Value of amniotic fluid IL-8 and Annexin A2 in prediction of preterm delivery in preterm labor and preterm premature rupture of membranes.

Science.gov (United States)

Jia, Xiaohui

2014-01-01

To investigate the clinical significance and value in the prediction of preterm delivery of combined amniotic fluid IL-8 and Annexin A2 levels in preterm premature rupture of membranes (PPROM) and preterm labor (PTL). Sixty pregnant women at < 32 gestational weeks who developed PTL were divided into a PPROM group and a non-PPROM group. Ten normal pregnant women served as a control group. IL-8 and Annexin A2 levels were measured in amniotic fluid samples from each patient. Amniotic fluid IL-8 and Annexin-A2 levels in PTL (PPROM and non-PPROM groups) were significantly higher than those of the controls (p < 0.05). The PPROM group displayed higher amniotic fluid Annexin-A2 levels than did the non-PPROM group, with a statistically significant difference (p < 0.05). The PPROM group showed higher amniotic fluid IL-8 levels than did the non-PPROM group; however, this was statistically insignificant (p = 0.56). Combined detection of amniotic fluid IL-8 and Annexin-A2 in the prediction of preterm delivery within 2 weeks of measurement showed sensitivity of 81.25%, specificity of 88.89% and PPV of 92.86%. Amniotic fluid IL-8 and Annexin-A2 levels are associated with the occurrence of PPROM and PTL. Combined detection of IL-8 and Annexin-A2 levels in identifying preterm delivery within 2 weeks in PTL and PPROM is of possible clinical and predictive value.

18F-labelled annexin V: a PET tracer for apoptosis imaging

International Nuclear Information System (INIS)

Murakami, Yoshihiro; Tatsumi, Mitsuyoshi; Ichise, Rikiya; Nishimura, Shintaro; Takamatsu, Hiroyuki; Noda, Akihiro; Taki, Junichi; Tait, Jonathan F.

2004-01-01

Annexin V can be used to detect apoptotic cells in vitro and in vivo, based on its ability to identify extracellular phosphatidylserine, which arises during apoptosis. In the present study, we examined the synthesis of fluorine-18 labelled annexin V as a positron emission tomography tracer for apoptosis imaging. The distribution of [ 18 F]annexin V and technetium-99m labelled annexin V, a well-characterised SPET tracer for apoptosis imaging, was compared. [ 18 F]annexin V was synthesised using N-succinimidyl 4-[ 18 F]fluorobenzoate as an 18 F labelling reagent. Synthesised and purified [ 18 F]annexin V was confirmed by SDS-PAGE. In an ex vivo imaging experiment, [ 18 F]annexin V was intravenously injected into rats 24 h after the induction of myocardial ischaemia, and accumulation in the left ventricle was examined. [ 18 F]annexin V accumulated in the infarct area of the left ventricle, where apoptotic cells were observed. In separate experiments, [ 18 F]annexin V or [ 99m Tc]annexin V was intravenously injected into ischaemic or normal animals, and the distribution of the tracers was compared. In ischaemic animals, accumulation of [ 18 F]annexin V and [ 99m Tc]annexin V in the infarct area was about threefold higher than in the non-infarct area. Furthermore, the ratio of accumulation in the normal heart to the blood radioactivity was not significantly different between the tracers. In normal animals, however, the uptake of [ 18 F]annexin V in the liver, spleen and kidney was much lower than that of [ 99m Tc]annexin V. The low uptake of [ 18 F]annexin V in these organs might represent an advantage over [ 99m Tc]annexin V. (orig.)

Development and evaluation of a novel (99mtc-labeled annexin A5 for early detection of response to chemotherapy.

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Kazuma Ogawa

Full Text Available (99mTc-HYNIC-annexin A5 can be considered as a benchmark in the field of apoptosis imaging. However, (99mTc-HYNIC-annexin A5 has characteristics of high uptake and long retention in non-target tissues such as kidney and liver. To minimize this problem, we developed a novel (99mTc-labeled annexin A5 using a bis(hydroxamamide derivative [C3(BHam2] as a bifunctional chelating agent, and evaluated its usefulness as an imaging agent for detecting apoptosis. The amino group of C3(BHam2 was converted to a maleimide group, and was coupled to thiol groups of annexin A5 pretreated with 2-iminothiolane. (99mTc labeling was performed by a ligand exchange reaction with (99mTc-glucoheptonate. Biodistribution experiments for both (99mTc-C3(BHam2-annexin A5 and (99mTc-HYNIC-annexin A5 were performed in normal mice. In addition, in tumor-bearing mice, the relationship between the therapeutic effects of chemotherapy (5-FU and the tumor accumulation of (99mTc-C3(BHam2-annexin A5 just after the first treatment of 5-FU was evaluated. (99mTc-C3(BHam2-annexin A5 was prepared with a radiochemical purity of over 95%. In biodistribution experiments, (99mTc-C3(BHam2-annexin A5 had a much lower kidney accumulation of radioactivity than (99mTc-HYNIC-annexin A5. In the organs for metabolism, such as liver and kidney, radioactivity after the injection of (99mTc-HYNIC-annexin A5 was residual for a long time. On the other hand, radioactivity after the injection of (99mTc-C3(BHam2-annexin A5 gradually decreased. In therapeutic experiments, tumor growth in the mice treated with 5-FU was significantly inhibited. Accumulation of (99mTc-C3(BHam2-annexin A5 in tumors significantly increased after 5-FU treatment. The accumulation of radioactivity in tumor correlated positively with the counts of TUNEL-positive cells. These findings suggest that (99mTc-C3(BHam2-annexin A5 may contribute to the efficient detection of apoptotic tumor response after chemotherapy.

Annexin A4 and A6 induce membrane curvature and constriction during cell membrane repair

DEFF Research Database (Denmark)

Boye, Theresa Louise; Maeda, Kenji; Pezeshkian, Weria

2017-01-01

Efficient cell membrane repair mechanisms are essential for maintaining membrane integrity and thus for cell life. Here we show that the Ca2+- and phospholipid-binding proteins annexin A4 and A6 are involved in plasma membrane repair and needed for rapid closure of micron-size holes. We demonstrate...... that annexin A4 binds to artificial membranes and generates curvature force initiated from free edges, whereas annexin A6 induces constriction force. In cells, plasma membrane injury and Ca2+ influx recruit annexin A4 to the vicinity of membrane wound edges where its homo-trimerization leads to membrane...... that induction of curvature force around wound edges is an early key event in cell membrane repair....

Annexin A1 is elevated in patients with COPD and affects lung fibroblast function

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Lai TW

2018-02-01

Full Text Available Tianwen Lai,1,* Yanyu Li,1,* Zongjiong Mai,2 Xiaoxia Wen,1 Yingying Lv,1 Zhanqing Xie,3 Quanchao Lv,1 Min Chen,1 Dong Wu,1 Bin Wu1 1Department of Respiratory and Critical Care Medicine, 2Department of Oncology, 3Department of Thoracic Surgery, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China *These authors contributed equally to this work Purpose: Fibrosis in peripheral airways is responsible for airflow limitation in chronic obstructive pulmonary disease (COPD. Annexin A1 modulates several key biological events during inflammation. However, little is known about its role in airway fibrosis in COPD. We investigated whether levels of Annexin A1 were upregulated in patients with COPD, and whether it promoted airway fibrosis.Methods: We quantified serum Annexin A1 levels in never-smokers (n=12, smokers without COPD (n=11, and smokers with COPD (n=22. Correlations between Annexin A1 expression and clinical indicators (eg, lung function were assessed. In vitro, human bronchial epithelial (HBE cells were exposed to cigarette smoke extract (CSE and Annexin A1 expression was assessed. Primary human lung fibroblasts were isolated from patients with COPD and effects of Annexin A1 on fibrotic deposition of lung fibroblasts were evaluated.Results: Serum Annexin A1 was significantly higher in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD guidelines stage III or IV than in those with GOLD stages I or II (12.8±0.8 ng/mL versus 9.8±0.7 ng/mL; p=0.016. Annexin A1 expression was negatively associated with airflow obstruction (forced expiratory volume in one second % predicted; r=−0.72, p<0.001. In vitro, Annexin A1 was significantly increased in CSE-exposed HBE cells in a time- and concentration-dependent manner. Annexin A1 promoted lung fibroblasts proliferation, migration, differentiation, and collagen deposition via the ERK1/2 and p38 mitogen-activated protein kinase pathways

Annexin-Phospholipid Interactions. Functional Implications

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Javier Turnay

2013-01-01

Full Text Available Annexins constitute an evolutionary conserved multigene protein superfamily characterized by their ability to interact with biological membranes in a calcium dependent manner. They are expressed by all living organisms with the exception of certain unicellular organisms. The vertebrate annexin core is composed of four (eight in annexin A6 homologous domains of around 70 amino acids, with the overall shape of a slightly bent ring surrounding a central hydrophilic pore. Calcium- and phospholipid-binding sites are located on the convex side while the N-terminus links domains I and IV on the concave side. The N-terminus region shows great variability in length and amino acid sequence and it greatly influences protein stability and specific functions of annexins. These proteins interact mainly with acidic phospholipids, such as phosphatidylserine, but differences are found regarding their affinity for lipids and calcium requirements for the interaction. Annexins are involved in a wide range of intra- and extracellular biological processes in vitro, most of them directly related with the conserved ability to bind to phospholipid bilayers: membrane trafficking, membrane-cytoskeleton anchorage, ion channel activity and regulation, as well as antiinflammatory and anticoagulant activities. However, the in vivo physiological functions of annexins are just beginning to be established.

Annexin A2 Mediates the Localization of Measles Virus Matrix Protein at the Plasma Membrane.

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Koga, Ritsuko; Kubota, Marie; Hashiguchi, Takao; Yanagi, Yusuke; Ohno, Shinji

2018-02-28

Annexins are a family of structurally related proteins that bind negatively charged membrane phospholipids in a Ca 2+ -dependent manner. Annexin A2 (AnxA2), a member of the family, has been implicated in a variety of cellular functions including the organization of membrane domains, vesicular trafficking and cell-cell adhesion. AnxA2 generally forms the heterotetrameric complex with a small Ca 2+ -binding protein S100A10. Measles virus (MV), a member of the family Paramyxoviridae , is an enveloped virus with a nonsegmented negative strand RNA genome. Knockdown of AnxA2 greatly reduced MV growth in cells, without affecting its entry and viral RNA production. In MV-infected, AnxA2-knockdown cells, the expression level of the matrix (M) protein, but not other viral proteins, was reduced compared with that in control cells, and the distribution of the M protein at the plasma membrane was decreased. The M protein lines the inner surface of the envelope and plays an important role in virus assembly by connecting the nucleocapsid to the envelope proteins. The M protein bound to AnxA2 independently of AnxA2's phosphorylation or its association with S100A10, and was co-localized with AnxA2 within cells. Truncation of the N-terminal 10 amino acid residues, but not the N-terminal 5 residues, compromised the ability of the M protein to interact with AnxA2 and localize at the plasma membrane. These results indicate that AnxA2 mediates the localization of the MV M protein at the plasma membrane by interacting with its N-terminal region (especially residues at positions 6-10), thereby aiding in MV assembly. IMPORTANCE Measles virus (MV) is an important human pathogen, still claiming ∼ 100,000 lives per year despite the presence of effective vaccines, and causes occasional outbreaks even in developed countries. Replication of viruses largely relies on the functions of host cells. Our study revealed that the reduction of the host protein annexin A2 compromises the replication of

"Nonclassical" secretion of annexin A2 to the lumenal side of the enterocyte brush border membrane

DEFF Research Database (Denmark)

Danielsen, E Michael; van Deurs, Bo; Hansen, Gert H

2003-01-01

side of the microvilli, showing an apical secretion by a "nonclassical" mechanism. In addition, annexin A2 was associated with surface-connected, deep apical tubules in the apical terminal web region and with an underlying pleiomorphic, tubulo-vesicular compartment (subapical compartment...

Distribution of 99Tcm-rh-Annexin vin tumor and expression relationship of bcl-2, bax after a single dose of chemotherapy

International Nuclear Information System (INIS)

Zhang Xin; Li Yaming; Zhang Yanjun; Tao Li; Zhu Yi; Yang Chun; Ji Xiaopeng; Zhao Ming; Tian Aijuan; Zhang Jianying; Zhao Zhenzhen

2007-01-01

The expression of bcl-2 and bax after the single dose of chemotherapy with 99 Tc m -rh-Annexin V as the tracer of tumor apoptosis imaging is studied. tumor cell apoptosis is examined by TUNEL methods, and the expression of bcl-2 and bax in tumor are determined by immunohistochemical methods. Single dose of chemotherapy significantly increased the tumor uptake of 99 Tc m -rh-annexin V and the positive number of TUNEL, as well as the expression of bax (P 99 Tc m -rh-annexin V in tumor reflectes not only the degree of apoptosis of tumor cells, but also the change of bax expression after the single dose of chemotherapy. (authors)

Role of annexin A5 in cisplatin-induced toxicity in renal cells: molecular mechanism of apoptosis.

Science.gov (United States)

Jeong, Jin-Joo; Park, Nahee; Kwon, Yeo-Jung; Ye, Dong-Jin; Moon, Aree; Chun, Young-Jin

2014-01-24

Annexin A5 belongs to a large family of calcium-binding and phospholipid-binding proteins and may act as an endogenous regulator of various pathophysiological processes. There is increasing evidence that annexin A5 is related to cytotoxicity, but the precise function of this protein has yet to be elucidated. In this study, we aimed to verify the function of annexin A5 in the apoptosis of renal epithelial cells. Real-time PCR and Western blot analysis, together with immunofluorescence analysis, showed that the expression of annexin A5 significantly increased in the presence of cisplatin in both human and rat renal epithelial cells. With regard to the mechanism of cisplatin-induced apoptosis, apoptosis-inducing factor (AIF) release into the cytosol was observed, and the underlying mechanism was identified as voltage-dependent anion channel (VDAC) oligomerization. Mitochondrial membrane potential (Δψm) was found to be greatly disrupted in cisplatin-treated cells. Moreover, cisplatin strongly induced translocation of annexin A5 into mitochondria. To understand the functional significance of annexin A5 in renal cell death, we used a siRNA-mediated approach to knock down annexin A5. Annexin A5 depletion by siRNA led to decreased annexin A5 translocation into mitochondria and significantly reduced VDAC oligomerization and AIF release. Annexin A5 siRNA also increased cell viability compared with the control. Moreover, expression of annexin A5 was induced by other nephrotoxicants such as CdCl2 and bacitracin. Taken together, our data suggest that annexin A5 may play a crucial role in cisplatin-induced toxicity by mediating the mitochondrial apoptotic pathway via the induction and oligomerization of VDAC.

Annexin C4 in A. fumigatus: a proteomics approach to understand the function.

OpenAIRE

Khalaj , Vahid; Azarian , Bahareh; Enayati , Somayeh; Vaziri , Behrouz

2011-01-01

International audience; Annexin C4 has been identified as a new member of fungal annexin family. In search of function, we have generated an annexin C4 disruptant strain of human pathogen, Aspergillus fumigatus. Detailed phenotypic analysis confirmed a non essential role of annexin C4 in the growth and sporulation of this pathogen. We applied a comparative proteomics strategy to understand the possible role of this protein in the fungus. The modification of respiratory chain proteins and stre...

Differential Modulation of Annexin I Binding Sites on Monocytes and Neutrophils

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H. S. Euzger

1999-01-01

Full Text Available Specific binding sites for the anti-inflammatory protein annexin I have been detected on the surface of human monocytes and polymorphonuclear leukocytes (PMN. These binding sites are proteinaceous in nature and are sensitive to cleavage by the proteolytic enzymes trypsin, collagenase, elastase and cathepsin G. When monocytes and PMN were isolated independently from peripheral blood, only the monocytes exhibited constitutive annexin I binding. However PMN acquired the capacity to bind annexin I following co-culture with monocytes. PMN incubation with sodium azide, but not protease inhibitors, partially blocked this process. A similar increase in annexin I binding capacity was also detected in PMN following adhesion to endothelial monolayers. We propose that a juxtacrine activation rather than a cleavage-mediated transfer is involved in this process. Removal of annexin I binding sites from monocytes with elastase rendered monocytes functionally insensitive to full length annexin I or to the annexin I-derived pharmacophore, peptide Ac2-26, assessed as suppression of the respiratory burst. These data indicate that the annexin I binding site on phagocytic cells may have an important function in the feedback control of the inflammatory response and their loss through cleavage could potentiate such responses.

Impact of Annexin A 7 Deficiency on FGF23 Plasma Concentrations

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Anja T. Umbach

2016-11-01

Full Text Available Background/Aims: The release of fibroblast growth factor FGF23, a powerful regulator of 1,25(OH2D3 formation and mineral metabolism, is stimulated by store-operated Ca2+ entry (SOCE, which is accomplished by the pore forming Ca2+ release activated channel protein Orai1. Regulators of Orai1 and thus FGF23 release include serum & glucocorticoid inducible kinase SGK1, a kinase up-regulated by glucocorticosteroids. Some effects of glucocorticoids require the presence of annexin A7, such as suppression of prostaglandin E2 in gastric glands. The present study thus explored whether annexin A7 impacts on FGF23 plasma levels. Methods: Comparisons were made between gene targeted mice lacking functional annexin A7 (Anx7-/- and their wild type littermates (Anx7+/+. Serum C-terminal-FGF23, intact FGF23, 1,25(OH2D3 and PTH concentrations were measured by ELISA or EIA. The serum and urinary phosphate concentrations were measured by colorimetry, the serum Ca2+ concentration and the urinary Ca2+ concentration by flame photometry. Results: Serum C-terminal FGF23 levels and corticosterone levels were significantly higher and serum 1,25(OH2 D3 and PTH levels were significantly lower in Anx7-/- than in Anx7+/+ mice. Water intake was slightly but significantly higher in Anx7-/- mice than in Anx7+/+ mice. No significant difference was observed between Anx7-/- and Anx7+/+ mice in urinary fluid excretion, plasma Ca2+ concentration, plasma phosphate concentration and urinary Ca2+ output. The urinary phosphate output was significantly lower in Anx7-/- mice than in Anx7+/+ mice. Conclusion: Annexin A7 deficiency upregulates FGF23 plasma levels, an effect paralleled by increased corticosterone plasma levels, as well as decreased 1,25(OH2 D3 and PTH plasma levels.

A low molecular weight zinc2+-dipicolylamine-based probe detects apoptosis during tumour treatment better than an annexin V-based probe

International Nuclear Information System (INIS)

Palmowski, Karin; Rix, Anne; Lederle, Wiltrud; Kiessling, Fabian; Behrendt, Florian F.; Mottaghy, Felix M.; Gray, Brian D.; Pak, Koon Y.; Palmowski, Moritz

2014-01-01

Molecular imaging of apoptosis is frequently discussed for monitoring cancer therapies. Here, we compare the low molecular weight phosphatidylserine-targeting ligand zinc 2+ -dipicolylamine (Zn 2+ -DPA) with the established but reasonably larger protein annexin V. Molecular apoptosis imaging with the fluorescently labelled probes annexin V (750 nm, 36 kDa) and Zn 2+ -DPA (794 nm, 1.84 kDa) was performed in tumour-bearing mice (A431). Three animal groups were investigated: untreated controls and treated tumours after 1 or 4 days of anti-angiogenic therapy (SU11248). Additionally, μPET with 18 F-FDG was performed. Imaging data were displayed as tumour-to-muscle ratio (TMR) and validated by quantitative immunohistochemistry. Compared with untreated control tumours, TUNEL staining indicated significant apoptosis after 1 day (P 2+ -DPA uptake increased significantly after 1 day (P 2+ -DPA, 18 F-FDG tumour uptake decreased significantly at days 1 (P 2+ -DPA than with the annexin V-based probe. Additionally, significant treatment effects were detectable as early using Zn 2+ -DPA as with measurements of the glucose metabolism using 18 F-FDG. (orig.)

Agrobacterium mediated transformation of annexin gene in tobacco ...

African Journals Online (AJOL)

STORAGESEVER

serves as a selectable marker system in plants and its amplification confirmed the presence of annexin ... annexin signaling to many different physiological pro- ..... Lane 7: pGPTV with annexin gene digested with EcoR1 and XbaI. Lane 8:.

Preparation and bioevaluation of 99Tcm-HYNIC-Annexin B1 as a novel radiotracer for apoptosis detection

International Nuclear Information System (INIS)

Luo Quanyong; Luo Qiong; Lu Hankui; Zhu Ruisen; Wang Fang; Zhang Yi; Sun Shuhan; Zhang Zhiyong; Liu Xingfeng

2008-01-01

Objective: Annexin B1, a novel Ca 2+ -dependent phosphatidylserine (PS)-binding protein, has been shown to have a high affinity for PS exposed on the surface of apoptotic cells or activated platelets. The aim of this study was to develop and bioevaluate an Annexin B1 based PS-targeting radiotracer labeled with 99 Tc m . Methods: Annexin B1 was indirectly labeled with 99 Tc m using hydrazinonicotinamide (HYNIC) as a bifunctional chelator agent. Binding assay with human activated platelets was used to evaluate the biological activity of 99 Tc m -HYNIC-Annexin B1 in vitro. The potential of 99 Tc m -HYNIC-Annexin B1 to detect apoptosis in vivo was evaluated in mice models with dexamethasone-inducecd thymus apoptosis and anti-Fas antibody induced liver apoptosis. The paired t-test was used to analyse the data. Results: The labeling procedure yielded a compound with radiochemical purity higher than 96% and good in vitro stability. Plate- lets binding assay indicated that 99 Tc m -HYNIC-Annexin B1 retained their PS binding activity in vitro. The percentage activity of injection dose per gram of tissue (% ID/g) of mouse thymus showed a 3.50-fold increase at 18 h after administration of dexamethasone compared with control mice (t=5.234, P 99 Tc m -HYNIC-Annexin B1 in the liver of anti-Fas antibody treated mice. The %ID/g of apoptotic murine liver showed a 2.02-fo1d increase at 2 h after the administration of anti-Fas antibody compared with control mice (t=6.178, P 99 Tc m -HYNIC-Annexin B1 can be prepared with high radiochemical purity and in vitro stability. These da- ta also suggest that 99 Tc m -HYNIC-Annexin B1 retains its in vitro and in vivo biological activities. It may therefore be useful as a novel radioligand for the noninvasive imaging of PS externalization associated with apoptosis. (authors)

Annexin A7 suppresses lymph node metastasis of hepatocarcinoma cells in a mouse model

International Nuclear Information System (INIS)

Jin, Yanling; Wang, Shaoqing; Chen, Wenjing; Zhang, Jun; Wang, Bo; Guan, Hongwei; Tang, Jianwu

2013-01-01

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death in China. This study investigated the effects of Annexin A7 (ANXA7) on the inhibition of HCC lymph node metastasis in a mouse model. The stable knockup and knockdown of Annexin A7-expressing HCC cells using Annexin A7 cDNA and shRNA vectors, respectively, were injected into a mouse footpad to establish primary and metastatic tumors in mice. On the 14th, 21st, and 28th days after HCC cells inoculation, the mice were sacrificed for inspection of primary and secondary tumors and immunohistochemistry of Annexin A7 expression. The lymph node metastasis rate of the F ANXA7-control group was 77%, and the lymph node metastasis rate of the F ANXA7-down group was 100% (p < 0.05). In contrast, the lymph node metastasis rate of the P ANXA7-up group was 0% and that of the P ANXA7-control group was 36% (p < 0.05). Furthermore, immunohistochemistry experiments revealed that the subcellular localization of Annexin A7 protein in both primary and lymph node-metastasized tumors was mainly in the cytosol. In addition, the expression of the 47 kDa and 51 kDa isoforms of Annexin A7 protein changed during tumor progression. This study indicated that Annexin A7 expression was able to inhibit HCC lymph node metastasis, whereas knockdown of Annexin A7 expression significantly induced HCC metastasis to local lymph nodes

Absence of annexin I expression in B-cell non-Hodgkin's lymphomas and cell lines

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Gopalakrishnan Velliyur K

2004-03-01

Full Text Available Abstract Background Annexin I, one of the 20 members of the annexin family of calcium and phospholipid-binding proteins, has been implicated in diverse biological processes including signal transduction, mediation of apoptosis and immunosuppression. Previous studies have shown increased annexin I expression in pancreatic and breast cancers, while it is absent in prostate and esophageal cancers. Results Data presented here show that annexin I mRNA and protein are undetectable in 10 out of 12 B-cell lymphoma cell lines examined. Southern blot analysis indicates that the annexin I gene is intact in B-cell lymphoma cell lines. Aberrant methylation was examined as a cause for lack of annexin I expression by treating cells 5-Aza-2-deoxycytidine. Reexpression of annexin I was observed after prolonged treatment with the demethylating agent indicating methylation may be one of the mechanisms of annexin I silencing. Treatment of Raji and OMA-BL-1 cells with lipopolysaccharide, an inflammation inducer, and with hydrogen peroxide, a promoter of oxidative stress, also failed to induce annexin I expression. Annexin I expression was examined in primary lymphoma tissues by immunohistochemistry and presence of annexin I in a subset of normal B-cells and absence of annexin I expression in the lymphoma tissues were observed. These results show that annexin I is expressed in normal B-cells, and its expression is lost in all primary B-cell lymphomas and 10 of 12 B-cell lymphoma cell lines. Conclusions Our results suggest that, similar to prostate and esophageal cancers, annexin I may be an endogenous suppressor of cancer development, and loss of annexin I may contribute to B-cell lymphoma development.

A low molecular weight zinc{sup 2+}-dipicolylamine-based probe detects apoptosis during tumour treatment better than an annexin V-based probe

Energy Technology Data Exchange (ETDEWEB)

Palmowski, Karin [RWTH-Aachen University, Department of Experimental Molecular Imaging, Aachen (Germany); University of Heidelberg, Department of Pneumology, Thoraxklinik Heidelberg, Heidelberg (Germany); Rix, Anne; Lederle, Wiltrud; Kiessling, Fabian [RWTH-Aachen University, Department of Experimental Molecular Imaging, Aachen (Germany); Behrendt, Florian F. [RWTH-Aachen University, Department of Nuclear Medicine, Aachen (Germany); Mottaghy, Felix M. [RWTH-Aachen University, Department of Nuclear Medicine, Aachen (Germany); Maastricht University Medical Center, Department of Nuclear Medicine, Maastricht (Netherlands); Gray, Brian D. [Molecular Targeting Technologies, Inc., West Chester, PA (United States); Pak, Koon Y. [University Medical Center Heidelberg, Academic Radiology Baden-Baden, Diagnostic and Interventional Radiology, Heidelberg (Germany); Palmowski, Moritz [RWTH-Aachen University, Department of Experimental Molecular Imaging, Aachen (Germany); RWTH-Aachen University, Department of Nuclear Medicine, Aachen (Germany); University Medical Center Heidelberg, Academic Radiology Baden-Baden, Diagnostic and Interventional Radiology, Heidelberg (Germany)

2014-02-15

Molecular imaging of apoptosis is frequently discussed for monitoring cancer therapies. Here, we compare the low molecular weight phosphatidylserine-targeting ligand zinc{sup 2+}-dipicolylamine (Zn{sup 2+}-DPA) with the established but reasonably larger protein annexin V. Molecular apoptosis imaging with the fluorescently labelled probes annexin V (750 nm, 36 kDa) and Zn{sup 2+}-DPA (794 nm, 1.84 kDa) was performed in tumour-bearing mice (A431). Three animal groups were investigated: untreated controls and treated tumours after 1 or 4 days of anti-angiogenic therapy (SU11248). Additionally, μPET with {sup 18} F-FDG was performed. Imaging data were displayed as tumour-to-muscle ratio (TMR) and validated by quantitative immunohistochemistry. Compared with untreated control tumours, TUNEL staining indicated significant apoptosis after 1 day (P < 0.05) and 4 days (P < 0.01) of treatment. Concordantly, Zn{sup 2+}-DPA uptake increased significantly after 1 day (P < 0.05) and 4 days (P < 0.01). Surprisingly, annexin V failed to detect significant differences between control and treated animals. Contrary to the increasing uptake of Zn{sup 2+}-DPA, {sup 18} F-FDG tumour uptake decreased significantly at days 1 (P < 0.05) and 4 (P < 0.01). Increase in apoptosis during anti-angiogenic therapy was detected significantly better with the low molecular weight probe Zn{sup 2+}-DPA than with the annexin V-based probe. Additionally, significant treatment effects were detectable as early using Zn{sup 2+}-DPA as with measurements of the glucose metabolism using {sup 18} F-FDG. (orig.)

Towards an easy access to Annexin-A5 protein binding block copolymer micelles

International Nuclear Information System (INIS)

Schmidt, Vanessa; Giacomelli, Cristiano; Brisson, Alain R.; Borsali, Redouane

2008-01-01

The formation of Annexin-A5 decorated (bio-functionalized) nanoparticles is of particular interest in micelle-mediated target drug delivery, in vivo magnetic resonance imaging, and controlled fabrication of biochips. This work describes an easy access to the synthesis and manipulation of block copolymer nano-objects exhibiting Annexin-A5 protein binding ability. Well-defined spherical micelles containing negatively charged phosphonic diacid groups - which are potential binding sites for Annexin-A5 proteins - at their hydrophilic periphery originate from the self-assembly of polystyrene-b-poly(2-phosphatethyl methacrylate-stat-2-hydroxyethyl methacrylate) (PS-b-P(PEMA-stat-HEMA)) amphiphilic macromolecules in aqueous media. PS-b-P(PEMA-stat-HEMA) can be prepared in a three-step phosphorylation/silylation/methanolysis procedure applied to PS-b-PHEMA precursors synthesized via Atom Transfer Radical Polymerization (ATRP). The herein discussed approach allows precise control over micellar dimensions and properties such as core radius (i.e., loading capacity), corona width, and density of phosphate groups at the micelle periphery

Small molecule inhibitors of the annexin A2 heterotetramer prevent human papillomavirus type 16 infection.

Science.gov (United States)

Woodham, Andrew W; Taylor, Julia R; Jimenez, Andrew I; Skeate, Joseph G; Schmidt, Thomas; Brand, Heike E; Da Silva, Diane M; Kast, W Martin

2015-01-01

High-risk human papillomavirus (HPV) infection leads to the development of several human cancers that cause significant morbidity and mortality worldwide. HPV type 16 (HPV16) is the most common of the cancer-causing genotypes and gains entry to the basal cells of the epithelium through a non-canonical endocytic pathway that involves the annexin A2/S100A10 heterotetramer (A2t). A2t is composed of two annexin A2 monomers bound to an S100A10 dimer and this interaction is a potential target to block HPV16 infection. Here, recently identified small molecule inhibitors of A2t (A2ti) were investigated for their ability to prevent HPV16 infection in vitro. A2ti were added to HeLa cells in increasing concentrations prior to the addition of HPV16. Cytotoxicity was evaluated via trypan blue exclusion. HPV16 pseudovirion infection and fluorescently labelled HPV16 capsid internalization was measured with flow cytometry. A2ti blocked HPV16 infection by 100% without substantial cellular toxicity or reduction in cell growth. Furthermore, A2ti blocked HPV16 entry into epithelial cells by 65%, indicating that the observed inhibition of HPV16 infection is in part due to a block in entry and that non-infectious entry may occur in the absence of A2t binding. These results demonstrate that targeting A2t may be an effective strategy to prevent HPV16 infection. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Yeast two-hybrid screening of proteins interacting with plasmin receptor subunit: C-terminal fragment of annexin A2.

Science.gov (United States)

Li, Qun; Laumonnier, Yves; Syrovets, Tatiana; Simmet, Thomas

2011-11-01

To identify proteins that interact with the C-terminal fragment of annexin A2 (A2IC), generated by plasmin cleavage of the plasmin receptor, a heterotetramer (AA2t) containing annexin A2. The gene that encodes the A2IC fragment was obtained from PCR-amplified cDNA isolated from human monocytes, and was ligated into the pBTM116 vector using a DNA ligation kit. The resultant plasmid (pBTM116-A2IC) was sequenced with an ABI PRISM 310 Genetic Analyzer. The expression of an A2IC bait protein fused with a LexA-DNA binding domain (BD) was determined using Western blot analysis. The identification of proteins that interact with A2IC and are encoded in a human monocyte cDNA library was performed using yeast two-hybrid screening. The DNA sequences of the relevant cDNAs were determined using an ABI PRISM BigDye terminator cycle sequencing ready reaction kit. Nucleotide sequence databases were searched for homologous sequences using BLAST search analysis (http://www.ncbi.nlm.nih.gov). Confirmation of the interaction between the protein LexA-A2IC and each of cathepsin S and SNX17 was conducted using a small-scale yeast transformation and X-gal assay. The yeast transformed with plasmids encoding the bait proteins were screened with a human monocyte cDNA library by reconstituting full-length transcription factors containing the GAL4-active domain (GAL4-AD) as the prey in a yeast two-hybrid approach. After screening 1×10(7) clones, 23 independent β-Gal-positive clones were identified. Sequence analysis and a database search revealed that 15 of these positive clones matched eight different proteins (SNX17, ProCathepsin S, RPS2, ZBTB4, OGDH, CCDC32, PAPD4, and actin which was already known to interact with annexin A2). A2IC A2IC interacts with various proteins to form protein complexes, which may contribute to the molecular mechanism of monocyte activation induced by plasmin. The yeast two-hybrid system is an efficient approach for investigating protein interactions.

Purification and immunolocalization of an annexin-like protein in pea seedlings

Science.gov (United States)

Clark, G. B.; Dauwalder, M.; Roux, S. J.

1992-01-01

As part of a study to identify potential targets of calcium action in plant cells, a 35-kDa, annexin-like protein was purified from pea (Pisum sativum L.) plumules by a method used to purify animal annexins. This protein, called p35, binds to a phosphatidylserine affinity column in a calcium-dependent manner and binds 45Ca2+ in a dot-blot assay. Preliminary sequence data confirm a relationship for p35 with the annexin family of proteins. Polyclonal antibodies have been raised which recognize p35 in Western and dot blots. Immunofluorescence and immunogold techniques were used to study the distribution and subcellular localization of p35 in pea plumules and roots. The highest levels of immunostain were found in young developing vascular cells producing wall thickenings and in peripheral root-cap cells releasing slime. This localization in cells which are actively involved in secretion is of interest because one function suggested for the animal annexins is involvement in the mediation of exocytosis.

An ANNEXIN-like protein from the cereal cyst nematode Heterodera avenae suppresses plant defense.

Directory of Open Access Journals (Sweden)

Changlong Chen

Full Text Available Parasitism genes encoding secreted effector proteins of plant-parasitic nematodes play important roles in facilitating parasitism. An annexin-like gene was isolated from the cereal cyst nematode Heterodera avenae (termed Ha-annexin and had high similarity to annexin 2, which encodes a secreted protein of Globodera pallida. Ha-annexin encodes a predicted 326 amino acid protein containing four conserved annexin domains. Southern blotting revealed that there are at least two homologies in the H. avenae genome. Ha-annexin transcripts were expressed within the subventral gland cells of the pre-parasitic second-stage juveniles by in situ hybridization. Additionally, expression of these transcripts were relatively higher in the parasitic second-stage juveniles by quantitative real-time RT-PCR analysis, coinciding with the time when feeding cell formation is initiated. Knockdown of Ha-annexin by method of barley stripe mosaic virus-based host-induced gene silencing (BSMV-HIGS caused impaired nematode infections at 7 dpi and reduced females at 40 dpi, indicating important roles of the gene in parasitism at least in early stage in vivo. Transiently expression of Ha-ANNEXIN in onion epidermal cells and Nicotiana benthamiana leaf cells showed the whole cell-localization. Using transient expression assays in N. benthamiana, we found that Ha-ANNEXIN could suppress programmed cell death triggered by the pro-apoptotic mouse protein BAX and the induction of marker genes of PAMP-triggered immunity (PTI in N. benthamiana. In addition, Ha-ANNEXIN targeted a point in the mitogen-activated protein kinase (MAPK signaling pathway downstream of two kinases MKK1 and NPK1 in N. benthamiana.

Annexins are instrumental for efficient plasma membrane repair in cancer cells.

Science.gov (United States)

Lauritzen, Stine Prehn; Boye, Theresa Louise; Nylandsted, Jesper

2015-09-01

Plasma membrane stress can cause damage to the plasma membrane, both when imposed by the extracellular environment and by enhanced oxidative stress. Cells cope with these injuries by rapidly activating their plasma membrane repair system, which is triggered by Ca(2+) influx at the wound site. The repair system is highly dynamic, depends on both lipid and protein components, and include cytoskeletal reorganization, membrane replacements, and membrane fusion events. Cancer cells experience enhanced membrane stress when navigating through dense extracellular matrix, which increases the frequency of membrane injuries. In addition, increased motility and oxidative stress further increase the risk of plasma membrane lesions. Cancer cells compensate by overexpressing Annexin proteins including Annexin A2 (ANXA2). Annexin family members can facilitate membrane fusion events and wound healing by binding to negatively charged phospholipids in the plasma membrane. Plasma membrane repair in cancer cells depends on ANXA2 protein, which is recruited to the wound site and forms a complex with the Ca(2+)-binding EF-hand protein S100A11. Here they regulate actin accumulation around the wound perimeter, which is required for wound closure. In this review, we will discuss the requirement for Annexins, S100 proteins and actin cytoskeleton in the plasma membrane repair response of cancer cells, which reveals a novel avenue for targeting metastatic cancers. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dietary flavonoids bind to mono-ubiquitinated annexin A1 in nuclei, and inhibit chemical induced mutagenesis

Energy Technology Data Exchange (ETDEWEB)

Hirata, Fusao, E-mail: fhirata@wayne.edu; Harada, Takasuke; Corcoran, George B.; Hirata, Aiko

2014-01-15

Highlight: • Nuclear mono-ubiquitinated annexin A1 is involved in DNA damage induced mutagenesis. • Dietary flavonoids bind to and inhibit purified mono-ubiquitinated annexin A1 helicase. • Dietary flavonoids show anti-mutagenic action. • Annexin A1 may serve as a putative target of cancer chemoprevention by flavonoids. - Abstract: In order to investigate the mechanisms of anti-mutagenic action by dietary flavonoids, we investigated if they inhibit mutation of the thymidine kinase (tk) gene in L5178Ytk(±) lymphoma cells. Silibinin, quercetin and genistein suppressed mutation of the tk gene induced in L5178Ytk(±) lymphoma cells by methyl methanesulfonate (MMS) and As{sup 3+}. Flavone and flavonol were less effective. To establish that mutation of the tk gene in L5178Ytk(±) lymphoma cells by MMS and As{sup 3+} is mediated through mono-ubiquitinated annexin A1, L5178Ytk(±) lymphoma cells were treated with annexin A1 anti-sense oligonucleotide. The treatment reduced mRNA as well as protein levels of annexin A1, and suppressed mutation of the tk gene. Nuclear extracts from L5178Ytk(±) lymphoma cells catalyzed translesion DNA synthesis with an oligonucleotide template containing 8-oxo-guanosine in an annexin A1 dependent manner. This translesion DNA synthesis was inhibited by the anti-mutagenic flavonoids, silibinin, quercetin and genistein, in a concentration dependent manner, but only slightly by flavone and flavonol. Because these observations implicate involvement of annexin A1 in mutagenesis, we examined if flavonoids suppress nuclear annexin A1 helicase activity. Silibinin, quercetin and genistein inhibited ssDNA binding, DNA chain annealing and DNA unwinding activities of purified nuclear mono-ubiquitinated annexin A1. Flavone and flavonol were ineffective. The apparent direct binding of anti-mutagenic flavonoids to the annexin A1 molecule was supported by fluorescence quenching. Taken together, these findings illustrate that nuclear annexin A1 may be

Dietary flavonoids bind to mono-ubiquitinated annexin A1 in nuclei, and inhibit chemical induced mutagenesis

International Nuclear Information System (INIS)

Hirata, Fusao; Harada, Takasuke; Corcoran, George B.; Hirata, Aiko

2014-01-01

Highlight: • Nuclear mono-ubiquitinated annexin A1 is involved in DNA damage induced mutagenesis. • Dietary flavonoids bind to and inhibit purified mono-ubiquitinated annexin A1 helicase. • Dietary flavonoids show anti-mutagenic action. • Annexin A1 may serve as a putative target of cancer chemoprevention by flavonoids. - Abstract: In order to investigate the mechanisms of anti-mutagenic action by dietary flavonoids, we investigated if they inhibit mutation of the thymidine kinase (tk) gene in L5178Ytk(±) lymphoma cells. Silibinin, quercetin and genistein suppressed mutation of the tk gene induced in L5178Ytk(±) lymphoma cells by methyl methanesulfonate (MMS) and As 3+ . Flavone and flavonol were less effective. To establish that mutation of the tk gene in L5178Ytk(±) lymphoma cells by MMS and As 3+ is mediated through mono-ubiquitinated annexin A1, L5178Ytk(±) lymphoma cells were treated with annexin A1 anti-sense oligonucleotide. The treatment reduced mRNA as well as protein levels of annexin A1, and suppressed mutation of the tk gene. Nuclear extracts from L5178Ytk(±) lymphoma cells catalyzed translesion DNA synthesis with an oligonucleotide template containing 8-oxo-guanosine in an annexin A1 dependent manner. This translesion DNA synthesis was inhibited by the anti-mutagenic flavonoids, silibinin, quercetin and genistein, in a concentration dependent manner, but only slightly by flavone and flavonol. Because these observations implicate involvement of annexin A1 in mutagenesis, we examined if flavonoids suppress nuclear annexin A1 helicase activity. Silibinin, quercetin and genistein inhibited ssDNA binding, DNA chain annealing and DNA unwinding activities of purified nuclear mono-ubiquitinated annexin A1. Flavone and flavonol were ineffective. The apparent direct binding of anti-mutagenic flavonoids to the annexin A1 molecule was supported by fluorescence quenching. Taken together, these findings illustrate that nuclear annexin A1 may be a novel

Increased alveolar soluble Annexin V promotes lung inflammation and fibrosis

OpenAIRE

Buckley, S.; Shi, W.; Xu, W.; Frey, M.R.; Moats, R.; Pardo, A.; Selman, M.; Warburton, D.

2015-01-01

The causes underlying the self-perpetuating nature of idiopathic pulmonary fibrosis (IPF), a progressive and usually lethal disease, remain unknown. We hypothesized that alveolar soluble Annexin V contributes to lung fibrosis, based on the observation that human IPF BALF containing high Annexin V levels promoted fibroblast involvement in alveolar epithelial wound healing that was reduced when Annexin V was depleted from the BALF.

Determination of autoantibodies to annexin XI in systemic autoimmune diseases

DEFF Research Database (Denmark)

Jorgensen, C S; Levantino, G; Houen, Gunnar

2000-01-01

Annexin XI, a calcyclin-associated protein, has been shown to be identical to a 56,000 Da antigen recognized by antibodies found in sera from patients suffering from systemic autoimmune diseases. In this work hexahistidine-tagged recombinant annexin XI (His6- rAnn XI) was used as antigen in ELISA...... experiments for determination of autoantibodies to annexin XI in sera of patients with systemic rheumatic autoimmune diseases. Immunoblotting with HeLa cell extract and with His6-rAnn XI as antigen was used for confirmation of positive ELISA results. We found eleven anti-annexin XI positive sera (3.9%) out...... of 282 sera from patients with systemic rheumatic diseases. The highest number of annexin XI positive sera were found in primary antiphospholipid syndrome (3/17), and in subacute lupus erythematosus (1/6), while lower frequencies of positive sera were found in patients with systemic sclerosis (5...

Amino acid sequence analysis of the annexin super-gene family of proteins.

Science.gov (United States)

Barton, G J; Newman, R H; Freemont, P S; Crumpton, M J

1991-06-15

The annexins are a widespread family of calcium-dependent membrane-binding proteins. No common function has been identified for the family and, until recently, no crystallographic data existed for an annexin. In this paper we draw together 22 available annexin sequences consisting of 88 similar repeat units, and apply the techniques of multiple sequence alignment, pattern matching, secondary structure prediction and conservation analysis to the characterisation of the molecules. The analysis clearly shows that the repeats cluster into four distinct families and that greatest variation occurs within the repeat 3 units. Multiple alignment of the 88 repeats shows amino acids with conserved physicochemical properties at 22 positions, with only Gly at position 23 being absolutely conserved in all repeats. Secondary structure prediction techniques identify five conserved helices in each repeat unit and patterns of conserved hydrophobic amino acids are consistent with one face of a helix packing against the protein core in predicted helices a, c, d, e. Helix b is generally hydrophobic in all repeats, but contains a striking pattern of repeat-specific residue conservation at position 31, with Arg in repeats 4 and Glu in repeats 2, but unconserved amino acids in repeats 1 and 3. This suggests repeats 2 and 4 may interact via a buried saltbridge. The loop between predicted helices a and b of repeat 3 shows features distinct from the equivalent loop in repeats 1, 2 and 4, suggesting an important structural and/or functional role for this region. No compelling evidence emerges from this study for uteroglobin and the annexins sharing similar tertiary structures, or for uteroglobin representing a derivative of a primordial one-repeat structure that underwent duplication to give the present day annexins. The analyses performed in this paper are re-evaluated in the Appendix, in the light of the recently published X-ray structure for human annexin V. The structure confirms most of

Kit formulation for 99mTc-labeling of recombinant Annexin V molecule with a C-terminally engineered cysteine

International Nuclear Information System (INIS)

Chunxiong Lu; Quanfu Jiang; Cheng Tan; Huixin Yu; Minjin Hu; Zichun Hua; Nanjing University, Nanjing

2015-01-01

A new formulation of a freeze-dried kit for the labeling of a novel recombinant Annexin V molecules (with a single cysteine residue at its C-terminal, Cys-Annexin V) with technetium-99m has been developed. Effects of the amount range of Cys-Annexin V, stannous chloride, glucoheptonate and disodium edetate on the radiolabeling yield were studied in details. The stabilities of 99m Tc-Cys-Annexin V and freeze-dried kits were performed, respectively. In vitro cell uptake studies showed the binding of 99m Tc-Cys-Annexin V was specific on testing with apoptotic H446 cells. Therefore, 99m Tc-Cys-Annexin V is a potential apoptosis imaging agent and further study is needed. (author)

Internalization of annexin A5-functionalized iron oxide particles by apoptotic Jurkat cells

NARCIS (Netherlands)

van Tilborg, Geralda A. F.; Geelen, Tessa; Duimel, Hans; Bomans, Paul H. H.; Frederik, Peter M.; Sanders, Honorius M. H. F.; Deckers, Niko M.; Deckers, Roel; Reutelingsperger, Chris P. M.; Strijkers, Gustav J.; Nicolay, Klaas

2009-01-01

Apoptosis plays an important role in the etiology of various diseases. Several studies have reported on the use of annexin A5-functionalized iron oxide particles for the detection of apoptosis with MRI, both in vitro and in vivo. The protein annexin A5 binds with high affinity to the phospholipid

99mTc rh-Annexin V for imaging apoptotic cells: Clinical experience

International Nuclear Information System (INIS)

Abdel-Dayem, H.M.; Sadek, S.; Heiba, S.; Steinmetz, N.; Cho, J.; Cook, W.; Klein, P.

2002-01-01

Introduction: 99m Tc rh-Annexin V (Apomate, Theseus Imaging Corp., Boston, MA), an investigational nuclear medicine agent for imaging apoptotic and necrotic cell death, is currently in Phase II-III clinical trials. Potential applications being evaluated include identification and localization of acute myocardial infarction, non-invasive assessment of cardiac transplant rejection, and early prediction of cancer chemotherapy response. The purposes of this presentation are: 1) To familiarize attendees with the biological basis of 99m Tc-Annexin V localization, the labeling procedure, biodistribution following I.V. injection, and dosimetric data; 2) In patients with acute myocardial infarction (AMI), dual isotope SPECT using 99m Tc-Annexin V and Thallium-201 was performed within 4 days from onset of AMI and 6 weeks later. It demonstrates the increased uptake of 99m Tc-Annexin V in the recent MI area correlating with the perfusion defect in the Thallium study. 99m Tc-Annexin V disappears in the follow-up scan 6 weeks later indicating that 99m Tc-Annexin V will be a clinically useful agent for determining the size and location of recent AMI and for differentiating AMI from myocardial scar. 3) To demonstrate examples of current applications in oncology for predicting chemo- and radiotherapy response in patients with small and non-small cell lung cancer, Hodgkin's and non-Hodgkin's malignant lymphoma and recurrent, metastatic or inoperable breast carcinoma. Early results show significant correlation with treatment response and patient survival. 4) To demonstrate unusual site of 99m Tc-Annexin V uptake in subdural hematoma and non-lactating breast 4 weeks post partum. In light of the current clinical studies of 99m Tc-Annexin V (Apomate) imaging and the potential approval for clinical use in the future, it is important for practicing nuclear medicine physicians to be aware of the normal distribution, expected patterns of uptake in various pathologic conditions, and unusual

Comparison of 99mTc-annexin A5 with 18F-FDG for the detection of atherosclerosis in ApoE-/- mice

International Nuclear Information System (INIS)

Zhao, Yan; Morita, Koichi; Tamaki, Nagara; Kuge, Yuji; Zhao, Songji; Inubushi, Masayuki; Strauss, H.W.; Blankenberg, Francis G.

2007-01-01

99m Tc-annexin A5, a marker of ongoing apoptosis, and 18 F-FDG, a marker of the increased metabolism of inflammatory cells, are supposed to be useful in the detection of metabolically active atheroma. This study reports a comparison of the intralesional distribution of these tracers in relation to lesion development in ApoE-/- mice. Male ApoE-/- mice (n = 12-14/group) were maintained on a Western-type diet after the age of 5 weeks. At 25 weeks, 99m Tc-annexin A5 or 18 F-FDG was injected and the aortas were harvested for autoradiography (ARG) and Oil Red O staining. Regional radioactivity accumulation was compared in relation to the Oil Red O staining score (ranging from 0 to 3, a semiquantitative parameter for evaluating lesion development). Both 99m Tc-annexin A5 and 18 F-FDG showed preferential uptake into atherosclerotic lesions, with higher uptake levels for 18 F-FDG (mean, 56.07 %ID x kg/m 2 ) than for 99m Tc-annexin A5 (mean, 10.38 %ID x kg/m 2 ). The regional uptake levels of each tracer correlated with the Oil Red O staining score (r = 0.65, p 99m Tc-annexin A5; r = 0.56, p 18 F-FDG). The uptake ratios of advanced lesions (score >0.5) to early lesions (score 99m Tc-annexin A5 than for 18 F-FDG (f = 4.73, p = 0.03). Both 99m Tc-annexin A5 and 18 F-FDG accumulate in atherosclerotic lesions and correlate with the severity of each lesion. The higher absolute uptake levels of 18 F-FDG may be advantageous for lesion detection, whereas the preferential uptake of 99m Tc-annexin A5 in advanced lesions may be a useful indicator of late-stage lesions or vulnerable plaque transformation. (orig.)

