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Sample records for beta pai-1 upa

  1. The complex between urokinase (uPA) and its type-1 inhibitor (PAI-1) in pulmonary adenocarcinoma: Relation to prognosis

    DEFF Research Database (Denmark)

    Pappot, Helle; Pedersen, Anders N; Brünner, Nils;

    2006-01-01

    In a lung cancer population comprising tumor tissue from 99 pulmonary adenocarcinoma patients, the relationship between tumor tissue level of the complex formed of urokinase (uPA) and its type-1 inhibitor (PAI-1) and survival was studied. The study included patient material previously investigated....... The amounts of uPA-PAI-1 complex measured in pulmonary adenocarcinoma tissue were within the same range as previously reported in breast cancer tissue (0.11-5.74 ng/mg protein). uPA and PAI-1 levels were weakly correlated to the uPA-PAI-1 complex, r = 0.52 and r = 0.47, respectively, and no relation was found...... these interactions and the clinical importance of the tissue levels of uPA, PAI-1 and uPA-PAI-1 complex, the results suggest further exploratory studies of the components in pulmonary adenocarcinomas and other cancers....

  2. The complex between urokinase (uPA) and its type-1 inhibitor (PAI-1) in pulmonary adenocarcinoma

    DEFF Research Database (Denmark)

    Pappot, Helle; Pedersen, Anders N.; Brünner, Nils;

    2006-01-01

    In a lung cancer population comprising tumor tissue from 99 pulmonary adenocarcinoma patients, the relationship between tumor tissue level of the complex formed of urokinase (uPA) and its type-1 inhibitor (PAI-1) and survival was studied. The study included patient material previously investigated....... The amounts of uPA-PAI-1 complex measured in pulmonary adenocarcinoma tissue were within the same range as previously reported in breast cancer tissue (0.11-5.74 ng/mg protein). uPA and PAI-1 levels were weakly correlated to the uPA-PAI-1 complex, r = 0.52 and r = 0.47, respectively, and no relation was found...... these interactions and the clinical importance of the tissue levels of uPA, PAI-1 and uPA-PAI-1 complex, the results suggest further exploratory studies of the components in pulmonary adenocarcinomas and other cancers....

  3. uPA and PAI-1-Related Signaling Pathways Differ between Primary Breast Cancers and Lymph Node Metastases12

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    Malinowsky, Katharina; Wolff, Claudia; Berg, Daniela; Schuster, Tibor; Walch, Axel; Bronger, Holger; Mannsperger, Heiko; Schmidt, Christian; Korf, Ulrike; Höfler, Heinz; Becker, Karl-Friedrich

    2012-01-01

    The supporting role of urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor 1 (PAI-1) in migration and invasion is well known. In addition, both factors are key components in cancer cell-related signaling. However, little information is available for uPA and PAI-1-associated signaling pathways in primary cancers and corresponding lymph node metastases. The aim of this study was to compare the expression of uPA and PAI-1-associated signaling proteins in 52 primary breast cancers and corresponding metastases. Proteins were extracted from formalin-fixed paraffin-embedded tissue samples of the primary tumors and metastases. Protein lysates were subsequently analyzed by reverse phase protein array for the expression of members of the PI3K/AKT (FAK, GSK3-β, ILK, pGSK3-β, PI3K, and ROCK) and the MAPK pathways (pp38, pSTAT3, and p38). A solid correlation of uPA expression existed between primary tumors and metastases, whereas PAI-1 expression did not significantly correlate between them. The correlations of uPA and PAI-1 with signaling pathways found in primary tumors did not persist in metastases. Analysis of single molecules revealed that some correlated well between tumors and metastases (FAK, pGSK3-β, ILK, Met, PI3K, ROCK, uPA, p38, and pp38), whereas others did not (PAI-1 and GSK3-β). Whether the expression of a protein correlated between tumor and metastasis or not was independent of the pathway the protein is related to. These findings hint at a complete deregulation of uPA and PAI-1-related signaling in metastases, which might be the reason why uPA and PAI-1 reached clinical relevance only for lymph node-negative breast cancer tissues. PMID:22496926

  4. uPA and PAI-1-Related Signaling Pathways Differ between Primary Breast Cancers and Lymph Node Metastases.

    Science.gov (United States)

    Malinowsky, Katharina; Wolff, Claudia; Berg, Daniela; Schuster, Tibor; Walch, Axel; Bronger, Holger; Mannsperger, Heiko; Schmidt, Christian; Korf, Ulrike; Höfler, Heinz; Becker, Karl-Friedrich

    2012-04-01

    The supporting role of urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor 1 (PAI-1) in migration and invasion is well known. In addition, both factors are key components in cancer cell-related signaling. However, little information is available for uPA and PAI-1-associated signaling pathways in primary cancers and corresponding lymph node metastases. The aim of this study was to compare the expression of uPA and PAI-1-associated signaling proteins in 52 primary breast cancers and corresponding metastases. Proteins were extracted from formalin-fixed paraffin-embedded tissue samples of the primary tumors and metastases. Protein lysates were subsequently analyzed by reverse phase protein array for the expression of members of the PI3K/AKT (FAK, GSK3-β, ILK, pGSK3-β, PI3K, and ROCK) and the MAPK pathways (pp38, pSTAT3, and p38). A solid correlation of uPA expression existed between primary tumors and metastases, whereas PAI-1 expression did not significantly correlate between them. The correlations of uPA and PAI-1 with signaling pathways found in primary tumors did not persist in metastases. Analysis of single molecules revealed that some correlated well between tumors and metastases (FAK, pGSK3-β, ILK, Met, PI3K, ROCK, uPA, p38, and pp38), whereas others did not (PAI-1 and GSK3-β). Whether the expression of a protein correlated between tumor and metastasis or not was independent of the pathway the protein is related to. These findings hint at a complete deregulation of uPA and PAI-1-related signaling in metastases, which might be the reason why uPA and PAI-1 reached clinical relevance only for lymph node-negative breast cancer tissues.

  5. Plasminogen activator inhibitor-1 (PAI-1 and urokinase plasminogen activator (uPA in sputum of allergic asthma patients.

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    Sebastian Zukowski

    2008-06-01

    Full Text Available Urokinase plasminogen activator (uPA and its inhibitor (PAI-1 have been associated with asthma. The aim of this study was to evaluate concentration of uPA and PAI-1 in induced sputum of house dust mite allergic asthmatics (HDM-AAs. The study was performed on 19 HDM-AAs and 8 healthy nonatopic controls (HCs. Concentration of uPA and PAI-1 was evaluated in induced sputum supernatants using ELISA method. In HDM-AAs the median sputum concentration of uPA (128 pg/ml; 95% CI 99 to 183 pg/ml and PAI-1 (4063 pg/ml; 95%CI 3319 to 4784 pg/ml were significantly greater than in HCs (17 pg/ml; 95%CI 12 to 32 pg/ml; p<0.001 and 626 pg/ml; 95%CI 357 to 961 pg/ml; p<0.001 for uPA and PAI-1 respectively. The sputum concentration of uPA correlated with sputum total cell count (r=0.781; p=0.0001 and with logarithmically transformed exhaled nitric oxide concentration (eNO (r=0.486; p=0.035 but not with FEV1 or bronchial reactivity to histamine. On the contrary, the sputum PAI-1 concentration correlated with FEV1 (r=-0,718; p=0.0005 and bronchial reactivity to histamine expressed as log(PC20 (r=-0.824; p<0.0001 but did not correlate with sputum total cell count or eNO. The results of this study support previous observations linking PAI-1 with airway remodeling and uPA with cellular inflammation. Moreover, the observed effect of uPA seems to be independent of its fibrynolytic activity.

  6. UPA and PAI-1 analysis from fixed tissues - new perspectives for a known set of predictive markers.

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    Malinowsky, K; Böllner, C; Hipp, S; Berg, D; Schmitt, M; Becker, K F

    2010-01-01

    The urokinase-type plasminogen activator (uPA) and its main inhibitor PAI-1 play key roles in tumor-associated processes such as the degradation of the extracellular matrix (ECM), tissue remodeling, cell adhesion and migration. Elevated expression of both molecules is known to correlate with negative outcomes in node negative breast cancer. To date, these molecules are the only prognostic markers to have reached the highest level of evidence (LOE I) in multi-centered clinical trials for prognosis of node negative breast cancer. Unfortunately, the clinical utility of these molecules as markers is limited by the use of enzyme-linked immunoassay (ELISA) tests for their detection. The ELISA relies on the use of fresh or frozen tissue, which are rarely available in routine clinical settings. In this review article, we provide an overview of the clinical relevance of uPA and PAI-1 and present alternative methods for their detection. Common uPA and PAI-1 detection methods discussed in literature include RT-PCR-based assays and classical immunohistochemistry approaches. In recent years, attempts have been made to isolate and analyze proteins of formalin fixed, paraffin embedded (FFPE) tissues. These new methods are of special interest because up to now neither RT-PCR nor immunohistochemistry are recommended for the detection of uPA and PAI-1. Here, we present an approach for the analysis of uPA and PAI-1 directly from FFPE tissues that may eventually overcome the limitations of current assays and make the use of both markers widely available for routine prognosis and therapy decisions for breast cancer patients.

  7. Signalling networks associated with urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in breast cancer tissues: new insights from protein microarray analysis.

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    Wolff, Claudia; Malinowsky, Katharina; Berg, Daniela; Schragner, Kerstin; Schuster, Tibor; Walch, Axel; Bronger, Holger; Höfler, Heinz; Becker, Karl-Friedrich

    2011-01-01

    The urokinase-type plasminogen activator (uPA) and the main uPA inhibitor PAI-1 play important roles in cell migration and invasion in both physiological and pathological contexts. Both factors are clinically applicable predictive markers in node-negative breast cancer patients that are used to stratify patients for adjuvant chemotherapy. In addition to their classical functions in plasmin regulation, both factors are key components in cancer-related cell signalling. Such signalling cascades are well described in cell culture systems, but a better understanding of uPA- and PAI-1-associated signalling networks in clinical tissues is needed. We examined the expression of uPA, PAI-1, and 21 signalling molecules in 201 primary breast cancer tissues using protein microarrays. Expression of uPA was significantly correlated with the expression of ERK and Stat3, while expression of PAI-1 was correlated with the uPA receptor and Akt activation, presumably via integrin and HER-receptor signalling. Analysis of uPA expression did not reveal any significant correlation with staging, grading or age of the patients. The PAI-1 expression was correlated with nodal stage. Network monitoring for uPA and PAI-1 in breast cancer reveals interactions with main signalling cascades and extends the findings from cell culture experiments. Our results reveal possible mechanisms underlying cancer development.

  8. Urokinase plasminogen activator (uPA and plasminogen activator inhibitor type-1 (PAI-1 in breast cancer - correlation with traditional prognostic factors

    Directory of Open Access Journals (Sweden)

    Lampelj Maja

    2015-12-01

    Full Text Available Background. Urokinase plasminogen activator (uPA and plasminogen activator inhibitor type-1 (PAI-1 play a key role in tumour invasion and metastasis. High levels of both proteolytic enzymes are associated with poor prognosis in breast cancer patients. The purpose of this study was to evaluate the correlation between traditional prognostic factors and uPA and PAI-1 expression in primary tumour of breast cancer patients.

  9. Concentrations of plasminogen activator inhibitor-1 (PAI-1 and urokinase plasminogen activator (uPA in induced sputum of asthma patients after allergen challenge.

    Directory of Open Access Journals (Sweden)

    Marcin Moniuszko

    2011-04-01

    Full Text Available Urokinase plasminogen activator (uPA and its inhibitor (PAI-1 are involved in tiisue remodeling and repair processes associated with acute and chronic inflammation. The aim of the study was to evaluate the effect of allergen challenge on concentration of uPA and PAI-1 in induced sputum of house dust mite allergic asthmatics (HDM-AAs. Thirty HDM-AAs and ten healthy persons (HCswere recruited for the study. In 24 HDM-AAs bronchial challenge with Dermatophagoides pteronyssinus (Dp and in 6 HDM-AAs sham challenege with saline were performed. In HDM-AAs sputum was induced 24 hours before (T0 and 24 hours (T24 after the challenge. Concentration of uPA and PAI-1 in induced sputum were determined using immunoenzymatic assays. At T0 in HDM-AAs mean sputum uPA (151 Âą 96 pg/ml and PAI-1 (4341 Âą 1262 pg/ml concentrations were higher than in HC (18.8 Âą 6.7 pg/ml; p=0.0002 and 596 Âą 180 pg/ml; p<0.0001; for uPA and PAI-1 respectively. After allergen challenge further increase in sputum uPA (187 Âą 144 pg/ml; p=0.03 and PAI-1 (6252 Âą 2323 pg/ml; p<0.0001 concentrations were observed. Moreover, in Dp challenged, but not in saline challenged HDM-AAs the mean uPA/PAI-1 ratio decreased significantly at T24. No significant increase in the studied parameters were found in sham challenged patients. In HDM-AAs allergen exposure leads to activation of the plasmin system in the airways. Greater increase of the PAI-1 concentration than uPA concentration after allergen challenge may promote airway remodeling and play an important role in the development of bronchial hyperreactivity.

  10. Concentrations of plasminogen activator inhibitor-1 (PAI-1 and urokinase plasminogen activator (uPA in induced sputum of asthma patients after allergen challenge

    Directory of Open Access Journals (Sweden)

    Krzysztof Kowal,

    2010-04-01

    Full Text Available Urokinase plasminogen activator (uPA and its inhibitor (PAI-1 are involved in tiisue remodeling and repairprocesses associated with acute and chronic inflammation. The aim of the study was to evaluate the effect of allergen challengeon concentration of uPA and PAI-1 in induced sputum of house dust mite allergic asthmatics (HDM-AAs. ThirtyHDM-AAs and ten healthy persons (HCswere recruited for the study. In 24 HDM-AAs bronchial challenge with Dermatophagoidespteronyssinus (Dp and in 6 HDM-AAs sham challenege with saline were performed. In HDM-AAs sputumwas induced 24 hours before (T0 and 24 hours (T24 after the challenge. Concentration of uPA and PAI-1 in induced sputumwere determined using immunoenzymatic assays. At T0 in HDM-AAs mean sputum uPA (151±96 pg/ml and PAI-1(4341±1262 pg/ml concentrations were higher than in HC (18.8±6.7 pg/ml; p=0.0002 and 596±180 pg/ml; p<0.0001; foruPA and PAI-1 respectively. After allergen challenge further increase in sputum uPA (187±144 pg/ml; p=0.03 and PAI-1(6252±2323 pg/ml; p<0.0001 concentrations were observed. Moreover, in Dp challenged, but not in saline challengedHDM-AAs the mean uPA/PAI-1 ratio decreased significantly at T24. No significant increase in the studied parameters werefound in sham challenged patients. In HDM-AAs allergen exposure leads to activation of the plasmin system in the airways.Greater increase of the PAI-1 concentration than uPA concentration after allergen challenge may promote airway remodelingand play an important role in the development of bronchial hyperreactivity.

  11. Cancer therapy trials employing level-of-evidence-1 disease forecast cancer biomarkers uPA and its inhibitor PAI-1

    DEFF Research Database (Denmark)

    Schmitt, Manfred; Harbeck, Nadia; Brünner, Nils;

    2011-01-01

    and III breast cancer therapy trials (Chemo-N0, NNBC-3 and Plan B), and introduces ongoing clinical trials targeting uPA in advanced cancers of the breast and pancreas, employing synthetic small-size drugs to counteract uPA activity (WX-UK1, Mesupron(®)). The therapeutic effect of a uPA-derived small......Clinical research on cancer biomarkers is essential in understanding recent discoveries in cancer biology and heterogeneity of the cancer disease. However, there are only a few examples of clinically useful studies that have identified cancer biomarkers with clinical benefit. Urokinase......-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor type 1 (PAI-1) are two of the few tumor tissue-associated cancer biomarkers that have been evaluated successfully and extensively in many preclinical and clinical studies for their clinical utility. Most of the studies have been...

  12. Common TNF-α, IL-1β, PAI-1, uPA, CD14 and TLR4 polymorphisms are not associated with disease severity or outcome from Gram negative sepsis

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    Eugen-Olsen Jesper

    2007-09-01

    Full Text Available Abstract Background Several studies have investigated single nucleotide polymorphisms (SNPs in candidate genes associated with sepsis and septic shock with conflicting results. Only few studies have combined the analysis of multiple SNPs in the same population. Methods Clinical data and DNA from consecutive adult patients with culture proven Gram negative bacteremia admitted to a Danish hospital between 2000 and 2002. Analysis for commonly described SNPs of tumor necrosis-α, (TNF-α, interleukin-1β (IL-1β, plasminogen activator-1 (PAI-1, urokinase plasminogen activator (uPA, CD14 and toll-like receptor 4 (TLR4 was done. Results Of 319 adults, 74% had sepsis, 19% had severe sepsis and 7% were in septic shock. No correlation between severity or outcome of sepsis was observed for the analyzed SNPs of TNF-α, IL-1β, PAI-1, uPA, CD14 or TLR-4. In multivariate Cox proportional hazard regression analysis, increasing age, polymicrobial infection and haemoglobin levels were associated with in-hospital mortality. Conclusion We did not find any association between TNF-α, IL-1β, PAI-1, uPA, CD14 and TLR4 polymorphisms and outcome of Gram negative sepsis. Other host factors appear to be more important than the genotypes studied here in determining the severity and outcome of Gram negative sepsis.

  13. Optimized immunohistochemistry in combination with image analysis: a reliable alternative to quantitative ELISA determination of uPA and PAI-1 for routine risk group discrimination in breast cancer.

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    Lang, D S; Heilenkötter, U; Schumm, W; Behrens, O; Simon, R; Vollmer, E; Goldmann, T

    2013-10-01

    The determination of the invasion markers urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) has further improved the possibilities for individualized therapy of breast cancer. To date, quantitative measurement by ELISA, that needs large amounts of fresh, frozen material, is the only standardized procedure for diagnostic purposes. Therefore, the aim of this study was the establishment of a reliable alternative method based on immunohistochemistry (IHC) and image analysis requiring only small amounts of fixed tumor tissue. Protein expression of uPA and PAI-1 was analyzed in HOPE-fixed tumor samples using tissue microarrays (TMAs) and semiquantitative image analysis. The results of both methods were significantly correlated and risk assessment showed an overall concordance of 78% (83/107; high- and low-risk) and of 94% (74/79) regarding only high-risk patients. The data demonstrate that optimized IHC in combination with image analysis can provide adequate clinical significance compared to ELISA-derived determination of uPA and PAI-1.

  14. Binding of PAI-1 to endothelial cells stimulated by thymosin beta4 and modulation of their fibrinolytic potential.

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    Boncela, Joanna; Smolarczyk, Katarzyna; Wyroba, Elzbieta; Cierniewski, Czeslaw S

    2006-01-13

    Our previous studies showed that thymosin beta4 (Tbeta4) induced the synthesis of plasminogen activator inhibitor-1 (PAI-1) in cultured human umbilical vein endothelial cells (HUVECs) via the AP-1 dependent mechanism and its enhanced secretion. In this work we provide evidence that the released PAI-1 is accumulated on the surface of HUVECs, exclusively in its active form, in a complex with alpha1-acid glycoprotein (AGP) that is also up-regulated and released from the cells. This mechanism is supported by several lines of experiments, in which expression of both proteins was analyzed by flow cytometry and their colocalization supported by confocal microscopy. PAI-1 did not bind to quiescent cells but only to the Tbeta4-activated endothelial cells. In contrast, significant amounts of AGP were found to be associated with the cells overexpressing enhanced green fluorescent protein (EGFP)-alpha1-acid glycoprotein (AGP) without Tbeta4 treatment. The AGP.PAI-1 complex was accumulated essentially at the basal surface of endothelial cells, and such cells showed (a) morphology characteristic for strongly adhered and spread cells and (b) significantly reduced plasmin formation. Taken together, these results provide the evidence supporting a novel mechanism by which active PAI-1 can be bound to the Tbeta4-activated endothelial cells, thus influencing their adhesive properties as well as their ability to generate plasmin.

  15. Plasminogen activator inhibitor with very long half-life (VLHL PAI-1) can reduce bleeding in PAI-1-deficient patients.

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    Jankun, Jerzy; Skrzypczak-Jankun, Ewa

    2013-08-01

    This review summarizes our current knowledge of plasminogen activator inhibitor (PAI-1) deficiency and proposes some novel treatments for this condition. PAI-1 is a fast acting inhibitor of tissue and urokinase plasminogen activators (tPA and uPA). PAI-1 controls/slows clot lysis triggered by tPA activated plasminogen. PAI-1 deficiency was once considered to be an extremely rare disorder characterized by frequent and prolonged bleeding episodes. PAI-1 deficiency is now thought to be more frequent than initially reported and is known to be caused by mutations in the PAI-1 gene that produce a dysfunctional PAI-1 protein or slow the secretion of PAI-1 into the circulation. PAI-1 deficiency is characterized by hyperfibrinolysis that results in frequent bleeding episodes. Patients with this condition form normal blood clots that are quickly lysed by unopposed tPA-activated plasmin. Spontaneous bleeding is rare in PAI-1 deficient patients, but moderate hemorrhaging of the knees, elbows, nose, and gums can be triggered by mild trauma. Additionally, prolonged bleeding after surgery is common and menstrual bleeding may be severe. Moderate PAI-1 deficiency is associated with a lifelong bleeding tendency, but severe deficiencies can be life-threatening. The diagnosis of this disorder remains challenging due to the lack of a clear definition of PAI-1 deficiency as well as a lack of standardized tests. Patients with mild PAI-1 deficiency may be treated with antifibrinolytic agents (ε-aminocaproic acid or tranexamic acid); however, not all patients respond well to these treatments. These patients may be treated with wild-type PAI-1; however, this molecule quickly converts into its inactive form. We propose to use PAI-1 with an extended half-life to treat these patients. PMID:23988002

  16. Direct interaction of the kringle domain of urokinase-type plasminogen activator (uPA) and integrin alpha v beta 3 induces signal transduction and enhances plasminogen activation.

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    Tarui, Takehiko; Akakura, Nobuaki; Majumdar, Mousumi; Andronicos, Nicholas; Takagi, Junichi; Mazar, Andrew P; Bdeir, Khalil; Kuo, Alice; Yarovoi, Serge V; Cines, Douglas B; Takada, Yoshikazu

    2006-03-01

    It has been questioned whether there are receptors for urokinase-type plasminogen activator (uPA) that facilitate plasminogen activation other than the high affinity uPA receptor (uPAR/CD87) since studies of uPAR knockout mice did not support a major role of uPAR in plasminogen activation. uPA also promotes cell adhesion, chemotaxis, and proliferation besides plasminogen activation. These uPA-induced signaling events are not mediated by uPAR, but mediated by unidentified, lower-affinity receptors for the uPA kringle. We found that uPA binds specifically to integrin alpha v beta 3 on CHO cells depleted of uPAR. The binding of uPA to alpha v beta 3 required the uPA kringle domain. The isolated uPA kringle domain binds specifically to purified, recombinant soluble, and cell surface alpha v beta 3, and other integrins (alpha 4 beta 1 and alpha 9 beta 1), and induced migration of CHO cells in an alpha v beta 3-dependent manner. The binding of the uPA kringle to alpha v beta 3 and uPA kringle-induced alpha v beta 3-dependent cell migration were blocked by homologous plasminogen kringles 1-3 or 1-4 (angiostatin), a known integrin antagonist. We studied whether the binding of uPA to integrin alpha v beta 3 through the kringle domain plays a role in plasminogen activation. On CHO cell depleted of uPAR, uPA enhanced plasminogen activation in a kringle and alpha v beta 3-dependent manner. Endothelial cells bound to and migrated on uPA and uPA kringle in an alpha v beta 3-dependent manner. These results suggest that uPA binding to integrins through the kringle domain plays an important role in both plasminogen activation and uPA-induced intracellular signaling. The uPA kringle-integrin interaction may represent a novel therapeutic target for cancer, inflammation, and vascular remodeling. PMID:16525582

  17. Procedures for the quantitative protein determination of urokinase and its inhibitor, PAI-1, in human breast cancer tissue extracts by ELISA.

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    Schmitt, Manfred; Sturmheit, Alexandra S; Welk, Anita; Schnelldorfer, Christel; Harbeck, Nadia

    2006-01-01

    The determination of the protein content of urokinase-type plasminogen activator (uPA) and its inhibitor, PAI-1, in breast cancer tissue extracts is used clinically to identify patients at risk to experience disease recurrence (metastasis) or early death. The serine protease uPA, in concert with its inhibitor PAI-1, promotes tumor cell adhesion, migration, and proliferation, as well as extracellular matrix degradation and, thus, facilitates tumor cell invasion and metastasis. The various technical steps to recover uPA and PAI-1 protein from archived breast cancer tissues and to quantitatively determine uPA and PAI-1 protein content in tumor tissue extracts by enzyme-linked immunosorbent assay (ELISA) are described in detail. The technical steps involved require fresh-frozen breast cancer tissue, a dismembrator machine (ball mill) to pulverize the tissue in the frozen state, detergent (Triton X-100) containing Tris-buffered saline to extract uPA and PAI-1 from the pulverized breast cancer tissue, an ultracentrifuge to separate the detergent fraction from cellular debris, uPA and PAI-1 ELISA kits, protein determination reagents, and a 96-well spectrophotometer (ELISA reader) to assess uPA, PAI-1, and total protein in the detergent extract. The uPA/PAI-1 ELISAs and the protein determination format described are robust and highly sensitive. In addition to the macromethod of tissue disintegration, we present a simple but sensitive micro-extraction procedure using cryostat sections or core biopsies as the source of breast cancer tissue. Such a technique allows rapid and quantitative determination of uPA and PAI-1, even in small breast cancer specimens.

  18. Modulation of plasminogen activator inhibitor-1 (PAI-1) by the naphthoquinone shikonin.

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    Han, Tingting; Zhang, Guangping; Yan, Dong; Yang, Hong; Ma, Tonghui; Ye, Zuguang

    2016-09-01

    Plasminogen activator inhibitor-1 (PAI-1) is a key negative regulator of the fibrinolytic system. Elevated levels of PAI-1 are associated with thrombosis and cardiovascular and metabolic diseases. Inhibition of PAI-1 activity represents a new strategy for antithrombotic and antifibrinolysis therapies. In this study, we systematically investigated the inhibitory effect of shikonin on PAI-1 activity. In the chromogenic substrate-based urokinase (uPA)/PAI-1 assay, we found that shikonin inhibited human PAI-1 activity with IC50 values of 30.68±2.32μM. This result was further confirmed by urokinase-type plasminogen activator (uPA)-mediated clot lysis assay. Mechanistic studies indicated that shikonin directly could bind to PAI-1 and prevent the binding of PAI-1 to uPA in a dose-dependent manner. Shikonin also blocked the formation of PAI-1/uPA complex, as shown by SDS/PAGE analysis. In the mouse arterial thrombosis model, intraperitoneal injection of shikonin at 1mgkg(-1) dose significantly prolonged tail bleeding time from 12.956±4.457min to 26.576±2.443min. It also reduced arterial thrombus weight from 0.01±0.001g to 0.006±0.001g (p<0.05). In a liver fibrosis treatment model, when shikonin was continuously injected intraperitoneally at a dose of 1mgkg(-1) over a two-week period, the hydroxyproline content in the mice plasma was significantly reduced and the degree of liver fibrosis was decreased significantly. Thus, shikonin may represent a novel small molecule inhibitor of PAI-1 that could have become a lead drug the treatment of thrombus and fibrosis. PMID:27476618

  19. Functional importance of PAI-1 glycosylation

    DEFF Research Database (Denmark)

    Christensen, Anni; Naessens, Dominik; Skottrup, Peter Durand;

    Structure-function studies of plasminogen activator inhibitor-1 (PAI-1) have previously been performed mostly with non-glycosylated material expressed in E. coli. We have now studied the importance of PAI-1 glycosylation for its functional properties. PAI-1 has 3 potential sites for N-linked glyc......Structure-function studies of plasminogen activator inhibitor-1 (PAI-1) have previously been performed mostly with non-glycosylated material expressed in E. coli. We have now studied the importance of PAI-1 glycosylation for its functional properties. PAI-1 has 3 potential sites for N...... attached at the 2 sites. Analysing the susceptibility of glycosylated and non-glycosylated PAI-1 to activity neutralisation by monoclonal antibodies, we found that the IC50-values for neutralisation by some monoclonal antibodies differed strongly between glycosylated and non-glycosylated PAI-1. The most...

  20. PAI-1 promoter 4G/5G polymorphism (rs1799768) contributes to tumor susceptibility: Evidence from meta-analysis

    OpenAIRE

    Xu, Xin; Xie, Yanqi; Lin, Yiwei; Xu, Xianglai; Zhu, Yi; Mao, Yeqing; Hu, Zhenghui; Wu, Jian; Chen, Hong; Zheng, Xiangyi; QIN, JIE; Xie, Liping

    2012-01-01

    Plasminogen activator inhibitor-1 (PAI-1), belonging to the urokinase plasminogen activation (uPA) system, is involved in cancer development and progression. The PAI-1 promoter 4G/5G polymorphism was shown to contribute to genetic susceptibility to cancer, although the results were inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The electronic databases PubMed, Scopus, Web of Science and Chinese National Knowledge Infrastructure (CNKI) were searched; d...

  1. PAI-1-regulated miR-21 defines a novel age-associated fibrogenic pathway in muscular dystrophy

    OpenAIRE

    Ardite, E.; Perdiguero, E.; Vidal, B.; Gutarra, S.; Serrano, A. L.; Munoz-Canoves, P.

    2012-01-01

    Disruption of skeletal muscle homeostasis by substitution with fibrotic tissue constitutes the principal cause of death in Duchenne muscular dystrophy (DMD) patients, yet the implicated fibrogenic mechanisms remain poorly understood. This study identifies the extracellular PAI-1/urokinase-type plasminogen activator (uPA) balance as an important regulator of microribonucleic acid (miR)–21 biogenesis, controlling age-associated muscle fibrosis and dystrophy progression. Genetic loss of PAI-1 in...

  2. Functional importance of PAI-1 glycosylation

    DEFF Research Database (Denmark)

    Christensen, Anni; Naessens, Dominik; Skottrup, Peter;

    2001-01-01

    Structure-function studies of plasminogen activator inhibitor-1 (PAI-1) have previously been performed mostly with non-glycosylated material expressed in E. coli. We have now studied the importance of PAI-1 glycosylation for its functional properties. PAI-1 has 3 potential sites for N......-linked glycosylation. Biochemical analysis of PAI-1 variants with substitutions of the Asn residues in each of these sites and expression in human embryonic kidney 293 (HEK293) cells showed that only Asn211 and Asn 267, but not Asn331 are glycosylated, and revealed a differential composition of the carbohydrate...... attached at the 2 sites. Analysing the susceptibility of glycosylated and non-glycosylated PAI-1 to activity neutralisation by monoclonal antibodies, we found that the IC50-values for neutralisation by some monoclonal antibodies differed strongly between glycosylated and non-glycosylated PAI-1. The most...

  3. Functional importance of PAI-1 glycosylation

    DEFF Research Database (Denmark)

    Christensen, Anni; Naessens, Dominik; Skottrup, Peter;

    Structure-function studies of plasminogen activator inhibitor-1 (PAI-1) have previously been performed mostly with non-glycosylated material expressed in E. coli. We have now studied the importance of PAI-1 glycosylation for its functional properties. PAI-1 has 3 potential sites for N......-linked glycosylation. Biochemical analysis of PAI-1 variants with substitutions of the Asn residues in each of these sites and expression in human embryonic kidney 293 (HEK293) cells showed that only Asn211 and Asn 267, but not Asn331 are glycosylated, and revealed a differential composition of the carbohydrate...... attached at the 2 sites. Analysing the susceptibility of glycosylated and non-glycosylated PAI-1 to activity neutralisation by monoclonal antibodies, we found that the IC50-values for neutralisation by some monoclonal antibodies differed strongly between glycosylated and non-glycosylated PAI-1. The most...

  4. Common TNF-alpha, IL-1 beta, PAI-1, uPA, CD14 and TLR4 polymorphisms are not associated with disease severity or outcome from Gram negative sepsis

    DEFF Research Database (Denmark)

    Jessen, Kristine Marie; Lindboe, Sarah Bjerre; Petersen, Anncatrine Luisa;

    2007-01-01

    Several studies have investigated single nucleotide polymorphisms (SNPs) in candidate genes associated with sepsis and septic shock with conflicting results. Only few studies have combined the analysis of multiple SNPs in the same population....

  5. Suppression of PAI-1 expression through inhibition of the EGFR-mediated signaling cascade in rat kidney fibroblast by ascofuranone.

    Science.gov (United States)

    Cho, Hyun-Ji; Kang, Jeong-Han; Kim, Teoan; Park, Kwang-Kyun; Kim, Cheorl-Ho; Lee, In-Seon; Min, Kwan-Sik; Magae, Junji; Nakajima, Hiroo; Bae, Young-Seuk; Chang, Young-Chae

    2009-05-15

    Fibrosis in glomerulosclerosis causes progressive loss of renal function. Transforming growth factor (TGF)-beta, one of the major profibrotic cytokines, induces the synthesis of plasminogen activator inhibitor (PAI)-1, a factor that plays a crucial role in the development of fibrosis. Here, we found that an isoprenoid antibiotic, ascofuranone, suppresses expression of profibrotic factors including matrix proteins and PAI-1 induced by TGF-beta in renal fibroblasts. Ascofuranone selectively inhibits phosphorylation of epidermal growth factor receptor (EGFR), and downstream kinases such as Raf-1, MEK-1/2, and ERK-1/2. PAI-1 transcription also is suppressed by treatment with kinase inhibitors for MEK-1/2 or EGFR, and with small interfering RNA for EGFR. Ascofuranone inhibits cellular metalloproteinase activity, and an inhibitor of metalloproteinases suppresses EGFR phosphorylation and PAI-1 transcription. These results suggest that ascofuranone suppresses expression of profibrotic factors through the inhibition of an EGFR-dependent signal transduction pathway activated by metalloproteinases.

  6. The High Affinity Binding Site on Plasminogen Activator Inhibitor-1 (PAI-1) for the Low Density Lipoprotein Receptor-related Protein (LRP1) Is Composed of Four Basic Residues.

    Science.gov (United States)

    Gettins, Peter G W; Dolmer, Klavs

    2016-01-01

    Plasminogen activator inhibitor 1 (PAI-1) is a serpin inhibitor of the plasminogen activators urokinase-type plasminogen activator (uPA) and tissue plasminogen activator, which binds tightly to the clearance and signaling receptor low density lipoprotein receptor-related protein 1 (LRP1) in both proteinase-complexed and uncomplexed forms. Binding sites for PAI-1 within LRP1 have been localized to CR clusters II and IV. Within cluster II, there is a strong preference for the triple CR domain fragment CR456. Previous mutagenesis studies to identify the binding site on PAI-1 for LRP1 have given conflicting results or implied small binding contributions incompatible with the high affinity PAI-1/LRP1 interaction. Using a highly sensitive solution fluorescence assay, we have examined binding of CR456 to arginine and lysine variants of PAI-1 and definitively identified the binding site as composed of four basic residues, Lys-69, Arg-76, Lys-80, and Lys-88. These are highly conserved among mammalian PAI-1s. Individual mutations result in a 13-800-fold increase in Kd values. We present evidence that binding involves engagement of CR4 by Lys-88, CR5 by Arg-76 and Lys-80, and CR6 by Lys-69, with the strongest interactions to CR5 and CR6. Collectively, the individual binding contributions account quantitatively for the overall PAI-1/LRP1 affinity. We propose that the greater efficiency of PAI-1·uPA complex binding and clearance by LRP1, compared with PAI-1 alone, is due solely to simultaneous binding of the uPA moiety in the complex to its receptor, thereby making binding of the PAI-1 moiety to LRP1 a two-dimensional surface-localized association. PMID:26555266

  7. Direct interaction of the kringle domain of urokinase-type plasminogen activator (uPA) and integrin alpha v beta 3 induces signal transduction and enhances plasminogen activation

    OpenAIRE

    Tarui, Takehiko; Akakura, Nobuaki; Majumdar, Mousumi; Andronicos, Nicholas; Takagi, Junichi; Mazar, Andrew P.; Bdeir, Khalil; Kuo, Alice; Yarovoi, Serge V.; Cines, Douglas B.; Takada, Yoshikazu

    2006-01-01

    It has been questioned whether there are receptors for urokinase-type plasminogen activator (uPA) that facilitate plasminogen activation other than the high affinity uPA receptor (uPAR/CD87) since studies of uPAR knockout mice did not support a major role of uPAR in plasminogen activation. uPA also promotes cell adhesion, chemotaxis, and proliferation besides plasminogen activation. These uPA-induced signaling events are not mediated by uPAR, but mediated by unidentified, lower-affinity recep...

  8. Effect of Heparin on the Cell Proliferation and u-PA/PAI-1 Expression on Glomeruli in Rat Anti-thy1 Glomerulonephritis%肝素对大鼠thy-1肾炎肾小球细胞增生和 u-PA/PAI?1表达的影响

    Institute of Scientific and Technical Information of China (English)

    秦蓉; 张农; 刘琛; 陈广平; 张秀荣; 郭慕依

    2000-01-01

    目的研究u-PA及其抑制物PAI-1在大鼠thy-1肾炎中的表达及意义,并探讨肝素治疗对其表达的影响。方法应用ABC免疫酶标法及图像分析技术,观察对照组、肾炎组和肝素组动物模型肾小球u-PA和PAI-1的表达情况,并与光镜下肾小球细胞计数作相关性分析。结果肝素组动物在其治疗后7、14、21 d时,肾小球细胞数明显减少,与肾炎组比较P值分别小于0.05或0. 01:肾炎组、肝素组肾小球u-PA和PAI-1的表达均高于对照组;于实验3、7、14和21 d时,肾炎组动物的肾小球细胞数增多与u-PA和PAI-1的表达呈正相关(P<0.05或0.01);肝素组于实验3、7 d时,肾小球细胞数的减少与PAI-1表达降低有关(P<0.05)。结论大鼠thy-1肾炎的肾小球细胞数增多与其u-PA和PAI-1表达程度呈正相关;肝素治疗可减轻大鼠thy-1肾炎肾小球细胞增生,其作用机制可能与病程早期对肾小球PAI-1表达的抑制有关%Purpose To investigate the significance of u-PA and PAI-1 expression on the glomeruli,and the effect of heparin on their expressions in rat anti-thy1 glomerulonephritis. Methods We analyzed the cell proliferation and the expression of u-PA/PAI-1 on the glomeruli by immunohistochemistry and quantitative analysis of immunostaining. Results The cell proliferation of the glomeruli decreased significantly at 7 th,14 th,21 st day after heparin treatment in comparison to the glomerulonephritic group(P<0.05 or 0.01).The expression of u-PA and PAI-1 on the glomeruli in glomerulonephritic and heparin-treated groups was higher than that in the control group.At 3 rd,7 th,14 th,21 st day,the glomerular hypercellularity in the glomerulonephritic group was closely related to the increased expression of u-PA and PAI-1(P<0.05 or 0.01).At 3 rd,7 th day,the decreased cell proliferation of the glomeruli in heparin-treated group had close relationship with the decreased expression of PAI-1(P<0.05).

  9. In black south africans from rural and urban communities, the 4G/5G PAI-1 polymorphism influences PAI-1 activity, but not plasma clot lysis time

    NARCIS (Netherlands)

    Z. de Lange (Zelda); D.C. Rijken (Dingeman); T. Hoekstra (Tiny); K.R. Conradie (Karin); J.C. Jerling (Johann); M. Pieters (Marlien)

    2013-01-01

    textabstractData on genetic and environmental factors influencing PAI-1 levels and their consequent effect on clot lysis in black African populations are limited. We identified polymorphisms in the promoter area of the PAI-1 gene and determined their influence on PAI-1act levels and plasma clot lysi

  10. In black South Africans from rural and urban communities, the 4G/5G PAI-1 polymorphism influences PAI-1 activity, but not plasma clot lysis time.

    Directory of Open Access Journals (Sweden)

    Zelda de Lange

    Full Text Available Data on genetic and environmental factors influencing PAI-1 levels and their consequent effect on clot lysis in black African populations are limited. We identified polymorphisms in the promoter area of the PAI-1 gene and determined their influence on PAI-1act levels and plasma clot lysis time (CLT. We also describe gene-environment interactions and the effect of urbanisation. Data from 2010 apparently healthy urban and rural black participants from the South African arm of the PURE study were cross-sectionally analysed. The 5G allele frequency of the 4G/5G polymorphism was 0.85. PAI-1act increased across genotypes in the urban subgroup (p = 0.009 but not significantly in the rural subgroup, while CLT did not differ across genotypes. Significant interaction terms were found between the 4G/5G polymorphism and BMI, waist circumference and triglycerides in determining PAI-1act, and between the 4G/5G polymorphism and fibrinogen and fibrinogen gamma prime in determining CLT. The C428T and G429A polymorphisms did not show direct relationships with PAI-1act or CLT but they did influence the association of other environmental factors with PAI-1act and CLT. Several of these interactions differed significantly between rural and urban subgroups, particularly in individuals harbouring the mutant alleles. In conclusion, although the 4G/5G polymorphism significantly affected PAI-1act, it contributed less than 1% to the PAI-1act variance. (Central obesity was the biggest contributor to PAI-1act variance (12.5%. Urbanisation significantly influenced the effect of the 4G/5G polymorphism on PAI-1act as well as gene-environment interactions for the C428T and G429A genotypes in determining PAI-1act and CLT.

  11. Ligustrazini Inhibits Endotoxin Induced PAI-1 Expression in Human Umbilical Vein Endothelial Cells

    Institute of Scientific and Technical Information of China (English)

    阮秋蓉; 邓仲端; 宋建新

    2001-01-01

    Plasminogen activator inhibitor 1 (PAI-1) is one of important coagulant factors. Endotoxin lipopolysaccharide (LPS) induces thrombosis by stimulating PAI-1 secretion of vascular cells (EC). Using sandwich enzyme-linked immunosorbent assay (ELISA) and Northern blot, was investigated the effects of Chinese medicine ligustrazini on PAI-1 expression in EC and LPS-stimulated EC. The results showed that ligustrazini inhibited both basal and LPS-induced PAI-1 mRNA expression in EC. The effect of ligustrazini on LPS-induced PAI-1 secretion worked in a dose-dependent manner. This study provided theoretic and experimental evidence for use of ligustrazini against septic shock and cardiovascular diseases.

