Di; Zhang, Xiang; Jia, Lin-Tao; Zhao, Jing [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Yang, An-Gang [State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi' an (China); Zhang, Rui, E-mail: ruizhang@fmmu.edu.cn [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Fan, Jing, E-mail: jingfan@fmmu.edu.cn [Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Bian, Ka, E-mail: kakamax85@hotmail.com [State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi' an (China); Department of Otolaryngology, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China)

    2015-08-07

    The classification of molecular subtypes of breast cancer improves the prognostic accuracy and therapeutic benefits in clinic. However, because of the complexity of breast cancer, more biomarkers and functional molecules need to be explored. Here, analyzing the data in a huge cohort of breast cancer patients, we found that Topoisomerase II alpha (TOP2a), an important target of chemotherapy is a biomarker for prognosis in luminal type breast cancer patients, but not in basal like or HER2 positive breast cancer patients. We identified that miR-139, a previous reported anti-metastatic microRNA targets 3’-untranslated region (3′UTR) of TOP2a mRNA. Further more, we revealed that the forced expression of miR-139 reduces the TOP2a expression at both mRNA and protein levels. And our functional experiments showed that the ectopic expression of miR-139 remarkably inhibits proliferation in luminal type breast cancer cells, while exogenous TOP2a expression could rescue inhibition of cell proliferation mediated by miR-139. Collectively, our present study demonstrates the miR-139-TOP2a regulatory axis is important for proliferation in luminal type breast cancer cells. This functional link may help us to further understand the specificity of subtypes of breast cancer and optimize the strategy of cancer treatment. - Highlights: • High levels of TOP2a expression are closely associated with poor prognosis in luminal type breast cancer patients. • TOP2a is a novel target of miR-139. • Overexpression of miR-139 inhibits proliferation in luminal type breast cancer cells. • TOP2a is essential for miR-139-induced growth arrest in luminal type breast cancer cells.

  10. Activation of SNAT1/SLC38A1 in human breast cancer: correlation with p-Akt overexpression

    International Nuclear Information System (INIS)

    Wang, Kuo; Cao, Fang; Fang, Wenzheng; Hu, Yongwei; Chen, Ying; Ding, Houzhong; Yu, Guanzhen

    2013-01-01

    SNAT1 is a subtype of the amino acid transport system A that has been implicated to play a potential role in cancer development and progression, yet its role in breast cancer remains unclear. In present study, we detected SNAT1 expression in breast cancers and explored its underlying mechanism in promoting breast carcinogenesis. RT-PCR and Western blotting were performed to analyze the transcription and protein levels of SNAT1 in breast cancer cell lines and fresh tissues. Tissue microarray blocks containing breast cancer specimens obtained from 210 patients were constructed. Expression of SNAT1 in these specimens was analyzed using immunohistochemical studies. SNAT1 was down-regulated by SNAT1-shRNA in breast cancer cells and the functional significance was measured. SNAT1 was up-regulated in breast cancer cell lines and breast cancer tissues. Overexpression of SNAT1 was observed in 127 cases (60.5%). Expression of SNAT1 was significantly associated with tumor size, nodal metastasis, advanced disease stage, Ki-67, and ER status. Suppression of endogenous SNAT1 leads to cell growth inhibition, cell cycle arrest, and apoptosis of 4T1 cells and lowered the phosphorylation level of Akt. SNAT1 expression correlated significantly with p-Akt expression in human breast cancer samples. The cross-talk between Akt signaling and SNAT1 might play a critical role in the development and progression of breast cancer, providing an important molecular basis for novel diagnostic markers and new attractive targets in the treatment of breast cancer patients

  11. MicroRNA-139 suppresses proliferation in luminal type breast cancer cells by targeting Topoisomerase II alpha

    International Nuclear Information System (INIS)

    Hua, Wei; Sa, Ke-Di; Zhang, Xiang; Jia, Lin-Tao; Zhao, Jing; Yang, An-Gang; Zhang, Rui; Fan, Jing; Bian, Ka