Biodistribution patterns of native and mutant 99mTc-labelled annexin V in mice

International Nuclear Information System (INIS)

Mariani, G.; Erba, P.; Pellegrino, D.; Volterrani, D.; Lazzeri, E.; Freer, G.; Bevilacqua, G.; Blankenberg, F.G.; Tait, J.F.; Strauss, H.W.

2003-01-01

Full text: Annexin is a 36 kD protein with high binding affinity to phosphatidylserine (PS), a phospholipid exposed on the membrane surface of cells upon activation of the enzyme caspase, the first step of apoptosis. Radiolabeled annexin V could thus be used for imaging apoptosis in-vivo. When the 319 amino acid protein is made by recombinant techniques and expressed as the human material, it can be radiolabeled with 99mTc after derivatization with a bifunctional agent such as HYNIC. Alternatively, the amino acid structure of the protein can be modified by producing annexin V mutants with an endogenous chelation site for 99mTc, the NH2 residue Ala-Gly-Gly-Cys-Gly-His-Met. Mutant annexin has similar affinity for membrane-bound PS as unmodified annexin. This study was performed to compare the biodistribution of 99mTc-labeled HYNIC annexin (HyA) to mutant annexin (MuA). 99mTc-labeling efficiency of the two annexin preparations was >99% by gel chromatography on Sephadex G10 columns. Groups of adult male mice (n 10, body weight 18-25 grams) were injected iv with either HyA or MuA (1-3 MBq, 3-9 μg/animal). Animals were sacrificed one hour later and dissected for organ biodistribution. Similar biodistribution was performed after pretreatment with cyclophosphamide (150 mg/kg ip 6-15 hr prior to the study). The results of the biodistribution study showed significantly reduced (p<0.05 to p<0.01) uptake of MuA versus HyA in the kidneys (Δ- 81.4%), spleen (Δ- 58.2%), liver (Δ- 56.2%), and bone marrow (Δ- 33.7%), while it was increased in lymph nodes (Δ+ 131%, p<0.001). Pretreatment with the pro-apoptotic agent cyclophosphamide induced significantly increased uptake of MuA (p<0.05) versus baseline in the heart (Δ+ 34.7%), spleen (Δ+ 30.1%) and bowel (Δ+ 44.5%), while uptake of HyA was increased only in the spleen (Δ+ 44.1%). The marked reduction in the renal, splenic, liver, and bone marrow localization of MuA compared to HyA in control animals outlines a pattern of

Preparation, in vitro and in vivo evaluation of 99mTc-Annexin B1: A novel radioligand for apoptosis imaging

International Nuclear Information System (INIS)

Luo Quanyong; Zhang Zhiyong; Wang Fang; Lu Hankui; Guo Yuzhi; Zhu Ruisen

2005-01-01

To develop a radiopharmaceutical for apoptosis imaging, Annexin B1, a new Ca 2+ -dependent phosphatidylserine (PS)-binding protein, was directly radiolabeled with 99m Tc. This procedure yields up to 96% of radiochemical purity and higher radiolabeling efficiency. The preparation has been found to be sufficiently stable in vitro. Binding assay with human activated platelets indicated that 99m Tc-Annexin B1 retained its PS binding activity. Biodistribution in mice revealed that 99m Tc-Annexin B1 rapidly cleared from the blood and predominantly accumulated in the kidney. The increase in hepatic uptake in anti-Fas antibody treated mice correlated to histologic evidence of fulminant hepatic apoptosis. These data suggest that 99m Tc-Annexin B1 can be used as a novel radiotracer to detect apoptosis in vivo

Clinical and prognostic role of annexin A2 in adamantinomatous craniopharyngioma.

Science.gov (United States)

Wang, Yuelong; Deng, Jiaojiao; Guo, Gang; Tong, Aiping; Peng, Xirui; Chen, Haifeng; Xu, Jianguo; Liu, Yi; You, Chao; Zhou, Liangxue

2017-01-01

Annexin A2 (AnxA2) is a highly conserved Ca2 + -regulated membrane binding protein, which affects cell mobility and tumor progression. Adamantinomatous craniopharyngioma (AdaCP) are a kind of epithelial tumors of the sellar region with high tendency to recur. Robust biomarkers are required to predict tumor behavior and to establish follow-up individualized treatment approaches. In this study, we firstly compared four surgical AdaCP samples with normal brain by two-dimensional gel electrophoresis (2DE) proteomic analysis. Potential prognostic biomarkers were further validated in a large cohort of 65 AdaCPs by immunohistochemistry. The effects of AnxA2 on AdaCP cells proliferation and migration were analyzed in vitro with isolated primary AdaCP cells as well as SV40T-immortalized cells. Finally, the gefitinib sensitivity of AdaCPs with differentially expressed AnxA2 and the potential molecular mechanisms were examined by flow cytometric analysis, Real-time PCR and immunoblot assays. Proteomic analysis indicated that AnxA2 was the protein spot with the most elevated expression in AdaCP samples. Immunohistochemistry assays indicated the expression level of AnxA2 was significantly higher in recurrent AdaCPs compared with primary ones. Moreover, AnxA2 + AdaCP cells exhibited enhanced proliferation and migration ability compared with AnxA2 - AdaCP cells in vitro. Further, we show that AnxA2 + AdaCP cells exhibited elevated expression of EGFR and downstream p-AKT (S308) and p-AKT (S473), and were more sensitive to tyrosine kinase inhibitor gefitinib. Our data suggest that AnxA2 may serve as a promising biomarker for AdaCP progression, recurrence and drug susceptibility. Our data support potential clinical implications for the follow-up treatment of AdaCP patients with high AnxA2 expression.

Proteins Annexin A2 and PSA in Prostate Cancer Biopsies Do Not Predict Biochemical Failure.

Science.gov (United States)

Lamb, David S; Sondhauss, Sven; Dunne, Jonathan C; Woods, Lisa; Delahunt, Brett; Ferguson, Peter; Murray, Judith; Nacey, John N; Denham, James W; Jordan, T William

2017-12-01

We previously reported the use of mass spectrometry and western blotting to identify proteins from tumour regions of formalin-fixed paraffin-embedded biopsies from 16 men who presented with apparently localized prostate cancer, and found that annexin A2 (ANXA2) appeared to be a better predictor of subsequent biochemical failure than prostate-specific antigen (PSA). In this follow-up study, ANXA2 and PSA were measured using western blotting of proteins extracted from biopsies from 37 men from a subsequent prostate cancer trial. No significant differences in ANXA2 and PSA levels were observed between men with and without biochemical failure. The statistical effect sizes were small, d=0.116 for ANXA2, and 0.266 for PSA. ANXA2 and PSA proteins measured from biopsy tumour regions are unlikely to be good biomarkers for prediction of the clinical outcome of prostate cancer presenting with apparently localized disease. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

The Annexin A1 Receptor FPR2 Regulates the Endosomal Export of Influenza Virus

Directory of Open Access Journals (Sweden)

Fryad Rahman

2018-05-01

Full Text Available The Formyl Peptide Receptor 2 (FPR2 is a novel promising target for the treatment of influenza. During viral infection, FPR2 is activated by annexinA1, which is present in the envelope of influenza viruses; this activation promotes virus replication. Here, we investigated whether blockage of FPR2 would affect the genome trafficking of influenza virus. We found that, upon infection and cell treatment with the specific FPR2 antagonist WRW4 or the anti-FPR2 monoclonal antibody, FN-1D6-AI, influenza viruses were blocked into endosomes. This effect was independent on the strain and was observed for H1N1 and H3N2 viruses. In addition, blocking FPR2signaling in alveolar lung A549 epithelial cells with the monoclonal anti-FPR2 antibody significantly inhibited virus replication. Altogether, these results show that FPR2signaling interferes with the endosomal trafficking of influenza viruses and provides, for the first time, the proof of concept that monoclonal antibodies directed against FPR2 inhibit virus replication. Antibodies-based therapeutics have emerged as attractive reagents in infectious diseases. Thus, this study suggests that the use of anti-FPR2 antibodies against influenza hold great promise for the future.

Technetium-99m-labeled annexin V imaging for detecting prosthetic joint infection in a rabbit model.

Science.gov (United States)

Tang, Cheng; Wang, Feng; Hou, Yanjie; Lu, Shanshan; Tian, Wei; Xu, Yan; Jin, Chengzhe; Wang, Liming

2015-05-01

Accurate and timely diagnosis of prosthetic joint infection is essential to initiate early treatment and achieve a favorable outcome. In this study, we used a rabbit model to assess the feasibility of technetium-99m-labeled annexin V for detecting prosthetic joint infection. Right knee arthroplasty was performed on 24 New Zealand rabbits. After surgery, methicillin-susceptible Staphylococcus aureus was intra-articularly injected to create a model of prosthetic joint infection (the infected group, n = 12). Rabbits in the control group were injected with sterile saline (n = 12). Seven and 21 days after surgery, technetium-99m-labeled annexin V imaging was performed in 6 rabbits of each group. Images were acquired 1 and 4 hours after injection of technetium-99m-labeled annexin V (150 MBq). The operated-to-normal-knee activity ratios were calculated for quantitative analysis. Seven days after surgery, increased technetium-99m-labeled annexin V uptake was observed in all cases. However, at 21 days a notable decrease was found in the control group, but not in the infected group. The operated-to-normal-knee activity ratios of the infected group were 1.84 ± 0.29 in the early phase and 2.19 ± 0.34 in the delay phase, both of which were significantly higher than those of the control group (P = 0.03 and P = 0.02). The receiver operator characteristic curve analysis showed that the operated-to-normal-knee activity ratios of the delay phase at 21 days was the best indicator, with an accuracy of 80%. In conclusion, technetium-99m-labeled annexin V imaging could effectively distinguish an infected prosthetic joint from an uninfected prosthetic joint in a rabbit model.

Prohibitin/annexin 2 interaction regulates fatty acid transport in adipose tissue

Science.gov (United States)

Salameh, Ahmad; Daquinag, Alexes C.; Staquicini, Daniela I.; An, Zhiqiang; Pasqualini, Renata; Kolonin, Mikhail G.

2016-01-01

We have previously identified prohibitin (PHB) and annexin A2 (ANX2) as proteins interacting on the surface of vascular endothelial cells in white adipose tissue (WAT) of humans and mice. Here, we demonstrate that ANX2 and PHB also interact in adipocytes. Mice lacking ANX2 have normal WAT vascularization, adipogenesis, and glucose metabolism but display WAT hypotrophy due to reduced fatty acid uptake by WAT endothelium and adipocytes. By using cell culture systems in which ANX2/PHB binding is disrupted either genetically or through treatment with a blocking peptide, we show that fatty acid transport efficiency relies on this protein complex. We also provide evidence that the interaction between ANX2 and PHB mediates fatty acid transport from the endothelium into adipocytes. Moreover, we demonstrate that ANX2 and PHB form a complex with the fatty acid transporter CD36. Finally, we show that the colocalization of PHB and CD36 on adipocyte surface is induced by extracellular fatty acids. Together, our results suggest that an unrecognized biochemical interaction between ANX2 and PHB regulates CD36-mediated fatty acid transport in WAT, thus revealing a new potential pathway for intervention in metabolic diseases. PMID:27468426

Low Annexin A1 expression predicts benefit from induction chemotherapy in oral cancer patients with moderate or poor pathologic differentiation grade

International Nuclear Information System (INIS)

Zhu, Dong-wang; Zhang, Chen-ping; Zhang, Zhi-yuan; Zhong, Lai-ping; Liu, Ying; Yang, Xiao; Yang, Cheng-zhe; Ma, Jie; Yang, Xi; Qiao, Jin-ke; Wang, Li-zhen; Li, Jiang

2013-01-01

The benefit of induction chemotherapy in locally advanced oral squamous cell carcinoma (OSCC) remains to be clearly defined. Induction chemotherapy is likely to be effective for biologically distinct subgroups of patients and biomarker development might lead to identification of the patients whose tumors are to respond to a particular treatment. Annexin A1 may serve as a biomarker for responsiveness to induction chemotherapy. The aim of this study was to investigate Annexin A1 expression in pre-treatment biopsies from a cohort of OSCC patients treated with surgery and post-operative radiotherapy or docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy followed by surgery and post-operative radiotherapy. Furthermore we sought to assess the utility of Annexin A1 as a prognostic or predictive biomarker. Immunohistochemical staining for Annexin A1 was performed in pre-treatment biopsies from 232 of 256 clinical stage III/IVA OSCC patients. Annexin A1 index was estimated as the proportion of tumor cells (low and high, <50% and ≥50% of stained cells, respectively) to Annexin A1 cellular membrane and cytoplasm staining. There was a significant correlation between Annexin A1 expression and pathologic differentiation grade (P=0.015) in OSCC patients. The proportion of patients with low Annexin A1 expression was significantly higher amongst those with moderate/poorly differentiated tumor (78/167) compared to those with well differentiated tumor (18/65). Multivariate Cox model analysis showed clinical stage (P=0.001) and Annexin A1 expression (P=0.038) as independent prognostic risk factors. Furthermore, a low Annexin A1 expression level was predictive of longer disease-free survival (P=0.036, HR=0.620) and locoregional recurrence-free survival (P=0.031, HR=0.607) compared to high Annexin A1 expression. Patients with moderate/poorly differentiated tumor and low Annexin A1 expression benefited from TPF induction chemotherapy as measured by distant metastasis

Effects of heavy particle irradiation on central nervous system

International Nuclear Information System (INIS)

Nojima, Kumie; Nakadai, Taeko; Khono, Yukio

2006-01-01

Effects of low dose heavy particle radiation to central nervous system were studied using human embryonal carcinoma (Ntera2=NT2) and Human neuroblastoma cell (NB1). They exposed to heavy ions and X ray 80% confluent cells in culture bottles. The cells were different type about growth and differentiation in the neuron. The apoptosis profile was measured by AnnexinV-EGFP, PI stained and fluorescence-activated cell sorter (FACS). Memory and learning function of adult mice were studied using water maze test after carbon- or iron-ion irradiation. Memory functions were rapidly decreased after irradiation both ions. Iron -ion group were recovered 20 weeks after irradiation C-ion group were recovered 25 weeks after irradiation. Tier memory were still keep at over 100 weeks after irradiation. (author)

Comparison of {sup 99m}Tc-annexin A5 with {sup 18}F-FDG for the detection of atherosclerosis in ApoE-/- mice

Energy Technology Data Exchange (ETDEWEB)

Zhao, Yan; Morita, Koichi; Tamaki, Nagara [Hokkaido University, Department of Nuclear Medicine, Graduate School of Medicine, Sapporo (Japan); Kuge, Yuji [Hokkaido University, Department of Tracer Kinetics, Graduate School of Medicine, Sapporo (Japan); Hokkaido University, Department of Molecular Imaging, Graduate School of Medicine, Sapporo (Japan); Kyoto University, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Zhao, Songji [Hokkaido University, Department of Nuclear Medicine, Graduate School of Medicine, Sapporo (Japan); Hokkaido University, Department of Tracer Kinetics, Graduate School of Medicine, Sapporo (Japan); Inubushi, Masayuki [Hokkaido University, Department of Molecular Imaging, Graduate School of Medicine, Sapporo (Japan); Strauss, H.W. [Memorial Sloan-Kettering Cancer Center, Department of Nuclear Medicine, New York, NY (United States); Blankenberg, Francis G. [Stanford University School of Medicine, Department of Pediatric Radiology, Palo Alto, CA (United States)

2007-11-15

{sup 99m}Tc-annexin A5, a marker of ongoing apoptosis, and {sup 18}F-FDG, a marker of the increased metabolism of inflammatory cells, are supposed to be useful in the detection of metabolically active atheroma. This study reports a comparison of the intralesional distribution of these tracers in relation to lesion development in ApoE-/- mice. Male ApoE-/- mice (n = 12-14/group) were maintained on a Western-type diet after the age of 5 weeks. At 25 weeks, {sup 99m}Tc-annexin A5 or {sup 18}F-FDG was injected and the aortas were harvested for autoradiography (ARG) and Oil Red O staining. Regional radioactivity accumulation was compared in relation to the Oil Red O staining score (ranging from 0 to 3, a semiquantitative parameter for evaluating lesion development). Both {sup 99m}Tc-annexin A5 and {sup 18}F-FDG showed preferential uptake into atherosclerotic lesions, with higher uptake levels for {sup 18}F-FDG (mean, 56.07 %ID x kg/m{sup 2}) than for {sup 99m}Tc-annexin A5 (mean, 10.38 %ID x kg/m{sup 2}). The regional uptake levels of each tracer correlated with the Oil Red O staining score (r = 0.65, p < 0.05 for {sup 99m}Tc-annexin A5; r = 0.56, p < 0.05 for {sup 18}F-FDG). The uptake ratios of advanced lesions (score >0.5) to early lesions (score <0.5) were significantly higher for {sup 99m}Tc-annexin A5 than for {sup 18}F-FDG (f = 4.73, p = 0.03). Both {sup 99m}Tc-annexin A5 and {sup 18}F-FDG accumulate in atherosclerotic lesions and correlate with the severity of each lesion. The higher absolute uptake levels of {sup 18}F-FDG may be advantageous for lesion detection, whereas the preferential uptake of {sup 99m}Tc-annexin A5 in advanced lesions may be a useful indicator of late-stage lesions or vulnerable plaque transformation. (orig.)

Annexin A4 fucosylation enhances its interaction with the NF-kB p50 and promotes tumor progression of ovarian clear cell carcinoma.

Science.gov (United States)

Wang, Huimin; Deng, Lu; Cai, Mingbo; Zhuang, Huiyu; Zhu, Liancheng; Hao, Yingying; Gao, Jian; Liu, Juanjuan; Li, Xiao; Lin, Bei

2017-12-08

To study the structural relationship between annexin A4 and the Lewis y antigen and compare their expression and significance in ovarian clear cell carcinoma, and to explore how annexin A4 fucose glycosylation effects the interaction between annexin A4 and NF-kB p50, and how it promotes tumour progression of ovarian clear cell carcinoma. Structural relationships between annexin A4 and Lewis y antigen were detected using immunoprecipitation. Annexin A4 and Lewis y antigen expression in various subtypes of ovarian cancer tissues was detected by immunohistochemistry, and the relation between their expression was examined. Any interactions between annexin A4 and NF-kB p50 in ovarian clear cell carcinoma were detected by co-immunoprecipitation. Then looked for changes in expression of Lewis y antigen, annexin A4, NF-kB p50 and a number of downstream related molecules before and after transfection annexin A4 or FUT1, and also analyzed changes in biological processes. Lewis y antigen is a part of annexin A4 structure. The expression rate of both annexin A4 and Lewis y antigen was significantly higher in ovarian clear cell carcinoma than in other subtypes of epithelial ovarian cancer, and are associated with the clinical stages, chemotherapy resistance and poor prognostic. The interaction between annexin A4 and NF-kB p50 promoted cell proliferation, adhesion, invasion, metastasis ability and autophagy, and inhibits apoptosis, Lewis y enhanced this interaction. Annexin A4 contains Lewis y structure, Lewis y antigen modification of annexin A4 enhances its interaction with NF-kB p50, which promotes ovarian clear cell carcinoma malignancy progression.

Melatonin may play a role in modulation of bax and bcl-2 expression levels to protect rat peripheral blood lymphocytes from gamma irradiation-induced apoptosis

International Nuclear Information System (INIS)

Mohseni, Mehran; Mihandoost, Ehsan; Shirazi, Alireza; Sepehrizadeh, Zargham; Bazzaz, Javad Tavakkoly; Ghazi-khansari, Mahmoud

2012-01-01

The close relationship between free radicals effects and apoptosis process has been proved. Melatonin has been reported as a direct free radical scavenger. We investigated the capability of melatonin in the modification of radiation-induced apoptosis and apoptosis-associated upstream regulators expression in rat peripheral blood lymphocytes. Rats were irradiated with a single whole body Cobalt 60-gamma radiation dose of 8 Gy at a dose rate of 101 cGy/min with or without melatonin pretreatments at different concentrations of 10 and 100 mg/kg body weight. The rats were divided into eight groups of control, irradiation-only, vehicle-only, vehicle plus irradiation, 10 mg/kg melatonin alone, 10 mg/kg melatonin plus irradiation, 100 mg/kg melatonin alone and 100 mg/kg melatonin plus irradiation. Rats were given an intraperitoneal (IP) injection of melatonin or the same volume of vehicle alone 1 h prior to irradiation. Blood samples were taken 4, 24, 48 and 72 h after irradiation for evaluation of flow cytometric analysis of apoptotic lymphocytes using Annexin V/PI assay and measurement of bax and bcl-2 expression using quantitative real-time PCR (RT 2 qPCR). Irradiation-only and vehicle plus irradiation showed an increase in the percentage of apoptotic lymphocytes significantly different from control group (P < 0.01), while melatonin pretreatments in a dose-dependent manner reduced it as compared with the irradiation-only and vehicle plus irradiation groups (P < 0.01) in all time points. This reduced apoptosis by melatonin was related to the downregulation of bax, upregulation of bcl-2, and therefore reduction of bax/bcl-2 ratio. Our results suggest that melatonin in these doses may provide modulation of bax and bcl-2 expression as well as bax/bcl-2 ratio to protect rat peripheral blood lymphocytes from gamma irradiation-induced apoptosis.

Melatonin may play a role in modulation of bax and bcl-2 expression levels to protect rat peripheral blood lymphocytes from gamma irradiation-induced apoptosis

Energy Technology Data Exchange (ETDEWEB)

Mohseni, Mehran [Department of Radiology and Medical Physics, Faculty of Paramedicine, Kashan University of Medical Sciences, Kashan (Iran, Islamic Republic of); Mihandoost, Ehsan, E-mail: mihandoost.e@gmail.com [Department of Medical Radiation Engineering, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Shirazi, Alireza [Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Sepehrizadeh, Zargham [Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Bazzaz, Javad Tavakkoly [Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Ghazi-khansari, Mahmoud [Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

2012-10-15

The close relationship between free radicals effects and apoptosis process has been proved. Melatonin has been reported as a direct free radical scavenger. We investigated the capability of melatonin in the modification of radiation-induced apoptosis and apoptosis-associated upstream regulators expression in rat peripheral blood lymphocytes. Rats were irradiated with a single whole body Cobalt 60-gamma radiation dose of 8 Gy at a dose rate of 101 cGy/min with or without melatonin pretreatments at different concentrations of 10 and 100 mg/kg body weight. The rats were divided into eight groups of control, irradiation-only, vehicle-only, vehicle plus irradiation, 10 mg/kg melatonin alone, 10 mg/kg melatonin plus irradiation, 100 mg/kg melatonin alone and 100 mg/kg melatonin plus irradiation. Rats were given an intraperitoneal (IP) injection of melatonin or the same volume of vehicle alone 1 h prior to irradiation. Blood samples were taken 4, 24, 48 and 72 h after irradiation for evaluation of flow cytometric analysis of apoptotic lymphocytes using Annexin V/PI assay and measurement of bax and bcl-2 expression using quantitative real-time PCR (RT{sup 2}qPCR). Irradiation-only and vehicle plus irradiation showed an increase in the percentage of apoptotic lymphocytes significantly different from control group (P < 0.01), while melatonin pretreatments in a dose-dependent manner reduced it as compared with the irradiation-only and vehicle plus irradiation groups (P < 0.01) in all time points. This reduced apoptosis by melatonin was related to the downregulation of bax, upregulation of bcl-2, and therefore reduction of bax/bcl-2 ratio. Our results suggest that melatonin in these doses may provide modulation of bax and bcl-2 expression as well as bax/bcl-2 ratio to protect rat peripheral blood lymphocytes from gamma irradiation-induced apoptosis.

99mTc-HYNIC-Annexin A5 in Oncology: Evaluating Efficacy of Anti-Cancer Therapies

International Nuclear Information System (INIS)

Schaper, Frédéric L.W.V.J.; Reutelingsperger, Chris P.

2013-01-01

Evaluation of efficacy of anti-cancer therapy is currently performed by anatomical imaging (e.g., MRI, CT). Structural changes, if present, become apparent 1–2 months after start of therapy. Cancer patients thus bear the risk to receive an ineffective treatment, whilst clinical trials take a long time to prove therapy response. Both patient and pharmaceutical industry could therefore profit from an early assessment of efficacy of therapy. Diagnostic methods providing information on a functional level, rather than a structural, could present the solution. Recent technological advances in molecular imaging enable in vivo imaging of biological processes. Since most anti-cancer therapies combat tumors by inducing apoptosis, imaging of apoptosis could offer an early assessment of efficacy of therapy. This review focuses on principles of and clinical experience with molecular imaging of apoptosis using Annexin A5, a widely accepted marker for apoptosis detection in vitro and in vivo in animal models. 99m Tc-HYNIC-Annexin A5 in combination with SPECT has been probed in clinical studies to assess efficacy of chemo- and radiotherapy within 1–4 days after start of therapy. Annexin A5-based functional imaging of apoptosis shows promise to offer a personalized medicine approach, now primarily used in genome-based medicine, applicable to all cancer patients

Macrophage migration inhibitory factor counter-regulates dexamethasone-induced annexin 1 expression and influences the release of eicosanoids in murine macrophages.

Science.gov (United States)

Sun, Yu; Wang, Yu; Li, Jia-Hui; Zhu, Shi-Hui; Tang, Hong-Tai; Xia, Zhao-Fan

2013-10-01

Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine and glucocorticoid (GC) counter-regulator, has emerged as an important modulator of inflammatory responses. However, the molecular mechanisms of MIF counter-regulation of GC still remain incomplete. In the present study, we investigated whether MIF mediated the counter-regulation of the anti-inflammatory effect of GC by affecting annexin 1 in RAW 264.7 macrophages. We found that stimulation of RAW 264.7 macrophages with lipopolysaccharide (LPS) resulted in down-regulation of annexin 1, while GC dexamethasone (Dex) or Dex plus LPS led to significant up-regulation of annexin 1 expression. RNA interference-mediated knockdown of intracellular MIF increased annexin 1 expression with or without incubation of Dex, whereas Dex-induced annexin 1 expression was counter-regulated by the exogenous application of recombinant MIF. Moreover, recombinant MIF counter-regulated, in a dose-dependent manner, inhibition of cytosolic phospholipase A2α (cPLA2α) activation and prostaglandin E2 (PGE2 ) and leukotriene B4 (LTB4 ) release by Dex in RAW 264.7 macrophages stimulated with LPS. Endogenous depletion of MIF enhanced the effects of Dex, reflected by further decease of cPLA2α expression and lower PGE2 and LTB4 release in RAW 264.7 macrophages. Based on these data, we suggest that MIF counter-regulates Dex-induced annexin 1 expression, further influencing the activation of cPLA2α and the release of eicosanoids. These findings will add new insights into the mechanisms of MIF counter-regulation of GC. © 2013 John Wiley & Sons Ltd.

Annexin A1 expression in a pooled breast cancer series : Association with tumor subtypes and prognosis

NARCIS (Netherlands)

Sobral-Leite, Marcelo; Wesseling, Jelle; Smit, Vincent T H B M; Nevanlinna, Heli; van Miltenburg, Martine H.; Sanders, Joyce; Hofland, Ingrid; Blows, Fiona M.; Coulson, Penny; Patrycja, Gazinska; Schellens, Jan H M; Fagerholm, Rainer; Heikkilä, Päivi; Aittomäki, Kristiina; Blomqvist, Carl; Provenzano, Elena; Ali, Hamid Raza; Figueroa, Jonine; Sherman, Mark; Lissowska, Jolanta; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli Matti; Hartikainen, Jaana M.; Phillips, Kelly Anne; Couch, Fergus J.; Olson, Janet E.; Vachon, Celine; Visscher, Daniel; Brenner, Hermann; Butterbach, Katja; Arndt, Volker; Holleczek, Bernd; Hooning, Maartje J.; Hollestelle, Antoinette; Martens, John W M; van Deurzen, Carolien H M; van de Water, Bob; Broeks, Annegien; Chang-Claude, Jenny; Chenevix-Trench, Georgia; Easton, Douglas F.; Pharoah, Paul D P; García-Closas, Montserrat; de Graauw, Marjo; Schmidt, Marjanka K.; Aghmesheh, Morteza; Amor, David; Andrews, Lesley; Antill, Yoland; Armitage, Shane; Arnold, Leanne; Balleine, Rosemary; Bankier, Agnes; Bastick, Patti; Beesley, Jonathan; Beilby, John; Bennett, Barbara; Bennett, Ian; Berry, Geoffrey; Blackburn, Anneke; Bogwitz, Michael; Brennan, Meagan; Brown, Melissa; Buckley, Michael; Burgess, Matthew; Burke, Jo; Butow, Phyllis; Byron, Keith; Callen, David; Campbell, Ian; Chauhan, Deepa; Chauhan, Manisha; Christian, Alice; Clarke, Christine; Colley, Alison; Cotton, Dick; Crook, Ashley; Cui, James; Culling, Bronwyn; Cummings, Margaret; Dawson, Sarah Jane; deFazio, Anna; Delatycki, Martin; Dickson, Rebecca; Dixon, Joanne; Dobrovic, Alexander; Dudding, Tracy; Edkins, Ted; Edwards, Stacey; Eisenbruch, Maurice; Farshid, Gelareh; Fawcett, Susan; Fellows, Andrew; Fenton, Georgina; Field, Michael; Firgaira, Frank; Flanagan, James; Fleming, Jean; Fong, Peter; Forbes, John; Fox, Stephen; French, Juliet; Friedlander, Michael; Gaff, Clara; Gardner, Mac; Gattas, Mike; George, Peter; Giles, Graham; Gill, Grantley; Goldblatt, Jack; Greening, Sian; Grist, Scott; Haan, Eric; Hardie, Kate; Harris, Marion; Hart, Stewart; Hayward, Nick; Healey, Sue; Heiniger, Louise; Hopper, John; Humphrey, Evelyn; Hunt, Clare; James, Paul; Jenkins, Mark; Jones, Alison; Kefford, Rick; Kidd, Alexa; Kiely, Belinda; Kirk, Judy; Koehler, Jessica; Kollias, James; Kovalenko, Serguei; Lakhani, Sunil; Leaming, Amanda; Leary, Jennifer; Lim, Jacqueline; Lindeman, Geoff; Lipton, Lara; Lobb, Liz; Mann, Graham; Marsh, Deborah; McLachlan, Sue Anne; Meiser, Bettina; Meldrum, Cliff; Milne, Roger; Mitchell, Gillian; Newman, Beth; Niedermayr, Eveline; Nightingale, Sophie; O'Connell, Shona; O'Loughlin, Imelda; Osborne, Richard; Pachter, Nick; Patterson, Briony; Peters, Lester; Phillips, Kelly; Price, Melanie; Purser, Lynne; Reeve, Tony; Reeve, Jeanne; Richards, Robert; Rickard, Edwina; Robinson, Bridget; Rudzki, Barney; Saleh, Mona; Salisbury, Elizabeth; Sambrook, Joe; Saunders, Christobel; Saunus, Jodi; Sayer, Robyn; Scott, Elizabeth; Scott, Rodney; Scott, Clare; Seshadri, Ram; Sexton, Adrienne; Sharma, Raghwa; Shelling, Andrew; Simpson, Peter; Southey, Melissa; Spurdle, Amanda; Suthers, Graeme; Sykes, Pamela; Tassell, Margaret; Taylor, Donna; Taylor, Jessica; Thierry, Benjamin; Thomas, Susan; Thompson, Ella; Thorne, Heather; Townshend, Sharron; Trainer, Alison; Tran, Lan; Tucker, Kathy; Tyler, Janet; Visvader, Jane; Walker, Logan; Walpole, Ian; Ward, Robin; Waring, Paul; Warner, Bev; Warren, Graham; Williams, Rachael; Wilson, Judy; Winship, Ingrid; Wu, Kathy; Young, Mary Ann; Bowtell, D.; Green, A.; Webb, P.; de Fazio, A.; Gertig, D.

2015-01-01

Background: Annexin A1 (ANXA1) is a protein related with the carcinogenesis process and metastasis formation in many tumors. However, little is known about the prognostic value of ANXA1 in breast cancer. The purpose of this study is to evaluate the association between ANXA1 expression, BRCA1/2

Expression of annexin and Annexin-mRNA in rat brain under influence of steroid drugs

NARCIS (Netherlands)

Voermans, PH; Go, KG; ter Horst, GJ; Ruiters, MHJ; Solito, E; Parente, L; James, HE; Marshall, LF; Reulen, HJ; Baethmann, A; Marmarou, A; Ito, U; Hoff, JT; Kuroiwa, T; Czernicki, Z

1997-01-01

Brain tissue of rats pretreated with methylprednisolone or with the 21-aminosteroid U74389F, and that of untreated control rats, was assessed for the expression of Annexin-l (Anx-1) and the transcription of its mRNA. For this purpose Anx-1 cDNA was amplified and simultaneously a T7-RNA-polymerase

Preparation and in vitro evaluation of human recombinant annexin V using for apoptosis

International Nuclear Information System (INIS)

Chen Daming; Beijing Univ., Beijing; Qi Benzhong; Yang Hongwei; Luo Zhifu; Zhang Jinrong; Jin Xiaohai; Jia Bing; Xie Hong; Ma Dalong

2004-01-01

Human recombinant Annexin V was produced by expression in E coli with high efficiency through genetic engineering. The technique procedure concerned in the temperature and time of vector expression, the basic routine and purification of proteins was established in order to obtain a large quantity of Annexin V. the results of SDS-PAGE analysis and the apoptosis detection of single cell of thymocytes of Balb/c mice using FITC-Annexin V caused by dexamethasone with availableness show that the mature Annexin V with high purity and biologic activity is obtained by ion exchange chromatography. The results of cell binding assay show that its KD is 8.53 nmol/mL and RT is 8.79 nmol/mL. (authors)

Diagnostic value of anti-annexin A5 antibodies in seropositive versus seronegative antiphospholipid syndrome patients

Directory of Open Access Journals (Sweden)

Gihan Omar

2018-04-01

Full Text Available Background: Current laboratory criteria for antiphospholipid syndrome (APS classification recommend testing positive for antiphospholipid (aPL antibodies. However, there appears to be a subset of patients with classical APS manifestations who test negative. Aim of the work: To analyze the potential clinical usefulness of testing for anti-annexin A5 antibodies in patients with APS and to study the effectiveness of testing for non-criteria aPLs in an attempt to increase the diagnostic yield, particularly in seronegative APS. Patients and methods: 60 APS patients were divided into two groups; 30 seropositive (SP-APS (group I and 30 age and sex matched seronegative (sN-APS testing negative for aPL antibodies. Serum assay for detection of isotypes of anti-annexin A5 antibodies (IgG and IgM were conducted. Results: The mean age of the patients was 32.9 ± 5.8 years, female:male 57:3 and disease duration in SP-APS versus sN-APS (10.17 ± 4.9 years versus 9.6 ± 5.5 years respectively. Secondary APS was present in 16(53.3% patients in group I compared to 3(10% in group II (p < 0.0001. The mean anti-AnxA5 IgG level was 10.7 ± 5.6 U/ml and IgM was 11.2 ± 7.1 U/ml and were comparable between the 2 groups. The obstetric and thrombotic morbidity had no significant differences between SP and sN-APS. The IgG and IgM levels significantly correlated with the pregnancy morbidity, venous and arterial thrombosis events and showed reasonable sensitivities in their prediction (IgG:71.2%,72.8% and 75.8%; IgM: 68%,67.8% and 71.4% respectively and specificities (IgG:75.9%,77.8% and 81.5%; IgM: 70.9%,73.1% and 73.7% respectively. Conclusion: anti-annexinA5 antibodies are promising for detecting obstetric and thrombotic morbidity in both SP- and sN-APS patients. Keywords: Antiphospholipid syndrome, Seropositive APS (SP-APS, Seronegative APS (sN-APS, Anti-annexin A5 antibodies

Apoptosis imaging with Iodine-124 labeled Annexin V in Fas-mediated hepatic apoptosis model

International Nuclear Information System (INIS)

Lee, Tae Sup; Woo, Kwang Sun; Chung, Wee Sup; Kim, Kyung Min; Kim, Jae Hong; Chun, Kwon Soo; Choi, Chang Woon; Lim, Sang Moo; Cheon, Gi Jeong

2006-01-01

Healthy cells and, to a lesser extent, malignant cells undergo apoptosis or programmed cell death in response to a variety of stimuli. At an early stage in this process the cell membrane changes so that phosphatidylserine (PS), a lipid normally present on the membrane's inner surface, is exposed on the outer surface. This change in the membrane can be detected by the binding of annexin V to the external PS, and this has formed the basis for an in vitro assay for apoptosis. Blankenberg et al. have applied annexin V to the in vivo imaging of apoptosis by labeling annexin V with 99mTc. With this technique, they have been able to image apoptosis. To extend the use of annexin V to PET, it would be very desirable to iodinate the molecule. The relatively long half-life (4.2 d) of the positron emitting iodine-124 presents several advantages. For example in vivo detection and quantification of longer term biological processes is possible. Also, this cyclotron-generated radionuclide can be prepared well in advance and the established radioiodine labeling techniques can be applied. However, there are some disadvantages such as a relatively low ratio of disintegrations resulting in positrons (23%) and a rather complex decay scheme resulting in several high-energy gamma emissions (0.6- 1.69 MeV). Despite this fact, iodine-124 is still considered to be suitable for positron emission tomography (PET). In this study, we are investigating the feasibility of apoptosis imaging using iodine-124 labeled annexin V in Fas-mediated hepatic apoptosis model

From Ugly Duckling to Swan: Unexpected Identification from Cell-SELEX of an Anti-Annexin A2 Aptamer Targeting Tumors

Science.gov (United States)

Cibiel, Agnes; Nguyen Quang, Nam; Gombert, Karine; Thézé, Benoit; Garofalakis, Anikitos; Ducongé, Frédéric

2014-01-01

Background Cell-SELEX is now widely used for the selection of aptamers against cell surface biomarkers. However, despite negative selection steps using mock cells, this method sometimes results in aptamers against undesirable targets that are expressed both on mock and targeted cells. Studying these junk aptamers might be useful for further applications than those originally envisaged. Methodology/Principal Findings Cell-SELEX was performed to identify aptamers against CHO-K1 cells expressing human Endothelin type B receptor (ETBR). CHO-K1 cells were used for negative selection of aptamers. Several aptamers were identified but no one could discriminate between both cell lines. We decided to study one of these aptamers, named ACE4, and we identified that it binds to the Annexin A2, a protein overexpressed in many cancers. Radioactive binding assays and flow cytometry demonstrated that the aptamer was able to bind several cancer cell lines from different origins, particularly the MCF-7 cells. Fluorescence microscopy revealed it could be completely internalized in cells in 2 hours. Finally, the tumor targeting of the aptamer was evaluated in vivo in nude mice xenograft with MCF-7 cells using fluorescence diffuse optical tomography (fDOT) imaging. Three hours after intravenous injection, the aptamer demonstrated a significantly higher uptake in the tumor compared to a scramble sequence. Conclusions/Significance Although aptamers could be selected during cell-SELEX against other targets than those initially intended, they represent a potential source of ligands for basic research, diagnoses and therapy. Here, studying such aptamers, we identify one with high affinity for Annexin A2 that could be a promising tool for biomedical application. PMID:24489826

99mTc-HYNIC-Annexin A5 in Oncology: Evaluating Efficacy of Anti-Cancer Therapies

Directory of Open Access Journals (Sweden)

Chris P. Reutelingsperger

2013-05-01

Full Text Available Evaluation of efficacy of anti-cancer therapy is currently performed by anatomical imaging (e.g., MRI, CT. Structural changes, if present, become apparent 1–2 months after start of therapy. Cancer patients thus bear the risk to receive an ineffective treatment, whilst clinical trials take a long time to prove therapy response. Both patient and pharmaceutical industry could therefore profit from an early assessment of efficacy of therapy. Diagnostic methods providing information on a functional level, rather than a structural, could present the solution. Recent technological advances in molecular imaging enable in vivo imaging of biological processes. Since most anti-cancer therapies combat tumors by inducing apoptosis, imaging of apoptosis could offer an early assessment of efficacy of therapy. This review focuses on principles of and clinical experience with molecular imaging of apoptosis using Annexin A5, a widely accepted marker for apoptosis detection in vitro and in vivo in animal models. 99mTc-HYNIC-Annexin A5 in combination with SPECT has been probed in clinical studies to assess efficacy of chemo- and radiotherapy within 1–4 days after start of therapy. Annexin A5-based functional imaging of apoptosis shows promise to offer a personalized medicine approach, now primarily used in genome-based medicine, applicable to all cancer patients.

Methotrexate-Induced Accumulation of Fluorescent Annexin V in Collagen-Induced Arthritis

Directory of Open Access Journals (Sweden)

Andreas Wunder

2005-01-01

Full Text Available We examined the accumulation of Cy5.5-labeled annexin V in the paws of mice with and without collagen-induced arthritis, with and without methotrexate (MTX treatment, by near-infrared fluorescence imaging. Fluorescence reflectance imaging (FRI of paws was performed 48 hr after MTX injection and at 10 min and 3 hr after the injection of Cy5.5-annexin V (1 nmol dye per mouse. With arthritic paws, MTX treatment caused a 7-fold increase in fluorescence intensity compared with the paws of untreated mice and a 4-fold increase compared to nonarthritic paws of MTX-treated mice (p < .001 each. Tissue samples of paws were examined histologically for Cy5.5 fluorescence and by TUNEL staining for apoptosis. Cy5.5-annexin V was seen in the hyperplastic synovia of MTX-treated mice, and TUNEL staining for apoptosis showed apoptotic cells in the hyperplastic synovia. Monitoring the uptake of Cy5.5-annexin V in arthritic paws by FRI provided a method of assessing a response to MTX, a response that was readily quantitated with simple instrumentation and that occurred before conventional measurements of treatment response.

Annexin IV (Xanx-4) has a functional role in the formation of pronephric tubules.

Science.gov (United States)

Seville, Rachel A; Nijjar, Sarbjit; Barnett, Mark W; Massé, Karine; Jones, Elizabeth A

2002-04-01

Vertebrate kidney organogenesis is characterised by the successive formation of the pronephros, the mesonephros and the metanephros. The pronephros is the first to form and is the functional embryonic kidney of lower vertebrates; although it is vestigial in higher vertebrates, it is a necessary precursor for the other kidney types. The Xenopus pronephros is a simple paired organ; each nephron consists of a single large glomus, one set of tubules and a single duct. The simple organisation of the pronephros and the amenability of Xenopus laevis embryos to manipulation make the Xenopus pronephros an attractive system in which to study organogenesis. It has been shown that pronephric tubules can be induced to form in presumptive ectodermal tissue by treatment with RA and activin. We have used this system in a subtractive hybridisation screen that resulted in the cloning of Xenopus laevis annexin IV (Xanx-4). Xanx-4 transcripts are specifically located to the developing pronephric tubules, and the protein to the luminal surface of these tubules. Temporal expression shows zygotic transcription is upregulated at the time of pronephric tubule specification and persists throughout pronephric development. The temporal and spatial expression pattern of Xanx-4 suggests it may have a role in pronephric tubule development. Overexpression of Xanx-4 yields no apparent phenotype, but Xanx-4 depletion, using morpholinos, produces a shortened, enlarged tubule phenotype. The phenotype observed can be rescued by co-injection of Xanx-4 mRNA. Although the function of annexins is not yet clear, studies have suggested a role for annexins in a number of cellular processes. Annexin IV has been shown to have an inhibitory role in the regulation of epithelial calcium-activated chloride ion conductance. The enlarged pronephric tubule phenotype observed may be attributed to incorrect modulation of exocytosis, membrane plasticity or ion channels and/or water homeostasis. In this study, we

Low Annexin A1 expression predicts benefit from induction chemotherapy in oral cancer patients with moderate or poor pathologic differentiation grade.

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Zhu, Dong-wang; Liu, Ying; Yang, Xiao; Yang, Cheng-zhe; Ma, Jie; Yang, Xi; Qiao, Jin-ke; Wang, Li-zhen; Li, Jiang; Zhang, Chen-ping; Zhang, Zhi-yuan; Zhong, Lai-ping

2013-06-21

The benefit of induction chemotherapy in locally advanced oral squamous cell carcinoma (OSCC) remains to be clearly defined. Induction chemotherapy is likely to be effective for biologically distinct subgroups of patients and biomarker development might lead to identification of the patients whose tumors are to respond to a particular treatment. Annexin A1 may serve as a biomarker for responsiveness to induction chemotherapy. The aim of this study was to investigate Annexin A1 expression in pre-treatment biopsies from a cohort of OSCC patients treated with surgery and post-operative radiotherapy or docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy followed by surgery and post-operative radiotherapy. Furthermore we sought to assess the utility of Annexin A1 as a prognostic or predictive biomarker. Immunohistochemical staining for Annexin A1 was performed in pre-treatment biopsies from 232 of 256 clinical stage III/IVA OSCC patients. Annexin A1 index was estimated as the proportion of tumor cells (low and high, benefited from TPF induction chemotherapy as measured by distant metastasis-free survival (P=0.048, HR=0.373) as well as overall survival (P=0.078, HR=0.410). Annexin A1 can be used as a prognostic biomarker for OSCC. Patients with moderate/poorly differentiated OSCC and low Annexin A1 expression can benefit from the addition of TPF induction chemotherapy to surgery and post-operative radiotherapy. Annexin A1 expression can potentially be used as a predictive biomarker to select OSCC patients with moderate/poorly differentiated tumor who may benefit from TPF induction chemotherapy.

99mTc-Hynic-annexin V imaging to evaluate inflammation and apoptosis in rats with autoimmune myocarditis

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Tokita, Naoki; Izumi, Tohru; Hasegawa, Shinji; Maruyama, Kaoru; Blankenberg, Francis G.; Tait, Jonathan F.; Strauss, William H.; Nishimura, Tsunehiko

2003-01-01

Inflammation and cell death are two important components of myocarditis. We evaluated the distribution of inflammation and apoptotic cell death in rats with autoimmune myocarditis using two radiotracers - technetium-99m Hynic-annexin V ( 99m Tc-annexin) as a marker of apoptotic cell death and carbon-14 deoxyglucose ( 14 C-DG) as a marker of inflammation - in comparison with histologic findings. Three, 7 and 14 weeks after immunization with porcine cardiac myosin (acute, subacute, and chronic phases, respectively) 99m Tc-annexin and 14 C-DG were injected. The uptake in the total heart was determined as the percentage of injected dose per gram (% ID/g) by tissue counting. Dual-tracer autoradiography with 99m Tc-annexin and 14 C-DG was performed. The distribution of each of these agents was compared with the results of hematoxylin and eosin staining to identify areas of inflammation, and TUNEL staining to identify areas of apoptosis. Total cardiac uptake of 99m Tc-annexin in the acute phase of myocarditis was significantly higher than that in normal rats (1.28%±0.30% vs 0.46%±0.01%; P 14 C-DG in the acute phase of myocarditis was significantly higher than that in normal rats (2.78%±0.95% vs 1.02%±0.25%; P 14 C-DG uptake; some also corresponded to areas of high 99m Tc-annexin uptake in the acute phase of myocarditis. 99m Tc-annexin localization was strongly correlated with the number of TUNEL-positive cells (P 14 C-DG showed no relationship with it. There is a marked difference in the distribution of inflammation and apoptotic cell death in the myocardium of animals with immune myocarditis. These changes are mirrored by the localization of 14 C-DG and 99m Tc-annexin. Sites of inflammation and zones of apoptotic cell death change over the course of immune myocarditis. (orig.)

The MiR-495/Annexin A3/P53 Axis Inhibits the Invasion and EMT of Colorectal Cancer Cells

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Zhigang Bai

2017-12-01

Full Text Available Background/Aims: More and more reports have shown that the dysregulation of miRNAs can contribute to the progression and metastasis of human cancers. Many studies have shown that the down-regulation of the miR-495 level occurs in a variety of cancers, including colorectal cancer (CRC. However, the precise molecular mechanisms of miR-495 in CRC have not been well clarified. In the current study, we investigated the biological functions and molecular mechanisms of miR-495 in CRC cell lines. Methods: qRT-PCR was used to determine the level of miR-495 in CRC cell lines and tissues. A miR-495 mimic and inhibitor were transfected into CRC cells, and the effects of miR-495 on the invasion and EMT were explored by qRT-PCR as well as transwell and Western blot assays. Meanwhile, luciferase assays were performed to validate Annexin A3 as a miR-495 target in CRC cells. Results: In our study, we found that miR-495 is down-regulated in CRC tissues and cell lines. Moreover, the low level of miR-495 was associated with increased expression of Annexin A3 in CRC tissues and cell lines. The invasion and EMT of CRC cells were suppressed by the overexpression of miR-495. However, the down-regulation of miR-495 promoted the invasion and EMT of CRC cells. Bioinformatics analysis predicted that Annexin A3 was a potential target gene of miR-495. Next, the luciferase reporter assay confirmed that miR-495 could directly target Annexin A3. Consistent with the effect of miR-495, the down-regulation of Annexin A3 by siRNA inhibited the invasion and EMT of CRC cells through the up-regulation of p53. The introduction of Annexin A3 in CRC cells partially blocked the effects of the miR-495 mimic. Conclusion: The introduction of miR-495 directly targeted Annexin A3 to inhibit the invasion and EMT of CRC cells by up-regulating p53, and the down-regulation of Annexin A3 was essential for inhibiting the invasion and EMT of CRC cells by overexpressing miR-495. Overall, the re

99mTc-HYNIC-annexin V SPECT imaging of acute stroke and its response to neuroprotective therapy with anti-Fas ligand antibody

International Nuclear Information System (INIS)

Blankenberg, Francis G.; Kalinyak, Judy; Cheng, Danye; Goris, Michael L.; Liu, Liping; Koike, Maya; Yenari, Midori Anne; Green, Allan; Vanderheyden, Jean-Luc; Tong, David C.