  12. A rapid detection method for PAI-1 promoter insertion/deletion polymorphism (4G/5G

    Directory of Open Access Journals (Sweden)

    Annichino-Bizzacchi Joyce M.

    1998-01-01

    Full Text Available Plasminogen activator inhibitor-1 (PAI-1 is an important inhibitor of fibrinolysis, and increased levels of PAI-1 are associated with atheroma and myocardial infarction. A common 4G/5G insertion/deletion polymorphism located in the promoter region of PAI-1 gene has been described associated with PAI-1 activity in plasma levels. Genotyping of this polymorphism is commonly conducted with an allele-specific oligonucleotide melting technique. In the present study, we describe a quick, easy method for genotyping 4G/5G polymorphism in the promoter region of the PAI-1 gene.

  13. Regulation of programmed cell death by plasminogen activator inhibitor type 1 (PAI-1)

    DEFF Research Database (Denmark)

    Lademann, Ulrik Axel; Rømer, Maria Unni Koefoed

    2008-01-01

    PA) observed in tumours; however, several lines of evidence suggest that PAI-1 may contribute directly to the pathology of the disease. PAI-1 has been reported to have an effect on most of the basic cellular processes including cell adhesion, cell migration, cell invasion, and cell proliferation and increasing...... numbers of reports suggest that PAI-1 also can regulate programmed cell death (PCD) in cancer cells and normal cells. A number of reports suggest that PAI-1 can inhibit PCD through its pro-adhesive/anti-proteolytic property whereas other reports suggest that PAI-1 induces PCD through its anti......-adhesive property.Furthermore,it has been suggested that PAI-1 can either induce or inhibit PCD though activation of cell signalling pathways.This review will focus on the regulation of programmed cell death by PAI-1 in both normal cells and cancer cells....

  14. Plasminogen activator inhibitor-1 removal using dextran sulphate columns. Evidence of PAI-1 homeostasis.

    LENUS (Irish Health Repository)

    Maher, Vincent M G

    2009-08-01

    Patients with high plasma plasminogen activator inhibitor-1 (PAI-1) antigen levels are prone to develop thrombosis. Lowering PAI-1 levels may offer a therapeutic option and help to better understand PAI-1 metabolism. We examined the effect on plasma PAI-1 levels of LDL-apheresis using dextran sulphate (DS) columns in 12 patients (9 male, 3 female, 49 +\\/- 10 years) with heterozygous familial hypercholesterolaemia and coronary artery disease. One plasma volume equivalent (2.3-4.0 l) was treated during each procedure (at flow rates of 23 +\\/- 2 ml\\/min). Lipids and PAI-1 antigen levels were measured in plasma before and immediately after 19 aphereses (once in 7 patients, twice in 3 patients and three times in 2 patients) and also at 3 and 7 days post apheresis in five of these patients and in the column eluates from 8 of these patients. DS-apheresis reduced plasma cholesterol (50 +\\/- 8%), triglyceride (45 +\\/- 27%), apolipoprotein B (59 +\\/- 10%) and PAI-1 antigen levels from 10.2 +\\/- 5.2 to 6.0 +\\/- 3.1 ng\\/ml (P = 0.005). The PAI-I changes were independent of circadian variation. PAI-I bound to the DS-columns (3.51 +\\/- 1.03 ng\\/ml filtered plasma) and the percent of filtered PAI-1 that was bound correlated inversely (r = -0.81, P < 0.02) with basal PAI-1 levels indicating a high affinity saturable binding process. In four patients, plasma PAI-1 levels post-apheresis were higher than expected based on the amount of PAI-removed by the DS columns. The difference between the expected and actual PAI-1 level post apheresis, reflecting PAI-1 secretion or extracellular redistribution, correlated inversely with basal PAI-1 levels (r = -0.83, P = 0.01). PAI-1 levels returned to baseline pre-apheresis values 7 days post apheresis. PAI-1 antigen may be removed from plasma without adverse effect, resulting temporarily in its extracellular redistribution and restoration to baseline levels over one week. PAI-1 redistribution particularly when baseline pre

  15. Tissue-specific PAI-1 gene expression and glycosylation pattern in insulin-resistant old rats.

    Science.gov (United States)

    Serrano, R; Barrenetxe, J; Orbe, J; Rodríguez, J A; Gallardo, N; Martínez, C; Andrés, A; Páramo, J A

    2009-11-01

    Increased levels of plasminogen activator inhibitor-1 (PAI-1) have been associated with obesity, aging, insulin resistance, and type 2 diabetes, conditions that contribute to increased cardiovascular risk. PAI-1 is expressed in a variety of tissues, but the cellular origin of plasma PAI-1 is unknown. To link insulin resistance, aging, and cardiovascular disease, we examined the expression and glycosylation pattern of PAI-1 in liver and white adipose tissue (WAT) from adult (3 mo) and insulin-resistant old (24 mo) Wistar rats. Glycosylated PAI-1 protein was also purified by affinity chromatography from endothelial culture supernatans to analyze its inhibitory activity. We also analyzed the contribution of adipocytes and stromal vascular cells from WAT to PAI-1 levels with aging. Aging caused a significant increase of PAI-1 mRNA (P < 0.001) in WAT that was predominantly due to the adipocytes and not to stroma-vascular cells, while there was no modification in liver from aged rats. Moreover, PAI-1 expression increased during preadipocyte differentiation (P < 0.001). Furthermore, we found a tissue-dependent PAI-1 glycosylation pattern: adipose tissue only expresses the glycosylated PAI-1 form, whereas the liver mainly expresses the nonglycosylated form. Finally, we also found evidences suggesting that the glycosylated PAI-1 form shows higher inhibitory activity than the nonglycosylated. Our data suggest that WAT may be a major source of the elevated plasma levels of PAI-1 in insulin-resistant old rats. Additionally, the high degree of PAI-1 glycosylation and activity, together with the significant increase in visceral fat in old rats, may well contribute to an increased cardiovascular risk associated with insulin-resistant states.

  16. Interaction of Plasminogen Activator Inhibitor Type-1 (PAI-1) with Vitronectin

    OpenAIRE

    Schröck, Florian Rudolf

    2005-01-01

    The serpin plasminogen activator inhibitor type-1 (PAI-1) is of importance in physiological processes such as fibrinolysis and thrombolysis as well as in pathophysiological processes like thrombosis, tumor cell adhesion or invasion, and metastasis. The interaction of PAI-1 with the extracellular matrix protein vitronectin (Vn) was implicated to play an important role in several of these processes and is therefore a possible target for therapeutic strategies. Understanding the PAI-1/Vn interac...

  17. Study on the expression of tPA and PAI-1 in endometriosis peritoneum treated by GnRH-a%GnRH-a对子宫内膜异位症腹膜纤溶相关因子tPA/PAI-1表达影响的研究

    Institute of Scientific and Technical Information of China (English)

    李孟慧; 冷金花; 李成龙; 史精华; 贾双征; 郎景和

    2012-01-01

    Objective; To investigate the expression levels of fibrinolytic factors in the endometriosis(EM) peritoneum and the different expressions after treated by GnRH-a. Method; Detect the expression levels of tPA,PAI-l and uPA of peritoneum from EM group and control group by immunohistochemistry methods. Investigate the effect of gonadotropin-releasing hormone analogue( GnRH-a) on the expression of those fibrinolytic factors. Results; The'levels of tPA,PAI-l and uPA from peritoneum of EM group were higher than those in the control group and there was statistically significant differences (P<0. 01). GnRH-a could up-regulate tPA levels, down-regulate PAI-1 and the difference was statistically significant (P<0. 05) ,but GnRH-a had no effect on uPA. Conclusions;Compared to the control group,EM group have the up-regulating of tPA,PAI-l,uPA,which may be the response of peritoneum to injuries; GnRH-a may promote fibrinolysis by regulating fibrinolytic factors, such as increasing tPA and decreasing PAI-1, and then inhibit the peritoneal adhesion formation.%目的:探讨子宫内膜异位症(EM)腹膜组织纤溶相关因子表达水平及使用促性腺激素释放激素类似物(GnRH-a)后表达的变化.方法:应用免疫组织化学方法检测组织型纤溶酶原激活物( tPA)、纤溶酶原激活物抑制剂(PAI)-1、尿激酶纤溶酶原激活物( uPA)在内异症和正常对照组腹膜组织中的表达.分析GnRH-a对各种纤溶相关因子表达的影响.结果:内异症腹膜组织中纤溶相关因子tPA、PAI-1、uPA表达均高于对照组腹膜组织的相应表达,差异有统计学意义(P<0.01).应用GnRH-a的EM组tPA表达水平明显升高,且PAI-1表达水平降低,差异有统计学意义(P<0.05),GnRH-a应用对uPA表达无明显影响.结论:与正常腹膜相比内异症腹膜组织纤溶相关因子tPA、PAI-1、uPA表达水平发生变化,纤溶活性的变化可能是腹膜对损伤发生的反应.GnRH-a应用使tPA表达升高、PAI-1表达

  18. Resveratrol Suppresses PAI-1 Gene Expression in a Human In Vitro Model of Inflamed Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Ivana Zagotta

    2013-01-01

    Full Text Available Increased plasminogen activator inhibitor-1 (PAI-1 levels are associated with a number of pathophysiological complications; among them is obesity. Resveratrol was proposed to improve obesity-related health problems, but the effect of resveratrol on PAI-1 gene expression in obesity is not completely understood. In this study, we used SGBS adipocytes and a model of human adipose tissue inflammation to examine the effects of resveratrol on the production of PAI-1. Treatment of SGBS adipocytes with resveratrol reduced PAI-1 mRNA and protein in a time- and concentration-dependent manner. Further experiments showed that obesity-associated inflammatory conditions lead to the upregulation of PAI-1 gene expression which was antagonized by resveratrol. Although signaling via PI3K, Sirt1, AMPK, ROS, and Nrf2 appeared to play a significant role in the modulation of PAI-1 gene expression under noninflammatory conditions, those signaling components were not involved in mediating the resveratrol effects on PAI-1 production under inflammatory conditions. Instead, we demonstrate that the resveratrol effects on PAI-1 induction under inflammatory conditions were mediated via inhibition of the NFκB pathway. Together, resveratrol can act as NFκB inhibitor in adipocytes and thus the subsequently reduced PAI-1 expression in inflamed adipose tissue might provide a new insight towards novel treatment options of obesity.

  19. The 4G/4G Genotype of PAI-1 Polymorphism Is Associated with Higher Plasma PAI-1 Concentrations and Mortality in Patients with Severe Sepsis.

    Directory of Open Access Journals (Sweden)

    Leonardo Lorente

    Full Text Available Two studies have reported that patients with the 4G/4G genotype of the plasminogen activator inhibitor-1 (PAI-1 genetic polymorphism had higher plasma PAI-1 concentrations and higher risk of death than those with the 4G/5G or 5G/5G genotypes; one study involved 175 children with meningococcal disease, and the other included 88 adult patients with septic shock. Thus, the objective of this study was to determine whether there is an association between carriage of the 4G/4G genotype, plasma PAI-1 concentrations and mortality in a large series of adult septic patients.An observational, prospective, multicenter study was carried out in six Spanish Intensive Care Units including severe septic patients. We determined the PAI-1 4G/5G polymorphism and plasma PAI-1 concentrations in all patients. The end-points of the study were 30-day and 6-month mortality.We included a total of 260 patients, 82 (31.5% with 4G/4G, 126 (48.5% with 4G/5G and 52 (20.0% with 5G/5G genotype. Multivariate logistic regression analysis showed that the 4G/4G genotype was associated with higher mortality at 30 days (Odds Ratio = 1.95; 95% CI = 1.063-3.561; p = 0.03 and at 6 months (Odds Ratio = 2.19; 95% CI = 1.221-3.934; p = 0.01, and that higher plasma PAI-1 concentrations were associated with higher mortality at 30 days (Odds Ratio = 1.01; 95% CI = 1.002-1.022; p = 0.02 at 6 months (Odds Ratio = 1.01; 95% CI = 1.003-1.023; p = 0.01. Multivariate linear regression analysis showed that increased plasma PAI-1 concentrations were associated with the PAI-1 4G/4G genotype (regression coefficient = 4.82; 95% CI = 3.227 to 6.406; p<0.001.The major findings of our study, to our knowledge the largest series reporting data about 4G/5G polymorphism of the PAI-1 gene, plasma PAI-1 concentrations and mortality in septic patients, were that septic patients with the 4G/4G genotype had higher plasma PAI-1 concentrations and higher risk of death than those with 4G/5G or 5G/5G genotypes.

  20. Protein Microarrays for Quantitative Detection of PAI-1 in Serum

    Institute of Scientific and Technical Information of China (English)

    Xu Ma; Qing-yun Zhang

    2012-01-01

    Objective:Plasminogen activator inhibitor-1 (PAl-1),one crucial component of the plasminogen activator system,is a major player in the pathogenesis of many vascular diseases as well as in cancer.High levels of PAI-1 in breast cancer tissue are associated with poor prognosis.The aim of this study is to evaluate rigorously the potential of serum PAl-1 concentration functioning as a general screening test in diagnostic or prognostic assays.Methods:A protein-microarray-based sandwich fluorescence immunoassay (FIA) was developed to detect PAl-1 in serum.Several conditions of this microarray-based FIA were optimized to establish an efficacious method.Serum specimens of 84 healthy women and 285 women with breast cancer were analyzed using the optimized FIA microarray.Results:The median serum PAl-1 level of breast cancer patients was higher than that of healthy women (109.7 ng/ml vs.63.4 ng/ml).Analysis of covariance revealed that PAl-1 levels of the two groups were significantly different (P<0.001) when controlling for an age effect on PAl-1 levels.However,PAl-1 values in TNM stage Ⅰ-Ⅳ patients respectively were not significantly different from each other.Conclusion:This microarray-based sandwich FIA holds potential for quantitative analysis of tumor markers such as PAl-1.

  1. Effect of aldosterone and glycyrrhetinic acid on the protein expression of PAI-1 and p22(phox) in human mononuclear leukocytes.

    Science.gov (United States)

    Calò, Lorenzo A; Zaghetto, Francesca; Pagnin, Elisa; Davis, Paul A; De Mozzi, Paola; Sartorato, Paola; Martire, Giuseppe; Fiore, Cristina; Armanini, Decio

    2004-04-01

    Aldosterone excess can produce heart and kidney fibrosis, which seem to be related to a direct effect of aldosterone at the level of specific receptors. We report a direct, mineralocorticoid-mediated effect on the protein expression of two markers of oxidative stress after incubation of mononuclear leukocytes with 1 x 10(-8) M aldosterone (p22(phox)/beta-actin = 1.38 +/- 0.05 and PAI-1/beta-actin = 1.80 +/- 0.05). The same effect was also found with 3 x 10(-5) M glycyrrhetinic acid, the principal constituent of licorice root (p22(phox)/beta-actin = 1.37 +/- 0.97 and PAI-1/beta-actin = 1.80 +/- 0.04). The effect of both aldosterone and glycyrrhetinic acid is blocked by incubation with added 1 x 10(-6) M of receptor-antagonist canrenone. Canrenone alone did not show any effect. PAI-1 related protein was also found using 4 x 10(-9) M aldosterone. Incubations with 1 x 10(-9) M for 3 hours as well as 1 x 10(-8) M aldosterone for 5, 10, and 20 minutes were ineffective for both proteins. These data support the previous finding of an involvement of mononuclear leukocytes in the pathogenesis of the oxidative stress induced by hyperaldosteronism. In addition, the results confirm our previous data on a direct effect of glycyrrhetinic acid at the level of mineralocorticoid receptors. PMID:15070972

  2. 4G/4G Genotype of PAI-1 Gene Is Associated With Reduced Risk of Stroke in Elderly

    NARCIS (Netherlands)

    Hoekstra, T.; Geleijnse, J.M.; Kluft, C.; Giltay, E.J.; Kok, F.J.; Schouten, E.G.

    2003-01-01

    Background and Purpose - Plasminogen activator inhibitor type 1 ( PAI- 1) is the main inhibitor of fibrinolysis, and high levels may increase the risk of cardiovascular disease. The 4G/ 5G polymorphism affects PAI- 1 gene transcription with lower levels of plasma PAI- 1 in the presence of the 5G all

  3. Crohn's disease but not chronic ulcerative colitis induces the expression of PAI-1 in enteric neurons

    DEFF Research Database (Denmark)

    Laerum, O.D.; Illemann, M.; Skarstein, A.;

    2008-01-01

    by immunohistochemical techniques. RESULTS: PAI-1 was found in a subset of neurons primarily located in the submucosal plexus of the small and large intestine in 24 of 28 cases (86%) with Crohn's disease, but in none of 17 cases with chronic ulcerative colitis and other severe inflammatory conditions in the intestinal......OBJECTIVES: Chronic inflammation of the intestinal wall is the common characteristic of Crohn's disease and ulcerative colitis; disorders, which in some cases can be difficult to distinguish. The inflammation also affects the local neuronal plexuses of the enteric nervous system. It is known....... CONCLUSIONS: PAI-1-positive neurons in inflammatory bowel disease are linked to chronic inflammation in Crohn's disease, implying PAI-1 as a potential parameter for the differential diagnosis between Crohn's disease and ulcerative colitis. The findings also suggest that PAI-1 in neurons is related to pain...

  4. Impact of Mesenchymal Stem Cell secreted PAI-1 on colon cancer cell migration and proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Hogan, Niamh M. [Discipline of Surgery, School of Medicine, National University of Ireland, Galway (Ireland); Joyce, Myles R. [Department of Colorectal Surgery, University College Hospital, Galway (Ireland); Murphy, J. Mary; Barry, Frank P.; O’Brien, Timothy [Regenerative Medicine Institute, National University of Ireland, Galway (Ireland); Kerin, Michael J. [Discipline of Surgery, School of Medicine, National University of Ireland, Galway (Ireland); Dwyer, Roisin M., E-mail: roisin.dwyer@nuigalway.ie [Discipline of Surgery, School of Medicine, National University of Ireland, Galway (Ireland)

    2013-06-14

    Highlights: •MSCs were directly co-cultured with colorectal cancer (CRC) cells on 3D scaffolds. •MSCs influence CRC protein/gene expression, proliferation and migration. •We report a significant functional role of MSC-secreted PAI-1 in colon cancer. -- Abstract: Mesenchymal Stem Cells are known to engraft and integrate into the architecture of colorectal tumours, with little known regarding their fate following engraftment. This study aimed to investigate mediators of Mesenchymal Stem Cell (MSC) and colon cancer cell (CCC) interactions. Mesenchymal Stem Cells and colon cancer cells (HT29 and HCT-116) were cultured individually or in co-culture on 3-dimensional scaffolds. Conditioned media containing all secreted factors was harvested at day 1, 3 and 7. Chemokine secretion and expression were analyzed by Chemi-array, ELISA (Macrophage migration inhibitory factor (MIF), plasminogen activator inhibitor type 1 (PAI-1)) and RQ-PCR. Colon cancer cell migration and proliferation in response to recombinant PAI-1, MSCs and MSCs + antibody to PAI-1 was analyzed using Transwell inserts and an MTS proliferation assay respectively. Chemi-array revealed secretion of a wide range of factors by each cell population, including PAI-1and MIF. ELISA analysis revealed Mesenchymal Stem Cells to secrete the highest levels of PAI-1 (MSC mean 10.6 ng/mL, CCC mean 1.01 ng/mL), while colon cancer cells were the principal source of MIF. MSC-secreted PAI-1 stimulated significant migration of both CCC lines, with an antibody to the chemokine shown to block this effect (67–88% blocking,). A cell-line dependant effect on CCC proliferation was shown for Mesenchymal Stem Cell-secreted PAI-1 with HCT-116 cells showing decreased proliferation at all concentrations, and HT29 cells showing increased proliferation in the presence of higher PAI-1 levels. This is the first study to identify PAI-1 as an important mediator of Mesenchymal Stem Cell/colon cancer cell interactions and highlights the

  5. Synthesis and in vivo preclinical evaluation of an 18F labeled uPA inhibitor as a potential PET imaging agent

    International Nuclear Information System (INIS)

    Introduction: The urokinase plasminogen activator (uPA) system is a proteolytic cascade involved in tumor invasion and metastasis. uPA and its inhibitor PAI-1 are described as biomarkers for breast cancer with the highest level of evidence. The present study describes the synthesis and first in vivo application of an activity based uPA PET probe. Methods: Based on the design of a small irreversible and selective uPA inhibitor we developed an 18F-labeled activity based probe for uPA imaging. Human uPA expressing MDA-MB-231-luc2-GFP cells were inoculated in the mammary fat pads of nude mice and treated with the probe once tumors reached a volume of 150 mm3. Scans were performed at 0.25, 0.75, 1.5, 4 and 6 h post injection. To evaluate tumor uptake in vivo and ex vivo data were gathered. Biodistribution data of the organs and tissues of interest were collected at all time points. Due to a relatively low tumor uptake, probe stability was further evaluated. Results: The uPA targeting PET tracer was produced in high purity and with good specific radioactivity. In vivo PET data showed a maximum tumor uptake of 2,51 ± 0,32 %ID/g at 4 h p.i. A significant correlation between in vivo and ex vivo tumor uptake calculation was found (R = 0.75; p < 0.01). Due to a high blood signal at all time points, probe stability was further examined revealing high plasma protein binding and low plasma stability. Conclusions: In vivo and ex vivo results clearly demonstrate that uPA expressing tumors can be detected with non-invasive PET imaging. Stability tests suggest that further optimization is needed to provide a better tumor-to-background contrast

  6. Inhibition of PAI-1 Limits Tumor Angiogenesis Regardless of Angiogenic Stimuli in Malignant Pleural Mesothelioma.

    Science.gov (United States)

    Takayama, Yusuke; Hattori, Noboru; Hamada, Hironobu; Masuda, Takeshi; Omori, Keitaro; Akita, Shin; Iwamoto, Hiroshi; Fujitaka, Kazunori; Kohno, Nobuoki

    2016-06-01

    Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor that secretes various angiogenic factors. The main inhibitor of plasminogen activators, PAI-1 (SERPINE1), has been implicated in tumor progression and angiogenesis, and high PAI-1 expression has been associated with poor prognosis in MPM patients. In this study, we examined the antiangiogenic effects of PAI-1 inhibition in MPM. We administered the PAI-1 inhibitor, SK-216, to orthotopic mouse models in which MPM cells expressing high levels of VEGF (VEGFA) or bFGF (FGF2) were intrapleurally transplanted. SK-216 administration reduced tumor weights and the degree of angiogenesis in intrapleural tumors, irrespective of their angiogenic expression profiles. In addition, a combination of SK-216 and the chemotherapeutic agent cisplatin significantly reduced tumor weights compared with monotherapy, prolonging the survival of animals compared with cisplatin treatment alone. Furthermore, SK-216 inhibited migration and tube formation of cultured human umbilical vein endothelial cells induced by various angiogenic factors known to be secreted by MPM. These findings suggest that PAI-1 inactivation by SK-216 may represent a general strategy for inhibiting angiogenesis, including for the treatment of MPM. Cancer Res; 76(11); 3285-94. ©2016 AACR. PMID:27197170

  7. HIF-2alpha-dependent PAI-1 induction contributes to angiogenesis in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Geis, Theresa, E-mail: geis@biochem.uni-frankfurt.de [Institute of Biochemistry I—Pathobiochemistry, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany); Döring, Claudia, E-mail: C.Doering@em.uni-frankfurt.de [Dr. Senckenberg Institute of Pathology, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany); Popp, Rüdiger, E-mail: popp@vrc.uni-frankfurt.de [Institute for Vascular Signalling, Centre for Molecular Medicine, Faculty of Medicine Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60596 Frankfurt am Main (Germany); Grossmann, Nina, E-mail: grossmann@biochem.uni-frankfurt.de [Institute of Biochemistry I—Pathobiochemistry, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany); Fleming, Ingrid, E-mail: fleming@vrc.uni-frankfurt.de [Institute for Vascular Signalling, Centre for Molecular Medicine, Faculty of Medicine Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60596 Frankfurt am Main (Germany); Hansmann, Martin-Leo, E-mail: m.l.hansmann@em.uni-frankfurt.de [Dr. Senckenberg Institute of Pathology, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany); Dehne, Nathalie, E-mail: dehne@biochem.uni-frankfurt.de [Institute of Biochemistry I—Pathobiochemistry, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany); Brüne, Bernhard, E-mail: b.bruene@biochem.uni-frankfurt.de [Institute of Biochemistry I—Pathobiochemistry, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany)

    2015-02-01

    Hypoxia promotes progression of hepatocellular carcinoma (HCC), not only affecting tumor cell proliferation and invasion, but also angiogenesis and thus, increasing the risk of metastasis. Hypoxia inducible factors (HIF)-1α and -2α cause adaptation of tumors to hypoxia, still with uncertainties towards the angiogenic switch. We created a stable knockdown of HIF-1α and HIF-2α in HepG2 cells and generated cocultures of HepG2 spheroids with embryonic bodies as an in vitro tumor model mimicking the cancer microenvironment. The naturally occuring oxygen and nutrient gradients within the cocultures allow us to question the role of distinct HIF isoforms in regulating HCC angiogenesis. In cocultures with a HIF-2α knockdown, angiogenesis was attenuated, while the knockdown of HIF-1α was without effect. Microarray analysis identified plasminogen activator inhibitor 1 (PAI-1) as a HIF-2α target gene in HepG2 cells. The knockdown of PAI-1 in HepG2 cells also lowered angiogenesis. Blocking plasmin, the downstream target of PAI-1, with aprotinin in HIF-2α knockdown (k/d) cells proved a cause–effect relation and restored angiogenesis, with no effect on control cocultures. Suggestively, HIF-2α increases PAI-1 to lower concentrations of active plasmin, thereby supporting angiogenesis. We conclude that the HIF-2α target gene PAI-1 favors the angiogenic switch in HCC. - Highlights: • HepG2 were cocultured with stem cells to mimic a cancer microenvironment in vitro. • A knockdown of HIF-2α reduces angiogenesis. • PAI-1 was identified as a HIF-2α target gene in HCC by microarray analysis. • HIF-2α induces the angiogenic switch via inhibition of plasmin.

  8. 4G5G-Polymorphismus des PAI-1-Genes und Restenoserisiko nach koronarer Stentimplantation

    OpenAIRE

    Lahn, Christina

    2005-01-01

    In dieser Studie wurde der 4G5G-Polymorphismus des PAI-1 von 1850 Patienten mit koronarer Stentimplantation, bei denen nach 6 Monaten eine angiographische Kontrolluntersuchung erfolgte und das klinische Follow-up über 1 Jahr erhoben wurde, evaluiert. Untersucht wurde, ob der Insertions-Deletions-Polymorphismus in der Promotorregion des PAI-1-Genes einen Einfluss auf die Instent-Restenose hat. Die 4G-Allel-Frequenz betrug 0,56. 32,5 % der für das 4G-Allel homozygoten Patienten entwickelten ein...

  9. The effect of thyroid hormones on the white adipose tissue gene expression of PAI-1 and its serum concentration

    Directory of Open Access Journals (Sweden)

    C. Biz

    2009-12-01

    Full Text Available Metabolic syndrome is associated with an increased risk of developing cardiovascular diseases and Plasminogen activator inhibitor 1 (PAI-1 overexpression may play a significant role in this process. A positive correlation between adipose tissue gene expression of PAI-1 and its serum concentration has been reported. Furthermore, high serum levels of thyroid hormones (T3 and T4 and PAI-1 have been observed in obese children. The present study evaluates the impact of thyroid hormone treatment on white adipose tissue PAI-1 gene expression and its serum concentration. Male Wistar rats (60 days old were treated for three weeks with T4 (50 µg/day, Hyper or with saline (control. Additionally, 3T3-L1 adipocytes were treated for 24 h with T4 (100 nM or T3 (100 nM. PAI-1 gene expression was determined by real-time PCR, while the serum concentration of PAI-1 was measured by ELISA using a commercial kit (Innovative Research, USA. Both the serum concentration of PAI-1 and mRNA levels were similar between groups in retroperitoneal and epididymal white adipose tissue. Using 3T3-L1 adipocytes, in vitro treatment with T4 and T3 increased the gene expression of PAI-1, suggesting non-genomic and genomic effects, respectively. These results demonstrate that thyroid hormones have different effects in vitro and in vivo on PAI-1 gene expression in adipocytes.

  10. Compression-induced HIF-1 enhances thrombosis and PAI-1 expression in mouse skin.

    Science.gov (United States)

    Kaneko, Maki; Minematsu, Takeo; Yoshida, Mikako; Nishijima, Yoshimi; Noguchi, Hiroshi; Ohta, Yasunori; Nakagami, Gojiro; Mori, Taketoshi; Sanada, Hiromi

    2015-09-01

    Pressure ulcers result from tissue hypoxia caused by external forces. Thrombosis due to external forces is considered important, and hypoxia inducible factor-1 (HIF-1) is a master regulator of pressure ulcer development. To date, however, their causal relationship has not been determined. This study therefore investigated the mutual relationship between thrombosis and HIF-1 activation in compressed mouse skin, based on a hypothesis that HIF-1 regulation by plasminogen activator inhibitor-1 (PAI-1) enhances thrombosis. Compression of mouse skin significantly increased the numbers of thrombi and HIF-1α-positive cells compared with control skin. A thrombosis inhibitor significantly reduced the numbers of HIF-1α-positive cells and an HIF-1 inhibitor significantly inhibited thrombosis in compressed skin tissue, suggesting a mutual relationship between thrombosis and HIF-1 activation. Compression of mouse skin also enhanced the level of Pai-1 messenger RNA expression, but this increase was significantly reduced by treatment with an HIF-1 inhibitor, whereas a thrombosis inhibitor had no effect. These results suggested the involvement of PAI-1 in HIF-1-enhanced thrombosis and that an additional factor participates in regulating Pai-1 expression in compressed skin. These findings may suggest new strategies in pressure ulcer management.

  11. Male-female differences in the genetic regulation of t-PA and PAI-1 levels in a Ghanaian population

    NARCIS (Netherlands)

    Schoenhard, J. A.; Asselbergs, F. W.; Poku, K. A.; Stocki, S. A.; Gordon, S.; Vaughan, D. E.; Brown, N. J.; Moore, J. H.; Williams, Scott M.

    2008-01-01

    Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) directly influence thrombus formation and degradation, and have been identified as risk factors for thromboembolic disease. Prior studies investigated determinants of t-PA and PAI-1 expression, but mainly in Cauca

  12. Effects of teneligliptin on PDMPs and PAI-1 in patients with diabetes on hemodialysis

    Directory of Open Access Journals (Sweden)

    Okuda Y

    2016-04-01

    Full Text Available Yoshinori Okuda,1 Seitaro Omoto,2 Takehito Taniura,3 Akira Shouzu,4 Shosaku Nomura,51Division of Internal Medicine, Meisei Memorial Hospital, 2Division of Internal Medicine, Kohrigaoka Yukeikai Hospital, 3Division of Internal Medicine, Daiwa Hospital, 4Division of Internal Medicine, Saiseikai Izuo Hospital, 5First Department of Internal Medicine, Kansai Medical University, Osaka, Japan Background: Cardiovascular disease (CVD is the main cause of death among hemodialysis (HD patients. The effects of the dipeptidyl peptidase-4 inhibitor teneligliptin on CVD-related biomarkers in patients with type 2 diabetes mellitus (T2DM receiving HD treatment are poorly understood. To determine whether teneligliptin has anti-CVD properties, we assessed its effects on soluble P-selectin (sP-selectin, platelet-derived microparticles (PDMPs, plasminogen activator inhibitor 1 (PAI-1, soluble E-selectin (sE-selectin, soluble vascular adhesion molecule 1 (sVCAM-1, and adiponectin plasma levels in HD and non-HD patients with T2DM. Methods: Patients with T2DM eligible for teneligliptin monotherapy or combination therapy (eg, teneligliptin plus a sulfonylurea were administered teneligliptin (20 mg/d once daily for 6 months. Plasma levels of sP-selectin, PDMPs, PAI-1, sE-selectin, sVCAM-1, and adiponectin were measured by enzyme-linked immunosorbent assay at baseline and after 3 months and 6 months of treatment. Results: Teneligliptin therapy significantly reduced plasma levels of sP-selectin, PDMPs, and PAI-1 compared with baseline levels, while significantly increasing adiponectin levels. sE-selectin and sVCAM-1 levels were significantly decreased only at 6 months. The reduction in sP-selectin, PDMPs, and PAI-1 was more significant in HD patients than in non-HD patients. However, the improvement in adiponectin levels was unchanged with HD treatment. Conclusion: By modulating PDMPs or PAI-1, teneligliptin shows an antiatherothrombotic effect that may be beneficial in

  13. The Effect of PAI-1 4G/5G Polymorphism and Clinical Factors on Coronary Artery Occlusion in Myocardial Infarction

    OpenAIRE

    Tajinder Kumar Parpugga; Vacis Tatarunas; Vilius Skipskis; Nora Kupstyte; Diana Zaliaduonyte-Peksiene; Vaiva Lesauskaite

    2015-01-01

    Objective. Data on the impact of PAI-1-675 4G/5G genotype for fibrinolysis during myocardial infarction are inconsistent. The aim of our study was to evaluate the association of clinical and genetic (PAI-1-675 4G/5G polymorphism) factors with coronary artery occlusion in patients with myocardial infarction. Materials and Methods. PAI-1-675 4G/5G detection was achieved by using Sanger sequencing in a sample of patients hospitalized for stent implantation due to myocardial infarction. We catego...

  14. Increased PAI-1 plasma levels and risk of death from dengue: No association with the 4G/5G promoter polymorphism

    NARCIS (Netherlands)

    A.T.A. Mairuhu; T.E. Setiati (Tatty); P. Koraka (Penelope); C.E. Hack (Erik); A. Leyte (Anja); S.M.H. Faradz (Sultana); H. ten Cate (Hugo); D.P.M. Brandjes (Dees); A.D.M.E. Osterhaus (Albert); P.H. Reitsma; E.C.M. van Gorp (Eric)

    2005-01-01

    textabstractBackground: Dengue virus infected patients have high plasminogen activator inhibitor type I (PAI-1) plasma concentrations. Whether the insertion/deletion (4G/5G) polymorphism in the promotor region of the PAI-1 gene is associated with increased PAI-1 plasma concentrations and with death

  15. PAI-1 modulates cell migration in a LRP1-dependent manner via β-catenin and ERK1/2

    DEFF Research Database (Denmark)

    Kozlova, Nina; Jensen, Jan Kristian; Chi, Tabughang Franklin;

    2015-01-01

    -catenin is important for that response. In addition, expression of β-catenin and β-catenin-dependent transcriptional activity were induced by PAI-1 in wild type MEFs, but not in LRP1-deficient cells. Moreover, PAI-1-induced ERK1/2 activation was more prominent in the LRP1-deficient cells and interestingly knockdown...... of β-catenin abolished this effect. Together, the data of the current study show that PAI-1 can promote cell migration via LRP1-dependent activation of the β-catenin and ERK1/2 MAPK pathway which may be important in stage-specific treatment of human diseases associated with high PAI-1 levels....

  16. Orphan nuclear receptor small heterodimer partner inhibits angiotensin II-stimulated PAI-1 expression in vascular smooth muscle cells

    OpenAIRE

    Lee, Kyeong-Min; Seo, Hye-Young; Kim, Mi-Kyung; Min, Ae-Kyung; Ryu, Seong-Yeol; Kim, Yoon-Nyun; Park, Young Joo; Choi, Hueng-Sik; Lee, Ki-Up; Park, Wan-Ju; Park, Keun-Gyu; Lee, In-Kyu

    2009-01-01

    Angiotensin II is a major effector molecule in the development of cardiovascular disease. In vascular smooth muscle cells (VSMCs), angiotensin II promotes cellular proliferation and extracellular matrix accumulation through the upregulation of plasminogen activator inhibitor-1 (PAI-1) expression. Previously, we demonstrated that small heterodimer partner (SHP) represses PAI-1 expression in the liver through the inhibition of TGF-β signaling pathways. Here, we investigated whether SHP inhibite...

  17. Prospective evaluation of prognostic factors uPA/PAI-1 in node-negative breast cancer: Phase III NNBC3-Europe trial (AGO, GBG, EORTC-PBG) comparing 6 × FEC versus 3 × FEC/3 × Docetaxel

    International Nuclear Information System (INIS)

    Today, more than 70% of patients with primary node-negative breast cancer are cured by local therapy alone. Many patients receive overtreatment by adjuvant chemotherapy due to inadequate risk assessment. So far, few clinical trials have prospectively evaluated tumor biology based prognostic factors. Risk assessment by a biological algorithm including invasion factors urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor type 1 (PAI-1) will assess up to 35-55% of node-negative patients as low-risk and thus avoid chemotherapy. In contrast, a clinical-pathological algorithm will only classify 20-40% of patients as low-risk. High-risk node-negative patients should receive chemotherapy. Anthracycline-based regimens are accepted as a standard, the additional benefit of taxanes remains an open question. The international NNBC3 ('Node Negative Breast Cancer 3-Europe') trial compares biological risk assessment (UP) using invasion factors uPA/PAI-1 with a clinical-pathological algorithm (CP). In this trial, the type of risk assessment (CP or UP) was chosen upfront by each center for its patients. Fresh frozen tissue was obtained to determine uPA/PAI-1 using an enzyme-linked immunosorbent assay (ELISA). Patients assessed as high-risk were stratified by human epidermal growth factor receptor 2 (HER2) status and then randomised to receive anthracycline-containing chemotherapy 5-Fluorouracil (F)/Epirubicin (E)/Cyclophosphymide (C) or an anthracycline-taxane sequence (FE100C*6 versus FE100C*3 followed by Docetaxel100*3). In this trial, 4,149 node-negative patients with operable breast cancer from 153 centers in Germany and France were included since 2002. Measurement of uPA/PAI-1 by ELISA was performed with standardised central quality assurance for 2,497 patients (60%) from 56 'UP'-centers. The NNBC 3-Europe trial showed that inclusion of patients into a clinical phase III trial is feasible based on biological testing of

  18. Cell density-dependent nuclear accumulation of ELK3 is involved in suppression of PAI-1 expression.

    Science.gov (United States)

    Tanaka, Shu; Nakao, Kazuyuki; Sekimoto, Toshihiro; Oka, Masahiro; Yoneda, Yoshihiro

    2013-07-01

    Cell-cell contact regulates the proliferation and differentiation of non-transformed cells, e.g., NIH/3T3 cells show growth arrest at high cell density. However, only a few reports described the dynamic behavior of transcription factors involved in this process. In this study, we showed that the mRNA levels of plasminogen activator inhibitor type 1 (PAI-1) decreased drastically at high cell density, and that ELK3, a member of the Ets transcription factor family, repressed PAI-1 expression. We also demonstrated that while ELK3 was distributed evenly throughout the cell at low cell density, it accumulated in the nucleus at high cell density, and that binding of DNA by ELK3 at the A domain facilitated its nuclear accumulation. Furthermore, we found that ETS1, a PAI-1 activator, occupied the ELK3-binding site within the PAI-1 promoter at low cell density, while it was released at high cell density. These results suggest that at high cell density, the switching of binding of transcription factors from ETS1 to ELK3 occurs at a specific binding site of the PAI-1 promoter, leading to the cell-density dependent suppression of PAI-1 expression. PMID:23708702

  19. Consequences of PAI-1 specific deletion in endothelium on radiation-induced intestinal damage

    International Nuclear Information System (INIS)

    Radiation-induced injury to healthy tissues is a real public health problem, since they are one of the most limiting factors that restrict efficiency of radiation therapy. This problematic is also part of the French Cancer Plan 2014-2017, and involves clinical research. Concepts surrounding the development of radiation-induced damage have gradually evolved into a contemporary and integrated view of the pathogenesis, involving all compartments of target tissue. Among them, endothelium seems to be central in the sequence of interrelated events that lead to the development of radiation-induced damage, although there are rare concrete elements that support this concept. By using new transgenic mouse models, this PhD project provides a direct demonstration of an endothelium-dependent continuum in evolution of radiation-induced intestinal damage. Indeed, changes in the endothelial phenotype through targeted deletion of the gene SERPINE1, chosen because of its key role in the development of radiation enteritis, influences various parameters of the development of the disease. Thus, lack of PAI-1 secretion by endothelial cells significantly improves survival of the animals, and limits severity of early and late tissue damage after a localized small bowel irradiation. Furthermore, these mice partially KO for PAI-1 showed a decrease in the number of apoptotic intestinal stem cells in the hours following irradiation, a decrease in the macrophages infiltrate density one week after irradiation, and a change in the polarization of macrophages throughout the pathophysiological process. In an effort to protect healthy tissues from radiation therapy side effects, without hindering the cancer treatment, PAI-1 seems to be an obvious therapeutic target. Conceptually, this work represents the direct demonstration of the link between endothelium phenotype and radiation enteritis pathogenesis. (author)

  20. Local transient unfolding of native state PAI-1 associated with serpin metastability

    DEFF Research Database (Denmark)

    Trelle, Morten Beck; Madsen, Jeppe B; Andreasen, Peter A;

    2014-01-01

    hydrogen/deuterium-exchange mass spectrometry (HDX-MS) it is shown that the serpin plasminogen activator inhibitor 1 (PAI-1) transiently unfolds under native condition, on a second-to-minute time scale. The unfolding regions comprise β-strand 5A as well as the underlying hydrophobic core, including β-strand......The metastability of the native fold makes serpin (serine protease inhibitor) proteins prone to pathological conformational change, often by insertion of an extra β-strand into the central β-sheet A. How this insertion is made possible is a hitherto unresolved question. By the use of advanced...

  1. uPA deficiency exacerbates muscular dystrophy in MDX mice

    OpenAIRE

    Suelves, Mònica; Vidal, Berta; Serrano, Antonio L.; Tjwa, Marc; Roma, Josep; López-Alemany, Roser; Luttun, Aernout; de Lagrán, María Martínez; Díaz, Maria Àngels; Jardí, Mercè; Roig, Manuel; Dierssen, Mara; Dewerchin, Mieke; Carmeliet, Peter; Muñoz-Cánoves, Pura

    2007-01-01

    Duchenne muscular dystrophy (DMD) is a fatal and incurable muscle degenerative disorder. We identify a function of the protease urokinase plasminogen activator (uPA) in mdx mice, a mouse model of DMD. The expression of uPA is induced in mdx dystrophic muscle, and the genetic loss of uPA in mdx mice exacerbated muscle dystrophy and reduced muscular function. Bone marrow (BM) transplantation experiments revealed a critical function for BM-derived uPA in mdx muscle repair via three mechanisms: (...