    2015-01-01

    The classification of molecular subtypes of breast cancer improves the prognostic accuracy and therapeutic benefits in clinic. However, because of the complexity of breast cancer, more biomarkers and functional molecules need to be explored. Here, analyzing the data in a huge cohort of breast cancer patients, we found that Topoisomerase II alpha (TOP2a), an important target of chemotherapy is a biomarker for prognosis in luminal type breast cancer patients, but not in basal like or HER2 positive breast cancer patients. We identified that miR-139, a previous reported anti-metastatic microRNA targets 3’-untranslated region (3′UTR) of TOP2a mRNA. Further more, we revealed that the forced expression of miR-139 reduces the TOP2a expression at both mRNA and protein levels. And our functional experiments showed that the ectopic expression of miR-139 remarkably inhibits proliferation in luminal type breast cancer cells, while exogenous TOP2a expression could rescue inhibition of cell proliferation mediated by miR-139. Collectively, our present study demonstrates the miR-139-TOP2a regulatory axis is important for proliferation in luminal type breast cancer cells. This functional link may help us to further understand the specificity of subtypes of breast cancer and optimize the strategy of cancer treatment. - Highlights: • High levels of TOP2a expression are closely associated with poor prognosis in luminal type breast cancer patients. • TOP2a is a novel target of miR-139. • Overexpression of miR-139 inhibits proliferation in luminal type breast cancer cells. • TOP2a is essential for miR-139-induced growth arrest in luminal type breast cancer cells

  12. The perception of children of elementary education about cardiorespiratory arrest

    Directory of Open Access Journals (Sweden)

    Mariélli Terassi

    2015-03-01

    Full Text Available Cardiorespiratory arrest (CRA is a serious situation that occurs frequently in public environments, which makes assistance training of the general population of great importance. The objective was to understand the perception of children on CRA. Qualitative research conducted with children 8-10 years old enrolled in a private elementary school with a constructive proposal. Data collection occurred between the months of October and November 2013 in a recorded collective interview. As a criterion for inclusion students should be enrolled in the institution and accept to participate in the research with the consent of a guardian. Thirty children participated in the study. The students were divided into four groups: 5th year, 4th year, 3rd year A and 3rd year B, with an average of 08 students per group. The interviews were analyzed using the Bardin content analysis methodology. From the speeches, two categories emerged: Child's prior knowledge on CRA and how to act on the event of a CRA. Children associate the event of sudden CRA to a condition in which the heart and/or lungs suddenly stop acting. Seeking emergency assistance was reported as one of the main actions to be taken if a person is unconscious. It was observed that the 5th graders had best prior knowledge about the topic CRA when compared to students in the 3rd year. The thematic approach of CRA in schools contributes to the exchange of experiences, awareness of children and building new knowledge-oriented health education.

  13. Patterns of premature physeal arrest: MR imaging of 111 children.

    Science.gov (United States)

    Ecklund, Kirsten; Jaramillo, Diego

    2002-04-01

    The purpose of this study was to use MR imaging, especially fat-suppressed three-dimensional (3D) spoiled gradient-recalled echo sequences, to identify patterns of growth arrest after physeal insult in children. We evaluated 111 children with physeal bone bridges (median age, 11.4 years) using MR imaging to analyze bridge size, location in physis, signal intensity, growth recovery lines, avascular necrosis, and metaphyseal cartilage tongues. Fifty-eight patients underwent fat-suppressed 3D spoiled gradient-recalled echo imaging with physeal mapping. The cause, bone involved, radiographic appearance, and surgical interventions (60/111) were also correlated. Data were analyzed with the two-tailed Fisher's exact test. Posttraumatic bridges, accounting for 70% (78/111) of patients, were most often distal, especially of the tibia (n = 43) and femur (n = 14), whereas those due to the other miscellaneous causes were more frequently proximal (p children is most often posttraumatic and disproportionately involves the distal tibia and femur where bridges tend to develop at the sites of earliest physiologic closure, namely anteromedially and centrally, respectively. MR imaging, especially with the use of fat-suppressed 3D spoiled gradient-recalled echo imaging, exquisitely shows the growth disturbance and associated abnormalities that may follow physeal injury and guides surgical management.