2006-01-01

The first aim of the study was to determine whether 99m Tc-HYNIC-annexin V, a marker of cellular stress and apoptosis, can detect ischemic injury in patients with acute stroke. Secondly, we wished to test radiolabeled annexin's ability to monitor therapy in a rodent model of focal ischemic injury. SPECT imaging of patients was performed between 1 and 2 h after intravenous injection of 30 mCi (1,110 MBq) of tracer. Eight MFL4 (anti-FasL) antibody-treated (400 μg i.p. days 0 and 3) and 21 control adult male Sprague-Dawley rats underwent small animal SPECT imaging with 5-10 mCi (185-370 MBq) of tracer, 1 and 6 days after a 2-h intraluminal thread occlusion of the left middle cerebral artery. Two patients with acute stroke had regions of multifocal annexin uptake that correlated with sites of restricted diffusion on MRI. Anti-FasL antibody treatment significantly reduced annexin uptake by 92% with a 60% decrease in the number of caspase-8 staining (apoptotic) neurons on day 1. On day 6, treated animals had an 80% reduction in tracer uptake with a 75% decrease in infarct size as compared with controls. Annexin uptake in controls and treated animals (day 6) linearly correlated with infarct size (r 2 =0.603, p=0.0036) and the number of TUNEL-positive (apoptotic) nuclei (r 2 =0.728, p=0.00084). Annexin imaging shows foci of increased uptake at sites of ischemic injury in patients with acute stroke. Annexin imaging can assess the effects of therapy for ischemic cerebral injury in rats, suggesting its potential as a non-invasive indicator of drug efficacy in future clinical trials. (orig.)

Evaluation of adenosine preconditioning with 99mTc-His10-annexin V in a porcine model of myocardium ischemia and reperfusion injury: preliminary study

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Ye Fei; Fang Wei; Wang Feng; Hua Zichun; Wang Zizheng; Yang Xiang

2011-01-01

Purpose: The goal of this study was to evaluate the feasibility of 99m Tc-His 10 -annexin V for the detection of acute myocardial cell death and to assess the effect of adenosine preconditioning in a porcine model of myocardium ischemia and reperfusion injury (RI). Materials and Methods: 99m Tc-His 10 -annexin V was prepared by one-step direct labeling, and RCP and radiostability were tested. The binding of 99m Tc-His 10 -annexin V to apoptosis was validated in vitro using camptothecin-induced Jurkat cells. In vivo biodistribution was determined in mice by the dissection method. Ischemia of 20-30 min was induced by balloon occlusion of the epicardial coronary artery of the porcine model (n=14). Adenosine was infused intravenously in six pigs before coronary occlusion. 99m Tc-His 10 -annexin V (n=12) was injected intravenously at 1 h after reperfusion. SPECT/CT was acquired at 3 h postinjection. Myocardial perfusion imaging (MPI) with 99m Tc-MIBI was also performed 1 day after His 10 -annexin V imaging. Cardiac tissues were analyzed postmortem using hematoxylin-and-eosin and TUNEL staining. Caspase-3 activity was measured to confirm the presence of apoptosis. Results: 99m Tc-His 10 -annexin V had a RCP >98% and high stability 2 h after radiolabeling; it could bind to apoptotic cells with high affinity. Biodistribution of 99m Tc-His 10 -annexin V showed a predominant uptake in the kidney and relatively low uptake in the myocardium, liver and gastrointestinal tract; rapid clearance from blood and kidney was observed. In the untreated group, intense uptake of His 10 -annexin V was visualized in the defect which was shown in MPI, whereas in the adenosine group a mild uptake of 99m Tc-His 10 -annexin was found in the risk area which showed no defects in the 99m Tc-MIBI image. TUNEL staining and activated caspase-3 confirmed the ongoing apoptosis in RI. Adenosine preconditioning significantly diminished the level of apoptosis. Uptake of His 10 -annexin V in RI correlated

Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-induced LDL receptor degradation.

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Nabil G Seidah

Full Text Available Proprotein convertase subtilisin/kexin-9 (PCSK9 enhances the degradation of hepatic low-density lipoprotein receptor (LDLR. Deletion of PCSK9, and loss-of-function mutants in humans result in lower levels of circulating LDL-cholesterol and a strong protection against coronary heart disease. Accordingly, the quest for PCSK9 inhibitors has major clinical implications. We have previously identified annexin A2 (AnxA2 as an endogenous binding partner and functional inhibitor of PCSK9. Herein, we studied the relevance of AnxA2 in PCSK9 inhibition and lipid metabolism in vivo. Plasma analyses of AnxA2(-/- mice revealed: i a ∼1.4-fold increase in LDL-cholesterol without significant changes in VLDLs or HDLs, and ii a ∼2-fold increase in circulating PCSK9 levels. Western blotting and immunohistochemistry of AnxA2(-/- tissues revealed that the LDLR was decreased by ∼50% in extrahepatic tissues, such as adrenals and colon. We also show that AnxA2-derived synthetic peptides block the PCSK9≡LDLR interaction in vitro, and adenoviral overexpression of AnxA2 in mouse liver increases LDLR protein levels in vivo. These results suggest that AnxA2 acts as an endogenous regulator of LDLR degradation, mostly in extrahepatic tissues. Finally, we identified an AnxA2 coding polymorphism, V98L, that correlates with lower circulating levels of PCSK9 thereby extending our results on the physiological role of AnxA2 in humans.

{sup 99m}Tc-HYNIC-annexin V SPECT imaging of acute stroke and its response to neuroprotective therapy with anti-Fas ligand antibody

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Blankenberg, Francis G.; Kalinyak, Judy; Cheng, Danye; Goris, Michael L. [Stanford University Hospital, Division of Pediatric Radiology/Department of Radiology, Palo Alto, CA (United States); Liu, Liping; Koike, Maya; Yenari, Midori Anne [University of California San Francisco and San Francisco Veterans Affairs Medical Center, Department of Neurology, San Francisco, CA (United States); Green, Allan; Vanderheyden, Jean-Luc [Theseus Imaging Corporation, Boston, MA (United States); Tong, David C. [Stanford University Hospital, Neurology and Neurological Sciences, Stanford, CA (United States)

2006-05-15

The first aim of the study was to determine whether {sup 99m}Tc-HYNIC-annexin V, a marker of cellular stress and apoptosis, can detect ischemic injury in patients with acute stroke. Secondly, we wished to test radiolabeled annexin's ability to monitor therapy in a rodent model of focal ischemic injury. SPECT imaging of patients was performed between 1 and 2 h after intravenous injection of 30 mCi (1,110 MBq) of tracer. Eight MFL4 (anti-FasL) antibody-treated (400 {mu}g i.p. days 0 and 3) and 21 control adult male Sprague-Dawley rats underwent small animal SPECT imaging with 5-10 mCi (185-370 MBq) of tracer, 1 and 6 days after a 2-h intraluminal thread occlusion of the left middle cerebral artery. Two patients with acute stroke had regions of multifocal annexin uptake that correlated with sites of restricted diffusion on MRI. Anti-FasL antibody treatment significantly reduced annexin uptake by 92% with a 60% decrease in the number of caspase-8 staining (apoptotic) neurons on day 1. On day 6, treated animals had an 80% reduction in tracer uptake with a 75% decrease in infarct size as compared with controls. Annexin uptake in controls and treated animals (day 6) linearly correlated with infarct size (r {sup 2}=0.603, p=0.0036) and the number of TUNEL-positive (apoptotic) nuclei (r {sup 2}=0.728, p=0.00084). Annexin imaging shows foci of increased uptake at sites of ischemic injury in patients with acute stroke. Annexin imaging can assess the effects of therapy for ischemic cerebral injury in rats, suggesting its potential as a non-invasive indicator of drug efficacy in future clinical trials. (orig.)

CELL DEATH DIFFERENTIATION IN BLACK HEADED RAMS SPERMATOZOA, USING FLUORESCENT LABELED ANNEXIN V

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M Ivanova-Kicheva

2008-11-01

Full Text Available Double staining kit of Annexin V Cy3.18/6-CFDA was used to investigate the changes in phospholipide asymmetry after treating sperm cells with dexamethasone. The % of spermatozoa with registered translocation of PS in treated with dexamethazone groups at the 10-th min and in control no treated varied from 2.74%±0.65 to 2.30%±0.89. After the 5 hour of incubation these % increased to 39.83±3.33 for the treated group and 23.44±1.12 for the control. It was concluded that Annexin V binding assay is more sensitive in the detection of deterioration in membrane function than other conventional methods such as motility analysis and supravital techniques.

Detection of focal hypoxic-ischemic injury and neuronal stress in a rodent model of unilateral MCA occlusion/reperfusion using radiolabeled annexin V

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Mari, Carina; Goris, Michael L. [Division of Nuclear Medicine, Department of Radiology, Stanford University Hospital, CA 94305, Stanford (United States); Karabiyikoglu, Murat; Yenari, Midori Anne [Departments of Neurosurgery and Neurology, Stanford University Hospital, CA 94305, Stanford (United States); Tait, Jonathan F. [Department of Laboratory Medicine, University of Washington Medical Center, WA 98195-7110, Seattle (United States); Blankenberg, Francis G. [Division of Nuclear Medicine, Department of Radiology, Stanford University Hospital, CA 94305, Stanford (United States); Division of Pediatric Radiology, Department of Radiology, Stanford University, Lucile Salter Packard Children' s Hospital, 725 Welch Road, Room 1673, CA 94305, Palo Alto (United States)

2004-05-01

In this study we wished to determine whether technetium-99m annexin V, an in vivo marker of cellular injury and death, could be used to noninvasively monitor neuronal injury following focal middle cerebral artery (MCA) occlusion/reperfusion injury. Sixteen adult male Sprague-Dawley rats (along with four controls) underwent left (unilateral) MCA intraluminal beaded thread occlusion for 2 h followed by reperfusion. One hour following tail vein injection of 5-10 mCi of {sup 99m}Tc-annexin V, animals underwent either single-photon emission computerized tomography (SPECT) or autoradiography followed by immunohistochemical analyses. There was abnormal, bilateral, multifocal uptake of {sup 99m}Tc-annexin V in each cerebral hemisphere as seen by both SPECT and autoradiography at 4 h and 1, 3, and 7 days after initiation of occlusion. The average maximal annexin V uptake at 4 h was 310%{+-}85% and 365%{+-}151% above control values (P<0.006) within the right and left hemispheres, respectively, peaking on day 3 with values of 925%{+-}734% and 1,194%{+-}643% (P<0.03) that decreased by day 7 to 489%{+-}233% and 785%{+-}225% (P<0.01). Total lesional volume of the left hemisphere was 226%, 261%, and 451% (P<0.03) larger than the right at 4, 24, and 72 h after injury, respectively. Annexin V localized to the cytoplasm of injured neurons ipsilateral to the site of injury as well as to otherwise normal-appearing neurons of the contralateral hemisphere as confirmed by dual fluorescent microscopy. It is concluded that there is abnormal bilateral, multifocal annexin V uptake, greater on the left than on the right side, within 4 h of unilateral left MCA ischemic injury and that the uptake peaks at 3 days and decreases by 7 days after injury. This pattern suggests that neuronal stress may play a role in the response of the brain to focal injury and be responsible for annexin V uptake outside the region of ischemic insult. (orig.)

Anti-Annexin V Antibodies: Association with Vascular Involvement and Disease Outcome in Patients with Systemic Sclerosis

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Iman A. Hassan

2010-04-01

Full Text Available Background: Systemic Sclerosis (SSc is characterized by skin thickening, fibrosis and vascular obliteration. The onset and course are heterogeneous. Prominent features include autoimmunity, inflammation and vascular damage. Aim of study: To measure the level of serum Anti-Annexin V antibodies in SSc patients and to study its significance in relation to vascular damage in these patients. Patients and methods: Twenty patients with SSc (12 with diffuse SSc and 8 with the limited form and 10 healthy age and sex matched volunteers as controls were all subjected to routine laboratory testing and immunological profiling including antinuclear, anti-Scl-70, anticentomere, anticardiolipin antibodies and anti-annexin V antibodies titres. Vascular damage was assessed by clinical examination and assessment of the disease activity score, nailfold capillaroscopy and colour flow Doppler of the renal arteries; Doppler echocardiography was used for assessing pulmonary hypertension. Results: Anti-annexin V antibodies were detected in 75% of patients. Comparisons between anti-annexin V in diffuse and limited subgroups showed no significance; however a statistically significant positive correlation was found between Anti-annexin V titre and the degree of vascular damage in SSc patients. Anti-annexin V increased significantly in patients with severe vascular damage in comparison with those less affected (15.3 ± 6.6 vs. 11.25 ± 3.6, P , 0.05. A significant positive correlation was found between Anti-annexin V titre and both the ACL titre (r = 0.79, P , 0.001 and the resistive index of the main renal artery (r = 0.42, P , 0.05. Conclusion: Anti-annexin V antibodies were significantly present in sera of patients with SSc. Patients with more severe forms of vascular damage had higher titres of these antibodies. Anti-annexin V antibodies are a sensitive predictor of vascular damage in SSc and could serve as a useful parameter in discriminating patients with a higher

Anti-Annexin V Antibodies: Association with Vascular Involvement and Disease Outcome in Patients with Systemic Sclerosis

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Reem A. Habeeb

2010-01-01

Full Text Available Background Systemic Sclerosis (SSc is characterized by skin thickening, fibrosis and vascular obliteration. The onset and course are heterogeneous. Prominent features include autoimmunity, inflammation and vascular damage. Aim of Study To measure the level of serum Anti-Annexin V antibodies in SSc patients and to study its significance in relation to vascular damage in these patients. Patients and Methods Twenty patients with SSc (12 with diffuse SSc and 8 with the limited form and 10 healthy age and sex matched volunteers as controls were all subjected to routine laboratory testing and immunological profiling including antinuclear, anti-Scl-70, anticentomere, anticardiolipin antibodies and anti-annexin V antibodies titres. Vascular damage was assessed by clinical examination and assessment of the disease activity score, nailfold capillaroscopy and colour flow Doppler of the renal arteries; Doppler echocardiography was used for assessing pulmonary hypertension. Results Anti-annexin V antibodies were detected in 75% of patients. Comparisons between anti-annexin V in diffuse and limited subgroups showed no significance; however a statistically significant positive correlation was found between Anti-annexin V titre and the degree of vascular damage in SSc patients. Anti-annexin V increased significantly in patients with severe vascular damage in comparison with those less affected (15.3 ± 6.6 vs. 11.25 ± 3.6, P < 0.05. A significant positive correlation was found between Anti-annexin V titre and both the ACL titre (r = 0.79, P < 0.001 and the resistive index of the main renal artery (r = 0.42, P < 0.05. Conclusion Anti-annexin V antibodies were significantly present in sera of patients with SSc. Patients with more severe forms of vascular damage had higher titres of these antibodies. Anti-annexin V antibodies are a sensitive predictor of vascular damage in SSc and could serve as a useful parameter in discriminating patients with a higher risk of

Tc-99m annexin V imaging and apoptosis staining in rabbit model of osteoarthritis

International Nuclear Information System (INIS)

Kang, Do Young; Jeong, Young Jin; Choi, Sun Mee; Lee, Sung Won; Chung, Won Tae; Yoo, Young Hyun

2004-01-01

Recent studies showed that, in osteoarthritis (OA), articular chondrocytes appeared to be eliminated by apoptosis. Tc-99mm Annexin V has been successfully used for non-invasive gamma imaging of apoptosis in tumor. myocardial infarction and transplantation. We studied Tc-99m Annexin V imaging and apoptosis staining in rabbit model of osteoarthritis. Osteoarthritis was induced in rabbits by intra-articular injection of 1.0 mg collagenase and surgical transection of leg ligament. Animals were dissected at 2, 4, 6 and 8 weeks after the initiation of the injections. For histological observation, the paraffin sections were stained with hematoxylin and eosin. To confirm that osteoarthritis was induced, immunohistochemistry to TRAIL was conducted on the sections and TRAIL positive cells was revealed by DAB. Tc-99m Annexin V was injected 16 ug/1 mCi/kg and regional images were acquired 10 and 60 min postinjection. A few days later Tc-99m MDP imaging was also acquired. Two weeks after injection, the surface layer of cartilage was lost, chondrocytes in the transitional zone have disappeared, and cleft in the transitional zone were shown. Four weeks after injection, moderate cell cloning in transitional and radial zone was appeared. Six weeks after injection, cell cloning was more apparent in the transitional and radial zones. Whereas TRAIL positive cells were not found in the chondrocytes from the control cartilage, most chondrocytes from the collagenase injected cartilage were TRAIL-positive. Tc-99m Annexin V imaging showed increase uptake in knee area of injuried side to normal side. And Tc-99m MDP imaging also had same findings. In rabbit model of osteoarthritis, apoptosis was detected by Tc-99m Annexin V imaging noninvasively and it was correlated by pathologic staining for apoptosis

Chapter 2: Irradiators

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NONE

2018-04-01

The chapter 2 presents the subjects: 1) gamma irradiators which includes: Category-I gamma irradiators (self-contained); Category-II gamma irradiators (panoramic and dry storage); Category-III gamma irradiators (self-contained in water); Category-IV gamma irradiators (panoramic and wet storage); source rack for Category-IV gamma irradiators; product transport system for Category-IV gamma irradiators; radiation shield for gamma irradiators; 2) accelerators which includes: Category-I Accelerators (shielded irradiator); Category-II Accelerators (irradiator inside a shielded room); Irradiation application examples.

Reciprocal regulation of annexin A2 and EGFR with Her-2 in Her-2 negative and herceptin-resistant breast cancer.

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Praveenkumar K Shetty

Full Text Available Alternative survival pathways are commonly seen to be upregulated upon inhibition of receptor tyrosine kinases (RTK, including Her-2. It is established that treatment with Herceptin leads to selective overexpression and activation of epidermal growth factor receptor (EGFR and Src which further contributes to oncogenesis in Herceptin resistant and triple negative breast cancer (TNBC patients. Here, we show a co-regulated upregulation in the expression of Annexin A2 (AnxA2, a known substrate of Src and one of the regulators of EGFR receptor endocytosis, in Herceptin resistant and Her-2 negative breast cancer. Immunohistochemical expression analysis revealed a reciprocal regulation between Her-2 and AnxA2 in breast cancer clinical samples as well as in cell lines as confirmed by protein and RNA analysis. The siRNA and Herceptin mediated downregulation/inhibition of Her-2 in Her-2 amplified cells induced AnxA2 expression and membrane translocation. In this study we report a possible involvement of AnxA2 in maintaining constitutively activated EGFR downstream signaling intermediates and hence in cell proliferation, migration and viability. This effect was consistent in Herceptin resistant JIMT-1 cells as well as in Her-2 negative breast cancer. The siRNA mediated AnxA2 downregulation leads to increased apoptosis, decreased cell viability and migration. Our studies further indicate the role of AnxA2 in EGFR-Src membrane bound signaling complex and ligand induced activation of downstream signaling pathways. Targeting this AnxA2 dependent positive regulation of EGFR signaling cascade may be of therapeutic value in Her-2 negative breast cancer.

Proteomic analysis of proton beam irradiated human melanoma cells.

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Sylwia Kedracka-Krok

Full Text Available Proton beam irradiation is a form of advanced radiotherapy providing superior distributions of a low LET radiation dose relative to that of photon therapy for the treatment of cancer. Even though this clinical treatment has been developing for several decades, the proton radiobiology critical to the optimization of proton radiotherapy is far from being understood. Proteomic changes were analyzed in human melanoma cells treated with a sublethal dose (3 Gy of proton beam irradiation. The results were compared with untreated cells. Two-dimensional electrophoresis was performed with mass spectrometry to identify the proteins. At the dose of 3 Gy a minimal slowdown in proliferation rate was seen, as well as some DNA damage. After allowing time for damage repair, the proteomic analysis was performed. In total 17 protein levels were found to significantly (more than 1.5 times change: 4 downregulated and 13 upregulated. Functionally, they represent four categories: (i DNA repair and RNA regulation (VCP, MVP, STRAP, FAB-2, Lamine A/C, GAPDH, (ii cell survival and stress response (STRAP, MCM7, Annexin 7, MVP, Caprin-1, PDCD6, VCP, HSP70, (iii cell metabolism (TIM, GAPDH, VCP, and (iv cytoskeleton and motility (Moesin, Actinin 4, FAB-2, Vimentin, Annexin 7, Lamine A/C, Lamine B. A substantial decrease (2.3 x was seen in the level of vimentin, a marker of epithelial to mesenchymal transition and the metastatic properties of melanoma.

sCD30, interleukin-1beta-converting enzyme and anti-Annexin V autoantibodies concentrations in heart transplant recipients.

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Zeglen, Sławomir; Zakliczyński, Michał; Nozyński, Jerzy; Rogala, Barbara; Zembala, Marian

2006-11-01

sCD30 and ICE/caspase-1 as apoptosis-regulating factors are suspected to be involved in the survival rate of immunocompetent cells during immunosuppression after allotransplantation. Serum CD30 and ICE/caspase-1 concentrations were estimated and associated with unspecific serum apoptosis marker--anti-Annexin V antibodies and myocardial biopsies results. 28 clinically stabile patients--heart transplant recipients at least 3 months after cardiac transplantation performed due to heart failure caused by ischaemic and/or congestive cardiomyopathy or/and primary valvular heart disease (26 men and 2 women, mean age=36.8 years, S.D.=7.6) with normal heart function assessed by use of ultrasound scan--were involved in the trial. The patients were divided and analyzed in two ways: first according to the results of elective endomyocardial biopsies and second to main immunosuppressive agent used. The enzyme immunoassay (CD30, Dako; interleukin-1beta-converting enzyme (ICE)/Caspase-1 ELISA and anti-Annexin V BENDER MedSystem) for soluble CD30, caspase-1 and anti-Annexin V autoantibodies serum levels was used. sCD30 and caspase-1 concentrations were non-significantly up-regulated in all analysed groups--with or without rejection signs or immunosuppressed with cyclosporine or especially tacrolimus. In contrast anti-Annexin V autoantibodies concentration was non-significantly down-regulated also in all studied groups. Moreover in the group with signs of transplant rejection, strong negative correlation between anti-Annexin antibodies and rejection grade was observed (-0.65, psCD30 and caspase-1 as well as the decrease in anti-Annexin V autoantibodies concentrations in heart recipients could be the result of post-transplant apoptosis disturbances. This tendency seems to be inhibited in a greater degree by tacrolimus than by cyclosporine. Anti-Annexin V autoantibodies might be considered as negative rejection markers due to their strong negative correlation with the rejection grade.

Molecular cloning and expression analysis of annexin A2 gene in sika deer antler tip

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Yanling Xia

2018-04-01

Full Text Available Objective Molecular cloning and bioinformatics analysis of annexin A2 (ANXA2 gene in sika deer antler tip were conducted. The role of ANXA2 gene in the growth and development of the antler were analyzed initially. Methods The reverse transcriptase polymerase chain reaction (RT-PCR was used to clone the cDNA sequence of the ANXA2 gene from antler tip of sika deer (Cervus Nippon hortulorum and the bioinformatics methods were applied to analyze the amino acid sequence of Anxa2 protein. The mRNA expression levels of the ANXA2 gene in different growth stages were examined by real time reverse transcriptase polymerase chain reaction (real time RT-PCR. Results The nucleotide sequence analysis revealed an open reading frame of 1,020 bp encoding 339 amino acids long protein of calculated molecular weight 38.6 kDa and isoelectric point 6.09. Homologous sequence alignment and phylogenetic analysis indicated that the Anxa2 mature protein of sika deer had the closest genetic distance with Cervus elaphus and Bos mutus. Real time RT-PCR results showed that the gene had differential expression levels in different growth stages, and the expression level of the ANXA2 gene was the highest at metaphase (rapid growing period. Conclusion ANXA2 gene may promote the cell proliferation, and the finding suggested Anxa2 as an important candidate for regulating the growth and development of deer antler.

Preclinical Validation of 99mTc–Annexin A5–128 in Experimental Autoimmune Myocarditis and Infective Endocarditis: Comparison with 99mTc–HYNIC–Annexin A5

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Khadija Benali

2015-01-01

Full Text Available Hydrazinonicotinamide–annexin A5 (HYNIC-Anx, a 99m technetium (99mTc-labeled agent targeting phosphatidylserine, proved to be sensitive for the detection of apoptosis and thrombosis but is no longer available for clinical use. A mutant of human annexin designed for direct 99mTc labeling (referred to as Anx A5–128 showed improved binding affinity to phosphatidylserine and is expected to be used in humans. We compared both radiotracers with regard to pharmacokinetics and diagnostic ability in animal models. Biodistribution studies were performed in normal rats. Radiolabeled Anx A5–128 and HYNIC-Anx were compared in cardiovascular settings involving phosphatidylserine expression: experimental autoimmune myocarditis and infective endocarditis. Initial blood clearance was faster for Anx A5–128 than for HYNIC-Anx, and tissue biodistribution was similar overall for both tracers. The diagnostic sensitivity of Anx A5–128 was excellent and comparable to that of HYNIC-Anx. Anx A5–128 showed biodistribution and diagnostic ability similar to those of the HYNIC-Anx derivative, supporting its translation to clinical use.

Distribution of 99Tcm-rh-Annexin V and its relationship with expression of survivin and Caspase-3 in tumors after a single dose of chemotherapy

International Nuclear Information System (INIS)

Zhang Xin; Zhang Yanjun; Tao Li; Zhu Yi; Yang Chun; Li Yaming; Zhang Jianying; Zhao Zhenzhen; Ji Xiaopeng; Zhao Ming; Tian Aijuan

2008-01-01

Objective: Recently, molecular imaging for detecting cellular apoptosis is developing rapidly. The aim of the study was to determine the effectiveness of imaging with 99 Tc m labelled recombinant human Annexin V ( 99 Tc m -rh-Annexin V) as a reflection of apoptosis in tumor, and related its distribution with expression of Survivin and Caspase-3 after a single dose of chemotherapy. Methods: Eight days after being inoculated with allogenic hepatoma cells (Hca-F25) into right axillary fossa, the mice (purebred 615) were randomly divided into two groups (control group A, n=9; and treated group B, n=10). Group B was received a single dose of chemotherapy intraperitoneally (cyclophosphamide, 150 mg/kg). Groups A and B were given 99 Tc m -rh-AnnexinV (3.7 MBq·0.5 μg -1 per mouse) intravenously 20 h later. Four hours after 99 Tc m -rh-Annexin V injection, the animals were imaged and sacrificed, and the tumor samples were weighed and the radioactivity was determined in a well-counter. The accumulation of 99 Tc m -rh-Annexin V in tumor was expressed as the percentage activity of injection dose per gram of tissue (% ID/g). Tumor cell apoptosis was examined by terminal deoxynueleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) method, and the expression of Survivin and Caspase-3 in tumor were determined with immunohistochemical method. SPSS 10.0 was used for data analysis. Results: Single dose chemotherapy tsignificantly increased the tumor uptake of 99 Tc m -rh-Annexin V [(0.478 ± 0.123)% ID/g vs (0.332 ± 0.061)% ID/g] and the positive number of TUNEL [(18.030 ± 5.600) cells/field vs (6.744 ± 2.325) cells/field], as well as the expression of Caspase-3 [(3.266 ± 0.482)% vs (2.387 ± 0.387)%, F was 10.502, 31.507, 18.971, respectively, all P 99 Tc m -rh-Annexin V correlated positively well with the expression of Caspase-3 and negatively with the expression of Survivin (P 99 Tc m -rh-Annexin V can not only reflect the extent of apoptosis

New markers of pancreatic cancer identified through differential gene expression analyses: claudin 18 and annexin A8.

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Karanjawala, Zarir E; Illei, Peter B; Ashfaq, Raheela; Infante, Jeffrey R; Murphy, Kathleen; Pandey, Akhilesh; Schulick, Richard; Winter, Jordan; Sharma, Rajni; Maitra, Anirban; Goggins, Michael; Hruban, Ralph H

2008-02-01

New markers to distinguish benign reactive glands from infiltrating ductal adenocarcinoma of the pancreas are needed. The gene expression patterns of 24 surgically resected primary infiltrating ductal adenocarcinomas of the pancreas were compared with 18 non-neoplastic samples using the Affymetrix U133 Plus 2.0 Arrays and the Gene Logic GeneExpress Software System. Gene fragments from 4 genes (annexin A8, claudin 18, CXCL5, and S100 A2) were selected from the fragments found to be highly expressed in infiltrating adenocarcinomas when compared with normal tissues. The protein expression of these genes was examined using immunohistochemical labeling of tissue microarrays. Claudin 18 labeled infiltrating carcinomas in a membranous pattern. When compared with normal and reactive ducts, claudin 18 was overexpressed, at least focally, in 159 of 166 evaluable carcinomas (96%). Strong and diffuse claudin 18 overexpression was most often seen in well-differentiated carcinomas (P=0.02). Claudin 18 was overexpressed in 51 of 52 cases (98%) of pancreatic intraepithelial neoplasia. Annexin A8 was at least focally overexpressed in 149 of 154 evaluable infiltrating carcinomas (97%). S100 A2 was at least focally overexpressed in 118 of 154 evaluable infiltrating carcinomas (77%). Non-neoplastic glands also frequently expressed S100 A2 diminishing its potential diagnostic utility. Immunolabeling with antibodies directed against CXCL5 did not reveal any significant differences in protein expression between infiltrating adenocarcinomas and normal pancreatic ducts. Claudin 18 and annexin A8 are frequently highly overexpressed in infiltrating ductal adenocarcinomas when compared with normal reactive ducts, suggesting a role for these molecules in pancreatic ductal adenocarcinomas. Furthermore, these may serve as diagnostic markers, as screening tests and as therapeutic targets.

Evaluation of adenosine preconditioning with {sup 99m}Tc-His{sub 10}-annexin V in a porcine model of myocardium ischemia and reperfusion injury: preliminary study

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Ye Fei [Department of Cardiology, Nanjing First Hospital Affiliated to Nanjing Medical University, 68 Changle Road, Nanjing 210006 (China); Fang Wei [Cardiovascular Institute and Fuwai Hospital, No. 167 Bei-Li-Shi-Lu, Beijing 100037 (China); Wang Feng, E-mail: fengwang1972cn@gmail.co [Department of Nuclear Medicine, Nanjing First Hospital Affiliated to Nanjing Medical University, 68 Changle Road, Nanjing 210006 (China); State Key Laboratory of Pharmaceutical Biotechnology, Department of Biochemistry, College of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093 (China); Hua Zichun [State Key Laboratory of Pharmaceutical Biotechnology, Department of Biochemistry, College of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093 (China); Wang Zizheng [Department of Nuclear Medicine, Nanjing First Hospital Affiliated to Nanjing Medical University, 68 Changle Road, Nanjing 210006 (China); Yang Xiang [State Key Laboratory of Pharmaceutical Biotechnology, Department of Biochemistry, College of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093 (China)

2011-05-15

Purpose: The goal of this study was to evaluate the feasibility of {sup 99m}Tc-His{sub 10}-annexin V for the detection of acute myocardial cell death and to assess the effect of adenosine preconditioning in a porcine model of myocardium ischemia and reperfusion injury (RI). Materials and Methods: {sup 99m}Tc-His{sub 10}-annexin V was prepared by one-step direct labeling, and RCP and radiostability were tested. The binding of {sup 99m}Tc-His{sub 10}-annexin V to apoptosis was validated in vitro using camptothecin-induced Jurkat cells. In vivo biodistribution was determined in mice by the dissection method. Ischemia of 20-30 min was induced by balloon occlusion of the epicardial coronary artery of the porcine model (n=14). Adenosine was infused intravenously in six pigs before coronary occlusion. {sup 99m}Tc-His{sub 10}-annexin V (n=12) was injected intravenously at 1 h after reperfusion. SPECT/CT was acquired at 3 h postinjection. Myocardial perfusion imaging (MPI) with {sup 99m}Tc-MIBI was also performed 1 day after His{sub 10}-annexin V imaging. Cardiac tissues were analyzed postmortem using hematoxylin-and-eosin and TUNEL staining. Caspase-3 activity was measured to confirm the presence of apoptosis. Results: {sup 99m}Tc-His{sub 10}-annexin V had a RCP >98% and high stability 2 h after radiolabeling; it could bind to apoptotic cells with high affinity. Biodistribution of {sup 99m}Tc-His{sub 10}-annexin V showed a predominant uptake in the kidney and relatively low uptake in the myocardium, liver and gastrointestinal tract; rapid clearance from blood and kidney was observed. In the untreated group, intense uptake of His{sub 10}-annexin V was visualized in the defect which was shown in MPI, whereas in the adenosine group a mild uptake of {sup 99m}Tc-His{sub 10}-annexin was found in the risk area which showed no defects in the {sup 99m}Tc-MIBI image. TUNEL staining and activated caspase-3 confirmed the ongoing apoptosis in RI. Adenosine preconditioning significantly

Annexin 1 and Melanocortin Peptide Therapy for Protection Against Ischaemic-Reperfusion Damage in the Heart

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F.N.E. Gavins

2006-01-01

Full Text Available Cardiovascular disease is a major cause of mortality within the western world affecting 2.7 million British people. This review highlights the beneficial effects of naturally occurring hormones and their peptides, in myocardial ischaemic-injury (MI models, a disease pathology in which cytokines and neutrophils play a causal role. Here we discuss two distinct classes of endogenous peptides: the steroid inducible annexin 1 and the melanocortin peptides. Annexin 1 and the melanocortins counteract the most important part of the host inflammatory response, namely, the process of leukocyte extravasation, as well as release of proinflammatory mediators. Their biological effects are mediated via the seven transmembrane G-protein-coupled receptors, the fMLP receptor family (or FPR, and the melanocortin receptors, respectively. Pharmacological analysis has demonstrated that the first 24 amino acids of the N-terminus (termed Ac2-26 are the most active region. Both exogenous annexin 1 and its peptides demonstrate cardioprotectiveness and continuing work is required to understand this annexin 1/FPR relationship fully. The melanocortin peptides are derived from a precursor molecule called the POMC protein. These peptides display potent anti-inflammatory effects in human and animal models of disease. In MI, the MC3R has been demonstrated to play an important role in mediating the protective effects of these peptides. The potential anti-inflammatory role for endogenous peptides in cardiac disease is in its infancy. The inhibition of cell migration and release of cytokines and other soluble mediators appears to play an important role in affording protection in ischaemic injury and thus may lead to potential therapeutic targets.

Annexins as organizers of cholesterol- and sphingomyelin-enriched membrane microdomains in Niemann-Pick type C disease.

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Domon, Magdalena; Nasir, Mehmet Nail; Matar, Gladys; Pikula, Slawomir; Besson, Françoise; Bandorowicz-Pikula, Joanna

2012-06-01

Growing evidence suggests that membrane microdomains enriched in cholesterol and sphingomyelin are sites for numerous cellular processes, including signaling, vesicular transport, interaction with pathogens, and viral infection, etc. Recently some members of the annexin family of conserved calcium and membrane-binding proteins have been recognized as cholesterol-interacting molecules and suggested to play a role in the formation, stabilization, and dynamics of membrane microdomains to affect membrane lateral organization and to attract other proteins and signaling molecules onto their territory. Furthermore, annexins were implicated in the interactions between cytosolic and membrane molecules, in the turnover and storage of cholesterol and in various signaling pathways. In this review, we focus on the mechanisms of interaction of annexins with lipid microdomains and the role of annexins in membrane microdomains dynamics including possible participation of the domain-associated forms of annexins in the etiology of human lysosomal storage disease called Niemann-Pick type C disease, related to the abnormal storage of cholesterol in the lysosome-like intracellular compartment. The involvement of annexins and cholesterol/sphingomyelin-enriched membrane microdomains in other pathologies including cardiac dysfunctions, neurodegenerative diseases, obesity, diabetes mellitus, and cancer is likely, but is not supported by substantial experimental observations, and therefore awaits further clarification.

(99m)Tc-Annexin A5 quantification of apoptotic tumor response: a systematic review and meta-analysis of clinical imaging trials.

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Belhocine, Tarik Z; Blankenberg, Francis G; Kartachova, Marina S; Stitt, Larry W; Vanderheyden, Jean-Luc; Hoebers, Frank J P; Van de Wiele, Christophe

2015-12-01

(99m)Tc-Annexin A5 has been used as a molecular imaging probe for the visualization, characterization and measurement of apoptosis. In an effort to define the quantitative (99m)Tc-annexin A5 uptake criteria that best predict tumor response to treatment, we performed a systematic review and meta-analysis of the results of all clinical imaging trials found in the literature or publicly available databases. Included in this review were 17 clinical trials investigating quantitative (99m)Tc-annexin A5 (qAnx5) imaging using different parameters in cancer patients before and after the first course of chemotherapy and/or radiation therapy. Qualitative assessment of the clinical studies for diagnostic accuracy was performed using the QUADAS-2 criteria. Of these studies, five prospective single-center clinical trials (92 patients in total) were included in the meta-analysis after exclusion of one multicenter clinical trial due to heterogeneity. Pooled positive predictive values (PPV) and pooled negative predictive values (NPV) (with 95% CI) were calculated using Meta-Disc software version 1.4. Absolute quantification and/or relative quantification of (99m)Tc-annexin A5 uptake were performed at baseline and after the start of treatment. Various quantitative parameters have been used for the calculation of (99m)Tc-annexin A5 tumor uptake and delta (Δ) tumor changes post-treatment compared to baseline including: tumor-to-background ratio (TBR), ΔTBR, tumor-to-noise ratio, relative tumor ratio (TR), ΔTR, standardized tumor uptake ratio (STU), ΔSTU, maximum count per pixel within the tumor volume (Cmax), Cmax%, absolute ΔU and percentage (ΔU%), maximum ΔU counts, semiquantitative visual scoring, percent injected dose (%ID) and %ID/cm(3). Clinical trials investigating qAnx5 imaging have included patients with lung cancer, lymphoma, breast cancer, head and neck cancer and other less common tumor types. In two phase I/II single-center clinical trials, an increase of ≥25% in

Quantitative analysis of self-association and mobility of annexin A4 at the plasma membrane.

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Crosby, Kevin C; Postma, Marten; Hink, Mark A; Zeelenberg, Christiaan H C; Adjobo-Hermans, Merel J W; Gadella, Theodorus W J

2013-05-07

Annexins, found in most eukaryotic species, are cytosolic proteins that are able to bind negatively-charged phospholipids in a calcium-dependent manner. Annexin A4 (AnxA4) has been implicated in diverse cellular processes, including the regulation of exocytosis and ion-transport; however, its precise mechanistic role is not fully understood. AnxA4 has been shown to aggregate on lipid layers upon Ca(2+) binding in vitro, a characteristic that may be critical for its function. We have utilized advanced fluorescence microscopy to discern details on the mobility and self-assembly of AnxA4 after Ca(2+) influx at the plasma membrane in living cells. Total internal reflection microscopy in combination with Förster resonance energy transfer reveals that there is a delay between initial plasma membrane binding and the beginning of self-assembly and this process continues after the cytoplasmic pool has completely relocated. Number-and-brightness analysis suggests that the predominant membrane bound mobile form of the protein is trimeric. There also exists a pool of AnxA4 that forms highly immobile aggregates at the membrane. Fluorescence recovery after photobleaching suggests that the relative proportion of these two forms varies and is correlated with membrane morphology. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Inflammation and cancer: role of annexin A1 and FPR2/ALX in proliferation and metastasis in human laryngeal squamous cell carcinoma.

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Thaís Santana Gastardelo

Full Text Available The anti-inflammatory protein annexin A1 (ANXA1 has been associated with cancer progression and metastasis, suggesting its role in regulating tumor cell proliferation. We investigated the mechanism of ANXA1 interaction with formylated peptide receptor 2 (FPR2/ALX in control, peritumoral and tumor larynx tissue samples from 20 patients, to quantitate the neutrophils and mast cells, and to evaluate the protein expression and co-localization of ANXA1/FPR2 in these inflammatory cells and laryngeal squamous cells by immunocytochemistry. In addition, we performed in vitro experiments to further investigate the functional role of ANXA1/FPR2 in the proliferation and metastasis of Hep-2 cells, a cell line from larynx epidermoid carcinoma, after treatment with ANXA1(2-26 (annexin A1 N-terminal-derived peptide, Boc2 (antagonist of FPR and/or dexamethasone. Under these treatments, the level of Hep-2 cell proliferation, pro-inflammatory cytokines, ANXA1/FPR2 co-localization, and the prostaglandin signalling were analyzed using ELISA, immunocytochemistry and real-time PCR. An influx of neutrophils and degranulated mast cells was detected in tumor samples. In these inflammatory cells of peritumoral and tumor samples, ANXA1/FPR2 expression was markedly exacerbated, however, in laryngeal carcinoma cells, this expression was down-regulated. ANXA1(2-26 treatment reduced the proliferation of the Hep-2 cells, an effect that was blocked by Boc2, and up-regulated ANXA1/FPR2 expression. ANXA1(2-26 treatment also reduced the levels of pro-inflammatory cytokines and affected the expression of metalloproteinases and EP receptors, which are involved in the prostaglandin signalling. Overall, this study identified potential roles for the molecular mechanism of the ANXA1/FPR2 interaction in laryngeal cancer, including its relationship with the prostaglandin pathway, providing promising starting points for future research. ANXA1 may contribute to the regulation of tumor growth

Leishmania promastigotes lack phosphatidylserine but bind annexin V upon permeabilization or miltefosine treatment.

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Adrien Weingärtner

Full Text Available The protozoan parasite Leishmania is an intracellular pathogen infecting and replicating inside vertebrate host macrophages. A recent model suggests that promastigote and amastigote forms of the parasite mimic mammalian apoptotic cells by exposing phosphatidylserine (PS at the cell surface to trigger their phagocytic uptake into host macrophages. PS presentation at the cell surface is typically analyzed using fluorescence-labeled annexin V. Here we show that Leishmania promastigotes can be stained by fluorescence-labeled annexin V upon permeabilization or miltefosine treatment. However, combined lipid analysis by thin-layer chromatography, mass spectrometry and (31P nuclear magnetic resonance (NMR spectroscopy revealed that Leishmania promastigotes lack any detectable amount of PS. Instead, we identified several other phospholipid classes such phosphatidic acid, phosphatidylethanolamine; phosphatidylglycerol and phosphatidylinositol as candidate lipids enabling annexin V staining.

Annexin A7 deficiency potentiates cardiac NFAT activity promoting hypertrophic signaling

International Nuclear Information System (INIS)

Voelkl, Jakob; Alesutan, Ioana; Pakladok, Tatsiana; Viereck, Robert; Feger, Martina; Mia, Sobuj; Schönberger, Tanja; Noegel, Angelika A.; Gawaz, Meinrad; Lang, Florian

2014-01-01

Highlights: • Cardiac Anxa7 expression was up-regulated following TAC. • The hypertrophic response following TAC was augmented in Anxa7-deficient mice. • Silencing of Anxa7 increased indicators of HL-1 cardiomyocytes hypertrophy. • Silencing of Anxa7 induced Nfatc1 nuclear translocation. • Silencing of Anxa7 enhanced NFAT-dependent transcriptional activity. - Abstract: Annexin A7 (Anxa7) is a cytoskeletal protein interacting with Ca 2+ signaling which in turn is a crucial factor for cardiac remodeling following cardiac injury. The present study explored whether Anxa7 participates in the regulation of cardiac stress signaling. To this end, mice lacking functional Anxa7 (anxa7 −/− ) and wild-type mice (anxa7 +/+ ) were investigated following pressure overload by transverse aortic constriction (TAC). In addition, HL-1 cardiomyocytes were silenced with Anxa7 siRNA and treated with isoproterenol. Transcript levels were determined by quantitative RT-PCR, transcriptional activity by luciferase reporter assay and protein abundance by Western blotting and confocal microscopy. As a result, TAC treatment increased the mRNA and protein levels of Anxa7 in wild-type mice. Moreover, TAC increased heart weight to body weight ratio and the cardiac mRNA levels of αSka, Nppb, Col1a1, Col3a1 and Rcan1, effects more pronounced in anxa7 −/− mice than in anxa7 +/+ mice. Silencing of Anxa7 in HL-1 cardiomyocytes significantly increased nuclear localization of Nfatc1. Furthermore, Anxa7 silencing increased NFAT-dependent transcriptional activity as well as αSka, Nppb, and Rcan1 mRNA levels both, under control conditions and following β-adrenergic stimulation by isoproterenol. These observations point to an important role of annexin A7 in the regulation of cardiac NFAT activity and hypertrophic response following cardiac stress conditions

Annexin A7 deficiency potentiates cardiac NFAT activity promoting hypertrophic signaling

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Voelkl, Jakob; Alesutan, Ioana; Pakladok, Tatsiana; Viereck, Robert; Feger, Martina; Mia, Sobuj [Department of Physiology, University of Tübingen, Tübingen (Germany); Schönberger, Tanja [Department of Cardiology and Cardiovascular Medicine, University of Tübingen, Tübingen (Germany); Noegel, Angelika A. [Center for Biochemistry, Institute of Biochemistry I, University of Cologne, Köln (Germany); Gawaz, Meinrad [Department of Cardiology and Cardiovascular Medicine, University of Tübingen, Tübingen (Germany); Lang, Florian, E-mail: florian.lang@uni-tuebingen.de [Department of Physiology, University of Tübingen, Tübingen (Germany)

2014-02-28

Highlights: • Cardiac Anxa7 expression was up-regulated following TAC. • The hypertrophic response following TAC was augmented in Anxa7-deficient mice. • Silencing of Anxa7 increased indicators of HL-1 cardiomyocytes hypertrophy. • Silencing of Anxa7 induced Nfatc1 nuclear translocation. • Silencing of Anxa7 enhanced NFAT-dependent transcriptional activity. - Abstract: Annexin A7 (Anxa7) is a cytoskeletal protein interacting with Ca{sup 2+} signaling which in turn is a crucial factor for cardiac remodeling following cardiac injury. The present study explored whether Anxa7 participates in the regulation of cardiac stress signaling. To this end, mice lacking functional Anxa7 (anxa7{sup −/−}) and wild-type mice (anxa7{sup +/+}) were investigated following pressure overload by transverse aortic constriction (TAC). In addition, HL-1 cardiomyocytes were silenced with Anxa7 siRNA and treated with isoproterenol. Transcript levels were determined by quantitative RT-PCR, transcriptional activity by luciferase reporter assay and protein abundance by Western blotting and confocal microscopy. As a result, TAC treatment increased the mRNA and protein levels of Anxa7 in wild-type mice. Moreover, TAC increased heart weight to body weight ratio and the cardiac mRNA levels of αSka, Nppb, Col1a1, Col3a1 and Rcan1, effects more pronounced in anxa7{sup −/−} mice than in anxa7{sup +/+} mice. Silencing of Anxa7 in HL-1 cardiomyocytes significantly increased nuclear localization of Nfatc1. Furthermore, Anxa7 silencing increased NFAT-dependent transcriptional activity as well as αSka, Nppb, and Rcan1 mRNA levels both, under control conditions and following β-adrenergic stimulation by isoproterenol. These observations point to an important role of annexin A7 in the regulation of cardiac NFAT activity and hypertrophic response following cardiac stress conditions.

Endothelial microparticles released by activated protein C protect beta cells through EPCR/PAR1 and annexin A1/FPR2 pathways in islets.

Science.gov (United States)

Kreutter, Guillaume; Kassem, Mohamad; El Habhab, Ali; Baltzinger, Philippe; Abbas, Malak; Boisrame-Helms, Julie; Amoura, Lamia; Peluso, Jean; Yver, Blandine; Fatiha, Zobairi; Ubeaud-Sequier, Geneviève; Kessler, Laurence; Toti, Florence

2017-11-01

Islet transplantation is associated with early ischaemia/reperfusion, localized coagulation and redox-sensitive endothelial dysfunction. In animal models, islet cytoprotection by activated protein C (aPC) restores islet vascularization and protects graft function, suggesting that aPC triggers various lineages. aPC also prompts the release of endothelial MP that bear EPCR, its specific receptor. Microparticles (MP) are plasma membrane procoagulant vesicles, surrogate markers of stress and cellular effectors. We measured the cytoprotective effects of aPC on endothelial and insulin-secreting Rin-m5f β-cells and its role in autocrine and paracrine MP-mediated cell crosstalk under conditions of oxidative stress. MP from aPC-treated primary endothelial (EC) or β-cells were applied to H 2 O 2 -treated Rin-m5f. aPC activity was measured by enzymatic assay and ROS species by dihydroethidium. The capture of PKH26-stained MP and the expression of EPCR were probed by fluorescence microscopy and apoptosis by flow cytometry. aPC treatment enhanced both annexin A1 (ANXA1) and PAR-1 expression in EC and to a lesser extent in β-cells. MP from aPC-treated EC (eM aPC ) exhibited high EPCR and annexin A1 content, protected β-cells, restored insulin secretion and were captured by 80% of β cells in a phosphatidylserine and ANXA1-dependent mechanism. eMP activated EPCR/PAR-1 and ANXA1/FPR2-dependent pathways and up-regulated the expression of EPCR, and of FPR2/ALX, the ANXA1 receptor. Cytoprotection was confirmed in H 2 O 2 -treated rat islets with increased viability (62% versus 48% H 2 O 2 ), reduced apoptosis and preserved insulin secretion in response to glucose elevation (16 versus 5 ng/ml insulin per 10 islets). MP may prove a promising therapeutic tool in the protection of transplanted islets. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model

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Desai, Sejal; Srambikkal, Nishad; Yadav, Hansa D.; Shetake, Neena; Balla, Murali M. S.; Kumar, Amit; Ray, Pritha; Ghosh, Anu

2016-01-01

Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE) in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells) tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander) WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated) when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2) and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper insight about

Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model.