  2. Elevated Cytokines, Thrombin and PAI-1 in Severe HCPS Patients Due to Sin Nombre Virus

    Directory of Open Access Journals (Sweden)

    Virginie Bondu

    2015-02-01

    Full Text Available Sin Nombre Hantavirus (SNV, Bunyaviridae Hantavirus is a Category A pathogen that causes Hantavirus Cardiopulmonary Syndrome (HCPS with case fatality ratios generally ranging from 30% to 50%. HCPS is characterized by vascular leakage due to dysregulation of the endothelial barrier function. The loss of vascular integrity results in non-cardiogenic pulmonary edema, shock, multi-organ failure and death. Using Electric Cell-substrate Impedance Sensing (ECIS measurements, we found that plasma samples drawn from University of New Mexico Hospital patients with serologically-confirmed HCPS, induce loss of cell-cell adhesion in confluent epithelial and endothelial cell monolayers grown in ECIS cultureware. We show that the loss of cell-cell adhesion is sensitive to both thrombin and plasmin inhibitors in mild cases, and to thrombin only inhibition in severe cases, suggesting an increasing prothrombotic state with disease severity. A proteomic profile (2D gel electrophoresis and mass spectrometry of HCPS plasma samples in our cohort revealed robust antifibrinolytic activity among terminal case patients. The prothrombotic activity is highlighted by acute ≥30 to >100 fold increases in active plasminogen activator inhibitor (PAI-1 which, preceded death of the subjects within 48 h. Taken together, this suggests that PAI-1 might be a response to the severe pathology as it is expected to reduce plasmin activity and possibly thrombin activity in the terminal patients.

  3. A low-glycemic-index diet reduces plasma PAI-1 activity in overweight women

    DEFF Research Database (Denmark)

    Jensen, Lotte

    diet. Still, the relevance of GI in preventing the metabolic syndrome is controversial. Objectives The main purpose of the present study was to investigate the effect of 10 weeks intake of a low glycemic index vs. a high glycemic index high-carbohydrate, low fat ad libitum diet on plasma PAI-1 activity...... to decrease during weight loss. However, the beneficial effects of healthy diets on PAI-1 levels may not solely depend on weight loss, but other factors may also play a role. For example better glycemic control has been observed in diabetic patients after a low glycemic index (GI) diet compared to a high GI...... and antigen levels in overweight women. Methods 45 healthy overweight women (BMI 27.6 ± 0.2 kg/m2) were randomly assigned to a parallel 10 week intervention with a low GI (n=23) or high GI (n=22) diet. Fasting blood samples were obtained before and after the 10 weeks. To study the postprandial effect of LGI...

  4. Relationship between plasminogen activator inhibitor type-1 (PAI-1 gene polymorphisms and osteoporosis in Turkish women

    Directory of Open Access Journals (Sweden)

    Merih Ozgen

    2012-11-01

    Full Text Available OBJECTIVE: The development of osteoporosis is associated with several risk factors, such as genetic structures that affect bone turnover and bone mass. The impact of genetic structures on osteoporosis is not known. Plasminogen activator inhibitor type-1 regulates the bone matrix and bone balance. This study assessed the correlation between plasminogen activator inhibitor type-1 gene 4G/5G polymorphisms and osteoporosis in a population of Turkish women. METHODS: A total of 195 postmenopausal female patients who were diagnosed with osteoporosis (Group I based on bone mineral density measurements via dual-energy x-ray absorptiometry and 90 females with no osteoporosis (Group II were included in this study. Correlations between PAI-1 gene 4G/5G polymorphisms and osteoporosis were investigated through the identification of PAI-1 gene 4G/5G polymorphism genotypes using the polymerase chain reaction. RESULTS: No significant differences in the genotype and allele frequency of 4G/5G plasminogen activator inhibitor type-1 polymorphisms were observed between the two groups, and both groups exhibited the most frequently observed 4G5G genotype. CONCLUSION: No correlation between the development of osteoporosis in the female Turkish population and 4G/5G plasminogen activator inhibitor type-1 gene polymorphisms was observed.

  5. Role of ACE and PAI-1 Polymorphisms in the Development and Progression of Diabetic Retinopathy.

    Directory of Open Access Journals (Sweden)

    Saba Saleem

    Full Text Available In the present study we determined the association of angiotensin converting enzyme (ACE and plasminogen activator inhibitor-1 (PAI-1 gene polymorphisms with diabetic retinopathy (DR and its sub-clinical classes in Pakistani type 2 diabetic patients. A total of 353 diabetic subjects including 160 DR and 193 diabetic non retinopathy (DNR as well as 198 healthy controls were genotyped by allele specific polymerase chain reaction (PCR for ACE Insertion/Deletion (ID polymorphism, rs4646994 in intron 16 and PAI-1 4G/5G (deletion/insertion polymorphism, rs1799768 in promoter region of the gene. To statistically assess the genotype-phenotype association, multivariate logistic regression analysis was applied to the genotype data of DR, DNR and control individuals as well as the subtypes of DR. The ACE genotype ID was found to be significantly associated with DR (p = 0.009, odds ratio (OR 1.870 [95% confidence interval (CI = 1.04-3.36] and its sub-clinical class non-proliferative DR (NPDR (p = 0.006, OR 2.250 [95% CI = 1.098-4.620], while PAI polymorphism did not show any association with DR in the current cohort. In conclusion in Pakistani population the ACE ID polymorphism was observed to be significantly associated with DR and NPDR, but not with the severe form of the disease i.e. proliferative DR (PDR.

  6. Increased PAI-1 plasma levels and risk of death from dengue: no association with the 4G/5G promoter polymorphism

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    ten Cate H

    2005-11-01

    Full Text Available Abstract Background Dengue virus infected patients have high plasminogen activator inhibitor type I (PAI-1 plasma concentrations. Whether the insertion/deletion (4G/5G polymorphism in the promotor region of the PAI-1 gene is associated with increased PAI-1 plasma concentrations and with death from dengue is unknown. We, therefore, investigated the relationship between the 4G/5G polymorphism and PAI-1 plasma concentrations in dengue patients and risk of death from dengue. Methods A total of 194 patients admitted to the Dr. Kariadi Hospital in Semarang, Indonesia, with clinical suspected severe dengue virus infection were enrolled. Blood samples were obtained on day of admission, days 1, 2 and 7 after admission and at a 1-month follow-up visit. Plasma concentrations of PAI-1 were measured using a sandwich ELISA kit. The PAI-1 4G/5G polymorphism was typed by allele-specific PCR analysis. Results Concentrations of PAI-1 on admission and peak values of PAI-1 during admission were higher than the values measured in healthy controls. Survival was significantly worse in patients with PAI-1 concentrations in the highest tertile (at admission: OR 4.7 [95% CI 0.9–23.8], peak value during admission: OR 6.3 [95%CI 1.3–30.8]. No association was found between the PAI-1 4G/5G polymorphism, and PAI-1 plasma concentrations, dengue disease severity and mortality from dengue. Conclusion These data suggest that the 4G/5G polymorphism has no significant influence on PAI-1 concentrations in dengue virus infected patients and is not associated with the risk of death from dengue. Other factors contributing to the variability of PAI-1 plasma concentrations in patients with dengue need to be explored.

  7. TGF-β induces p53/Smads complex formation in the PAI-1 promoter to activate transcription

    Science.gov (United States)

    Kawarada, Yuki; Inoue, Yasumichi; Kawasaki, Fumihiro; Fukuura, Keishi; Sato, Koichi; Tanaka, Takahito; Itoh, Yuka; Hayashi, Hidetoshi

    2016-01-01

    Transforming growth factor β (TGF-β) signaling facilitates tumor development during the advanced stages of tumorigenesis, but induces cell-cycle arrest for tumor suppression during the early stages. However, the mechanism of functional switching of TGF-β is still unknown, and it is unclear whether inhibition of TGF-β signaling results amelioration or exacerbation of cancers. Here we show that the tumor suppressor p53 cooperates with Smad proteins, which are TGF-β signal transducers, to selectively activate plasminogen activator inhibitor type-1 (PAI-1) transcription. p53 forms a complex with Smad2/3 in the PAI-1 promoter to recruit histone acetyltransferase CREB-binding protein (CBP) and enhance histone H3 acetylation, resulting in transcriptional activation of the PAI-1 gene. Importantly, p53 is required for TGF-β-induced cytostasis and PAI-1 is involved in the cytostatic activity of TGF-β in several cell lines. Our results suggest that p53 enhances TGF-β-induced cytostatic effects by activating PAI-1 transcription, and the functional switching of TGF-β is partially caused by p53 mutation or p53 inactivation during cancer progression. It is expected that these findings will contribute to optimization of TGF-β-targeting therapies for cancer. PMID:27759037

  8. The Effect of PAI-1 4G/5G Polymorphism and Clinical Factors on Coronary Artery Occlusion in Myocardial Infarction

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    Tajinder Kumar Parpugga

    2015-01-01

    Full Text Available Objective. Data on the impact of PAI-1-675 4G/5G genotype for fibrinolysis during myocardial infarction are inconsistent. The aim of our study was to evaluate the association of clinical and genetic (PAI-1-675 4G/5G polymorphism factors with coronary artery occlusion in patients with myocardial infarction. Materials and Methods. PAI-1-675 4G/5G detection was achieved by using Sanger sequencing in a sample of patients hospitalized for stent implantation due to myocardial infarction. We categorized the patients into two groups: patients with coronary artery occlusion and patients without coronary artery occlusion according to angiographic evaluation. Results. We identified n=122 (32.4% 4G/4G, n=186 (49.5% 4G/5G, and n=68 (18.1% 5G/5G PAI-1 genotype carriers. Univariate and multivariate analysis showed that only the 4G/5G genotype was associated with coronary artery occlusion (OR: 1.656 and 95% CI: 1.009–2.718, p=0.046. Conclusions. Our results showed that carriers of PAI-1 4G/5G genotype with myocardial infarction have increased odds of coronary artery occlusion more than 1.6 times in comparison to the carriers of homozygous genotypes.

  9. Ascochlorin suppresses TGF-β1-induced PAI-1 expression through the inhibition of phospho-EGFR in rat kidney fibroblast cells.

    Science.gov (United States)

    Cho, Hyun-Ji; Kang, Jeong-Han; Jeong, Ji-Hak; Jeong, Yun-Jeong; Park, Kwan-Kyu; Park, Yoon-Yub; Moon, Yong-Suk; Kim, Hong-Tae; Chung, Il-Kyung; Kim, Cheorl-Ho; Chang, Hyeun-Wook; Chang, Young-Chae

    2012-04-01

    Fibrosis is induced by the excessive and abnormal deposition of extracellular matrix (ECM) with various growth factors in tissues. Transforming growth factor-β1 (TGF-β1), the growth factor involved in fibrosis, modulates ECM synthesis and accumulation. TGF-β1 enhances the production of stimulators of ECM synthesis such as plasminogen activator inhibitor type 1 (PAI-1). As such, PAI-1 expression directly influences the proteolysis, invasion, and accumulation of ECM. It was shown in this study that ascochlorin, a prenylpenl antiobiotic, prevents the expression of profibrotic factors, such as PAI-1 and collagen type I, and that the TGF-β1-induced PAI-1 promoter activity is inhibited by ascochlorin. Ascochlorin abolishes the phosphorylation of the EGFR-MEK-ERK signaling pathway to regulate the TGF-β1-induced expression of PAI-1 without the inhibition of TβRII phosphorylation. Furthermore, the MEK inhibitor and EGFR siRNA block PAI-1 expression, and the Raf-1, MEK, and ERK signaling pathways for the regulation of PAI-1 expression. Ascochlorin suppresses the matrix metalloproteinases (MMPs) activity to activate the heparin-binding EGF-like growth factor (HB-EGF), to induce the phosphorylation of EGFR, and the MMPs inhibitor suppresses EGFR phosphorylation and the PAI-1 mRNA levels. These results suggest that ascochlorin prevents the expression of PAI-1 via the inhibition of an EGFR-dependent signal transduction pathway activated by MMPs.

  10. TF、TFPI、tPA、PAI1在DIC和DIC前期的检测及意义探讨%Investigation of TF,TFPI,t-PA and PAI-1 in Patients pre DIC and DIC and Their Significance

    Institute of Scientific and Technical Information of China (English)

    段朝霞; 杨林花

    2008-01-01

    目的 观察凝血和纤维蛋白溶解系统在弥漫性血管内凝血(disseminated intravascular coagulation,DIC)前期和DIC期的变化,为早期发现和治疗DIC提供依据.方法 ELISA 法检测DIC前期、DIC期、非DIC患者血浆组织因子(tissue factor,TF)和组织因子途径抑制物(tissue factor pathway inhibitor,TFPI),组织型纤维蛋白酶原活化剂(tissue type plasminogen activator,t PA)及其抑制物PAI 1(plasminogen activator inhibitor 1)和D 二聚体浓度.比较TF/TFPI和t PA/PAI 1比值.结果 在DIC发生发展过程中,TF、TFPI、t PA、PAI 1和D 二聚体均增高,DIC前期TF/TFPI比值增高,DIC期t PA/PAI 1比值增高.结论 DIC的发生发展与凝血系统和纤维蛋白溶解系统失平衡有关,DIC前期TFPI对TF抑制不足可能是DIC凝血和血栓形成的主要原因,TF/TFPI可以作为DIC前期指标,提示有DIC趋势;DIC的出血可能主要与PAI 1对t PA 抑制不足继发纤维蛋白溶解亢进相关,该研究可为今后应用抗纤维蛋白溶解药物治疗DIC提供理论依据.

  11. Inhibition of PAI-1 release from human endothelial cells by Angelica keiskei Koidzumi (Ashitaba chalcones is structure-dependent

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    Naoki Ohkura

    2015-12-01

    Full Text Available Angelica keiskei Koidzumi (Ashitaba is a traditional herbal medicine and it is also regarded in Japan as a health food that might have antithrombotic properties. Ashitaba exudate suppresses lipopolysaccharide (LPS-induced plasma plasminogen activator inhibitor 1 (PAI-1, a risk factor for thrombotic diseases in mice. Xanthoangelol (XA and 4-hydroxyderricin (4-HD comprise > 95% of total chalcones from Ashitaba exudates that also contain trace amounts of other chalcone subtypes. The present study aimed to determine the effects of Ashitaba chalcones including xanthoangelols B (XB, D (XD, E (XE, F (XF and XA as well as 4-HD on PAI-1 levels in the medium of stimulated human EA.hy926 endothelial cells. Xanthoangelol (10 and #61549;M inhibited PAI-1 production at a rate of 77.1%, whereas the inhibition rates of XB, XD, XE and 4-HD were not significant. Xanthoangelol F was highly cytotoxic and thus its ability to inhibit PAI-1 production could not be evaluated. The side hydrocarbon chain of XA played an important role in the excretion of inhibitory activity. Small modifications of the hydrocarbon chain or small functional groups on the A ring measurably influenced the inhibitory activity of xanthoangelols. These findings warrant future research towards an understanding of the mechanism of antithrombotic action of Ashitaba as herbal medicine or antithrombotic health food. [J Intercult Ethnopharmacol 2015; 4(4.000: 355-357

  12. Relationship between visceral fat and PAI-1 in overweight men and women before and after weight loss

    NARCIS (Netherlands)

    Kockx, M.; Leenen, R.; Seidell, J.; Princen, H.M.G.; Kooistra, T.

    1999-01-01

    This study was aimed at evaluating the relationship between visceral fat accumulation and plasma plasminogen activator inhibitor-1 (PAI-1) levels in healthy, obese men and women undergoing weight loss therapy. The subjects, 25 men and 25 premenopausal women, aged between 26 and 49 years, with an ini

  13. Myocardial infarction and arterial thrombosis in identical newborn twins with homozygosity for the PAI-1 4 G/5 G polymorphism

    OpenAIRE

    De Lucia, Vittoria; Andreassi, Maria Grazia; Sabatini, Laura; Ait-Ali, Lamia; Spadoni, Isabella; Giusti, Sandra

    2009-01-01

    Myocardial infarction in the perinatal period, in the absence of congenital heart disease or coronary artery lesions, is rare. The most common etiology described are the thromboembolism and perinatal asphyxia. We report a case of monozygotic twins who developed, after birth, acute vascular events and both had PAI-1 4G/4G homozygosity.

  14. Determination of expression of PAI-1 in sera of patients with breast cancer by antibody microarray%抗体芯片技术检测乳腺癌患者血清中PAI-1的表达

    Institute of Scientific and Technical Information of China (English)

    宋燕; 刘雪凯; 张青云

    2014-01-01

    目的 采用抗体芯片技术检测乳腺癌患者血清中纤溶酶原激活物抑制因子-1(plasminogen activator inhibitor,PAI-1)的表达.方法 制备鼠抗人PAI-1单抗腹水及多抗,经ProteinA-Sepharose-4B柱纯化后,点至醛基玻片上(点样浓度均分别为1和0.1 mg/ml),制备抗体芯片,加入待测血清(分别进行1∶2、1∶10、1∶100稀释),利用晶芯Luxscan 10K-A芯片扫描仪扫描,芯片图象分析软件晶芯SpotData Pro分析后,获得最适点样浓度和血清稀释倍数.采用优化后的抗体芯片法检测202份乳腺癌患者和204份健康体检者血清样本中PAI-1的表达.结果 确定点样单抗最适浓度为1 mg/ml,血清最适稀释倍数为1∶100.PAI-1在204份健康体检者血清样本中阳性率为4.4%(9/204),在202份乳腺癌患者血清中的总体阳性率为25.2%,特异性为96%;其中119份发生转移和83份未发生转移的乳腺癌患者血清中PAI-1阳性率分别为35.3%(42/119)和10.8%(9 /83),阳性率随肿瘤的分期进展而升高.结论 PAI-1在乳腺癌患者血清中的表达明显高于健康体检者,且随着肿瘤的分期进展阳性率升高,其有望成为新的乳腺癌血清筛查指标.

  15. Dual Diverse Dynamic Reversible Actions of Ankaferd on EPCR and PAI-1 Inside Vascular Endothelial Cells With and Without LPS

    Directory of Open Access Journals (Sweden)

    Afife Karabıyık

    2012-12-01

    Full Text Available OBJECTIVE: Ankaferd Blood Stopper (ABS comprises a mixture of the plants Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum ve Urtica dioica. ABS has been used as a topical haemostatic agent because of its antihaemorrhagic effect. Its haemostatic mechanism of action remains to be investigated. ABS does not affect individual levels of the coagulation factors II, V, VII, VIII, IX, X, XI and XIII. The aim of this study was to investigate the effects of ABS on endothelium and immune response. So, we investigated the possible changes in EPCR and PAI-1 without and with LPS-challenge inside HUVECs. METHODS: 10 μL and 100 μL ABS is given to HUVECs in 5 min., 25 min., and 50 min.,6 hour and 24 hour time periods. 10 μg/ mL LPS has been added for one hour to observe the effects of LPS challenge on HUVECs and then the cells have been treated with ABS for the time period of 5 min., 25 min., 50 min. and 6 hours to observe ABS-effects on HUVECs. Total RNAs were isolated from HUVECs and then EPCR ve PAI-1 mRNA expression levels were investigated. RESULTS: It was microscopically observed that cells arised from the surface and adhered to each other after the ABS application to the HUVECs. Also, after 24 hours cells returned the normal growth and physiology. It suggests that the adhesive cellular functions of ABS may be reversible. 10 µl ABS have negative effect on EPCR and PAI-1 expressions. Moreover the effects increases with 100 µl ABS. EPCR and PAI-1 expression increased by time with LPS and 10 µl ABS. Expressions were very low during the first hour when LPS and 100 µl ABS were given but at the end of 6 hour, EPCR and PAI-1 expression increased similar to LPS and 10 µl ABS experiment. CONCLUSION: In this study, we observed that Ankaferd has dual diverse dynamic reversible actions depend on dose and concentration on EPCR and PAI-1 inside vascular endothelial cells in the model of HUVEC. ABS might have a role on numerous cellular

  16. Induction of plasminogen activator inhibitor type-1 (PAI-1 by hypoxia and irradiation in human head and neck carcinoma cell lines

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    Mengele Karin

    2007-07-01

    Full Text Available Abstract Background Squamous cell carcinoma of the head and neck (SCCHN often contain highly radioresistant hypoxic regions, nonetheless, radiotherapy is a common treatment modality for these tumours. Reoxygenation during fractionated radiotherapy is desired to render these hypoxic tumour regions more radiosensitive. Hypoxia additionally leads to up-regulation of PAI-1, a protein involved in tumour progression and an established prognostic marker for poor outcome. However, the impact of reoxygenation and radiation on PAI-1 levels is not yet clear. Therefore, we investigated the kinetics of PAI-1 expression and secretion after hypoxia and reoxygenation, and determined the influence of ionizing radiation on PAI-1 levels in the two human SCCHN cell lines, BHY and FaDu. Methods HIF-1α immunoblot was used to visualize the degree of hypoxia in the two cell lines. Cellular PAI-1 expression was investigated by immunofluorescence microscopy. ELISA was used to quantify relative changes in PAI-1 expression (cell lysates and secretion (cell culture supernatants in response to various lengths (2 – 4 h of hypoxic exposure (2, reoxygenation (24 h, 20 % O2, and radiation (0, 2, 5 and 10 Gy. Results HIF-1α expression was induced between 2 and 24 h of hypoxic exposure. Intracellular PAI-1 expression was significantly increased in BHY and FaDu cells as early as 4 h after hypoxic exposure. A significant induction in secreted PAI-1 was seen after 12 to 24 h (BHY and 8 to 24 h (FaDu hypoxia, as compared to the normoxic control. A 24 h reoxygenation period caused significantly less PAI-1 secretion than a 24 h hypoxia period in FaDu cells. Irradiation led to an up-regulation of PAI-1 expression and secretion in both, BHY and FaDu cells. Conclusion Our data suggest that both, short-term (~4 – 8 h and long-term (~20 – 24 h hypoxic exposure could increase PAI-1 levels in SCCHN in vivo. Importantly, radiation itself could lead to PAI-1 up-regulation in head and

  17. Lectin-like oxidized low-density lipoprotein receptor 1 mediates the effect of Bezafibrate on expression of PAI-1 induced by ox-LDL in HUVECs%LOX-1介导苯扎贝特对ox-LDL所引起PAI-1表达的影响

    Institute of Scientific and Technical Information of China (English)

    申晓彧; 屈巧芳; 薛丽霞; 曾秋棠

    2008-01-01

    目的 探讨苯扎贝特对ox-LDL所诱导HUVECs表达PAI-1的影响及是否通过LOX-1介导.方法 体外培养HUVECs,RT-PCR检测PAI-1 mRNA表达,ELISA法观察PAI-1蛋白含量表达.结果 ox-LDL组,PAI-1 mKNA和蛋白表达明显增加(P<0.05),poly(Ⅰ)组,PAI-1 mRNA和蛋白表达明显减少(P<0.05);不同浓度苯扎贝特组,PAI-1 mRNA和蛋白表达明显减少(P<0.05),组间比较差异有统计学意义,呈浓度依赖关系(P<0.05);Poly(Ⅰ)+100μmol/L苯扎贝特组,与未加poly(Ⅰ)组比较,PAI-1mR-NA和蛋白表达均明显减少(P<0.05).结论 LOX-1介导了ox-LDL所诱导HUVECs PAI-1的表达;苯扎贝特可以下调ox-LDL所诱导的HUVECs PAI-1的表达,呈浓度依赖关系,部分机制可能通过LOX-1介导.

  18. Evaluation of 12-Lipoxygenase (12-LOX and Plasminogen Activator Inhibitor 1 (PAI-1 as Prognostic Markers in Prostate Cancer

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    Tomasz Gondek

    2014-01-01

    Full Text Available In carcinoma of prostate, a causative role of platelet 12-lipoxygenase (12-LOX and plasminogen activator inhibitor 1 (PAI-1 for tumor progression has been firmly established in tumor and/or adjacent tissue. Our goal was to investigate if 12-LOX and/or PAI-1 in patient’s plasma could be used to predict outcome of the disease. The study comprised 149 patients (age 70±9 divided into two groups: a study group with carcinoma confirmed by positive biopsy of prostate (n=116 and a reference group (n=33 with benign prostatic hyperplasia (BPH. The following parameters were determined by the laboratory test in plasma or platelet-rich plasma: protein level of 12-LOX, PAI-1, thromboglobulin (TGB, prostate specific antigen (PSA, C-reactive protein (CRP, hemoglobin (HGB, and hematocrit (HCT, as well as red (RBC and white blood cells (WBC, number of platelets (PLT, international normalized ratio of blood clotting (INR, and activated partial thromboplastin time (APTT. The only difference of significance was noticed in the concentration of 12-LOX in platelet rich plasma, which was lower in cancer than in BPH group. Standardization to TGB and platelet count increases the sensitivity of the test that might be used as a biomarker to assess risk for prostate cancer in periodically monitored patients.

  19. PPAR{alpha} deficiency augments a ketogenic diet-induced circadian PAI-1 expression possibly through PPAR{gamma} activation in the liver

    Energy Technology Data Exchange (ETDEWEB)

    Oishi, Katsutaka, E-mail: k-ooishi@aist.go.jp [Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki (Japan); Uchida, Daisuke [Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki (Japan); Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki (Japan); Ohkura, Naoki [Department of Clinical Molecular Biology, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamihara, Kanagawa (Japan); Horie, Shuichi [Department of Clinical Biochemistry, Kagawa Nutrition University, Sakado, Saitama (Japan)

    2010-10-15

    Research highlights: {yields} PPAR{alpha} deficiency augments a ketogenic diet-induced circadian PAI-1 expression. {yields} Hepatic expressions of PPAR{gamma} and PCG-1{alpha} are induced by a ketogenic diet. {yields} PPAR{gamma} antagonist attenuates a ketogenic diet-induced PAI-1 expression. {yields} Ketogenic diet advances the phase of circadian clock in a PPAR{alpha}-independent manner. -- Abstract: An increased level of plasminogen activator inhibitor-1 (PAI-1) is considered a risk factor for cardiovascular diseases, and PAI-1 gene expression is under the control of molecular circadian clocks in mammals. We recently showed that PAI-1 expression is augmented in a phase-advanced circadian manner in mice fed with a ketogenic diet (KD). To determine whether peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}) is involved in hypofibrinolytic status induced by a KD, we examined the expression profiles of PAI-1 and circadian clock genes in PPAR{alpha}-null KD mice. Chronic administration of bezafibrate induced the PAI-1 gene expression in a PPAR{alpha}-dependent manner. Feeding with a KD augmented the circadian expression of PAI-1 mRNA in the hearts and livers of wild-type (WT) mice as previously described. The KD-induced mRNA expression of typical PPAR{alpha} target genes such as Cyp4A10 and FGF21 was damped in PPAR{alpha}-null mice. However, plasma PAI-1 concentrations were significantly more elevated in PPAR{alpha}-null KD mice in accordance with hepatic mRNA levels. These observations suggest that PPAR{alpha} activation is dispensable for KD-induced PAI-1 expression. We also found that hyperlipidemia, fatty liver, and the hepatic expressions of PPAR{gamma} and its coactivator PCG-1{alpha} were more effectively induced in PPAR{alpha}-null, than in WT mice on a KD. Furthermore, KD-induced hepatic PAI-1 expression was significantly suppressed by supplementation with bisphenol A diglycidyl ether, a PPAR{gamma} antagonist, in both WT and PPAR

  20. Increased Serum PAI-1 Levels in Subjects with Metabolic Syndrome and Long-Term Adverse Mental Symptoms: A Population-Based Study

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    Anne Huotari

    2010-01-01

    Full Text Available Depression is an independent risk factor for cardiovascular diseases and is associated with metabolic syndrome (MetS. Levels of plasminogen activator inhibitor-1 (PAI-1, an inhibitor of tissue-type and urokinase-type plasminogen activators, are associated with MetS. To clarify the role of PAI-1 in subjects with long-term adverse mental symptomatology (LMS; including depression and MetS, we measured circulating PAI-1 levels in controls (n=111, in subjects with MetS and free of mental symptoms (n=42, and in subjects with both MetS and long-term mental symptoms (n=70. PAI-1 increased linearly across the three groups in men. In logistic regression analysis, men with PAI-1 levels above the median had a 3.4-fold increased likelihood of suffering from the comorbidity of long-term adverse mental symptoms and MetS, while no such associations were detected in women. In conclusion, our results suggest that in men high PAI-1 levels are independently associated with long-term mental symptomatology.

  1. The Role of TPA I/D and PAI-1 4G/5G Polymorphisms in Multiple Sclerosis

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    Maja Živković

    2014-01-01

    Full Text Available Background. Previous studies have shown impaired fibrinolysis in multiple sclerosis (MS and implicated extracellular proteolytic enzymes as important factors in demyelinating neuroinflammatory disorders. Tissue-type plasminogen activator (t-PA and its inhibitor (PAI-1 are key molecules in both fibrinolysis and extracellular proteolysis. In the present study, an association of the TPA Alu I/D and PAI-1 4G/5G polymorphisms with MS was analyzed within the Genomic Network for Multiple Sclerosis (GENoMS. Methods. The GENoMS includes four populations (Croatian, Slovenian, Serbian, and Bosnian and Herzegovinian sharing the same geographic location and a similar ethnic background. A total of 885 patients and 656 ethnically matched healthy blood donors with no history of MS in their families were genotyped using PCR-RFLP. Results. TPA DD homozygosity was protective (OR = 0.79, 95% CI 0.63–0.99, P=0.037 and PAI 5G5G was a risk factor for MS (OR = 1.30, 95% CI 1.01–1.66, P=0.038. A significant effect of the genotype/carrier combination was detected in 5G5G/I carriers (OR = 1.39 95% CI 1.06–1.82, P=0.017. Conclusions. We found a significantly harmful effect of the combination of the PAI-1 5G/5G genotype and TPA I allele on MS susceptibility, which indicates the importance of gene-gene interactions in complex diseases such as MS.

  2. Genetic variants in TGFβ-1 and PAI-1 as possible risk factors for cardiovascular disease after radiotherapy for breast cancer

    International Nuclear Information System (INIS)

    Background and purpose: It has been established that radiotherapy can increase cardiovascular disease (CVD) risk. Genetic variants, which play a role in the tissue, damage response and angiogenesis regulating TGFβ pathway might give us insight into the mechanisms underlying radiation-induced CVD. We examined the effects of two polymorphisms, TGFβ1 29C > T and PAI-1 5G > 4G, on CVD incidence. Materials and methods: This retrospective cohort study included 422 10-year breast cancer survivors, aged 4G and CVD risk. Conclusion: Our study suggests there might be an association between the TGFβ1 29C > T polymorphism and CVD risk in long-term breast cancer survivors.

  3. Association of a PAI-1 Gene Polymorphism and Early Life Infections with Asthma Risk, Exacerbations, and Reduced Lung Function

    Science.gov (United States)

    Kim, Dong Young; Oh, Sam S.; Torgerson, Dara R.; Pino-Yanes, Maria; Hu, Donglei; Sen, Saunak; Huntsman, Scott; Eng, Celeste; Farber, Harold J.; Rodriguez-Cintron, William; Rodriguez-Santana, Jose R.; Serebrisky, Denise; Thyne, Shannon M.; Borrell, Luisa N.; Williams, L. Keoki; DuPont, William; Seibold, Max A.; Burchard, Esteban G.; Avila, Pedro C.; Kumar, Rajesh

    2016-01-01

    Background Plasminogen activator inhibitor-1 (PAI-1) is induced in airways by virus and may mediate asthmatic airway remodeling. We sought to evaluate if genetic variants and early life lower respiratory infections jointly affect asthma risk. Methods We included Latino children, adolescents, and young adults aged 8–21 years (1736 subjects with physician-diagnosed asthma and 1747 healthy controls) from five U.S. centers and Puerto Rico after excluding subjects with incomplete clinical or genetic data. We evaluated the independent and joint effects of a PAI-1 gain of function polymorphism and bronchiolitis / Respiratory Syncytial Virus (RSV) or other lower respiratory infections (LRI) within the first 2 years of life on asthma risk, asthma exacerbations and lung function. Results RSV infection (OR 9.9, 95%CI 4.9–20.2) and other LRI (OR 9.1, 95%CI 7.2–11.5) were independently associated with asthma, but PAI-1 genotype was not. There were joint effects on asthma risk for both genotype-RSV (OR 17.7, 95% CI 6.3–50.2) and genotype-LRI (OR 11.7, 95% CI 8.8–16.4). A joint effect of genotype-RSV resulted in a 3.1-fold increased risk for recurrent asthma hospitalizations. In genotype-respiratory infection joint effect analysis, FEV1% predicted and FEV1/FVC % predicted were further reduced in the genotype-LRI group (β -2.1, 95% CI -4.0 to -0.2; β -2.0, 95% CI -3.1 to -0.8 respectively). Similarly, lower FEV1% predicted was noted in genotype-RSV group (β -3.1, 95% CI -6.1 to -0.2) with a trend for lower FEV1/FVC % predicted. Conclusions A genetic variant of PAI-1 together with early life LRI such as RSV bronchiolitis is associated with an increased risk of asthma, morbidity, and reduced lung function in this Latino population. PMID:27556405

  4. p53- and PAI-1-mediated induction of C-X-C chemokines and CXCR2: importance in pulmonary inflammation due to cigarette smoke exposure.

    Science.gov (United States)

    Tiwari, Nivedita; Marudamuthu, Amarnath S; Tsukasaki, Yoshikazu; Ikebe, Mitsuo; Fu, Jian; Shetty, Sreerama

    2016-03-15

    We previously demonstrated that tumor suppressor protein p53 augments plasminogen activator inhibitor-1 (PAI-1) expression in alveolar epithelial cells (AECs) during chronic cigarette smoke (CS) exposure-induced lung injury. Chronic lung inflammation with elevated p53 and PAI-1 expression in AECs and increased susceptibility to and exacerbation of respiratory infections are all associated with chronic obstructive pulmonary disease (COPD). We recently demonstrated that preventing p53 from binding to the endogenous PAI-1 mRNA in AECs by either suppressing p53 expression or blockading p53 interactions with the PAI-1 mRNA mitigates apoptosis and lung injury. Within this context, we now show increased expression of the C-X-C chemokines (CXCL1 and CXCL2) and their receptor CXCR2, and the intercellular cellular adhesion molecule-1 (ICAM-1), in the lung tissues of patients with COPD. We also found a similar increase in lung tissues and AECs from wild-type (WT) mice exposed to passive CS for 20 wk and in primary AECs treated with CS extract in vitro. Interestingly, passive CS exposure of mice lacking either p53 or PAI-1 expression resisted an increase in CXCL1, CXCL2, CXCR2, and ICAM-1. Furthermore, inhibition of p53-mediated induction of PAI-1 expression by treatment of WT mice exposed to passive CS with caveolin-1 scaffolding domain peptide reduced CXCL1, CXCL2, and CXCR2 levels and lung inflammation. Our study reveals that p53-mediated induction of PAI-1 expression due to chronic CS exposure exacerbates lung inflammation through elaboration of CXCL1, CXCL2, and CXCR2. We further provide evidence that targeting this pathway mitigates lung injury associated with chronic CS exposure.

  5. JNK suppression is essential for 17β-Estradiol inhibits prostaglandin E2-Induced uPA and MMP-9 expressions and cell migration in human LoVo colon cancer cells

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    Chen Wei-Kung

    2011-08-01

    Full Text Available Abstract Background Epidemiological studies demonstrate that the incidence and mortality rates of colorectal cancer in women are lower than in men. However, it is unknown if 17β-estradiol treatment is sufficient to inhibit prostaglandin E2 (PGE2-induced cellular motility in human colon cancer cells. Methods We analyzed the protein expression of urokinase plasminogen activator (uPA, tissue plasminogen activator (tPA, matrix metallopeptidases (MMPs, plasminogen activator inhibitor-1 (PAI-1 and tissue inhibitor of metalloproteinases (TIMPs, and the cellular motility in PGE2-stimulated human LoVo cells. 17β-Estradiol and the inhibitors including LY294002 (Akt activation inhibitor, U0126 (ERK1/2 inhibitor, SB203580 (p38 MAPK inhibitor, SP600125 (JNK1/2 inhibitor, QNZ (NFκB inhibitor and ICI 182 780 were further used to explore the inhibitory effects of 17β-estradiol on PGE2-induced LoVo cell motility. Student's t-test was used to analyze the difference between the two groups. Results Upregulation of urokinase plasminogen activator (uPA, tissue plasminogen activator (tPA and matrix metallopeptidases (MMPs is reported to associate with the development of cancer cell mobility, metastasis, and subsequent malignant tumor. After administration of inhibitors including LY294002, U0126, SB203580, SP600125 or QNZ, we found that PGE2 treatment up-regulated uPA and MMP-9 expression via JNK1/2 signaling pathway, thus promoting cellular motility in human LoVo cancer cells. However, PGE2 treatment showed no effects on regulating expression of tPA, MMP-2, plasminogen activator inhibitor-1 (PAI-1, tissue inhibitor of metalloproteinase-1, -2, -3 and -4 (TIMP-1, -2, -3 and -4. We further observed that 17β-estradiol treatment inhibited PGE2-induced uPA, MMP-9 and cellular motility by suppressing activation of JNK1/2 in human LoVo cancer cells. Conclusions Collectively, these results suggest that 17β-estradiol treatment significantly inhibits PGE2-induced motility

  6. uPA, uPAR and TGFβ₁ expression during early and late post myocardial infarction period in rat myocardium.

    Science.gov (United States)

    Stavropoulou, Anastasia; Philippou, Anastassios; Halapas, Antonios; Sourla, Antigone; Pissimissis, Nikolaos; Koutsilieris, Michael

    2010-01-01

    The expression patterns of transforming growth factor beta 1 (TGFβ₁), urokinase-type plasminogen activator (uPA) and uPA receptor (uPAR) were analysed after artery ligation-induced myocardial infarction (MI) in the rat myocardium. uPA and uPAR expressions were significantly increased both at transcriptional and protein level during early phase post MI period (uPA at 1 hour and uPAR at 24 hours post infarction). TGFβ1 mRNA expression profile revealed a significant increase of TGFβ1 expression from day 4 up to 8 weeks post infarction. These data suggest that the need for an increasing TGFβ₁ bioavailability during the post-infarction period in rat myocardium is achieved in the early post MI period by an increased expression of uPA/uPAR proteolytic system (indirect activation of latent TGFβ₁) and in the late post MI period by direct regulation of TGFβ₁ expression. It is therefore concluded that differential regulation of the TGFβ₁ bioavailability may be a crucial step of the repair mechanisms during the post MI infarction period in the rat myocardium.

  7. 脂肪细胞分化过程中影响PAI-1基因转录表达的Dex和C/EBPs顺式调控元件的分析%Analysis of a Novel Dexamethasone Response Element and a Putative C/EBPs cis-Motif: Controlling PAI-1 Gene Expression During Adipocyte Differentiation

    Institute of Scientific and Technical Information of China (English)

    陈可洋; 马春姑; 汤其群; 宋后燕

    2002-01-01

    在研究胰岛素(Ins)、地塞米松(Dex)和甲基异丁基黄嘌呤(Mix)对脂肪细胞分化过程中PAI-1基因表达的影响基础上,为进一步探讨Ins、Dex调控PAI-1基因转录表达的调控机制,应用DNA重组技术,构建含萤光素酶(luciferase)报告基因和PAI-1启动子不同长度片段的嵌合质粒,转染3T3-L1前脂肪细胞并测定报告基因荧光素酶的活性.结果表明,小鼠PAI-1基因起动子-690至-850碱基序列之间有一个Dex的正调控元件.用计算机软件进行分析发现:Dex顺式元件位于PAI-1启动子的-750至-770碱基序列.其组成为:5′ GGTAACCTCTGTTCTCAT 3′.同时还发现在PAI-1启动子的-720至-740碱基序列中,存在一个C/EBPs的结合元件5′CCAAT3′并用凝胶电泳迁移实验对这些元件进行了鉴定.表明Dex正是通过激活转录因子(糖皮质激素受体,GR)和C/EBPα一起与各自的顺式元件结合来促进PAI-1基因的表达.%It has been reported that there is a significant increase in PAI-1 expression level in obese subjects. To explore the linkage between PAI-1 gene expression and obesity, the restriction enzymes and DNA recombination technologies were used to construct the chimeric plasmids with luciferase and different lengths of PAI-1 promoter. After transfection of the chimeric plasmids into 3T3-L1 preadipocyte and detection of luciferase activity, the results indicated that a positive dexamethasone cis-acting element (bases -690 to -850) may be present in mouse PAI-1 promoter. In addition, computer analysis using Match-Search Software found that a new motif of DexRE (dexamethasone response element) 5′ GGTAACCTCTGTTCTCAT 3′ and a putative C/EBPs binding site (cis-motif) exist respectively in the fragment (nucleotides -751 to -770) of, and a sequence (bases -720 to -740) of, mouse PAI-1 promoter,and GMSA and competition assays identified that the trans-acting factors induced by dexamethasone can specifically bind to those cis-motifs. Meanwhile

  8. Up-Regulation of PAI-1 and Down-Regulation of uPA Are Involved in Suppression of Invasiveness and Motility of Hepatocellular Carcinoma Cells by a Natural Compound Berberine

    OpenAIRE

    Xuanbin Wang; Ning Wang; Hongliang Li; Ming Liu; Fengjun Cao; Xianjun Yu; Jingxuan Zhang; Yan Tan; Longchao Xiang; Yibin Feng

    2016-01-01

    Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death and its prognosis remains poor due to the high risk of tumor recurrence and metastasis. Berberine (BBR) is a natural compound derived from some medicinal plants, and accumulating evidence has shown its potent anti-tumor activity with diverse action on tumor cells, including inducing cancer cell death and blocking cell cycle and migration. Molecular targets of berberine involved in its inhibitory effect on the i...