  14. Cardiac Arrest After Status Epilepticus: Bupropion and Ecstasy Intoxication

    Directory of Open Access Journals (Sweden)

    Zübeyde Tuba Duran

    2018-04-01

    Full Text Available Bupropion is a monocyclic antidepressant that has been known to cause seizures in high therapeutic doses or acute high doses. Bupropion is a selective norepinephrine, dopamine and minimally serotonin reuptake inhibitor. Overdose of bupropion may lead to recurrent seizures, hypoxia and death. It is important to be aware in terms of bradycardia-asystole as a significant consequence of seizure and hypoxia. Patients using high dose of bupropion should be closely monitored in terms of cardiological and neurological. In this study, we presented a 19 year-old female patient who did not have previous history of epilepsy but who used oral bupropion to reduce nicotine addiction. A status epilepticus and cardiac arrest developed in a case receiving 1,8 g bupropion for suicide. 3.4-methylenedioxy-N-methylamphetamine (MDMA and benzodiazepine were detected in urine sample. We did not find any cases in the literature related to MDMA and bupropion overdose. Therefore, we presented this rare case.

  15. Prehospital traumatic cardiac arrest: the cost of futility.

    Science.gov (United States)

    Rosemurgy, A S; Norris, P A; Olson, S M; Hurst, J M; Albrink, M H

    1993-09-01

    Of 12,462 trauma patients cared for by prehospital services from October 1, 1989 to March 31, 1991, 138 patients underwent CPR at the scene or during transport because of the absence of blood pressure, pulse, and respiration. Ninety-six (70%) suffered blunt trauma, 42 (30%) suffered penetrating trauma. Sixty (43%) were transported by air utilizing county-wide transport protocols. None of the patients survived. Aggregate care cost $871,186.00. In 11 cases (8%), tissue for transplantation was procured (only corneas). Trauma patients who require CPR at the scene or in transport die. Infrequent organ procurement does not seem to justify the cost (primarily borne by hospitals), consumption of resources, and exposure of health care providers to occupational health hazards. The wisdom of transporting trauma victims suffering cardiopulmonary arrest at the scene or during transport must be questioned. Allocation of resources to these patients is not an insular medical issue, but a broad concern for our society, and society should decide if the "cost of futility" is excessive.

  16. Early prognostication markers in cardiac arrest patients treated with hypothermia.

    Science.gov (United States)

    Karapetkova, M; Koenig, M A; Jia, X

    2016-03-01

    Established prognostication markers, such as clinical findings, electroencephalography (EEG) and biochemical markers, used by clinicians to predict neurological outcome after cardiac arrest (CA) are altered under therapeutic hypothermia (TH) conditions and their validity remains uncertain. MEDLINE and Embase were searched for evidence on the current standards for neurological outcome prediction for out-of-hospital CA patients treated with TH and the validity of a wide range of prognostication markers. Relevant studies that suggested one or several established biomarkers and multimodal approaches for prognostication are included and reviewed. Whilst the prognostic accuracy of various tests after TH has been questioned, pupillary light reflexes and somatosensory evoked potentials are still strongly associated with negative outcome for early prognostication. Increasingly, EEG background activity has also been identified as a valid predictor for outcome after 72 h after CA and a preferred prognostic method in clinical settings. Neuroimaging techniques, such as magnetic resonance imaging and computed tomography, can identify functional and structural brain injury but are not readily available at the patient's bedside because of limited availability and high costs. A multimodal algorithm composed of neurological examination, EEG-based quantitative testing and somatosensory evoked potentials, in conjunction with newer magnetic resonance imaging sequences, if available, holds promise for accurate prognostication in CA patients treated with TH. In order to avoid premature withdrawal of care, prognostication should be performed more than 72 h after CA. © 2015 EAN.

  17. DNA damage mediated transcription arrest: Step back to go forward.

    Science.gov (United States)

    Mullenders, Leon

    2015-12-01

    The disturbance of DNA helix conformation by bulky DNA damage poses hindrance to transcription elongating due to stalling of RNA polymerase at transcription blocking lesions. Stalling of RNA polymerase provokes the formation of R-loops, i.e. the formation of a DNA-RNA hybrid and a displaced single stranded DNA strand as well as displacement of spliceosomes. R-loops are processed into DNA single and double strand breaks by NER factors depending on TC-NER factors leading to genome instability. Moreover, stalling of RNA polymerase induces a strong signal for cell cycle arrest and apoptosis. These toxic and mutagenic effects are counteracted by a rapid recruitment of DNA repair proteins to perform transcription coupled nucleotide excision repair (TC-NER) to remove the blocking DNA lesions and to restore transcription. Recent studies have highlighted the role of backtracking of RNA polymerase to facilitate TC-NER and identified novel factors that play key roles in TC-NER and in restoration of transcription. On the molecular level these factors facilitate stability of the repair complex by promotion and regulation of various post-translational modifications of NER factors and chromatin substrate. In addition, the continuous flow of new factors that emerge from screening assays hints to several regulatory levels to safeguard the integrity of transcription elongation after disturbance by DNA damage that have yet to be explored. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Adrenaline in cardiac arrest: Prefilled syringes are faster.