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Sejal Desai

Full Text Available Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2 and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper

{sup 99m}Tc-Annexin A5 quantification of apoptotic tumor response: a systematic review and meta-analysis of clinical imaging trials

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Belhocine, Tarik Z. [Western University, Biomedical Imaging Research Centre (BIRC), London, Ontario (Canada); Blankenberg, Francis G. [Lucile Salter Packard Children' s Hospital, Stanford, Division of Pediatric Radiology, Department of Radiology, Palo Alto, CA (United States); Kartachova, Marina S. [Medical Center Alkmaar, Department of Nuclear Medicine, Alkmaar (Netherlands); Stitt, Larry W. [LW Stitt Statistical Services, London, Ontario (Canada); Vanderheyden, Jean-Luc [JLVMI Consulting LLC, Waukesha, WI (United States); Hoebers, Frank J.P. [Maastricht University Medical Centre, Department of Radiation Oncology (MAASTRO Clinic), GROW School for Oncology and Developmental Biology, Maastricht (Netherlands); Wiele, Christophe van de [University Hospital Ghent, Department of Nuclear Medicine and Radiology, Ghent (Belgium)

2015-12-15

{sup 99m}Tc-Annexin A5 has been used as a molecular imaging probe for the visualization, characterization and measurement of apoptosis. In an effort to define the quantitative {sup 99m}Tc-annexin A5 uptake criteria that best predict tumor response to treatment, we performed a systematic review and meta-analysis of the results of all clinical imaging trials found in the literature or publicly available databases. Included in this review were 17 clinical trials investigating quantitative {sup 99m}Tc-annexin A5 (qAnx5) imaging using different parameters in cancer patients before and after the first course of chemotherapy and/or radiation therapy. Qualitative assessment of the clinical studies for diagnostic accuracy was performed using the QUADAS-2 criteria. Of these studies, five prospective single-center clinical trials (92 patients in total) were included in the meta-analysis after exclusion of one multicenter clinical trial due to heterogeneity. Pooled positive predictive values (PPV) and pooled negative predictive values (NPV) (with 95 % CI) were calculated using Meta-Disc software version 1.4. Absolute quantification and/or relative quantification of {sup 99m}Tc-annexin A5 uptake were performed at baseline and after the start of treatment. Various quantitative parameters have been used for the calculation of {sup 99m}Tc-annexin A5 tumor uptake and delta (Δ) tumor changes post-treatment compared to baseline including: tumor-to-background ratio (TBR), ΔTBR, tumor-to-noise ratio, relative tumor ratio (TR), ΔTR, standardized tumor uptake ratio (STU), ΔSTU, maximum count per pixel within the tumor volume (Cmax), Cmax%, absolute ΔU and percentage (ΔU%), maximum ΔU counts, semiquantitative visual scoring, percent injected dose (%ID) and %ID/cm{sup 3}. Clinical trials investigating qAnx5 imaging have included patients with lung cancer, lymphoma, breast cancer, head and neck cancer and other less common tumor types. In two phase I/II single-center clinical trials

Expression of Annexin-A1 and Galectin-1 Anti-Inflammatory Proteins and mRNA in Chronic Gastritis and Gastric Cancer

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Yvana Cristina Jorge

2013-01-01

Full Text Available Objective. The anti-inflammatory proteins annexin-A1 and galectin-1 have been associated with tumor progression. This scenario prompted us to investigate the relationship between the gene and protein expression of annexin-A1 (ANXA1/AnxA1 and galectin-1 (LGALS1/Gal-1 in an inflammatory gastric lesion as chronic gastritis (CG and gastric adenocarcinoma (GA and its association with H. pylori infection. Methods. We analyzed 40 samples of CG, 20 of GA, and 10 of normal mucosa (C by the quantitative real-time PCR (qPCR technique and the immunohistochemistry assay. Results. High ANXA1 mRNA expression levels were observed in 90% (36/40 of CG cases (mean relative quantification RQ = 4.26 ± 2.03 and in 80% (16/20 of GA cases (mean RQ = 4.38 ± 4.77. However, LGALS1 mRNA levels were high (mean RQ = 2.44 ± 3.26 in 60% (12/20 of the GA cases, while low expression was found in CG (mean RQ = 0.43±3.13; P<0.01. Normal mucosa showed modest immunoreactivity in stroma but not in epithelium, while stroma and epithelium displayed an intense immunostaining in CG and GA for both proteins. Conclusion. These results have provided evidence that galectin-1 and mainly annexin-A1 are overexpressed in both gastritis and gastric cancer, suggesting a strong association of these proteins with chronic gastric inflammation and carcinogenesis.

Annexin A10 optimally differentiates between intrahepatic cholangiocarcinoma and hepatic metastases of pancreatic ductal adenocarcinoma: a comparative study of immunohistochemical markers and panels.

Science.gov (United States)

Kälsch, Julia; Padden, Juliet; Bertram, Stefanie; Pott, Leona L; Reis, Henning; Westerwick, Daniela; Schaefer, Christoph M; Sowa, Jan-P; Möllmann, Dorothe; Fingas, Christian; Dechȇne, Alexander; Sitek, Barbara; Eisenacher, Martin; Canbay, Ali; Ahrens, Maike; Baba, Hideo A

2017-05-01

Discriminating intrahepatic cholangiocarcinoma (ICC) from hepatic metastases of pancreatic ductal adenocarcinoma (mPDAC) can be challenging. While pathologists might depend on clinical information regarding a primary tumor, their diagnosis will lead the patient either to potentially curative surgery (for ICC) or to palliation (for mPDAC). Beyond the validation of recently published potential biomarkers for PDAC (primary or metastatic) in a large cohort, we assessed diagnostic performance of the most promising candidates in the challenging task of discriminating metastatic PDAC (mPDAC) from ICC. In a training set of 87 ICC and 88 pPDAC, our previously identified biomarkers Annexin A1 (ANXA1), ANXA10, and ANXA13 were tested and compared with 11 published biomarkers or panels (MUCIN 1, Agrin, S100P, MUC5 AC, Laminin, VHL, CK 17, N-Cadherin, ELAC2, PODXL and HSPG2). Biomarkers with best results were further tested in an independent series of biopsies of 27 ICC and 36 mPDAC. Highest AUC values (between 0.72 and 0.84) for the discrimination between ICC and pPDAC were found in the training set for Annexin A1, Annexin A10, MUC5 AC, CK17, and N-Cadherin. These markers were further tested on an independent series of liver biopsies containing ICC or mPDAC. Diagnostic characteristics were evaluated for individual markers as well as for 3× panels. ANXA 10 showed the highest diagnostic potential of all single markers, correctly classifying 75% of mPDAC and 85% of ICC. Our results suggest that ANXA10 may be useful to differentiate between ICC and mPDAC, when only a tissue specimen is available.

Evaluation of radiolabelled annexin A5 for scintigraphic imaging of cell processes (necrosis/apoptosis) in cardiovascular diseases

International Nuclear Information System (INIS)

Sarda-Mantel, L.

2007-03-01

Annexin A5, a 35KDa protein, specifically binds with high affinity to phosphatidylserine (P.S.) which is actively redistributed to the external leaflet of plasmic membranes in apoptotic cells and activated platelets. Annexin A5 radiolabelled with 99m Tc( 99m Tc-ANX5) was developed by Strauss (stanford, Usa) to image apoptosis in vivo: tumours cells apoptosis induced by chemo-radiotherapy, ischemia/reperfusion lesions in animals and patients, graft rejection. Additionally, many in vitro data suggest that annexin A5 also stains necrosis (membrane disruption), which occurs in all types of cell death. This preclinical work aimed to evaluate the potential interest of 99m Tc-ANX5 imaging as a clinical tool in cardiovascular diseases. Four studies performed in rat models of myocardial infarction by coronary ligation and ischemia-reperfusion, and in rat models of subacute and acute (isoproterenol-induced) myocarditis show the ability of 99m Tc-ANX5 to detect in vivo cardio myocytes death by apoptosis and necrosis. Another study demonstrates that 99m Tc-ANX5 is highly accurate to evaluate in vivo the biological activity of parietal thrombus in a rat model of elastase-induced abdominal aortic aneurysm. These results suggest that 99m Tc-ANX5 imaging could be used in patients for non invasive diagnosis, prognostic evaluation in acute myocarditis and in various thrombotic cardiovascular diseases. (author)

Irradiation creep induced anisotropy in a/2 dislocation populations

International Nuclear Information System (INIS)

Gelles, D.S.

1984-05-01

The contribution of anisotropy in Burgers vector distribution to irradiation creep behavior has been largely ignored in irradiation creep models. However, findings on Frank loops suggest that it may be very important. Procedures are defined to identify the orientations of a/2 Burgers vectors for dislocations in face-centered cubic crystals. By means of these procedures the anisotropy in Burgers vector populations was determined for three Nimonic PE16 pressurized tube specimens irradiated under stress. Considerable anisotropy in Burgers vector population develops during irradiation creep. It is inferred that dislocation motion during irradiation creep is restricted primarily to a climb of a/2 dislocations on 100 planes. Effect of these results on irradiation creep modeling and deformation induced irradiation growth is considered

Proresolving protein Annexin A1: The role in type 2 diabetes mellitus and obesity.

Science.gov (United States)

Pietrani, Nathalia T; Ferreira, Cláudia N; Rodrigues, Kathryna F; Perucci, Luiza O; Carneiro, Fernanda S; Bosco, Adriana A; Oliveira, Marina C; Pereira, Solange S; Teixeira, Antônio L; Alvarez-Leite, Jacqueline I; Ferreira, Adaliene V; Sousa, Lirlândia P; Gomes, Karina B

2018-04-17

Annexin A1 (AnxA1) is a protein involved in inflammation resolution that might be altered in obesity-associated type 2 diabetes mellitus (DM), which is a chronic inflammatory disease. The aim of this study was to evaluate AnxA1 serum levels in individuals with and without DM stratified according to the body mass index (BMI), and the dynamic of AnxA1 expression in adipose tissue from humans with obesity and non-obesity. Serum samples were obtained from 41 patients with DM (lean, overweight and obese) and 40 controls, and adipose tissue samples were obtained from 16 individuals with obesity (with or without DM), and 15 controls. DM patients showed similar AnxA1 serum levels when compared to controls. However, when the individuals were stratified according to BMI, AnxA1 levels were higher in individuals with obesity than lean or overweight, and in overweight compared to lean individuals. Moreover, AnxA1 was correlated positively with IL-6 levels. AnxA1 levels were also positively correlated with BMI, waist circumference and waist-to-hip ratio. Furthermore, higher levels of cleaved AnxA1 were observed in adipose tissue from individuals with obesity, independently of DM status. Enhanced levels of AnxA1 in serum of individuals with obesity suggest an attempt to counter-regulate the systemic inflammation process in this disease. However, the higher levels of cleaved AnxA1 in the adipose tissue of individuals with obesity could compromise its anti-inflammatory and proresolving actions, locally. Considering our data, AnxA1 cleavage in the adipose tissue, despite increased serum levels of this protein, and consequently the failure in inflammation resolution, suggests an important pathophysiological mechanism involved in inflammatory status observed in obesity. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Potato Annexin STANN1 Promotes Drought Tolerance and Mitigates Light Stress in Transgenic Solanum tuberosum L. Plants

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Szalonek, Michal; Sierpien, Barbara; Rymaszewski, Wojciech; Gieczewska, Katarzyna; Garstka, Maciej; Lichocka, Malgorzata; Sass, Laszlo; Paul, Kenny; Vass, Imre; Vankova, Radomira; Dobrev, Peter; Szczesny, Pawel; Marczewski, Waldemar; Krusiewicz, Dominika; Strzelczyk-Zyta, Danuta; Hennig, Jacek; Konopka-Postupolska, Dorota

2015-01-01

Annexins are a family of calcium- and membrane-binding proteins that are important for plant tolerance to adverse environmental conditions. Annexins function to counteract oxidative stress, maintain cell redox homeostasis, and enhance drought tolerance. In the present study, an endogenous annexin, STANN1, was overexpressed to determine whether crop yields could be improved in potato (Solanum tuberosum L.) during drought. Nine potential potato annexins were identified and their expression characterized in response to drought treatment. STANN1 mRNA was constitutively expressed at a high level and drought treatment strongly increased transcription levels. Therefore, STANN1 was selected for overexpression analysis. Under drought conditions, transgenic potato plants ectopically expressing STANN1 were more tolerant to water deficit in the root zone, preserved more water in green tissues, maintained chloroplast functions, and had higher accumulation of chlorophyll b and xanthophylls (especially zeaxanthin) than wild type (WT). Drought-induced reductions in the maximum efficiency and the electron transport rate of photosystem II (PSII), as well as the quantum yield of photosynthesis, were less pronounced in transgenic plants overexpressing STANN1 than in the WT. This conferred more efficient non-photochemical energy dissipation in the outer antennae of PSII and probably more efficient protection of reaction centers against photooxidative damage in transgenic plants under drought conditions. Consequently, these plants were able to maintain effective photosynthesis during drought, which resulted in greater productivity than WT plants despite water scarcity. Although the mechanisms underlying this stress protection are not yet clear, annexin-mediated photoprotection is probably linked to protection against light-induced oxidative stress. PMID:26172952

Potato Annexin STANN1 Promotes Drought Tolerance and Mitigates Light Stress in Transgenic Solanum tuberosum L. Plants.

Science.gov (United States)

Szalonek, Michal; Sierpien, Barbara; Rymaszewski, Wojciech; Gieczewska, Katarzyna; Garstka, Maciej; Lichocka, Malgorzata; Sass, Laszlo; Paul, Kenny; Vass, Imre; Vankova, Radomira; Dobrev, Peter; Szczesny, Pawel; Marczewski, Waldemar; Krusiewicz, Dominika; Strzelczyk-Zyta, Danuta; Hennig, Jacek; Konopka-Postupolska, Dorota

2015-01-01

Annexins are a family of calcium- and membrane-binding proteins that are important for plant tolerance to adverse environmental conditions. Annexins function to counteract oxidative stress, maintain cell redox homeostasis, and enhance drought tolerance. In the present study, an endogenous annexin, STANN1, was overexpressed to determine whether crop yields could be improved in potato (Solanum tuberosum L.) during drought. Nine potential potato annexins were identified and their expression characterized in response to drought treatment. STANN1 mRNA was constitutively expressed at a high level and drought treatment strongly increased transcription levels. Therefore, STANN1 was selected for overexpression analysis. Under drought conditions, transgenic potato plants ectopically expressing STANN1 were more tolerant to water deficit in the root zone, preserved more water in green tissues, maintained chloroplast functions, and had higher accumulation of chlorophyll b and xanthophylls (especially zeaxanthin) than wild type (WT). Drought-induced reductions in the maximum efficiency and the electron transport rate of photosystem II (PSII), as well as the quantum yield of photosynthesis, were less pronounced in transgenic plants overexpressing STANN1 than in the WT. This conferred more efficient non-photochemical energy dissipation in the outer antennae of PSII and probably more efficient protection of reaction centers against photooxidative damage in transgenic plants under drought conditions. Consequently, these plants were able to maintain effective photosynthesis during drought, which resulted in greater productivity than WT plants despite water scarcity. Although the mechanisms underlying this stress protection are not yet clear, annexin-mediated photoprotection is probably linked to protection against light-induced oxidative stress.

Potato Annexin STANN1 Promotes Drought Tolerance and Mitigates Light Stress in Transgenic Solanum tuberosum L. Plants.

Directory of Open Access Journals (Sweden)

Michal Szalonek

Full Text Available Annexins are a family of calcium- and membrane-binding proteins that are important for plant tolerance to adverse environmental conditions. Annexins function to counteract oxidative stress, maintain cell redox homeostasis, and enhance drought tolerance. In the present study, an endogenous annexin, STANN1, was overexpressed to determine whether crop yields could be improved in potato (Solanum tuberosum L. during drought. Nine potential potato annexins were identified and their expression characterized in response to drought treatment. STANN1 mRNA was constitutively expressed at a high level and drought treatment strongly increased transcription levels. Therefore, STANN1 was selected for overexpression analysis. Under drought conditions, transgenic potato plants ectopically expressing STANN1 were more tolerant to water deficit in the root zone, preserved more water in green tissues, maintained chloroplast functions, and had higher accumulation of chlorophyll b and xanthophylls (especially zeaxanthin than wild type (WT. Drought-induced reductions in the maximum efficiency and the electron transport rate of photosystem II (PSII, as well as the quantum yield of photosynthesis, were less pronounced in transgenic plants overexpressing STANN1 than in the WT. This conferred more efficient non-photochemical energy dissipation in the outer antennae of PSII and probably more efficient protection of reaction centers against photooxidative damage in transgenic plants under drought conditions. Consequently, these plants were able to maintain effective photosynthesis during drought, which resulted in greater productivity than WT plants despite water scarcity. Although the mechanisms underlying this stress protection are not yet clear, annexin-mediated photoprotection is probably linked to protection against light-induced oxidative stress.

Expression of annexin-A1 and galectin-1 anti-inflammatory proteins and mRNA in chronic gastritis and gastric cancer.

Science.gov (United States)

Jorge, Yvana Cristina; Mataruco, Mayra Mioto; Araújo, Leandro Pires; Rossi, Ana Flávia Teixeira; de Oliveira, Juliana Garcia; Valsechi, Marina Curado; Caetano, Alaor; Miyazaki, Kenji; Fazzio, Célia Sebastiana de Jesus; Thomé, Jorge Alberto; Rahal, Paula; Oliani, Sonia Maria; Silva, Ana Elizabete

2013-01-01

The anti-inflammatory proteins annexin-A1 and galectin-1 have been associated with tumor progression. This scenario prompted us to investigate the relationship between the gene and protein expression of annexin-A1 (ANXA1/AnxA1) and galectin-1 (LGALS1/Gal-1) in an inflammatory gastric lesion as chronic gastritis (CG) and gastric adenocarcinoma (GA) and its association with H. pylori infection. We analyzed 40 samples of CG, 20 of GA, and 10 of normal mucosa (C) by the quantitative real-time PCR (qPCR) technique and the immunohistochemistry assay. High ANXA1 mRNA expression levels were observed in 90% (36/40) of CG cases (mean relative quantification RQ = 4.26  ±  2.03) and in 80% (16/20) of GA cases (mean RQ = 4.38  ±  4.77). However, LGALS1 mRNA levels were high (mean RQ = 2.44  ±  3.26) in 60% (12/20) of the GA cases, while low expression was found in CG (mean RQ = 0.43 ± 3.13; P gastritis and gastric cancer, suggesting a strong association of these proteins with chronic gastric inflammation and carcinogenesis.

Role of lipoxygenases and lipoxin A(4)/annexin-1 receptor in gastric protection induced by 20% ethanol or sodium salicylate in rats.

Science.gov (United States)

Peskar, Brigitta M; Ehrlich, Karlheinz; Schuligoi, Rufina; Peskar, Bernhard A

2009-01-01

The role of cyclooxygenases and prostaglandins in experimental models of gastroprotection is well established. We investigated the effects of the 5-lipoxygenase inhibitor A63162, the 12-lipoxygenase inhibitor baicalein and the 15-lipoxygenase inhibitor PD146176 as well as the nonspecific lipoxin A(4)/annexin-1 antagonist Boc1 on adaptive protection induced by 20% ethanol against 70% ethanol, and on protection induced by sodium salicylate against the mucosal-damage-aggravating effects of celecoxib and dexamethasone during local ischemia-reperfusion in rats. It was found that both types of gastroprotection were antagonized by the lipoxygenase inhibitors and the lipoxin A(4)/annexin-1 antagonist in doses that have no direct damaging effect on gastric mucosa. The results suggest that not only cyclooxygenases, but also active lipoxygenases and, possibly, annexin-1 are required for these types of gastroprotection to occur. Copyright 2009 S. Karger AG, Basel.

First Pregnancy, Somatic and Psychological Status of a 4-Year-Old Child Born following Annexin V TESA Sperm Separation

Directory of Open Access Journals (Sweden)

Krzysztof Lukaszuk

2015-10-01

Full Text Available Introduction - Sperm DNA integrity is a crucial paternal factor affecting fertilization and pregnancy rates, as well as embryo development. Case - The present case report describes the successful pregnancy after testicular sperm aspiration (TESA combined with intracytoplasmic sperm injection (ICSI (TESA-ICSI in a couple where the male presented high sperm DNA fragmentation. In order to sort damaged sperm presenting DNA fragmentation, magnetic activated cell sorting (MACS with annexin V microbeads (MACS Miltenyi Biotec, Teterow, Germany was used. Conclusion - The authors present the first description of a successful medical case using TESA-ICSI annexin V sperm sorting. Additionally, a follow-up of the child at the age of 4 years old was done.

Intraoperative Detection of Cell Injury and Cell Death with an 800 nm Near-Infrared Fluorescent Annexin V Derivative

Science.gov (United States)

Ohnishi, Shunsuke; Vanderheyden, Jean-Luc; Tanaka, Eiichi; Patel, Bhavesh; De Grand, Alec; Laurence, Rita G.; Yamashita, Kenichiro; Frangioni, John V.

2008-01-01

The intraoperative detection of cell injury and cell death is fundamental to human surgeries such as organ transplantation and resection. Because of low autofluorescence background and relatively high tissue penetration, invisible light in the 800 nm region provides sensitive detection of disease pathology without changing the appearance of the surgical field. In order to provide surgeons with real-time intraoperative detection of cell injury and death after ischemia/reperfusion (I/R), we have developed a bioactive derivative of human annexin V (annexin800), which fluoresces at 800 nm. Total fluorescence yield, as a function of bioactivity, was optimized in vitro, and final performance was assessed in vivo. In liver, intestine and heart animal models of I/R, an optimal signal to background ratio was obtained 30 min after intravenous injection of annexin800, and histology confirmed concordance between planar reflectance images and actual deep tissue injury. In summary, annexin800 permits sensitive, real-time detection of cell injury and cell death after I/R in the intraoperative setting, and can be used during a variety of surgeries for rapid assessment of tissue and organ status. PMID:16869796

Bystander apoptosis in human cells mediated by irradiated blood plasma

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Vinnikov, Volodymyr, E-mail: vlad.vinnikov@mail.ru [Grigoriev Institute for Medical Radiology of the National Academy of Medical Science of Ukraine (Ukraine); Lloyd, David; Finnon, Paul [Centre for Radiation, Chemical and Environmental Hazards of the Health Protection Agency of the United Kingdom (United Kingdom)

2012-03-01

Following exposure to high doses of ionizing radiation, due to an accident or during radiotherapy, bystander signalling poses a potential hazard to unirradiated cells and tissues. This process can be mediated by factors circulating in blood plasma. Thus, we assessed the ability of plasma taken from in vitro irradiated human blood to produce a direct cytotoxic effect, by inducing apoptosis in primary human peripheral blood mononuclear cells (PBM), which mainly comprised G{sub 0}-stage lymphocytes. Plasma was collected from healthy donors' blood irradiated in vitro to 0-40 Gy acute {gamma}-rays. Reporter PBM were separated from unirradiated blood with Histopaque and held in medium with the test plasma for 24 h at 37 Degree-Sign C. Additionally, plasma from in vitro irradiated and unirradiated blood was tested against PBM collected from blood given 4 Gy. Apoptosis in reporter PBM was measured by the Annexin V test using flow cytometry. Plasma collected from unirradiated and irradiated blood did not produce any apoptotic response above the control level in unirradiated reporter PBM. Surprisingly, plasma from irradiated blood caused a dose-dependent reduction of apoptosis in irradiated reporter PBM. The yields of radiation-induced cell death in irradiated reporter PBM (after subtracting the respective values in unirradiated reporter PBM) were 22.2 {+-} 1.8% in plasma-free cultures, 21.6 {+-} 1.1% in cultures treated with plasma from unirradiated blood, 20.2 {+-} 1.4% in cultures with plasma from blood given 2-4 Gy and 16.7 {+-} 3.2% in cultures with plasma from blood given 6-10 Gy. These results suggested that irradiated blood plasma did not cause a radiation-induced bystander cell-killing effect. Instead, a reduction of apoptosis in irradiated reporter cells cultured with irradiated blood plasma has implications concerning oncogenic risk from mutated cells surviving after high dose in vivo irradiation (e.g. radiotherapy) and requires further study.

Bystander apoptosis in human cells mediated by irradiated blood plasma

International Nuclear Information System (INIS)

Vinnikov, Volodymyr; Lloyd, David; Finnon, Paul

2012-01-01

Following exposure to high doses of ionizing radiation, due to an accident or during radiotherapy, bystander signalling poses a potential hazard to unirradiated cells and tissues. This process can be mediated by factors circulating in blood plasma. Thus, we assessed the ability of plasma taken from in vitro irradiated human blood to produce a direct cytotoxic effect, by inducing apoptosis in primary human peripheral blood mononuclear cells (PBM), which mainly comprised G 0 -stage lymphocytes. Plasma was collected from healthy donors’ blood irradiated in vitro to 0–40 Gy acute γ-rays. Reporter PBM were separated from unirradiated blood with Histopaque and held in medium with the test plasma for 24 h at 37 °C. Additionally, plasma from in vitro irradiated and unirradiated blood was tested against PBM collected from blood given 4 Gy. Apoptosis in reporter PBM was measured by the Annexin V test using flow cytometry. Plasma collected from unirradiated and irradiated blood did not produce any apoptotic response above the control level in unirradiated reporter PBM. Surprisingly, plasma from irradiated blood caused a dose-dependent reduction of apoptosis in irradiated reporter PBM. The yields of radiation-induced cell death in irradiated reporter PBM (after subtracting the respective values in unirradiated reporter PBM) were 22.2 ± 1.8% in plasma-free cultures, 21.6 ± 1.1% in cultures treated with plasma from unirradiated blood, 20.2 ± 1.4% in cultures with plasma from blood given 2–4 Gy and 16.7 ± 3.2% in cultures with plasma from blood given 6–10 Gy. These results suggested that irradiated blood plasma did not cause a radiation-induced bystander cell-killing effect. Instead, a reduction of apoptosis in irradiated reporter cells cultured with irradiated blood plasma has implications concerning oncogenic risk from mutated cells surviving after high dose in vivo irradiation (e.g. radiotherapy) and requires further study.

The Role of (99m)Tc-Annexin V Apoptosis Scintigraphy in Visualizing Early Stage Glucocorticoid-Induced Femoral Head Osteonecrosis in the Rabbit.

Science.gov (United States)

Wang, Xiaolong; Liu, Yu; Wang, Xuemei; Liu, Rui; Li, Jianbo; Zhang, Guoliang; Li, Qiang; Wang, Lei; Bai, Zhigang; Zhao, Jianmin

2016-01-01

To validate the ability of (99m)Tc-Annexin V to visualize early stage of glucocorticoid-induced femoral head necrosis by comparing with (99m)Tc-MDP bone scanning. Femoral head necrosis was induced in adult New Zealand white rabbits by intramuscular injection of methylprednisolone. (99m)Tc-Annexin scintigraphy and (99m)Tc-MDP scans were performed before and 5, 6, and 8 weeks after methylprednisolone administration. Rabbits were sacrificed at various time points and conducted for TUNEL and H&E staining. All methylprednisolone treated animals developed femoral head necrosis; at 8 weeks postinjection, destruction of bone structure was evident in H&E staining, and apoptosis was confirmed by the TUNEL assay. This was matched by (99m)Tc-Annexin V images, which showed a significant increase in signal over baseline. Serial (99m)Tc-Annexin V scans revealed that increased (99m)Tc-Annexin V uptake could be observed in 5 weeks. In contrast, there was no effect on (99m)Tc-MDP signal until 8 weeks. The TUNEL assay revealed that bone cell apoptosis occurred at 5 weeks. (99m)Tc-Annexin V is superior to (99m)Tc-MDP for the early detection of glucocorticoid-induced femoral head necrosis in the rabbit and may be a better strategy for the early detection of glucocorticoid-induced femoral head necrosis in patients.

Irradiation of UO2

International Nuclear Information System (INIS)

Stevanovic, M.

1965-10-01

Based on the review of the available literature concerned with UO 2 irradiation, this paper describes and explains the phenomena initiated by irradiation of the UO 2 fuel in a reactor dependent on the burnup level and temperature. A comprehensive review of UO 2 radiation damage studies is given as a broad research program. This part includes the abilities of our reactor as well as needed elements for such study. The third part includes the definitions of the specific power, burnup level and temperature in the center of the fuel element needed for planning and performing the irradiation. Methods for calculating these parameters are included [sr

Domains I and IV of annexin A2 affect the formation and integrity of in vitro capillary-like networks.

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Aase M Raddum

Full Text Available Annexin A2 (AnxA2 is a widely expressed multifunctional protein found in different cellular compartments. In spite of lacking a hydrophobic signal peptide, AnxA2 is found at the cell surface of endothelial cells, indicative of a role in angiogenesis. Increased extracellular levels of AnxA2 in tumours correlate with neoangiogenesis, metastasis and poor prognosis. We hypothesised that extracellular AnxA2 may contribute to angiogenesis by affecting endothelial cell-cell interactions and motility. To address this question, we studied the effect of heterotetrameric and monomeric forms of AnxA2, as well as its two soluble domains on the formation and maintenance of capillary-like structures by using an in vitro co-culture system consisting of endothelial and smooth muscle cells. In particular, addition of purified domains I and IV of AnxA2 potently inhibited the vascular endothelial growth factor (VEGF-dependent formation of the capillary-like networks in a dose-dependent manner. In addition, these AnxA2 domains disrupted endothelial cell-cell contacts in preformed capillary-like networks, resulting in the internalisation of vascular endothelial (VE-cadherin and the formation of VE-cadherin-containing filopodia-like structures between the endothelial cells, suggesting increased cell motility. Addition of monoclonal AnxA2 antibodies, in particular against Tyr23 phosphorylated AnxA2, also strongly inhibited network formation in the co-culture system. These results suggest that extracellular AnxA2, most likely in its Tyr phosphorylated form, plays a pivotal role in angiogenesis. The exogenously added AnxA2 domains most likely mediate their effects by competing with endogenous AnxA2 for extracellular factors necessary for the initiation and maintenance of angiogenesis, such as those involved in the formation/integrity of cell-cell contacts.

¹¹¹In-DOTA-Annexin V for imaging of apoptosis during HSV1-tk/GCV prodrug activation gene therapy in mice with NG4TL4 sarcoma.

Science.gov (United States)

Lin, Ming-Hsien; Wu, Shih-Yen; Wang, Hsin-Ell; Liu, Ren-Shyan; Chen, Jyh-Cheng

2016-02-01

Apoptosis has been suggested as a cytocidal mechanism of the HSV1-tk-expressing cells when exposed to ganciclovir (GCV). This study evaluated the efficacy of (111)In-labeled Annexin V for monitoring tumor responses during prodrug activation gene therapy with HSV1-tk and GCV. Annexin V was conjugated to DOTA using N-hydroxysulfosuccinimide (sulfo-NHS) and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC), labeled with (111)In-InCl3 and purified using size exclusion chromatography to give (111)In-DOTA-Annexin V conjugate. The radiochemical yield and the radiochemical purity of (111)In-DOTA-Annexin V were 74±12% and 98±3%, respectively (n=10). (111)In-DOTA-BSA was prepared similarly. An in vitro study to demonstrate the apoptosis of NG4TL4-STK cells after GCV treatment has been performed. Mice bearing NG4TL4-STK and NG4TL4-WT tumors were treated with GCV (10 mg/kg daily) by i.p. injection for 7 consecutive days. Before and during the GCV treatment, biodistribution studies and scintigraphic imaging were performed at 2h post injection of the radiotracers. The uptake of (111)In-DOTA-Annexin V in treated cells (13.41±1.30%) was 4.1 times higher than that in untreated cells (3.21±0.37%). The GCV-induced cell apoptosis in NG4TL4-STK tumor resulted in a significantly increasing accumulation of (111)In-DOTA-Annexin V (1.92±0.32%ID/g at day 0, 4.79±0.86%ID/g at day 2, 4.56±0.58%ID/g at day 4) was observed, but not for that of (111)In-DOTA-BSA. During consecutive GCV treatment, scintigraphic imaging with (111)In-DOTA-Annexin V revealed high uptake in NG4TL4-STK tumor compared with that in NG4TL4-WT tumor. However, no specific (111)In-DOTA-BSA accumulation in NG4TL4-STK and NG4TL4-WT tumors was observed throughout the course of GCV treatment. This study demonstrated that (111)In-DOTA-Annexin V can be used for monitoring tumor cell apoptosis during prodrug activation gene therapy with HSV1-tk and GCV for cancer treatment. Copyright © 2015 Elsevier Ltd. All rights

Evaluation of radiolabelled annexin A5 for scintigraphic imaging of cell processes (necrosis/apoptosis) in cardiovascular diseases; Evaluation de radiotraceurs derives de l'annexine A5 pour l'imagerie scintigraphique de processus cellulaires (apoptose/necrose/thrombose) en pathologie cardiovasculaire (Ressource electronique)

Energy Technology Data Exchange (ETDEWEB)

Sarda-Mantel, L

2007-03-15

Annexin A5, a 35KDa protein, specifically binds with high affinity to phosphatidylserine (P.S.) which is actively redistributed to the external leaflet of plasmic membranes in apoptotic cells and activated platelets. Annexin A5 radiolabelled with {sup 99m}Tc({sup 99m}Tc-ANX5) was developed by Strauss (stanford, Usa) to image apoptosis in vivo: tumours cells apoptosis induced by chemo-radiotherapy, ischemia/reperfusion lesions in animals and patients, graft rejection. Additionally, many in vitro data suggest that annexin A5 also stains necrosis (membrane disruption), which occurs in all types of cell death. This preclinical work aimed to evaluate the potential interest of {sup 99m}Tc-ANX5 imaging as a clinical tool in cardiovascular diseases. Four studies performed in rat models of myocardial infarction by coronary ligation and ischemia-reperfusion, and in rat models of subacute and acute (isoproterenol-induced) myocarditis show the ability of {sup 99m}Tc-ANX5 to detect in vivo cardio myocytes death by apoptosis and necrosis. Another study demonstrates that {sup 99m}Tc-ANX5 is highly accurate to evaluate in vivo the biological activity of parietal thrombus in a rat model of elastase-induced abdominal aortic aneurysm. These results suggest that {sup 99m}Tc-ANX5 imaging could be used in patients for non invasive diagnosis, prognostic evaluation in acute myocarditis and in various thrombotic cardiovascular diseases. (author)

Fabrication, irradiation and post-irradiation examinations of MO2 and UO2 sphere-pac and UO2 pellet fuel pins irradiated in a PWR loop

International Nuclear Information System (INIS)

Linde, A. van der; Lucas Luijckx, H.J.B.; Verheugen, J.H.N.

1981-04-01

Three fuel pin bundles, R-109/1, 2 and 3, were irradiated in a PWR loop in the HFR at Petten during respectively 131, 57 and 57 effective full power days at average powers of approximately 39 kW.m -1 and at peak powers of approximately 60 kW.m -1 . The results of the post-irradiation examinations of these fuel bundles are presented. (Auth.)

{sup 99m}Tc Hynic-rh-Annexin V scintigraphy for in vivo imaging of apoptosis in patients with head and neck cancer treated with chemoradiotherapy

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Hoebers, Frank J.P.; Bois, Josien de; Herk, Marcel van; Rasch, Coen R.N.; Verheij, Marcel [The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Department of Radiotherapy, Amsterdam (Netherlands); Kartachova, Marina; Valdes Olmos, Renato A. [The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Brekel, Michiel W.M. van den [The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital and Academic Medical Center, Department of Head and Neck Oncology and Surgery, Amsterdam (Netherlands); Tinteren, Harm van [The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Biometrics Department, Amsterdam (Netherlands)

2008-03-15

The purpose of this study was to determine the value of {sup 99m}Tc Hynic-rh-Annexin-V-Scintigraphy (TAVS), a non-invasive in vivo technique to demonstrate apoptosis in patients with head and neck squamous cell carcinoma. TAVS were performed before and within 48 h after the first course of cisplatin-based chemoradiation. Radiation dose given to the tumour at the time of post-treatment TAVS was 6-8 Gy. Single-photon emission tomography data were co-registered to planning CT scan. Complete sets of these data were available for 13 patients. The radiation dose at post-treatment TAVS was calculated for several regions of interest (ROI): primary tumour, involved lymph nodes and salivary glands. Annexin uptake was determined in each ROI, and the difference between post-treatment and baseline TAVS represented the absolute Annexin uptake: Delta uptake ({delta}U). In 24 of 26 parotid glands, treatment-induced Annexin uptake was observed. Mean {delta}U was significantly correlated with the mean radiation dose given to the parotid glands (r = 0.59, p = 0.002): Glands that received higher doses showed more Annexin uptake. {delta}U in primary tumour and pathological lymph nodes showed large inter-patient differences. A high correlation was observed on an inter-patient level (r = 0.71, p = 0.006) between the maximum {delta}U in primary tumour and in the lymph nodes. Within the dose range of 0-8 Gy, Annexin-V-scintigraphy showed a radiation-dose-dependent uptake in parotid glands, indicative of early apoptosis during treatment. The inter-individual spread in Annexin uptake in primary tumours could not be related to differences in dose or tumour volume, but the Annexin uptake in tumour and lymph nodes were closely correlated. This effect might represent a tumour-specific apoptotic response. (orig.)

Monitoring Cell Death in Regorafenib-Treated Experimental Colon Carcinomas Using Annexin-Based Optical Fluorescence Imaging Validated by Perfusion MRI.

Directory of Open Access Journals (Sweden)

Philipp M Kazmierczak

Full Text Available To investigate annexin-based optical fluorescence imaging (OI for monitoring regorafenib-induced early cell death in experimental colon carcinomas in rats, validated by perfusion MRI and multiparametric immunohistochemistry.Subcutaneous human colon carcinomas (HT-29 in athymic rats (n = 16 were imaged before and after a one-week therapy with regorafenib (n = 8 or placebo (n = 8 using annexin-based OI and perfusion MRI at 3 Tesla. Optical signal-to-noise ratio (SNR and MRI tumor perfusion parameters (plasma flow PF, mL/100mL/min; plasma volume PV, % were assessed. On day 7, tumors underwent immunohistochemical analysis for tumor cell apoptosis (TUNEL, proliferation (Ki-67, and microvascular density (CD31.Apoptosis-targeted OI demonstrated a tumor-specific probe accumulation with a significant increase of tumor SNR under therapy (mean Δ +7.78±2.95, control: -0.80±2.48, p = 0.021. MRI detected a significant reduction of tumor perfusion in the therapy group (mean ΔPF -8.17±2.32 mL/100 mL/min, control -0.11±3.36 mL/100 mL/min, p = 0.036. Immunohistochemistry showed significantly more apoptosis (TUNEL; 11392±1486 vs. 2921±334, p = 0.001, significantly less proliferation (Ki-67; 1754±184 vs. 2883±323, p = 0.012, and significantly lower microvascular density (CD31; 107±10 vs. 182±22, p = 0.006 in the therapy group.Annexin-based OI allowed for the non-invasive monitoring of regorafenib-induced early cell death in experimental colon carcinomas, validated by perfusion MRI and multiparametric immunohistochemistry.

Inhibition of Langerhans cell maturation by human papillomavirus type 16: a novel role for the annexin A2 heterotetramer in immune suppression.

Science.gov (United States)

Woodham, Andrew W; Raff, Adam B; Raff, Laura M; Da Silva, Diane M; Yan, Lisa; Skeate, Joseph G; Wong, Michael K; Lin, Yvonne G; Kast, W Martin

2014-05-15

High-risk human papillomaviruses (HPVs) are sexually transmitted viruses causally associated with several cancers. During its natural life cycle, HPV16, the most common high-risk genotype, infects the epithelial basal cells in a process facilitated through a recently identified receptor, the annexin A2 heterotetramer (A2t). During infection, HPV16 also interacts with Langerhans cells (LC), the APC of the epithelium, inducing immune suppression, which is mediated by the HPV16 L2 minor capsid protein. Despite the importance of these virus-immune cell interactions, the specific mechanisms of HPV16 entry into LC and HPV16-induced immune suppression remain undefined. An N-terminal peptide of HPV16 L2 (aa 108-126) has been shown to specifically interact with A2t. In this study, we show that incubation of human LC with this peptide blocks binding of HPV16. Inhibiting this interaction with an A2t ligand or by small interfering RNA downregulation of A2t significantly decreases HPV16 internalization into LC in an L2-dependent manner. A2t is associated with suppression of LC maturation as demonstrated through attenuated secretion of Th1-associated cytokines and decreased surface expression of MHC class II on LC exposed to A2t. Conversely, small molecule inhibition of A2t prevents HPV16-induced suppression of LC immune function as indicated by significantly increased secretion of inflammatory cytokines and surface expression of CD86 in HPV16 treated LC pre-exposed to A2t inhibitors. These results demonstrate that HPV16 suppresses LC maturation through an interaction with A2t, revealing a novel role for this protein.

Regulation of annexins following infection like tissue damage – investigated by 2-dimensional gel electrophoresis

DEFF Research Database (Denmark)

Wulff, Tune; Nielsen, Michael Engelbrecht

are regulated after tissue damaged on the protein level. These proteins have been assign to functions like regulation of coagulation, apoptosis, and exocytosis, indicating their importance following infection and subsequent repair in fish. In addition the regulation observed in this study are supported...... an established model. In the model infection is mimicked by a well-defined tissue damage allowing each fish to be equally affected. Samples were taken 7 days after tissue damage and included samples from the damaged tissue, internal control and an external control. Changes in protein expression between the wound...... by previous findings on the mRNA level, where both proteins are regulated following infection. In conclusion this study show regulation on the protein level of two members of the annexin protein family after infection like tissue damage....

Annexin A2 in Proliferative Vitreoretinopathy

Science.gov (United States)

2017-10-01

that breaches the blood-retinal barrier, leakage of plasma proteins and circulating blood cells, possibly together with local hypoxia, conspire to...immunofluorescence staining to document the migration of A2-positive cells from the RPE to the surface of the retina in PVR (Fig. 3). We have also detected a few...readily detected (Fig. 9B, 9C). Cells in both groups were also positive for A2. These data indicate that expression of A2 in both RPE cells and

Study of 99Tcm-annexin V distribution in inferior vena cava thrombus models of rabbits

International Nuclear Information System (INIS)

Wu Dayong; Zhang Wenyan; Bian Yanzhu; Hu Yujing

2013-01-01

To study 99 Tc m -Annexin V distribution in inferior vena cava thrombus models of rabbits and uptake of 99 Tc m -Annexin V in fresh and old venous thrombus. Rabbits (n=15) were randomly grouped into 3 groups (the fresh thrombus group, old thrombus group, and control group). The rabbits of two thrombus groups developed inferior vena cava thrombus models by operations. The control group received sham operation. The fresh thrombus group and control group rabbits were injected 99 Tc m -Annexin V after operating 1 d; the old thrombus group 14 d. After 1 h all rabbits were killed by injecting overdose pentobarbital sodium. The thrombus (or the inferior vena cava about 3 cm below inferior pole of right kidney level in the control group rabbits), blood, thrombus area inferior vena cava, head lateral inferior vena cava (except the control group), thigh muscle, stomach, myocardium, pulmonary, liver, kidney, spleen, bone and small intestine were obtained from all group rabbits. The ex tissue and blood were weighed and measured by a Well-type detector. The percentage of the injected dose per gram of ex tissue (or blood) was calculated by the above data. The thrombus to blood, thrombus area inferior vena cava, head lateral inferior vena cava and thigh muscle ratios were calculated by percentage of the injected dose per gram of ex tissue (or blood). The test was used to compare the fresh thrombus group and old thrombus group by SPSS 17.0. The percentage of' the injected dose per gram of thrombi (0.01894± 0.002 16% ID/g) in the fresh thrombus group was higher than the old thrombus group (0.00473±0.001 28% ID/g), P<0.05. The thrombus to blood, thrombus area inferior vena cava, head lateral inferior vena cava and muscle ratios (3.42±1.06, 26.32±13.60, 31.23 ±16.00, 111.62±52.23) in the fresh thrombus group were higher than the old thrombus group (0.98±0.09, 5.12±2.01, 6.25±2.38, 21.82±5.93), P<0.05 for all. All the thrombi of the fresh thrombus group were confirmed

Structure of a C-terminal AHNAK peptide in a 1:2:2 complex with S100A10 and an acetylated N-terminal peptide of annexin A2

International Nuclear Information System (INIS)

Ozorowski, Gabriel; Milton, Saskia; Luecke, Hartmut

2013-01-01

Structure of a 20-amino-acid peptide of AHNAK bound asymmetrically to the AnxA2–S100A10A heterotetramer (1:2:2 symmetry) provides insights into the atomic level interactions that govern this membrane-repair scaffolding complex. AHNAK, a large 629 kDa protein, has been implicated in membrane repair, and the annexin A2–S100A10 heterotetramer [(p11) 2 (AnxA2) 2 )] has high affinity for several regions of its 1002-amino-acid C-terminal domain. (p11) 2 (AnxA2) 2 is often localized near the plasma membrane, and this C2-symmetric platform is proposed to be involved in the bridging of membrane vesicles and trafficking of proteins to the plasma membrane. All three proteins co-localize at the intracellular face of the plasma membrane in a Ca 2+ -dependent manner. The binding of AHNAK to (p11) 2 (AnxA2) 2 has been studied previously, and a minimal binding motif has been mapped to a 20-amino-acid peptide corresponding to residues 5654–5673 of the AHNAK C-terminal domain. Here, the 2.5 Å resolution crystal structure of this 20-amino-acid peptide of AHNAK bound to the AnxA2–S100A10 heterotetramer (1:2:2 symmetry) is presented, which confirms the asymmetric arrangement first described by Rezvanpour and coworkers and explains why the binding motif has high affinity for (p11) 2 (AnxA2) 2 . Binding of AHNAK to the surface of (p11) 2 (AnxA2) 2 is governed by several hydrophobic interactions between side chains of AHNAK and pockets on S100A10. The pockets are large enough to accommodate a variety of hydrophobic side chains, allowing the consensus sequence to be more general. Additionally, the various hydrogen bonds formed between the AHNAK peptide and (p11) 2 (AnxA2) 2 most often involve backbone atoms of AHNAK; as a result, the side chains, particularly those that point away from S100A10/AnxA2 towards the solvent, are largely interchangeable. While the structure-based consensus sequence allows interactions with various stretches of the AHNAK C-terminal domain, comparison

Evaluation of radiolabeling of annexin A5 with technetium-99m: influence of the labeling methods on physico-chemical and biological properties of the compounds

International Nuclear Information System (INIS)

Santos, Josefina da Silva

2009-01-01

Annexin A5 (ANXA5) is an intracellular human protein of 36 kDa with high affinity for membrane-bound phosphatidylserine that is selectively exposed on the surface of cells undergoing apoptosis. Apoptosis is important in normal physiology and innumerous pathologic states. Clinical applications for ANXA5 imaging are being developed in oncology, organ transplantation and cardiovascular diseases. Many strategies to radiolabel the protein have been described, including direct labeling, derivatization through a bifunctional chelating agent (BFC), production of mutated protein or peptide analogs. Several 99 mTc-labeling techniques have been reported using different cores, including [Tc=O] +3 , [Tc]HYNIC, [Tc≡N]+2 and [Tc(CO 3 )] +1 . In this study, we evaluated the influence of 99 mTc cores on biological behavior and physico-chemical properties of radiolabeled annexin. Radiolabeling procedure using [Tc≡N] +2 core was a two-step procedure including the reaction of 99 mTcO4 - with SDH in the presence of SnCl 2 and PDTA to obtain the intermediate 99 mTcN-SDH, and successive addition of ANXA5. The results obtained were not satisfactory, despite the high efficiency in the production of the intermediate. The [Tc=O] +3 core was produced using the ethylene dicysteine (EC) as BFC. TSTU was employed in the derivatization to produce the corresponding hydroxysuccinimide ester. Different ANXA5:EC ratios were studied and all labeling conditions resulted in high radiochemical yield but with differences in lipophilicity, stability, biological distribution and affinity for apoptotic cells. The HYNIC-ANXA5 also produced the labeled protein with high radiochemical yield. The stability of the radiolabeled ANXA5 was evaluated after storing at room temperature, at 2 - 8 degree C and in human serum at 37 degree C. The analysis of these results showed that the 99 mTc-EC-ANXA5 (ratio 10-2) was the most stable compound in all the studied conditions. Partition coefficient assay resulted in

Irradiation techniques at BR2 reactor

International Nuclear Information System (INIS)

Hebel, W.

1978-01-01

Since 1963 the material testing reactor BR2 at Mol is operated for the realisation of numerous research programs and experiments on the behavior of materials under nuclear radiation and in particular under intensive neutron exposure. During this period special irradiation techniques and experimental devices were developed according to the desiderata of the different experiments and to the irradiation possibilities offered at BR2. The design and the operating characteristics of quite a number of those irradiation rigs of proven reliability may be used or can be made available for new irradiation experiments. A brief description is given of some typical irradiation devices designed and constructed by CEN/SCK, Technology and Energy Dpt. They are compiled according to their main use for the different research and development programs realized at BR2. Their eventual application however for different objectives could be possible. A final chapter summarizes the principal irradiation conditions offered by BR2 reactor. (author)

Characterization of death of human fetal bone marrow CD34+ cells after different dose of γ-irradiation

International Nuclear Information System (INIS)

Xiang Yingsong; Yang Rujun; Tang Gusheng

2001-01-01

Objective: To investigate the characterization of death of the human hematopoietic stem cells after irradiation. Methods: Human fetal bone marrow mononuclear cells were irradiated with different doses of 60 Co γ-rays at different high dose rates. Apoptosis and necrosis of CD34 + cells were analyzed by flow cytometry, following three-color labelling with PE-CD34/FITC-Annexin V/7AAD at different times after irradiation. Results: The death of CD34 + cells after 5 Gy and 8 Gy irradiation showed a continuous process of reproductive death during the first week,and the main death type was apoptosis. A majority of CD34 + cells died of necrosis during the first day after 10 Gy and 12 Gy irradiation, and all of them died within a week. Conclusion: Niches are continuously vacated every day within a week following irradiation and reproductive death of hematopoietic stem cells occurred

Induction of Lipocalin2 in a Rat Model of Lung Irradiation

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Sadaf Sultan

2016-04-01

Full Text Available Previously, we showed that lipocalin2 (LCN2 serum levels increased after liver irradiation and during acute-phase conditions. Here, we evaluate LCN2 expression and serum levels after single-dose lung irradiation with 25 Gy, percutaneously administered to the lung of randomly-paired male Wistar rats. Due to the concave anatomy of the lung recesses, the irradiation field included the upper part of the liver. No rat died due to irradiation. In control tissue, lung immunohistochemistry showed a high constitutive expression of LCN2+ granulocytes. LCN2 mRNA levels in lung tissue increased up to 24 h (9 ± 2.3-fold after irradiation. However, serum LCN2 levels remained undetectable after lung irradiation. LCN2 expression in the upper part of the liver increased up to 4.2-fold after lung irradiation, but the lower liver showed an early decrease. Acute-phase cytokines (IL-1β and TNF-α showed a significant increase on transcript level in both lung and upper liver, whilst the lower liver did not show any considerable increase. In conclusion, constitutive expression of LCN2 in local immune cells demonstrates its local role during stress conditions in the lung. The absence of LCN2 in the serum strengthens our previous findings that the liver is the key player in secreting LCN2 during stress conditions with liver involvement.