  9. 高脂饮食小鼠脂肪组织中PAI-1、FOXC2及FOXO1表达的研究%Study of expression of PAI-1, FOXC2 and FOXO1 in adipose tissue of mice with high fat diet

    Institute of Scientific and Technical Information of China (English)

    刘亚莉; 易佳丽; 刘剑辉; 牛丽凤

    2014-01-01

    Objective To study the expression level of PAI-1, FOXC2 and FOXO1 in high fat diet of visceral fat and subcutaneous fat tissue,and to investigate the mechanism of different types of obesity.Methods 20 mouse were randomLy divided into control group and high fat group, and given normal diet and high fat diet for 12 weeks. Serum PAI-1,the expression level of PAI-1, FOXC2 and FOXO1 mRNA in epididymal tissue and subcutaneous fat were determined. Results The body weight, serum PAI-1 levels of high fat group were significantly higher than those of the control group. Within the group, PAI-1,FOXC2, mRNA expression of mouse epididymal adipose tissue were significantly higher than those of the subcutaneous adipose tissue, and the expression of FOXO1mRNA of mouse epididymal adipose tissue was significantly lower than that of subcutaneous adipose tissue, with statistical significance difference. Conclusion Expression levels of serum PAI-1 are different between normal weight mice and obese mice,and expression of fat PAI-1, FOXC2and FOXO1 in visceral fat and subcutaneous are also different. This difference may be one of the mechanisms of different types of obesity.%目的:研究高脂饮食喂养小鼠内脏脂肪和皮下脂肪组织中PAI-1、FOXC2及FOXO1表达水平,探讨不同类型肥胖的机制。方法20只小鼠随机分为对照组和高脂组,分别给予正常饮食和高脂饮食喂养12周。测定血清PAI-1以及附睾周围组织及皮下脂肪中PAI-1、FOXC2及FOXO1 mRNA的表达水平。结果高脂组小鼠体质量、血清PAI-1水平均显著高于对照组。组内比较小鼠附睾周围脂肪组织PAI-1、FOXC2mRNA表达显著高于皮下脂肪组织;FOXO1mRNA表达显著低于于皮下脂肪组织,差异有统计学意义。结论正常体重小鼠和肥胖小鼠血清PAI-1水平表达不同,内脏脂肪和皮下脂肪PAI-1、FOXC2及FOXO1表达也存在差别,这种差别可能是不同类型肥胖的机制之一。

  10. Visceral fat accumulation is an important determinant of PAI-1 levels in young, nonobese men and women: Modulation by cross-sex hormone administration

    NARCIS (Netherlands)

    Giltay, E.J.; Elbers, J.M.H.; Gooren, L.J.G.; Emeis, J.J.; Kooistra, T.; Asscheman, H.; Stehouwer, C.D.A.

    1998-01-01

    Increased plasminogen activator inhibitor type-1 (PAI-1) levels, leading to impaired fibrinolysis, are associated with increased visceral fat in middle-aged and obese subjects. It is unknown, however, whether this association is independent of other disturbances clustered in the insulin resistance s

  11. Concomitant Administration of Different Doses of Simvastatin with Ivabradine Influence on PAI-1 and Heart Rate in Normo- and Hypercholesterolaemic Rats

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    Jacek Owczarek

    2012-01-01

    Full Text Available Ivabradine is a novel heart rate lowering agent that inhibits If ionic current in the sinus node and demonstrates antiischaemic and antianginal activity. The aim of the paper was to investigate the effect its dose-dependent drug-drug interaction with simvastatin inhibitor HMGCo-A has on PAI-1 blood level, heart rate and blood pressure. The experiments were performed in hyper- and normocholesterolemic Wistar rats receiving simvastatin (1 and 20 mg×kg−1 bw with ivabradine (10 mg×kg−1 bw during a 4-week period. Ivabradine exacerbated the decrease of PAI-1 in normocholesterolemic animals receiving simvastatin at a dose of 1 mg/kg bw and was not observed to have any significant influence on the PAI-1 values in rats receiving 20 mg×kg−1 bw simvastatin. Ivabradine, coadministered with simvastatin given at a dose of 20 mg×kg−1 bw, significantly slowed the heart rate in normocholesterolaemic and hypercholesterolaemic groups as compared to the group receiving ivabradine alone. Conclusion. The administration of ivabradine to normocholesterolaemic and hypercholesterolaemic rats receiving simvastatin significantly exacerbated the slowing of heart rate with no effect on blood pressure. The administration of ivabradine has been shown to demonstrate different effects on PAI-1 values depending on lipid disorders.

  12. PAI-1基因4G/5G多态性与肥胖型多囊卵巢综合征的相关性研究*%Correlations between 4G/5G Polymorphism in Plasminogen Activator Inhibitor-1(PAI-1)Gene and Obese Polycystic Ovarian Syndrome

    Institute of Scientific and Technical Information of China (English)

    庄朝辉; 沈宗姬; 黄亚珍; 徐文新

    2013-01-01

    Objective:To investigate the prevalence of 4G/5G polymorphism of plasminogen activator inhibitor-1(PAI-1)gene in obese polycystic ovary syndrome(PCOS)and their relationships between insulin sensitivity and plasma fibrinolysis function,to find a new way to prevent obesity and insulin resistance of obese PCOS.Method:135 patients and 124 controls were selected.Body mass index(BMI)and waist-to-hip(WHR) ratio were determined.Based on the BMI,the PCOS patients were divided into two groups:74 patients without obesity and 61 patients with obesity.Blood samples were obtained for DNA analysis.PAI-1 plasma levels,fasting insulin and fasting glucose were measured by the ELISA in all subjects.The 4G/5G polymorphic site of the PAI-1 gene promoter region was amplified by the polymerase chain reaction(PCR).We evaluate insulin resistance with Homa-IR and measure insulin sensitivityindex(ISI).Result:Comparison of the clinical data:BMI,WHR,fasting insulin,Homa-IR in patients with obesity were significant greater than those in patients without obesity,the difference was statistically significant between the groups(P<0.05);The PCOS group had significantly higher 4G/4G than the control group,whereas there were significantly less 5G/5G.PCOS women have higher levels of PAI-1 compared with the control group(P<0.05).There was no statistical difference of genotype distribution between patients with obesity and patients without obesity, whereas there was a statistically significant difference in the PAI-1 levels among the groups(P<0.05).Conclusion:The presence of the 4G allele in PAI-1 promoter region of the gene further increases the PAI-1 levels.PAI-1 gene polymorphism 4G genetype may be correlated with PCOS in Chinese women.PAI-1 gene polymorphism 4G genetype may be not correlated with obesity of PCOS in Chinese women.Anti-PAI-1 study may be a new way to prevent obesity and insulin resistance of obese PCOS.%  目的:通过研究肥胖型多囊卵巢综合征(PCOS)纤

  13. Elevated circulating PAI-1 levels are related to lung function decline, systemic inflammation, and small airway obstruction in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Wang H

    2016-09-01

    Full Text Available Hao Wang,1,2,* Ting Yang,1,2,* Diandian Li,1,2 Yanqiu Wu,1,2 Xue Zhang,1,2 Caishuang Pang,1,2 Junlong Zhang,3 Binwu Ying,3 Tao Wang,1,2 Fuqiang Wen1,2 1Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China *These authors contributed equally to this work Background: Plasminogen activator inhibitor-1 (PAI-1 and soluble urokinase-type plasminogen activator receptor (suPAR participate in inflammation and tissue remolding in various diseases, but their roles in chronic obstructive pulmonary disease (COPD are not yet clear. This study aimed to investigate if PAI-1 and suPAR were involved in systemic inflammation and small airway obstruction (SAO in COPD. Methods: Demographic and clinical characteristics, spirometry examination, and blood samples were obtained from 84 COPD patients and 51 healthy volunteers. Serum concentrations of PAI-1, suPAR, tissue inhibitor of metalloproteinase-1 (TIMP-1, Matrix metalloproteinase-9 (MMP-9, and C-reactive protein (CRP were detected with Magnetic Luminex Screening Assay. Differences between groups were statistically analyzed using one-way analysis of variance or chi-square test. Pearson’s partial correlation test (adjusted for age, sex, body mass index, cigarette status, and passive smoke exposure and multivariable linear analysis were used to explore the relationships between circulating PAI-1 and indicators of COPD. Results: First, we found that serum PAI-1 levels but not suPAR levels were significantly increased in COPD patients compared with healthy volunteers (125.56±51.74 ng/mL versus 102.98±36.62 ng/mL, P=0.007. Then, the

  14. 代谢综合征大血管病变与PAI-1、hs-CRP水平及心脑血管危险因素相关性研究%The association of macroangiopathy with levels of PAI-1 and C-reactive protein and cerebro-cardiovascular risk factors in metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    周善存; 罗进才; 王少波; 梁志丽; 张煜; 邓黎

    2010-01-01

    Objective To explore the changes in levels of plasminogen activator inhibitor-1 (PAI-1) and C-reactive protein (CRP) in patients with metabolic syndrome and their significance.Methods Levels of hs - CRP, PAI-1 and blood glucose, lipids, and FFA were determined in 77 patients with metabolic syndrome(40 with macroangiopathy and 37 with no complications)and 30 healthy subjects and then were compared. Results Levels of he - CRP and PAI- 1 were significnatly higher in the group with macroangiopathy than in the group with no complications and the control group(P<0.01).Conclusions Levels of hs - CRP and PAI-1 are closely related with macroangiopathy in metabolic syndrome. the diagnosis, treatment and prevention of metabolic syndrome with macorangiopathy.%目的 研究代谢综合征大血管病变患者血浆纤溶酶原激活物抑制物-1(PAI-1)、血清超敏C反应蛋白(hs-CRP)水平变化和意义.方法 检测77例代谢综合征患者(其中大血管病变患者40例,无并发症患者37例)PAI-1、hs-CRP及血糖、血脂、游离脂肪酸(FFA)等生化指标水平,与30例健康对照组比较,并进行各指标之间的相关分析.结果 代谢综合征大血管病变组患者PAI-1、hs-CRP水平明显高于正常对照组及无并发症组,且差异有统计学意义(P<0.01).结论 PAI-1、hs-CRP水平与代谢综合征大血管病变有密切关系,PAI-1、hs-CRP水平检测对代谢综合征大血管并发症的诊断、预防和治疗具有很好的价值.

  15. The Association between PAI-1 Gene Promoter Polymorphism and Serum Serpin E1, MDA, and Hs-CRP Levels in Coronary Artery Disease

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    Ansar Karimian

    2016-09-01

    Full Text Available Background: Coronary Artery Disease (CAD is caused by atherosclerosis. Studies have shown that a number of factors, including cellular binding molecules such as Plasminogen Activator Inhibitor-1 (PAI-1, lipid peroxidation, inflammation, and hemostasis, are closely related to development and progression of CAD. Objectives: The present case-control study aimed to evaluate the association between Plasminogen Activator Inhibitor-1 (PAI-1 4G/5G polymorphism and oxidative stress markers and Coronary Artery Disease (CAD. Patients and Methods: Blood was drawn and DNA was extracted from 90 subjects (46 patients with angiographically diagnosed CAD and 44 age- and sex-matched healthy controls. The 4G/5G polymorphism of PAI-1 was detected by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP analysis. Besides, the risk factors, serpin E1, Malondialdehyde (MDA, high-sensitivity C-Reactive Protein (hs-CRP, and lipid profile serum levels were measured by standard methods and were compared between the two study groups using independent samples t-test, one-way ANOVA, and Mann-Whitney U test as appropriated. Results: Results: The frequency of 4G/4G genotype of PAI-1 gene was higher in the CAD patients than in the controls (28/46 (60.87% vs. 8/44 (18.18%, P < 0.01. Additionally, the serpin E1 plasma level was significantly higher in the CAD group carrying the 4G allele compared to those homozygous for the 5G allele (P = 0.016. Besides, a significant difference was found between the 4G/4G and 5G/5G subjects of the CAD group regarding plasma High-Density Lipoprotein (HDL (P < 0.01. Also, significant differences were observed among the three genotypes of both groups concerning the plasma levels of cholesterol, triglyceride, and Low-Density Lipoprotein (LDL. However, no significant correlation was found between PAI-1 gene polymorphism and MDA serum level, hs-CRP, and risk of CAD. Conclusion: The findings of this study suggested that 4G/4G PAI

  16. Relationship of metabolic syndrome and its components with -844 G/A and HindIII C/G PAI-1 gene polymorphisms in Mexican children

    Directory of Open Access Journals (Sweden)

    De la Cruz-Mosso Ulises

    2012-03-01

    Full Text Available Abstract Background Several association studies have shown that -844 G/A and HindIII C/G PAI-1 polymorphisms are related with increase of PAI-1 levels, obesity, insulin resistance, glucose intolerance, hypertension and dyslipidemia, which are components of metabolic syndrome. The aim of this study was to analyze the allele and genotype frequencies of these polymorphisms in PAI-1 gene and its association with metabolic syndrome and its components in a sample of Mexican mestizo children. Methods This study included 100 children with an age range between 6-11 years divided in two groups: a 48 children diagnosed with metabolic syndrome and b 52 children metabolically healthy without any clinical and biochemical alteration. Metabolic syndrome was defined as the presence of three or more of the following criteria: fasting glucose levels ≥ 100 mg/dL, triglycerides ≥ 150 mg/dL, HDL-cholesterol th percentile, systolic blood pressure (SBP and diastolic blood pressure (DBP ≥ 95th percentile and insulin resistance HOMA-IR ≥ 2.4. The -844 G/A and HindIII C/G PAI-1 polymorphisms were analyzed by PCR-RFLP. Results For the -844 G/A polymorphism, the G/A genotype (OR = 2.79; 95% CI, 1.11-7.08; p = 0.015 and the A allele (OR = 2.2; 95% CI, 1.10-4.43; p = 0.015 were associated with metabolic syndrome. The -844 G/A and A/A genotypes were associated with increase in plasma triglycerides levels (OR = 2.6; 95% CI, 1.16 to 6.04; p = 0.02, decrease in plasma HDL-cholesterol levels (OR = 2.4; 95% CI, 1.06 to 5.42; p = 0.03 and obesity (OR = 2.6; 95% CI, 1.17-5.92; p = 0.01. The C/G and G/G genotypes of the HindIII C/G polymorphism contributed to a significant increase in plasma total cholesterol levels (179 vs. 165 mg/dL; p = 0.02 in comparison with C/C genotype. Conclusions The -844 G/A PAI-1 polymorphism is related with the risk of developing metabolic syndrome, obesity and atherogenic dyslipidemia, and the HindIII C/G PAI-1 polymorphism was associated with the

  17. 阿托伐他汀对高血压病患者血浆sICAM-1水平和PAI-1活性的影响%Effects of Atorvastatin on Plasma Level of sICAM-1 and PAI-1 Activity in Patients with Essential Hypertension

    Institute of Scientific and Technical Information of China (English)

    陈然; 黄红光; 刘江陵; 程春; 黄玉艳

    2011-01-01

    [Objective]To explore the change of plasma level of soluble intercellular adhesion molecule -1 (sICAM- 1) and plasminogen activator inhibitor-1(PAI-1) activity and the effect of atorvastatin on them in patients with essential hypertension.[Methods]Enzyme linked immunosorbent assay(ELISA) and spectrophotmetric assay were used to measure the plasma level of sICAM-1 and PAI-1 activity in 155 patients with mild to moderate essential hypertension before and after atorvastatin treatment and 8 normal controls.[Results]Plasma level of sICAM-1 and PAI-1 activity in hypertensive patients were significantly higher than those in normal controls( P <0.01 and P <0.05).Plasma level of sICAM-1 and PAI-1 activity in hypertensive patients significantly decreased after 8 weeks of atorvastatin treatment( P <0.01 and P <0.05).[Conclusion]Compared with normal people, the plasma level of sICAM-1 and PAI-1 activity in hypertensive patients increase significantly.Atorvastatin can not only decrease blood lipids, but also decrease the level of sICAM-1 and PAI-1 activity, and reduce the incidence of the complications of hypertension.%[目的]探讨高血压病(EH)患者血浆细胞间粘附分子-1(sICAM-1)水平和纤溶酶原激活物抑制剂-1(PAI-1)活性的变化及阿托伐他汀对其的影响.[方法]采用酶联免疫吸附法(ELISA)、发色底物显色法分别对155例轻至中度高血压患者应用阿托伐他汀治疗前后和正常对照组者血浆sICAM-1水平和PAI-1活性进行检测.[结果]高血压患者血浆sICAM-1水平和PAI-1活性明显高于正常对照组(P<0.01及P<0.05),经阿托伐他汀治疗8周后其浓度明显下降(P<0.01及P<0.05).[结论]高血压病患者血浆sICAM-1水平和PAI-1活性较正常人明显升高,阿托伐他汀在有效调脂的同时能降低高血压患者血sICAM-1浓度和PAI-1活性,减少高血压并发症的发生.

  18. 麦没食子儿茶素没食子酸酯对TNF-α诱导的内皮细胞中PAI-1表达的影响及机制研究%(-)-Epigallocatechin Gallate inhibits TNF-α-induced PAI-1 Production in Vascular Endothelial Cells

    Institute of Scientific and Technical Information of China (English)

    曹艳丽; 王涤非; 王晓黎; 孟馨; 张锦; 单忠艳

    2012-01-01

    目的 探讨绿茶的主要成分麦没食子儿茶素没食子酸酯(EGCG)在血管内皮细胞中对肿瘤坏死因子-α(TNF-α)所诱导的纤溶酶原激活物抑制物-1(PAI-1)表达的影响及机制.方法 利用人脐静脉内皮细胞体外培养方法,分别与TNF-α和/或EGCG孵育,运用蛋白免疫印迹方法检测内皮细胞中磷酸化细胞外调节蛋白激酶1/2(p-ERK1/2)和肿瘤坏死因子受体1(TNFRl)蛋白表达,应用酶联免疫吸附法方法检测细胞液中PAI-1水平.结果 TNF-α以浓度依赖和时间依赖方式增加内皮细胞中PAI-1的表达.EGCG可抑制TNF-α所诱导的PAI-1的表达,并可抑制ERK1/2磷酸化.TNF-α的刺激可使TNFR1表达明显减少,而EGCG可抑制这一作用.结论 EGCG可能通过抑制ERK1/2的磷酸化,从而抑制TNF-α所诱导的PAI-1的表达,同时可减少TNF-α对TNFR1的抑制作用,在改善肥胖、胰岛素抵抗及相关心血管疾病中起着重要作用.%Objective To investigate the effects of (-)-Epigallocatechin gallate (EGCG), the major catechin derived from green tea, on vascular endothelial TNF-α-induced plasminogen activator inhibitor-1 (PAI-1) production and its mechanisms. Methods Human umbilical vein endothelial cells were cultured and incubated with TNF-α and/or EGCG. The expressions of phosphor-extracellular regulated protein kinase 1/2 (p-ERK1/2) and tumor necrosis factor receptor 1 (TNFR1) protein were quantified by western blotting, and PAI-1 levels were measured by enzyme-linked immunosorbent assay. Results TNF-α increased PAI-1 production in both a concentration- and time-dependent manner. EGCG prevented TNF-α mediated PAI-1 production and reduced phosphorylation of ERK1/2. TNF-α stimulation resulted in a significant decrease in TNFR1, but EGCG prevented such decrease. Conclusion EGCG inhibits TNF-α-induced PAI-1 production. Moreover, EGCG inhibits ERK1/2 phosphorylation as well as TNF-α-mediated reduction in TNFR1, which subsequently results in

  19. Correlation between Expression of P38 MAPK-Signaling and uPA in Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Yanchun Han; Luying Liu; Dongxia Yan; Guihua Wang

    2008-01-01

    OBJECTIVE To study the expression of phosphorylated p38 mitogen.Activated protein kinase(p-p38)and uPA and the correlation of their expression with breast cancer Clinic.patholodiCal characteristics,and to investigate the role of the p38MAPK-signaling pathway in regulating uPA expression in breast cancer cells.METHODS Immunohistochemistry(S-P)was used to test the expression of P-p38 and uPA in 60 specimens of breast cancer tissues.Western blots were adopted to detect expression of the p-p38 and uPA proteins in MDA-MB-231 and MCF-7 breast cancer cells.And uPA expression after treatment with SB203580,a specific inhibitor of p38 MAPK.RESULTS The positive rate of the P.P38 protein and uPA protein expression in the breast cancer tissues was 56.7% and 60.0%.Respectively.The expression of P.P38 was positively related to the expression of uPA(r=0.316,P0.05).The expression of p-p38 and uPA in MDA. MB-231 cells was higher than that in MCF.7 cells.SB203580 inhibited the p38 MAPK pathway and reduced uPA protein expression.CONCLUSI0N The p38 MAPK-signaling pathway promotes breast cancer malignant progression by up.Regulating uPA expression,and it may be an important process in breast cancer invasion and metastasis.

  20. ACE、PAI-1基因多态性与T2DM患者合并冠心病的关系%Relationship between Polymorphisms of PAI-1 Gene,ACE Gene and T2DM Combined with Coronary Heart Disease

    Institute of Scientific and Technical Information of China (English)

    刘玉华; 梁雪玲; 莫笑莲; 黄秋霞

    2009-01-01

    目的:探讨血管紧张素转换酶(angiotensin 1-converting enzyme,ACE)基因、纤溶酶原激活物抑制物-1(plasminogen activator inhibitor-1,PAI-1)基因多态性与2型糖尿病(type 2 diabetes,T2DM)患者冠状动脉粥样硬化性心脏病(coronary heart disease,CHD)的关系.方法:对100例单纯T2DM患者、60例T2DM合并冠心病患者进行ACE基因、PAI-1基因多态性检测,比较两组患者基因型及等位基因分布频率的差异;并进行Logistic多元回归分析影响T2DM患者冠心病的危险因素.结果:冠心病组患者PAI-1基因型频率、4G等位基因频率携带者比例较单纯T2DM患者显著增高(P<0.05)Logistic多元回归分析发现冠心病和PAI-1基因型密切相关.结论:PAI-1基因多态性可能是T2DM患者合并冠心病的危险因素.

  1. The change of PAI-1 and TNF-α in old patients with metabolic syndrome and the effect of metformin%PAI-1和TNF-α在老年代谢综合征患者中的变化及二甲双胍对其影响

    Institute of Scientific and Technical Information of China (English)

    邓满香; 刘慧霞; 张骥; 杨幼波

    2012-01-01

    Objective To explore the correlation of PAI-1 and TNF-α and the pathophysiology of the metabolic syndrome (MS) and coronary heart disease,and explore the role of metformin in the MS.Methods Sixty cases of old patients with the MS were chosen.These patients were divided into two groups at random.One group interfered with living style and metformin,the other group only interfered with living style.The activity of PAI-1 was detected by chromogenic substrate method,and the level of TNF-α was detected by ELISA assay.Results (1) The levels of PAI-1 and TNF-α in the MS patients [(0.95 ± 0.05) AU/ml,(24.81 ± 3.87)ng/ml] were significantly higher than in normal old people[(0.66 ± 0.10)AU/ml,(10.76 ±2.00) ng/ml] (P <0.001) ;(2)The levels of PAI-1 and TNF-α in the MS patients with CHD [(0.96 ± 0.05) AU/ml,(26.12 ± 2.83) ng/ml] were significantly higher than those in the patients without CHD [(0.94 ± 0.03) AU/ml,(23.71 ± 4.27) ng/ml] (P < 0.05) ;(3)The activity of PAI-1 and the level of TNF-α in the metformin group was decreased significantly [△ was (0.20 ± 0.17)AU/ml,(4.42 ± 0.85ng/ml),P <0.01],and metformin can improve the components of the MS.Conclusions The old patients with MS is prone to develop cardiac vascular disease.PAI-1 and TNF-α participate in pathophysiology of the MS and its complication.Metformin can inhibit the expression of PAI-1 and TNF-α to suppress the components of the MS,and block the complication of the MS.%目的 探讨纤溶酶原激活物抑制剂-1(PAI-1)及肿瘤坏死因子-α(TNF-α)与代谢综合征(Metabolic syndrome,MS)及并发冠心病发病的关系,并探讨二甲双胍对PAI-1、TNF-α及MS的影响.方法 老年MS患者60例,分成两组各30例:二甲双胍组予生活方式及二甲双胍干预治疗,生活干预组仅予生活方式干预.另选择同期健康体检者30例为对照组,发色底物法检测血浆PAI-1水平,ELISA法检测TNF-α水平.结果 (1)老年MS患者血PAI-1活性、TNF-α水平[(0

  2. PAI-1基因4G/5G多态性与PCOS糖代谢、肥胖的相关性研究%4G/5G Polymorphism of Plasminogen Activator Inhibitor-1 (PAI-1) Gene in Polycystic Ovarian Syndrome and its Correlation with Glucose Metabolism and Obese Status

    Institute of Scientific and Technical Information of China (English)

    赵君利; 陈子江; 赵跃然; 王来城; 赵力新; 唐蓉; 马增香; 石玉华

    2006-01-01

    目的:探讨纤溶酶原激活物抑制因子-1(PAI-1)基因启动子4G/5G多态性与多囊卵巢综合征(PCOS)糖代谢、肥胖的关系.方法:PCR-RFLP法检测42例正常育龄妇女,101例PCOS患者[根据糖代谢情况分为A、B、C组;根据体重指数(BMI)分为肥胖、非肥胖组]PAI-1基因启动子4G/5G位点插入或缺失多态性,比较组间多态基因型分布及体重指数(BMI)、胰岛素抵抗指数(Homa-IR)、胰岛素敏感指数(ISI).结果:①BMI、Homa-IR指标PCOS糖代谢C组>B组>A组、肥胖PCOS组>非肥胖PCOS组,ISI则相反,差异均有显著性(P<0.05).②PCOS组不同糖代谢组PAI-1基因4G/5G多态基因型分布无差异,但PCOS组、PCOS糖代谢异常C组与对照组、PCOS非肥胖组与肥胖组之间比较有统计学差异(x2=4.439、4.018、4.151;P均<0.05);4G型(4G/4G基因型)PCOS组、PCOS糖代谢异常C组与非肥胖PCOS组分布显著高于相应对照组与肥胖PCOS组;5G型(4G/5G+5G/5G基因型)分布相反.结论:①PCOS患者高PAI-1 4G/4G多态基因型,可能是其高PAI-1活性现象的重要遗传基础.②PAI-1基因启动子4G/5G多态性可能与PCOS患者糖代谢异常、非肥胖PCOS发病、病情进展有关.

  3. Serum tetranectin is an independent prognostic marker in colorectal cancer and weakly correlated with plasma suPAR, plasma PAI-1 and serum CEA

    DEFF Research Database (Denmark)

    Høgdall, Claus K; Christensen, Ib J; Stephens, Ross W;

    2002-01-01

    to have an independent prognostic value for survival (log TN: HR = 0.47, 95% CI: 0.29-0.76); log soluble uPAR: HR = 1.65, 95% CI: 1.18-2.31; log CEA: HR = 1.I1, 95% CI: 1.03-1.20). Based on the multivariate model, a patient with a combination of low levels of TN and PAI-1 and elevated levels of...... prognostic factor in patients with colorectal cancer. TN may be valuable as a prognostic variable in future studies evaluating new treatment strategies for colorectal cancer....

  4. Associação de níveis plasmáticos de PAI-1 e polimorfismo 4G/5G em pacientes com doença arterial coronariana

    Directory of Open Access Journals (Sweden)

    Luciana Moreira Lima

    2011-12-01

    Full Text Available FUNDAMENTO: O polimorfismo 4G/5G do inibidor ativador do plasminogênio tipo 1 (PAI-1 pode influenciar a expressão do PAI-1. Níveis plasmáticos elevados de PAI-1 estão associados com Doença Arterial Coronariana (DAC. OBJETIVO: O presente estudo investigou a influência do polimorfismo 4G/5G do PAI-1 nos níveis plasmáticos de PAI-1 e sua associação com DAC avaliada por angiografia coronária. MÉTODOS: Foi avaliada amostra de sangue de 35 indivíduos com artérias coronárias angiograficamente normais, 31 indivíduos apresentando ateromatose leve/moderada, 57 indivíduos apresentando ateromatose grave e 38 indivíduos saudáveis (controles. Em pacientes e controles, o polimorfismo 4G/5G do PAI-1 foi determinado por amplificação da proteína-C reativa utilizando primers específicos de alelo. Os níveis plasmáticos de PAI-1 foram quantificados pelo ensaio ELISA (American Diagnostica. RESULTADOS: Não houve diferença entre os grupos quanto a sexo, idade e índice de massa corporal. Níveis plasmáticos de PAI-1 e frequência do genótipo 4G/4G mostravam-se significativamente maiores no grupo com ateromatose grave em comparação com os outros grupos (p 70% (p < 0,001. CONCLUSÃO: O achado mais importante deste estudo foi a associação entre o genótipo 4G/4G, elevados níveis plasmáticos de PAI-1 e estenose coronariana superior a 70% em indivíduos brasileiros. Ainda não foi estabelecido se elevados níveis plasmáticos de PAI-1 são um fator decisivo para o agravamento da aterosclerose ou se são uma consequência.

  5. Concomitant lack of MMP9 and uPA disturbs physiological tissue remodeling

    DEFF Research Database (Denmark)

    Lund, Ida K; Nielsen, Boye S; Almholt, Kasper;

    2011-01-01

    -type plasminogen activator (tPA)-catalyzed plasminogen activation is critical to accomplish normal gestation in mice. Gestation was also affected by simultaneous lack of MMP9 and the uPA receptor (uPAR). Interestingly, uPA-deficiency additionally exacerbated the effect of MMP9-deficiency on bone growth...... and an additive effect caused by combined lack in MMP9 and uPA was observed during healing of cutaneous wounds. By comparison, MMP9-deficiency combined with absence of either tPA or uPAR resulted in no significant effect on wound healing, indicating that the role of uPA during wound healing is independent of u...

  6. BioKnife, a uPA activity-dependent oncolytic Sendai virus, eliminates pleural spread of malignant mesothelioma via simultaneous stimulation of uPA expression.

    Science.gov (United States)

    Morodomi, Yosuke; Yano, Tokujiro; Kinoh, Hiroaki; Harada, Yui; Saito, Satoru; Kyuragi, Ryoichi; Yoshida, Kumi; Onimaru, Mitsuho; Shoji, Fumihiro; Yoshida, Tsukihisa; Ito, Kensaku; Shikada, Yasunori; Maruyama, Riichiroh; Hasegawa, Mamoru; Maehara, Yoshihiko; Yonemitsu, Yoshikazu

    2012-04-01

    Malignant pleural mesothelioma (MPM) is highly intractable and readily spreads throughout the surface of the pleural cavity, and these cells have been shown to express urokinase-type plasminogen activator receptor (uPAR). We here examined the potential of our new and powerful recombinant Sendai virus (rSeV), which shows uPAR-specific cell-to-cell fusion activity (rSeV/dMFct14 (uPA2), named "BioKnife"), for tumor cell killing in two independent orthotopic xenograft models of human. Multicycle treatment using BioKnife resulted in the efficient rescue of these models, in association with tumor-specific fusion and apoptosis. Such an effect was also seen on both MSTO-211H and H226 cells in vitro; however, we confirmed that the latter expressed uPAR but not uPA. Of interest, infection with BioKnife strongly facilitated the uPA release from H226 cells, and this effect was completely abolished by use of either pyrrolidine dithiocarbamate (PDTC) or BioKnife expressing the C-terminus-deleted dominant negative inhibitor for retinoic acid-inducible gene-I (RIG-IC), indicating that BioKnife-dependent expression of uPA was mediated by the RIG-I/nuclear factor-κB (NF-κB) axis, detecting RNA viral genome replication. Therefore, these results suggest a proof of concept that the tumor cell-killing mechanism via BioKnife may have significant potential to treat patients with MPM that is characterized by frequent uPAR expression in a clinical setting. PMID:22314292

  7. Portal Vein Thrombosis in a Preterm Newborn with Mutation of the MTHFR and PAI-1 Genes and Sepsis by Candida parapsilosis.

    Science.gov (United States)

    Giuffrè, Mario; Verso, Clelia Lo; Serra, Gregorio; Moceri, Giovanni; Cimador, Marcello; Corsello, Giovanni

    2016-09-01

    Objective This report discusses the role of both congenital and acquired risk factors in the pathogenesis of portal vein thrombosis (PVT). Study Design We describe the clinical management and treatment of PVT in a preterm newborn with a homozygous mutation of the methylenetetrahydrofolate reductase (MTHFR) and plasminogen activator inhibitor-1 (PAI-1) genes and sepsis by Candida parapsilosis. Results Although literature data suggest a minor role of genetic factors in thrombophilia in the case of only one mutation, we hypothesize that combined thrombophilic genetic defects may have a cumulative effect and significantly increase the thrombotic risk. Conclusion It could be appropriate to include more detailed analyses of procoagulant and fibrinolytic factors in the diagnostic workup of neonatal thrombosis, also through the investigation of genetic polymorphisms. The anticoagulant therapy and the removal of concurrent risk factors remain basic steps for the adequate management and prevention of complications. PMID:27603544

  8. Poised transcription factories prime silent uPA gene prior to activation.

    Directory of Open Access Journals (Sweden)

    Carmelo Ferrai

    2010-01-01

    Full Text Available The position of genes in the interphase nucleus and their association with functional landmarks correlate with active and/or silent states of expression. Gene activation can induce chromatin looping from chromosome territories (CTs and is thought to require de novo association with transcription factories. We identify two types of factory: "poised transcription factories," containing RNA polymerase II phosphorylated on Ser5, but not Ser2, residues, which differ from "active factories" associated with phosphorylation on both residues. Using the urokinase-type plasminogen activator (uPA gene as a model system, we find that this inducible gene is predominantly associated with poised (S5p(+S2p(- factories prior to activation and localized at the CT interior. Shortly after induction, the uPA locus is found associated with active (S5p(+S2p(+ factories and loops out from its CT. However, the levels of gene association with poised or active transcription factories, before and after activation, are independent of locus positioning relative to its CT. RNA-FISH analyses show that, after activation, the uPA gene is transcribed with the same frequency at each CT position. Unexpectedly, prior to activation, the uPA loci internal to the CT are seldom transcriptionally active, while the smaller number of uPA loci found outside their CT are transcribed as frequently as after induction. The association of inducible genes with poised transcription factories prior to activation is likely to contribute to the rapid and robust induction of gene expression in response to external stimuli, whereas gene positioning at the CT interior may be important to reinforce silencing mechanisms prior to induction.

  9. Overexpression of SlUPA-like induces cell enlargement, aberrant development and low stress tolerance through phytohormonal pathway in tomato.

    Science.gov (United States)

    Cui, Baolu; Hu, Zongli; Hu, Jingtao; Zhang, Yanjie; Yin, Wencheng; Zhu, Zhiguo; Feng, Ye; Chen, Guoping

    2016-01-01

    upa20 induces cell enlargement and hypertrophy development. In our research, overexpression of SlUPA-like, orthologous to upa20, severely affected the growth of vegetative and reproductive tissues. Wilted leaves curled upwardly and sterile flowers were found in transgenic lines. Through anatomical analysis, palisade and spongy tissues showed fluffy and hypertrophic development in transgenic plants. Gene expression analysis showed that GA responsive, biosynthetic and signal transduction genes (e.g. GAST1, SlGA20OXs, SlGA3OXs, SlGID1s, and SlPREs) were significantly upregulated, indicating that GA response is stimulated by overproduction of SlUPA-like. Furthermore, SlUPA-like was strongly induced by exogenous JA and wounding. Decreased expression of PI-I and induced expression of SlJAZs (including SlJAZ2, SlJAZ10 and SlJAZ11) were observed in transgenic plants, suggesting that JA response is repressed. In addition, SlUPA-like overexpressed plant exhibited more opened stoma and higher water loss than the control when treated with dehydration stress, which was related to decreased ABA biosynthesis, signal transduction and response. Particularly, abnormal developments of transgenic plants promote the plant susceptibility to Xanthomonas campestris pv. campestris. Therefore, it is deduced from these results that SlUPA-like plays vital role in regulation of plant development and stress tolerance through GA, JA and ABA pathways. PMID:27025226

  10. A comparison among HER2, TP53, PAI-1, angiogenesis, and proliferation activity as prognostic variables in tumours from 408 patients diagnosed with early breast cancer

    DEFF Research Database (Denmark)

    Offersen, Birgitte Vrou; Alsner, Jan; Olsen, Karen Ege;

    2008-01-01

    BACKGROUND: The prognostic potential of HER2, TP53 mutations, PAI-1 protein levels, angiogenesis and proliferation were investigated in tumours from 408 patients with early breast cancer followed >10 years. One hundred and sixty seven patients (41%) died from breast cancer. MATERIALS AND METHODS...

  11. BioKnife, a uPA Activity-dependent Oncolytic Sendai Virus, Eliminates Pleural Spread of Malignant Mesothelioma via Simultaneous Stimulation of uPA Expression

    OpenAIRE

    Morodomi, Yosuke; Yano, Tokujiro; Kinoh, Hiroaki; Harada, Yui; Saito, Satoru; Kyuragi, Ryoichi; Yoshida, Kumi; Onimaru, Mitsuho; Shoji, Fumihiro; Yoshida, Tsukihisa; Ito, Kensaku; Shikada, Yasunori; Maruyama, Riichiroh; Hasegawa, Mamoru; Maehara, Yoshihiko

    2012-01-01

    Malignant pleural mesothelioma (MPM) is highly intractable and readily spreads throughout the surface of the pleural cavity, and these cells have been shown to express urokinase-type plasminogen activator receptor (uPAR). We here examined the potential of our new and powerful recombinant Sendai virus (rSeV), which shows uPAR-specific cell-to-cell fusion activity (rSeV/dMFct14 (uPA2), named “BioKnife”), for tumor cell killing in two independent orthotopic xenograft models of human. Multicycle ...

  12. 螺内酯对2型糖尿病大鼠血管PAI-1mRNA表达的影响%Influence of Spironolactone on the Expression of PAI-1 mRNA in Aorta of Rats with Type 2 Diabetes Mellitus

    Institute of Scientific and Technical Information of China (English)

    李秀成; 韩刚; 孙侃; 常向云; 李军

    2013-01-01

    [目的]探讨非选择性醛固酮(aldsterone,ALD)受体拮抗剂-螺内酯(Spironolactone,SPI)对2型糖尿病(type 2 diabetic mellitus,T2DM)大鼠血管纤溶酶原激活物抑制剂-1(plasminogen activator inhibitor-1,PAI-1)mRNA的表达的影响.[方法] 高脂高糖喂养加小剂量链脲佐菌素(streptozotocin,STZ)腹腔注射法建立2型糖尿病大鼠模型,将成膜的T2DM大鼠随机分为糖尿病对照组(DM-C组)和SPI干预组(DM-S组),继续高脂高糖喂养,正常对照组(NC组)大鼠继续给予普通饲料喂养,其中DM-S组每天给予SPI 40 mg/(kg·d)灌胃,NC组和DM-C组每天等量蒸馏水灌胃.每2周监测大鼠体重和血糖水平,第16周末处死大鼠,收集血液标本,检测空腹血糖(FBG)、糖化血红蛋白(HbA1c﹪)、甘油三酯(TG)、胆固醇(TG)、血钾(K+).用RT-PCR法检测各组大鼠胸主动脉PAI-1 mRNA表达.[结果]DM-C组和DM-S组大鼠FBG、HbA1c﹪、TG均显著高于NC组(P<0.01),而DM-S组和DM-C组比较差异无统计学意义(P>0.05);三组之间的血K+水平比较差异无统计学意义(P>0.05);DM-C组和DM-S组大鼠胸主动脉PAI-1 mRNA的表达显著高于NC组(P<0.01),且DM-C组高于DM-S组(P<0.05).[结论] SPI能通过下调T2DM大鼠主动脉PAI-1mRNA的表达而发挥血管保护作用.%[Objective]To explore the influence of nonselective aldosterone(ALD) receptor antagonist-spirono-lactone(SPI) on the expression of type-1 plasminogen activator inhibitor(PAI-l) mRNA in rats with type 2 diabetes mellitus(T2DM). [Methods] The model of T2DM rats was established by being fed with high-sucrose-high-fat diet and intraperitoneally injected with low dose streptozotocin(STZ). Rat models of T2DM were randomly divided into diabetes mellitus control group (group DM-C) and SPI intervention group (group DM-S). Each rat in group DM-C and DM-S was continuously fed with high-sucrose-high-fat diet. Rats in normal control group (group NO were fed with routine animal feeds. Group DM-S was

  13. Circulating Levels of PAI-1 and SERPINE1 4G/4G Polymorphism Are Predictive of Poor Prognosis in HCC Patients Undergoing TACE

    Directory of Open Access Journals (Sweden)

    Rosa Divella

    2015-08-01

    Full Text Available Although several molecular markers have been proposed as prognostic of disease progression in Hepatocellular carcinoma (HCC, predictive markers of response to treatment are still unsatisfactory. Here, we propose a genetic polymorphism as a potential predictive factor of poor prognosis in HCC patients treated with transcatheter arterial chemoembolization (TACE. In particular, we show that the guanosine insertion/deletion polymorphism in the promoter region of SERPINE1 gene at the −675 bp position, named 4G/4G, predicts poor prognosis in a cohort of 75 patients with HCC undergoing TACE. By a combination of ELISA and SERPINE1 promoter study, we found that the presence of elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1 in patients with 4G/4G genotype is significantly associated with reduced overall survival compared to patients with 5G/5G or 4G/5G genotype in HCC patients after TACE. Our analysis provided evidence that variation in SERPINE1 gene plays a role in defining the outcome in patients treated with TACE. In addition to a poor disease outcome, the 4G/4G variant represents an unfavorable predictive factor for response to chemotherapy as well.

  14. Cloning and Analysis of the Promoter Region of Rat uPA Gene

    Institute of Scientific and Technical Information of China (English)

    Yan LIU; Jin-wen XIONG; Li-gang CHEN; Yong-hong TIAN; Cheng-liang XIONG

    2007-01-01

    Objective To clone and analyze the promoter sequence of rat urokinase plasminogen activator protein gene.Methods The genomic DNA was extracted from rat testicular tissue. According to urokinase plasminogen activator, the gene sense primer and antisense primer of uPA gene were designed and synthesized, then Touch-Down PCR were performed. After proper purification, the PCR product was sequenced, analyzed with the promoter prediction software and compared with the DNA sequence of rattuas urokinase plasminogen activator.Results The cloned uPA gene was about 1 572 bp in length, which contained a full open-reading frame with 21 bp in length exons, and the upper region of transcriptional start was 1 551 bp in length which was eucaryon transcriptional control area.The 5' UTR had a promoter region including a non-responsive TATA-box. Not only the GC-box binding region was found in this gene, but also active protein 1 (AP1) and SP1 were seen in other regions.Conclusion A 1 572 bp uPA gene fragment (GenBank accession No. X65651) was obtained from rat genomic DNA library, containing eucaryon transcriptional control area with a promoter region, non-conspicuous TATA-box, GC-box and an extron. A non-responsive TATA-box is located at the upper -30 region.