    Science.gov (United States)

    Helm, Claire; Gillett, Mark

    2015-08-01

    Standard ampoules and prefilled syringes of adrenaline are widely available in Australasian EDs for use in cardiac arrest. We hypothesise that prefilled syringes can be administered more rapidly and accurately when compared with the two available standard ampoules. This is a triple arm superiority study comparing the time to i.v. administration and accuracy of dosing of three currently available preparations of adrenaline. In their standard packaging, prefilled syringes were on average more than 12 s faster to administer than the 1 mL 1:1000 ampoules and more than 16 s faster than the 10 mL 1:10,000 ampoules (P adrenaline utilising a Minijet (CSL Limited, Parkville, Victoria, Australia) is faster than using adrenaline in glass ampoules presented in their plastic packaging. Removing the plastic packaging from the 1 mL (1 mg) ampoule might result in more rapid administration similar to the Minijet. Resuscitation personnel requiring rapid access to adrenaline should consider storing it as either Minijets or ampoules devoid of packaging. These results might be extrapolatable to other clinical scenarios, including pre-hospital and anaesthesia, where other drugs are required for rapid use. © 2015 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

  19. Risk for Arrest: The Role of Social Bonds in Protecting Foster Youth Making the Transition to Adulthood

    Science.gov (United States)

    Cusick, Gretchen Ruth; Havlicek, Judy R.; Courtney, Mark E.

    2012-01-01

    This study examines a sample of foster youth at the onset of the transition to adulthood and explores how social bonds are related to the risk of arrest during adulthood. Drawing from official arrest records, event history models are used to examine the time to arrest. Because individuals may be at risk for different types of crime, competing risk regression models are used to distinguish among arrests for drug-related, nonviolent, or violent crimes. Between the ages of 17–18 and 24, 46% of former foster youth experience an arrest. Arrests were evenly distributed across drug, nonviolent, and violent crimes columns. Although findings fail to support the significance of social bonds to interpersonal domains, bonds to employment and education are associated with a lower risk for arrest. Child welfare policy and practice implications for building connections and protections around foster youth are discussed. PMID:22239390

  20. Breast Cancer Immunotherapy

    Institute of Scientific and Technical Information of China (English)

    Juhua Zhou; Yin Zhong

    2004-01-01

    Breast cancer is a leading cause of cancer-related deaths in women worldwide. Although tumorectomy,radiotherapy, chemotherapy and hormone replacement therapy have been used for the treatment of breast cancer, there is no effective therapy for patients with invasive and metastatic breast cancer. Immunotherapy may be proved effective in treating patients with advanced breast cancer. Breast cancer immunotherapy includes antibody based immunotherapy, cancer vaccine immunotherapy, adoptive T cell transfer immunotherapy and T cell receptor gene transfer immunotherapy. Antibody based immunotherapy such as the monoclonal antibody against HER-2/neu (trastuzumab) is successfully used in the treatment of breast cancer patients with over-expressed HER-2/neu, however, HER-2/neu is over-expressed only in 25-30% of breast cancer patients. Cancer vaccine immunotherapy is a promising method to treat cancer patients. Cancer vaccines can be used to induce specific anti-tumor immunity in breast cancer patients, but cannot induce objective tumor regression. Adoptive T cell transfer immunotherapy is an effective method in the treatment of melanoma patients. Recent advances in anti-tumor T cell generation ex vivo and limited clinical trial data have made the feasibility of adoptive T cell transfer immunotherapy in the treatment of breast cancer patients. T cell receptor gene transfer can redirect the specificity of T cells. Chimeric receptor, scFv(anti-HER-2/neu)/zeta receptor, was successfully used to redirect cytotoxic T lymphocyte hybridoma cells to obtain anti-HER-2/neu positive tumor cells, suggesting the feasibility of treatment of breast cancer patients with T cell receptor gene transfer immunotherapy. Clinical trials will approve that immunotherapy is an effective method to cure breast cancer disease in the near future.