Annexin A2 in Proliferative Vitreoretinopathy

Science.gov (United States)

2016-10-01

normal architecture of the Anxa2+/+ retina with loss of defined cell layers and retraction of the retina to form a mass containing pigmented cells...ectopic presence of RPE cells, and no retraction of the retina. In the Anxa2-/- eye, the normal architecture of the retina and its typical distribution...eyes. For semi-quantitative scoring, we have devised an overall PVR Histology Index ( PHI ) (Figure 2). The PHI is based on the degree of retinal

The Effect of Lycopene Preexposure on UV-B-Irradiated Human Keratinocytes

Science.gov (United States)

Ascenso, Andreia; Pedrosa, Tiago; Pinho, Sónia; Pinho, Francisco; de Oliveira, José Miguel P. Ferreira; Cabral Marques, Helena; Oliveira, Helena; Simões, Sandra; Santos, Conceição

2016-01-01

Lycopene has been reported as the antioxidant most quickly depleted in skin upon UV irradiation, and thus it might play a protective role. Our goal was to investigate the effects of preexposure to lycopene on UV-B-irradiated skin cells. Cells were exposed for 24 h to 10 M lycopene, and subsequently irradiated and left to recover for another 24 h period. Thereafter, several parameters were analyzed by FCM and RT-PCR: genotoxicity/clastogenicity by assessing the cell cycle distribution; apoptosis by performing the Annexin-V assay and analyzing gene expression of apoptosis biomarkers; and oxidative stress by ROS quantification. Lycopene did not significantly affect the profile of apoptotic, necrotic and viable cells in nonirradiated cells neither showed cytostatic effects. However, irradiated cells previously treated with lycopene showed an increase in both dead and viable subpopulations compared to nonexposed irradiated cells. In irradiated cells, lycopene preexposure resulted in overexpression of BAX gene compared to nonexposed irradiated cells. This was accompanied by a cell cycle delay at S-phase transition and consequent decrease of cells in G0/G1 phase. Thus, lycopene seems to play a corrective role in irradiated cells depending on the level of photodamage. Thus, our findings may have implications for the management of skin cancer. PMID:26664697

Corrosion of electron-irradiated Zr-2.5Nb and Zircaloy-2

International Nuclear Information System (INIS)

Woo, O.-T.; McDougall, G.M.; Hutcheon, R.M.; Urbanic, V.F.; Griffiths, M.; Coleman, C.E.

2000-01-01

We used 10-MeV electrons to rapidly produce radiation damage in zirconium alloys, investigated whether electrons produced the same microstructural changes as neutrons, then performed post-irradiation corrosion tests to determine whether electron-irradiated materials displayed similar corrosion behavior to neutron-irradiated materials. Two irradiations were completed using 10-MeV electrons with the beam normal to thin disks of material of 4 diameter slightly larger than the beam. The beam distribution. and disk cooling were designed to produce radial temperature and dose distributions having maxima at the disk center. A high-temperature irradiation was performed on annealed Zr-2.5Nb disks, achieving a central dose of 1.3 dpa and at a central temperature of ∼450 deg C. After irradiation, the samples contained needle-like β-Nb precipitates in the α-Zr matrix similar to those produced by neutrons. A low-temperature irradiation was performed on half-moon disks of Zr-2.5Nb and Zircaloy-2 pressure tube materials at 310 deg C central temperature and 1.3-dpa central dose. Dislocation loops were observed, again similar to those produced in neutron-irradiated materials. Some of the high-temperature electron-irradiated disks were exposed to 300 deg C moist air (saturated with D 2 O), and in separate tests, high- and low-temperature irradiated disks were corroded in 300 deg C D 2 0 (11.0 pD at room temperature) in an autoclave. Measurements of oxide thickness by Fourier Transform Infrared Reflectance (FTIR) spectroscopy showed that electron irradiation reduced the corrosion rate of Zr-2.5Nb compared with that of unirradiated material, as observed for neutron irradiation. For exposures to moist air and to D 2 O, the theoretical deuterium uptakes for the electron-irradiated materials were, respectively, about 4 times and 1.5 to 2 times those for the unirradiated materials. This is also in good agreement with results for neutron-irradiated pressure tube materials. Thus, 10-Me

Quantitative Proteomic Profiling the Molecular Signatures of Annexin A5 in Lung Squamous Carcinoma Cells

OpenAIRE

Sun, Bing; Bai, Yuxin; Zhang, Liyuan; Gong, Linlin; Qi, Xiaoyu; Li, Huizhen; Wang, Faming; Chi, Xinming; Jiang, Yulin; Shao, Shujuan

2016-01-01

Lung cancer remains the leading cancer killer around the world. It's crucial to identify newer mechanism-based targets to effectively manage lung cancer. Annexin A5 (ANXA5) is a protein kinase C inhibitory protein and calcium dependent phospholipid-binding protein, which may act as an endogenous regulator of various pathophysiological processes. However, its molecular mechanism in lung cancer remains poorly understood. This study was designed to determine the mechanism of ANXA5 in lung cancer...

Inhibition of Langerhans cell maturation by human papillomavirus type 16: a novel role for the annexin A2 heterotetramer in immune suppression1

Science.gov (United States)

Woodham, Andrew W.; Raff, Adam B.; Raff, Laura M.; Da Silva, Diane M.; Yan, Lisa; Skeate, Joseph G.; Wong, Michael K.; Lin, Yvonne G.; Kast, W. Martin

2014-01-01

High-risk human papillomaviruses (HPV) are sexually transmitted viruses causally associated with several cancers. During its natural life cycle, HPV16, the most common high-risk genotype, infects the epithelial basal cellsin a process facilitated through a recently identified receptor, the annexin A2 heterotetramer (A2t). During infection, HPV16 also interacts with Langerhans cells (LC), the antigen presenting cells of the epithelium, inducing immune suppression, which is mediated by the HPV16 L2 minor capsid protein. Despite the importance of these virus-immune cell interactions, the specific mechanisms of HPV16 entry into LC and HPV16-induced immune suppression remain undefined. An N-terminal peptide of HPV16 L2 (aa 108-126) has been shown to specifically interact with A2t. Here, we show that incubation of human LC with this peptide blocks binding of HPV16. Inhibiting this interaction with an A2t ligand or by siRNA downregulation of A2t, significantly decreases HPV16 internalization into LC in an L2-dependent manner. A2t is associated with suppression of LC maturation as demonstrated through attenuated secretion of Th1-associated cytokines and decreased surface expression of MHC II on LC exposed to A2t. Conversely, small molecule inhibition of A2t prevents HPV16-induced suppression of LC immune function as indicated by significantly increased secretion of inflammatory cytokines and surface expression of CD86 in HPV16 treated LC pre-exposed to A2t inhibitors. These results demonstrate that HPV16 suppresses LC maturation through an interaction with A2t, revealing a novel role for this protein. PMID:24719459

In vitro and in vivo evaluation of [{sup 99m}Tc]-labeled tricarbonyl His-annexin A5 as an imaging agent for the detection of phosphatidylserine-expressing cells

Energy Technology Data Exchange (ETDEWEB)

Vangestel, Christel, E-mail: christel.vangestel@ugent.b [Department of Gastroenterology, Ghent University Hospital, 9000-B Ghent (Belgium); Peeters, Marc [Department of Gastroenterology, Ghent University Hospital, 9000-B Ghent (Belgium); Oltenfreiter, Ruth; D' Asseler, Yves [Department of Nuclear Medicine and Radiology, Ghent University Hospital, 9000-B Ghent (Belgium); Staelens, Steven [Department of Medical Signal and Image Processing Group, Faculty of Engineering, Ghent University-IBBT, 9000-B Ghent (Belgium); Van Steenkiste, Magali [Department of Radiopharmacy, Ghent University, 9000-B Ghent (Belgium); Philippe, Jan [Department of Clinical Biology, Microbiology and Immunology, Ghent University, 9000-B Ghent (Belgium); Kusters, Dennis; Reutelingsperger, Chris [Department of Biochemistry, Cardiovascular Research Institute, University of Maastricht, 6200 MD Maastricht (Netherlands); Van Damme, Nancy [Department of Gastroenterology, Ghent University Hospital, 9000-B Ghent (Belgium); Van de Wiele, Christophe [Department of Nuclear Medicine and Radiology, Ghent University Hospital, 9000-B Ghent (Belgium)

2010-11-15

Introduction: Apoptosis is one of the mechanisms behind successful chemotherapy and radiation treatment. Radiolabeled annexin A5 has been demonstrated to be a successful tool in the detection of apoptosis following chemotherapy in vivo. Methods: His-tagged annexin A5 was labeled with [{sup 99m}Tc]-tricarbonyl and evaluated as apoptosis imaging radiotracer in vitro and in vivo. The binding of the radiotracer was evaluated in Colo205 cells stimulated with 5-FU (1 mM) for 4 and 24 h, and confirmed by flow cytometry. Biodistribution and dosimetric studies were performed in healthy nude mice (n=5) via planar scintigraphy. [{sup 99m}Tc]-(CO){sub 3} His-annexin A5 was also evaluated for in vivo imaging of spontaneous apoptosis in Colo205-bearing mice (n=12). Results: The labeling procedure yielded a compound with 95-99% radiochemical purity and good in vitro stability. In vitro binding experiments indicated that the radiotracer retained its PS-binding activity. [{sup 99m}Tc]-(CO){sub 3} His-annexin A5 rapidly cleared from the blood and predominantly accumulated in the kidneys. Absorbed dose (per organ) was found to be 116{+-}64 {mu}Gy/MBq for the kidneys and 10.38{+-}0.50 {mu}Gy/MBq for the liver. The effective dose was 7.00{+-}0.28 {mu}Sv/MBq. Spontaneous apoptosis in Colo205-bearing mice was visualised by [{sup 99m}Tc]-(CO){sub 3} His-annexin A5 SPECT and correlated well with caspase-3 immunostaining (R=0.867, P<.01). Conclusion: [{sup 99m}Tc]-(CO){sub 3} His-annexin A5 may be a useful novel radioligand for the in vivo detection of cell death associated with PS expression. A simple, noninvasive way of detecting apoptosis in vivo could have many applications including a better understanding of the extent and timing of apoptosis in response to cancer therapies and assessment of early tumor response.

In vivo prediction of anti-tumor effect of 3-bromopyruvate in hepatocellular carcinoma using Tc-99m labeled annexin-v imaging

Energy Technology Data Exchange (ETDEWEB)

Kim, Won; Yoon, Jung Hwan; Kim, Chung Yang [Seoul National University College of Medicine, Seoul (Korea, Republic of); Cheon, Gi Jeoog; Lee, Tae Sup; Woo, Kwang Sun; Chung, Wee Sup [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

2005-07-01

We have recently demonstrated that hypoxia stimulates hepatocellular carcinoma (HCC) cell growth through hexokinase II induction, and its inhibition induces apoptotic cell death through activating mitochondrial apoptotic signaling cascades. In this study, we were apt to evaluate the antitumoral effect of 3-bromopyruvate (3-BP) on in vivo model of HCC by apoptotic imaging using Tc-99m labeled annexin V. In vivo model of HCC was established in C3H mice intradermally implanted with MH134 cells, a mouse HCC cell line, and 3-BP (0, 5, 10 mg/kg) was subsequently administered intraperitoneally. Tc-99m-HYNIC-annexin V (185 KBq) was injected via tail vein at one and three days after the 3-BP treatment, planar scan was acquired at a hour after the injection using gamma camera. The anti-tumor effect was evaluated by measuring tumor volumes and quantification of apoptotic cells using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Tumor volume was significantly reduced in mice treated with 3-BP in a dose-dependent manner (mean tumor volume 1.07 vs. 0.58 vs. 0.39 cm{sup 3} in 3-BP 0, 5, 10 mg/kg, respectively: p=0.047). The percentage of TUNEL staining-positive cells was significantly increased in 3-BP-treated mice (0.53 vs. 1.40 vs. 1.84% in 3-BP 0, 5, 10 mg/kg, respectively; p=0.018). On Tc-99m-HYNIC annexin V imaging, tumor-to-background uptake ratio (UR) was 1.92 at one day and 4.23 at three days after 3-BP treatment of 5 mg/kg (non-treated tumor showed UR of 2.93). Apoptosis-inducing anti-tumor effect of 3-BP was able to be demonstrated in in vivo model of HCC by apoptotic in vivo imaging using Tc-99m-HYNIC annexin V.

In vivo prediction of anti-tumor effect of 3-bromopyruvate in hepatocellular carcinoma using Tc-99m labeled annexin-v imaging

International Nuclear Information System (INIS)

Kim, Won; Yoon, Jung Hwan; Kim, Chung Yang; Cheon, Gi Jeoog; Lee, Tae Sup; Woo, Kwang Sun; Chung, Wee Sup

2005-01-01

We have recently demonstrated that hypoxia stimulates hepatocellular carcinoma (HCC) cell growth through hexokinase II induction, and its inhibition induces apoptotic cell death through activating mitochondrial apoptotic signaling cascades. In this study, we were apt to evaluate the antitumoral effect of 3-bromopyruvate (3-BP) on in vivo model of HCC by apoptotic imaging using Tc-99m labeled annexin V. In vivo model of HCC was established in C3H mice intradermally implanted with MH134 cells, a mouse HCC cell line, and 3-BP (0, 5, 10 mg/kg) was subsequently administered intraperitoneally. Tc-99m-HYNIC-annexin V (185 KBq) was injected via tail vein at one and three days after the 3-BP treatment, planar scan was acquired at a hour after the injection using gamma camera. The anti-tumor effect was evaluated by measuring tumor volumes and quantification of apoptotic cells using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Tumor volume was significantly reduced in mice treated with 3-BP in a dose-dependent manner (mean tumor volume 1.07 vs. 0.58 vs. 0.39 cm 3 in 3-BP 0, 5, 10 mg/kg, respectively: p=0.047). The percentage of TUNEL staining-positive cells was significantly increased in 3-BP-treated mice (0.53 vs. 1.40 vs. 1.84% in 3-BP 0, 5, 10 mg/kg, respectively; p=0.018). On Tc-99m-HYNIC annexin V imaging, tumor-to-background uptake ratio (UR) was 1.92 at one day and 4.23 at three days after 3-BP treatment of 5 mg/kg (non-treated tumor showed UR of 2.93). Apoptosis-inducing anti-tumor effect of 3-BP was able to be demonstrated in in vivo model of HCC by apoptotic in vivo imaging using Tc-99m-HYNIC annexin V

Corrosion of electron-irradiated Zr-2.5Nb and Zircaloy-2

Energy Technology Data Exchange (ETDEWEB)

Woo, O.-T.; McDougall, G.M.; Hutcheon, R.M.; Urbanic, V.F.; Griffiths, M.; Coleman, C.E

2000-07-01

We used 10-MeV electrons to rapidly produce radiation damage in zirconium alloys, investigated whether electrons produced the same microstructural changes as neutrons, then performed post-irradiation corrosion tests to determine whether electron-irradiated materials displayed similar corrosion behavior to neutron-irradiated materials. Two irradiations were completed using 10-MeV electrons with the beam normal to thin disks of material of 4 diameter slightly larger than the beam. The beam distribution. and disk cooling were designed to produce radial temperature and dose distributions having maxima at the disk center. A high-temperature irradiation was performed on annealed Zr-2.5Nb disks, achieving a central dose of 1.3 dpa and at a central temperature of {approx}450 deg C. After irradiation, the samples contained needle-like {beta}-Nb precipitates in the {alpha}-Zr matrix similar to those produced by neutrons. A low-temperature irradiation was performed on half-moon disks of Zr-2.5Nb and Zircaloy-2 pressure tube materials at 310 deg C central temperature and 1.3-dpa central dose. Dislocation loops were observed, again similar to those produced in neutron-irradiated materials. Some of the high-temperature electron-irradiated disks were exposed to 300 deg C moist air (saturated with D{sub 2}O), and in separate tests, high- and low-temperature irradiated disks were corroded in 300 deg C D{sub 2}0 (11.0 pD at room temperature) in an autoclave. Measurements of oxide thickness by Fourier Transform Infrared Reflectance (FTIR) spectroscopy showed that electron irradiation reduced the corrosion rate of Zr-2.5Nb compared with that of unirradiated material, as observed for neutron irradiation. For exposures to moist air and to D{sub 2}O, the theoretical deuterium uptakes for the electron-irradiated materials were, respectively, about 4 times and 1.5 to 2 times those for the unirradiated materials. This is also in good agreement with results for neutron-irradiated pressure

Structure of a C-terminal AHNAK peptide in a 1:2:2 complex with S100A10 and an acetylated N-terminal peptide of annexin A2

Energy Technology Data Exchange (ETDEWEB)

Ozorowski, Gabriel [University of California, Irvine, Irvine, CA 92697-3900 (United States); University of California, Irvine, Irvine, CA 92697-3900 (United States); Milton, Saskia [University of California, Irvine, Irvine, CA 92697-3900 (United States); Luecke, Hartmut, E-mail: hudel@uci.edu [University of California, Irvine, Irvine, CA 92697-3900 (United States); University of California, Irvine, Irvine, CA 92697-3900 (United States); University of California, Irvine, Irvine, CA 92697 (United States); University of California, Irvine, Irvine, CA 92697 (United States)

2013-01-01

Structure of a 20-amino-acid peptide of AHNAK bound asymmetrically to the AnxA2–S100A10A heterotetramer (1:2:2 symmetry) provides insights into the atomic level interactions that govern this membrane-repair scaffolding complex. AHNAK, a large 629 kDa protein, has been implicated in membrane repair, and the annexin A2–S100A10 heterotetramer [(p11){sub 2}(AnxA2){sub 2})] has high affinity for several regions of its 1002-amino-acid C-terminal domain. (p11){sub 2}(AnxA2){sub 2} is often localized near the plasma membrane, and this C2-symmetric platform is proposed to be involved in the bridging of membrane vesicles and trafficking of proteins to the plasma membrane. All three proteins co-localize at the intracellular face of the plasma membrane in a Ca{sup 2+}-dependent manner. The binding of AHNAK to (p11){sub 2}(AnxA2){sub 2} has been studied previously, and a minimal binding motif has been mapped to a 20-amino-acid peptide corresponding to residues 5654–5673 of the AHNAK C-terminal domain. Here, the 2.5 Å resolution crystal structure of this 20-amino-acid peptide of AHNAK bound to the AnxA2–S100A10 heterotetramer (1:2:2 symmetry) is presented, which confirms the asymmetric arrangement first described by Rezvanpour and coworkers and explains why the binding motif has high affinity for (p11){sub 2}(AnxA2){sub 2}. Binding of AHNAK to the surface of (p11){sub 2}(AnxA2){sub 2} is governed by several hydrophobic interactions between side chains of AHNAK and pockets on S100A10. The pockets are large enough to accommodate a variety of hydrophobic side chains, allowing the consensus sequence to be more general. Additionally, the various hydrogen bonds formed between the AHNAK peptide and (p11){sub 2}(AnxA2){sub 2} most often involve backbone atoms of AHNAK; as a result, the side chains, particularly those that point away from S100A10/AnxA2 towards the solvent, are largely interchangeable. While the structure-based consensus sequence allows interactions with various

Biochemical and immunological characterization of annexin B30 from Clonorchis sinensis excretory/secretory products.

Science.gov (United States)

He, Lei; Ren, Mengyu; Chen, Xueqing; Wang, Xiaoyun; Li, Shan; Lin, Jinsi; Liang, Chi; Liang, Pei; Hu, Yue; Lei, Huali; Bian, Meng; Huang, Yan; Wu, Zhongdao; Li, Xuerong; Yu, Xinbing

2014-07-01

Clonorchis sinensis has been classified as group I biological carcinogen for cholangiocarcinoma by the World Health Organization. Biological studies on excretory/secretory products (ESPs) enabled us to understand the pathogenesis mechanism of C. sinensis and develop new strategies for the prevention of clonorchiasis. In this study, sequence analysis showed that annexin B30 from C. sinensis (CsANXB30) is composed of four annexin repeats which were characterized by type II and III Ca(2+)-binding sites or KGD motif with the capability of Ca(2+)-binding. In addition, immunoblot assay revealed that recombinant CsANXB30 (rCsANXB30) could be recognized by the sera from rats infected with C. sinensis and the sera from rats immunized by CsESPs. Real-time PCR showed that its transcriptional level was the highest at the stage of metacercaria. Immunofluorescence assay was employed to confirm that CsANXB30 was distributed in the tegument, intestine, and egg of adult worms, as well as the tegument and vitellarium of metacercaria. rCsANXB30 was able to bind phospholipid in a Ca(2+)-dependent manner and human plasminogen in a dose-dependent manner. Moreover, cytokine and antibody measurements indicated that rats subcutaneously immunized with rCsANXB30 developed a strong IL-10 production in spleen cells and a high level of IgG1 isotype, indicating that rCsANXB30 could trigger specific humoral and cellular immune response in rats. The present results implied that CsANXB30 might be involved in a host-parasite interaction and affected the immune response of the host during C. sinensis infection.

Detection of 2-alkylcyclobutanones as a marker of irradiated avocado

Energy Technology Data Exchange (ETDEWEB)

Alvarez, Damaris L. Moreno, E-mail: damaris@ceaden.edu.cu [Centro de Aplicaciones Tecnologicas y Desarrolo Nuclear (CEADEN), Habana (Cuba); Werner, Dalal [Technical Institute for Food Industry (AERIAL), Strasbourg (France). Technology Resource Centre; Villavicencio, Anna Lucia C.H. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2013-07-01

The 2-alkylcyclobutanones are compound only formed in processed foods with ionizing radiations, which are used as markers to detect foods that have been irradiated and they have some content of fat. The samples were irradiated in a dose 7 kGy, the extraction was carried out for the Shoxlet method and the detection for the EN 1785 Standard. The results showed the utility of the 2- alkylcyclobutanone marker for the identification of irradiated foods. The obtained results showed that the avocado can be identification by the marked 2-TCB. (author)

Detection of 2-alkylcyclobutanones as a marker of irradiated avocado

International Nuclear Information System (INIS)

Alvarez, Damaris L. Moreno; Werner, Dalal

2013-01-01

The 2-alkylcyclobutanones are compound only formed in processed foods with ionizing radiations, which are used as markers to detect foods that have been irradiated and they have some content of fat. The samples were irradiated in a dose 7 kGy, the extraction was carried out for the Shoxlet method and the detection for the EN 1785 Standard. The results showed the utility of the 2- alkylcyclobutanone marker for the identification of irradiated foods. The obtained results showed that the avocado can be identification by the marked 2-TCB. (author)

Annexin A2 promotes the migration and invasion of human hepatocellular carcinoma cells in vitro by regulating the shedding of CD147-harboring microvesicles from tumor cells.

Directory of Open Access Journals (Sweden)

Wei Zhang

Full Text Available It has been reported that Annexin A2 (ANXA2 is up-regulated in hepatocellular carcinoma (HCC, but the roles of ANXA2 in the migration and invasion of HCC cells have not been determined. In this study, we found that ANXA2-specific siRNA (si-ANXA2 significantly inhibited the migration and invasion of HCC cells co-cultured with fibroblasts in vitro. In addition, the production of MMP-2 by fibroblasts cultured in supernatant collected from si-ANXA2-transfected HCC cells was notably down-regulated. ANXA2 was also found to be co-localized and co-immunoprecipitated with CD147. Further investigation revealed that the expression of ANXA2 in HCC cells affected the shedding of CD147-harboring membrane microvesicles, acting as a vehicle for CD147 in tumor-stromal interactions and thereby regulating the production of MMP-2 by fibroblasts. Together, these results suggest that ANXA2 enhances the migration and invasion potential of HCC cells in vitro by regulating the trafficking of CD147-harboring membrane microvesicles.

URAM-2 Cryogenic Irradiation Facility

CERN Document Server

Shabalin, E P; Kulikov, S A; Kulagin, E N; Melihov, V V; Belyakov, A A; Golovanov, L B; Borzunov, Yu T; Konstantinov, V I; Androsov, A V

2002-01-01

The URAM-2 irradiation facility has been built and mounted at the channel No. 3 of the IBR-2 reactor. It was constructed for study of radiolysis effects by fast neutron irradiation in some suitable for effective cold neutron production materials (namely: solid methane, methane hydrate, water ice, etc.). The facility cooling system is based on using liquid helium as a coolant material. The original charging block of the rig allows the samples to be loaded by condensing gas into irradiation cavity or by charging beads of ice prepared before. Preliminary tests for each facility block and assembling them at the working position were carried out. Use of the facility for study accumulation of chemical energy under irradiation at low temperature in materials mentioned above and its spontaneous release was started.

Irradiation capsules VISA-2a-f, chapter VI

International Nuclear Information System (INIS)

Pavicevic, M.

1962-01-01

Irradiation capsules VISA-2a, b,c,d, and e were constructed in Saclay according to the drawings from Vinca and according to the demand of the experimentators. This chapter VI includes documentation for each type of capsule, review about each experiment within the VISA-2 project, the objective and purpose of the experiment as well as experimental device. Irradiation capsule VISA-2f was placed in the RA reactor core in September 1962. It was completely manufactured in Vinca including sample holders and leak tight shells. It will remain in the reactor core for about month in order to obtain the integral fast neutron flux [sr

Annexin A6 contributes to the invasiveness of breast carcinoma cells by influencing the organization and localization of functional focal adhesions

Energy Technology Data Exchange (ETDEWEB)

Sakwe, Amos M., E-mail: asakwe@mmc.edu [Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208 (United States); Koumangoye, Rainelli; Guillory, Bobby [Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208 (United States); Ochieng, Josiah [Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208 (United States); Center for Aids Health Disparity Research, Meharry Medical College, Nashville, TN 37208 (United States); Department of Cancer Biology, Vanderbilt University, Nashville, TN (United States)

2011-04-01

The interaction of annexin A6 (AnxA6) with membrane phospholipids and either specific extracellular matrix (ECM) components or F-actin suggests that it may influence cellular processes associated with rapid plasma membrane reorganization such as cell adhesion and motility. Here, we examined the putative roles of AnxA6 in adhesion-related cellular processes that contribute to breast cancer progression. We show that breast cancer cells secrete annexins via the exosomal pathway and that the secreted annexins are predominantly cell surface-associated. Depletion of AnxA6 in the invasive BT-549 breast cancer cells is accompanied by enhanced anchorage-independent cell growth but cell-cell cohesion, cell adhesion/spreading onto collagen type IV or fetuin-A, cell motility and invasiveness were strongly inhibited. To explain the loss in adhesion/motility, we show that vinculin-based focal adhesions in the AnxA6-depleted BT-549 cells are elongated and randomly distributed. These focal contacts are also functionally defective because the activation of focal adhesion kinase and the phosphoinositide-3 kinase/Akt pathway were strongly inhibited while the MAP kinase pathway remained constitutively active. Compared with normal human breast tissues, reduced AnxA6 expression in breast carcinoma tissues correlates with enhanced cell proliferation. Together this suggests that reduced AnxA6 expression contributes to breast cancer progression by promoting the loss of functional cell-cell and/or cell-ECM contacts and anchorage-independent cell proliferation.

Annexin A6 contributes to the invasiveness of breast carcinoma cells by influencing the organization and localization of functional focal adhesions

International Nuclear Information System (INIS)

Sakwe, Amos M.; Koumangoye, Rainelli; Guillory, Bobby; Ochieng, Josiah

2011-01-01

The interaction of annexin A6 (AnxA6) with membrane phospholipids and either specific extracellular matrix (ECM) components or F-actin suggests that it may influence cellular processes associated with rapid plasma membrane reorganization such as cell adhesion and motility. Here, we examined the putative roles of AnxA6 in adhesion-related cellular processes that contribute to breast cancer progression. We show that breast cancer cells secrete annexins via the exosomal pathway and that the secreted annexins are predominantly cell surface-associated. Depletion of AnxA6 in the invasive BT-549 breast cancer cells is accompanied by enhanced anchorage-independent cell growth but cell-cell cohesion, cell adhesion/spreading onto collagen type IV or fetuin-A, cell motility and invasiveness were strongly inhibited. To explain the loss in adhesion/motility, we show that vinculin-based focal adhesions in the AnxA6-depleted BT-549 cells are elongated and randomly distributed. These focal contacts are also functionally defective because the activation of focal adhesion kinase and the phosphoinositide-3 kinase/Akt pathway were strongly inhibited while the MAP kinase pathway remained constitutively active. Compared with normal human breast tissues, reduced AnxA6 expression in breast carcinoma tissues correlates with enhanced cell proliferation. Together this suggests that reduced AnxA6 expression contributes to breast cancer progression by promoting the loss of functional cell-cell and/or cell-ECM contacts and anchorage-independent cell proliferation.

Annexin-1 Mediates Microglial Activation and Migration via the CK2 Pathway during Oxygen–Glucose Deprivation/Reperfusion

Directory of Open Access Journals (Sweden)

Shuangxi Liu

2016-10-01

Full Text Available Annexin-1 (ANXA1 has shown neuroprotective effects and microglia play significant roles during central nervous system injury, yet the underlying mechanisms remain unclear. This study sought to determine whether ANXA1 regulates microglial response to oxygen–glucose deprivation/reperfusion (OGD/R treatment and to clarify the downstream molecular mechanism. In rat hippocampal slices, OGD/R treatment enhanced the ANXA1 expression in neuron, the formyl peptide receptor (FPRs expression in microglia, and the microglial activation in the CA1 region (cornu ammonis 1. These effects were reversed by the FPRs antagonist Boc1. The cell membrane currents amplitude of BV-2 microglia (the microglial like cell-line was increased when treated with Ac2-26, the N-terminal peptide of ANXA1. Ac2-26 treatment enhanced BV-2 microglial migration whereas Boc1 treatment inhibited the migration. In BV-2 microglia, both the expression of the CK2 target phosphorylated α-E-catenin and the binding of casein kinase II (CK2 with α-E-catenin were elevated by Ac2-26, these effects were counteracted by the CK2 inhibitor TBB and small interfering (si RNA directed against transcripts of CK2 and FPRs. Moreover, both TBB and siRNA-mediated inhibition of CK2 blocked Ac2-26-mediated BV-2 microglia migration. Our findings indicate that ANXA1 promotes microglial activation and migration during OGD/R via FPRs, and CK2 target α-E-catenin phosphorylation is involved in this process.

AGR-2 Irradiation Test Final As-Run Report, Rev 2

Energy Technology Data Exchange (ETDEWEB)

Collin, Blaise P. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2014-08-01

This document presents the as-run analysis of the AGR-2 irradiation experiment. AGR-2 is the second of the planned irradiations for the Advanced Gas Reactor (AGR) Fuel Development and Qualification Program. Funding for this program is provided by the U.S. Department of Energy as part of the Very High Temperature Reactor (VHTR) Technical Development Office (TDO) program. The objectives of the AGR-2 experiment are to: (a) Irradiate UCO (uranium oxycarbide) and UO₂ (uranium dioxide) fuel produced in a large coater. Fuel attributes are based on results obtained from the AGR-1 test and other project activities. (b) Provide irradiated fuel samples for post-irradiation experiment (PIE) and safety testing. (c) Support the development of an understanding of the relationship between fuel fabrication processes, fuel product properties, and irradiation performance. The primary objective of the test was to irradiate both UCO and UO₂ TRISO (tri-structural isotropic) fuel produced from prototypic scale equipment to obtain normal operation and accident condition fuel performance data. The UCO compacts were subjected to a range of burnups and temperatures typical of anticipated prismatic reactor service conditions in three capsules. The test train also includes compacts containing UO₂ particles produced independently by the United States, South Africa, and France in three separate capsules. The range of burnups and temperatures in these capsules were typical of anticipated pebble bed reactor service conditions. The results discussed in this report pertain only to U.S. produced fuel. In order to achieve the test objectives, the AGR-2 experiment was irradiated in the B-12 position of the Advanced Test Reactor (ATR) at Idaho National Laboratory (INL) for a total irradiation duration of 559.2 effective full power days (EFPD). Irradiation began on June 22, 2010, and ended on October 16, 2013, spanning 12 ATR power cycles and approximately three and a

Irradiation effects in UO2 and CeO2

International Nuclear Information System (INIS)

Ye, Bei; Oaks, Aaron; Kirk, Mark; Yun, Di; Chen, Wei-Ying; Holtzman, Benjamin; Stubbins, James F.

2013-01-01

Single crystal CeO 2 , as a surrogate material to UO 2 , was irradiated with 500 keV xenon ions at 800 °C while being observed using in situ transmission electron microscopy (TEM). Experimental results show the formation and growth of defect clusters including dislocation loops and cavities as a function of increasing atomic displacement dose. At high dose, the dislocation loop structure evolves into an extended dislocation line structure, which appears to remain stable to the high dose levels examined in this study. A high concentration of cavities was also present in the microstructure. Despite high atomic displacement doses, the specimen remained crystalline to a cumulated dose of 5 × 10 15 ions/cm 2 , which is consistent with the known stability of the fluorite structure under high dose irradiation. Kinetic Monte Carlo calculations show that oxygen mobility is substantially higher in hypo-stoichiometric UO 2 /CeO 2 than hyper-stoichiometric systems. This result is consistent with the ability of irradiation damage to recover even at intermediate irradiation temperatures

Dysferlin, annexin A1, and mitsugumin 53 are upregulated in muscular dystrophy and localize to longitudinal tubules of the T-system with stretch.

Science.gov (United States)

Waddell, Leigh B; Lemckert, Frances A; Zheng, Xi F; Tran, Jenny; Evesson, Frances J; Hawkes, Joanne M; Lek, Angela; Street, Neil E; Lin, Peihui; Clarke, Nigel F; Landstrom, Andrew P; Ackerman, Michael J; Weisleder, Noah; Ma, Jianjie; North, Kathryn N; Cooper, Sandra T

2011-04-01

Mutations in dysferlin cause an inherited muscular dystrophy because of defective membrane repair. Three interacting partners of dysferlin are also implicated in membrane resealing: caveolin-3 (in limb girdle muscular dystrophy type 1C), annexin A1, and the newly identified protein mitsugumin 53 (MG53). Mitsugumin 53 accumulates at sites of membrane damage, and MG53-knockout mice display a progressive muscular dystrophy. This study explored the expression and localization of MG53 in human skeletal muscle, how membrane repair proteins are modulated in various forms of muscular dystrophy, and whether MG53 is a primary cause of human muscle disease. Mitsugumin 53 showed variable sarcolemmal and/or cytoplasmic immunolabeling in control human muscle and elevated levels in dystrophic patients. No pathogenic MG53 mutations were identified in 50 muscular dystrophy patients, suggesting that MG53 is unlikely to be a common cause of muscular dystrophy in Australia. Western blot analysis confirmed upregulation of MG53, as well as of dysferlin, annexin A1, and caveolin-3 to different degrees, in different muscular dystrophies. Importantly, MG53, annexin A1, and dysferlin localize to the t-tubule network and show enriched labeling at longitudinal tubules of the t-system in overstretch. Our results suggest that longitudinal tubules of the t-system may represent sites of physiological membrane damage targeted by this membrane repair complex.

AGC-2 Specimen Post Irradiation Data Package Report

Energy Technology Data Exchange (ETDEWEB)

Windes, William Enoch [Idaho National Lab. (INL), Idaho Falls, ID (United States); Swank, W. David [Idaho National Lab. (INL), Idaho Falls, ID (United States); Rohrbaugh, David T. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Cottle, David L. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2015-08-01

This report documents results of the post-irradiation examination material property testing of the creep, control, and piggyback specimens from the irradiation creep capsule Advanced Graphite Creep (AGC)-2 are reported. This is the second of a series of six irradiation test trains planned as part of the AGC experiment to fully characterize the neutron irradiation effects and radiation creep behavior of current nuclear graphite grades. The AGC-2 capsule was irradiated in the Idaho National Laboratory Advanced Test Reactor at a nominal temperature of 600°C and to a peak dose of 5 dpa (displacements per atom). One-half of the creep specimens were subjected to mechanical stresses (an applied stress of either 13.8, 17.2, or 20.7 MPa) to induce irradiation creep. All post-irradiation testing and measurement results are reported with the exception of the irradiation mechanical strength testing, which is the last destructive testing stage of the irradiation testing program. Material property tests were conducted on specimens from 15 nuclear graphite grades using a similar loading configuration as the first AGC capsule (AGC-1) to provide easy comparison between the two capsules. However, AGC-2 contained an increased number of specimens (i.e., 487 total specimens irradiated) and replaced specimens of the minor grade 2020 with the newer grade 2114. The data reported include specimen dimensions for both stressed and unstressed specimens to establish the irradiation creep rates, mass and volume data necessary to derive density, elastic constants (Young’s modulus, shear modulus, and Poisson’s ratio) from ultrasonic time-of-flight velocity measurements, Young’s modulus from the fundamental frequency of vibration, electrical resistivity, and thermal diffusivity and thermal expansion data from 100–500°C. No data outliers were determined after all measurements were completed. A brief statistical analysis was performed on the irradiated data and a limited comparison between

Solar control on irradiated Ta2O2 thin films

International Nuclear Information System (INIS)

Baydogan, N. D.; Zayim, E. Oe.

2007-01-01

Thin films consisting of Ta 2 O 5 have been used in industry in applications related to thin-film capacitors, optical waveguides, and antireflection coatings on solar cells. Ta 2 O 5 films are used for several special applications as highly refractive material and show different optical properties depending on the deposition methods. Sol-gel technique has been used for the preparation of Ta 2 O 5 thin films. Ta 2 O 5 thin films were prepared by sol-gel proses on glass substrates to obtain good quality films. These films were exposed to gamma radiation from Co-60 radioisotope. Ta 2 O 5 coated thin films were placed against the source and irradiated for 8 different gamma doses; between 0.35 and 21.00 kGy at room temperature. Energetic gamma ray can affect the samples and change its colour. On the other hand some of the Ta 2 O 5 coated thin films were irradiated with beta radiation from Sr-90 radioisotope. The effect of gamma irradiation on the solar properties of Ta 2 O 5 films is compared with that of beta irradiation. The solar properties of the irradiated thin films differ significantly from those of the unirradiated ones. After the irradiation of the samples transmittance and reflectance are measured for solar light between 300 and 2100 nm, by using Perkin Elmer Lambda 9 UV/VIS/NIR Spectrophotometer. Change in the direct solar transmittance, reflectance and absorptance with absorbed dose are determined. Using the optical properties, the redistribution of the absorbed component of the solar radiation and the shading coefficient (SC) are calculated as a function of the convective heat-transfer coefficient. Solar parameters are important for the determination of the shading coefficient. When the secondary internal heat transfer factor (qi), direct solar transmittance (□ e ), and solar factor (g) are known, it is possible to determine shading coefficient via the dose rates. The shading coefficient changes as the dose rate is increased. In this study, the shading

A strategy for isolation of cDNAs encoding proteins affecting human intestinal epithelial cell growth and differentiation: characterization of a novel gut-specific N-myristoylated annexin.

Science.gov (United States)

Wice, B M; Gordon, J I

1992-01-01

differentiation/translocation up the villus. Immunocytochemical studies reveal that the intestine-specific annexin (ISA) is associated with the plasma membrane of undifferentiated, proliferating crypt epithelial cells as well as differentiated villus enterocytes. In polarized enterocytes, the highest concentrations of ISA are found at the apical compared to basolateral membrane. In vitro studies using an octapeptide derived from residues 2-9 of the primary translation product of ISA mRNA and purified myristoyl-CoA:protein N-myristoyltransferase suggested that it is N-myristoylated. In vivo labeling studies confirmed that myristate is covalently attached to ISA via a hydroxylamine resistant amide linkage. The restricted cellular expression and acylation of ISA distinguish it from other known annexins.(ABSTRACT TRUNCATED AT 400 WORDS)

Technetium 99m-labeled annexin v scintigraphy of platelet activation in vegetations of experimental endocarditis

International Nuclear Information System (INIS)

Rouzet, F.; Sarda-Mantel, L.; Le Guludec, D.; Rouzet, F.; Sarda-Mantel, L.; LeGuludec, D.; Rouzet, F.; Sarda-Mantel, L.; Le Guludec, D.; Hernandez, M.D.; Louedec, L.; Michel, J.B.; Hervatin, F.; Lefort, A.; Fantin, B.; Duval, X.; Duval, X.; Hernandez, M.D.

2008-01-01

Background: The pathophysiology of infective endocarditis involves a pathogen/host tissue interaction, leading to formation of infected thrombotic vegetations. Annexin V is a ligand of phosphatidyl-serines exposed by activated platelets and apoptotic cells. Because vegetations are platelet-fibrin clots in which platelet pro-aggregant activity is enhanced by bacterial colonization, we investigated the ability of annexin V labeled with technetium 99m Tc ( 99m Tc-ANX) to provide functional imaging of these vegetations in experimental models of infective endocarditis. This ability was assessed in rabbits and rats because of the different interest of these 2 species in preclinical analysis. Methods and Results: Non-bacterial thrombotic endocarditis was induced with the use of a catheter left indwelling through the aortic or tricuspid valve, and animals were injected with either a bacterial inoculum or saline. Scintigraphic investigations were performed 5 days later and showed a higher 99m Tc-ANX uptake by vegetations in infected versus non-infected animals (ratio,1.3 for in vivo acquisitions and 2 for autoradiography; P ≤ 0.0001 for all), whereas no significant uptake was present in controls. Right-sided endocarditis was associated with pulmonary uptake foci corresponding to emboli. Histological analysis of vegetations showed a specific uptake of 99m Tc-ANX at the interface between circulating blood and vegetation. In parallel, underlying myocardial tissue showed myocyte apoptosis and mucoid degeneration, without extracellular matrix degradation at this stage. Conclusions: 99m Tc-ANX is suitable for functional imaging of platelet-fibrin vegetations in endocarditis, as well as embolic events. 99m Tc-ANX uptake reflects mainly platelet activation in the luminal layer of vegetations. This uptake is enhanced by bacterial colonization. (authors)

UO2-PuO2 fuel pin capsule-irradiations of the test series FR 2-5a

International Nuclear Information System (INIS)

Dienst, W.; Goetzmann, O.; Schulz, B.

1975-06-01

In the capsule-irradiation test series FR 2-5a, short UO 2 -PuO 2 fuel pins (80 mm fuel length) of 7 mm diameter were irradiated in a thermal neutron flux at mean rod powers of 400 - 450 W/cm and mean cladding surface temperatures of 500 - 550 0 C to burnups of 0.6, 1.8 and 5.0 at% (U + Pu). Void volume redistribution in the fuel pins was examined in micrographs of cross-sections by measuring crack widths, central void diameters, and fuel porosity. The width of the radial cracks at the outer fuel rim was taken as a basis for measuring the irradiation-induced densification of the UO 2 -PuO 2 fuel. The result was that the final fuel density after irradiation-induced densification amounted to 92 - 94% TD and had already been reached after 0.6 at% burnup. The porosity measurement on fuel cross-sections was to show a possible dependence of the radial porosity redistribution on the initial sintered density. Examining the fuel pin diameters after irradiation showed permanent cladding strains after 5 at% burnup, which must be due to mechanical interaction with the fuel. To judge if the chemical compatibility between the fuel and the cladding of Cr-Ni-stainless steel 1.4988, the depths of chemical attack on the cladding inside was measured by micrographs of fuel pin cross-sections. (orig./GSC) [de

Arabidopsis annexin1 mediates the radical-activated plasma membrane Ca²+- and K+-permeable conductance in root cells.

Science.gov (United States)

Laohavisit, Anuphon; Shang, Zhonglin; Rubio, Lourdes; Cuin, Tracey A; Véry, Anne-Aliénor; Wang, Aihua; Mortimer, Jennifer C; Macpherson, Neil; Coxon, Katy M; Battey, Nicholas H; Brownlee, Colin; Park, Ohkmae K; Sentenac, Hervé; Shabala, Sergey; Webb, Alex A R; Davies, Julia M

2012-04-01

Plant cell growth and stress signaling require Ca²⁺ influx through plasma membrane transport proteins that are regulated by reactive oxygen species. In root cell growth, adaptation to salinity stress, and stomatal closure, such proteins operate downstream of the plasma membrane NADPH oxidases that produce extracellular superoxide anion, a reactive oxygen species that is readily converted to extracellular hydrogen peroxide and hydroxyl radicals, OH•. In root cells, extracellular OH• activates a plasma membrane Ca²⁺-permeable conductance that permits Ca²⁺ influx. In Arabidopsis thaliana, distribution of this conductance resembles that of annexin1 (ANN1). Annexins are membrane binding proteins that can form Ca²⁺-permeable conductances in vitro. Here, the Arabidopsis loss-of-function mutant for annexin1 (Atann1) was found to lack the root hair and epidermal OH•-activated Ca²⁺- and K⁺-permeable conductance. This manifests in both impaired root cell growth and ability to elevate root cell cytosolic free Ca²⁺ in response to OH•. An OH•-activated Ca²⁺ conductance is reconstituted by recombinant ANN1 in planar lipid bilayers. ANN1 therefore presents as a novel Ca²⁺-permeable transporter providing a molecular link between reactive oxygen species and cytosolic Ca²⁺ in plants.

Dexamethasone-induced and estradiol-induced CREB activation and annexin 1 expression in CCRF-CEM lymphoblastic cells: evidence for the involvement of cAMP and p38 MAPK

Directory of Open Access Journals (Sweden)

M. Castro-caldas

2003-01-01

Full Text Available Aims: Annexin 1 (ANXA1, a member of the annexin family of calcium-binding and phospholipid-binding proteins, is a key mediator of the anti-inflammatory actions of steroid hormones. We have previously demonstrated that, in the human lymphoblastic CCRF-CEM cell line, both the synthetic glucocorticoid hormone, dexamethasone (Dex, and the estrogen hormone, 17β-estradiol (E2β, induce the synthesis of ANXA1, by a mechanism independent of the activation of their nuclear receptors. Recently, it was reported that the gene coding for ANXA1 contains a cAMP-responsive element (CRE. In this work, we investigated whether Dex and E2β were able to induce the activation of CRE binding proteins (CREB in the CCRF-CEM cells. Moreover, we studied the intracellular signalling pathways involved in CREB activation and ANXA1 synthesis in response to Dex and E2β; namely, the role of cAMP and the p38 mitogen-activated protein kinase (MAPK.

The biological effect of 125I seed continuous low dose rate irradiation in CL187 cells

Directory of Open Access Journals (Sweden)

Zhuang Hong-Qing

2009-01-01

Full Text Available Abstract Background To investigate the effectiveness and mechanism of 125I seed continuous low-dose-rate irradiation on colonic cell line CL187 in vitro. Methods The CL187 cell line was exposed to radiation of 60Coγ ray at high dose rate of 2 Gy/min and 125I seed at low dose rate of 2.77 cGy/h. Radiation responses to different doses and dose rates were evaluated by colony-forming assay. Under 125I seed low dose rate irradiation, a total of 12 culture dishes were randomly divided into 4 groups: Control group, and 2, 5, and 10 Gy irradiation groups. At 48 h after irradiation, apoptosis was detected by Annexin and Propidium iodide (PI staining. Cell cycle arrests were detected by PI staining. In order to investigate the influence of low dose rate irradiation on the MAPK signal transduction, the expression changes of epidermal growth factor receptor (EGFR and Raf under continuous low dose rate irradiation (CLDR and/or EGFR monoclonal antibodies were determined by indirect immunofluorescence. Results The relative biological effect (RBE for 125I seeds compared with 60Co γ ray was 1.41. Apoptosis rates of CL187 cancer cells were 13.74% ± 1.63%, 32.58% ± 3.61%, and 46.27% ± 3.82% after 2 Gy, 5 Gy, and 10 Gy irradiation, respectively; however, the control group apoptosis rate was 1.67% ± 0.19%. G2/M cell cycle arrests of CL187 cancer cells were 42.59% ± 3.21%, 59.84% ± 4.96%, and 34.61% ± 2.79% after 2 Gy, 5 Gy, and 10 Gy irradiation, respectively; however, the control group apoptosis rate was 26.44% ± 2.53%. P 2/M cell cycle arrest. After low dose rate irradiation, EGFR and Raf expression increased, but when EGFR was blocked by a monoclonal antibody, EGFR and Raf expression did not change. Conclusion 125I seeds resulted in more effective inhibition than 60Co γ ray high dose rate irradiation in CL187 cells. Apoptosis following G2/M cell cycle arrest was the main mechanism of cell-killing effects under low dose rate irradiation. CLDR could

Technetium 99m-labeled annexin v scintigraphy of platelet activation in vegetations of experimental endocarditis

Energy Technology Data Exchange (ETDEWEB)

Rouzet, F.; Sarda-Mantel, L.; Le Guludec, D. [Nucl Med Serv, Grp Hosp Bichat Claude Bernard, AP-HP, Paris (France); Rouzet, F.; Sarda-Mantel, L.; LeGuludec, D. [Univ Denis Diderot Paris 7, UMR S773, Paris (France); Rouzet, F.; Sarda-Mantel, L.; Le Guludec, D. [INSERM, U773, Paris (France); Hernandez, M.D.; Louedec, L.; Michel, J.B. [Univ Paris 07, CHU Xavier Bichat, INSERM, U698, Paris (France); Hervatin, F. [CEA, DSV, DRM, SHFJ, Orsay (France); Lefort, A.; Fantin, B. [Univ Denis Diderot Paris 7, EA 3964, Paris (France); Duval, X. [Univ Denis Diderot Paris 7, INSERM, CIC 007, Paris (France); Duval, X. [Univ Denis Diderot Paris 7, AP-HP, Grp Hosp Bichat Claude Bernard, Ctr Invest Clin, Paris (France); Hernandez, M.D. [Univ Guadalajara, DeptPathol, Guadalajara 44430, Jalisco (Mexico)

2008-07-01

Background: The pathophysiology of infective endocarditis involves a pathogen/host tissue interaction, leading to formation of infected thrombotic vegetations. Annexin V is a ligand of phosphatidyl-serines exposed by activated platelets and apoptotic cells. Because vegetations are platelet-fibrin clots in which platelet pro-aggregant activity is enhanced by bacterial colonization, we investigated the ability of annexin V labeled with technetium {sup 99m}Tc ({sup 99m}Tc-ANX) to provide functional imaging of these vegetations in experimental models of infective endocarditis. This ability was assessed in rabbits and rats because of the different interest of these 2 species in preclinical analysis. Methods and Results: Non-bacterial thrombotic endocarditis was induced with the use of a catheter left indwelling through the aortic or tricuspid valve, and animals were injected with either a bacterial inoculum or saline. Scintigraphic investigations were performed 5 days later and showed a higher {sup 99m}Tc-ANX uptake by vegetations in infected versus non-infected animals (ratio,1.3 for in vivo acquisitions and 2 for autoradiography; P {<=} 0.0001 for all), whereas no significant uptake was present in controls. Right-sided endocarditis was associated with pulmonary uptake foci corresponding to emboli. Histological analysis of vegetations showed a specific uptake of {sup 99m}Tc-ANX at the interface between circulating blood and vegetation. In parallel, underlying myocardial tissue showed myocyte apoptosis and mucoid degeneration, without extracellular matrix degradation at this stage. Conclusions: {sup 99m}Tc-ANX is suitable for functional imaging of platelet-fibrin vegetations in endocarditis, as well as embolic events. {sup 99m}Tc-ANX uptake reflects mainly platelet activation in the luminal layer of vegetations. This uptake is enhanced by bacterial colonization. (authors)

AGR-2 Irradiation Test Final As-Run Report

Energy Technology Data Exchange (ETDEWEB)

Collin, Blaise P. [Idaho National Lab. (INL), Idaho Falls, ID (United States). VHTR Program

2014-08-01

This document presents the as-run analysis of the AGR-2 irradiation experiment. AGR-2 is the second of the planned irradiations for the Advanced Gas Reactor (AGR) Fuel Development and Qualification Program. Funding for this program is provided by the U.S. Department of Energy as part of the Very High Temperature Reactor (VHTR) Technology Development Office (TDO) program. The objectives of the AGR-2 experiment are to: 1. Irradiate UCO (uranium oxycarbide) and UO₂ (uranium dioxide) fuel produced in a large coater. Fuel attributes are based on results obtained from the AGR-1 test and other project activities. 2. Provide irradiated fuel samples for post-irradiation experiment (PIE) and safety testing. 3. Support the development of an understanding of the relationship between fuel fabrication processes, fuel product properties, and irradiation performance. The primary objective of the test was to irradiate both UCO and UO₂ TRISO (tristructural isotropic) fuel produced from prototypic scale equipment to obtain normal operation and accident condition fuel performance data. The UCO compacts were subjected to a range of burnups and temperatures typical of anticipated prismatic reactor service conditions in three capsules. The test train also includes compacts containing UO₂ particles produced independently by the United States, South Africa, and France in three separate capsules. The range of burnups and temperatures in these capsules were typical of anticipated pebble bed reactor service conditions. The results discussed in this report pertain only to U.S.-produced fuel.