  15. Tetrahydrocurcumin inhibits HT1080 cell migration and invasion via downregulation of MMPs and uPA

    Institute of Scientific and Technical Information of China (English)

    Supachai YODKEEREE; Spiridione GARBISA; Pomngarm LIMTRAKUL

    2008-01-01

    Aim: Tetrahydrocurcumin (THC) is an active metabolite of curcumin. It has been reported to have similar pharmacological activity to curcumin. The proteases that participate in extracellular matrix (ECM) degradation are involved in cancer cell metastasis. The present study investigates the effect of an ultimate metabolite of curcumin, THC, on the invasion and motility of highly-metastatic HT1080 human fibrosarcoma cells. Methods: The effect of THC on HTI080 cell invasion and migration was determined using Boyden chamber assay. Cell-adhesion assay was used for examining the binding of cells to ECM molecules. Zymography assay was used to analyze the effect of THC on matrix metalloproteinase (MMP)-2, MMP-9, and urokinase plasminogen activator (uPA) secretion from HT1080 cells. Tissue inhibitor of metalloproteinase (TIMP)-2 and membrane-type 1 matrix metalloproteinase (MT1-MMP) proteins levels were analyzed by Western blotting. Results: Treatment with THC reduced HT1080 cell invasion and migration in a dose-dependent manner. THC also decreased the cell adhesion to Matrigel and laminin-coated plates. Analysis by zymography demonstrated that treatment with THC reduced the levels of MMP-2, MMP-9, and uPA. THC also inhibited the levels of MT1-MMP and TIMP-2 proteins detected by Western blot analysis. Conclusion: Our findings revealed that THC reduced HT1080 cell invasion and migration. The inhibition of cancer cell invasion is associated with the downregulation of ECM degradation enzymes and the inhibition of cell adhesion to ECM proteins.

  16. MnTE-2-PyP reduces prostate cancer growth and metastasis by suppressing p300 activity and p300/HIF-1/CREB binding to the promoter region of the PAI-1 gene.

    Science.gov (United States)

    Tong, Qiang; Weaver, Michael R; Kosmacek, Elizabeth A; O'Connor, Brian P; Harmacek, Laura; Venkataraman, Sujatha; Oberley-Deegan, Rebecca E

    2016-05-01

    To improve radiation therapy-induced quality of life impairments for prostate cancer patients, the development of radio-protectors is needed. Our previous work has demonstrated that MnTE-2-PyP significantly protects urogenital tissues from radiation-induced damage. So, in order for MnTE-2-PyP to be used clinically as a radio-protector, it is fully necessary to explore the effect of MnTE-2-PyP on human prostate cancer progression. MnTE-2-PyP inhibited prostate cancer growth in the presence and absence of radiation and also inhibited prostate cancer migration and invasion. MnTE-2-PyP altered p300 DNA binding, which resulted in the inhibition of HIF-1β and CREB signaling pathways. Accordingly, we also found that MnTE-2-PyP reduced the expression of three genes regulated by HIF-1β and/or CREB: TGF-β2, FGF-1 and PAI-1. Specifically, MnTE-2-PyP decreased p300 complex binding to a specific HRE motif within the PAI-1 gene promoter region, suppressed H3K9 acetylation, and consequently, repressed PAI-1 expression. Mechanistically, less p300 transcriptional complex binding is not due to the reduction of binding between p300 and HIF-1/CREB transcription factors, but through inhibiting the binding of HIF-1/CREB transcription factors to DNA. Our data provide an in depth mechanism by which MnTE-2-PyP reduces prostate cancer growth and metastasis, which validates the clinical use of MnTE-2-PyP as a radio-protector to enhance treatment outcomes in prostate cancer radiotherapy. PMID:26944191

  17. 尿激酶型纤溶酶原激活物抑制剂1参与非小细胞肺癌的侵袭与转移%PAI-1 involve in invasion and metastasis of non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    刘明; 周承志; 欧阳铭

    2015-01-01

    目的:探讨尿激酶型纤溶酶原激活物抑制剂1(PAI-1)的表达与非小细胞肺癌(NSCLC)的浸润转移的关系。方法应用免疫组化的方法,观察68例 NSCLC 患者标本中 PAI-1在肺癌组织中的表达及细胞定位,分析其与肺癌病理类型、分期、转移的关系。检测 PAI-1在 NSCLC 细胞系中的表达,分析其与转移相关分子基质金属蛋白酶9的关系,观察细胞因子复合物 Cytomix(TGF-β1+IL-1β+IFN-γ)刺激 A549细胞后 PAI-1的变化及 PAI-1 siRNA 转染对其侵袭能力的影响。结果在 NSCLC 组织标本中,PAI-1的表达主要分布于细胞胞浆,部分可为细胞膜或细胞核,表达可见于肿瘤细胞、间质成纤维细胞、血管内皮细胞及部分巨噬细胞,阳性表达率分别为64.7%、44.1%、25.0%、22.1%(P <0.01)。PAI-1高表达多见于Ⅱ~Ⅲ期、有远处转移的肺癌患者。PAI-1在不同 NSCLC 细胞系具有不同的表达水平,且与转移相关蛋白基质金属蛋白酶9的表达一致。Cytomix 刺激可导致 PAI-1表达的上调,使A549细胞转分化为具有侵袭性的梭形细胞,而给予 PAI-1 siRNA 能抑制该表型的出现。结论 PAI-1在肺癌组织中高表达,提示其在肿瘤发生过程中发挥一定的作用,其不同的表达模式提示其不同的功能需要,PAI-1的表达与转移密切相关。%Objective To investigate the expression and clinical significance of plasminogen activator inhibitor-1 (PAI-1 )in non-small cell lung cancer (NSCLC).Methods Immunohistochemistry was applied to evaluate the expression of PAI-1 protein in 68 paraffin-embedded specimens with NSCLC, the correlations of their expression to the clinicopathologic characteristics of patients were analyzed.The expression and correlations of PAI-1 and matrix metalloprotein-9,and the role of PAI-1 in cell invasion were investigated in NSCLC cell lines by cytomix (transforming growth factor-β1 + interleukin-1β+interferon-γ)stimulation and PAI-1 si

  18. Osmium (VI) complexes of the 3', 5'-dinucleoside monophosphates, ApU and UpA.

    Science.gov (United States)

    Daniel, F B; Behrman, E J

    1976-02-10

    The dinucleoside monophosphates, ApU and UpA, react with potassium osmate (VI) and 2,2'-bipyridyl to form the corresponding oxo-osmium (VI) bipyridyl sugar ester in which the osmate group is bonded to the terminal 2',3'-glycol. Osmium (VIII) tetroxide and 2,2'-bipyridyl react with the dinucleosides to form the corresponding oxo-osmium (VI) bipyridyl heterocyclic esters which result from addition of the tetroxide to the 5,6-double bond of the uracil residue. Although capable of transesterification reactions, these heterocyclic esters are exceptionally stable toward exchange reactions in solution. No apparent exchange was observed after 1 month. This reaction thus seems promising for single-site osmium labeling in polynucleotides.

  19. Flow cytometry evaluation of urokinase-type plasminogen activator receptor (UPA-R) in acute myeloid leukemia cells.

    Science.gov (United States)

    Castagnari, B; Moretti, S; Latorraca, A; Rigolin, G M; Balsamo, R; Lanza, F; Castoldi, G L

    1995-01-01

    The aim of this study was to investigate by flow cytometry the expression of the UPA-R (Urokinase type plasminogen activator receptor-CD87) on the blastic population of AML and ALL patients in order to evaluate whether the presence of this molecule could be associated with peculiar clinical and biologic features of leukemic cells. Five different monoclonal antibodies (MoAbs) (clones: 3B10#; VIM5*; 109#; 68#; 100#) were used in order to detect the distinct forms of this cellular receptor. Cell reactivity varied significantly from case to case, also depending on the MoAb used for the flow cytometry analysis. In brief, 3B10# and VIM5* MoAbs were found to be positive in more than 90% of monocytes and neutrophils from healthy subjects, while the number of positive cells was decreased (60%) using the 109# MoAb. However, either 68# and 100# MoAbs recognised only a low number of blood monocytes and neutrophils (8-20%), while lymphocytes were unreactive with all the five UPA-R MoAbs. ALL cells were found to be CD87 negative in all cases. Blasts from AML showed a heterogeneous pattern of expression for the UPA-R MoAbs, being the reactivity strictly dependent on the MoAb used, and, to a higher extent, on the degree and type of maturation of the blastic cells. The number of blasts recognising 3B10# and VIM5* MoAbs was significantly higher than that reacting with the remaining MoAbs irrespective of the FAB subtype. Since proteolytic enzymes, like UPA, play a key role in the dissolution of the extracellular matrix, and in facilitating the cell egress from the bone marrow, it is conceivable that the expression of the UPA-R could contribute to the invasive properties and, possibly, metastatic potential of leukemic cells. PMID:8519488

  20. Study on the relationship between plasma expressions of certain vascular endothelial dysfunction related markers (ET-1, vWF and PAI-1) and development of macro-vascular lesions in patients with type 2 diabetes mellitus (DM2)

    International Nuclear Information System (INIS)

    Objective: To explore the relationship between the plasma expression of certain vascular endothelial dysfunction related markers (ET-1, vWF, PAI-1) and development of macrovascular lesions in patients with DM2. Methods: Plasma ET-1 (with RIA) and plasminogen activator inhibitor-1, PTI-1), von willebrand factor, vWF (with ELISA) levels were determined in 65 DM2 patients complicated with macro-vascular lesions, 54 DM2 patients without macro-vascular lesions and 46 controls. The blood triglyceride (TG) total cholesterol (TH) and fasting sugar (fBG) levels were also measured with biochemistry. Fasting insulin levels were measured with MEIA method. Results: The plasma levels of ET-1, vWF and PAI-1 in all the diabetic patients were significantly higher than those in controls (P0.05), but the fBI, fBG levels were significantly higher than those in controls (P<0.05). Conclusion: Endothelial dysfunction related markers increased more in diabetics with vascular lesions (ET-1 significantly, the other two increased but not significantly). (authors)

  1. Adiposidade corporal, mas não resistência insulínica, associa-se ao polimorfismo -675 4G/5G no gene PAI-1 em uma amostra de crianças mexicanas

    Directory of Open Access Journals (Sweden)

    Ulises de la Cruz-Mosso

    2013-10-01

    Full Text Available OBJETIVO: Elaboramos este estudo para avaliar se o polimorfismo -675 4G/5G no gene inibidor 1 do ativador do plasminogênio se associa à obesidade e à resistência insulínica em crianças mexicanas. MÉTODOS: Foi realizado um estudo transversal em 174 crianças, 89 delas com peso normal e 85 obesas, variando sua idade de 6 a 13 anos. Todas as crianças eram do estado de Guerrero e foram recrutadas de três escolas primárias na cidade de Chilpancingo, México. Os níveis de insulina foram determinados por prova imunoenzimática. Foi usado o modelo de avaliação da homeostase para determinar resistência insulínica. O polimorfismo -675 4G/5G no gene PAI-1 foi analisado pelo método reação de polimerase em cadeia-polimorfismo no comprimento dos fragmentos de restrição. RESULTADOS: A prevalência de resistência insulínica no grupo obeso foi mais alta (49,41% do que no grupo com peso normal (16,85%. O polimorfismo 4G/5G do PAI-1 foi encontrado em equilíbrio de Hardy Weinberg. O genótipo 4G/5G contribuiu para um aumento significativo da relação cintura-quadril (β = 0,02, p = 0,006, da circunferência da cintura (β = 4,42, p = 0,009 e da espessura da prega subescapular (β = 1,79, p = 0,04, mas não se relacionou com a resistência insulínica. CONCLUSÃO: O genótipo -675 4G/5G do gene PAI-1 se associou a aumento da adiposidade corporal em crianças mexicanas.

  2. Neutralisation of uPA with a monoclonal antibody reduces plasmin formation and delays skin wound healing in tPA-deficient mice

    DEFF Research Database (Denmark)

    Jögi, Annika; Rønø, Birgitte; Lund, Ida K;

    2010-01-01

    Proteolytic degradation by plasmin and metalloproteinases is essential for epidermal regeneration in skin wound healing. Plasminogen deficient mice have severely delayed wound closure as have mice simultaneously lacking the two plasminogen activators, urokinase-type plasminogen activator (u......PA) and tissue-type plasminogen activator (tPA). In contrast, individual genetic deficiencies in either uPA or tPA lead to wound healing kinetics with no or only slightly delayed closure of skin wounds....

  3. CFTR suppresses tumor progression through miR-193b targeting urokinase plasminogen activator (uPA) in prostate cancer.

    Science.gov (United States)

    Xie, C; Jiang, X H; Zhang, J T; Sun, T T; Dong, J D; Sanders, A J; Diao, R Y; Wang, Y; Fok, K L; Tsang, L L; Yu, M K; Zhang, X H; Chung, Y W; Ye, L; Zhao, M Y; Guo, J H; Xiao, Z J; Lan, H Y; Ng, C F; Lau, K M; Cai, Z M; Jiang, W G; Chan, H C

    2013-05-01

    Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is expressed in the epithelial cells of a wide range of organs/tissues from which most cancers are derived. Although accumulating reports have indicated the association of cancer incidence with genetic variations in CFTR gene, the exact role of CFTR in cancer development and the possible underlying mechanism have not been elucidated. Here, we report that CFTR expression is significantly decreased in both prostate cancer cell lines and human prostate cancer tissue samples. Overexpression of CFTR in prostate cancer cell lines suppresses tumor progression (cell growth, adhesion and migration), whereas knockdown of CFTR leads to enhanced malignancies both in vitro and in vivo. In addition, we demonstrate that CFTR knockdown-enhanced cell proliferation, cell invasion and migration are significantly reversed by antibodies against either urokinase plasminogen activator (uPA) or uPA receptor (uPAR), which are known to be involved in various malignant traits of cancer development. More interestingly, overexpression of CFTR suppresses uPA by upregulating the recently described tumor suppressor microRNA-193b (miR-193b), and overexpression of pre-miR-193b significantly reverses CFTR knockdown-enhanced malignant phenotype and abrogates elevated uPA activity in prostate cancer cell line. Finally, we show that CFTR gene transfer results in significant tumor repression in prostate cancer xenografts in vivo. Taken together, the present study has demonstrated a previously undefined tumor-suppressing role of CFTR and its involvement in regulation of miR-193b in prostate cancer development. PMID:22797075

  4. Recombinant nematode anticoagulant protein c2 inhibits cell invasion by decreasing uPA expression in NSCLC cells.

    Science.gov (United States)

    Tong, Yu; Yue, Jun; Mao, Meng; Liu, Qingqing; Zhou, Jing; Yang, Jiyun

    2015-04-01

    Nematode anticoagulant protein c2 (NAPc2) is an 85-residue polypeptide originally isolated from the hematophagous hookworm, Ancylostoma caninum. Several studies have shown that rNAPc2 inhibits the growth of primary and metastatic tumors in mice independently of its ability to initiate coagulation. We obtained bioactive recombinant rNAPc2 by splicing of the rNAPc2-intein-CBD fusion proteins expressed in E. coli ER2566. In the in vitro assay, rNAPc2 obviously inhibited the invasive ability of non-small cell lung cancer (NSCLC) cells in a dose-dependent manner. Furthermore, rNAPc2 suppressed tumor growth in vivo by daily intraperitoneal injection of rNAPc2 in an NSCLC cell xenograft model of nude mice. Respectively, rNAPc2 downregulated the production of urokinase plasminogen activator (uPA) (P<0.05) and suppressed nuclear factor-κB (NF-κB) activity. We also identified that inhibition of NF-κB activity impaired cell invasion and reduced the uPA production in NSCLC cells. Meanwhile, NF-κB was found to directly bind to the uPA promoter in vitro. These results demonstrated that rNAPc2 inhibits cell invasion at least in part through the downregulation of the NF-κB-dependent metastasis-related gene expression in NSCLC. Our results also suggest that uPA, a known metastasis-promoting gene, is indirectly regulated by rNAPc2 through NF-κB activation. These results indicate that rNAPc2 may be a potent agent for the prevention of NSCLC progression. PMID:25672417

  5. Effect of CD86 blockage on the expressions of TGF-β1, MMP-9, TIMP-3 and PAI-1 proteins and outcome of pregnancy in murine abortion-prone model

    Institute of Scientific and Technical Information of China (English)

    FU XI ZHAO; YUAN YUAN ZHANG; RUN HUA LIU; SHUAN MING LI

    2006-01-01

    In the present study, the effect of blockage of the costimulatory signal CD86 at time of implantation on the expressions of TGF-β1, MMP-9, TIMP-3 and PAI-1 proteins at the maternal-fetal interface and the outcome of pregnancy in murine abortion-prone model was investigated, in which the CBA/J × DBA/2 matings were used as the abortion-prone model and the CBA/J × BALB/c matings used as the normal pregnant model. The study was performed in following three groups: 2 groups of the abortion-prone model, which were experimental group and control experimental group, and 1 group of normal pregnant model, and each group had 10 pregnant CBA/J mice exclusively. Female pregnant CBA/J mice in the experimental group received an intraperitoneal (i. p.) injection of 100 μg of antimouse CD86 mAb in 200 μl of PBS at day 4.5 of gestation, and the irrelevant-isotope matched rat IgG2b was administrated in the control experimental group with the same dosage and at same time. For the normal pregnant group, no treatment was given. The pregnant CBA/J mice were killed on day 13.5 of gestation. Then, the embryo resorption rate was calculated and the expressions of TGF-β1, MMP-9,TIMP3 and PAI-1 were detected by using immunohistochemical methods. It was demonstrated that the embryo resorption rate in the experimental group was significantly reduced in comparison with that in the control experimental group (χ2=7.441, P=0.006), but there was no significant difference with that in normal pregnant group (χ2=0.016, P=0.898). The expressions of TGF-β1 and PAI-1 in the experimental group were significantly increased in comparison with that in the control experimental group (P =0.010, P = 0.003, respectively), with no significant difference from that in the normal pregnant group (P = 0.500). However, the expression of MMP-9 in the experimental group was significantly reduced in comparison with that in the control experimental group (P=0.012) with no significant difference from that in the

  6. Life Testing of the Vapor Compression Distillation Urine Processing Assembly (VCD/UPA) at the Marshall Space Flight Center

    Science.gov (United States)

    Wieland, Paul O.

    1998-01-01

    Wastewater and urine generated on the International Space Station will be processed to recover pure water. The method selected is vapor compression distillation (VCD). To verify the long-term reliability and performance of the VCD Urine Processing Assembly (UPA), accelerated life testing was performed at the Marshall Space Flight Center (MSFC) from January 1993 to April 1996. Two UPAS, the VCD-5 and VCD-5A, were tested for 204 days and 665 days, respectively. The compressor gears and the distillation centrifuge drive belt were found to have an operating life of approximately 4800 hours. Precise alignment of the flex-spline of the fluids pump is essential to avoid failure of the pump after about 400 hours of operation. Also, leakage around the seals of the drive shaft of the fluids pump and purge pump must be eliminated for continued good performance. Results indicate that, with some design and procedural modifications and suitable quality control, the required performance and operational life can be met with the VCD/UPA.

  7. Life testing of the vapor compression distillation urine processor assembly (VCD/UPA) at the Marshall Space Flight Center.

    Science.gov (United States)

    Wieland, P

    1998-01-01

    Wastewater and urine generated on the International Space Station (ISS) will be processed to recover pure water using vapor compression distillation (VCD). To verify the long-term reliability and performance of the VCD Urine Processor Assembly (UPA), life testing was performed at the Marshall Space Flight Center (MSFC) from January 1993 to April 1996. Two UPAs, the VCD-5 and VCD-5A, were tested for 204 days and 665 days, respectively. The compressor gears and the distillation centrifuge drive belt were found to have operating lives of approximately 4800 h, equivalent to 3.9 years of operation on ISS for a crew of three at an average processing rate of 1.76 kg/h (3.87 lb/h). Precise alignment of the flex-splines of the fluids and purge pump motor drives is essential to avoid premature failure after about 400 h of operation. Results indicate that, with some design and procedural modifications and suitable quality control, the required performance and operational life can be met with the VCD/UPA. PMID:11540460

  8. Thrombophilic Genetic Factors PAI-1, MTHFRC677T, V Leiden 506Q, and Prothrombin 20210A in Noncirrhotic Portal Vein Thrombosis and Budd-Chiari Syndrome in a Caucasian Population

    Directory of Open Access Journals (Sweden)

    Mario D’Amico

    2013-01-01

    Full Text Available Thrombophilic genetic factors PAI-1, MTHFRC677T, V Leiden 506Q, and Prothrombin 20210A were studied as risk factors in 235 Caucasian subjects: 85 patients with abdominal thrombosis (54 with portal vein thrombosis (PVT and 31 with Budd-Chiari syndrome (BCS without liver cirrhosis or hepatocellular carcinoma and 150 blood bank donors. Seventy-five patients with PVT/BCS showed associated disease or particular clinical status (46 PVT/29 BCS: 37 myeloproliferative neoplasm (20 PVT/17 BCS, 12 abdominal surgery (10 PVT/2 BCS, 10 contraception or pregnancy (6 PVT/4 BCS, 7 abdominal acute disease (6 PVT/1 BCS, and 9 chronic disease (4 PVT/5 BCS; ten patients did not present any association (8 PVT/2 BCS. PAI-14G-4G, MTHFR677TT, and V Leiden 506Q were significantly frequent (OR 95% CI and χ2 test with P value in abdominal thrombosis; in these patients PAI-14G-4G and MTHFR677TT distributions deviated from that expected from a population in the Hardy-Weinberg equilibrium (PAI-1: χ2=13.8, P<0.001; MTHFR677: χ2=7.1, P<0.01, whereas the equilibrium was respected in healthy controls. V Leiden Q506 and Prothrombin 20210A were in the Hardy-Weinberg equilibrium both in patients with abdominal thrombosis and healthy controls. Our study shows an important role of PAI-14G-4G and MTHFR677TT in abdominal thrombosis without liver cirrhosis or hepatocellular carcinoma.

  9. Relationship between proinsulin, insulin resistance and activity of plasminogen activator inhibitor-1 in patients with coronary heart disease%冠心病患者血清胰岛素原、胰岛素抵抗与PAI-1水平的相关性

    Institute of Scientific and Technical Information of China (English)

    谢勇; 贾恩志; 杨志健; 曹克将

    2008-01-01

    目的 评价冠心病患者血清胰岛素原(PI)水平、胰岛素抵抗(IR)状态及其与纤溶酶原激活物抑制物I(PAI-1)的相关性.方法 经冠状动脉造影证实的冠心病患者66例和非冠心病对照者42例,采用单克隆抗体生物素-亲和素夹心放大酶联免疫分析法测定血清PI及真胰岛素(TI)水平,采用ELISA法定量测定血浆PAI-1含量;应用Pearson直线相关和多元逐步回归,分析PI和体内稳态模式评估(HOMA)指数水平与PAI-1的相关性.结果 冠心病患者PAI-1与HOMA指数和PI水平呈正相关(P<0.01);多元逐步同归分析显示PAI-1分别与HOMA指数、PI水平呈正相关.结论 冠心病患者血浆PAI-1水平与HOMA指数和PI水平呈独立正相关;纤溶功能异常是PI、IR影响冠心病发病的重要中间环节.

  10. Signaling through urokinase and urokinase receptor in lung cancer cells requires interactions with beta1 integrins.

    Science.gov (United States)

    Tang, Chi-Hui; Hill, Marla L; Brumwell, Alexis N; Chapman, Harold A; Wei, Ying

    2008-11-15

    The urokinase receptor (uPAR) is upregulated upon tumor cell invasion and correlates with poor lung cancer survival. Although a cis-interaction with integrins has been ascribed to uPAR, whether this interaction alone is critical to urokinase (uPA)- and uPAR-dependent signaling and tumor promotion is unclear. Here we report the functional consequences of point mutations of uPAR (H249A-D262A) that eliminate beta1 integrin interactions but maintain uPA binding, vitronectin attachment and association with alphaV integrins, caveolin and epidermal growth factor receptor. Disruption of uPAR interactions with beta1 integrins recapitulated previously reported findings with beta1-integrin-derived peptides that attenuated matrix-dependent ERK activation, MMP expression and in vitro migration by human lung adenocarcinoma cell lines. The uPAR mutant cells acquired enhanced capacity to adhere to vitronectin via uPAR-alphaVbeta5-integrin, rather than through the uPAR-alpha3beta1-integrin complex and they were unable to initiate uPA signaling to activate ERK, Akt or Stat1. In an orthotopic lung cancer model, uPAR mutant cells exhibited reduced tumor size compared with cells expressing wild-type uPAR. Taken together, the results indicate that uPAR-beta1-integrin interactions are essential to signals induced by integrin matrix ligands or uPA that support lung cancer cell invasion in vitro and progression in vivo. PMID:18940913

  11. The tissue plasminogen activator-plasminogen proteolytic cascade accelerates amyloid-beta (Abeta) degradation and inhibits Abeta-induced neurodegeneration.

    Science.gov (United States)

    Melchor, Jerry P; Pawlak, Robert; Strickland, Sidney

    2003-10-01

    Accumulation of the amyloid-beta (Abeta) peptide depends on both its generation and clearance. To better define clearance pathways, we have evaluated the role of the tissue plasminogen activator (tPA)-plasmin system in Abeta degradation in vivo. In two different mouse models of Alzheimer's disease, chronically elevated Abeta peptide in the brain correlates with the upregulation of plasminogen activator inhibitor-1 (PAI-1) and inhibition of the tPA-plasmin system. In addition, Abeta injected into the hippocampus of mice lacking either tPA or plasminogen persists, inducing PAI-1 expression and causing activation of microglial cells and neuronal damage. Conversely, Abeta injected into wild-type mice is rapidly cleared and does not cause neuronal degeneration. Thus, the tPA-plasmin proteolytic cascade aids in the clearance of Abeta, and reduced activity of this system may contribute to the progression of Alzheimer's disease.

  12. Measurement of plasminogen activator system components in plasma and tumor tissue extracts obtained from patients with breast cancer: an EORTC Receptor and Biomarker Group collaboration.

    NARCIS (Netherlands)

    Grebenchtchikov, N.I.; Maguire, T.M.; Riisbro, R.; Geurts-Moespot, A.; O'Donovan, N.; Schmitt, M.; McGreal, G.; McDermott, E.; O'Higgins, N.; Brunner, N.; Sweep, C.G.J.; Duffy, M.J.

    2005-01-01

    The plasminogen activator (PA) system comprises the 2 serine proteases, urokinase PA (uPA) and tissue PA (tPA), the 2 serpin inhibitors, PAI-1 and PAI-2 and the uPA receptor (uPAR; CD87). High levels of uPA, PAI-1, uPA-PAI-1 complex and uPAR in breast cancer tissue are associated with poor prognosis

  13. Beta-amyloidolysis and glutathione in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Lasierra-Cirujeda J

    2013-04-01

    Full Text Available J Lasierra-Cirujeda,1 P Coronel,2 MJ Aza,3 M Gimeno2 1CM Hematológico SC, Logroño, La Rioja, Spain; 2Tedec-Meiji Farma, SA, Alcalá de Henares, Madrid, Spain; 3Pharmaceutical Act, Ministry of Health, Regional Government, La Rioja, Spain Abstract: In this review, we hypothesized the importance of the interaction between the brain glutathione (GSH system, the proteolytic tissue plasminogen activator (t-PA/plasminogen/plasmin system, regulated by plasminogen activator inhibitor (PAI-1, and neuroserpin in the pathogenesis of Alzheimer's disease. The histopathological characteristic hallmark that gives personality to the diagnosis of Alzheimer's disease is the accumulation of neurofibroid tangles located intracellularly in the brain, such as the protein tau and extracellular senile plaques made primarily of amyloidal substance. These formations of complex etiology are intimately related to GSH, brain protective antioxidants, and the proteolytic system, in which t-PA plays a key role. There is scientific evidence that suggests a relationship between aging, a number of neurodegenerative disorders, and the excessive production of reactive oxygen species and accompanying decreased brain proteolysis. The plasminogen system in the brain is an essential proteolytic mechanism that effectively degrades amyloid peptides ("beta-amyloidolysis" through action of the plasmin, and this physiologic process may be considered to be a means of prevention of neurodegenerative disorders. In parallel to the decrease in GSH levels seen in aging, there is also a decrease in plasmin brain activity and a progressive decrease of t-PA activity, caused by a decrease in the expression of the t-PA together with an increase of the PAI-1 levels, which rise to an increment in the production of amyloid peptides and a lesser clearance of them. Better knowledge of the GSH mechanism and cerebral proteolysis will allow us to hypothesize about therapeutic practices. Keywords: glutathione

  14. ACE、PAI-1基因多态性对新诊断T2DM患者颈动脉内中膜厚度进展的预测作用%The predicting effects of ACE gene and PAI-I gene polymorphisms on CCA-IMT progression in newly diagnosed T2DM

    Institute of Scientific and Technical Information of China (English)

    刘玉华; 周智广; 谭少珍; 林健; 唐炜立; 刘志文; 何霞; 熊斌

    2009-01-01

    Objective The study was to investigate the relationship among angiotensin 1-converting enzyme(ACE), plasminogen activator inhibitor-1 (PAI-1)gene polymorphisms and the common carotid artery (CCA-IMT), and the predicting effects of them on CCA-IMT in newly diagnosed type 2 diabetes (T2DM). Methods The polymorphisms of ACE (I/D) gene and PAI-I (4G/5G) gene were deter-mined by polymemse chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific polymerase chain reaction (AS-PCR) method in 308 cases with T2DM. CCA-IMT was compared among the groups with different genotypes of ACE and PAI-1. The in-dependent or synergistic effects of the ACE I/D and PAI-1 40/5G polymorphisms on CCA-IMT in 308 patients with T2DM were analyzed with multivariate linear regression. Then the 156 newly diagnosed type 2 diabetics (durations< I year) without AS received the maltifactorial targeted intervention, including taking aspirin and controlling blood glucose, blood pressure, blood lipid and body weight. The differences of metabolic control, ACE (I/D) and PAId (40/5G) gene polymorphisms were analyzed. Logistic regression analysis was used to analyze the eorrelation among the CCA-IMT, ACE (I/D) and PAI-1 (4G/5G) polymorphisms. Results Patients with ACE DD genotypes had higher CCA-IMT than those with ACE-Ⅱ or ACE ID genotypes. Patients with both ACE DD and PAI-1 404G genotypes had a higher CCA-IMT than those with any other pairs of genotypes. Multivariate linear regression analysis showed that ACE DD and PAI-1 4G4G gene polymorphisms had synergistic effect on the CCA-IMT in T2DM patients. After 2 years multifactorial intervention, the frequencies of PAI-1 4G alleles and 404G genotypas were lower than those in the CCA-IMT non-inereasing group. Conclusions These findings indicate that the ACE-DD geno-type and its synergistic effects with the PAI-1 4G/4G genotype are independent risk factors for the CCA-IMT in T2DM patients. Under multi-factorial intervention for 2

  15. Urokinase plasminogen activator and plasminogen activator inhibitor type-1 in nonsmall-cell lung cancer: relation to prognosis and angiogenesis

    DEFF Research Database (Denmark)

    Offersen, Birgitte Vrou; Pfeiffer, Per; Andreasen, Peter;

    2007-01-01

    BACKGROUND: Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) have previously been suggested as prognostic markers in nonsmall-cell lung carcinomas (NSCLC). We investigate whether uPA and PAI-1 are prognostic markers in NSCLC and whether they are related...... identified as non-angiogenic we found significantly lower contents of both uPA and PAI-1 as compared to angiogenic tumours, thus we hypothesize that uPA and PAI-1 stimulate angiogenesis in NSCLC. Udgivelsesdato: 2007-Apr...

  16. Tenecteplase (TNK-tPA - ein neues Fibrinolytikum mit herausragenden Eigenschaften: Einzelbolusgabe, hohe Fibrinspezifität, PAI-1-Resistenz, körpergewichtsadaptierte Dosierung und geringe Blutungsrate für Hochrisikopatienten

    Directory of Open Access Journals (Sweden)

    Huber K

    2002-01-01

    Full Text Available Mit Tenecteplase (TNK-tPA; METALYSE® in Kombination mit dem niedermolekularen Heparin Enoxaparin (LOVENOX® wurde ein vorläufiger Endpunkt in der Weiterentwicklung neuer Fibrinolytika erreicht. Die einfache Applikationsweise (als Einzelbolus in Kombination mit den Eigenschaften einer hohen Fibrinselektivität, einer Resistenz gegenüber dem natürlichen Inhibitor PAI-1 sowie eine verhältnismäßig geringe Blutungskomplikationsrate bei Hochrisikopatienten könnten dazu beitragen Tenecteplase (+ Enoxaparin als neuen "Goldstandard" der medikamentösen Reperfusionstherapie des akuten STEMI zu etablieren. Tenecteplase würde sich potentiell als Fibrinolytikum der ersten Wahl überall dort anbieten, wo die Etablierung einer prähospitalen Fibrinolysetherapie angezeigt ist. Die Kombinationstherapie (halbe Dosis Tenecteplase mit GP IIb/IIIa-Rezeptorblockern (Volldosis gehört noch nicht zum klinischen Standardrepertoire der medikamentösen Reperfusionstherapie und sollte vorerst wissenschaftlichen Untersuchungen vorbehalten sein (Stichwort "facilitated PCI". Auch die Frage, ob eine frühe medikamentöse Reperfusion (mittels Fibrinolytikum, GP IIb/IIIa-Blocker oder Kombinationstherapie mit einer unmittelbar nachfolgenden koronaren Intervention verknüpft werden soll, muß erst in prospektiven Studien untersucht werden und erfordert neben den erhöhten Kosten auch ein hohes Maß an Kooperation und Organisation.

  17. The effect of Smad4 siRNA on transforming growth factor-β-induced-PAI-1 expression%Smad4小分子干扰RNA对转化生长因子-β诱导的纤溶酶原激活物抑制剂-1表达的影响

    Institute of Scientific and Technical Information of China (English)

    郭宝良; 仲雷; 闫朝歧; 张建国; 邹小明; 杨宝峰

    2009-01-01

    目的 探讨Smad4小分子干扰RNA(siRNA)对转化生长因子(TGF)-β诱导纤溶酶原激活物抑制剂(PAI)-1的表达的影响及作用机制.方法 将Smad4 siRNA转染入肝星状细胞24h后行TGF-β(1μg/L)刺激,24、48 h后收集细胞.利用萤光素酶报告基因法测定Smad结合转写因子的活性;Northern印迹分析技术检测PAI-1 mRNA表达的变化;Western印迹分析观察Smad4蛋白、PAI-1蛋白的变化.结果 Smad4 siRNA能抑制Smad4蛋白(3.0±0.1比16.0±0.5)表达;Smad4 siRNA抑制TGF-β1和ALK5激活的4×SBE荧光素酶报告基因活性;TGF-β时间依赖性促进PAI-1 mRNA表达,24 h达高峰;Smad4 siRNA从mRNA(1.3±0.1比6.5±0.2)和蛋白(1.50±0.15比5.52±0.36)水平抑制TGF-β激活的PAL-1的表达.结论 Smad4 siRNA能够有效地阻断TGF-β诱导的PAI-1表达.%Objective The activation of transforming growth factor-β (TGF-β) has been implicated in liver fibrotic diseases by regulating plasminogen activator inhibitor (PAI-1) expression.This study aims at elucidating whether Smad4 small interference RNA (siRNA) can be used to suppress the TGF-β-induced PAI-1 in hepatic steUate cells (HSCs).Methods Smad4 siRNA was intreduced to HSCs by transient transfection for 24 h and stimulated by TGF-β (1 μg/L) for 24 or 48 h.The activities of Smad binding element (SBE) reporter was measured by a luciferase reporter assay.The expression of Smad4 protein was detected by immunoblot analysis.The expression of PAI-1 mRNA and protein was determined by Northern blot and immunoblot analysis,repsectively.Results Smad4 siRNA abrogated the Smad4 protein expression (3.0 ± 0.1 vs 16.0 ± 0.5).Smad4 siRNA inhibited both TGF-β1-and TGF-β type Ⅰ constitutively active receptor (ALK5) -induced 4 × SBE luciferase reporter activity, respectively.Smad4 siRNA inhibited TGF-β1-induced PAI-1 mRNA (1.3 ± 0.1 vs 6.5±0.2) and protein (1.50±0.15 vs 5.52 ± 0.36) expression.Conclusion These results indicate that Smad4 siRNA could provide a

  18. Plasminogen activation independent of uPA and tPA maintains wound healing in gene-deficient mice

    DEFF Research Database (Denmark)

    Lund, Leif R; Green, Kirsty A; Stoop, Allart A;

    2006-01-01

    Simultaneous ablation of the two known activators of plasminogen (Plg), urokinase-type (uPA) and the tissue-type (tPA), results in a substantial delay in skin wound healing. However, wound closure and epidermal re-epithelialization are significantly less impaired in uPA;tPA double-deficient mice...... than in Plg-deficient mice. Skin wounds in uPA;tPA-deficient mice treated with the broad-spectrum matrix metalloproteinase (MMP) inhibitor galardin (N-[(2R)-2-(hydroxamido-carbonylmethyl)-4-methylpentanoyl]-L-tryptophan methylamide) eventually heal, whereas skin wounds in galardin-treated Plg......-deficient mice do not heal. Furthermore, plasmin is biochemically detectable in wound extracts from uPA;tPA double-deficient mice. In vivo administration of a plasma kallikrein (pKal)-selective form of the serine protease inhibitor ecotin exacerbates the healing impairment of uPA;tPA double-deficient wounds...

  19. Production of factor VIII by human liver sinusoidal endothelial cells transplanted in immunodeficient uPA mice.

    Directory of Open Access Journals (Sweden)

    Marina E Fomin

    Full Text Available Liver sinusoidal endothelial cells (LSECs form a semi-permeable barrier between parenchymal hepatocytes and the blood. LSECs participate in liver metabolism, clearance of pathological agents, immunological responses, architectural maintenance of the liver and synthesis of growth factors and cytokines. LSECs also play an important role in coagulation through the synthesis of Factor VIII (FVIII. Herein, we phenotypically define human LSECs isolated from fetal liver using flow cytometry and immunofluorescence microscopy. Isolated LSECs were cultured and shown to express endothelial markers and markers specific for the LSEC lineage. LSECs were also shown to engraft the liver when human fetal liver cells were transplanted into immunodeficient mice with liver specific expression of the urokinase-type plasminogen activator (uPA transgene (uPA-NOG mice. Engrafted cells expressed human Factor VIII at levels approaching those found in human plasma. We also demonstrate engraftment of adult LSECs, as well as hepatocytes, transplanted into uPA-NOG mice. We propose that overexpression of uPA provides beneficial conditions for LSEC engraftment due to elevated expression of the angiogenic cytokine, vascular endothelial growth factor. This work provides a detailed characterization of human midgestation LSECs, thereby providing the means for their purification and culture based on their expression of CD14 and CD32 as well as a lack of CD45 expression. The uPA-NOG mouse is shown to be a permissive host for human LSECs and adult hepatocytes, but not fetal hepatoblasts. Thus, these mice provide a useful model system to study these cell types in vivo. Demonstration of human FVIII production by transplanted LSECs encourages further pursuit of LSEC transplantation as a cellular therapy for the treatment of hemophilia A.

  20. A serpin-induced extensive proteolytic susceptibility of urokinase-type plasminogen activator implicates distortion of the proteinase substrate-binding pocket and oxyanion hole in the serpin inhibitory mechanism.

    Science.gov (United States)

    Egelund, R; Petersen, T E; Andreasen, P A

    2001-02-01

    The formation of stable complexes between serpins and their target serine proteinases indicates formation of an ester bond between the proteinase active-site serine and the serpin P1 residue [Egelund, R., Rodenburg, K.W., Andreasen, P.A., Rasmussen, M.S., Guldberg, R.E. & Petersen, T.E. (1998) Biochemistry 37, 6375-6379]. An important question concerning serpin inhibition is the contrast between the stability of the ester bond in the complex and the rapid hydrolysis of the acyl-enzyme intermediate in general serine proteinase-catalysed peptide bond hydrolysis. To answer this question, we used limited proteolysis to detect conformational differences between free urokinase-type plasminogen activator (uPA) and uPA in complex with plasminogen activator inhibitor-1 (PAI-1). Whereas the catalytic domain of free uPA, pro-uPA, uPA in complex with non-serpin inhibitors and anhydro-uPA in a non-covalent complex with PAI-1 was resistant to proteolysis, the catalytic domain of PAI-1-complexed uPA was susceptible to proteolysis. The cleavage sites for four different proteinases were localized in specific areas of the C-terminal beta-barrel of the catalytic domain of uPA, providing evidence that the serpin inhibitory mechanism involves a serpin-induced massive rearrangement of the proteinase active site, including the specificity pocket, the oxyanion hole, and main-chain binding area, rendering the proteinase unable to complete the normal hydrolysis of the acyl-enzyme intermediate. The distorted region includes the so-called activation domain, also known to change conformation on zymogen activation.

  1. Life Testing of the Vapor Compression Distillation/Urine Processing Assembly (VCD/UPA) at the Marshall Space Flight Center (1993 to 1997)

    Science.gov (United States)

    Wieland, P.; Hutchens, C.; Long, D.; Salyer, B.

    1998-01-01

    Wastewater and urine generated on the International Space Station will be processed to recover pure water using vapor compression distillation (VCD). To verify the long-term reliability and performance of the VCD Urine Processor Assembly (UPA), life testing was performed at the Marshall Space Flight Center (MSFC) from January 1993 to April 1996. Two UPA'S, the VCD-5 and VCD-5A, were tested for 204 days and 665 days, respectively. The compressor gears and the distillation centrifuge drive belt were found to have operating lives of approximately 4,800 hours, equivalent to 3.9 years of operation on ISS for a crew of three at an average processing rate of 1.76 kg/h (3.97 lb/h). Precise alignment of the flex-splines of the fluids and purge pump motor drives is essential to avoid premature failure after about 400 hours of operation. Results indicate that, with some design and procedural modifications and suitable quality control, the required performance and operational life can be met with the VCD/UPA.