Advance of apoptosis imaging with radiolabeled annexin V in tumor research

International Nuclear Information System (INIS)

Huang Daijuan

2003-01-01

One of the most important reasons that cause tumor is decrease or complete absence of apoptosis of tumor cells. Conversely successful anti-tumor therapy is correlated with the introduction of apoptosis into tumor cells. Radiolabeled annexin V is used to image in vivo the phosphatidylserine (PS) that explode on the outer surface of cell membrane after apoptosis so that apoptosis can be detected on the early stage. This imaging method can be introduced into the research of tumor in order to help direct the choose of tumor therapy, inspect the effect and evaluate the prognosis

Mechanical properties of irradiated 9Cr-2WVTa steel

International Nuclear Information System (INIS)

Klueh, R.L.; Alexander, D.J.; Rieth, M.

1998-01-01

An Fe-9Cr-2W-0.25V-0.07Ta-0.1C (9Cr-2WVTa) steel has excellent strength and impact toughness before and after irradiation in the Fast Flux Test Facility and the High Flux Reactor (HFR). The ductile-brittle transition temperature (DBTT) increased only 32 C after 28 dpa at 365 C in FFTF, compared to a shift of ∼60 C for a 9Cr-2WV steel--the same as the 9Cr-2WVTa steel but without tantalum. This difference occurred despite the two steels having similar tensile but without tantalum. This difference occurred despite the two steels having similar tensile properties before and after irradiation. The 9Cr-2WVTa steel has a smaller prior-austenite grain size, but otherwise microstructures are similar before irradiation and show similar changes during irradiation. The irradiation behavior of the 9Cr-2WVTa steel differs from the 9Cr-2WV steel and other similar steels in two ways: (1) the shift in DBTT of the 9Cr-2WVTa steel irradiated in FFTF does not saturate with fluence by ∼28 dpa, whereas for the 9Cr-2WV steel and most similar steels, saturation occurs at <10 dpa, and (2) the shift in DBTT for 9Cr-2WVTa steel irradiated in FFTF and HFR increased with irradiation temperature, whereas it decreased for the 9Cr-2WV steel, as it does for most similar steels. The improved properties of the 9Cr-2WVTa steel and the differences with other steels were attributed to tantalum in solution

Kraft cooking of gamma irradiated wood, (2)

International Nuclear Information System (INIS)

Inaba, Masamitsu; Meshitsuka, Gyosuke; Ishizu, Atsushi; Nakano, Junzo

1981-01-01

Pre-irradiation of wood in alkaline aqueous ethanol increases kraft pulp yield by up to 1.2%, as already reported. In order to clarify the mechanism of the pulp yield gain, the behaviors of lignin and carbohydrates during pre-irradiation and cooking were investigated. The results are summarized as follows: 1) γ-Irradiation of guaiacylethane in alkaline aqueous ethanol produced 5-(1-hydroxyethyl)-guaicylethane, which is formed by radical coupling between α-hydroxyethyl radical from ethanol and guaiacylethane radical having an unpaired electron at C-5. 5,5'-Dehydrodiguaiacylethane, which may be a predominant product produced by γ-irradiation in the absence of ethanol, was also detected. 2) The yield of vanillin obtained by nitrobenzene oxidation of MWL decreased with an increase of γ-ray dosage. The presence of ethanol during γ-irradiation lessened the extent of this decrease and also the degradation of cellobiose. 3) Gel filtration of the products obtained by γ-irradiation of MWL and cellobiose in the presence of 14 C-ethanol showed the possible combination between ethanol and MWL or cellobiose. 4) Molecular weight distributions of kraft lignin obtained from pre-irradiated beech chips were compared with those obtained from unirradiated chips. This result shows that γ-irradiation in the presence of ethanol decreases the ability of lignin to condense during kraft cooking. (author)

AGR-2 Irradiation Test Final As-Run Report

Energy Technology Data Exchange (ETDEWEB)

Collin, Blaise P. [Idaho National Lab. (INL), Idaho Falls, ID (United States). VHTR Program

2014-08-01

This document presents the as-run analysis of the AGR-2 irradiation experiment. AGR-2 is the second of the planned irradiations for the Advanced Gas Reactor (AGR) Fuel Development and Qualification Program. Funding for this program is provided by the U.S. Department of Energy as part of the Very High Temperature Reactor (VHTR) Technical Development Office (TDO) program. The objectives of the AGR-2 experiment are to: (a) Irradiate UCO (uranium oxycarbide) and UO₂ (uranium dioxide) fuel produced in a large coater. Fuel attributes are based on results obtained from the AGR-1 test and other project activities. (b) Provide irradiated fuel samples for post-irradiation experiment (PIE) and safety testing. (c) Support the development of an understanding of the relationship between fuel fabrication processes, fuel product properties, and irradiation performance. The primary objective of the test was to irradiate both UCO and UO₂ TRISO (tri-structural isotropic) fuel produced from prototypic scale equipment to obtain normal operation and accident condition fuel performance data. The UCO compacts were subjected to a range of burnups and temperatures typical of anticipated prismatic reactor service conditions in three capsules. The test train also includes compacts containing UO₂ particles produced independently by the United States, South Africa, and France in three separate capsules. The range of burnups and temperatures in these capsules were typical of anticipated pebble bed reactor service conditions. The results discussed in this report pertain only to U.S. produced fuel.

Radiation-induced heart disease due to intrathonacic tumor radiotherapy of a single dose to the rabbits' heart

International Nuclear Information System (INIS)

Zhou Weibing; Feng Yan; Chen Jiayi; Luo Quanyong

2007-01-01

Objective: To observe the changes of radiation-induced heart disease (RIHD) in the rabbits irradiated in clinical related dose, and to evaluate the apoptosis and hypoxia in the irradiated heart by the new scintigraphic agents of 99 Tc m -HL91 and 99 Tc m -Annexin V of heart SPECT. Methods: Tenty-four New Zealand white rabbits 4-month old and 2-3 kg by weight were divided into two groups. Group 1 (clinical related dose group): 16 irradiated by a single close from 0 to 18 Gy. Group 2 (high dose group): 8 irradiated dose from 22 to 80 Gy. The serum cTnI/CKMB, ECG, and heart SPECT(using 99 Tc m -MIBI, 99 Tc m -HL91 and 99 Tc m -Annexin V as agents) were detected before and after irradiation. The animals were followed for 5 months. Then biopsy of rabbit heart was performed and pathologic examination was made by H.E. stain. Results: In the 16 rabbits of clinical related dose group, none died of RIHD. Whereas 2 rabbits died of RIHD in the high dose group. One died of myocardial infarction and the other of congestive heart failure. According to the Stewart introduced heart lesion grading system, of the clinical close ann, there were moderate in 1 rabbit, minimal in 14; and of the high dose ann, it was severe in 2, marked in 1, moderate in 5. The parallel relation was observed between the ECG results and the pathological changes (χ 2 =0.08, P=0.771). Serum value of cTnI, was elevated at the 12th hour after irradiation reaching the peak and maintained for 4 months. However, it came down in the 5th month. The difference of serum cTnI value before and after radiation was statistically significant. Myocardial perfusion scintigraphy tested by heart SPECT ( 99 Tc m -MIBI) showed defects was present in all irradiated rabbits. The relationship between the defects and radiation dose or between the defects and the real RIHD was uncertain. The SPECT images displayed that 99 Tc m -HL91 and 99m Tc-Annexin V did not accumulate in the irradiated heart. Conclusions: No serious damage is

Detection of irradiated chicken by 2-alkylcyclobutanone analysis

International Nuclear Information System (INIS)

Tanabe, Hiroko; Goto, Michiko; Miyahara, Makoto

2001-01-01

Chicken meat irradiated at 0.5 kGy or higher doses were identified by GC/MS method analyzing 2-dodecylcyclobutanone (2-DCB) and 2-tetradecylcyclobutanone (2-TCB), which are formed from palmitic acid and stearic acid respectively, and isolated using extraction procedures of soxhlet-florisil chromatography. Many fat-containing foods have oleic acid in abundance as parent fatty acid, and chicken meat contains palmitoleic acid to the amount as much as stearic acid. In this study, we detected 2-tetradec-5'-enylcyclobutanone (2-TeCB) and 2-dodec-5'-enylcyclobutanone (2-DeCB) in chicken meat, which are formed from oleic acid and palmitoleic acid by irradiation respectively, using GC/MS method. Sensitivity in detection of both 2-TeCB and 2-DeCB were lower than that of 2-DCB. However, at least 0.57 μg/g/fat of 2-TeCB was detected in chicken meat irradiated at 0.5 kGy, so 2-TeCB seems to be a useful marker for the identification of irradiated foods containing fat. On the contrary, 2-DeCB was not detected clearly at low doses. This suggests that 2-DeCB may be a useful marker for irradiated fat in the food having enough amount of palmitoleic acid needed to analysis. In addition, 2-tetradecadienylcyclobutanone, which is formed from linoleic acid was also found in chicken meat. (author)

Summary report on the fuel performance modeling of the AFC-2A, 2B irradiation experiments

Energy Technology Data Exchange (ETDEWEB)

Pavel G. Medvedev

2013-09-01

The primary objective of this work at the Idaho National Laboratory (INL) is to determine the fuel and cladding temperature history during irradiation of the AFC-2A, 2B transmutation metallic fuel alloy irradiation experiments containing transuranic and rare earth elements. Addition of the rare earth elements intends to simulate potential fission product carry-over from pyro-metallurgical reprocessing. Post irradiation examination of the AFC-2A, 2B rodlets revealed breaches in the rodlets and fuel melting which was attributed to the release of the fission gas into the helium gap between the rodlet cladding and the capsule which houses six individually encapsulated rodlets. This release is not anticipated during nominal operation of the AFC irradiation vehicle that features a double encapsulated design in which sodium bonded metallic fuel is separated from the ATR coolant by the cladding and the capsule walls. The modeling effort is focused on assessing effects of this unanticipated event on the fuel and cladding temperature with an objective to compare calculated results with the temperature limits of the fuel and the cladding.

RERTR-12 Insertion 2 Irradiation Summary Report

International Nuclear Information System (INIS)

Perez, D.M.; Chang, G.S.; Wachs, D.M.; Roth, G.A.; Woolstenhulme, N.E.

2012-01-01

The Reduced Enrichment for Research and Test Reactor (RERTR) experiment RERTR-12 was designed to provide comprehensive information on the performance of uranium-molybdenum (U-Mo) based monolithic fuels for research reactor applications.1 RERTR-12 insertion 2 includes the capsules irradiated during the last three irradiation cycles. These capsules include Z, Y1, Y2 and Y3 type capsules. The following report summarizes the life of the RERTR-12 insertion 2 experiment through end of irradiation, including as-run neutronic analysis results, thermal analysis results and hydraulic testing results.

Role of lipoxygenases and the lipoxin A(4)/annexin 1 receptor in ischemia-reperfusion-induced gastric mucosal damage in rats.

Science.gov (United States)

Peskar, Brigitta M; Ehrlich, Karlheinz; Schuligoi, Rufina; Peskar, Bernhard A

2009-01-01

Rat gastric mucosal damage was induced by ischemia-reperfusion. The 5-lipoxygenase inhibitors MK886 and A63162, the 12-lipoxygenase inhibitor baicalein, the 15-lipoxygenase inhibitor PD146176 and the lipoxin (LX) A(4)/annexin 1 antagonist Boc1 increased mucosal damage in a dose-dependent manner. Low doses of these compounds, which have no effects on mucosal integrity, cause severe damage when combined with low doses of indomethacin, celecoxib or dexamethasone. 16,16-Dimethylprostaglandin (PG) E(2) and LXA(4) can replace each other in preventing mucosal injury induced by either cyclooxygenase or lipoxygenase inhibitors. The results suggest that not only cyclooxygenases, but also lipoxygenases have a role in limiting gastric mucosal damage during ischemia-reperfusion. Copyright 2009 S. Karger AG, Basel.

Potato Annexin STANN1 Promotes Drought Tolerance and Mitigates Light Stress in Transgenic Solanum tuberosum L. Plants

Czech Academy of Sciences Publication Activity Database

Szalonek, M.; Sierpien, B.; Rymaszewski, W.; Gieczewska, K.; Vaňková, Radomíra; Dobrev, Petre; Szczesny, P.; Marczewski, W.; Krusiewicz, D.; Strzelczyk-Zyta, D.; Konopka-Postupolska, D.

2015-01-01

Roč. 10, č. 7 (2015), e0132683 E-ISSN 1932-6203 Institutional support: RVO:61389030 Keywords : MEDIATED OXIDATIVE STRESS * VIOLAXANTHIN DE-EPOXIDASE * BRASSICA-JUNCEA ANNEXIN-3 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.057, year: 2015

Effects of low priming dose irradiation on cell cycle arrest of HepG2 cells caused by high dose irradiation

International Nuclear Information System (INIS)

Xia Jingguang; Jin Xiaodong; Chinese Academy of Sciences, Beijing; Li Wenjian; Wang Jufang; Guo Chuanling; Gao Qingxiang

2005-01-01

Human hepatoma cells hepG2 were irradiated twice by 60 Co γ-rays with a priming dose of 5 cGy and a higher dose of 3 Gy performed 4h or 8h after the low dose irradiation. Effects of the priming dose irradiation on cell cycle arrest caused by high dose were examined with flow cytometry. Cells in G 2 /M phase accumulated temporarily after the 5 cGy irradiation, and proliferation of tumor cells was promoted significantly by the low dose irradiation. After the 3 Gy irradiation, G 2 phase arrest occurred, and S phase delayed temporally. In comparison with 3 kGy irradiation only, the priming dose delivered 4h prior to the high dose irradiation facilitated accumulation of hepG2 cells in G 2 /M phase, whereas the priming dose delivered 8h prior to the high dose irradiation helped the cells to overcome G 2 arrest. It was concluded that effects of the priming dose treatment on cell cycle arrest caused by high dose irradiation were dependent on time interval between the two irradiations. (authors)

Food Irradiation Newsletter. V. 12, no. 2

International Nuclear Information System (INIS)

1988-07-01

This Newsletter reports activities of two ICGFI training workshops convened in Santiago, Chile, and Rehovot, Israel, in the past six months. The summary report of the FAO/IAEA Seminar on Food Irradiation for Developing Countries in Africa is also included. A follow-up to this Seminar is the ''Co-ordinated Research Programme on Food Irradiation for African Countries'' which will be implemented as soon as funds become available. Further, this issue contains a report of the Working Group on Food Irradiation of the European Society for Nuclear Agriculture convened in Stara Zagora, Bulgaria in 1987 and status reports of practical applications of food irradiation in different countries. 2 tabs

Significance of apoptotic cell death after γ-irradiation

International Nuclear Information System (INIS)

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

2003-01-01

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

D2-H2 equilibration over γ-irradiated zeolites

International Nuclear Information System (INIS)

Novakova, J.; Wichterlova, B.

1987-01-01

D 2 -H 2 equilibration was studied at 77 and 298 K over HY, AlHY, HZSM-5 and Alsub(x)Osub(y)HZSM-5 zeolites which had been γ-irradiated at 77 and/or 298 K. The exchange rate was found to be higher at the lower temperature regardless of the temperature of irradiation. Moreover, at 77 K the exchange rates were similar and more stable over the individual zeolites than at 298 K, thus indicating a common reaction path at 77 K. The exchange rate at 298 K depended on the zeolite type: it was more stable and higher over HZSM-5 than over HY, and extra-lattice Al increased both these properties on HY as well as on HZSM-5. The reaction mechanism is discussed in connection with the nature of defects generated by γ-irradiation. (author)

The post irradiation examination of a sphere-pac (UPu)C fuel pin irradiated in the BR-2 reactor (MFBS 7 experiment)

International Nuclear Information System (INIS)

Smith, L.; Aerne, E.T.; Buergisser, B.; Flueckiger, U.; Hofer, R.; Petrik, F.

1979-09-01

A pin fuelled with Swiss made (UPu)C microspheres has been successfully irradiated to a peak burn-up of 6% fima in the Belgian BR2 Reactor. The pin, rated up to 95 kW/m, was intact after irradiation and exhibited a peak strain of just over 0.5%. The results of the post irradiation examination are reported. (Auth.)

Irradiation of UO{sub 2}; Ozracivanje UO{sub 2}

Energy Technology Data Exchange (ETDEWEB)

Stevanovic, M [Institute of nuclear sciences Boris Kidric, Vinca, Beograd (Yugoslavia)

1965-10-15

Based on the review of the available literature concerned with UO{sub 2} irradiation, this paper describes and explains the phenomena initiated by irradiation of the UO{sub 2} fuel in a reactor dependent on the burnup level and temperature. A comprehensive review of UO{sub 2} radiation damage studies is given as a broad research program. This part includes the abilities of our reactor as well as needed elements for such study. The third part includes the defions of the specific power, burnup level and temperature in the center of the fuel element needed for planning and performing the irradiation. Methods for calculating these parameters are includedSerb. Na osnovu pregleda dostupne literature o ozracivanju UO{sub 2} u ovom radu su izlozene i objasnjene pojave koje nastaju pri ozracivanju goriva od UO{sub 2} u reaktoru do razlicitih stepena izgaranja i na razlicitim temperaturama. Pored toga, dat je pregled svih mogucih ispitivanja na radijacionom ostecenju UO{sub 2} u formi sirokog programa istrazivanja. Ovaj deo je dopunjen sudom o mogucnostima naseg reaktora kao i o elementima koji su potrebni za ovakav rad. U trecem delu su izlozeni definicija parametara: specificna snaga, stepen izgaranja i temperatura centra goriva i njihovo izracunavanje za potrebe postavljanja i izvodjenja ozracivanja (author)

Sprout inhibition of potatoes by electron irradiation, (2)

International Nuclear Information System (INIS)

Furuta, Junichiro; Hiraoka, Eiichi; Okamoto, Shinichi; Fujishiro, Masatoshi; Kanazawa, Tamotsu; Ohnishi, Tokuhiro; Tsujii, Yukio; Hori, Shiro

1982-01-01

Sprouting of potatoes are inhibited usually by the gamma-ray irradiation. The buds of potatoes exist in a very thin layer near surface of each tuber. So the inhibition will be performed sufficiently by surface irradiation using electron beams. To irradiate all surfaces of each potato uniformly, the authors prepare a new apparatus which is a conveyer passing under an electron beam scanner of accelerator rotating the potatoes by many rotating rollers. The sprout inhibition experiment of potatoes was performed by following three methods to obtain the performance of this apparatus, and the results were compared. 1) turn over irradiation method --- potatoes were arranged in one layer in plastic baskets and were irradiated on the conveyor. After irradiation, the potatoes were turned over and were irradiated again. 2) rotating irradiation method --- potatoes were rotated on the rotating roller apparatus set on the conveyer and were passed under the electron beam scanner. 3) rotating irradiation method with an improved rotating roller apparatus --- the rotating rollers have many protuberances on their surface to irradiate all of potato surface more uniform. 550 keV electron beams by Cockcroft-Walton type accelerator were used for the irradiation and the irradiated dose was 5 to 20 krad. 40 pieces of potates, ''Danshaku'' variety yielded in June 1981, were irradiated for each dose in the beginning of August. Prior to these irradiation experiments, the dose and dose uniformity were checked by the agar color dosimeters. After the irradiation, potatoes were stored in natural condition and their sprouting was observed. The potatoes irradiated by the improved rotating roller apparatus were almost completely sprout-inhibited by 20 krad irradiation. (author)

Fabrication, irradiation and post-irradiation examinations of MO2 and UO2 sphere-pac and UO2 pellet fuel pins irradiated in a PWR loop

International Nuclear Information System (INIS)

Linde, A. van der; Lucas Luijckx, H.J.B.; Verheugen, J.H.N.

1982-01-01

The document reports in detail the fuel pin fabrication data and describes the irradiation conditions and history. All the relevant results of the non-destructive and destructive post-irradiation examinations are reported. They include: visual inspection and chemical analysis of crud; length and diameter measurements; neutron radiography and gamma scanning; juncture tests and fission gas analysis (including residual gas in fuel samples); microscopy and alpha + beta/gamma autoradiography; microprobe investigations; burn-up and isotopic analysis; and hydrogen analysis in clad. The data and observations obtained are discussed in detail and conclusions are given. The irradiation and post-irradiation examinations of the R-109 pins have shown the safe, pre-calculable performance of LWR fuel pins containing mixed-oxide sphere-pac fuel with the fissile material mainly present in the large spheres

Production yields of 2-alkylcyclobutanones in irradiated foods

Energy Technology Data Exchange (ETDEWEB)

Marchioni, E.; Ennahar, S. [Universite de Strasbourg, Illkirch (France). Faculte de Pharmacie. Lab. de Chimie Analytique et Sciences de l' Aliment], e-mail: marchion@unistra.fr, e-mail: ennahar@unistra.fr; Horvatovich, P. [University of Groningen (Netherlands). Dept. of Pharmacy. Analytical Biochemistry], e-mail: p.l.horvatovich@rug.nl; Ndiaye, B. [Centre Hospitalier National de Fann, Dakar (Senegal)], e-mail: ibamath@hotmail.com

2009-07-01

2-alkycyclobutanones are formed by irradiation exclusively, and are considered as unique radiolytic product (URP). Because of the URP character of the 2-alkycyclobutanones, these compounds are good marker of irradiation treatment. The European Committee for Standardization (CEN) developed an analytical method (EN 1785) for detection of 2-alkycyclobutanones having a detection limit of 0.2 pmol, limiting the application to foodstuffs treated for microbial disinfection (doses > 0.5 kGy), with fat content higher than 1.0 g %. The use of this EN 1785 and the supercritical extraction analytical methods allowed the determination of the production yields of 2-alkycyclobutanones in broad range of foodstuffs. The obtained production yields were between 0.20 and 12.21 nmol/mmol fatty acid/kGy), and showed strong dependency from he nature of the food matrix. The amount 2-alkycyclobutanones intake from irradiated foodstuffs by consumer calculated based on production yields determined in this work show, that the doses used in toxicological studies were much higher, than that are consumed by human through eating irradiated foods. (author)

Production yields of 2-alkylcyclobutanones in irradiated foods

International Nuclear Information System (INIS)

Marchioni, E.; Ennahar, S.

2009-01-01

2-alkycyclobutanones are formed by irradiation exclusively, and are considered as unique radiolytic product (URP). Because of the URP character of the 2-alkycyclobutanones, these compounds are good marker of irradiation treatment. The European Committee for Standardization (CEN) developed an analytical method (EN 1785) for detection of 2-alkycyclobutanones having a detection limit of 0.2 pmol, limiting the application to foodstuffs treated for microbial disinfection (doses > 0.5 kGy), with fat content higher than 1.0 g %. The use of this EN 1785 and the supercritical extraction analytical methods allowed the determination of the production yields of 2-alkycyclobutanones in broad range of foodstuffs. The obtained production yields were between 0.20 and 12.21 nmol/mmol fatty acid/kGy), and showed strong dependency from he nature of the food matrix. The amount 2-alkycyclobutanones intake from irradiated foodstuffs by consumer calculated based on production yields determined in this work show, that the doses used in toxicological studies were much higher, than that are consumed by human through eating irradiated foods. (author)

Detection of irradiated prawns using 2-alkyl-cyclobutanones

International Nuclear Information System (INIS)

McMurray, B.T.; Hamilton, J.T.G.; Stevenson, M.H.

1994-01-01

The use of ionizing radiation for the preservation of food has been under investigation for many years but yet has to receive worldwide acceptance. Although irradiation can be carefully controlled, it is generally accepted that the development of tests for detection of irradiated food would enhance consumer confidence and might help to enforce labelling regulations. The alkylcyclobutanones are reported to be the only cyclic compounds formed as the products of the radiolysis of saturated triglycerides. The synthesis of 2-dodecylcyclobutanone (DCB) and 2-tetradecylcyclobutanone (TCB) has been carried out. Using irradiated chicken meat as the model for a fat-containing food, both cyclobutanones have been extracted with solvent and then identified by gas chromatography-mass spectrometry. DCB and TCB have been detected in chicken meat irradiated at doses well below 10 kGy and were not detectable in unirradiated chicken. Systematic studies have been undertaken to confirm the specificity of these compounds as markers for irradiation treatment. The presence of both DCB and TCB in other irradiated meats and irradiated liquid whole egg has been confirmed. The feasibility of applying the method to low- fat-containing foods, such as prawns, is now underway. Preliminary studies have shown that both DCB and TCB have been detected in prawns irradiated at doses likely to be used commercially. 3 refs. (author)

Irradiation damages in Ti3SiC2

International Nuclear Information System (INIS)

Nappe, J.C.; Grosseau, Ph.; Guilhot, B.; Audubert, F.; Beauvy, M.

2007-01-01

Carbides, by their remarkable properties, are considered as possible materials (fuel cans) in reactor of generation IV. Among those studied, Ti 3 SiC 2 is particularly considered because it joins both the ceramics and metals properties. Nevertheless, its behaviour under irradiation is not known. Characterizations have been carried out on samples irradiated at 75 MeV krypton ions. They have revealed that TiO 2 (formed at the surface of Ti 3 SiC 2 ) is pulverized by the irradiation and that the crystal lattice of Ti 3 SiC 2 dilates with c. (O.M.)

Final report on graphite irradiation test OG-2

International Nuclear Information System (INIS)

Price, R.J.; Beavan, L.A.

1975-01-01

Results are presented of dimensional, thermal expansivity, thermal conductivity, Young's modulus, and tensile strength measurements on specimens of nuclear graphites irradiated in capsule OG-2. About half the irradiation space was allocated to H-451 near-isotropic petroleum-coke-based graphite or its subsized prototype grade H-429. Most of these specimens had been previously irradiated. Virgin specimens of another near-isotropic graphite, grade TS-1240, were irradiated. Some previously irradiated specimens of needle-coke-based H-327 graphite and pitch-coke-based P 3 JHAN were also included

Effect of 14N ion irradiation on Bi2Sr2CaCu2Oy superconductors

International Nuclear Information System (INIS)

Sharma, M.L.; Ashwini Kumar, P.K.; Sarkar, S.K.; Virdi, G.S.; Rup, R.

1993-01-01

The effect of 14 N ion irradiation on a bulk Bi 2 Sr 2 CaCu 2 O y high-T c superconducting system has been studied. The incident energy was kept at 150 keV and the irradiation dose varied between 1 x 10 11 cm -2 and 1 x 10 16 cm -2 . It has been observed that the resistive transition occurs at lower temperatures for the irradiated specimens and the width (10-90% transition) of the superconducting transition decreases. Scanning transmission electron microscopy and x-ray diffraction (XRD) studies were carried out to evaluate the change in surface microstructure and XRD peak intensities due to irradiation. The results are discussed in the light of the similarity of atomic sizes of N and O atoms. (author)

An immune response manifested by the common occurrence of annexins I and II autoantibodies and high circulating levels of IL-6 in lung cancer

Science.gov (United States)

Brichory, Franck M.; Misek, David E.; Yim, Anne-Marie; Krause, Melissa C.; Giordano, Thomas J.; Beer, David G.; Hanash, Samir M.

2001-01-01

The identification of circulating tumor antigens or their related autoantibodies provides a means for early cancer diagnosis as well as leads for therapy. The purpose of this study was to identify proteins that commonly induce a humoral response in lung cancer by using a proteomic approach and to investigate biological processes that may be associated with the development of autoantibodies. Aliquots of solubilized proteins from a lung adenocarcinoma cell line (A549) and from lung tumors were subjected to two-dimensional PAGE, followed by Western blot analysis in which individual sera were tested for primary antibodies. Sera from 54 newly diagnosed patients with lung cancer and 60 patients with other cancers and from 61 noncancer controls were analyzed. Sera from 60% of patients with lung adenocarcinoma and 33% of patients with squamous cell lung carcinoma but none of the noncancer controls exhibited IgG-based reactivity against proteins identified as glycosylated annexins I and/or II. Immunohistochemical analysis showed that annexin I was expressed diffusely in neoplastic cells in lung tumor tissues, whereas annexin II was predominant at the cell surface. Interestingly, IL-6 levels were significantly higher in sera of antibody-positive lung cancer patients compared with antibody-negative patients and controls. We conclude that an immune response manifested by annexins I and II autoantibodies occurs commonly in lung cancer and is associated with high circulating levels of an inflammatory cytokine. The proteomic approach we have implemented has utility for the development of serum-based assays for cancer diagnosis as we report in this paper on the discovery of antiannexins I and/or II in sera from patients with lung cancer. PMID:11504947

Neutron irradiation damage in Al2O3 and Y2O3

International Nuclear Information System (INIS)

Clinard, F.W. Jr.; Bunch, J.M.; Ranken, W.A.

1975-01-01

Two ceramics under consideration for use in fusion reactors, Al 2 O 3 and Y 2 O 3 , were irradiated in the EBR-II fission reactor at 650, 875, and 1025 0 K to fluences between 2 and 6 x 10 21 n/cm 2 (E greater than 0.1 MeV). Samples evaluated include sapphire, Lucalox, alumina, Y 2 O 3 , and Y 2 O 3 -10 percent ZrO 2 (Yttralox). All Al 2 O 3 specimens swelled significantly (1 to 3 percent), with most of the growth observed in sapphire along the c-axis at the higher temperatures. Al 2 O 3 samples irradiated at 875 to 1025 0 K contained a high density of small aligned ''pores''. Irradiated Y 2 O 3 -based ceramics exhibited dimensional stability and a defect content consisting primarily of unresolved damage and/or dislocation loops. The behavior of these ceramics under irradiation is discussed, and the relevance of fission neutron damage studies to fusion reactor applications is considered. (auth)

Irradiation Alters MMP-2/TIMP-2 System and Collagen Type IV Degradation in Brain

Energy Technology Data Exchange (ETDEWEB)

Lee, Won Hee [School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia (United States); Warrington, Junie P.; Sonntag, William E. [Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (United States); Lee, Yong Woo, E-mail: ywlee@vt.edu [School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia (United States); Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia (United States)

2012-04-01

Purpose: Blood-brain barrier (BBB) disruption is one of the major consequences of radiation-induced normal tissue injury in the central nervous system. We examined the effects of whole-brain irradiation on matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) and extracellular matrix (ECM) degradation in the brain. Methods and Materials: Animals received either whole-brain irradiation (a single dose of 10 Gy {gamma}-rays or a fractionated dose of 40 Gy {gamma}-rays, total) or sham-irradiation and were maintained for 4, 8, and 24 h following irradiation. mRNA expression levels of MMPs and TIMPs in the brain were analyzed by real-time reverse transcriptase-polymerase chain reaction (PCR). The functional activity of MMPs was measured by in situ zymography, and degradation of ECM was visualized by collagen type IV immunofluorescent staining. Results: A significant increase in mRNA expression levels of MMP-2, MMP-9, and TIMP-1 was observed in irradiated brains compared to that in sham-irradiated controls. In situ zymography revealed a strong gelatinolytic activity in the brain 24 h postirradiation, and the enhanced gelatinolytic activity mediated by irradiation was significantly attenuated in the presence of anti-MMP-2 antibody. A significant reduction in collagen type IV immunoreactivity was also detected in the brain at 24 h after irradiation. In contrast, the levels of collagen type IV were not significantly changed at 4 and 8 h after irradiation compared with the sham-irradiated controls. Conclusions: The present study demonstrates for the first time that radiation induces an imbalance between MMP-2 and TIMP-2 levels and suggests that degradation of collagen type IV, a major ECM component of BBB basement membrane, may have a role in the pathogenesis of brain injury.

Irradiation Alters MMP-2/TIMP-2 System and Collagen Type IV Degradation in Brain

International Nuclear Information System (INIS)

Lee, Won Hee; Warrington, Junie P.; Sonntag, William E.; Lee, Yong Woo

2012-01-01

Purpose: Blood-brain barrier (BBB) disruption is one of the major consequences of radiation-induced normal tissue injury in the central nervous system. We examined the effects of whole-brain irradiation on matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) and extracellular matrix (ECM) degradation in the brain. Methods and Materials: Animals received either whole-brain irradiation (a single dose of 10 Gy γ-rays or a fractionated dose of 40 Gy γ-rays, total) or sham-irradiation and were maintained for 4, 8, and 24 h following irradiation. mRNA expression levels of MMPs and TIMPs in the brain were analyzed by real-time reverse transcriptase-polymerase chain reaction (PCR). The functional activity of MMPs was measured by in situ zymography, and degradation of ECM was visualized by collagen type IV immunofluorescent staining. Results: A significant increase in mRNA expression levels of MMP-2, MMP-9, and TIMP-1 was observed in irradiated brains compared to that in sham-irradiated controls. In situ zymography revealed a strong gelatinolytic activity in the brain 24 h postirradiation, and the enhanced gelatinolytic activity mediated by irradiation was significantly attenuated in the presence of anti-MMP-2 antibody. A significant reduction in collagen type IV immunoreactivity was also detected in the brain at 24 h after irradiation. In contrast, the levels of collagen type IV were not significantly changed at 4 and 8 h after irradiation compared with the sham-irradiated controls. Conclusions: The present study demonstrates for the first time that radiation induces an imbalance between MMP-2 and TIMP-2 levels and suggests that degradation of collagen type IV, a major ECM component of BBB basement membrane, may have a role in the pathogenesis of brain injury.

AGC-2 Irradiation Report

Energy Technology Data Exchange (ETDEWEB)

Rohrbaugh, David Thomas [Idaho National Lab. (INL), Idaho Falls, ID (United States); Windes, William [Idaho National Lab. (INL), Idaho Falls, ID (United States); Swank, W. David [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2016-06-01

The Next Generation Nuclear Plant (NGNP) will be a helium-cooled, very high temperature reactor (VHTR) with a large graphite core. In past applications, graphite has been used effectively as a structural and moderator material in both research and commercial high temperature gas cooled reactor (HTGR) designs.[ , ] Nuclear graphite H 451, used previously in the United States for nuclear reactor graphite components, is no longer available. New nuclear graphites have been developed and are considered suitable candidates for the new NGNP reactor design. To support the design and licensing of NGNP core components within a commercial reactor, a complete properties database must be developed for these current grades of graphite. Quantitative data on in service material performance are required for the physical, mechanical, and thermal properties of each graphite grade with a specific emphasis on data related to the life limiting effects of irradiation creep on key physical properties of the NGNP candidate graphites. Based on experience with previous graphite core components, the phenomenon of irradiation induced creep within the graphite has been shown to be critical to the total useful lifetime of graphite components. Irradiation induced creep occurs under the simultaneous application of high temperatures, neutron irradiation, and applied stresses within the graphite components. Significant internal stresses within the graphite components can result from a second phenomenon—irradiation induced dimensional change. In this case, the graphite physically changes i.e., first shrinking and then expanding with increasing neutron dose. This disparity in material volume change can induce significant internal stresses within graphite components. Irradiation induced creep relaxes these large internal stresses, thus reducing the risk of crack formation and component failure. Obviously, higher irradiation creep levels tend to relieve more internal stress, thus allowing the

Precipitation in Zr-2.5Nb enhanced by proton irradiation

Energy Technology Data Exchange (ETDEWEB)

Cann, C. D.; So, C. B.; Styles, R. C.; Coleman, C. E.

1993-08-15

A 3.6 MeV proton irradiation of annealed Zr-2.5Nb has been performed to determine whether proton irradiation will enhance the precipitation of Nb-rich {beta}-phase precipitates within the {alpha}-grains. a transmission electron microscope examination of a foil after irradiation at 770 K for 18 h and at 720 K for 264.5 h to a total damage of 0.94 dpa revealed a fine dispersion of precipitates within the {alpha}-grains. Electron diffraction analysis of the precipitates found they have lattice plane spacings consistent with the Nb-rich {beta}-phase. This result is in agreement with the {beta}phase precipitation observed following neutron irradiation, and thus it supports the use of proton irradiation to simulate neutron-irradiation effects in Zr-2.5Nb.

Precipitation in Zr-2.5Nb enhanced by proton irradiation

International Nuclear Information System (INIS)

Cann, C.D.; So, C.B.; Styles, R.C.; Coleman, C.E.

1993-08-01

A 3.6 MeV proton irradiation of annealed Zr-2.5Nb has been performed to determine whether proton irradiation will enhance the precipitation of Nb-rich β-phase precipitates within the α-grains. a transmission electron microscope examination of a foil after irradiation at 770 K for 18 h and at 720 K for 264.5 h to a total damage of 0.94 dpa revealed a fine dispersion of precipitates within the α-grains. Electron diffraction analysis of the precipitates found they have lattice plane spacings consistent with the Nb-rich β-phase. This result is in agreement with the βphase precipitation observed following neutron irradiation, and thus it supports the use of proton irradiation to simulate neutron-irradiation effects in Zr-2.5Nb

Progresses in studies on 2-alkylcyclobutanones in irradiated lipid-containing foods

International Nuclear Information System (INIS)

Zhang Haiwei; Ha Yiming; Wang Feng

2007-01-01

When foods are irradiated, the free fatty acids and triacylglycerides in the food are decomposed to 2-alkylcyclobutanones (2-ACBs), which have been one of the focuses in food irradiation studies since they were dis- covered in irradiated lipid-containing foods. As specific markers, 2-ACBs could be used to detect irradiated food. The production and stability of 2-ACBs are affected strongly by the irradiation does and temperature and preservation conditions, etc. On the other hand, potential health hazard assessments of 2-ACBs have been studied extensively. Re- cent progresses in 2-ACBs detecting methods from irradiated food, toxicological studies on 2-ACBs, and factors affecting production and stability of 2-ACBs are reviewed in this paper. (authors)

Young women with polycystic ovary syndrome have raised levels of circulating annexin V-positive platelet microparticles.

Science.gov (United States)

Willis, G R; Connolly, K; Ladell, K; Davies, T S; Guschina, I A; Ramji, D; Miners, K; Price, D A; Clayton, A; James, P E; Rees, D A

2014-12-01

Are circulating microparticles (MPs) altered in young women with polycystic ovary syndrome (PCOS)? Women with PCOS have elevated concentrations of circulating platelet-derived MPs, which exhibit increased annexin V binding and altered microRNA (miR) profiles compared with healthy volunteers. Some studies have shown that cardiovascular risk is increased in young women with PCOS but the mechanisms by which this occurs are uncertain. Circulating MPs are elevated in patients with cardiovascular disease but the characteristics of MPs in patients with PCOS are unclear. Case-control study comprising 17 women with PCOS (mean ± SD; age 31 ± 7 years, BMI 29 ± 6 kg/m(2)) and 18 healthy volunteers (age 31 ± 6 years, BMI 30 ± 6 kg/m(2)). The study was conducted in a University hospital. Nanoparticle tracking analysis (NTA) and flow cytometry (CD41 platelet, CD11b monocyte, CD144 endothelial) were used to determine MP size, concentration, cellular origin and annexin V positivity (reflecting phosphatidylserine exposure). Fatty acid analysis was performed by gas chromatography and MP miR expression profiles were compared by microarray. PCOS subjects showed increased MP concentrations compared with healthy volunteers (mean ± SD; 11.5 ± 5 × 10(12)/ml versus 10.0 ± 4 × 10(12)/ml, respectively; P = 0.03), which correlated with the homeostasis model of insulin resistance (r = 0.53, P = 0.03). This difference was predominantly seen in MPs whose size was in the small exosomal range (PCOS patients showed a greater percentage of annexin V(+) MPs compared with healthy volunteers (84 ± 18 versus 74 ± 24%, respectively, P = 0.05) but the cellular origin of MPs, which were predominantly platelet-derived (PCOS: 99 ± 0.9%; controls: 99 ± 2.5%), did not differ. MP fatty acid concentration and composition was similar between groups but 16 miRs were differentially expressed (P PCOS were classified by the Rotterdam criteria, which describes a less severe metabolic phenotype than other

Irradiation of UO2 specimens with molten cores in a pressurized water loop. Test X-2-x

International Nuclear Information System (INIS)

Bain, A.S.

1961-08-01

Two Zircaloy-2 clad specimens containing stoichiometric UO 2 pellets were irradiated in a pressurized water loop for 379 hours at heat ratings sufficient to cause central melting of the UO 2 . There was no appearance of localized overheating or accelerated corrosion of the sheath, but the diametral increases were considerably larger than those observed in loop specimens irradiated at lower heat ratings. The length increases, however, were approximately the same as those measured for specimens at lower ratings. There was a clearly visible demarcation between UO 2 that had been molten and that which had not. The value of ∫ 500 o C Tm kdθ = 74 ± W/cm was essentially the same as that obtained from the short-duration tests in the Hydraulic Rabbit, indicating there is no marked decrease in thermal conductivity of the UO 2 fuel in irradiations up to 379 hours. (author)

Synthesis, characterization, and potential use of 2-dodecylcyclobutanone as a marker for irradiated chicken

International Nuclear Information System (INIS)

Boyd, D.R.; Crone, A.V.J.; Hamilton, J.T.G.; Hand, M.V.; Stevenson, M.H.; Stevenson, P.J.

1991-01-01

The synthesis and characterization of 2-dodecylcyclobutanone is described. Solvent extraction techniques for the isolation of this compound from irradiated minced chicken meat and its detection by selected ion monitoring are outlined. The compound was not detected in either raw or cooked nonirradiated minced chicken meat by the methods used, but its presence was confirmed in the irradiated samples. 2-Dodecylcyclobutanone was detectable for 20 days postirradiation. The dose (4.7 kGy) of irradiation applied was below the recommended upper limit for food (10 kGy), and this compound may have potential as a marker for irradiated chicken meat and for other foods containing lipid

Regulation of prostaglandin E2 synthesis after brain irradiation

International Nuclear Information System (INIS)

Moore, Amy H.; Olschowka, John A.; Williams, Jacqueline P.; Okunieff, Paul; O'Banion, M. Kerry

2005-01-01

Purpose: A local tissue reaction, termed neuroinflammation, occurs after irradiation of brain tissue. Previous work suggested that cyclooxygenase (COX)-2 activity was important for changes in gene expression associated with neuroinflammation as well as increased prostaglandin E 2 (PGE 2 ) levels seen after radiation treatment. Methods and materials: To begin to determine the contributions of other enzymes involved in PGE 2 production, we examined protein levels of COX-1 and COX-2 as well as 2 PGE synthases (membrane and cytosolic PGES) 4 h after 35 Gy single dose irradiation to the brains of C3HeN mice. We also evaluated the effects of specific COX inhibitors on PGE 2 production and PGES expression. Results: As expected, COX-2 expression increased after radiation exposure. Brain irradiation also increased tissue protein levels for both PGES isoforms. Specific COX-2 inhibition with NS398 lowered brain PGE 2 levels by about 60%. Surprisingly, COX-1 inhibition with SC560 completely prevented the elevation of PGE 2 seen after irradiation. Interestingly, NS398 reduced the membrane-associated PGES isoform, whereas SC560 treatment lowered cytosolic isoform levels below those seen in unirradiated controls. Conclusions: Taken together, these data indicate that both cyclooxygenases contribute to PGE 2 production in irradiated brain and reveal dependence of PGES isoforms expression on specific cyclooxygenase activities

HYDROXYCHLOROQUINE REDUCES BINDING OF ANTIPHOSPHOLIPID ANTIBODIES TO SYNCYTIOTROPHOBLASTS AND RESTORES ANNEXIN A5 EXPRESSION

Science.gov (United States)

Wu, Xiao-Xuan; Guller, Seth; Rand, Jacob H.

2011-01-01

Objectives Antibody-mediated disruption of the annexin A5 (AnxA5) anticoagulant shield has been posited to be a thrombogenic mechanism in the antiphospholipid syndrome. We recently showed that the antimalarial drug, hydroxychloroquine, dissociates antiphospholipid immune complexes and restores AnxA5 binding to planar phospholipid bilayer. Using quantitative immunoassays, we demonstrated similar effects on BeWo trophoblasts. We therefore investigated the effects of the drug on localization of AnxA5 in primary cultures of human placental syncytiotrophoblasts (SCTs). Study Laser confocal microscopy with computer-based morphometric analysis was used to localize AnxA5 and antiphospholipid antibodies on SCTs exposed to polyclonal and monoclonal antiphospholipid and control IgGs. Results Hydroxychloroquine reversed the effects of the antiphospholipid antibodies on the SCTs by markedly reducing IgG binding and restoring AnxA5 expression. Conclusions These results provide the first morphologic evidence for this effect of hydroxychloroquine on human placental SCTs and support the possibility of novel treatments that target antiphospholipid antibody binding. PMID:21871597

AGR-2 irradiation test final as-run report, Rev. 1

International Nuclear Information System (INIS)

2014-01-01

This document presents the as-run analysis of the AGR-2 irradiation experiment. AGR-2 is the second of the planned irradiations for the Advanced Gas Reactor (AGR) Fuel Development and Qualification Program. Funding for this program is provided by the U.S. Department of Energy as part of the Very High Temperature Reactor (VHTR) Technical Development Office (TDO) program. The objectives of the AGR-2 experiment are to: (a) Irradiate UCO (uranium oxycarbide) and UO 2 (uranium dioxide) fuel produced in a large coater. Fuel attributes are based on results obtained from the AGR-1 test and other project activities; (b) Provide irradiated fuel samples for post-irradiation experiment (PIE) and safety testing; and, (c) Support the development of an understanding of the relationship between fuel fabrication processes, fuel product properties, and irradiation performance. The primary objective of the test was to irradiate both UCO and UO 2 TRISO (tri-structural isotropic) fuel produced from prototypic scale equipment to obtain normal operation and accident condition fuel performance data. The UCO compacts were subjected to a range of burnups and temperatures typical of anticipated prismatic reactor service conditions in three capsules. The test train also includes compacts containing UO 2 particles produced independently by the United States, South Africa, and France in three separate capsules. The range of burnups and temperatures in these capsules were typical of anticipated pebble bed reactor service conditions. The results discussed in this report pertain only to U.S. produced fuel. In order to achieve the test objectives, the AGR-2 experiment was irradiated in the B-12 position of the Advanced Test Reactor (ATR) at Idaho National Laboratory (INL) for a total irradiation duration of 559.2 effective full power days (EFPD). Irradiation began on June 22, 2010, and ended on October 16, 2013, spanning 12 ATR power cycles and approximately three and a half calendar years. The

Ductility loss of ion-irradiated zircaloy-2 in iodine

International Nuclear Information System (INIS)

Shimada, M.; Terasawa, M.; Yamamoto, S.; Kamei, H.; Koizumi, K.

1981-01-01

An ion bombardment simulation technique for neutron irradiation was applied to 'thick' materials to study the effect of radiation damage on the ductility change in Zircaloy-2 in an iodine environment. Specimens were prepared from actual cladding tubes and, prior to the irradiation, they were heat-treated in vacuo at 450, 580, and 700/degree/C for 2 h. Irradiation was performed by 52-MeV alpha particles up to the 0.32 displacements per atom (dpa) at 340/degree/C. Ductility loss begins to appear after 0.03 dpa irradiation, both in iodine and argon gas environments. The iodine presence resulted in ductility reduction, compared with the argon result in all irradiation dose ranges examined. The stress applied during irradiation caused ductility loss to commence at lower dosage than in the case of stress-free irradiation. These results are discussed in relation to the existing stress corrosion cracking models

Specific heat of MgB2 after irradiation

International Nuclear Information System (INIS)

Wang Yuxing; Bouquet, Frederic; Sheikin, Ilya; Toulemonde, Pierre; Revaz, Bernard; Eisterer, Michael; Weber, Harald W; Hinderer, Joerg; Junod, Alain

2003-01-01

We studied the effect of disorder on the superconducting properties of polycrystalline MgB 2 by specific-heat measurements. In the pristine state, these measurements give a bulk confirmation of the presence of two superconducting gaps with 2Δ 0 /k B T c =1.3 and 3.9 with nearly equal weights. The scattering introduced by irradiation suppresses T c and tends to average the two gaps although less than predicted by theory. We also found that by a suitable irradiation process by fast neutrons, a substantial bulk increase of dH c2 /dT at T c can be obtained without sacrificing more than a few degrees in T c . The upper critical field of the sample after irradiation exceeds 28 T at T→0

Mast cell heterogeneity and anti-inflammatory annexin A1 expression in leprosy skin lesions.