  2. Simultaneous knockdown of uPA and MMP9 can reduce breast cancer progression by increasing cell-cell adhesion and modulating EMT genes

    Science.gov (United States)

    Moirangthem, Anuradha; Bondhopadhyay, Banashree; Mukherjee, Mala; Bandyopadhyay, Arghya; Mukherjee, Narendranath; Konar, Karabi; Bhattacharya, Shubham; Basu, Anupam

    2016-01-01

    In cancer progression, proteolytic enzymes like serine proteases and metalloproteinases degrade the basement membrane enabling the tumor cells to invade the adjacent tissues. Thus, invasion and metastasis are augmented by these enzymes. Simultaneous silencing of uPA and MMP9 in breast cancer cells decreased the wound healing, migratory, invasive and adhesive capacity of the cells. After simultaneous down regulation, cells were seen to be arrested in the cell cycle. There was a remarkable increase in the expression of cell to cell adhesion molecule E–cadherin, and decrease in Vimentin and Snail expression. In addition, there was a significant decrease in the expression of the stem cell marker Oct-4. In the breast tumor samples it has been observed that, tumors, expressing higher level of uPA and MMP9, express less amount of E–cadherin. It has also been observed that few tumors also show, Vimentin positive in the ductal epithelial area. Thus, our model can help for checking the aggressive tumor invasion by blocking of uPA and MMP9. Our present observations also give the concept of the presence of aggressive epithelial cells with mesenchymal nature in the tumor micro-environment, altering the expression of EMT genes. PMID:26906973

  3. Expression and functional characterization of a recombinant targeted toxin with an uPA cleavable linker in Pichia pastoris.

    Science.gov (United States)

    Zhu, Wen he; Sun, Miao nan; Wang, Yong sheng; Sun, De Jun; Zhang, Shao xuan

    2011-04-01

    A recombinant targeted toxin (Disintegrin-Conj-Mel) was developed that contained a disintegrin connected to cytotoxic melittin by a urokinase plasminogen activator (uPA)-cleavable linker. This recombinant targeted toxin was designed to target tumor cells expressing integrin αvβ3. The fusion gene was expressed under the control of the promoter AOX1 in Pichia pastoris. Electrophoresis by SDS-PAGE and Western blotting assays of culture broth from a methanol-induced expression strain, demonstrated that an approximately 13 kDa fusion protein was secreted into the culture medium. The molecular weight was that calculated from the predicted amino acid sequence. After optimizing the growth and expression conditions of the transformant strain, about 160 mg/L of the recombinant protein was achieved. The recombinant protein was purified to more than 95% purity by SP Sepharose ion exchange chromatography and Sephadex G-75 gel filtration chromatography. The hemolysis bioactivity test revealed that the fusion had no hemolytic activity or cytotoxicity against uPA non-expressing 293 cells, but exerted dose-dependent inhibition on uPA-expressing A549 cell proliferation. PMID:21144903

  4. Construction of a single lentiviral vector containing tetracycline-inducible Alb-uPA for transduction of uPA expression in murine hepatocytes.

    Directory of Open Access Journals (Sweden)

    Jiasi Bai

    Full Text Available The SCID-beige/Alb-uPA mouse model is currently the best small animal model available for viral hepatitis infection studies [1]. But the construction procedure is often costly and time-consuming due to logistic and technical difficulties. Thus, the widespread application of these chimeric mice has been hampered [2]. In order to optimize the procedure, we constructed a single lentiviral vector containing modified tetracycline-regulated system to control Alb-uPA gene expression in the cultured hepatocytes. The modified albumin promoter controlled by tetracycline (Tet-dependent transactivator rtTA2S-M2 was integrated into a lentiviral vector. The full-length uPA cDNA was inserted into another lentiviral vector containing PTight, a modified Tet-responsive promoter. Two vectors were then digested by specific enzymes and ligated by DNA ligase 4. The ligated DNA fragment was inserted into a modified pLKO.1 cloning vector and the final lentiviral vector was then successfully constructed. H2.35 cell, Lewis lung carcinoma, primary kidney, primary hepatic interstitial and CT26 cells were infected with recombinant lentivirus at selected MOI. The expression of uPA induced by DOX was detectable only in the infected H2.35 cells, which was confirmed by real-time PCR and Western blot analysis. Moreover, DOX induced uPA expression on the infected H2.35 cells in a dose-dependent manner. The constructed single lentiviral vector has many biological advantages, including that the interested gene expression under "Tet-on/off" system is controlled by DOX in a dose-depending fashion only in murine liver cells, which provides an advantage for simplifying generation of conditional transgenic animals.

  5. Ganodermanontriol (GDNT) exerts its effect on growth and invasiveness of breast cancer cells through the down-regulation of CDC20 and uPA

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Jiahua; Jedinak, Andrej [Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States); Sliva, Daniel, E-mail: dsliva@iuhealth.org [Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States); Department of Medicine, School of Medicine, Indiana University, Indianapolis, IN (United States); Indiana University Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN (United States)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Ganodermanontriol (GDNT), a Ganoderma mushroom alcohol, inhibits growth of breast cancer cells. Black-Right-Pointing-Pointer CDC20 is over-expressed in tumors but not in the tumor surrounding tissue in breast cancer patients. Black-Right-Pointing-Pointer GDNT inhibits expression of CDC20 in breast cancer cells. Black-Right-Pointing-Pointer GDNT inhibits cell adhesion, cell migration and cell invasion of breast cancer cells. Black-Right-Pointing-Pointer GDNT inhibits secretion of uPA and down-regulates expression of uPAR in breast cancer cells. -- Abstract: Ganoderma lucidum is a medicinal mushroom that has been recognized by Traditional Chinese Medicine (TCM). Although some of the direct anticancer activities are attributed to the presence of triterpenes-ganoderic and lucidenic acids-the activity of other compounds remains elusive. Here we show that ganodermanontriol (GDNT), a Ganoderma alcohol, specifically suppressed proliferation (anchorage-dependent growth) and colony formation (anchorage-independent growth) of highly invasive human breast cancer cells MDA-MB-231. GDNT suppressed expression of the cell cycle regulatory protein CDC20, which is over-expressed in precancerous and breast cancer cells compared to normal mammary epithelial cells. Moreover, we found that CDC20 is over-expressed in tumors when compared to the tissue surrounding the tumor in specimens from breast cancer patients. GDNT also inhibited invasive behavior (cell adhesion, cell migration, and cell invasion) through the suppression of secretion of urokinase-plasminogen activator (uPA) and inhibited expression of uPA receptor. In conclusion, mushroom GDNT is a natural agent that has potential as a therapy for invasive breast cancers.

  6. Does Council Tax Valuation Band (CTVB correlate with Under-Privileged Area 8 (UPA8 score and could it be a better 'Jarman Index'?

    Directory of Open Access Journals (Sweden)

    Taylor Gordon

    2001-11-01

    Full Text Available Abstract Background Widespread scepticism persists on the use of the Under-Privileged Area (UPA8 score of Jarman in distributing supplementary resources to so-attributed 'deprived' UK general practices. The search for better 'needs' markers continues. Having already shown that Council Tax Valuation Band (CTVB is a predictor of UK GP workload, we compare, here, CTVB of residence of a random sample of patients with their respective 'Jarman' scores. Methods Correlation coefficient is calculated between (i the CTVB of residence of a randomised sample of patients from an English general practice and (ii the UPA8 scores of the relevant enumeration districts in which they live. Results There is a highly significant correlation between the two measures despite modest study size of 478 patients (85% response. Conclusions The proposal that CTVB is a marker of deprivation and of clinical demand should be examined in more detail: it correlates with 'Jarman', which is already used in NHS resource allocation. But unlike 'Jarman', CTVB is simple, objective, and free of the problems of Census data. CTVB, being household-based, can be aggregated at will.

  7. Skip Regulates TGF-β1-Induced Extracellular Matrix Degrading Proteases Expression in Human PC-3 Prostate Cancer Cells

    Directory of Open Access Journals (Sweden)

    Victor Villar

    2013-01-01

    Full Text Available Purpose. To determine whether Ski-interacting protein (SKIP regulates TGF-β1-stimulated expression of urokinase-type plasminogen activator (uPA, matrix metalloproteinase-9 (MMP-9, and uPA Inhibitor (PAI-1 in the androgen-independent human prostate cancer cell model. Materials and Methods. PC-3 prostate cancer cell line was used. The role of SKIP was evaluated using synthetic small interference RNA (siRNA compounds. The expression of uPA, MMP-9, and PAI-1 was evaluated by zymography assays, RT-PCR, and promoter transactivation analysis. Results. In PC-3 cells TGF-β1 treatment stimulated uPA, PAI-1, and MMP-9 expressions. The knockdown of SKIP in PC-3 cells enhanced the basal level of uPA, and TGF-β1 treatment inhibited uPA production. Both PAI-1 and MMP-9 production levels were increased in response to TGF-β1. The ectopic expression of SKIP inhibited both TGF-β1-induced uPA and MMP-9 promoter transactivation, while PAI-1 promoter response to the factor was unaffected. Conclusions. SKIP regulates the expression of uPA, PAI-1, and MMP-9 stimulated by TGF-β1 in PC-3 cells. Thus, SKIP is implicated in the regulation of extracellular matrix degradation and can therefore be suggested as a novel therapeutic target in prostate cancer treatment.

  8. Uniform {sup 15}N- and {sup 15}N/{sup 13}C-labeling of proteins in mammalian cells and solution structure of the amino terminal fragment of u-PA

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, A.P.; Petros, A.M.; Meadows, R.P.; Mazar, A.P.; Nettesheim, D.G.; Pederson, T.M.; Fesik, S.W. [Abbott Laboratories, Abbott Park, IL (United States)

    1994-12-01

    Urokinase-type plasminogen activator (u-PA) is a 54-kDa glycoprotein that catalyzes the conversion of plasminogen to plasmin, a broad-specificity protease responsible for the degradation of fibrin clots and extracellular matrix components. The u-PA protein consists of three individual modules: a growth factor domain (GFD), a kringle, and a serine protease domain. The amino terminal fragment (ATF) includes the GFD-responsible for u-PA binding to its receptor-and the kringle domains. This protein was expressed and uniformly {sup 15}N-and {sup 15}N/{sup 13}C-labeled in mammalian cells by methods that will be described. In addition, we present the three-dimensional structure of ATF that was derived from 1299 NOE-derived distance restraints along with the {phi} angle and hydrogen bonding restraints. Although the individual domains in the structures were highly converged, the two domains are structurally independent. The overall structures of the individual domains are very similar to the structures of homologous proteins. However, important structural differences between the growth factor domain of u-PA and other homologous proteins were observed in the region that has been implicated in binding the urokinase receptor. These results may explain, in part, why other growth factors show no appreciable affinity for the urokinase receptor.

  9. Correlation of plasminogen activator inhibitor-1 and transforming growth factor-beta with diabetic nephropathy in type 2 diabetes mellitus%血浆纤溶酶原激活物抑制物1及血清转化生长因子β与2型糖尿病肾病的相关性研究

    Institute of Scientific and Technical Information of China (English)

    徐丰博; 刘惠兰; 孙懿

    2012-01-01

    目的 研究2型糖尿病肾病(DN)及单纯2型糖尿病(T2DM)患者血浆纤溶酶原激活物抑制物1(PAI-1)及血清转化生长因子β(TGF-β)水平的变化.并进一步探讨在T2DM患者中血浆PAI-1和血清TGF-β的关系.方法 T2DM患者93例,其中T2DM无蛋白尿患者(DM组)37例;微量蛋白尿患者(DN 1组)27例,尿白蛋白/肌酐(A/C)20~200 mg/g;显著蛋白尿患者(DN 2组)29例,A/C>200 mg/g.选取正常对照组32例,均为健康体检者.所有检测对象过夜禁食10~12小时后,于清晨空腹抽取肘静脉血4 ml,其中2 ml不抗凝血用于生化指标检测.酶联免疫吸附试验(ELISA)测定血浆PAI-1、TGF-β水平.结果 ①血浆PAI-1水平DN1、DN2组显著高于正常对照组,(69.28±18.61) ng/L、(69.43±17.86) ng/L vs (51.97±30.11) ng/L(P<0.05).②血清TGF-β水平DM、DN1、DN2组显著高于正常对照组,分别为(137.99±21.47) ng/L、(180.36±40.45) ng/L、(298.92±77.37) ng/L vs(100.65±24.21) ng/L(均P<0.01).③血清TGF-β和血浆PAI-1水平无明显相关性.④血浆PAI-1水平及血清TGF-β水平升高是T2DM并发肾病的危险因素.结论 T2DM合并肾病患者血浆PAI-1水平、血清TGF-β水平升高,两项指标可以预测T2DM合并肾病的危险.%Objective Plasma plasminogen activator inhibitor-1 (PAI-1) and transforming growth factor-beta (TGF-fj) level of type 2 diabetes patients were studied for exploring the pathophysiological mechanism. Methods According to the standards of diabetic diagnosis and typing put forward by ADA in 1997,a total of 93 unrelated patients with type 2 diabetes were randomly recruited in the study. These patients were further divided into type 2 diabetes with nephropathy (DN1,DN2) and without nephropathy (DN) according to their urinary albumin to creatinine ratio (A/C). At the same time,32 healthy controls were selected from population for regular physical examination in the hospital. The levels of PAI-1 and TGF-β were measured by enzyme

  10. Ku80 as a novel receptor for thymosin beta4 that mediates its intracellular activity different from G-actin sequestering.

    Science.gov (United States)

    Bednarek, Radoslaw; Boncela, Joanna; Smolarczyk, Katarzyna; Cierniewska-Cieslak, Aleksandra; Wyroba, Elzbieta; Cierniewski, Czeslaw S

    2008-01-18

    Our data demonstrate that increased intracellular expression of thymosin beta4(Tbeta4) is necessary and sufficient to induce plasminogen activator inhibitor type 1 (PAI-1) gene expression in endothelial cells. To describe the mechanism of this effect, we produced Tbeta4 mutants with impaired functional motifs and tested their intracellular location and activity. Cytoplasmic distributions of Tbeta4((AcSDKPT/4A)), Tbeta4((KLKKTET/7A)), and Tbeta4((K16A)) mutants fused with green fluorescent protein did not differ significantly from those of wild-type Tbeta4. Overexpression of Tbeta4, Tbeta4((AcSDKPT/4A)), and Tbeta4((K16A)) affected intracellular formation of actin filaments. As expected, Tbeta4((K16A)) uptake by nuclei was impaired. On the other hand, overexpression of Tbeta4((KLKKTET/7A)) resulted in developing the actin filament network typical of adhering cells, indicating that the mutant lacked the actin binding site. The mechanism by which intracellular Tbeta4 induced the PAI-1 gene did not depend upon the N-terminal tetrapeptide AcSDKP and depended only partially on its ability to bind G-actin or enter the nucleus. Both Tbeta4 and Tbeta4((AcSDKPT/4A)) induced the PAI-1 gene to the same extent, whereas mutants Tbeta4((KLKKTET/7A)) and Tbeta4((K16A)) retained about 60% of the original activity. By proteomic analysis, the Ku80 subunit of ATP-dependent DNA helicase II was found to be associated with Tbeta4. Ku80 and Tbeta4 consistently co-immunoprecipitated in a complex from endothelial cells. Co-transfection of endothelial cells with the Ku80 deletion mutants and Tbeta4 showed that the C-terminal arm domain of Ku80 is directly involved in this interaction. Furthermore, down-regulation of Ku80 by specific short interference RNA resulted in dramatic reduction in PAI-1 expression at the level of both mRNA and protein synthesis. These data suggest that Ku80 functions as a novel receptor for Tbeta4 and mediates its intracellular activity.

  11. Expression and clinical significance of Hpa and uPA in thyroid carcinoma%Hpa、uPA 在分化型甲状腺癌组织中表达的临床意义

    Institute of Scientific and Technical Information of China (English)

    李建业; 鲁凯; 姚壮凯; 耿强; 张哲雄; 孙志超

    2015-01-01

    Objective To study the relationship between heparanase( Hpa) , urokinase type plasminogen activator( uPA) expression and lymph node metastasis in thyroid carcinoma.Methods Immunohistochemieal SP method was used to analyze the expression of Hpa and uPA in 113 cases of thyroid carcinoma and 134 cases of be-nign thyroid nodules.The expression of Hpa and uPA in thyroid carcinoma and its clinical significance were ana-lyzed.Results The positive expression rate of Hpa and uPA in thyroid carcinoma and benign nodular thyroid tis-sue were 82.30%,16.42%and 89.38%, 11.19%.The positive expression rate of Hpa and uPA in carcinoma tissues with lymph metastasis and without metastasis were 93.94%,100% and 65.96%,74.47%.Expression of Hpa and uPA in thyroid carcinoma group was significantly higher than that of benign thyroid nodules group( P<0.001) .The rate of positive expression in lymph metastatic tissues were significantly higher than those in tissue without metastasis( P<0.001) .Hpa and uPA expression in thyroid carcinoma tissues was positively correlated( r=0.437, P=0.021).Conclusion The expression of Hpa and uPA is closely related with the occurrence and metastasis of thyroid carcinoma.%目的:研究乙酰肝素酶( heparanase,Hpa)、尿激酶纤溶酶原激活剂( urokinase type plasmino-gen activator,uPA)在甲状腺癌组织中的表达与淋巴结转移的关系。方法采用免疫组化SP法检测113例甲状腺癌及134例良性甲状腺结节组织中Hpa、uPA蛋白的表达情况,分析Hpa、uPA蛋白在甲状腺癌中表达及其临床意义。结果 Hpa、uPA在甲状腺癌及良性甲状腺结节组织中表达阳性率分别为82.30%、89.38%和16.42%、11.19%,甲状腺癌组织中Hpa、uPA的表达高于良性甲状腺结节(P<0.001)。在甲状腺癌有、无淋巴结转移组Hpa、uPA蛋白表达阳性率分别93.94%、100%和65.96%、74.47%,甲状腺癌组织中有周围淋巴结转移组Hpa、uPA的表达高于

  12. Immunocytochemical Phenotyping of Disseminated Tumor Cells in Bone Marrow by uPA Receptor and CK18: Investigation of Sensitivity and Specificity of an Immunogold/Alkaline Phosphatase Double Staining Protocol

    OpenAIRE

    Allgayer, Heike; Heiss, Markus Maria; Riesenberg, Rainer; Babic, Rudolf; Jauch, Karl Walter; Schildberg, Friedrich Wilhelm

    1997-01-01

    Phenotyping of cytokeratin (CK) 18-positive cells in bone marrow is gaining increasing importance for future prognostic screening of carcinoma patients. Urokinase-type plasminogen activator receptor (uPA-R) is one example of a potential aggressive marker for those cells. However, a valid and reliable double staining method is needed. Using monoclonal antibodies against uPA-R and CK18, we modified an immunogold/alkaline phosphatase double staining protocol. UPA-R/CK18-positive tumor cell contr...

  13. Redes de atenção às urgências e emergências: pré-avaliação das Unidades de Pronto Atendimento (UPAs em uma região metropolitana do Brasil Urgent and emergency care networks: a pre-evaluation of the First Aid Units (UPAs in a metropolitan region of Brazil

    Directory of Open Access Journals (Sweden)

    Greciane Soares da Silva

    2012-12-01

    Full Text Available OBJETIVOS: um estudo avaliativo, exploratório das UPAs na região metropolitana do Recife, no ano de 2011. MÉTODOS: considerou-se a descrição da intervenção, o delineamento do modelo lógico, o envolvimento dos interessados e a construção de perguntas avaliativas. Realizou-se abordagem de três fases interativas, utilizando, para sua operacionalização, a análise documental, entrevistas e Conferência de Consenso. O modelo lógico elaborado subsidiou a construção de matriz com critérios e indicadores, que foi submetida a um comitê de informantes-chave para obtenção do consenso. RESULTADOS: a matriz de critérios e indicadores resultante do consenso é composta de três níveis de análise (assistência à saúde, integração interistitucional e gestão com 41 critérios e 74 indicadores avaliativos. Com base no modelo lógico, na Conferência de Consenso, na matriz de critérios/indicadores e nas considerações sistematizadas dos inte-ressados, foram elaboradas 14 perguntas avaliativas. CONCLUSÕES: as UPAs encontram-se adequadas à rea-lização de avaliações, pois se verificou que os elementos identificados no modelo lógico são condizentes com as condições que a intervenção possui para alcançar suas metas e objetivos.OBJECTIVES: an exploratory evaluative study of the UPAs in a metropolitan region of Brazil in 2011. METHODS: the intervention was described, the logical model outlined, along with the involvement of stakeholders, and evaluation questions drawn up. The three interactive phases approach was carried out using document analysis, interviews and consensus conferencing. The logical model was based on building up a matrix of criteria and indicators that was submitted to a committee of key informants with a view to obtaining consensus. RESULTS: the matrix of criteria and indicators resulting from the consensus comprises three levels of analysis (health care, inter-institutional interaction and management with 41

  14. Periodontitis is characterized by elevated PAI-1 activity

    NARCIS (Netherlands)

    Bizzarro, S.; van der Velden, U.; ten Heggeler, J. M. A. G.; Leivadaros, E.; Hoek, F. J.; Gerdes, V. E. A.; Bakker, S. J. L.; Gans, R. O. B.; ten Cate, H.; Loos, B. G.

    2007-01-01

    Objectives: Periodontitis is a chronic infectious disease and has been associated with cardiovascular diseases (CVD). We investigated whether plasma levels of markers of a prothrombotic state were elevated in patients with periodontitis in comparison with healthy controls. Materials and methods: Unt

  15. Plasmin system of Alzheimer's disease patients: CSF analysis.

    Science.gov (United States)

    Martorana, Alessandro; Sancesario, Giulia M; Esposito, Zaira; Nuccetelli, Marzia; Sorge, Roberto; Formosa, Amanda; Dinallo, Vincenzo; Bernardi, Giorgio; Bernardini, Sergio; Sancesario, Giuseppe

    2012-07-01

    Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by the extracellular deposit of Amyloid beta (Aβ), mainly of the Amyloid beta(1-42) (Aβ(1-42)) peptide in the hippocampus and neocortex leading to progressive cognitive decline and dementia. The possible imbalance between the Aβ production/degradation process was suggested to contribute to the pathogenesis of AD. Among others, the serine protease plasmin has shown to be involved in Aβ(1-42) clearance, a hypothesis strengthened by neuropathological studies on AD brains. To explore whether there is a change in plasmin system in CSF of AD patients, we analyzed CSF samples from AD and age-matched controls, looking at plasminogen, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) protein levels and t-PA and urokinase plasminogen activator (u-PA) enzymatic activities. We also measured Aβ(1-42), total-tau and phospho-tau (181) CSF levels and sought for a possible relationship between them and plasmin system values. Our findings showed that t-PA, plasminogen and PAI-1 levels, as t-PA enzymatic activity, remained unchanged in AD with respect to controls; u-PA activity was not detected. We conclude that CSF analysis of plasminogen system does not reflect changes observed post-mortem. Unfortunately, the CSF detection of plasmin system could not be a useful biomarker for either AD diagnosis or disease progression. However, these findings do not exclude the possible involvement of the plasmin system in AD.

  16. BETA-S, Multi-Group Beta-Ray Spectra

    International Nuclear Information System (INIS)

    1 - Description of program or function: BETA-S calculates beta-decay source terms and energy spectra in multigroup format for time-dependent radionuclide inventories of actinides, fission products, and activation products. Multigroup spectra may be calculated in any arbitrary energy-group structure. The code also calculates the total beta energy release rate from the sum of the average beta-ray energies as determined from the spectral distributions. BETA-S also provides users with an option to determine principal beta-decaying radionuclides contributing to each energy group. The CCC-545/SCALE 4.3 (or SCALE4.2) code system must be installed on the computer before installing BETA-S, which requires the SCALE subroutine library and nuclide-inventory generation from the ORIGEN-S code. 2 - Methods:Well-established models for beta-energy distributions are used to explicitly represent allowed, and 1., 2. - and 3. -forbidden transition types. Forbidden non-unique transitions are assumed to have a spectral shape of allowed transitions. The multigroup energy spectra are calculated by numerically integrating the energy distribution functions using an adaptive Simpson's Rule algorithm. Nuclide inventories are obtained from a binary interface produced by the ORIGEN-S code. BETA-S calculates the spectra for all isotopes on the binary interface that have associated beta-decay transition data in the ENSDF-95 library, developed for the BETA-S code. This library was generated from ENSDF data and contains 715 materials, representing approximately 8500 individual beta transition branches. 3 - Restrictions on the complexity of the problem: The algorithms do not treat positron decay transitions or internal conversion electrons. The neglect of positron transitions in inconsequential for most applications involving aggregate fission products, since most of the decay modes are via electrons. The neglect of internal conversion electrons may impact on the accuracy of the spectrum in the low

  17. Quantitative RT-PCR assays for the determination of urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 mRNA in primary tumor tissue of breast cancer patients: comparison to antigen quantification by ELISA.

    NARCIS (Netherlands)

    Biermann, J.C.; Holzscheiter, L.; Kotzsch, M.; Luther, T.; Kiechle-Bahat, M.; Sweep, F.C.; Span, P.N.; Schmitt, M.; Magdolen, V.

    2008-01-01

    Urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor type 1 (PAI-1) play a key role in tumor-associated processes such as the degradation of extracellular matrix proteins, tissue remodeling, cell adhesion, migration, and invasion. High antigen levels of uPA an

  18. A combination of desmopressin and docetaxel inhibit cell proliferation and invasion mediated by urokinase-type plasminogen activator (uPA) in human prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Hiroshi; Klotz, Laurence H. [Division of Urology, Sunnybrook Health Sciences Center, Toronto, ON (Canada); Sugar, Linda M. [Department of Pathology, Sunnybrook Health Sciences Center, Toronto, ON (Canada); Kiss, Alexander [Department of Research Design and Biostatistics, Institute for Clinical Evaluative Sciences, Sunnybrook Health Sciences Center, Toronto, ON (Canada); Venkateswaran, Vasundara, E-mail: vasundara.venkateswaran@sunnybrook.ca [Division of Urology, Sunnybrook Health Sciences Center, Toronto, ON (Canada)

    2015-08-28

    Background: This study was designed to assess the effectiveness of a combination treatment using both desmopressin and docetaxel in prostate cancer treatment. Desmopressin is a well-known synthetic analogue of the antidiuretic hormone vasopressin. It has recently been demonstrated to inhibit tumor progression and metastasis in in vivo models. Docetaxel is widely used for the treatment of castration resistant prostate cancer (CRPC) patients. However, durable responses have been uncommon to date. In this study, we investigated the anti-tumor effect of desmopressin in combination with docetaxel in vitro and in vivo. Methods: Two prostate cancer cells (PC3, LNCaP) were treated with different concentrations of desmopressin alone, docetaxel alone, and a combination of desmopressin and docetaxel. Cell proliferation was determined by MTS assay. The anti-invasive and anti-migration potential of desmopressin and in combination with docetaxel were examined by wound healing assay, migration chamber assay, and matrigel invasion assay. Results: The combination of desmopressin and docetaxel resulted in a significant inhibition of PC3 and LNCaP cell proliferation (p < 0.01). Additionally, cell migration and invasion were also inhibited by the combination when compared to that of either treatment alone in PC3 cells (p < 0.01). The anti-tumor effect of this combination treatment was associated with down-regulation of both urokinase-type plasminogen activator (uPA) and matrix metalloproteinase (MMP-2 and MMP-9) in PC3 cells. Conclusions: We are the first to elucidate the anti-tumor and anti-metastatic potential of desmopressin in combination with docetaxel in a prostate cancer model via the uPA-MMP pathway. Our finding could potentially contribute to the therapeutic profile of desmopressin and enhance the efficacy of docetaxel based treatment for CRPC. - Highlights: • Desmopressin inhibits cell proliferation in prostate cancer cells. • The expression of cyclin A and CDK2

  19. Plasminogen Activator System and Breast Cancer: Potential Role in Therapy Decision Making and Precision Medicine.

    Science.gov (United States)

    Gouri, Adel; Dekaken, Aoulia; El Bairi, Khalid; Aissaoui, Arifa; Laabed, Nihad; Chefrour, Mohamed; Ciccolini, Joseph; Milano, Gérard; Benharkat, Sadek

    2016-01-01

    Shifting from the historical TNM paradigm to the determination of molecular and genetic subtypes of tumors has been a major improvement to better picture cancerous diseases. The sharper the picture is, the better will be the possibility to develop subsequent strategies, thus achieving higher efficacy and prolonged survival eventually. Recent studies suggest that urokinase-type plasminogen activator (uPA), uPA Receptor (uPAR), and plasmino-gen activator inhibitor-1 (PAI-1) may play a critical role in cancer invasion and metastasis. Consistent with their role in cancer dissemination, high levels of uPA, PAI-1, and uPAR in multiple cancer types correlate with dismal prognosis. In this respect, upfront determination of uPA and PAI-1 as invasion markers has further opened up the possibilities for individualized therapy of breast cancer. Indeed, uPA and PAI-1 could help to classify patients on their risk for metastatic spreading and subsequent relapse, thus helping clinicians in their decision-making process to propose, or not propose, adjuvant therapy. This review covers the implications for cancer diagnosis, prognosis, and therapy of uPA and PAI-1, and therefore how they could be major actors in the development of a precision medicine in breast cancer. PMID:27578963

  20. Gene expression of fibrinolytic factors urokinase plasminogen activator and plasminogen activator inhibitor-1 in rabbit temporo-mandibular joint cartilage with disc displacement

    Institute of Scientific and Technical Information of China (English)

    ZHAN Jing; GU Zhi-yuan; WU Li-qun; ZHANG Yin-kai; HU Ji-an

    2005-01-01

    Background The urokinase plasminogen activator system is believed to play an important role in degradation of the extracellular matrix associated with cartilage and bone destruction; however its precise roles in temporomandibular disorders have not yet been clarified. The aims of this study were to investigate the gene expression of fibrinolytic factors urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in the articular cartilage of rabbit temporomandibular joint (TMJ) with disc displacement (DD) and to probe the relationship between fibrinolytic activity and cartilage remodeling. Methods Disc displacement of right joints was performed in 36 of 78 rabbits under investigation. The animals were sacrificed at 4 days and 1, 2, 4, 8 and 12 weeks after surgery, respectively. The right joints of these animals were harvested and processed for the examination of mRNA expression of uPA and PAI-1 in articular cartilage using in situ hybridization techniques. Results The expression of uPA and PAI-1 was co-expressed weakly in the chondrocytes from transitive zone to hypertrophic zone and mineralized zone, while no hybridizing signals were shown in proliferative zone and superficial zone in control rabbits. The most striking was the up-regulation of uPA and PAI-1 mRNA in 4-day rabbits postoperatively at the onset of cartilage degeneration. The strongest hybridizing signals for uPA and PAI-1 were seen in 2-week rabbits postoperatively. After 2 weeks, the expression of uPA and PAI-1 began to decrease and reached nearly normal level at 12 weeks. Conclusions The expression of the uPA/PAI-1 system coincides with the pathological changes in condylar cartilage after DD. The uPA/PAI-1 system may be one of the essential mediators in articular cartilage remodeling.

  1. Levered and unlevered Beta

    OpenAIRE

    Fernandez, Pablo

    2003-01-01

    We prove that in a world without leverage cost the relationship between the levered beta ( L) and the unlevered beta ( u) is the No-costs-of-leverage formula: L = u + ( u - d) D (1 - T) / E. We also analyze 6 alternative valuation theories proposed in the literature to estimate the relationship between the levered beta and the unlevered beta (Harris and Pringle (1985), Modigliani and Miller (1963), Damodaran (1994), Myers (1974), Miles and Ezzell (1980), and practitioners) and prove that all ...

  2. Realized Beta GARCH

    DEFF Research Database (Denmark)

    Hansen, Peter Reinhard; Lunde, Asger; Voev, Valeri Radkov

    2014-01-01

    as the beta. We apply the model to a large set of assets and find the conditional betas to be far more variable than usually found with rolling-window regressions based exclusively on daily returns. In the empirical part of the paper, we examine the cross-sectional as well as the time variation...... of the conditional beta series during the financial crises....

  3. Betting Against Beta

    DEFF Research Database (Denmark)

    Frazzini, Andrea; Heje Pedersen, Lasse

    We present a model with leverage and margin constraints that vary across investors and time. We find evidence consistent with each of the model’s five central predictions: (1) Since constrained investors bid up high-beta assets, high beta is associated with low alpha, as we find empirically for U.......S. equities, 20 international equity markets, Treasury bonds, corporate bonds, and futures; (2) A betting-against-beta (BAB) factor, which is long leveraged low beta assets and short high-beta assets, produces significant positive risk-adjusted returns; (3) When funding constraints tighten, the return...... of the BAB factor is low; (4) Increased funding liquidity risk compresses betas toward one; (5) More constrained investors hold riskier assets....

  4. Betting against Beta

    DEFF Research Database (Denmark)

    Frazzini, Andrea; Heje Pedersen, Lasse

    2014-01-01

    We present a model with leverage and margin constraints that vary across investors and time. We find evidence consistent with each of the model's five central predictions: (1) Because constrained investors bid up high-beta assets, high beta is associated with low alpha, as we find empirically...... for US equities, 20 international equity markets, Treasury bonds, corporate bonds, and futures. (2) A betting against beta (BAB) factor, which is long leveraged low-beta assets and short high-beta assets, produces significant positive risk-adjusted returns. (3) When funding constraints tighten......, the return of the BAB factor is low. (4) Increased funding liquidity risk compresses betas toward one. (5) More constrained investors hold riskier assets....

  5. Roughing up Beta

    DEFF Research Database (Denmark)

    Bollerslev, Tim; Li, Sophia Zhengzi; Todorov, Viktor

    Motivated by the implications from a stylized equilibrium pricing framework, we investigate empirically how individual equity prices respond to continuous, or \\smooth," and jumpy, or \\rough," market price moves, and how these different market price risks, or betas, are priced in the cross......-section of expected returns. Based on a novel highfrequency dataset of almost one-thousand individual stocks over two decades, we find that the two rough betas associated with intraday discontinuous and overnight returns entail significant risk premiums, while the intraday continuous beta is not priced in the cross......-section. An investment strategy that goes long stocks with high jump betas and short stocks with low jump betas produces significant average excess returns. These higher risk premiums for the discontinuous and overnight market betas remain significant after controlling for a long list of other firm characteristics...

  6. Functional Stability of Plasminogen Activator Inhibitor-1

    Directory of Open Access Journals (Sweden)

    Songul Yasar Yildiz

    2014-01-01

    Full Text Available Plasminogen activator inhibitor-1 (PAI-1 is the main inhibitor of plasminogen activators, such as tissue-type plasminogen activator (t-PA and urokinase-type plasminogen activator (u-PA, and a major regulator of the fibrinolytic system. PAI-1 plays a pivotal role in acute thrombotic events such as deep vein thrombosis (DVT and myocardial infarction (MI. The biological effects of PAI-1 extend far beyond thrombosis including its critical role in fibrotic disorders, atherosclerosis, renal and pulmonary fibrosis, type-2 diabetes, and cancer. The conversion of PAI-1 from the active to the latent conformation appears to be unique among serpins in that it occurs spontaneously at a relatively rapid rate. Latency transition is believed to represent a regulatory mechanism, reducing the risk of thrombosis from a prolonged antifibrinolytic action of PAI-1. Thus, relying solely on plasma concentrations of PAI-1 without assessing its function may be misleading in interpreting the role of PAI-1 in many complex diseases. Environmental conditions, interaction with other proteins, mutations, and glycosylation are the main factors that have a significant impact on the stability of the PAI-1 structure. This review provides an overview on the current knowledge on PAI-1 especially importance of PAI-1 level and stability and highlights the potential use of PAI-1 inhibitors for treating cardiovascular disease.

  7. Retraction: "Down-regulation of uPA and uPAR by 3,3'-diindolylmethane contributes to the inhibition of cell growth and migration of breast cancer cells" by Ahmad et al.

    Science.gov (United States)

    2016-08-01

    The above article, published online on August 19, 2009 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor in Chief, Gary S. Stein, and Wiley Periodicals, Inc. The retraction has been agreed following an investigation from Wayne State University involving the third author and the corresponding author that found Figure 5C to be inappropriately re-used and re-labeled. REFERENCE Ahmad A, Kong D, Wang Z, Sarkar SH, Banerjee S, Sarkar FH. 2009. Down-regulation of uPA and uPAR by 3,3'-diindolylmethane contributes to the inhibition of cell growth and migration of breast cancer cells. J Cell Biochem 108:916-925; doi: 10.1002/jcb.22323.

  8. Retraction: "Down-regulation of uPA and uPAR by 3,3'-diindolylmethane contributes to the inhibition of cell growth and migration of breast cancer cells" by Ahmad et al.

    Science.gov (United States)

    2016-08-01

    The above article, published online on August 19, 2009 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor in Chief, Gary S. Stein, and Wiley Periodicals, Inc. The retraction has been agreed following an investigation from Wayne State University involving the third author and the corresponding author that found Figure 5C to be inappropriately re-used and re-labeled. REFERENCE Ahmad A, Kong D, Wang Z, Sarkar SH, Banerjee S, Sarkar FH. 2009. Down-regulation of uPA and uPAR by 3,3'-diindolylmethane contributes to the inhibition of cell growth and migration of breast cancer cells. J Cell Biochem 108:916-925; doi: 10.1002/jcb.22323. PMID:27301886

  9. Use of DSC and DMA Techniques to Help Investigate a Material Anomaly for PTFE Used in Processing a Piston Cup for the Urine Processor Assembly (UPA) on International Space Station (ISS)

    Science.gov (United States)

    Wingard, Doug

    2010-01-01

    Human urine and flush water are eventually converted into drinking water with the Urine Processor Assembly (UPA) aboard the International Space Station (ISS). This conversion is made possible through the Distillation Assembly (DA) of the UPA. One component of the DA is a molded circular piston cup made of virgin polytetrafluoroethylene (PTFE). The piston cup is assembled to a titanium component using eight fasteners and washers. Molded PTFE produced for spare piston cups in the first quarter of 2010 was different in appearance and texture, and softer than material molded for previous cups. For the suspect newer PTFE material, cup fasteners were tightened to only one-half the required torque value, yet the washers embedded almost halfway into the material. The molded PTFE used in the DA piston cup should be Type II, based on AMS 3667D and ASTM D4894 specifications. The properties of molded PTFE are considerably different between Type I and II materials. Engineers working with the DA thought that if Type I PTFE was molded by mistake instead of Type II material, that could have resulted in the anomalous material properties. Typically, the vendor molds flat sheet PTFE from the same material lot used to mold the piston cups, and tensile testing as part of quality control should verify that the PTFE is Type II material. However, for this discrepant lot of material, such tensile data was not available. Differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) were two of the testing techniques used at the NASA/Marshall Space Flight Center (MSFC) to investigate the anomaly for the PTFE material. Other techniques used on PTFE specimens were: Shore D hardness testing, tensile testing on dog bone specimens and a qualitative estimation of porosity by optical and scanning electron microscopy.

  10. Forward-Looking Betas

    DEFF Research Database (Denmark)

    Christoffersen, Peter; Jacobs, Kris; Vainberg, Gregory

    -looking. This paper introduces a radically different approach to estimating market betas. Using the tools in Bakshi and Madan (2000) and Bakshi, Kapadia and Madan (2003) we employ the information embedded in the prices of individual stock options and index options to compute our forward-looking market beta...

  11. Proteins and carbohydrates in nipple aspirate fluid predict the presence of atypia and cancer in women requiring diagnostic breast biopsy

    Directory of Open Access Journals (Sweden)

    Qin Wenyi

    2012-02-01

    Full Text Available Abstract Background Herein we present the results of two related investigations. The first study determined if concentrations in breast nipple discharge (ND of two proteins (urinary plasminogen activator, uPA and its inhibitor, PAI-1 predicted the presence of breast atypia and cancer in pre- and/or postmenopausal women requiring surgery because of a suspicious breast lesion. The second study assessed if these proteins increased the predictive ability of a carbohydrate (Thomsen Friedenreich, TF which we previously demonstrated predicted the presence of disease in postmenopausal women requiring surgery. Methods In the first study we prospectively enrolled 79 participants from whom we collected ND, measured uPA and PAI-1 and correlated expression with pathologic findings. In the second study we analyzed 35 (uPA and PAI-1 in 24, uPA in an additional 11 ND samples collected from different participants requiring breast surgery, all of whom also had TF results. Results uPA expression was higher in pre- and PAI-1 in postmenopausal women with 1 cancer (DCIS or invasive vs. either no cancer (atypia or benign pathology, p = .018 and .025, respectively, or benign pathology (p = .017 and .033, respectively; and 2 abnormal (atypia or cancer versus benign pathology (p = .018 and .052, respectively. High uPA and PAI-1 concentrations and age were independent predictors of disease in premenopausal women, with an area under the curve (AUC of 83-87% when comparing diseased vs. benign pathology. uPA, TF, and age correctly classified 35 pre- and postmenopausal women as having disease or not 84-91% of the time, whereas combining uPA+PAI-1+TF correctly classified 24 women 97-100% of the time. Conclusions uPA and PAI-1 concentrations in ND were higher in women with atypia and cancer compared to women with benign disease. Combining uPA, PAI-1 and TF in the assessment of women requiring diagnostic breast surgery maximized disease prediction. The assessment of these

  12. The effect of hedgehog signaling pathway on c - jun, uPA expression of breast cancer cells MDA- MB - 231%Hedgehog通路对乳腺癌细胞MDA—MB-231c—jun、uPA表达的影响和机制

    Institute of Scientific and Technical Information of China (English)

    隆玲; 邓华瑜; 姜容; 陈黎

    2011-01-01

    目的:研究Hedgehog信号转导通路对人乳腺癌细胞MDA—MB-231c—jun、uPA表达的影响和作用机制,认识其在侵袭转移中的意义。方法:应用Hedgehog信号通路抑制剂Cyclopamine作用人乳腺癌细胞MDA—MB-231,Transwell小室进行侵袭迁移实验;Western blotting检测P—c—itin、uPA蛋白的水平:RT—PCR检测Gli1、c—jun和uPA的mRNA水平。结果:应用Cyclopamine后,细胞的侵袭迁移能力明显下降;P—c—Jun、uPA蛋白表达减少;Gli1、c—iun和uPAmRNA水平降低。结论:Hedgehog信号通路可通过活化c—jun上调uPA的表达,促进乳腺癌细胞MDA—MB-231细胞的侵袭转移。%Objective: To explore the effect and the possible mechanisms of Hedgehog singaling pathway on expression of c - jun, uPA in MDA - MB - 231 cells. Methods: Invasion and metastasis of MDA- MB- 231 cells were evaluated with transwell chamber.The expression of P- c- jun and uPA were detected by Western blot. The mRNA levels of Gli 1, c - jun and uPA were measured by reverse transcriplion - poly - merage chain reaction ( RT - PCR ). Results : When MDA - MB - 231 cells were treated with Cyclopamine, invasion and metastasis were depressed. The expression level of P- c- Jun and uPA were decreased. The mRNA levels of Ghl, c-jun and uPA were also reduced. Conclusion: invasion, metastasis and uPA level can be induced by activeled Hedgehog singnaling nathwav with activation of c - iun.