Science.gov (United States)

Costa, Maurício B; Mimura, Kallyne K O; Freitas, Aline A; Hungria, Emerith M; Sousa, Ana Lúcia O M; Oliani, Sonia M; Stefani, Mariane M A

2018-03-29

Mast cells (MCs) have important immunoregulatory roles in skin inflammation. Annexin A1 (ANXA1) is an endogenous anti-inflammatory protein that can be expressed by mast cells, neutrophils, eosinophils, monocytes, epithelial and T cells. This study investigated MCs heterogeneity and ANXA1 expression in human dermatoses with special emphasis in leprosy. Sixty one skin biopsies from 2 groups were investigated: 40 newly diagnosed untreated leprosy patients (18 reaction-free, 11 type 1 reaction/T1R, 11 type 2 reaction/T2R); 21 patients with other dermatoses. Tryptase/try+ and chymase/chy + phenotypic markers and toluidine blue stained intact/degranulated MC counts/mm 2 were evaluated. Try + /chy + MCs and ANXA1 were identified by streptavidin-biotin-peroxidase immunostaining and density was reported. In leprosy, degranulated MCs outnumbered intact ones regardless of the leprosy form (from tuberculoid/TT to lepromatous/LL), leprosy reactions (reactional/reaction-free) and type of reaction (T1R/T2R). Compared to other dermatoses, leprosy skin lesions showed lower numbers of degranulated and intact MCs. Try + MCs outnumbered chy + in leprosy lesions (reaction-free/reactional, particularly in T2R), but not in other dermatoses. Compared to other dermatoses, ANXA1 expression, which is also expressed in mast cells, was higher in the epidermis of leprosy skin lesions, independently of reactional episode. In leprosy, higher MC degranulation and differential expression of try + /chy + subsets independent of leprosy type and reaction suggest that the Mycobacterium leprae infection itself dictates the inflammatory MCs activation in skin lesions. Higher expression of ANXA1 in leprosy suggests its potential anti-inflammatory role to maintain homeostasis preventing tissue and nerve damage. Copyright © 2018 Elsevier Ltd. All rights reserved.

H+ irradiation effect in Co-doped BaFe2As2 single crystals

International Nuclear Information System (INIS)

Nakajima, Y.; Tsuchiya, Y.; Taen, T.; Tamegai, T.; Kitamura, H.; Murakami, T.

2011-01-01

The effect of H + irradiation on the suppression of Tc in Co-doped BaFe 2 As 2 . H + irradiation introduces nonmagnetic scattering centers. Critical Scattering rate is much higher than that expected in s±-pairing scenario. We report the suppression of the critical temperature T c in single crystalline Ba(Fe 1-x Co x ) 2 As 2 at under-, optimal-, and over-doping levels by 3 MeV proton irradiation. T c decreases and residual resistivity increases monotonically with increasing the dose. The low-temperature resistivity does not show the upturn in contrast with the α-particle irradiated NdFeAs(O,F), which suggests that proton irradiation introduces nonmagnetic scattering centers. Critical scattering rates for all samples obtained by three different ways are much higher than that expected in s±-pairing scenario based on inter-band scattering due to antiferro-magnetic spin fluctuations.

Fabrication and post-irradiation examination of a zircaloy-2 clad UO2-1.5 wt% PuO2 fuel pin irradiated in PWL, CIRUS

International Nuclear Information System (INIS)

Sah, D.N.; Sahoo, K.C.; Chatterjee, S.; Majumdar, S.; Kamath, H.S.; Ramachandran, R.; Bahl, J.K.; Purushottam, D.S.C.; Ramakumar, M.S.; Sivaramakrishnan, K.S.; Roy, P.R.

1977-01-01

A zircaloy-2 clad UO 2 -1.5 wt% PuO 2 fuel pin was fabricated at the Radiometallurgy Section of the Bhabha Atomic Research Centre, Bombay, for irradiation in the pressurised water loop in CIRUS. Requisite development work related to powder conditioning, blending, pressing and sintering parameters was carried out to meet the exacting fuel pellet specifications of CANDU fuel. The fuel pin ruptured while being irradiated in the pressurised water loop in CIRUS, after experiencing a low burn-up of 507 MWD/MTM and was subsequently examined at the Radiometallurgy Hot Cells Facility. The results showed that internal clad hydriding led to primary failure of the fuel pin. Subsequent ingress of the coolant water caused excessive swelling of the thermal insulating magnesia pellets located at the ends of the fuel column. The swelling of magnesia pellets caused severe rupturing of the fuel pin at the two ends. The delayed rupturing of the fuel pin at the upper end, caused the fuel column to be displaced downwards by 5.85mm. (author)

Swift heavy ion irradiated SnO_2 thin film sensor for efficient detection of SO_2 gas

International Nuclear Information System (INIS)

Tyagi, Punit; Sharma, Savita; Tomar, Monika; Singh, Fouran; Gupta, Vinay

2016-01-01

Highlights: • Response of Ni"7"+ ion irradiated (100 MeV) SnO_2 film have been performed. • Effect of irradiation on the structural and optical properties of SnO_2 film is studied. • A decrease in operating temperature and increased response is seen after irradiation. - Abstract: Gas sensing response studies of the Ni"7"+ ion irradiated (100 MeV) and non-irradiated SnO_2 thin film sensor prepared under same conditions have been performed towards SO_2 gas (500 ppm). The effect of irradiation on the structural, surface morphological, optical and gas sensing properties of SnO_2 thin film based sensor have been studied. A significant decrease in operating temperature (from 220 °C to 60 °C) and increased sensing response (from 1.3 to 5.0) is observed for the sample after irradiation. The enhanced sensing response obtained for the irradiated SnO_2 thin film based sensor is attributed to the desired modification in the surface morphology and material properties of SnO_2 thin film by Ni"7"+ ions.

Molybdenum-UO2 cerment irradiation at 1145 K

Science.gov (United States)

Mcdonald, G.

1971-01-01

Two molybdenum-UO2 cermet fuel pins were fission heated in a helium-cooled loop at a temperature of 1145 K and to a total burnup of 5.3 % of the U-235. After irradiation the fuel pins were measured to check dimensional stability, punctured at the plenums to determine fission gas release, and examined metallographically to determine the effect of irradiation. Burnup was determined in several sections of the fuel pin. The results of the postirradiation examination indicated: (1) There was no visible change in the fuel pins on irradiation under the above conditions. (2) The maximum swelling of the fuel pins was less than 1%. (3) There was no migration of UO2 and no visible interaction between the molybdenum and the UO2. (4) Approximately 12% of the fission gas formed was released from the cermet cone into the gas plenum.

Thoria-fuel irradiation. Program to irradiate 80% ThO2/20% UO2 ceramic pellets at the Savannah River Plant

International Nuclear Information System (INIS)

Pickett, J.B.

1982-02-01

This report describes the fabrication of proliferation-resistant thorium oxide/uranium oxide ceramic fuel pellets and preparations at the Savannah River Laboratory (SRL) to irradiate those materials. The materials were fabricated in order to study head end process steps (decladding, tritium removal, and dissolution) which would be required for an irradiated proliferation-resistant thorium based fuel. The thorium based materials were also to be studied to determine their ability to withstand average commercial light water reactor (LWR) irradiation conditions. This program was a portion of the Thorium Fuel Cycle Technology (TFCT) Program, and was coordinated by the Oak Ridge National Laboratory (ORNL) under the Consolidated Fuel Reprocessing Program (CFRP). The fuel materials were to be irradiated in a Savannah River Plant (SRP) reactor at conditions simulating the heat ratings and burnup of a commercial LWR. The program was terminated due to a de-emphasis of the TFCT Program, following completion of the fabrication of the fuel and the modified assemblies which were to be used in the SRP reactor. The reactor grade ceramic pellets were fabricated for SRL by Battelle, Pacific Northwest Laboratories. Five fuel types were prepared: 100% UO 2 pellets (control); 80% ThO 2 /20% UO 2 pellets; approximately 80% ThO 2 /20% UO 2 + 0.25 CaO (dissolution aid) pellets; 100% UO 2 hybrid pellets (prepared from sol-gel microspheres); and 100% ThO 2 pellets (control). All of the fuel materials were transferred to SRL from PNL and were stored pending a subsequent reactivation of the TFCT Programs

Irradiation effects on plasma diagnostic components (2)

International Nuclear Information System (INIS)

Nishitani, Takeo; Sugie, Tatsuo

2002-03-01

Irradiation tests on a number of diagnostic components under fission neutrons, gamma-rays and 14 MeV neutrons have been carried out as a part of the ITER technology R and D program. UV range transmission losses of a KU-1 quartz were measured during 14 MeV neutron and 60 Co gamma-ray irradiation. Significant transmission losses were observed in the wavelength of 200-300 nm. Five kinds of ITER round robin fibers were irradiated in JMTR and the 60 Co gamma-ray irradiation facility. KS-4V, KU-H2G and F-doped fibers have a rather good radiation hardness, which might be available just outside of the vacuum vessel in ITER. Mica substrate bolometer was irradiated in JMTR up to 0.1 dpa. During the cool down phase of the first cycle all connections went open circuit. The use of gold meanders in the bolometer might be problematic in ITER. The magnetic probes were irradiated in JMTR. Drift of 10 - 40 mVs for 1000s was observed with a digital longterm integrator, however, which might be induced not only by RIEMF but also drift inside the integrator itself. ITER-relevant magnetic coil could be made with MI-cables, whose electric drift for 1000-s integration is less than 0.5 mVs. (author)

Synthesis of a 2-Furylpyrazoline Derivative Using Microwave Irradiation

Directory of Open Access Journals (Sweden)

Suban Syed Shafi

2009-08-01

Full Text Available A simple method for the synthesis of pyrazoline derivative containing furan moiety was developed. Thus, 5-(6-bromo-1,3-benzodioxol-5-yl-3-(2-furyl-1-(3-methyl-phenyl-4,5-dihydro-1H-pyrazole was synthesized using microwave irradiation and it was characterized by NMR, IR, and LCMS.

Microstructural examination of irradiated zircaloy-2 pressure tube material

International Nuclear Information System (INIS)

Srivastava, D.; Tewari, R.; Dey, G.K.; Sah, D.N.; Banerjee, S.

2005-01-01

Irradiation induced microstructural changes in Zr alloys strongly influence the creep, growth and mechanical properties of pressure tube material. Since dimensional changes and mechanical property degradation can limit the life of pressure tube, it is essential to study and develop an understanding of the microstructure produced by neutron irradiation, by examining samples taken from the irradiated components. In the present work, an effort has been made to examine, microstructure of the Zircaloy-2 pressure tube material irradiated in the Indian Pressurized Heavy Water Reactor (PHWR). The present work is a first step towards a comprehensive program of characterization of microstructure of reactor materials after irradiation to different fluence levels in power reactors. In this study, samples from a Zircaloy-2 pressure tube, which had been in operation in the high flux region of Rajasthan Atomic Power Station Unit 1, for a period for 6.77 effective full power years (EFPYs), have been prepared and examined. The samples selected from the tube are expected to have a cumulative radiation damage of about 3 dpa. Samples prepared from the off cuts of RAPS-1 pressure tubes were also studied for examining the unirradiated microstructure of the material. The samples were examined in a 200kV JEOL 2000 FX microscope. This paper presents the distinct features observed in irradiated sample and a comprehensive comparison of the microstructures of the unirradiated and irradiated material. The effect of annealing on the annihilation of the defects generated during irradiation has been also studied. The bright field micrographs revealed that microstructure of the irradiated samples was different in many respects from the microstructure of the unirradiated samples. The presence of defect structure in the form of loops etc could be seen in the irradiated sample. These loops were mostly c-type loops lying in the basal plane. The dissolution and redistribution of the precipitates were

Proteomic profile in glomeruli of type-2 diabetic KKAy mice using 2-dimensional differential gel electrophoresis.

Science.gov (United States)

Liu, Xiaodan; Yang, Gang; Fan, Qiuling; Wang, Lining

2014-12-17

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease. To search for glomerular proteins associated with early-stage DN, glomeruli of spontaneous type 2 diabetic KKAy mice were analyzed by 2-dimensional differential gel electrophoresis (2D-DIGE). Glomeruli of 20-week spontaneous type 2 diabetic KKAy mice and age-matched C57BL/6 mice were isolated by kidney perfusion with magnetic beads. Proteomic profiles of glomeruli were investigated by using 2D-DIGE and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Western blot analysis was used to confirm the results of proteomics. Immunohistochemical and semi-quantitative analysis were used to confirm the differential expression of prohibitin and annexin A2 in glomeruli. We identified 19 differentially expressed proteins - 17 proteins were significantly up-regulated and 2 proteins were significantly down-regulated in glomeruli of diabetic KKAy mice. Among them, prohibitin and annexin A2 were up-regulated and Western blot analysis validated the same result in proteomics. Immunohistochemical analysis also revealed up-regulation of prohibitin and annexin A2 in glomeruli of KKAy mice. Our findings suggest that prohibitin and annexin A2 may be associated with early-stage DN. Further functional research might help to reveal the pathogenesis of DN.

Modification of WS2 nanosheets with controllable layers via oxygen ion irradiation

Science.gov (United States)

Song, Honglian; Yu, Xiaofei; Chen, Ming; Qiao, Mei; Wang, Tiejun; Zhang, Jing; Liu, Yong; Liu, Peng; Wang, Xuelin

2018-05-01

As one kind of two-dimensional materials, WS2 nanosheets have drawn much attention with different kinds of research methods. Yet ion irradiation method was barely used for WS2 nanosheets. In this paper, the structure, composition and optical band gap (Eg) of the multilayer WS2 films deposited by chemical vapor deposition (CVD) method on sapphire substrates before and after oxygen ion irradiation with different energy and fluences were studied. Precise tailored layer-structures and a controllable optical band gap of WS2 nanosheets were achieved after oxygen ion irradiation. The results shows higher energy oxygen irradiation changed the shape from triangular shaped grains to irregular rectangle shape but did not change 2H-WS2 phase structure. The intensity of E2g1 (Г) and A1g (Г) modes decreased and have small shifts after oxygen ion irradiation. The peak frequency difference between the E2g1 (Г) and A1g (Г) modes (Δω) decreased after oxygen ion irradiation, and this result indicates the number of layers decreased after oxygen ion irradiation. The Eg decreased with the increase of the energy and the fluence of oxygen ions. The number of layers, thickness and optical band gap changed after ion irradiation with different ion fluences and energies. The results proposed a new strategy for precise control of multilayer nanosheets and demonstrated the high applicability of ion irradiation in super-capacitors, field effect transistors and other applications.

Protection of vanillin derivative VND3207 on genome damage and apoptosis of human lymphoblastoid cells induced by γ-ray irradiation

International Nuclear Information System (INIS)

Huang Rui; Huang Bo; He Xingpeng; Xu Qinzhi; Wang Yu; Zhou Pingkun

2009-01-01

To determine the protective effect of vanillin derivative VND3207 on the genome damage and apoptosis of human lymphoblastoid AHH-1 cells induced by γ-ray irradiation, the techniques of single-cell gel electrophoresis, micronucleus test, Annexin V-FACS assay, and the double-fluorescein staining and fluorescent microscope observation were used. Neutral single-cell gel electrophoresis showed that the initial DNA double-strand breaks caused by 2 Gy 60 Co γ-ray was significantly decreased by VND3207 in the range of 540 μmol/L. This significant phenomenonwas demonstrated by the fact that the comet tail-moment was significantly shortened and the DNA content in the comet tail was reduced when the cells were protected with VND3207, and the radio-protective effect increases along with the increasing of drug concentration. Similarly, the yield of micronucleus was reduced by 540 μmol/L of VND3207 in a concentration-dependency in AHH-1 cells irradiated with 0.5 Gy, 1.0 Gy and 2.0 Gy 60 Co γ-rays. 40 μmol/L VND3207 resulted in 40% reduction in the yield of micronucleus induced by 2.0 Gy. The occurrence of apoptosis enhanced along with the time from 8 h to 48 h post 4 Gy irradiation, and 40 μmol/L of VND3207 significantly decreased the induction of apoptosis. This work has further demonstrated a good protection of VND3207 on γ-ray-induced cell genome damage and apoptosis. (authors)

Fabrication of inert matrices for heterogeneous transmutation. EFTTRA-T2 (RAS 2) irradiation programme

International Nuclear Information System (INIS)

Boshoven, J.G.; Hein, H.; Konings, R.J.M.

1996-07-01

This report describes the fabrication of targets containing inert matrices for the heterogeneous transmutation of plutonium and minor actinides. These targets will be irradiated in the EFTTRA-T2 (RAS-2) irradiation programme. The selection, preparation and characterization of the inert matrices and fabrication and loading of the irradiation capsules are discussed. (orig.)

Crystal plasticity modeling of irradiation growth in Zircaloy-2

Science.gov (United States)

Patra, Anirban; Tomé, Carlos N.; Golubov, Stanislav I.

2017-08-01

A physically based reaction-diffusion model is implemented in the visco-plastic self-consistent (VPSC) crystal plasticity framework to simulate irradiation growth in hcp Zr and its alloys. The reaction-diffusion model accounts for the defects produced by the cascade of displaced atoms, their diffusion to lattice sinks and the contribution to crystallographic strain at the level of single crystals. The VPSC framework accounts for intergranular interactions and irradiation creep, and calculates the strain in the polycrystalline ensemble. A novel scheme is proposed to model the simultaneous evolution of both, number density and radius, of irradiation-induced dislocation loops directly from experimental data of dislocation density evolution during irradiation. This framework is used to predict the irradiation growth behaviour of cold-worked Zircaloy-2 and trends compared to available experimental data. The role of internal stresses in inducing irradiation creep is discussed. Effects of grain size, texture and external stress on the coupled irradiation growth and creep behaviour are also studied and compared with available experimental data.

Irradiation damages in Ti{sub 3}SiC{sub 2}; Dommages d'irradiation dans Ti{sub 3}SiC{sub 2}

Energy Technology Data Exchange (ETDEWEB)

Nappe, J.C.; Grosseau, Ph. [Ecole Nationale Superieure des Mines, Centre SPIN, Lab. PMMC et LPMG UMR CNRS 5148, 42 - Saint-Etienne (France); Guilhot, B. [Ecole Nationale Superieure des Mines, Centre CIS, 42 - Saint-Etienne (France); Audubert, F.; Beauvy, M. [CEA Cadarache, 13 - Saint-Paul-lez-Durance (France). Dept. d' Etudes des Combustibles; Iacconi, Ph.; Benabdesselam, M. [Nice Univ. - Sophia Antipolis, Lab. LPES-CRESA, 06 (France)

2007-07-01

Carbides, by their remarkable properties, are considered as possible materials (fuel cans) in reactor of generation IV. Among those studied, Ti{sub 3}SiC{sub 2} is particularly considered because it joins both the ceramics and metals properties. Nevertheless, its behaviour under irradiation is not known. Characterizations have been carried out on samples irradiated at 75 MeV krypton ions. They have revealed that TiO{sub 2} (formed at the surface of Ti{sub 3}SiC{sub 2}) is pulverized by the irradiation and that the crystal lattice of Ti{sub 3}SiC{sub 2} dilates with c. (O.M.)

Heavy ion irradiation induces autophagy in irradiated C2C12 myoblasts and their bystander cells

International Nuclear Information System (INIS)

Hino, Mizuki; Tajika, Yuki; Hamada, Nobuyuki

2010-01-01

Autophagy is one of the major processes involved in the degradation of intracellular materials. Here, we examined the potential impact of heavy ion irradiation on the induction of autophagy in irradiated C2C12 mouse myoblasts and their non-targeted bystander cells. In irradiated cells, ultrastructural analysis revealed the accumulation of autophagic structures at various stages of autophagy (id est (i.e.) phagophores, autophagosomes and autolysosomes) within 20 min after irradiation. Multivesicular bodies (MVBs) and autolysosomes containing MVBs (amphisomes) were also observed. Heavy ion irradiation increased the staining of microtubule-associated protein 1 light chain 3 and LysoTracker Red (LTR). Such enhanced staining was suppressed by an autophagy inhibitor 3-methyladenine. In addition to irradiated cells, bystander cells were also positive with LTR staining. Altogether, these results suggest that heavy ion irradiation induces autophagy not only in irradiated myoblasts but also in their bystander cells. (author)

Study of gamma irradiation effect on commercial TiO2 photocatalyst

International Nuclear Information System (INIS)

Bello Lamo, M.P.; Williams, P.; Reece, P.; Lumpkin, G.R.; Sheppard, L.R.

2014-01-01

The aim of this work is to understand the effect of gamma irradiation on commercial TiO 2 photocatalyst for water treatment applications. Previous studies concluded that gamma-irradiation is able to modify the electronic properties of TiO 2 based photocatalysts and consequently their photocatalytic performance. However, there are some discrepancies in the literature where on one hand a significant enhancement of the material properties is reported and on the other hand only a weak effect is observed. In this study a surface effect on TiO 2 is confirmed by using low and medium gamma irradiation doses. - Highlights: • Gamma irradiated TiO 2 is investigated for photocatalytic water treatment. • By low gamma doses, no change in surface properties is observed. • However, a surface defect is found for gamma irradiated TiO 2 at higher doses. • XPS measurements showed an increase of hydroxyl groups. • That may cause a variation of its adsorption capacity

Irradiation of novel MTR fuel plates in BR2

International Nuclear Information System (INIS)

Verboomen, B.; Aoust, Th.; Beeckmans De Westmeerbeeck, A.; De Raedt, Ch.

2000-01-01

Since the end of 1999, novel MTR fuel plates with very high-density meat are being irradiated in BR2. The purpose of the irradiation is to investigate the behaviour of these fuel plates under very severe reactor operation conditions. The novel fuel plates are inserted in two standard six-tube BR2 fuel elements in the locations normally occupied by the standard outer fuel plates. The irradiation in BR2 was prepared by carrying out detailed neutron Monte Carlo calculations of the whole BR2 core containing the two experimental fuel elements for various positions in the reactor and for various azimuthal orientations of the fuel elements. Comparing the thus determined fission density levels and azimuthal profiles in the new MTR fuel plates irradiated in the various channels allowed the experimenters to choose the most appropriate BR2 channel and the most appropriate fuel element orientation. (author)

Endogenous annexin A1 counter-regulates bleomycin-induced lung fibrosis

Directory of Open Access Journals (Sweden)

Flower Roderick J

2011-10-01

Full Text Available Abstract Background The balancing functions of pro/anti-inflammatory mediators of the complex innate responses have been investigated in a variety of experimental inflammatory settings. Annexin-A1 (AnxA1 is one mediator of endogenous anti-inflammation, affording regulation of leukocyte trafficking and activation in many contexts, yet its role in lung pathologies has been scarcely investigated, despite being highly expressed in lung cells. Here we have applied the bleomycin lung fibrosis model to AnxA1 null mice over a 21-day time-course, to monitor potential impact of this mediator on the control of the inflammatory and fibrotic phases. Results Analyses in wild-type mice revealed strict spatial and temporal regulation of the Anxa1 gene, e.g. up-regulation in epithelial cells and infiltrated granulocytes at day 7, followed by augmented protein levels in alveolar macrophages by day 21. Absence of AnxA1 caused increases in: i the degree of inflammation at day 7; and ii indexes of fibrosis (assessed by deposition of hydroxyproline in the lung at day 7 and 21. These alterations in AnxA1 null mice were paralleled by augmented TGF-β1, IFN-γ and TNF-α generation compared to wild-type mice. Finally, treatment of wild type animals with an AnxA1 peptido-mimetic, given prophylactically (from day 0 to 21 or therapeutically (from day 14 onward, ameliorated both signs of inflammation and fibrosis. Conclusion Collectively these data reveal a pathophysiological relevance for endogenous AnxA1 in lung inflammation and, more importantly, fibrosis, and may open new insights for the pharmacological treatment of lung fibrosis.

Role of annexin gene and its regulation during zebrafish caudal fin regeneration.

Science.gov (United States)

Saxena, Sandeep; Purushothaman, Sruthi; Meghah, Vuppalapaty; Bhatti, Bhawna; Poruri, Akhila; Meena Lakshmi, Mula G; Sarath Babu, Nukala; Narasimha Murthy, Ch Lakshmi; Mandal, Komal K; Kumar, Arvind; Idris, Mohammed M

2016-05-01

The molecular mechanism of epimorphic regeneration is elusive due to its complexity and limitation in mammals. Epigenetic regulatory mechanisms play a crucial role in development and regeneration. This investigation attempted to reveal the role of epigenetic regulatory mechanisms, such as histone H3 and H4 lysine acetylation and methylation during zebrafish caudal fin regeneration. It was intriguing to observe that H3K9,14 acetylation, H4K20 trimethylation, H3K4 trimethylation and H3K9 dimethylation along with their respective regulatory genes, such as GCN5, SETd8b, SETD7/9, and SUV39h1, were differentially regulated in the regenerating fin at various time points of post-amputation. Annexin genes have been associated with regeneration; this study reveals the significant up-regulation of ANXA2a and ANXA2b transcripts and their protein products during the regeneration process. Chromatin immunoprecipitation and PCR analysis of the regulatory regions of the ANXA2a and ANXA2b genes demonstrated the ability to repress two histone methylations, H3K27me3 and H4K20me3, in transcriptional regulation during regeneration. It is hypothesized that this novel insight into the diverse epigenetic mechanisms that play a critical role during the regeneration process may help to strategize the translational efforts, in addition to identifying the molecules involved in vertebrate regeneration. © 2016 by the Wound Healing Society.

Silicon/HfO2 interface: Effects of proton irradiation

International Nuclear Information System (INIS)

Maurya, Savita; Radhakrishna, M.

2015-01-01

Substrate oxide interfaces are of paramount importance in deciding the quality of the semiconductor devices. In this work we have studied how 200 keV proton irradiation affects the interface of a 13 nm thick, atomic layer deposited hafnium dioxide on silicon substrate. Pre- and post-irradiation electrical measurements are used to quantify the effect of proton irradiation for varying electrode geometries. Proton irradiation introduces positive charge in the oxide and at the interface of Si/HfO 2 interface. The gate current is not very much affected under positive injection since the induced positive charge is compensated by the injected electrons. Current voltage characteristics under negative bias get affected by the proton irradiation

Hydrogen irradiation on TiO{sub 2} nano-thin films

Energy Technology Data Exchange (ETDEWEB)

Heidari, Sh.; Mohammadizadeh, M.R. [University of Tehran, Superconductivity Research Laboratory (SRL), Department of Physics, Tehran (Iran, Islamic Republic of); Mahjour-Shafiei, M. [University of Tehran, Department of Physics, Tehran (Iran, Islamic Republic of); Larijani, M.M.; Malek, M. [Science and Technology Research Institute, Agricultural, Medical and Industrial Research School, Karaj (Iran, Islamic Republic of)

2015-10-15

Titanium dioxide thin films were coated on soda-lime glass substrates using spray pyrolysis method with a thickness of 152 ± 10 nm. The films were irradiated with hydrogen ions at room temperature at various beam energies and fluences. Optimized incident beam energy and beam fluence were obtained to improve photocatalytic and hydrophilicity properties of TiO{sub 2} thin films by narrowing the band gap. Samples were characterized by scanning electron microscopy to study the surface morphology and by UV-Vis absorption spectroscopy to measure the band gap. The optical band gap of H-doped anatase TiO{sub 2} thin films irradiated with hydrogen beam with energies of 2 and 4 keV and a fluence of 10{sup 15} ions/cm{sup 2} was narrowed from 3.34 eV (before irradiation) to 3.04 and 2.92 eV (after irradiation), respectively. The irradiated sample with energy of 4 keV with a fluence of 10{sup 15} ions/cm{sup 2} has the best improvement. This is attributed to the contraction of the band gap and to the increase in surface active site. Furthermore, it was observed that photocatalytic and hydrophilicity properties of this sample were improved, as well. (orig.)

Irradiation effects on Fe distributions in zircaloy-2 and Zr-2.5Nb

International Nuclear Information System (INIS)

Zou, H.; Hood, G.M.; Roy, J.A.

1995-03-01

Irradiation of large-grained Zr-2.5Nb (ZN) and Zircaloy-2 (Zy) with 1.5 MeV Ar ions to a fluence of ∼ 10 20 /m 2 (≡ 10 dpa) at 50, 300 and 420 deg C leads to enhanced α-phase Fe levels of 250-1500 ppma, compared to equivalent non-irradiated state values of ∼ 70 ppma. In ZN the β-phase Fe levels fell from about 6000 to 3500 ppma: this result accords, qualitatively, with the loss of Fe from the β-phase following in-service neutron irradiation. Measurements on Zy showed that the Fe concentrations were higher near the specimen surfaces. Limited data for Ni distributions in Zy show similar (to Fe) behaviour. (author). 18 refs., 2 tabs

Transfer of phagocytosed particles to the parasitophorous vacuole of Leishmania mexicana is a transient phenomenon preceding the acquisition of annexin I by the phagosome.

Science.gov (United States)

Collins, H L; Schaible, U E; Ernst, J D; Russell, D G

1997-01-01

The eukaryotic intracellular pathogen Leishmania mexicana resides inside macrophages contained within a membrane bound parasitophorous vacuole which, as it matures, acquires the characteristics of a late endosomal compartment. This study reports the selectivity of fusion of this compartment with other particle containing vacuoles. Phagosomes containing zymosan or live Listeria monocytogenes rapidly fused with L. mexicana parasitophorous vacuoles, while those containing latex beads or heat killed L. monocytogenes failed to do so. Fusigenicity of phagosomes was not primarily dependent on the receptor utilized for ingestion, as opsonization with defined ligands could not overcome the exclusion of either latex beads or heat killed organisms. However modulation of intracellular pH by pharmacological agents such as chloroquine and ammonium chloride increased delivery of live Listeria and also induced transfer of previously excluded particles. The absence of fusion correlated with the acquisition of annexin I, a putative lysosomal targeting, molecule, on the phagosome membrane. We propose that the acquisition of cellular membrane constituents such as annexin I during phagosome maturation can ultimately direct the fusion pathway of the vesicles formed and have described a model system to further document changes in vesicle fusigenicity within cells.

Radiation enhanced reactivation of irradiated human adenovirus type 2 in human cells

International Nuclear Information System (INIS)

Jeeves, W.P.

1981-04-01

Radiation-enhanced reactivation (ER) of a radiation-damaged mammalian virus is the term given to the observation that the survival of irradiated virus can be enhanced by irradiation of an appropriate host cell prior to infection. In this work, both UV-enhanced reactivation (UVER) and gamma-ray-enhanced reactivation (γRER) of irradiated human adenovirus type 2 (AD 2) were studied in a variety of normal and DNA repair-deficient human fibroblast host cell strains. In order to examine the lesion specificity of ER in human cells, experiments were performed using UV-irradiated and γ-irradiated virus. The investigation was carried out using a sensitive technique of indirect immunofluorescence, according to which irradiated and unirradiated cell cultures were infected with irradiated or unirradiated AD 2 and were subsequently examined for the presence of viral structural antigens ('V' Ag) at a fixed time after infection

Specific heat of MgB_2 after irradiation

OpenAIRE

Wang, Yuxing; Bouquet, Frederic; Sheikin, Ilya; Toulemonde, Pierre; Revaz, Bernard; Eisterer, Michael; Weber, Harald W.; Hinderer, Joerg; Junod, Alain

2002-01-01

We studied the effect of disorder on the superconducting properties of polycrystalline MgB_2 by specific-heat measurements. In the pristine state, these measurements give a bulk confirmation of the presence of two superconducting gaps with 2 Delta 0 / k_B T_c = 1.3 and 3.9 with nearly equal weights. The scattering introduced by irradiation suppresses T_c and tends to average the two gaps although less than predicted by theory. We also found that by a suitable irradiation process by fast neutr...

Response of mesenchymal stem cells in mice to 3.5 Gy X-ray irradiation

International Nuclear Information System (INIS)

Su Wenxia; Liu Huimin; Chen Yonghong; Zeng Wen; Liu Wenli; Sun Hanying

2011-01-01

Objective: To investigate the response of mesenchymal stem cells in mice to medium-dose X-ray irradiation in vitro. Methods: The mouse mesenchymal stem cell line C3H10T1/2 was submitted to 3.5 Gy X-ray irradiation. Hoechst33258 staining of adherent cells and Annexin V-FITC staining and flow cytometry analysis of suspension cells were performed respectively to assess cellular apoptosis at 3, 6, 12, 24, 48, 72 h and 1 week after irradiation. SA-β-gal staining was performed to analyze the cellular senescence at 24, 48, 72 h and 1 week after irradiation. The mRNA level of both Fas with its ligand FasL and p53 with its downstream target p21 WAF1 were measured by Real-Time PCR analysis. The expression of Fas protein was determined by immunofluorescence staining. Results: An increased apoptosis was observed at 3 h after irradiation with apoptosis rate 11.72% ± 1.61% (t=9.01, P<0.01), the apoptosis rate reached the peak level at 12 h 20.52% ± 1.96% (t=16.27, P<0.01), and then declined progressively to normal level at 48 h 4.93% ±0.46% (t=2.26, P>0.05). The SA-β-gal positive rate of post-radiation cells at 72 h was 53.33% ± 5.62%, significantly higher than that of normal control 3.24% ± 0.39% (t=17.77, P<0.01). The level of Fas, FasL mRNA was found to be elevated 3 h after irradiation with a peak at 12 h, and no differences were found l week later. The level of Fas protein was observed to reach the peak at 12 h after irradiation. The occurrence of peak level of Fas/FasL mRNA and protein was consistent with that of apoptosis of C3H10T1/2 cell. A transient up-regulation of p53, p21 WAF1 mRNA expression was found at 12 h after irradiation followed by a significant increase later at 72 h after irradiation. The occurrence of the two peaks of p53, p21 WAF1 mRNA expression were coincident with that of cellular apoptosis and senescence, respectively. The levels of p53, p21 WAF1 mRNA in senescence group were significantly higher than those of apoptosis group (t=17.85, 13

Targeting single-walled carbon nanotubes for the treatment of breast cancer using photothermal therapy

Science.gov (United States)

Neves, Luis Filipe Ferreira

.5 to 5.0 nm. Confocal microscopy was used to prove the binding of the conjugates to human endothelial cells grown in vitro. Proliferating endothelial cells were used to determine the optimal near-infrared (NIR) laser irradiation settings (energy density = 200 J/cm2), which would not induce cell cytotoxicity from the laser itself. A 2 hour incubation with the conjugate followed by a washing step and NIR irradiation (wavelength = 980 nm, power = 1 W/cm2, time = 200 seconds) was enough to induce significant cell death (≈55 %), without significant damage to the control samples. Administration of the same conjugates i.v. in Balb/cJ female mice resulted in detectable accumulation of the SWNTs in the tumor tissues, with minimal retention in the kidneys 24 hours post-administration. A dosage of 0.82 mg/kg of SWNTs administered i.v. and followed one day later by a NIR irradiation (wavelength = 980 nm, power = 1 W/cm2, time = 175 seconds) led to complete disappearance of implanted 4T1 mouse mammary tumors for the majority of the animals from the treatment groups, within a few days. The combination of the photothermal therapy with a low dosage (50 mg/kg) of the immunoadjuvant cyclophosphamide, given 2 days before NIR irradiation, was also evaluated; this resulted in increased survival. Histological findings revealed the complete obliteration of the tumors treated from the original site, with complete regeneration of the skin epithelial layer and absence of cancer cells. In conclusion, this research was successful in demonstrating that SWNTs could be targeted to the tumor vasculature in vivo and then could be heated by NIR irradiation to completely kill mouse mammary tumors implanted in immune-competent mice. There is evidence that the co-administration of the immunostimulant cyclophosphamide caused increased survival of the mice. It is recommended that future work be directed to exploring methods to increase the concentration of the SWNT-annexin V conjugate in the tumor and to

ATM phosphorylation in HepG2 cells following continuous low dose-rate irradiation

International Nuclear Information System (INIS)

Mei Quelin; Du Duanming; Chen Zaizhong; Liu Pengcheng; Yang Jianyong; Li Yanhao

2008-01-01

Objective: To investigate the change of ATM phosphorylation in HepG2 cells following a continuous low dose-rate irradiation. Methods: Cells were persistently exposed to low dose-rate (8.28 cGy/h) irradiation. Indirect immunofluorescence and Western blot were used to detect the expression of ATM phosphorylated proteins. Colony forming assay was used to observe the effect of a low dose-rate irradiation on HepG2 cell survival. Results: After 30 min of low dose-rate irradiation, the phosphorylation of ATM occurred. After 6 h persistent irradiation, the expression of ATM phosphorylated protein reached the peak value, then gradually decreased. After ATM phosphorylation was inhibited with Wortmannin, the surviving fraction of HepG2 cells was lower than that of the irradiation alone group at each time point (P<0.05). Conclusions: Continuous low dose-rate irradiation attenuated ATM phosphorylation, suggesting that continuous low dose-rate irradiation has a potential effect for increasing the radiosensitivity of HepG2 cells. (authors)

TEM examination of irradiated zircaloy-2 pressure tube material

International Nuclear Information System (INIS)

Srivastava, D.; Tewari, R.; Dey, G.K.; Sharma, B.P.; Sah, D.N.; Banerjee, Suparna; Sahoo, K.C.

2005-09-01

In the present work, microstructure of the zircaloy-2 pressure tube material irradiated in the Indian Pressurized Heavy Water RAPP-1. Reactor (PHWR) has been examined for the first time using transmission electron microscope (TEM). The samples were obtained from a zircaloy-2 pressure tube, which had been in operation in the high flux region of Rajasthan Atomic Power Station Unit -1, for a period for 6.77 effective full power years (EFPYs) and expected to have a cumulative radiation damage of about 3 dpa. In this study irradiated microstructure has been characterized and compared it with the microstructure of the unirradiated pressure tube samples. The effect of irradiation on the hydriding behaviour is also studied. (author)

Proteomic Identification of an Upregulated Isoform of Annexin A3 in the Spinal Cords of Rats in a Neuropathic Pain Model

Directory of Open Access Journals (Sweden)

Wangyuan Zou

2017-09-01

Full Text Available Neuropathic pain (NP is induced by nerve damage or a disturbance in the peripheral or central nervous systems. Nerve damage causes the activation of sensitizing mechanisms in the peripheral and central nervous systems, which induces transcriptional and post-transcriptional alterations in sensory nerves. However, the underlying mechanisms of NP remain elusive. In the study, Two-dimensional gel electrophoresis (2DGE-based comparative proteomics identified 38 differential gel spots, and 15 differentially expressed proteins (DEPs between the sham and the chronic constriction injury (CCI-induced neuropathic pain rats. Of them, Annexin A3 (ANXA3 was significantly increased after CCI with Western blot analysis and immunofluorescence imaging. A lentivirus delivering ANXA3 shRNA (LV-shANXA3 was administered intrathecally to determine the analgesic effects of ANXA3 on allodynia and hyperalgesia in a CCI-induced neuropathic pain model in rats. Further study showed that LV-shANXA3 reversed the upregulation of ANXA3, alleviated CCI-induced mechanical allodynia and thermal hyperalgesia. The study indicated that ANXA3 may play an important role in neuropathic pain.

Food irradiation newsletter. Vol. 15, no. 2

International Nuclear Information System (INIS)

1991-10-01

This newsletter contains brief summaries of three coordinated research meetings held in 1991: irradiation in combination with other processes for improving food quality; application of irradiation technique for food processing in Africa; and food irradiation programme for Middle East and European countries. The first Workshop on Public Information on Food Irradiation is summarized, and a Coordinated Research Programme on Irradiation as a Quarantine Treatment of Mites, Nematodes and Insects other than Fruit Fly is announced. This issue also contains a report on the status of food irradiation in China, and a supplement lists clearances of irradiated foods. Tabs

Neutron irradiation of seeds 2

Energy Technology Data Exchange (ETDEWEB)

1968-10-01

The irradiation of seeds with the fast neutron of research reactors has been hampered by difficulties in accurately measuring dose and in obtaining repeatable and comparable results. Co-ordinated research under an international program organized by the FAO and IAEA has already resulted in significant improvements in methods of exposing seeds in research reactors and in obtaining accurate dosimetry. This has been accomplished by the development of a standard reactor facility for the neutron irradiation of seeds and standard methods for determining fast-neutron dose and the biological response after irradiation. In this program various divisions of the IAEA and the Joint FAO/IAEA Division co-operate with a number of research institutes and reactor centres throughout the world. Results of the preliminary experiments were reported in Technical Reports Series No. 76, ''Neutron Irradiation of Seeds''. This volume contains the proceedings of a meeting of co-operators in the FAO/IAEA Neutron Seed Irradiation Program and other active scientists in this field. The meeting was held in Vienna from 11 to 15 December 1967. Refs, figs and tabs.

Neutron irradiation of seeds 2

International Nuclear Information System (INIS)

1968-01-01

The irradiation of seeds with the fast neutron of research reactors has been hampered by difficulties in accurately measuring dose and in obtaining repeatable and comparable results. Co-ordinated research under an international program organized by the FAO and IAEA has already resulted in significant improvements in methods of exposing seeds in research reactors and in obtaining accurate dosimetry. This has been accomplished by the development of a standard reactor facility for the neutron irradiation of seeds and standard methods for determining fast-neutron dose and the biological response after irradiation. In this program various divisions of the IAEA and the Joint FAO/IAEA Division co-operate with a number of research institutes and reactor centres throughout the world. Results of the preliminary experiments were reported in Technical Reports Series No. 76, ''Neutron Irradiation of Seeds''. This volume contains the proceedings of a meeting of co-operators in the FAO/IAEA Neutron Seed Irradiation Program and other active scientists in this field. The meeting was held in Vienna from 11 to 15 December 1967. Refs, figs and tabs

Brittle-fracture potential of irradiated Zircaloy-2 pressure tubes

Science.gov (United States)

Huang, F. H.

1993-12-01

Neutron irradiation can degrade the fracture toughness of Zircaloy-2 and may cause highly irradiated reactor components of this material to fail in a brittle manner. The effects of radiation embrittlement on the structural integrity of N Reactor pressure tubes are studied by performing KIc and JIc fracture toughness testing on samples cut from the Zircaloy-2 tubes periodically removed from the reactor. A fluence of 6 × 10 25n/ m2 ( E > 1 MeV) reduced the fracture toughness of the material by 40 to 50%. The fracture toughness values appear to saturate at 260°C with fluences above 3 × 10 25n/ m2 ( E > 1 MeV), but continue to decline with increasing fluence at temperatures below 177°C. Present and previous results obtained from irradiated pressure tubes indicate that the brittle-fracture potential of Zircaloy-2 increases with decreasing temperature and increasing fluence. Fractographic examinations of the fracture surfaces of irradiated samples reveal that circumferential hydride formation significantly influenced fracture morphology by providing sites for easy crack nucleation and leaving deep cracks. However, the deep cracks created at the hydride platelets in specimens containing less than 220 ppm hydrogen are not believed to be the major cause of degradation in postirradiation fracture toughness.

Specific heat of MgB{sub 2} after irradiation

Energy Technology Data Exchange (ETDEWEB)

Wang Yuxing [Universite de Geneve, Departement de physique de la matiere condensee, 24 quai Ernest-Ansermet, CH-1211 Geneva (Switzerland); Bouquet, Frederic [Universite de Geneve, Departement de physique de la matiere condensee, 24 quai Ernest-Ansermet, CH-1211 Geneva (Switzerland); Sheikin, Ilya [Universite de Geneve, Departement de physique de la matiere condensee, 24 quai Ernest-Ansermet, CH-1211 Geneva (Switzerland); Toulemonde, Pierre [Universite de Geneve, Departement de physique de la matiere condensee, 24 quai Ernest-Ansermet, CH-1211 Geneva (Switzerland); Revaz, Bernard [Universite de Geneve, Departement de physique de la matiere condensee, 24 quai Ernest-Ansermet, CH-1211 Geneva (Switzerland); Eisterer, Michael [Atominstitut der Oesterreichischen Universitaeten, A-1020 Vienna (Austria); Weber, Harald W [Atominstitut der Oesterreichischen Universitaeten, A-1020 Vienna (Austria); Hinderer, Joerg [GHMFL, Max-Planck Institute Grenoble, BP 166, F-38042, Grenoble (France); Junod, Alain [Universite de Geneve, Departement de physique de la matiere condensee, 24 quai Ernest-Ansermet, CH-1211 Geneva (Switzerland)

2003-02-19

We studied the effect of disorder on the superconducting properties of polycrystalline MgB{sub 2} by specific-heat measurements. In the pristine state, these measurements give a bulk confirmation of the presence of two superconducting gaps with 2{delta}{sub 0}/k{sub B}T{sub c}=1.3 and 3.9 with nearly equal weights. The scattering introduced by irradiation suppresses T{sub c} and tends to average the two gaps although less than predicted by theory. We also found that by a suitable irradiation process by fast neutrons, a substantial bulk increase of dH{sub c2}/dT at T{sub c} can be obtained without sacrificing more than a few degrees in T{sub c}. The upper critical field of the sample after irradiation exceeds 28 T at T{yields}0.

Shallow irradiation of Citrus Unshiu by cathod ray, 2

International Nuclear Information System (INIS)

Takano, Hiroyuki; Kawashima, Koji; Umeda, Keiji

1978-01-01

The effect of 150 Krad cathode ray irradiation on the shelf life and quality of ''Citrus Unshiu'' was investigated. Citrus Unshiu (Japanese mandarin orange ''Satsuma'') were kept at 5 0 C for 2 months without pretreatment and irradiated. Both irradiated and non-irradiated samples were stored in the special storage boxes in which temperature, humidity and sterile air circulation were controlled. After 44 days, the percentage of spoiled oranges in irradiated and non-irradiated samples stored at 8 0 C were 57.5% and 64% respectively, on the other hand when stored at 3 0 C the percentage were 26% and 51% respectively. Rate of spoilage was significantly lower in the irradiated samples than non-irradiated ones. Irradiated effect on the shelf life extension was more conspicuous when the storage temperature was kept at 3 0 C. By the sensory examination, any difference for taste and flavor between irradiated and non-irradiated samples was not detected. The taste and flavor of the oranges stored at 8 0 C changed worse after long time storage but when stored at 3 0 C, such tendency was not observed. Undesirable odor and flavor were not detected by the panel with the irradiated samples in this experiment. The results showed that shelf life of the ''Citrus Unshiu'' could be extended by the combination of irradiation with 150 Krad cathode ray and storage at 3 0 C. (auth.)

Irradiation-induced doping of Bismuth Telluride Bi2Te3

International Nuclear Information System (INIS)

Rischau, Carl Willem

2014-01-01

Bismuth Telluride Bi 2 Te 3 has attracted enormous attention because of its thermoelectric and topological insulator properties. Regarding its bulk band structure Bi 2 Te 3 is a band insulator with an energy gap of around 150-170 meV. However, the native anti-site defects that are present in real samples always dope this band insulator and shift the chemical potential into the valence or conduction band. In this PhD, the Fermi surface of as-grown and electron irradiated p-type Bi 2 Te 3 single crystals has been investigated extensively using electrical transport experiments. For moderate hole concentrations (p ∼< 5 x 10 18 cm -3 ), it is confirmed that electrical transport can be explained by a six-valley model and the presence of strong Zeeman-splitting. At high doping levels (p≅5 x 10 18 cm -3 ), the hole concentrations determined from Hall and Shubnikov-de Haas (SdH) effect differ significantly which is attributed to an impurity/defect band introduced by the anti-site defects. In this work, we show that it is possible to dope p-type Bi 2 Te 3 in a very controlled manner using electron-irradiation by performing detailed in- and ex-situ electrical transport studies on samples irradiated at room and at low temperatures with 2.5 MeV electrons. These studies show that the defects induced at both irradiation temperatures act as electron donors and can thus be used to convert the conduction from p- to n-type. The point of optimal compensation is accompanied by an increase of the low-temperature resistivity by several orders of magnitude. Irradiation at room temperature showed that both the p-type samples obtained after irradiation to intermediate doses as well as the samples in which the conduction has been converted to n-type by irradiation, still have a well defined Fermi surface as evidenced by SdH oscillations. By studying the Hall coefficient in-situ during low temperature electron irradiation, the coexistence of electron- and hole-type carriers was evidenced

Irradiation behaviour of UO2/Mo porous cermets for thermionic converters

International Nuclear Information System (INIS)

Stora, J.P.; Kauffmann, Y.

1975-01-01

Two types of UO 2 Mo porous cernets have been fabricated and irradiated in a Cythere irradiation device. The first cermet is constituted by little bits of dense fuel in which the two constituants are finely dispersed. The whole open porosity is located between the granules. This type of cermet is called breche (33.4vol%UO 2 , 51vol%Mo, 14.8vol%porosity). At the end of the irradiation the burn up was 19000MWd/t(U) and neither swelling of the cermet nor deformation of the can were noted. On the contrary, a shrinkage of the emitter was observed attributed to a fuel densification under irradiation. The second type of cermet is called macrogranule (36vol%UO 2 , 49vol%Mo 15vol%porosity). UO 2 granules of 0.07cm mean diameter are dispersed in the molybdenum matrix. The porosity is regularly distributed all around the UO 2 kernels. The post irradiation metrology shows that the emitter is fairly stable. Only a slight ovalisation of about 0.5% was noted, but the granules of UO 2 were redistributed inside the molybdenum matrix, overlapping the metallic cavity by a condensation-evaporation process. The matrix has crept into the central void and consequently the volume has grown and the whole porosity has increased from about 15% to about 23%. This creeping is due to the fission gas pressure in the molybdenum cavities after 3000 hours of irradiation. In conclusion two types of cermets have shown good behaviour under irradiation and should allow lifetimes of several thousand hours of operation for thermionic fuel elements [fr

Bending force constant of gamma-ray irradiated NaNO2

International Nuclear Information System (INIS)

Kwun, S.I.; Allavena, M.

1976-01-01

The origin of the new peak appearing near the ν 2 i.r. absorption band of the NO 2 - group in γ-ray irradiated NaNO 2 ferroelectric crystal is explained by using a model which assumes that some of the Na + ions are displaced from their original sites after irradiation, perturbing the vibrational motion of NO 2 - . In this framework, the bending force constant of the perturbed NO 2 - group is calculated using a modified version of the CNDO/2 method, which can take into account the environmental effects on the local crystal site considered. The values of the bending force constant of virginal and irradiated NaNO 2 obtained are 1.19 md/A and 1.27 md/A respectively. The vibrational bending mode of the perturbed NO 2 - groups seems responsible for the additional i.r. absorption band observed experimentally at 835 cm -1 . (author)

Training manual on food irradiation technology and techniques. 2. ed.

International Nuclear Information System (INIS)

1982-01-01

The objective of the revised Training Manual is to help scientists to acquire the necessary knowledge needed for performing proper research and development work in the field of food irradiation. The Manual presents an up-to-date picture of the current state of food irradiation and reflects the important advances made in the technology of food irradiation, in the radiation chemistry of foods, in the microbiology of irradiated foods, in wholesomeness and standardization. It contains the following chapters: (1) Radionuclides and radiation; (2) Radiation detection and measurement; (3) Radiation protection; (4) Radiation chemistry; (5) Effects of radiation on living organisms; (6) Preservation of foods; (7) Radiation preservation of foods; (8) Packaging; (9) Combination processes; (10) Limitations of food irradiation; (11) Wholesomeness of irradiated foods; (12) Government regulation of irradiated foods; (13) Food irradiation facilities; (14) Commercial aspects of food irradiation; (15) Literature sources. The practical part of the Manual contains a revised and expanded series of detailed laboratory exercises in the use of ionizing radiation for food processing

Investigation of microstructure and mechanical properties of proton irradiated Zircaloy 2

Energy Technology Data Exchange (ETDEWEB)

Sarkar, Apu, E-mail: asarkar@barc.gov.in [Mechanical Metallurgy Division, Bhabha Atomic Reserch Centre, Mumbai, 400 085 (India); Kumar, Ajay [Nuclear Physics Division, Bhabha Atomic Reserch Centre, Mumbai, 400 085 (India); Mukherjee, S.; Sharma, S.K.; Dutta, D.; Pujari, P.K. [Radiochemistry Division, Bhabha Atomic Research Centre, Mumbai, 400 085 (India); Agarwal, A.; Gupta, S.K.; Singh, P. [Ion Accelerator Development Division, Bhabha Atomic Research Centre, Mumbai, 400 085 (India); Chakravartty, J.K. [Mechanical Metallurgy Division, Bhabha Atomic Reserch Centre, Mumbai, 400 085 (India)

2016-10-15

Samples of Zircaloy 2 have been irradiated with 4 MeV protons to two different doses. Microstructures of the unirradiated and irradiated samples have been characterized by Electron Back Scatter Diffraction (EBSD), X-ray diffraction line profile analysis (XRDLPA), Positron Annihilation Lifetime Spectroscopy (PALS) and Coincident Doppler Broadening (CDB) Spectroscopy. Tensile tests and micro hardness measurements have been carried out at room temperature to assess the changes in mechanical properties of Zircaloy 2 due to proton irradiation. The correlation of dislocation density, grain size and yield stress of the irradiated samples indicated that an increase in dislocation density due to irradiation is responsible for the change in mechanical behavior of irradiated Zircaloy.

Irradiation-induced amorphization of Cd2Nb2O7 pyrochlore

International Nuclear Information System (INIS)

Meldrum, A.; White, C. W.; Keppens, V.; Boatner, L. A.; Ewing, R. C.

2001-01-01

Several investigations have recently been undertaken in order to achieve a more complete understanding of the radiation-damage mechanisms in A 2 B 2 O 7 pyrochlore-structure compounds. The present work represents the first systematic study of the irradiation-induced amorphization of a pyrochlore with A- and B-site cation valences of +2 and +5, respectively. Relatively large single crystals of Cd 2 Nb 2 O 7 were grown for these experiments. In situ ion-irradiation experiments were carried out in a transmission electron microscope in conjunction with ex situ Rutherford backscattering measurements of ion-irradiated Cd 2 Nb 2 O 7 single crystals. Cd 2 Nb 2 O 7 can be amorphized in situ by Ne or Xe ions at temperatures up to 480 and 620 K, respectively. At room temperature, the amorphization fluence was 36 times higher for 280 keV Ne + than for 1200 keV Xe 2+ , corresponding to a displacement dose that was higher by a factor of 3. Disordering of Cd and Nb over the available cation sites occurs at intermediate ion doses prior to amorphization. The temperature dependence of the amorphization dose is modeled, and the results are compared to those of a previous model. The bulk-sample Rutherford backscattering spectroscopy (RBS) results were generally consistent with the in situ TEM measurements. Effects of crystallographic orientation and ion charge state had relatively little effect on the damage accumulation in bulk crystals. The RBS data are consistent with a defect-accumulation, cascade-overlap model of amorphization of Cd 2 Nb 2 O 7 , as are the in situ TEM observations

The Assessment of Parameters Affecting the Quality of Cord Blood by the Appliance of the Annexin V Staining Method and Correlation with CFU Assays

Directory of Open Access Journals (Sweden)

Teja Falk Radke

2013-01-01

Full Text Available The assessment of nonviable haematopoietic cells by Annexin V staining method in flow cytometry has recently been published by Duggleby et al. Resulting in a better correlation with the observed colony formation in methylcellulose assays than the standard ISHAGE protocol, it presents a promising method to predict cord blood potency. Herein, we applied this method for examining the parameters during processing which potentially could affect cord blood viability. We could verify that the current standards regarding time and temperature are sufficient, since no significant difference was observed within 48 hours or in storage at 4°C up to 26°C. However, the addition of DMSO for cryopreservation alone leads to an inevitable increase in nonviable haematopoietic stem cells from initially 14.8% ± 4.3% to at least 30.6% ± 5.5%. Furthermore, CFU-assays with varied seeding density were performed in order to evaluate the applicability as a quantitative method. The results revealed that only in a narrow range reproducible clonogenic efficiency (ClonE could be assessed, giving at least a semiquantitative estimation. We conclude that both Annexin V staining method and CFU-assays with defined seeding density are reliable means leading to a better prediction of the final potency. Especially Annexin V, due to its fast readout, is a practical tool for examining and optimising specific steps in processing, while CFU-assays add a functional confirmation.

Unirradiated UO2 in irradiated zirconium alloy sheathing

International Nuclear Information System (INIS)

MacDonald, R.D.; Hardy, D.G.; Hunt, C.E.L.; Scoberg, J.A.

1979-07-01

Zircaloy-clad UO 2 fuel elements have defected in power reactors when element power outputs were raised significantly after a long irradiation at low power. We have irradiated fuel elements fabricated from fresh UO 2 pellets and zirconium alloy sheaths previously irradiated without fuel. This gave a fuel element with radiation-damaged low-ductility sheathing but with no fission products in the fuel. The elements were power boosted in-reactor to linear power outputs up to 84 kW/m for two five-day periods. No elements defected despite sheath strains of 0.82 percent at circumferential ridge postions. Half of these elements were subsequently soaked at low power to build up the fission product inventory in the fuel and then power boosted to 63 kW/m for a third time. Two elements defected on this final boost. We conclude that these defects were caused by fission product induced stress-corrosion cracking and that this mechanism plays an importent role in power reactor fuel defects. (auth)

Determination of 2-alkylcyclobutanones in ultraviolet light-irradiated fatty acids, triglycerides, corn oil, and pork samples: Identifying a new source of 2-alkylcyclobutanones.

Science.gov (United States)

Meng, Xiangpeng; Chan, Wan

2017-02-15

Previous studies have established that 2-alkylcyclobutanones (2-ACBs) are unique radiolytic products in lipid-containing foods that could only be formed through exposure to ionizing radiation, but not by any other means of physical/heat treatment methods. Therefore, 2-ACBs are currently the marker molecules required by the European Committee for Standardization to be used to identify foods irradiated with ionizing irradiation. Using a spectrum of state-of-the-art analytical instruments, we present in this study for the first time that the generation of 2-ACBs was also possible when fatty acids and triglycerides are exposed to a non-ionizing, short-wavelength ultraviolet (UV-C) light source. An irradiation dosage-dependent formation of 2-ACBs was also observed in UV-C irradiated fatty acids, triglycerides, corn oil, and pork samples. With UV-C irradiation becoming an increasingly common food treatment procedure, it is anticipated that the results from this study will alert food scientists and regulatory officials to a potential new source for 2-ACBs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Swift heavy ion irradiated SnO{sub 2} thin film sensor for efficient detection of SO{sub 2} gas

Energy Technology Data Exchange (ETDEWEB)

Tyagi, Punit; Sharma, Savita [Department of Physics and Astrophysics, University of Delhi, Delhi 110007 (India); Tomar, Monika [Department of Physics, Miranda House, University of Delhi, Delhi 110007 (India); Singh, Fouran [Inter University Accelerator Center, Aruna Asaf Ali Marg, New Delhi 110067 (India); Gupta, Vinay, E-mail: drguptavinay@gmail.com [Department of Physics and Astrophysics, University of Delhi, Delhi 110007 (India)

2016-07-15

Highlights: • Response of Ni{sup 7+} ion irradiated (100 MeV) SnO{sub 2} film have been performed. • Effect of irradiation on the structural and optical properties of SnO{sub 2} film is studied. • A decrease in operating temperature and increased response is seen after irradiation. - Abstract: Gas sensing response studies of the Ni{sup 7+} ion irradiated (100 MeV) and non-irradiated SnO{sub 2} thin film sensor prepared under same conditions have been performed towards SO{sub 2} gas (500 ppm). The effect of irradiation on the structural, surface morphological, optical and gas sensing properties of SnO{sub 2} thin film based sensor have been studied. A significant decrease in operating temperature (from 220 °C to 60 °C) and increased sensing response (from 1.3 to 5.0) is observed for the sample after irradiation. The enhanced sensing response obtained for the irradiated SnO{sub 2} thin film based sensor is attributed to the desired modification in the surface morphology and material properties of SnO{sub 2} thin film by Ni{sup 7+} ions.

Oxidation kinetic changes of UO2 by additive addition and irradiation

International Nuclear Information System (INIS)

You, Gil-Sung; Kim, Keon-Sik; Min, Duck-Kee; Ro, Seung-Gy

2000-01-01

The kinetic changes of air-oxidation of UO 2 by additive addition and irradiation were investigated. Several kinds of specimens, such as unirradiated-UO 2 , simulated-UO 2 for spent PWR fuel (SIMFUEL), unirradiated-Gd-doped UO 2 , irradiated-UO 2 and -Gd-doped UO 2 , were used for these experiments. The oxidation results represented that the kinetic patterns among those samples are remarkably different. It was also revealed that the oxidation kinetics of irradiated-UO 2 seems to be more similar to that of unirradiated-Gd-doped UO 2 than that of SIMFUEL

Post irradiation examination of type 316 stainless steels for in-pile Oarai water loop No.2 (OWL-2)

International Nuclear Information System (INIS)

Shibata, Akira; Kimura, Tadashi; Nagata, Hiroshi; Aoyama, Masashi; Kanno, Masaru; Ohmi, Masao

2010-11-01

The Oarai water loop No.2 (OWL-2) was installed in JMTR in 1972 for the purpose of irradiation experiments of fuel element and component material for light water reactors. Type 316 stainless steels (SSs) were used for tube material of OWL-2 in the reactor. But data of mechanical properties of highly irradiated Type 316 SSs has been insufficient since OWL-2 was installed. Therefore surveillance tests of type 316 SSs which were irradiated up to 3.4x10 25 n/m 2 in fast neutron fluence (>1 MeV) were performed. Meanwhile type 316 stainless steel (SS) is widely used in JMTR such as other irradiation apparatus and irradiation capsule, and additional data of type 316 SSs irradiated higher is required. Therefore post irradiation examinations of surveillance specimens made of type 316 SSs which were irradiated up to 1.0x10 26 n/m 2 in fast neutron fluence were performed and reported in this paper. In this result of surveillance tests of type 316 SSs irradiated up to 1.0x10 26 n/m 2 , tensile strength increase with increase of Neutron fluence and total elongation decreased with increase of Neutron fluence compared to unirradiated specimens and specimens irradiated up to 3.4x10 25 n/m 2 . This tendency has good agreement with results of 10 24 - 10 25 n/m 2 in fast neutron fluence. More than 37% in total elongation was confirmed in all test conditions. It was confirmed that type 316 SS irradiated up to 1.0x10 26 n/m 2 in fast neutron fluence has enough ductility as structure material. (author)

Ceramography of Irradiated tristructural isotropic (TRISO) Fuel from the AGR-2 Experiment

Energy Technology Data Exchange (ETDEWEB)

Rice, Francine Joyce [Idaho National Lab. (INL), Idaho Falls, ID (United States); Stempien, John Dennis [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2016-09-01

Ceramography was performed on cross sections from four tristructural isotropic (TRISO) coated particle fuel compacts taken from the AGR-2 experiment, which was irradiated between June 2010 and October 2013 in the Advanced Test Reactor (ATR). The fuel compacts examined in this study contained TRISO-coated particles with either uranium oxide (UO2) kernels or uranium oxide/uranium carbide (UCO) kernels that were irradiated to final burnup values between 9.0 and 11.1% FIMA. These examinations are intended to explore kernel and coating morphology evolution during irradiation. This includes kernel porosity, swelling, and migration, and irradiation-induced coating fracture and separation. Variations in behavior within a specific cross section, which could be related to temperature or burnup gradients within the fuel compact, are also explored. The criteria for categorizing post-irradiation particle morphologies developed for AGR-1 ceramographic exams, was applied to the particles in the AGR-2 compacts particles examined. Results are compared with similar investigations performed as part of the earlier AGR-1 irradiation experiment. This paper presents the results of the AGR-2 examinations and discusses the key implications for fuel irradiation performance.

Food Irradiation Newsletter. V. 11, no. 2

International Nuclear Information System (INIS)

1987-09-01

This issue includes a report of the ICGFI's Workshop on Food Irradiation for Food Control Officials, convened in Budapest, Hungary, May 1987. To provide further assurance on the safety and wholesomeness of irradiated food in general and details about polyploidy (increase in number of chromosomes) resulting from consumption of freshly irradiated wheat in particular, ICGFI Secretariat issued a fact sheet on ''Safety and Wholesomeness of Irradiated Foods: International Status - Facts and Figures'' to its member countries in July 1987. The Newsletter also contains summary reports of two important market testings of irradiated food, i.e. papaya in California in March and strawberries in France in June, which proved that consumers will buy irradiated foods, and status reports on food irradiation in France and Mexico. Ref, 1 tab

Experience of the irradiation method under mixed gas (95% O2 plus 5% CO2) inhalation

International Nuclear Information System (INIS)

Ikeda, Michio; Tazaki, Eio

1978-01-01

The irradiation method under mixed gas of 95% O 2 plus CO 2 inhalation at one atomosphere was discussed to improve therapeutic results, in malignant tumors which are not greatly sensitive to irradiation. Randomized study was done in each attending institute, with common protocols. As a result, no positive effect was recognized in irradiation method under mixed gas inhalation with daily dose of 200 rad and 5 fractions per week, which is widely used clinically. But when irradiation dose was increased up to 500 to 600 rad per fraction, effect of the mixed gas was remarkable. But against this, observing for years, results in irradiation under mixed gas inhalation were not always related to the improvement of the long term survival. (author)

Scientific activities in support of the BR2 operation and irradiation programmes

International Nuclear Information System (INIS)

Koonen, E.

2006-01-01

One of the major characteristics of the BR2 reactor is the fact that the core configuration is essentially variable. This allows to optimize the irradiation conditions of various experiments and to minimize the fuel consumption. In order to do that, BR2 has its own autonomous reactor physics cell. In order to allow for on-line measurements of the major irradiation parameters, BR2 has extended its own proven data acquisition system to serve this purpose. This system, called BIDASSE (for BR2 Integrated Data Acquisition System for Survey and Experiments), originally designed for the follow-up of all BR2 operational parameters, is since several years extensively used for experiments. The object rives of research at the BR2 are to evaluate and adjust provisional irradiation conditions by adjustments of the environment, axial and azimuthal positioning of the samples, global power level, ... ; to deliver reliable, well defined irradiation condition and fluence data during and after irradiation; to assist the designer of new irradiation devices by simulations and neutronic optimisations of design options and o provide the experimenters with accurate on-line information on the evolution of their ongoing irradiation projects

The effect of gamma-irradiation of Fe2O3 suspension

International Nuclear Information System (INIS)

Adachi, Motoaki; Irie, Setsuko; Kinoshita, Shosaku

1979-01-01

The effect of γ-irradiation on the sedimentation of suspended particles in distilled water has not been satisfactorily considered for disappearance of this effect. Therefore, we investigated the increase in sedimentation by irradiation, it's reappearance and the dependency on the coagulation. The following conclusion became clear; 1) the irradiation against Fe 2 O 3 suspension has the ability to increase the sedimentation velocity of interface and to decrease the turbidity, 2) these phenomena are due to the increase of coagulation induced by irradiation. (author)

Induction of annexin-1 at transcriptional and posttranscriptional level in rat brain by methylprednisolone and the 21-aminosteroid U74389F

NARCIS (Netherlands)

Voermans, PH; Go, KG; TerHorst, GJ; Ruiters, MHJ; Solito, E; Parente, L

1996-01-01

BRAIN tissue of rats pretreated with methylprednisolone or with the 21-aminosteroid U74389F, and that of untreated control rats, was assessed for the expression of annexin-l (Anx-1) and the transcription of its mRNA. For this purpose Anx-1 cDNA was amplified and simultaneously a T7-RNA-polymerase

Food irradiation - 2nd all-German conference. Proceedings

International Nuclear Information System (INIS)

Walz, E.; Ehlermann, D.A.E.

1993-01-01

The 2nd conference on 'Food Irradiation' in re-united Germany took place in Eggenstein-Leopoldshafen at the Karlsruhe Nuclear Research Centre, 9th to 10th December 1992. Participants came from government investigating agencies and research institutions of the German Federal Government and the Federal States. Abstracts focus on issues of food laws and certification of irradiation treatment. (UHE) [de

Post irradiation examinations on UMo full-sized plates - IRIS2 experiment

International Nuclear Information System (INIS)

Huet, F.; Noirot, J.; Marelle, V.; Dubois, S.; Boulcourt, P.; Sacristan, P.; Naury, S.; Lemoine, P.

2005-01-01

IRIS2 irradiation was the last irradiation of 4 full sized plates launched by CEA for the French UMo group to test in which operating conditions the coarse porosity forms in the UMo/Al interaction product. IRIS2 consists in four plates with high uranium loading and U-7wt%Mo atomised powder irradiated up to 60 days at OSIRIS reactor in IRIS device at a peak power of 238 W.cm -2 . The results show that in the tested conditions pillowing of the plate started from a fission density over 2.10 21 fission.cm -3 . Moreover, they show that the fission products and impurities have a key-role in the origin of the excessive plate swelling. (author)

Irradiation creep of the mixed oxide UPuO2

International Nuclear Information System (INIS)

Combette, Patrick; Milet, Claude

1976-01-01

The irradiation creep under compression of the mixed oxide UO 2 -PuO 2 was studied up to fission yields of 6x10 13 fcm -3 s -1 , under stresses -2 , in the temperature range 700-900 deg C. The creep rate is proportional to the applied stress and fission yield, athermal in the studied temperature range and non-dependent of burnup (up to 30000MWjt -1 ). In a sample under compression, swelling is observed due to the formation of fission products during the irradiation and the swelling rate is of the same order that in a cladded fuel element [fr

Relationship of 99mTc-HYNIC annexin V uptake to microvessel density, FasL and MMP-9 expression, and the number of tumour-infiltrating lymphocytes in head and neck carcinoma

International Nuclear Information System (INIS)

Vermeersch, Hubert; Loose, David; Mervillie, Kris; Cuvelier, Claude; Lahorte, Christophe; Slegers, Guido; Dierck, Rudi Andre; Van de Wiele, Christophe; Steinmetz, Neil

2004-01-01

This study reports on the relationship between quantitative 99m Tc-HYNIC radiolabelled annexin V tumour uptake measurements, Fas ligand (FasL) expression, matrix metalloproteinase-9 (MMP-9) expression, microvessel density (MVD) and the number of tumour-infiltrating lymphocytes in squamous cell carcinoma of the head and neck (SCCHN) patients. Twenty-eight patients (24 men and 4 women; mean age 59 years, range 43-83 years) suffering from a primary (n, number of patients=22) or locally recurrent (n=6) SCCHN were studied. All patients underwent a spiral CT scan, allowing estimation of lesion size in three dimensions, and 99m Tc-HYNIC annexin V scintigraphy within 1 week of each other. Biopsies or resection of the suspected primary tumour or local recurrence for histopathological analysis were performed on all patients within a period of 10 days following 99m Tc-HYNIC annexin V scintigraphy. The percentage uptake of the injected dose of 99m Tc-HYNIC annexin V in visible tumour lesions on scintigrams divided by the tumour volume, derived from CT, was related to MVD and to histological score (HSCORE) values for MMP-9 and FasL expression as well as to the number of tumour-infiltrating lymphocytes (CD45 staining). Median percentage absolute tumour uptake of the injected dose/cm 3 tumour volume derived from tomographic images was 0.0001% (SD 0.0001%) at 5-6 h p.i. (range: 0.000007-0.0003%). Mean HSCORE for MMP-9 tumour staining was 2.1 (SD 0.84). Mean HSCORE for FasL tumour staining was 2.49 (SD 0.92). At the sites of tumour containing the highest number of vessels, the mean MVD was 20 vessels/field at the hot spot (range 1-73). The median number of tumour-infiltrating lymphocytes was 500 (range 100-5,000). The percentage absolute tumour uptake of the injected dose/cm 3 tumour volume derived from tomographic images correlated linearly with FasL HSCORES(r=0.47, P=0.02). No correlation was found between the percentage absolute tumour uptake of the injected dose/cm 3 tumour

Pressure and temperature phase diagram of Gd{sub 2}Ti{sub 2}O{sub 7} under irradiation

Energy Technology Data Exchange (ETDEWEB)

Catillon, G. [Université Paris-Est, G2I, EA4119, 5 Blvd. Descartes, F-77454 Marne la Vallée Cedex 2 (France); Chartier, A., E-mail: alain.chartier@cea.fr [CEA, DEN, DMN, SCCME, F-91191 Gif-Sur-Yvette Cedex (France)

2014-11-21

The pressure and temperature phase diagram of Gd{sub 2}Ti{sub 2}O{sub 7} under irradiation are calculated by means of molecular dynamics calculations. The critical temperature for amorphization obeys a linear law with pressure. Gd{sub 2}Ti{sub 2}O{sub 7} under irradiation transits towards the fluorite above this temperature and amorphizes below. The configuration of the Ti interstitial reveals to be the key of the amorphizability of Gd{sub 2}Ti{sub 2}O{sub 7}. Its stability depends upon disorder and pressure. Low pressure promotes the stabilization of Ti linked-polyhedra that drive the system to the amorphous state under irradiation. Conversely, high pressure activates its destabilization to interstitials that recombine with vacancies, driving the system to the fluorite structure under irradiation.

Ion-irradiation-induced phase transformation in rare earth sesquioxides (Dy2O3,Er2O3,Lu2O3)

International Nuclear Information System (INIS)

Tang, M.; Lu, P.; Valdez, J.A.; Sickafus, K.E.

2006-01-01

Polycrystalline pellets of cubic C-type rare earth structure (Ia3) Dy 2 O 3 , Er 2 O 3 , and Lu 2 O 3 were irradiated at cryogenic temperature (120 K) with 300 keV Kr ++ ions to a maximum fluence of 1x10 20 Kr/m 2 . Irradiated specimens were examined using grazing incidence x-ray diffraction and transmission electron microscopy. Ion irradiation leads to different radiation effects in these three materials. First, Dy 2 O 3 begins to transform to a monoclinic B-type rare earth structure (C2/m) at a peak dose of ∼5 displacements per atom (dpa) (corresponding to a fluence of 2x10 19 Kr/m 2 ). This transformation is nearly complete at a peak dose of 25 dpa (a fluence of 1x10 20 Kr/m 2 ). Er 2 O 3 also transforms to the B-type structure, but the transformation starts at a higher irradiation dose of about 15-20 dpa [a fluence of about (6-8)x10 19 Kr/m 2 ]. Lu 2 O 3 was found to maintain the C-type structure even at the highest irradiation dose of 25 dpa (a fluence of 1x10 20 Kr/m 2 ). No C-to-B transformation was observed in Lu 2 O 3 . The irradiation dose dependence of the C-to-B phase transformation observed in Dy 2 O 3 , Er 2 O 3 , and Lu 2 O 3 is closely related to the temperature dependence of the C-to-B phase transformation found in phase diagrams for these three materials

Pulse laser irradiation into superconducting MgB2 detector

International Nuclear Information System (INIS)

Fujiwara, Daisuke; Miki, Shigehito; Satoh, Kazuo; Yotsuya, Tsutomu; Shimakage, Hisashi; Wang, Zhen; Okayasu, Satoru; Katagiri, Masaki; Machida, Masahiko; Kato, Masaru; Ishida, Takekazu

2005-01-01

We performed 20-ps pulse laser irradiation experiments on a MgB 2 neutron detector to know a thermal-relaxation process for designing a MgB 2 neutron detector. The membrane-type structured MgB 2 device was fabricated to minimize the heat capacity of sensing part of a detector as well as to enhance its sensitivity. We successfully observed a thermal-relaxation signal resulting from pulse laser irradiation by developing a detection circuit. The response time was faster than 1 μs, meaning that the detector would be capable of counting neutrons at a rate of more than 10 6 events per second

Effects of the auto irradiation in KBr:Eu2+ crystals

International Nuclear Information System (INIS)

Perez S, R.; Aceves, R.

2002-01-01

In KCl :Eu 2+ crystals and in KBr :Eu 2+ crystals it has been detected the effect of the auto irradiation with 40 K isotope. In this work, a study of auto irradiation thermoluminescence in KBr :Eu 2+ crystals with different Eu 2+ concentrations and different thermal treatments is presented. The form of the Tl curve shows mainly a sparkle at 110 Centigrade degrees. The sparkle intensity increases linearly in a time interval around 3600 sec. After this time the increase of intensity was slower. In the linear interval, the lukewarm effects are almost scornful. The analysis of results is looked to the relation between the thermoluminescence and the Eu 2+ additions. It is discussed the form of the curve comparing it with the Tl induced by external irradiation sources on this type of materials. Also it is discussed the temporary dependence of the quantity of induced defects. Finally, the Tl intensity results for crystals with and without previous luke warms are compared. (Author)

Postirradiation examination results for the Irradiation Effects Scoping Test 2

International Nuclear Information System (INIS)

Mehner, A.S.

1977-01-01

The postirradiation examination results are reported for two rods from the second scoping test (IE-ST-2) of the Nuclear Regulatory Commission Irradiation Effects Program. The rods were irradiated in the in-pile test loop of the Power Burst Facility at the Idaho National Engineering Laboratory. Rod IE-005 was fabricated from fresh fuel and cladding previously irradiated in the Saxton Reactor. Rod IE-006, fabricated from fresh fuel and unirradiated cladding, was equipped with six developmental cladding surface thermocouples. The rods were preconditioned, power ramped, and then subjected to film boiling operation. The performance of the rods and the developmental thermocouples are evaluated from the post irradiation examination results. The effects of prior irradiation damage in cladding are discussed in relation to fuel rod behavior during a power ramp and subsequent film boiling operation

Surface properties of UV irradiated PC–TiO{sub 2} nanocomposite film

Energy Technology Data Exchange (ETDEWEB)

Jaleh, B., E-mail: bkjaleh@yahoo.com; Shahbazi, N.

2014-09-15

Highlights: • Production of PC–TiO{sub 2} nanocomposite films. • Fully characterization of PC–TiO{sub 2} nanocomposite films. • Influence of UV irradiation on surface properties and hardness of PC–TiO{sub 2} nanocomposite film. - Abstract: In this work, polycarbonate–TiO{sub 2} nanocomposite films were prepared with two different percentages. The structure of samples were studied by X-ray diffraction. Thermal stability of the nanocomposites was studied by thermogravimetric analysis (TGA). The polycarbonate and polycarbonate–TiO{sub 2} nanocomposite films were exposed by UV light at different irradiation times. The effects of UV irradiation on the surface properties of samples have been studied by different characterization techniques, viz. scanning electron microscopy (SEM), FTIR spectroscopy, X-ray photoelectron spectroscopy (XPS), contact angle measurement and Vickers microhardness tester. Hydrophilicity and surface energy of UV treated samples varied depending on UV irradiation time. TGA curves showed that nanocomposite films have higher resistance to thermal degradation compared to polycarbonate. XPS analysis shows that surface of samples become more oxidized due to UV irradiation. For nanocomposite film, the smallest contact angle was observed in association with the longest UV irradiation time. The contact angle significantly decreased from 90° to 12° after 15 h of UV irradiation. It is observed that the hardness of the nanocomposite films increases after UV irradiation.

TiO2 film/Cu2O microgrid heterojunction with photocatalytic activity under solar light irradiation.

Science.gov (United States)

Zhang, Junying; Zhu, Hailing; Zheng, Shukai; Pan, Feng; Wang, Tianmin

2009-10-01

Coupling a narrow-band-gap semiconductor with TiO(2) is an effective method to produce photocatalysts that work under UV-vis light irradiation. Usually photocatalytic coupled-semiconductors exist mainly as powders, and photocatalytic activity is only favored when a small loading amount of narrow-band-gap semiconductor is used. Here we propose a heavy-loading photocatalyst configuration in which 51% of the surface of the TiO(2) film is covered by a Cu(2)O microgrid. The coupled system shows higher photocatalytic activity under solar light irradiation than TiO(2) and Cu(2)O films. This improved performance is due to the efficient charge transfer between the two phases and the similar opportunity each has to be exposed to irradiation and adsorbates.

Behavior of high resistance to He{sup 2+} induced irradiation damage in metallic glass

Energy Technology Data Exchange (ETDEWEB)

Wang, Bin [Key Laboratory of Materials Modification by Laser, Ion and Electron Beams (Dalian University of Technology), Ministry of Education, Dalian 116024 (China); Mei, Xianxiu, E-mail: xxmei@dlut.edu.cn [Key Laboratory of Materials Modification by Laser, Ion and Electron Beams (Dalian University of Technology), Ministry of Education, Dalian 116024 (China); Hou, Wenjing; Wang, Younian [Key Laboratory of Materials Modification by Laser, Ion and Electron Beams (Dalian University of Technology), Ministry of Education, Dalian 116024 (China); Wang, Zhiguang [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Dong, Chuang [Key Laboratory of Materials Modification by Laser, Ion and Electron Beams (Dalian University of Technology), Ministry of Education, Dalian 116024 (China)

2013-10-01

Highlights: •Metallic glasses and W were irradiated with 500 keV He{sup 2+} at different fluences. •Metallic glasses could maintain amorphous state at different irradiation fluences. •The resistance to He{sup 2+} irradiation of metallic glasses was superior to the one in W metal. •Cu- and Zr-based metallic glasses had better resistance to He{sup 2+} irradiation. -- Abstract: This study details the irradiation of various metallic glasses ((Cu{sub 47}Zr{sub 45}Al{sub 8}){sub 98.5}Y{sub 1.5}, Zr{sub 64}Cu{sub 17.8}Ni{sub 10.7}Al{sub 7.5}, Co{sub 61.2}B{sub 26.2}Si{sub 7.8}Ta{sub 4.8}) and metallic W using He{sup 2+} ions with an energy of 500 keV at irradiation fluences of 2 × 10{sup 17}, 1 × 10{sup 18} and 2 × 10{sup 18} ions/cm{sup 2} to investigate the radiation-resistant properties of these metallic glasses compared to the conventional irradiation-resistant material W. These three metallic glasses were able to maintain an amorphous state during these irradiation fluences. There was no significant irradiation damage at the low irradiation fluence. When the irradiation fluence was increased to 2 × 10{sup 18} ions/cm{sup 2}, a damage layer appeared up to a distance corresponding to the range of the ions away from the surfaces of the Cu- and Zr-based metallic glasses without any visible damage on the surface. Significant surface stripping damage appeared in the Co-based metallic glass. Relatively speaking, surface layer peeling appeared in metallic W along the crystal boundary at a fluence of 1 × 10{sup 18} ions/cm{sup 2}. When the fluence was increased to 2 × 10{sup 18} ions/cm{sup 2}, multilayer peeling, stripping, etc. appeared. The roughness of the Cu- and Zr-based metallic glass showed further smoothing with increasing fluence, while the opposite occurred in the Co-based metallic glass. Within the wavelength range of 400–1700 nm, after irradiation of He{sup 2+} at a fluence of 1 × 10{sup 18} ions/cm{sup 2}, the reflectance of the Cu-based and Co

Luminescence spectroscopic observation of singlet oxygen formation in extra virgin olive oil as affected by irradiation light wavelengths, 1,4-diazabicyclo[2.2.2]octane, irradiation time, and oxygen bubbling.

Science.gov (United States)

Jung, Mun Y; Choi, Dong S; Park, Ki H; Lee, Bosoon; Min, David B

2011-01-01

A spectrofluorometer equipped with a highly sensitive near-IR InGaAs detector was used for the direct visualization of singlet oxygen emission at 1268 nm in olive oil during light irradiation with various different wavelengths. The virgin olive oil in methylene chloride (20% w/v, oxygen saturated) was irradiated at the 301, 417, 454, 483, and 668 nm, then the emission at 1268 nm, singlet oxygen dimole decaying was observed. The result showed the highest production of (1)O(2) with light irradiation at 417 nm, and followed by at 668 nm in virgin olive oil, indicating that pheophytin a and chlorophyll a were the most responsible components for the production of singlet oxygen. The UV light irradiations at the wavelength of 200, 250, and 300 nm did not induce any detectable luminescence emission at 1268 nm, but 350 nm produced weak emission at 1269 nm. The quantity of (1)O(2) produced with excitation at 350 nm was about 1/6 of that of irradiation at 417 nm. Addition of an efficient (1)O(2) quencher, 1,4-diazabicyclo[2.2.2]octane, in virgin olive oil in methylene chloride greatly decreased the luminescence emission at 1268 nm, confirming the singlet oxygen production in olive oil. Singlet oxygen production was more efficient in oxygen-purged virgin olive oil than in oxygen non-purged olive oil. This represents first report on the direct observation of singlet oxygen formation in olive oil as well as in real-food system after visible light illumination. Practical Application: The present results show the positive evidence of the singlet oxygen involvement in rapid oxidative deterioration of virgin olive oil under visible light. This paper also shows the effects of different wavelength of light irradiation on the formation of singlet oxygen in olive oil. The present results would provide important information for the understanding of the mechanism involved in rapid oxidative quality deterioration of virgin olive oil under light illumination and for searching the

Plant responses to UV-B irradiation are modified by UV-A irradiation

International Nuclear Information System (INIS)

Middleton, E.M.; Teramura, A.H.

1993-01-01

The increasing UV-B radiation (0.28-0.32 μm) reaching the earth's surface is an important concern. Plant response in artificial UV-B irradiation studies has been difficult to assess, especially regarding photosynthetic pigments, because the fluorescent lamps also produce UV-A (0.32-0.40μm) radiation which is involved with blue light in pigment synthesis. Both UV-A and UV-B irradiances were controlled in two glasshouse experiments conducted under relatively high PPFD (> 1300μmol m -2 s -1 ) at two biologically effective daily UV-B irradiances (10.7 and 14.1 kJ m -2 ); UV-A irradiances were matched in Controls (∼5, 9 kJ m -2 ). Normal, chlorophyll-deficient, and flavonoid-deficient isolines of soybean cultivar, Clark, were utilized. Many growth/ pigment variables exhibited a statistically significant interaction between light quality and quantity: in general, UV-A radiation moderated the damaging effects of UV-B radiation. Regression analyses demonstrated that a single negative function related photosynthetic efficiency to carotenoid Content (r 2 =0.73, P≤0.001), implying a open-quotes costclose quotes in maintaining carotenoids for photoprotection. A stomatal limitation to photosynthesis was verified and carotenoid content was correlated with UV-B absorbing compound levels, in UV-B irradiated plants

Structural, morphological and optical investigations on electron-beam irradiated PbF2-TeO2-B2O3-Eu2O3 glasses

Science.gov (United States)

Wagh, Akshatha; Petwal, Vikash; Dwivedi, Jishnu; Upadhyaya, V.; Raviprakash, Y.; Kamath, Sudha D.

2016-09-01

Combined structural, optical and morphological studies were carried out on Eu2O3 doped PbF2-TeO2-B2O3 glass samples, before and after being subjected to electron beam of energy 7.5 MeV. XRD confirmed the amorphous nature of the glasses even after 150 kGy electron beam irradiation. Densities of the irradiated samples showed slightly greater values when compared to their respective values before irradiation, which proved the increase in the compaction of the network. The intensities of the three prominent bands; B-O-B linkages, BO4 units and BO3 units of FT-IR spectra, of the titled glasses, showed slight decrease after electron beam irradiation. The decrement in the values of energy band gap and shift in cut-off wavelength towards red edge, proved the formation of color centers in the glass network after irradiation. The change in Hunter L values, through color measurement was a proof for the Farbe/color/absorption centers created in the glass sites after irradiation.

Defect trap model of gas behaviour in UO2 fuel during irradiation

International Nuclear Information System (INIS)

Szuta, A.

2003-01-01

Fission gas behaviour is one of the central concern in the fuel design, performance and hypothetical accident analysis. The report 'Defect trap model of gas behaviour in UO 2 fuel during irradiation' is the worldwide literature review of problems studied, experimental results and solutions proposed in related topics. Some of them were described in details in the report chapters. They are: anomalies in the experimental results; fission gas retention in the UO 2 fuel; microstructure of the UO 2 fuel after irradiation; fission gas release models; defect trap model of fission gas behaviour; fission gas release from UO 2 single crystal during low temperature irradiation in terms of a defect trap model; analysis of dynamic release of fission gases from single crystal UO 2 during low temperature irradiation in terms of defect trap model; behaviour of fission gas products in single crystal UO 2 during intermediate temperature irradiation in terms of a defect trap model; modification of re-crystallization temperature of UO 2 in function of burnup and its impact on fission gas release; apparent diffusion coefficient; formation of nanostructures in UO 2 fuel at high burnup; applications of the defect trap model to the gas leaking fuel elements number assessment in the nuclear power station (VVER-PWR)

Relationship of {sup 99m}Tc-HYNIC annexin V uptake to microvessel density, FasL and MMP-9 expression, and the number of tumour-infiltrating lymphocytes in head and neck carcinoma

Energy Technology Data Exchange (ETDEWEB)

Vermeersch, Hubert; Loose, David [Department of Head and Neck Surgery, University Hospital Ghent (Belgium); Mervillie, Kris; Cuvelier, Claude [Department of Pathology, University Hospital Ghent (Belgium); Lahorte, Christophe; Slegers, Guido [Department of Radiopharmacy, Ghent University (Belgium); Dierck, Rudi Andre; Van de Wiele, Christophe [Division of Nuclear Medicine, University Hospital Ghent, De Pintelaan 185B, 9000, Ghent (Belgium); Steinmetz, Neil [Theseus Imaging Corporation, Cambridge, Massachusetts (United States)

2004-07-01

This study reports on the relationship between quantitative {sup 99m}Tc-HYNIC radiolabelled annexin V tumour uptake measurements, Fas ligand (FasL) expression, matrix metalloproteinase-9 (MMP-9) expression, microvessel density (MVD) and the number of tumour-infiltrating lymphocytes in squamous cell carcinoma of the head and neck (SCCHN) patients. Twenty-eight patients (24 men and 4 women; mean age 59 years, range 43-83 years) suffering from a primary (n, number of patients=22) or locally recurrent (n=6) SCCHN were studied. All patients underwent a spiral CT scan, allowing estimation of lesion size in three dimensions, and {sup 99m}Tc-HYNIC annexin V scintigraphy within 1 week of each other. Biopsies or resection of the suspected primary tumour or local recurrence for histopathological analysis were performed on all patients within a period of 10 days following {sup 99m}Tc-HYNIC annexin V scintigraphy. The percentage uptake of the injected dose of {sup 99m}Tc-HYNIC annexin V in visible tumour lesions on scintigrams divided by the tumour volume, derived from CT, was related to MVD and to histological score (HSCORE) values for MMP-9 and FasL expression as well as to the number of tumour-infiltrating lymphocytes (CD45 staining). Median percentage absolute tumour uptake of the injected dose/cm{sup 3} tumour volume derived from tomographic images was 0.0001% (SD 0.0001%) at 5-6 h p.i. (range: 0.000007-0.0003%). Mean HSCORE for MMP-9 tumour staining was 2.1 (SD 0.84). Mean HSCORE for FasL tumour staining was 2.49 (SD 0.92). At the sites of tumour containing the highest number of vessels, the mean MVD was 20 vessels/field at the hot spot (range 1-73). The median number of tumour-infiltrating lymphocytes was 500 (range 100-5,000). The percentage absolute tumour uptake of the injected dose/cm{sup 3} tumour volume derived from tomographic images correlated linearly with FasL HSCORES(r=0.47, P=0.02). No correlation was found between the percentage absolute tumour uptake of the

Heavy-Section Steel Irradiation Program. Volume 2, No. 2: Semiannual progress report, April--September 1991

International Nuclear Information System (INIS)

Corwin, W.R.

1994-10-01

Goal is to provide a thorough, quantitative assessment of the effects of neutron irradiation on the material behavior, and in particular the fracture toughness properties, of typical pressure vessel stools as they relate to light-water reactor pressure-vessel integrity. Effects of specimen size, material chemistry, product form and microstructure, irradiation fluence, flux, temperature and spectrum, and post-irradiation annealing are being examined on a wide range of fracture properties. The HSSI Program is into 10 tasks: (1) program management, (2) K Ic curve shift in high-copper welds, (3) K Ia curve shift in high-copper welds, (4) irradiation effects on cladding, (5) K Ic and K Ia curve shifts in low upper-shelf welds, (6) irradiation effects in a commercial low upper-sheer weld, (7) microstructural analysis of irradiation effects, (8) in-service aged material evaluations, (9) correlation monitor materials, and (10) special technical assistance. This report provides an overview of the activities within each of these tasks from April to September 1991

X-ray irradiation activates K+ channels via H2O2 signaling.

Science.gov (United States)

Gibhardt, Christine S; Roth, Bastian; Schroeder, Indra; Fuck, Sebastian; Becker, Patrick; Jakob, Burkhard; Fournier, Claudia; Moroni, Anna; Thiel, Gerhard

2015-09-09

Ionizing radiation is a universal tool in tumor therapy but may also cause secondary cancers or cell invasiveness. These negative side effects could be causally related to the human-intermediate-conductance Ca2+-activated-K+-channel (hIK), which is activated by X-ray irradiation and affects cell proliferation and migration. To analyze the signaling cascade downstream of ionizing radiation we use genetically encoded reporters for H2O2 (HyPer) and for the dominant redox-buffer glutathione (Grx1-roGFP2) to monitor with high spatial and temporal resolution, radiation-triggered excursions of H2O2 in A549 and HEK293 cells. The data show that challenging cells with ≥1 Gy X-rays or with UV-A laser micro-irradiation causes a rapid rise of H2O2 in the nucleus and in the cytosol. This rise, which is determined by the rate of H2O2 production and glutathione-buffering, is sufficient for triggering a signaling cascade that involves an elevation of cytosolic Ca2+ and eventually an activation of hIK channels.

Fabrication of irradiation capsule for IASCC irradiation tests (2). Irradiation capsule for crack propagation test (Joint research)

International Nuclear Information System (INIS)

Ide, Hiroshi; Matsui, Yoshinori; Kawamata, Kazuo; Taguchi, Taketoshi; Kanazawa, Yoshiharu; Onuma, Yuichi; Watanabe, Hiroyuki; Inoue, Shuichi; Izumo, Hironobu; Ishida, Takuya; Saito, Takashi; Ishitsuka, Etsuo; Kawamura, Hiroshi; Kaji, Yoshiyuki; Ugachi, Hirokazu; Tsukada, Takashi

2008-03-01

It is known that irradiation Assisted Stress Corrosion Cracking (IASCC) occurs when austenitic stainless steel components used for light water reactor (LWR) are irradiated for a long period. In order to evaluate the high aging of the nuclear power plant, the study of IASCC becomes the important problem. The specimens irradiated in the reactor were evaluated by post irradiation examination in the past study. For the appropriate evaluation of IASCC, it is necessary to test it under the simulated LWR conditions; temperature, water chemistry and irradiation conditions. In order to perform in-pile SCC test, saturated temperature capsule (SATCAP) was developed. There are crack growth test, crack propagation test and so on for in-pile SCC test. In this report, SATCAP for crack propagation test is reported. (author)

Effects of heavy-ion irradiation on the vortex state in Ba(Fe1-xCox)2As2

International Nuclear Information System (INIS)

Tamegai, T.; Tsuchiya, Y.; Taen, T.; Nakajima, Y.; Okayasu, S.; Sasase, M.

2010-01-01

We report effects of heavy-ion irradiation in Ba(Fe 1-x Co x ) 2 As 2 single crystals. The columnar defects with about 40% of the irradiation dose are confirmed by transmission electron microscopy. Magneto-optical imaging and bulk magnetization measurements reveal strong enhancement of the critical current density in the irradiated region. The vortex creep rate is also strongly suppressed by the columnar defects. Effects of heavy-ion irradiation into Ba(Fe 1-x Co x ) 2 As 2 and cuprate superconductors are compared.

Development of irradiated UO2 thermal conductivity model

International Nuclear Information System (INIS)

Lee, Chan Bock; Bang Je-Geon; Kim Dae Ho; Jung Youn Ho

2001-01-01

Thermal conductivity model of the irradiated UO 2 pellet was developed, based upon the thermal diffusivity data of the irradiated UO 2 pellet measured during thermal cycling. The model predicts the thermal conductivity by multiplying such separate correction factors as solid fission products, gaseous fission products, radiation damage and porosity. The developed model was validated by comparison with the variation of the measured thermal diffusivity data during thermal cycling and prediction of other UO 2 thermal conductivity models. Since the developed model considers the effect of gaseous fission products as a separate factor, it can predict variation of thermal conductivity in the rim region of high burnup UO 2 pellet where the fission gases in the matrix are precipitated into bubbles, indicating that decrease of thermal conductivity by bubble precipitation in rim region would be significantly compensated by the enhancing effect of fission gas depletion in the UO 2 matrix. (author)

Behaviour of high purity UO2/H2O interfaces under helium beam irradiation in deaerated conditions

International Nuclear Information System (INIS)

Mendes, E.

2005-11-01

A question put within the framework of the nuclear fuel storage worn in geological site is what become to them in the presence of water. The aim of a fundamental program, of PRECCI project (ECA), is to highlight the behaviour of interfaces which can be used as models for the interfaces nuclear spent fuel/water if the fuel is uranium UO 2 dioxide. This doctorate is interested in the effect of the alpha activity which is the only one that exist in the spent fuel after long periods. The aim is to identify the mechanisms of alteration and of leaching of surfaces under alpha irradiation. A method is developed to irradiate UO 2 /H 2 O interfaces in deaerated conditions with the beam of He 2+ produced by a cyclotron. The He 2+ ions cross an UO 2 disc and emerge in water with an energy of 5 MeV. Leachings under irradiation are carried with a large range of particles flux. The post-irradiation characterization of the surface of the discs realised by micro-Raman spectroscopy allowed to identify the alteration layer. It is made up of studtite UO 2 (O 2 ),4H 2 O, and of schoepite UO 3 ,xH 2 O. The analysis of the solutions shows that the uranium release strongly increases. The electrochemical properties of the interfaces under irradiation strongly differ from those before irradiation. This work allows to propose that the radiolytic species seen by the interface are it during the heterogeneous phase of evolution of the traces and are species of short lives. Modeling show that the radiolytic radicals species can migrate toward the interface and react with the UO 2 surface. (author)

Postirradiation examination results for the Irradiation Effects Test 2

International Nuclear Information System (INIS)

Ploger, S.A.; Kerwin, D.K.; Croucher, D.W.

1978-01-01

This report presents the postirradiation examination results of Test IE-2 in the Irradiation Effects Test Series conducted under the Thermal Fuels Behavior Program. The objectives of this test were to evaluate the influence of previous cladding irradiation and fuel-cladding diametral gap on fuel rod behavior during a power ramp and during film boiling operation. Test IE-2, conducted in the Power Burst Facility at the Idaho National Engineering Laboratory, employed two 0.97-m-long pressurized water reactor type fuel rods fabricated from previously irradiated zircaloy-4 cladding and two similar rods fabricated from unirradiated cladding. The four rods were subjected to a preconditioning period, followed by a power ramp to an average peak rod power of 68 kW/m and steady state operation for one hour at an individual rod coolant mass flux of 4880 kg/s . m 2 . After a flow reduction to 2550 kg/s . m 2 , film boiling occurred on three rods. An additional flow reduction to 2245 kg/s . m 2 produced film boiling on the remaining fuel rod. Maximum time in film boiling was 90 s. None of the four fuel rods failed during the test. Damage caused by film boiling, as characterized by oxidation, oxide spalling, and collapse at fuel pellet interfaces, was found on all four rods. Film boiling regions on these rods showed evidence of fuel melting, fuel centerline void formation, and internal cladding oxidation resulting from fuel-cladding reaction. Effects of fuel-cladding diametral gap and cladding irradiation are summarized. Measured temperatures and metallographically estimated temperatures are compared at several axial fuel rod locations

VHTR-fuel irradiation capsules for VT-1 hole of JRR-2

International Nuclear Information System (INIS)

Kikuchi, Teruo; Kikuchi, Akira; Tobita, Tsutomu; Kashimura, Satoru; Miyasaka, Yasuhiko

1977-02-01

Irradiations of VHTR fuels were made in the VT-1 irradiation hole of JRR-2. Three capsules, VP-1, VP-2 and VP-4, which contained fuel compacts, were irradiated for 300 hr at temperatures of 950 0 , 1370 0 and 1500 0 C up to the estimated burn-ups of 0.74, 0.87 and 0.80%FIMA, respectively. And, to study the amoeba effect of fuel particles, two capsules, VP-3 and VP-5, were irradiated for 300 hr at temperatures of 1650 0 and 1670 0 C up to the estimated burn-ups of 0.38 and 0.33%FIMA, respectively. (auth.)

An Analysis of the Thermal and Structure Behaviour of the UO2-PuO2-Fuel in the Irradiation Experiment of the UO2-PuO2-Fuel in the Irradiation Experiment FR2 Capsule Test Series 5a