  13. Neutrinoless double beta decay

    Indian Academy of Sciences (India)

    Kai Zuber

    2012-10-01

    The physics potential of neutrinoless double beta decay is discussed. Furthermore, experimental considerations as well as the current status of experiments are presented. Finally, an outlook towards the future, work on nuclear matrix elements and alternative processes is given.

  14. Beta-carotene

    Science.gov (United States)

    ... chemotherapy for a blood cancer called lymphoblastic leukemia. Mental performance. Some evidence suggests that taking beta-carotene ... One is water-based, and the other is oil-based. Studies show that the water-based version ...

  15. [High beta tokamak research

    International Nuclear Information System (INIS)

    Our activities on High Beta Tokamak Research during the past 20 months of the present grant period can be divided into six areas: reconstruction and modeling of high beta equilibria in HBT; measurement and analysis of MHD instabilities observed in HBT; measurements of impurity transport; diagnostic development on HBT; numerical parameterization of the second stability regime; and conceptual design and assembly of HBT-EP. Each of these is described in some detail in the sections of this progress report

  16. {beta} - amyloid imaging probes

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jae Min [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    Imaging distribution of {beta} - amyloid plaques in Alzheimer's disease is very important for early and accurate diagnosis. Early trial of the {beta} -amyloid plaques includes using radiolabeled peptides which can be only applied for peripheral {beta} - amyloid plaques due to limited penetration through the blood brain barrier (BBB). Congo red or Chrysamine G derivatives were labeled with Tc-99m for imaging {beta} - amyloid plaques of Alzheimer patient's brain without success due to problem with BBB penetration. Thioflavin T derivatives gave breakthrough for {beta} - amyloid imaging in vivo, and a benzothiazole derivative [C-11]6-OH-BTA-1 brought a great success. Many other benzothiazole, benzoxazole, benzofuran, imidazopyridine, and styrylbenzene derivatives have been labeled with F-18 and I-123 to improve the imaging quality. However, [C-11]6-OH-BTA-1 still remains as the best. However, short half-life of C-11 is a limitation of wide distribution of this agent. So, it is still required to develop an Tc-99m, F-18 or I-123 labeled agent for {beta} - amyloid imaging agent.

  17. Tumor marker utility and prognostic relevance of cathepsin B, cathepsin L, urokinase-type plasminogen activator, plasminogen activator inhibitor type-1, CEA and CA 19-9 in colorectal cancer

    International Nuclear Information System (INIS)

    Cathepsin B and L (CATB, CATL), urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 play an important role in colorectal cancer invasion. The tumor marker utility and prognostic relevance of these proteases have not been evaluated in the same experimental setting and compared with that of CEA and CA-19-9. Protease, CEA and CA 19-9 serum or plasma levels were determined in 56 patients with colorectal cancer, 25 patients with ulcerative colitis, 26 patients with colorectal adenomas and 35 tumor-free control patients. Protease, CEA, CA 19-9 levels have been determined by ELISA and electrochemiluminescence immunoassay, respectively; their sensitivity, specificity, diagnostic accuracy have been calculated and correlated with clinicopathological staging. The protease antigen levels were significantly higher in colorectal cancer compared with other groups. Sensitivity of PAI-1 (94%), CATB (82%), uPA (69%), CATL (41%) were higher than those of CEA or CA 19-9 (30% and 18%, respectively). PAI-1, CATB and uPA demonstrated a better accuracy than CEA or CA 19-9. A combination of PAI-1 with CATB or uPA exhibited the highest sensitivity value (98%). High CATB, PAI-1, CEA and CA 19-9 levels correlated with advanced Dukes stages. CATB (P = 0.0004), CATL (P = 0.02), PAI-1 (P = 0.01) and CA 19-9 (P = 0.004) had a significant prognostic impact. PAI-1 (P = 0.001), CATB (P = 0.04) and CA 19-9 (P = 0.02) proved as independent prognostic variables. At the time of clinical detection proteases are more sensitive indicators for colorectal cancer than the commonly used tumor markers. Determinations of CATB, CATL and PAI-1 have a major prognostic impact in patients with colorectal cancer

  18. Beta and Gamma Gradients

    DEFF Research Database (Denmark)

    Løvborg, Leif; Gaffney, C. F.; Clark, P. A.;

    1985-01-01

    Experimental and/or theoretical estimates are presented concerning, (i) attenuation within the sample of beta and gamma radiation from the soil, (ii) the gamma dose within the sample due to its own radioactivity, and (iii) the soil gamma dose in the proximity of boundaries between regions...... of differing radioactivity. It is confirmed that removal of the outer 2 mm of sample is adequate to remove influence from soil beta dose and estimates are made of the error introduced by non-removal. Other evaluations include variation of the soil gamma dose near the ground surface and it appears...

  19. Double beta decay experiments

    International Nuclear Information System (INIS)

    The great sensitivity of double beta decay to neutrino mass and right handed currents has motivated many new and exciting attempts to observe this elusive nuclear phenomenon directly. Experiments in operation and other coming on line in the next one or two years are expected to result in order-of-magnitude improvements in detectable half lives for both the two-neutrino and no-neutrino modes. A brief history of double beta decay experiments is presented together with a discussion of current experimental efforts, including a gas filled time projection chamber being used to study selenium-82. (author)

  20. Practicas de cuidado que poseen las adolescentes gestantes que asisten al curso de preparación para la maternidad y paternidad “un proyecto de vida” en la UPA 10 abastos de la localidad 8ª DE Kennedy durante el periodo de agosto a noviembre del 2009 / Care practices that have the pregnant teenagers who attended the course of preparation for maternity and paternity "one life project" in the UPA 10 abastos of the Kennedy locality 8th during the period of august to november 2009

    OpenAIRE

    Beltrán Granados, Laura Alejandra; Díaz Córdoba , Ingrid Carolina; Lizcano Ortega , Mabel Rocío

    2009-01-01

    Con el objetivo de identificar las Prácticas de Cuidado que poseen las Adolescentes Gestantes que asistieron al Curso de Preparación para la Maternidad y Paternidad “Un Proyecto de Vida” en la UPA 10 Abastos de la localidad 8ª de Kennedy durante el periodo de Agosto a Noviembre de 2009, se desarrolló un estudio descriptivo de corte transversal, en una muestra de 23 Adolescentes Gestantes (menores de 20 años), implementando el instrumento “Prácticas de cuidado que realizan consigo mismas y con...

  1. Evaluation of neutrino masses from $m_{\\beta\\beta}$ values

    CERN Document Server

    Khrushchov, V V

    2008-01-01

    A neutrino mass matrix is considered under conditions of the CP invariance and the negligible reactor mixing $\\theta_{13}$ angle. Absolute mass values for three neutrinos are evaluated in normal and inverted hierarchy spectra on the ground of data for oscillation mixing neutrino parameters and effective neutrino mass entering into a probability of neutrinoless two beta decay $m_{\\beta\\beta}$ values.

  2. Trichoderma .beta.-glucosidase

    Science.gov (United States)

    Dunn-Coleman, Nigel; Goedegebuur, Frits; Ward, Michael; Yao, Jian

    2006-01-03

    The present invention provides a novel .beta.-glucosidase nucleic acid sequence, designated bgl3, and the corresponding BGL3 amino acid sequence. The invention also provides expression vectors and host cells comprising a nucleic acid sequence encoding BGL3, recombinant BGL3 proteins and methods for producing the same.

  3. Applied Beta Dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Rich, B.L.

    1986-01-01

    Measurements of beta and/or nonpenetrating exposure results is complicated and past techniques and capabilities have resulted in significant inaccuracies in recorded results. Current developments have resulted in increased capabilities which make the results more accurate and should result in less total exposure to the work force. Continued development of works in progress should provide equivalent future improvements.

  4. Neutrinoless Double Beta Decay

    CERN Document Server

    Päs, Heinrich

    2015-01-01

    We review the potential to probe new physics with neutrinoless double beta decay $(A,Z) \\to (A,Z+2) + 2 e^-$. Both the standard long-range light neutrino mechanism as well as short-range mechanisms mediated by heavy particles are discussed. We also stress aspects of the connection to lepton number violation at colliders and the implications for baryogenesis.

  5. Interferon Beta-1b Injection

    Science.gov (United States)

    Interferon beta-1b injection is used to reduce episodes of symptoms in patients with relapsing-remitting (course ... and problems with vision, speech, and bladder control). Interferon beta-1b is in a class of medications ...

  6. Genetics Home Reference: beta thalassemia

    Science.gov (United States)

    ... for Disease Control and Prevention Centre for Genetics Education (Australia) Cold Spring Harbor Laboratory: Your Genes Your Health Disease InfoSearch: Beta Thalassemia Genomics Education Programme (UK) MalaCards: dominant beta-thalassemia Merck Manual ...

  7. Beta emitters and radiation protection

    DEFF Research Database (Denmark)

    Jødal, Lars

    2009-01-01

    BACKGROUND. Beta emitters, such as 90Y, are increasingly being used for cancer treatment. However, beta emitters demand other precautions than gamma emitters during preparation and administration, especially concerning shielding. AIM. To discuss practical precautions for handling beta emitters...... on the outside of the primary shielding material. If suitable shielding is used and larger numbers of handlings are divided among several persons, then handling of beta emitters can be a safe procedure....

  8. Misleading Betas: An Educational Example

    Science.gov (United States)

    Chong, James; Halcoussis, Dennis; Phillips, G. Michael

    2012-01-01

    The dual-beta model is a generalization of the CAPM model. In the dual-beta model, separate beta estimates are provided for up-market and down-market days. This paper uses the historical "Anscombe quartet" results which illustrated how very different datasets can produce the same regression coefficients to motivate a discussion of the…

  9. TGF-beta and osteoarthritis.

    NARCIS (Netherlands)

    Blaney Davidson, E.N.; Kraan, P.M. van der; Berg, W.B. van den

    2007-01-01

    OBJECTIVE: Cartilage damage is a major problem in osteoarthritis (OA). Growth factors like transforming growth factor-beta (TGF-beta) have great potential in cartilage repair. In this review, we will focus on the potential therapeutic intervention in OA with TGF-beta, application of the growth facto

  10. Beta-thalassemia.

    Science.gov (United States)

    Galanello, Renzo; Origa, Raffaella

    2010-05-21

    Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC) transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands), dilated myocardiopathy, liver fibrosis and cirrhosis). Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes), gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely, deletions in the beta

  11. Beta-thalassemia

    Directory of Open Access Journals (Sweden)

    Origa Raffaella

    2010-05-01

    Full Text Available Abstract Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands, dilated myocardiopathy, liver fibrosis and cirrhosis. Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes, gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely

  12. Coroutine Sequencing in BETA

    DEFF Research Database (Denmark)

    Kristensen, Bent Bruun; Madsen, Ole Lehrmann; Møller-Pedersen, Birger;

    In object-oriented programming, a program execution is viewed as a physical model of some real or imaginary part of the world. A language supporting object-oriented programming must therefore contain comprehensive facilities for modeling phenomena and concepts form the application domain. Many ap...... applications in the real world consist of objects carrying out sequential processes. Coroutines may be used for modeling objects that alternate between a number of sequential processes. The authors describe coroutines in BETA...

  13. Beta decay for pedestrians

    CERN Document Server

    Lipkin, Harry Jeannot

    1962-01-01

    The ""pedestrian approach"" was developed to describe some essentially simple experimental results and their theoretical implications in plain language. In this graduate-level text, Harry J. Lipkin presents simply, but without oversimplification, the aspects of beta decay that can be understood without reference to the formal theory; that is, the reactions that follow directly from conservation laws and elementary quantum mechanics.The pedestrian treatment is neither a substitute for a complete treatment nor a watered-down version.

  14. Integration of BETA with Eclipse

    DEFF Research Database (Denmark)

    Andersen, Peter; Madsen, Ole Lehrmann; Enevoldsen, Mads Brøgger

    2004-01-01

    This paper presents language interoperability issues appearing in order to implement support for the BETA language in the Java-based Eclipse integrated development environment. One of the challenges is to implement plug-ins in BETA and be able to load them in Eclipse. In order to do this, some form...... of language interoperability between Java and BETA is required. The first approach is to use the Java Native Interface and use C to bridge between Java and BETA. This results in a workable, but complicated solution. The second approach is to let the BETA compiler generate Java class files. With this approach...... it is possible to implement plug-ins in BETA and even inherit from Java classes. In the paper the two approaches are described together with part of the mapping from BETA to Java class files. http://www.sciencedirect.com/science/journal/15710661...

  15. Regulation of beta cell replication

    DEFF Research Database (Denmark)

    Lee, Ying C; Nielsen, Jens Høiriis

    2008-01-01

    Beta cell mass, at any given time, is governed by cell differentiation, neogenesis, increased or decreased cell size (cell hypertrophy or atrophy), cell death (apoptosis), and beta cell proliferation. Nutrients, hormones and growth factors coupled with their signalling intermediates have been...... suggested to play a role in beta cell mass regulation. In addition, genetic mouse model studies have indicated that cyclins and cyclin-dependent kinases that determine cell cycle progression are involved in beta cell replication, and more recently, menin in association with cyclin-dependent kinase...... inhibitors has been demonstrated to be important in beta cell growth. In this review, we consider and highlight some aspects of cell cycle regulation in relation to beta cell replication. The role of cell cycle regulation in beta cell replication is mostly from studies in rodent models, but whether...

  16. Beta cell adaptation in pregnancy

    DEFF Research Database (Denmark)

    Nielsen, Jens Høiriis

    2016-01-01

    Pregnancy is associated with a compensatory increase in beta cell mass. It is well established that somatolactogenic hormones contribute to the expansion both indirectly by their insulin antagonistic effects and directly by their mitogenic effects on the beta cells via receptors for prolactin...... and growth hormone expressed in rodent beta cells. However, the beta cell expansion in human pregnancy seems to occur by neogenesis of beta cells from putative progenitor cells rather than by proliferation of existing beta cells. Claes Hellerström has pioneered the research on beta cell growth for decades......, but the mechanisms involved are still not clarified. In this review the information obtained in previous studies is recapitulated together with some of the current attempts to resolve the controversy in the field: identification of the putative progenitor cells, identification of the factors involved...

  17. LHCb: $2\\beta_s$ measurement at LHCb

    CERN Multimedia

    Conti, G

    2009-01-01

    A measurement of $2\\beta_s$, the phase of the $B_s-\\bar{B_s}$ oscillation amplitude with respect to that of the ${\\rm b} \\rightarrow {\\rm c^{+}}{\\rm W^{-}}$ tree decay amplitude, is one of the key goals of the LHCb experiment with first data. In the Standard Model (SM), $2\\beta_s$ is predicted to be $0.0360^{+0.0020}_{-0.0016} \\rm rad$. The current constraints from the Tevatron are: $2\\beta_{s}\\in[0.32 ; 2.82]$ at 68$\\%$CL from the CDF experiment and $2\\beta_{s}=0.57^{+0.24}_{-0.30}$ from the D$\\oslash$ experiment. Although the statistical uncertainties are large, these results hint at the possible contribution of New Physics in the $B_s-\\bar{B_s}$ box diagram. After one year of data taking at LHCb at an average luminosity of $\\mathcal{L}\\sim2\\cdot10^{32}\\rm cm^{-2} \\rm s^{-1}$ (integrated luminosity $\\mathcal{L}_{\\rm int}\\sim 2 \\rm fb^{-1}$), the expected statistical uncertainty on the measurement is $\\sigma(2\\beta_s)\\simeq 0.03$. This uncertainty is similar to the $2\\beta_s$ value predicted by the SM.

  18. Distal hinge of plasminogen activator inhibitor-1 involves its latency transition and specificities toward serine proteases

    Directory of Open Access Journals (Sweden)

    Shaltiel Shmuel

    2003-07-01

    Full Text Available Abstract Background The plasminogen activator inhibitor-1 (PAI-1 spontaneously converts from an inhibitory into a latent form. Specificity of PAI-1 is mainly determined by its reactive site (Arg346-Met347, which interacts with serine residue of tissue-type plasminogen activator (tPA with concomitant formation of SDS-stable complex. Other sites may also play roles in determining the specificity of PAI-1 toward serine proteases. Results To understand more about the role of distal hinge for PAI-1 specificities towards serine proteases and for its conformational transition, wild type PAI-1 and its mutants were expressed in baculovirus system. WtPAI-1 was found to be about 12 fold more active than the fibrosarcoma PAI-1. Single site mutants within the Asp355-Arg356-Pro357 segment of PAI-1 yield guanidine activatable inhibitors (a that can still form SDS stable complexes with tPA and urokinase plasminogen activator (uPA, and (b that have inhibition rate constants towards plasminogen activators which resemble those of the fibrosarcoma inhibitor. More importantly, latency conversion rate of these mutants was found to be ~3–4 fold faster than that of wtPAI-1. We also tested if Glu351 is important for serine protease specificity. The functional stability of wtPAI-1, Glu351Ala, Glu351Arg was about 18 ± 5, 90 ± 8 and 14 ± 3 minutes, respectively, which correlated well with both their corresponding specific activities (84 ± 15 U/ug, 112 ± 18 U/ug and 68 ± 9 U/ug, respectively and amount of SDS-stable complex formed with tPA after denatured by Guanidine-HCl and dialyzed against 50 mM sodium acetate at 4°C. The second-order rate constants of inhibition for uPA, plasmin and thrombin by Glu351Ala and Glu351Arg were increased about 2–10 folds compared to wtPAI-1, but there was no change for tPA. Conclusion The Asp355-Pro357 segment and Glu351 in distal hinge are involved in maintaining the inhibitory conformation of PAI-1. Glu351 is a specificity

  19. UROKINASE-TYPE PLASMINOGEN ACTIVATOR, ITS RECEPTOR AND INHIBITOR EXPRESSION IN HEPATOCELLULAR CARCINOMA RELATION TO CANCER INVASIVENESS AND PROGNOSIS

    Institute of Scientific and Technical Information of China (English)

    Zheng Qi; Tang Zhaoyou; Wu Zhiquan; Shi Daren; Tang Huibin; Zhu Yunsong; Song Houyan

    1998-01-01

    Objective:To study the relevance of uPA, uPAR and PAI-1 to hepatocellular carcinoma (HCC). Methods:The expression at protein level of uPA, uPAR and PAI-1was determined in 48 cases of HCC and 12 cases of benign tumors of liver (as control) by immunohistochemistry.Results: When compared to cancer-adjacent liver tissue and the control, positive rate of immune staining for uPA,uPAR and PAI-1 on cell membrane were significantly higher in HCC cells (P<0.05). Positive staining of uPA and uPAR was seen in 16 of 22 and 19 of 22 cases of HCC with invasion, respectively (P<0.01 and P<0.001). In 8 of 8cases with cancer embolus, and in 6 of 6 cases with lymph node metastasis was the expression of positive uPAR.Compared with 2 of 17 cases without recurrence, uPAR was positive in 15 of 17 recurrent cases (P<0.01). In 36cases who survived, 17 was positive uPAR and 15 positive PAI-1, while in 12 cases who died 2 years after surgery, 12were positive for uPAR and 9 positive PAI-1, respectively (P<0.01 and P<0.05). In 15 positive cases for all three parameters, 11 had cancer invasion and 7 died within 2 years, while in negative cases, 2 had invasion and none died within 2 years (P<0.05). Conclusion: Expression of.uPA, uPAR and PAI-1 is increased in HCC, uPA and uPAR may contribute significantly to HCC invasion and metastasis. uPAR and PAI-1 are associated with poor prognosis of HCC.

  20. Xeroradiography in. beta. -thalassaemia

    Energy Technology Data Exchange (ETDEWEB)

    Scutellari, P.N.; Orzincolo, C.; Tamarozzi, R.

    1985-01-01

    Xeroradiographic investigations of the skull, hand, and elbow were performed on 27 patients with homozygous ..beta..-thalassaemia. The results were compared with plain radiographic examinations. Xeroradiography, because of its technical properties (i.e. edge contrast enhancement and wide latitude), was shown to demonstrate cortical thinning of long bones, swelling of the diploic space in the skull, and reticulated patterns in the elbow better than standard radiography. Moreover, the use of 'positive' mode imaging was shown to have advantages in the study of the skull and extremities.

  1. Double beta decay: present status

    OpenAIRE

    Barabash, A. S.

    2008-01-01

    The present status of double beta decay experiments (including the search for $2\\beta^{+}$, EC$\\beta^{+}$ and ECEC processes) are reviewed. The results of the most sensitive experiments are discussed. Average and recommended half-life values for two-neutrino double beta decay are presented. Conservative upper limits on effective Majorana neutrino mass and the coupling constant of the Majoron to the neutrino are established as $ < 0.75$ eV and $ < 1.9 \\cdot 10^{-4}$, respectively. Proposals fo...

  2. Simultaneous beta and gamma spectroscopy

    Science.gov (United States)

    Farsoni, Abdollah T.; Hamby, David M.

    2010-03-23

    A phoswich radiation detector for simultaneous spectroscopy of beta rays and gamma rays includes three scintillators with different decay time characteristics. Two of the three scintillators are used for beta detection and the third scintillator is used for gamma detection. A pulse induced by an interaction of radiation with the detector is digitally analyzed to classify the type of event as beta, gamma, or unknown. A pulse is classified as a beta event if the pulse originated from just the first scintillator alone or from just the first and the second scintillator. A pulse from just the third scintillator is recorded as gamma event. Other pulses are rejected as unknown events.

  3. Scintillator based beta batteries

    Science.gov (United States)

    Rensing, Noa M.; Tiernan, Timothy C.; Shirwadkar, Urmila; O'Dougherty, Patrick; Freed, Sara; Hawrami, Rastgo; Squillante, Michael R.

    2013-05-01

    Some long-term, remote applications do not have access to conventional harvestable energy in the form of solar radiation (or other ambient light), wind, environmental vibration, or wave motion. Radiation Monitoring Devices, Inc. (RMD) is carrying out research to address the most challenging applications that need power for many months or years and which have undependable or no access to environmental energy. Radioisotopes are an attractive candidate for this energy source, as they can offer a very high energy density combined with a long lifetime. Both large scale nuclear power plants and radiothermal generators are based on converting nuclear energy to heat, but do not scale well to small sizes. Furthermore, thermo-mechanical power plants depend on moving parts, and RTG's suffer from low efficiency. To address the need for compact nuclear power devices, RMD is developing a novel beta battery, in which the beta emissions from a radioisotope are converted to visible light in a scintillator and then the visible light is converted to electrical power in a photodiode. By incorporating 90Sr into the scintillator SrI2 and coupling the material to a wavelength-matched solar cell, we will create a scalable, compact power source capable of supplying milliwatts to several watts of power over a period of up to 30 years. We will present the latest results of radiation damage studies and materials processing development efforts, and discuss how these factors interact to set the operating life and energy density of the device.

  4. Beta section Beta: biogeographical patterns of variation and taxonomy.

    NARCIS (Netherlands)

    Letschert, J.P.W.

    1993-01-01

    In Chapter 1 an account is given of the historical subdivision of the genus Beta and its sections, and the relations of the sections are discussed. Emphasis is given to the taxonomic treatment of wild section Beta by various authors. The Linnaean names B. vulgaris L. and B. maritima L. are lectotypi

  5. Lysosomal degradation of receptor-bound urokinase-type plasminogen activator is enhanced by its inhibitors in human trophoblastic choriocarcinoma cells

    DEFF Research Database (Denmark)

    Jensen, Poul Henning; Christensen, Erik Ilsø; Ebbesen, P.;

    1990-01-01

    We have studied the effect of plasminogen activator inhibitors PAI-1 and PAI-2 on the binding of urokinase-type plasminogen activator (u-PA) to its receptor in the human choriocarcinoma cell line JAR. With 125I-labeled ligands in whole-cell binding assays, both uncomplexed u-PA and u-PA-inhibitor...... for the removal of u-PA after its complex formation with a specific inhibitor. The data suggest a novel mechanism by which receptor-mediated endocytosis is initiated by the binding of a secondary ligand. Full text...

  6. Urokinase-type plasminogen activator-like proteases in teleosts lack genuine receptor-binding epidermal growth factor-like domains

    DEFF Research Database (Denmark)

    Bager, René; Kristensen, Thomas K.; Jensen, Jan;

    2012-01-01

    proteases, zfuPA-a and zfuPA-b, which by several criteria are the fish orthologs of mammalian uPA. Thus, both proteases catalyze the activation of fish plasminogen efficiently and both proteases are inhibited rapidly by plasminogen activator inhibitor-1 (PAI-1). But zfuPA-a differs from mammalian u...

  7. Two distinct expression patterns of urokinase, urokinase receptor and plasminogen activator inhibitor-1 in colon cancer liver metastases

    DEFF Research Database (Denmark)

    Illemann, Martin; Bird, Nigel; Majeed, Ali;

    2009-01-01

    Metastatic growth and invasion by colon cancer cells in the liver requires the ability of the cancer cells to interact with the new tissue environment. Plasmin(ogen) is activated on cell surfaces by urokinase-type PA (uPA), and is regulated by uPAR and plasminogen activator inhibitor-1 (PAI-1......). To compare the expression patterns of uPA, uPAR and PAI-1 in colon cancer with that in their liver metastases, we analysed matched samples from 14 patients. In all 14 primary colon cancers, we found upregulation of uPAR, uPA mRNA and PAI-1 in primarily stromal cells at the invasive front. In 5 of the 14......, whereas 8 of the remaining 9 showed direct contact between the cancer cells and the liver parenchyma. We conclude that there are 2 distinct patterns of expression of uPAR, uPA and PAI-1 in colon cancer liver metastases and that these correlate closely with 2 morphological growth patterns. These findings...

  8. The pro-urokinase plasminogen-activation system in the presence of serpin-type inhibitors and the urokinase receptor

    DEFF Research Database (Denmark)

    Behrendt, Niels; List, Karin; Andreasen, Peter A;

    2003-01-01

    The reciprocal pro-enzyme activation system of plasmin, urokinase-type plasminogen activator (uPA) and their respective zymogens is a potent mechanism in the generation of extracellular proteolytic activity. Plasminogen activator inhibitor type 1 (PAI-1) acts as a negative regulator. This system ...

  9. mRNA expression of genes involved in inflammation and haemostasis in equine fibroblast-like synoviocytes following exposure to lipopolysaccharide, fibrinogen and thrombin

    DEFF Research Database (Denmark)

    Andreassen, Stine Mandrup; Berg, Lise Charlotte; Nielsen, Søren Saxmose;

    2015-01-01

    ) and protease activator receptor 1 (PAR-1) was assessed using quantitative real time reverse transcriptase PCR. Results: LPS caused a significant increase in mRNA expression of SAA, IL-6, MCP-1 and uPA, and a decrease in TF, PAI-1 and PAR-1 when compared to non-treated cells. Treatment with thrombin resulted...

  10. Beta Function and Anomalous Dimensions

    DEFF Research Database (Denmark)

    Pica, Claudio; Sannino, Francesco

    2011-01-01

    We demonstrate that it is possible to determine the coefficients of an all-order beta function linear in the anomalous dimensions using as data the two-loop coefficients together with the first one of the anomalous dimensions which are universal. The beta function allows to determine the anomalous...

  11. The best-beta CAPM

    NARCIS (Netherlands)

    L. Zou

    2006-01-01

    The issue of 'best-beta' arises as soon as potential errors in the Sharpe-Lintner-Black capital asset pricing model (CAPM) are acknowledged. By incorporating a target variable into the investor preferences, this study derives a best-beta CAPM (BCAPM) that maintains the CAPM's theoretical appeal and

  12. RAVEN Beta Release

    Energy Technology Data Exchange (ETDEWEB)

    Rabiti, Cristian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Alfonsi, Andrea [Idaho National Lab. (INL), Idaho Falls, ID (United States); Cogliati, Joshua Joseph [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mandelli, Diego [Idaho National Lab. (INL), Idaho Falls, ID (United States); Kinoshita, Robert Arthur [Idaho National Lab. (INL), Idaho Falls, ID (United States); Wang, Congjian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Maljovec, Daniel Patrick [Idaho National Lab. (INL), Idaho Falls, ID (United States); Talbot, Paul William [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-02-01

    This documents the release of the Risk Analysis Virtual Environment (RAVEN) code. A description of the RAVEN code is provided, and discussion of the release process for the M2LW-16IN0704045 milestone. The RAVEN code is a generic software framework to perform parametric and probabilistic analysis based on the response of complex system codes. RAVEN is capable of investigating the system response as well as the input space using Monte Carlo, Grid, or Latin Hyper Cube sampling schemes, but its strength is focused toward system feature discovery, such as limit surfaces, separating regions of the input space leading to system failure, using dynamic supervised learning techniques. RAVEN has now increased in maturity enough for the Beta 1.0 release.

  13. Beta systems error analysis

    Science.gov (United States)

    1984-01-01

    The atmospheric backscatter coefficient, beta, measured with an airborne CO Laser Doppler Velocimeter (LDV) system operating in a continuous wave, focussed model is discussed. The Single Particle Mode (SPM) algorithm, was developed from concept through analysis of an extensive amount of data obtained with the system on board a NASA aircraft. The SPM algorithm is intended to be employed in situations where one particle at a time appears in the sensitive volume of the LDV. In addition to giving the backscatter coefficient, the SPM algorithm also produces as intermediate results the aerosol density and the aerosol backscatter cross section distribution. A second method, which measures only the atmospheric backscatter coefficient, is called the Volume Mode (VM) and was simultaneously employed. The results of these two methods differed by slightly less than an order of magnitude. The measurement uncertainties or other errors in the results of the two methods are examined.

  14. RAVEN Beta Release

    International Nuclear Information System (INIS)

    This documents the release of the Risk Analysis Virtual Environment (RAVEN) code. A description of the RAVEN code is provided, and discussion of the release process for the M2LW-16IN0704045 milestone. The RAVEN code is a generic software framework to perform parametric and probabilistic analysis based on the response of complex system codes. RAVEN is capable of investigating the system response as well as the input space using Monte Carlo, Grid, or Latin Hyper Cube sampling schemes, but its strength is focused toward system feature discovery, such as limit surfaces, separating regions of the input space leading to system failure, using dynamic supervised learning techniques. RAVEN has now increased in maturity enough for the Beta 1.0 release.

  15. Beta Beams Implementation at CERN

    CERN Document Server

    Hansen, Christian

    2011-01-01

    Beta Beam,the concept of generating a pure and intense (anti) neutrino beam by letting accelerated radioactive ions beta decay in a storage ring, called Decay Ring (DR), is the base of one of the proposed next generation neutrino oscillation facilities, necessary for a complete study of the neutrino oscillation parameter space. Sensitivities of the unknown neutrino oscillation parameters depend on the Decay Ring's ion intensity and of it's duty factor (the filled ratio of the ring). Therefore efficient ion production, stripping, bunching, acceleration and storing are crucial sub-projects under study and development within the Beta Beam collaboration. Specifically the feasibility of these tasks as parts of a Beta Beam implementation at CERN will be discussed in this report. The positive impact of the large {\\theta}13 indications from T2K on the Beta Beam performance will also be discussed.

  16. Decreased expression of the plasminogen activator inhibitor type 1 is involved in degradation of extracellular matrix surrounding cervical cancer stem cells.

    Science.gov (United States)

    Sato, Masakazu; Kawana, Kei; Adachi, Katsuyuki; Fujimoto, Asaha; Yoshida, Mitsuyo; Nakamura, Hiroe; Nishida, Haruka; Inoue, Tomoko; Taguchi, Ayumi; Takahashi, Juri; Kojima, Satoko; Yamashita, Aki; Tomio, Kensuke; Nagamatsu, Takeshi; Wada-Hiraike, Osamu; Oda, Katsutoshi; Osuga, Yutaka; Fujii, Tomoyuki

    2016-02-01

    The plasminogen activator (PA) system consists of plasminogen activator inhibitor type 1 (PAI-1), urokinase-type plasminogen activator and its receptor (uPA and uPAR). PAI-1 inhibits the activation of uPA (which converts plasminogen to plasmin), and is involved in cancer invasion and metastasis, by remodeling the extracellular matrix (ECM) through regulating plasmin. Cancer stem cells (CSCs) are a small subset of cells within tumors, and are thought to be involved in tumor recurrence and metastasis. Considering these facts, we investigated the relationship between PAI-1 and cervical CSCs. We used ALDH1 as a marker of cervical CSCs. First, we demonstrated that culturing ALDH1-high cells and ALDH-low cells on collagen IV-coted plates increased their expression of active PAI-1 (ELISA), and these increases were suggested to be at mRNA expression levels (RT-qPCR). Secondly, we demonstrated PAI-1 was indeed involved in the ECM maintenance. With gelatin zymography assays, we found that ALDH1-high cells and ALDH-low cells expressed pro-matrix metalloproteinase-2 (pro-MMP-2) irrespective of their coatings. With gelatinase/collagenase assay kit, we confirmed that collagenase activity was increased when ALDH1-low cells were exposed to TM5275, a small molecule inhibitor of PAI-1. Putting the data together, we hypothesized that cancer cells adhered to basal membrane secrete abundant PAI-1, on the other hand, cancer cells (especially CSCs rather than non-CSCs) distant from basal membrane secrete less PAI-1, which makes the ECM surrounding CSCs more susceptible to degradation. Our study could be an explanation of conflicting reports, where some researchers found negative impacts of PAI-1 expression on clinical outcomes and others not, by considering the concept of CSCs.

  17. [Serum beta 2 microglobulin (beta 2M) following renal transplantation].

    Science.gov (United States)

    Pacheco-Silva, A; Nishida, S K; Silva, M S; Ramos, O L; Azjen, H; Pereira, A B

    1994-01-01

    Although there was an important improvement in graft and patient survival the last 10 years, graft rejection continues to be a major barrier to the success of renal transplantation. Identification of a laboratory test that could help to diagnose graft rejection would facilitate the management of renal transplanted patients. PURPOSE--To evaluate the utility of monitoring serum beta 2M in recently transplanted patients. METHODS--We daily determined serum beta 2M levels in 20 receptors of renal grafts (10 from living related and 10 from cadaveric donors) and compared them to their clinical and laboratory evolution. RESULTS--Eight patients who presented immediate good renal function following grafting and did not have rejection had a mean serum beta 2M of 3.7 mg/L on the 4th day post transplant. The sensitivity of the test for the diagnosis of acute rejection was 87.5%, but the specificity was only 46%. Patients who presented acute tubular necrosis (ATN) without rejection had a progressive decrease in their serum levels of beta 2M, while their serum creatinine changed as they were dialyzed. In contrast, patients with ATN and concomitance of acute rejection or CSA nephrotoxicity presented elevated beta 2M and creatinine serum levels. CONCLUSION--Daily monitoring of serum beta 2M does not improve the ability to diagnose acute rejection in patients with good renal function. However, serum beta 2M levels seemed to be useful in diagnosing acute rejection or CSA nephrotoxicity in patients with ATN.

  18. Characterization of urokinase receptor expression by human placental trophoblasts.

    Science.gov (United States)

    Zini, J M; Murray, S C; Graham, C H; Lala, P K; Karikó, K; Barnathan, E S; Mazar, A; Henkin, J; Cines, D B; McCrae, K R

    1992-06-01

    The processes of implantation and placentation are both dependent on the invasion and remodeling of the uterine endometrium and vasculature by trophoblasts. Because the secretion and autocrine binding of urokinase (uPA) appears to be a common mechanism used by cells to facilitate plasmin-dependent tissue invasion, we measured the production of uPA and expression of uPA receptors by trophoblasts. Prourokinase bound specifically, reversibly, and with high affinity to cultured trophoblasts, via the uPA epidermal growth factor-like domain. Trophoblasts derived from two first-trimester placentae bound more prourokinase than cells isolated from term placentae. Furthermore, in vitro differentiation of cultured cytotrophoblasts into syncytiotrophoblasts was associated with diminished expression of urokinase receptors and a parallel decrease in the cellular content of uPA receptor mRNA. Trophoblasts also secreted prourokinase and plasminogen activator inhibitors types 1 and 2 (PAI-1 and PAI-2). Although prourokinase was secreted in amounts sufficient to endogenously saturate trophoblast uPA receptors, trophoblasts secreted greater amounts of PAI-1 and PAI-2 than uPA, and no net plasminogen activator activity was detected in trophoblast conditioned medium. In contrast, plasminogen added directly to cultured trophoblasts was readily converted to plasmin. Although the invasion and remodeling of uterine tissues by trophoblasts is a complex process dependent on several proteases of varying specificity, our findings suggest that the expression and modulation of urokinase receptors on the trophoblast cell surface may play an important role in this process. PMID:1316787

  19. Intuitionistic Fuzzy Generalized Beta Closed Mappings

    OpenAIRE

    D. Jayanthi

    2014-01-01

    In this paper we introduce intuitionistic fuzzy generalized beta closed mappings and intuitionistic fuzzy generalized beta open mappings. We investigate some of their properties. We also introduce intuitionistic fuzzy M-generalized beta closed mappings as well as intuitionistic fuzzy M-generalized beta open mappings. We provide the relation between intuitionistic fuzzy M-generalized beta closed mappings and intuitionistic fuzzy generalized beta closed mappings.

  20. EXPRESSION AND ROLE OF PLASMINOGEN SYSTEM IN PROCESS OF RESTENOSIS

    Institute of Scientific and Technical Information of China (English)

    ZHAO Hai-guang; LU Xin-wu; HUANG Ying; JIANG Mi-er

    2005-01-01

    Objective To study the expression and role of plasminogen system in the process of restenosis.Methods We established a double-injury model of atherosclerotic restenosis in rabbit iliac artery mimicking human arterial restenosis. The time course of tissue plaminogen activator (tPA), urokinase plasminogen activator (uPA), urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) was investigated by immunohistochemistry. The mRNA expression of uPA and uPAR were detected after vascular procedures by in situ hybridization. Results In uninjured arteries, the weak expression of tPA and PAI-1 was detected in intimal and endothelial cells. The expression of tPA, uPA, uPAR and PAI-1 was significantly induced after double-injury, but after double-injury 14d, the expression of tPA restore to preinjury levels. The expression of uPA and uPAR in intimal was higher than that of media and maintain high levels in intimal within 42d and 56d. Conclusion Whereas t-PA is primarily involved in clot dissolution and play a limited role in the process of restenosis, in plasminogen system, uPA and uPAR play a prominent role in the process of restenosis.

  1. Effect of beta blockade and beta stimulation on stage fright.

    Science.gov (United States)

    Brantigan, C O; Brantigan, T A; Joseph, N

    1982-01-01

    Stage fright, physiologically the "fight or flight" reaction, is a disabling condition to the professional musician. Because it is mediated by the sympathetic nervous system, we have investigated the effects of beta blockade on musical performance with propranolol in a double blind fashion and the effects of beta stimulation using terbutaline. Stage fright symptoms were evaluated in two trials, which included a total of 29 subjects, by questionnaire and by the State Trai Anxiety Inventory. Quality of musical performance was evaluated by experienced music critics. Beta blockade eliminates the physical impediments to performance caused by stage fright and even eliminates the dry mouth so frequently encountered. The quality of musical performance as judged by experienced music critics is significantly improved. This effect is achieved without tranquilization. Beta stimulating drugs increase stage fright problems, and should be used in performing musicians only after consideration of the detrimental effects which they may have on musical performance. PMID:6120650

  2. Experiments on double beta decay

    Energy Technology Data Exchange (ETDEWEB)

    Busto, J. [Neuchatel Univ. (Switzerland). Inst. de Physique

    1996-11-01

    The Double Beta Decay, and especially ({beta}{beta}){sub 0{nu}} mode, is an excellent test of Standard Model as well as of neutrino physics. From experimental point of view, a very large number of different techniques are or have been used increasing the sensitivity of this experiments quite a lot (the factor of 10{sup 4} in the last 20 years). In future, in spite of several difficulties, the sensitivity would be increased further, keeping the interest of this very important process. (author) 4 figs., 5 tabs., 21 refs.

  3. Dosimetry of {beta} extensive sources; Dosimetria de fuentes {beta} extensas

    Energy Technology Data Exchange (ETDEWEB)

    Rojas C, E.L.; Lallena R, A.M. [Departamento de Fisica Moderna, Universidad de Granada, E-18071 Granada (Spain)

    2002-07-01

    In this work, we have been studied, making use of the Penelope Monte Carlo simulation code, the dosimetry of {beta} extensive sources in situations of spherical geometry including interfaces. These configurations are of interest in the treatment of the called cranealfaringyomes of some synovia leisure of knee and other problems of interest in medical physics. Therefore, its application can be extended toward problems of another areas with similar geometric situation and beta sources. (Author)

  4. Beta-gamma discriminator circuit

    International Nuclear Information System (INIS)

    The major difficulty encountered in the determination of beta-ray dose in field conditions is generally the presence of a relatively high gamma-ray component. Conventional dosimetry instruments use a shield on the detector to estimate the gamma-ray component in comparison with the beta-ray component. More accurate dosimetry information can be obtained from the measured beta spectrum itself. At Los Alamos, a detector and discriminator circuit suitable for use in a portable spectrometer have been developed. This instrument will discriminate between gammas and betas in a mixed field. The portable package includes a 256-channel MCA which can be programmed to give a variety of outputs, including a spectral display, and may be programmed to read dose directly

  5. Peginterferon Beta-1a Injection

    Science.gov (United States)

    ... symptoms such as headaches, bone or muscle aches, fever, chills, and tiredness during your treatment with peginterferon beta- ... not go away: headache muscle or joint pain fever chills weakness Some side effects can be serious. If ...

  6. The urokinase receptor (uPAR facilitates clearance of Borrelia burgdorferi.

    Directory of Open Access Journals (Sweden)

    Joppe W R Hovius

    2009-05-01

    Full Text Available The causative agent of Lyme borreliosis, the spirochete Borrelia burgdorferi, has been shown to induce expression of the urokinase receptor (uPAR; however, the role of uPAR in the immune response against Borrelia has never been investigated. uPAR not only acts as a proteinase receptor, but can also, dependently or independently of ligation to uPA, directly affect leukocyte function. We here demonstrate that uPAR is upregulated on murine and human leukocytes upon exposure to B. burgdorferi both in vitro as well as in vivo. Notably, B. burgdorferi-inoculated C57BL/6 uPAR knock-out mice harbored significantly higher Borrelia numbers compared to WT controls. This was associated with impaired phagocytotic capacity of B. burgdorferi by uPAR knock-out leukocytes in vitro. B. burgdorferi numbers in vivo, and phagocytotic capacity in vitro, were unaltered in uPA, tPA (low fibrinolytic activity and PAI-1 (high fibrinolytic activity knock-out mice compared to WT controls. Strikingly, in uPAR knock-out mice partially backcrossed to a B. burgdorferi susceptible C3H/HeN background, higher B. burgdorferi numbers were associated with more severe carditis and increased local TLR2 and IL-1beta mRNA expression. In conclusion, in B. burgdorferi infection, uPAR is required for phagocytosis and adequate eradication of the spirochete from the heart by a mechanism that is independent of binding of uPAR to uPA or its role in the fibrinolytic system.

  7. Synthesis of Beta Pyridyl Carbinol Tartrate

    Directory of Open Access Journals (Sweden)

    S. K. Shukla

    1968-04-01

    Full Text Available A process for the synthesis of Beta pyridine carboxylic acid ethy1 ester starting from quinoline has been developed. Beta-pyridine carboxylic acid ethy1 ester on reduction with lithium aluminium hydride gave Beta-pyridy1 carbinol which on treatment tartaric acid yielded Beta-pyridy1 carbinol tartrate, a vaso dilator known in trade as "Ronicoltartrate".

  8. Apollo applications of beta fiber glass

    Science.gov (United States)

    Naimer, J.

    1971-01-01

    The physical characteristics of Beta fiber glass are discussed. The application of Beta fiber glass for fireproofing the interior of spacecraft compartments is described. Tests to determine the flammability of Beta fiber glass are presented. The application of Beta fiber glass for commercial purposes is examined.

  9. Increase of plasminogen activator inhibitor-1 and decrease of transforming growth factor-b1 in children with dengue haemorrhagic fever in Indonesia.

    NARCIS (Netherlands)

    Djamiatun, K.; Faradz, S.M.; Setiati, T.E.; Netea, M.G.; Ven, A.J.A.M. van der; Dolmans, W.M.V.

    2011-01-01

    Mortality in children with severe dengue haemorrhagic fever (DHF) in Indonesia is high. The origin of the elevated plasminogen activator inhibitor-1 (PAI-1) levels in these children is unclear. We measured PAI-1, transforming growth factor-beta1 (TGF-beta1), platelet counts, plasma leakage and liver

  10. Chemotactic effect of urokinase-type plasminogen activator on mouse spermatozoa in vitro

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The aim of this study is to investigate the chemotactic effect of urokinase-type plasminogen activator (uPA)on mouse spermatozoa.Capillary assays were applied to study the chemotactic activity of ascending and descending gradients of uPA.Firstly,the chemotactic effect of an ascending gradient of uPA on mouse spermatozoa was observed by counting the number of spermatozoa that migrated into the capillary after incubation with uPA for 5,10,20,and 30 min,respectively,compared with that after incubation with F10.Twenty minutes was a suitable incubation time to obtain a plateau of sperm accumulation.Meanwhile,to confirm the specific effect of uPA on mouse sperm chemotaxis,uPA inhibitor (PAI-1)and anti-uPAR rabbit IgG were added to the test solution containing 20 U/mL uPA,respectively.To exclude the possibility that PAI-1 and anti-uPAR rabbit IgG may affect sperm accumulation nonspecifically,PAIl and anti-uPAR rabbit IgG were added to F10,respectively.It was found that the chemotactic effect of uPA was neutralized completely by PAI-1 and anti-uPAR rabbit IgG.PAI-1 and anti-uPAR rabbit IgG had no neutralizing effect on the sperm chemotactic effect.Lastly,the sperm chemotaxis response to a descending gradient of uPA was also observed.Taken together,the results suggest that uPA can induce sperm chemotaxis in vitro by binding to its receptor on the sperm membrane and may act as a chemoattractant in precontacting sperm-egg communication thereby increasing the chance encounter of spermatozoa and eggs.

  11. Vasodilatory mechanisms of beta receptor blockade.

    OpenAIRE

    Rath, Géraldine; Balligand, Jean-Luc; Dessy, Chantal

    2012-01-01

    Beta-blockers are widely prescribed for the treatment of a variety of cardiovascular pathologies. Compared to traditional beta-adrenergic antagonists, beta-blockers of the new generation exhibit ancillary properties such as vasodilation through different mechanisms. This translates into a more favorable hemodynamic profile. The relative affinities of beta-adrenoreceptor antagonists towards the three beta-adrenoreceptor isotypes matter for predicting their functional impact on vasomotor contro...

  12. Tables of double beta decay data

    Energy Technology Data Exchange (ETDEWEB)

    Tretyak, V.I. [AN Ukrainskoj SSR, Kiev (Ukraine)]|[Strasbourg-1 Univ., 67 (France). Centre de Recherches Nucleaires; Zdesenko, Y.G. [AN Ukrainskoj SSR, Kiev (Ukraine)

    1995-12-31

    A compilation of experimental data on double beta decay is presented. The tables contain the most stringent known experimental limits or positive results of 2{beta} transitions of 69 natural nuclides to ground and excited states of daughter nuclei for different channels (2{beta}{sup -}; 2{beta}{sup +}; {epsilon}{beta}{sup +}; 2{epsilon}) and modes (0{nu}; 2{nu}; 0{nu}M) of decay. (authors). 189 refs., 9 figs., 3 tabs.

  13. The GERDA experiment on 0{nu}{beta}{beta} decay

    Energy Technology Data Exchange (ETDEWEB)

    Freund, Kai [Eberhard Karls Universitaet Tuebingen (Germany); Collaboration: GERDA-Collaboration

    2012-07-01

    The Gerda (Germanium Detector Array) collaboration searches for the neutrinoless double beta decay (0{nu}{beta}{beta}) of {sup 76}Ge. The existence of this decay would give rise to the assumption that the neutrino is a Majorana particle, i.e. its own antiparticle. A measured half-life could be used to determine the effective neutrino mass and hence resolve the neutrino mass hierarchy problem. Germanium diodes, isotopically enriched in {sup 76}Ge, are used as both source and detector. Due to the low rate of this decay (T{sub 1/2}>10{sup 25} y), the experimental background must be reduced to a level of 10{sup -2}counts/(kg y keV) or better in the region around Q{sub {beta}{beta}}. To minimize background from cosmogenically produced secondary particles, a low Z shielding is employed. Thus, the naked diodes are operated in a liquid argon cryostat, which is surrounded by a water tank acting as both passive shield and active muon Cherenkov veto. Gerda started the commissioning runs in 2010 and in November 2011, the first phase of data taking with enriched detectors has begun. In this talk, the first year of the experiment is summarized.

  14. In-trap decay spectroscopy for {beta}{beta} decays

    Energy Technology Data Exchange (ETDEWEB)

    Brunner, Thomas

    2011-01-18

    The presented work describes the implementation of a new technique to measure electron-capture (EC) branching ratios (BRs) of intermediate nuclei in {beta}{beta} decays. This technique has been developed at TRIUMF in Vancouver, Canada. It facilitates one of TRIUMF's Ion Traps for Atomic and Nuclear science (TITAN), the Electron Beam Ion Trap (EBIT) that is used as a spectroscopy Penning trap. Radioactive ions, produced at the radioactive isotope facility ISAC, are injected and stored in the spectroscopy Penning trap while their decays are observed. A key feature of this technique is the use of a strong magnetic field, required for trapping. It radially confines electrons from {beta} decays along the trap axis while X-rays, following an EC, are emitted isotropically. This provides spatial separation of X-ray and {beta} detection with almost no {beta}-induced background at the X-ray detector, allowing weak EC branches to be measured. Furthermore, the combination of several traps allows one to isobarically clean the sample prior to the in-trap decay spectroscopy measurement. This technique has been developed to measure ECBRs of transition nuclei in {beta}{beta} decays. Detailed knowledge of these electron capture branches is crucial for a better understanding of the underlying nuclear physics in {beta}{beta} decays. These branches are typically of the order of 10{sup -5} and therefore difficult to measure. Conventional measurements suffer from isobaric contamination and a dominating {beta} background at theX-ray detector. Additionally, X-rays are attenuated by the material where the radioactive sample is implanted. To overcome these limitations, the technique of in-trap decay spectroscopy has been developed. In this work, the EBIT was connected to the TITAN beam line and has been commissioned. Using the developed beam diagnostics, ions were injected into the Penning trap and systematic studies on injection and storage optimization were performed. Furthermore, Ge

  15. The microbial oxidation of (-)-beta-pinene by Botrytis cinerea.

    Science.gov (United States)

    Farooq, Afgan; Choudhary, M Iqbal; Tahara, Satoshi; Rahman, Atta-ur; Başer, K Hüsnü Can; Demirci, Fatih

    2002-01-01

    (-)-beta-pinene, a flavor and fragrance monoterpene is an important constituent of essential oils of many aromatic plants. It was oxidized by a plant-pathogenic fungus, Botrytis cinerea to afford four metabolites characterized as (-)-6a-hydroxy-beta-pinene, (-)-4beta,5beta-dihydroxy-beta-pinene, (-)-2beta,3beta-dihydroxypinane, and (-)-4beta-hydroxy-beta-pinene-6-one by detailed spectroscopic studies along with other known metabolites.

  16. Mechanism of inactivation of alanine racemase by beta, beta, beta-trifluoroalanine

    International Nuclear Information System (INIS)

    The alanine racemases are a group of PLP-dependent bacterial enzymes that catalyze the racemization of alanine, providing D-alanine for cell wall synthesis. Inactivation of the alanine racemases from the Gram-negative organism Salmonella typhimurium and Gram-positive organism Bacillus stearothermophilus with beta, beta, beta-trifluoroalanine has been studied. The inactivation occurs with the same rate constant as that for formation of a broad 460-490-nm chromophore. Loss of two fluoride ions per mole of inactivated enzyme and retention of [1-14C]trifluoroalanine label accompany inhibition, suggesting a monofluoro enzyme adduct. Partial denaturation (1 M guanidine) leads to rapid return of the initial 420-nm chromophore, followed by a slower (t1/2 approximately 30 min-1 h) loss of the fluoride ion and 14CO2 release. At this point, reduction by NaB3H4 and tryptic digestion yield a single radiolabeled peptide. Purification and sequencing of the peptide reveals that lysine-38 is covalently attached to the PLP cofactor. A mechanism for enzyme inactivation by trifluoroalanine is proposed and contrasted with earlier results on monohaloalanines, in which nucleophilic attack of released aminoacrylate on the PLP aldimine leads to enzyme inactivation. For trifluoroalanine inactivation, nucleophilic attack of lysine-38 on the electrophilic beta-difluoro-alpha, beta-unsaturated imine provides an alternative mode of inhibition for these enzymes

  17. Smart Beta or Smart Alpha

    DEFF Research Database (Denmark)

    Winther, Kenneth Lillelund; Steenstrup, Søren Resen

    2016-01-01

    Smart beta has become the flavor of the decade in the investment world with its low fees, easy access to rewarded risk premiums, and appearance of providing good investment results relative to both traditional passive benchmarks and actively managed funds. Although we consider it well documented......-documented smart beta risk premiums and still motivate active managers to avoid value traps, too highly priced small caps, defensives, etc. By constructing the equity portfolios of active managers that resemble the most widely used risk premiums, we show that the returns and risk-adjusted returns measures...

  18. Effects of Nebivolol on Endothelial Gene Expression during Oxidative Stress in Human Umbilical Vein Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Ulisse Garbin

    2008-01-01

    Full Text Available The endothelium plays a key role in the development of atherogenesis and its inflammatory and proliferative status influences the progression of atherosclerosis. The aim of this study is to compare the effects of two beta blockers such as nebivolol and atenolol on gene expression in human umbilical vein endothelial cells (HUVECs following an oxidant stimulus. HUVECs were incubated with nebivolol or atenolol (10 micromol/L for 24 hours and oxidative stress was induced by the addition of oxidized (ox-LDL. Ox-LDL upregulated adhesion molecules (ICAM-1, ICAM-2, ICAM-3, E-selectin, and P-selectin; proteins linked to inflammation (IL-6 and TNFalpha, thrombotic state (tissue factor, PAI-1 and uPA, hypertension such as endothelin-1 (ET-1, and vascular remodeling such as metalloproteinases (MMP-2, MMP-9 and protease inhibitor (TIMP-1. The exposure of HUVECs to nebivolol, but not to atenolol, reduced these genes upregulated by oxidative stress both in terms of protein and RNA expression. The known antioxidant properties of the third generation beta blocker nebivolol seem to account to the observed differences seen when compared to atenolol and support the specific potential protective role of this beta blocker on the expression of a number of genes involved in the initiation and progression of atherosclerosis.

  19. Novel anthracycline-spacer-beta-glucuronide, -beta-glucoside, and -beta-galactoside prodrugs for application in selective chemotherapy

    NARCIS (Netherlands)

    Leenders, RGG; Damen, EWP; Bijsterveld, EJA; Scheeren, HW; Houba, PHJ; van der Meulen-Muileman, IH; Boven, E; Haisma, HJ

    1999-01-01

    A series of anthracycline prodrugs containing an immolative spacer was synthesized for application in selective chemotherapy. The prodrugs having the general structure anthracycline-spacer-beta-glycoside were designed to be activated by beta-glucuronidase or beta-galactosidase. Prodrugs with -chloro

  20. Constraining neutrinoless double beta decay

    International Nuclear Information System (INIS)

    A class of discrete flavor-symmetry-based models predicts constrained neutrino mass matrix schemes that lead to specific neutrino mass sum-rules (MSR). We show how these theories may constrain the absolute scale of neutrino mass, leading in most of the cases to a lower bound on the neutrinoless double beta decay effective amplitude.

  1. Beta Cell Workshop 2013 Kyoto

    DEFF Research Database (Denmark)

    Heller, R Scott; Madsen, Ole D; Nielsen, Jens Høiriis

    2013-01-01

    The very modern Kyoto International Conference Center provided the site for the 8th workshop on Beta cells on April 23-26, 2013. The preceding workshops were held in Boston, USA (1991); Kyoto, Japan (1994); Helsingør, Denmark (1997); Helsinki, Finland (2003); El Perello, Spain (2006); Peebles...

  2. Abstraction Mechanisms in the BETA Programming Language

    DEFF Research Database (Denmark)

    Kristensen, Bent Bruun; Madsen, Ole Lehrmann; Møller-Pedersen, Birger;

    1983-01-01

    The BETA programming language is developed as part of the BETA project. The purpose of this project is to develop concepts, constructs and tools in the field of programming and programming languages. BETA has been developed from 1975 on and the various stages of the language are documented in [BETA...... a]. The application area of BETA is programming of embedded as well as distributed computing systems. For this reason a major goal has been to develop constructs that may be efficiently implemented. Furthermore the BETA language is intended to have a few number of basic but general constructs....... It is then necessary that the abstraction mechanisms are powerful in order to define more specialized constructs. BETA is an object oriented language like SIMULA 67 ([SIMULA]) and SMALLTALK ([SMALLTALK]). By this is meant that a construct like the SIMULA class/subclass mechanism is fundamental in BETA. In contrast...

  3. Neutron Beta Decay Studies with Nab

    CERN Document Server

    Baeßler, S; Alonzi, L P; Balascuta, S; Barrón-Palos, L; Bowman, J D; Bychkov, M A; Byrne, J; Calarco, J R; Chupp, T; Vianciolo, T V; Crawford, C; Frlež, E; Gericke, M T; Glück, F; Greene, G L; Grzywacz, R K; Gudkov, V; Harrison, D; Hersman, F W; Ito, T; Makela, M; Martin, J; McGaughey, P L; McGovern, S; Page, S; Penttilä, S I; Počanić, D; Rykaczewski, K P; Salas-Bacci, A; Tompkins, Z; Wagner, D; Wilburn, W S; Young, A R

    2012-01-01

    Precision measurements in neutron beta decay serve to determine the coupling constants of beta decay and allow for several stringent tests of the standard model. This paper discusses the design and the expected performance of the Nab spectrometer.

  4. How Do Beta Blocker Drugs Affect Exercise?

    Science.gov (United States)

    ... Stroke More How do beta blocker drugs affect exercise? Updated:Aug 5,2015 Beta blockers are a ... about them: Do they affect your ability to exercise? The answer can vary a great deal, depending ...

  5. The beta subunit of casein kinase II

    DEFF Research Database (Denmark)

    Boldyreff, B; Piontek, K; Schmidt-Spaniol, I;

    1991-01-01

    cDNAs encoding the beta subunit of pig and mouse CKII were isolated. The porcine cDNA was expressed as a fusion protein in Escherichia coli and used for the production of anti-CKII-beta subunit specific antibodies.......cDNAs encoding the beta subunit of pig and mouse CKII were isolated. The porcine cDNA was expressed as a fusion protein in Escherichia coli and used for the production of anti-CKII-beta subunit specific antibodies....

  6. Neoclassical transport in high [beta] tokamaks

    Energy Technology Data Exchange (ETDEWEB)

    Cowley, S.C.

    1992-12-01

    Neoclassical, transport in high [beta] large aspect ratio tokamaks is calculated. The variational method introduced by Rosenbluth, et al., is used to calculate the full Onsager matrix in the banana regime. These results are part of a continuing study of the high [beta] large aspect ratio equilibria introduced in Cowley, et al. All the neoclassical coefficients are reduced from their nominal low [beta] values by a factor ([var epsilon]/q[sup 2][beta])[sup [1/2

  7. Beta measurements at Department of Energy facilities

    International Nuclear Information System (INIS)

    Pacific Northwest Laboratory performed a two-step process to characterize the current beta measurement practices at DOE facilities. PNL issued a survey questionnaire on beta measurement practices to DOE facilities and reported the results. PNL measured beta doses and spectra at seven selected DOE facilities and compared selected measurement techniques in the facility environment. This report documents the results of the radiation field measurements and the comparison of measurement techniques at the seven facilities. Data collected included beta dose and spectral measurements at seven DOE facilities that had high beta-to-gamma ratios (using a silicon surface barrier spectrometer, a plastic scintillator spectrometer, and a multielement beta dosimeter). Other dosimeters and survey meters representative of those used at DOE facilities or under development were also used for comparison. Field spectra were obtained under two distinct conditions. Silicon- and scintillation-based spectrometer systems were used under laboratory conditions where high beta-to-gamma dose ratios made the beta spectra easier to observe and analyze. In the second case, beta spectrometers were taken into actual production and maintenance areas of DOE facilities. Analyses of beta and gamma spectra showed that 234Th- /sup 234m/Pa, 231Th, 137Cs, and 90Sr/90Y were the major nuclides contributing to beta doses at the facilities visited. Beta doses from other fission products and 60Co were also measured, but the potential for exposure was less significant. 21 refs., 64 figs., 18 tabs

  8. Measurement of the beta asymmetry in neutron beta decay

    International Nuclear Information System (INIS)

    Neutron beta decay is the simplest semi-leptonic weak decay and described accurately by the standard model using the first CKM-matrix element and the ratio of vector and axial vector couplings, λ. With more than a dozen observables it is a sensitive probe for investigating the nature of weak interaction and to search for physics beyond the standard model. In the past, measuring the beta asymmetry A in polarized neutron decay has been the most precise way of determining λ and nowadays it allows - together with other observables - to derive limits on non-standard model interactions, such as scalar and tensor couplings. The neutron decay spectrometer Perkeo III was installed at the PF1B cold neutron beam site at the Institut Laue-Langevin to measure the beta asymmetry. By using a pulsed beam combined with an improved detector design a significant reduction of several systematic uncertainties has been achieved compared to the predecessor, Perkeo II. In this talk recent results of the measurements with Perkeo III will be presented. In particular, we show the energy distribution of the electrons together with the calibration tools for the detectors.

  9. Beta thalassaemia mutations in Turkish Cypriots.

    OpenAIRE

    Sozuoz, A; Berkalp, A; A. Figus; Loi, A; Pirastu, M.; Cao, A

    1988-01-01

    Using oligonucleotide hybridisation or restriction endonuclease analysis, we have characterised the molecular defect in 94 patients with thalassaemia major and four with thalassaemia intermedia of Turkish Cypriot descent. We found that four mutations, namely beta+ IVS-1 nt 110, beta zero IVS-1 nt, beta+ IVS-1 nt 6, and beta+ IVS-2 nt 745 were prevalent, accounting for 69.9%, 11.7%, 8.7%, and 5.6% respectively of the beta thalassaemia chromosomes. This information may help in the organisation ...

  10. Plan beta: Core or Cusp?

    CERN Document Server

    Richardson, Thomas; Lehnert, Matt

    2013-01-01

    The inner profile of Dark Matter (DM) halos remains one of the central problems in small-scale cosmology. At present, the problem can not be resolved in dwarf spheroidal galaxies due to a degeneracy between the DM profile and the velocity anisotropy beta of the stellar population. We discuss a method which can break the degeneracy by exploiting 3D positions and 1D line-of-sight (LOS) velocities. With the full 3D spatial information, we can determine precisely what fraction of each stars LOS motion is in the radial and tangential direction. This enables us to infer the anisotropy parameter beta directly from the data. The method is particularly effective if the galaxy is highly anisotropic. Finally, we argue that such a test could be applied to Sagittarius and potentially other dwarfs with RR Lyrae providing the necessary depth information.

  11. Beta spectrum of 185W

    International Nuclear Information System (INIS)

    The measurement of the shape of the first forbidden beta transition of 185W is interesting from the point of view of the fact that this nucleus belongs to the deformed region 150185W is carried out employing an optimized Siegbahn-Slatis beta ray spectrometer and the result is compared with the theoretical shape factor incorporating Nilsson's wavefunctions using Simms formalism. The experimental shape factor is fitted to the correction factor C(W)=k(1+aW) with α=0.0026+-0.0432. The theoretical shape factor computed following the matrix elements due to Nilsson model is in good agreement with the present experimental shape factor. The value Λ(2.358) computed in the present measurement in the light of Nilsson model matrix elements of 185W is in agreement with the predicted value (2.4) of J.J. Fujita. (author)

  12. Review of double beta experiments

    OpenAIRE

    Sarazin, X.

    2012-01-01

    C13-10-22.1 International audience This paper gives a review of the double beta experimental techniques and projects, in the search for the Majorana neutrino. The purpose of this review is to detail, for each technique, the different origins of background, how they can be identified, and how they can be reduced. Advantages and limitations of the different techniques are discussed. 1. Introduction The neutrino is one of the most puzzling elementary particle with very unique properties. I...

  13. Myokardinfarkt und Beta-Blocker

    Directory of Open Access Journals (Sweden)

    Stühlinger H-G

    2003-01-01

    Full Text Available Im Rahmen eines akuten koronaren Syndroms (akuter Herzinfarkt, Angina pectoris kommt es, aufgrund eines Ungleichgewichtes zwischen Angebot und Bedarf, zu einem akuten Mangel an Sauerstoff im Herzmuskel. Ursache ist eine reduzierte Sauerstoffzufuhr durch verengte bzw. verschlossene Gefäße. Bis zur Behebung der Ursache vergehen oft mehrere Stunden. In dieser Phase muß - durch Verminderung des Sauerstoffbedarfs im Herzmuskel - eine Verlangsamung der Nekroseentwicklung erreicht werden. Das Ausmaß der Nekrose wird reduziert, somit die für die Langzeitprognose wichtige Linksventrikelfunktion verbessert. Eine Verminderung des Sauerstoffbedarfs erreicht man durch kontrollierte Frequenzsenkung mittels intravenöser Beta-Blockade. In optimaler Weise wird diese Methode durch die Anwendung eines kardioselektiven Beta-Blockers mit kurzer Halbwertszeit durchgeführt. Beta-Blocker haben nicht nur auf die Nekroseentwicklung, sondern auch auf die Inzidenz von Rhythmusstörungen - besonders in der Akutphase - Auswirkungen. Vor allem die mit dieser therapeutischen Maßnahme verbundene Reduktion von Kammerflimmern ist von großer Bedeutung.

  14. DMPD: Immunoreceptor-like signaling by beta 2 and beta 3 integrins. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17913496 Immunoreceptor-like signaling by beta 2 and beta 3 integrins. Jakus Z, Fod...) Show Immunoreceptor-like signaling by beta 2 and beta 3 integrins. PubmedID 17913496 Title Immunoreceptor-like signaling by beta... 2 and beta 3 integrins. Authors Jakus Z, Fodor S, Abram CL

  15. Role of Urokinase-type Plasminogen Activator in the Precontact Sperm-egg Communication and Fertility of Mice in vitro

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To explore the role of urokinase-type plasminogen activator(uPA) in precontact sperm-egg communication and fertility of mice in vitro.Methods Firstly, sperm chemotaxis (SC) induced by uPA was assayed by measuring the sperm densities in capillaries with a descending gradient or no gradient of uPA respectively. Secondly, the role of uPAR that exists in sperm plasma membrane in SC was studied by examining the change of sperm density in capillary after incubating spermatozoa with anti-uPAR antibody. Thirdly, SC induced by eggs, which had been treated with uPA, PAI-1 and anti-uPAR beforehand respectively, was assayed to study the role of uPA in PSEC. Lastly, the fertilization capability of spermatozoa treated with uPA was examined by counting the number of fertilized eggs.Results 1)The density of spermatozoa that migrated down the gradient of uPA into the capillary was significantly lower than that into the capillary containing no-gradient uPA. 2) When uPAR of spermatozoa was inhibited by anti-uPAR antibody, the density of spermatozoa that migrated into the capillary with ascending gradient of uPA decreased correspondingly. 3) The density of spermatozoa attracted by eggs, which were treated with uPA beforehand, increased significantly than that of attracted by non-treated eggs. On the contrary, the sperm density decreased correspondingly when the egg was treated with PAI-1. 4) The number of fertilized eggs increased significantly after the spermatozoa used here was treated with uPA beforehand.Conclusion uPA could induce SC of mice sperm in vitro through the uPAR on its membrane, enhance the capability of egg inducing SC, and promote spermatozoa to fertilize eggs. Thus, uPA may act as an attractant in PSEC, increase the chance encounter of spermatozoa and eggs, therefore, enhance the fertility success correspondingly.This study, in some degree, provides an evidence that uPA may be used as a new medicine and diagnostic reagent for male infertility.

  16. Beta-dosimetry studies at LLNL

    International Nuclear Information System (INIS)

    This paper summarizes three beta-dosimetry studies made recently at the Lawrence Livermore National Laboratory. The first study was to determine the beta-gamma exposure rates at the Los Alamos Godiva IV Critical Assembly. The beta spectra from the assembly were evaluated using absorption curves and the beta-gamma dose-rate ratios were determined at various distances from the assembly. A comparison was made of the doses determined using two types of TLD personnel dosimeters and a film badge. The readings of an Eberline RO-7 instrument and the dose rates determined by TLDs were compared. Shielding provided by various metals, gloves, and clothing were measured. The second study was to determine the beta energy response of the Eberline RO-7 instrument based on measurements made with the PTB beta sources. This study required additional calibration points for the PTB sources which were made using extrapolation chamber measurements. The third study resulted in two techniques to determine the beta energy (E/sub max/) from the readings of this-window portable survey instruments. Both techniques are based on the readings obtained using aluminium filters. One technique is for field application, requires one filter, and provides a quick estimate of the beta energy in three energy groups: 1.5 MeV. The second technique is more complex requiring measurements with two or three filters, but gives the beta energy and the approximate shape of the beta spectrum. 9 references, 6 figures

  17. Beta

    Science.gov (United States)

    This chapter covers the use of wild beets in sugar beet improvement, including the basic botany of the species, its distribution; geographical locations of genetic diversity; morphology; cytology and karyotype; genome size; taxonomic position; agricultural status (model plant/weeds/invasive species/...

  18. Binding of transforming growth factor-beta (TGF-beta) to pregnancy zone protein (PZP). Comparison to the TGF-beta-alpha 2-macroglobulin interaction.

    Science.gov (United States)

    Philip, A; Bostedt, L; Stigbrand, T; O'Connor-McCourt, M D

    1994-04-15

    Pregnancy zone protein (PZP) is quantitatively the most important pregnancy-associated plasma protein and it has strong similarity to alpha 2-macroglobulin. Since alpha 2-macroglobulin is a binding protein for transforming growth factors-beta (TGF-beta), it was of interest to test whether the related protein, PZP, also binds to these growth-regulatory proteins. Using affinity-labelling methods, we demonstrate that PZP binds both TGF-beta 1 and TGF-beta 2 and that the binding characteristics are similar to those of the TGF-beta-alpha 2-macroglobulin interaction. TGF-beta 2 and TGF-beta 1 bind to PZP in a predominantly noncovalent manner in vitro. TGF-beta 1 and TGF-beta 2 bind to both the dimeric and tetrameric forms of PZP. Our studies also indicate that PZP binds TGF-beta 2 with higher affinity than TGF-beta 1. Finally, we demonstrate that PZP inhibits the binding of TGF-beta 1 and TGF-beta 2 to their cell surface receptors. The increased level of PZP during pregnancy may affect the action of TGF-beta by regulating the distribution, clearance and/or general availability of TGF-beta. The preferential binding of TGF-beta 2 over TGF-beta 1 by PZP implies that PZP may differentially regulate the action of TGF-beta 1 and TGF-beta 2.

  19. On gaps in Rényi $\\beta$-expansions of unity for $\\beta > 1$ an algebraic number.

    OpenAIRE

    Verger-Gaugry, Jean-Louis

    2006-01-01

    Let $\\beta> 1$ be an algebraic number. We study the strings of zeros (“gaps”) in the Rényi $\\beta$ -expansion $d_{\\beta}(1)$ of unity which controls the set $\\mathbb{Z}_{\\beta}$ of $\\beta$-integers. Using a version of Liouville's inequality which extends Mahler's and Güting's approximation theorems, the strings of zeros in $d_{\\beta}(1)$ are shown to exhibit a “gappiness” asymptotically bounded above by $log(M(\\beta ))/ log(\\beta)$, where $M(\\beta)$ is the Mahler measure of $\\beta$ . The proo...

  20. Resistance training & beta-hydroxy-beta-methylbutyrate supplementation on hormones

    Directory of Open Access Journals (Sweden)

    Hamid Arazi

    2015-10-01

    Full Text Available RESUMOIntroduction:In recent years, there was an increased interest on the effects of beta-hydroxy-beta-methylbutyrate (HMB supplementation on skeletal muscle due to its anti-catabolic effects.Objectives:To investigate the effect of HMB supplementation on body composition, muscular strength and anabolic-catabolic hormones after resistance training.Methods:Twenty amateur male athletes were randomly assigned to supplement and control groups in a double-blind crossover design and participated in four weeks resistance training. Before and after the test period fasting blood samples were obtained to determine anabolic (the growth hormone and testosterone and catabolic (cortisol hormones, and fat mass, lean body mass (LBM and muscular strength were measured. Dependent and independent t-tests were used to analyze data.Results:After the training period, there were no significant differen-ces between the groups with respect to fat mass, LBM and anabolic-catabolic hormones. HMB supplementation resulted in a significantly greater strength gain (p≤0.05.Conclusion:Greater increase in strength for HMB group was not accompanied by body composition and basal circulating anabolic-catabolic hormonal changes. It seems that HMB supplementation may have beneficial effects on neurological adaptations of strength gain.

  1. Activity and expression of urokinase-type plasminogen activator and matrix metalloproteinases in human colorectal cancer

    International Nuclear Information System (INIS)

    Matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase-type plasminogen activator (uPA) are involved in colorectal cancer invasion and metastasis. There is still debate whether the activity of MMP-2 and MMP-9 differs between tumors located in the colon and rectum. We designed this study to determine any differences in the expression of MMP-2, MMP-9 and uPA system between colon and rectal cancer tissues. Cancer tissue samples were obtained from colon carcinoma (n = 12) and rectal carcinomas (n = 10). MMP-2 and MMP-9 levels were examined using gelatin zymography and Western blotting; their endogenous inhibitors, tissue inhibitor of metalloproteinase-2 (TIMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1), were assessed by Western blotting. uPA, uPAR and PAI-1 were examined using enzyme-linked immunosorbent assay (ELISA). The activity of uPA was assessed by casein-plasminogen zymography. In both colon and rectal tumors, MMP-2, MMP-9 and TIMP-1 protein levels were higher than in corresponding paired normal mucosa, while TIMP-2 level in tumors was significantly lower than in normal mucosa. The enzyme activities or protein levels of MMP-2, MMP-9 and their endogenous inhibitors did not reach a statistically significant difference between colon and rectal cancer compared with their normal mucosa. In rectal tumors, there was an increased activity of uPA compared with the activity in colon tumors (P = 0.0266), however urokinase-type plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) showed no significant difference between colon and rectal cancer tissues. These findings suggest that uPA may be expressed differentially in colon and rectal cancers, however, the activities or protein levels of MMP-2, MMP-9, TIMP-1, TIMP-2, PAI-1 and uPAR are not affected by tumor location in the colon or the rectum

  2. GSK3beta is involved in JNK2-mediated beta-catenin inhibition.

    Directory of Open Access Journals (Sweden)

    Dong Hu

    Full Text Available BACKGROUND: We have recently reported that mitogen-activated protein kinase (MAPK JNK1 downregulates beta-catenin signaling and plays a critical role in regulating intestinal homeostasis and in suppressing tumor formation. This study was designed to determine whether JNK2, another MAPK, has similar and/or different functions in the regulation of beta-catenin signaling. METHODOLOGY AND PRINCIPAL FINDINGS: We used an in vitro system with manipulation of JNK2 and beta-catenin expression and found that activated JNK2 increased GSK3beta activity and inhibited beta-catenin expression and transcriptional activity. However, JNK2-mediated downregulation of beta-catenin was blocked by the proteasome inhibitor MG132 and GSK3beta inhibitor lithium chloride. Moreover, targeted mutations at GSK3beta phosphorylation sites (Ser33 and Ser37 of beta-catenin abrogated JNK2-mediated suppression of beta-catenin. In vivo studies further revealed that JNK2 deficiency led to upregulation of beta-catenin and increase of GSK3-beta phosphorylation in JNK2-/- mouse intestinal epithelial cells. Additionally, physical interaction and co-localization among JNK2, beta-catenin and GSK3beta were observed by immunoprecipitation, mammalian two-hybridization assay and confocal microscopy, respectively. CONCLUSION AND SIGNIFICANCE: In general, our data suggested that JNK2, like JNK1, interacts with and suppresses beta-catenin signaling in vitro and in vivo, in which GSK3beta plays a key role, although previous studies have shown distinct functions of JNK1 and JNK2. Our study also provides a novel insight into the crosstalk between Wnt/beta-catenin and MAPK JNKs signaling.

  3. Hyper-beta-alaninemia associated with beta-aminoaciduria and gamma-aminobutyricaciduaia, somnolence and seizures.

    Science.gov (United States)

    Scriver, C R; Pueschel, S; Davies, E

    1966-03-24

    Hyper-beta-alaninemia was found in a somnolent, convulsing infant. Hyper-beta-aminoaciduria (beta-ala, betaAIB and taurine) was also observed, varying directly with plasma beta-alanine concentration. The beta-aminoaciduria is explained by the interaction between beta-alanine and a specific cellular-transport system with preference for beta-amino compounds. Gamma-aminobutyricaciduria was also observed, its excretion being independent of beta-alanine levels. Dietary modifications, pyridoxine, pantothenic acid and antibiotic therapy were not beneficial. Post-mortem tissues had elevated levels of beta-alanine and carnosine; GABA levels in brain were probably elevated for the age of the patient. A proposed block in beta-alanine-alpha-ketoglutarate transaminase would expand the free beta-alanine pool, thus increasing tissue carnosine. beta-Alanine is a central-nervous-system depressant. Associated inhibition of GABA transaminase and displacement of GABA from central-nervous-system binding sites would produce GABAuria and convulsions. PMID:17926374

  4. Beta-2-mikroglobulin ved medicinske sygdomme

    DEFF Research Database (Denmark)

    Hansen, P B; Olsen, Niels Vidiendal

    1989-01-01

    Beta-2-microglobulin (beta 2M) is a low-molecular protein which is filtered freely over the glomeruli. Under normal circumstances, more than 99.9% is resorbed in the proximal tubuli of the kidneys and is metabolized there. In renal disease with damage to this segment of the nephron, eg acute tubulo......-interstitial nephropathy, increased quantities of beta 2M are excreted in the urine. If the rate of glomerular filtration is reduced, serum-beta 2M is increased and this is also the case in persons with increased cell division despite normal renal function. Serum-beta 2M is, therefore, raised in numerous malignant...... diseases and reflects the size of the tumour mass. During cytostatic treatment of myelomatosis and chronic lymphatic leukaemia, the serum-beta 2M levels decrease on remission and increase on relapse. In acute leukaemia and malignant lymphoma with infiltration of the CNS, similar conditions prevail for CSF...

  5. Hypersomnolence with beta-adrenergic blockers.

    Science.gov (United States)

    Thachil, J; Zeller, J R; Kochar, M S

    1987-11-01

    An elderly, mildly demented, hypertensive male patient developed hypersomnolence on administration of propranolol for treatment of hypertension; no other cause for hypersomnolence was detected. Upon replacement of propranolol with atenolol, he felt better but continued to be quite somnolent. When atenolol was discontinued, he reported to have lack of sleep. On readministration of subtherapeutic doses of the same beta-adrenergic blocking agents, he once again experienced excessive sleepiness. By discontinuing beta-blocking agents and introducing captopril, he felt much better, became pleasant and talkative, and blood pressure was well controlled. Beta antagonists are important drugs in the management of many cardiovascular problems. Propranolol, a lipophilic beta-blocking agent, and atenolol, a hydrophilic beta-blocking agent, are two of the major agents currently used clinically in the United States. Numerous neuropsychiatric side-effects of the beta-adrenergic blocking drugs have been reported, but hypersomnolence is not readily recognized as one of them. PMID:3665616

  6. Beta blockers: A new role in chemotherapy

    OpenAIRE

    Nagaraja, Archana S; Sadaoui, Nouara C.; Lutgendorf, Susan K.; Ramondetta, Lois M.; Sood, Anil K

    2013-01-01

    Beta-blockers are a class of drugs widely used to treat cardiac, respiratory and other ailments. They act by blocking beta-adrenergic receptor–mediated signalling. Studies in various cancers have shown that patients taking a beta-blocker have higher survival and lower recurrence and metastasis rates. This is supported by several preclinical and in vitro studies showing that adrenergic activation modulates apoptosis, promotes angiogenesis and other cancer hallmarks, and these effects can be ab...

  7. The pancreatic beta cell surface proteome

    OpenAIRE

    Stützer, I.; Esterházy, D.; Stoffel, M.

    2012-01-01

    The pancreatic beta cell is responsible for maintaining normoglycaemia by secreting an appropriate amount of insulin according to blood glucose levels. The accurate sensing of the beta cell extracellular environment is therefore crucial to this endocrine function and is transmitted via its cell surface proteome. Various surface proteins that mediate or affect beta cell endocrine function have been identified, including growth factor and cytokine receptors, transporters, ion channels and prote...

  8. Constructions for a bivariate beta distribution

    OpenAIRE

    Olkin, Ingram; Trikalinos, Thomas A.

    2014-01-01

    The beta distribution is a basic distribution serving several purposes. It is used to model data, and also, as a more flexible version of the uniform distribution, it serves as a prior distribution for a binomial probability. The bivariate beta distribution plays a similar role for two probabilities that have a bivariate binomial distribution. We provide a new multivariate distribution with beta marginal distributions, positive probability over the unit square, and correlations over the full ...

  9. Milk Intolerance, Beta-Casein and Lactose

    OpenAIRE

    Sebely Pal; Keith Woodford; Sonja Kukuljan; Suleen Ho

    2015-01-01

    True lactose intolerance (symptoms stemming from lactose malabsorption) is less common than is widely perceived, and should be viewed as just one potential cause of cows’ milk intolerance. There is increasing evidence that A1 beta-casein, a protein produced by a major proportion of European-origin cattle but not purebred Asian or African cattle, is also associated with cows’ milk intolerance. In humans, digestion of bovine A1 beta-casein, but not the alternative A2 beta-casein, releases beta-...

  10. Milk Intolerance, Beta-Casein and Lactose

    Directory of Open Access Journals (Sweden)

    Sebely Pal

    2015-08-01

    Full Text Available True lactose intolerance (symptoms stemming from lactose malabsorption is less common than is widely perceived, and should be viewed as just one potential cause of cows’ milk intolerance. There is increasing evidence that A1 beta-casein, a protein produced by a major proportion of European-origin cattle but not purebred Asian or African cattle, is also associated with cows’ milk intolerance. In humans, digestion of bovine A1 beta-casein, but not the alternative A2 beta-casein, releases beta-casomorphin-7, which activates μ-opioid receptors expressed throughout the gastrointestinal tract and body. Studies in rodents show that milk containing A1 beta-casein significantly increases gastrointestinal transit time, production of dipeptidyl peptidase-4 and the inflammatory marker myeloperoxidase compared with milk containing A2 beta-casein. Co-administration of the opioid receptor antagonist naloxone blocks the myeloperoxidase and gastrointestinal motility effects, indicating opioid signaling pathway involvement. In humans, a double-blind, randomized cross-over study showed that participants consuming A1 beta-casein type cows’ milk experienced statistically significantly higher Bristol stool values compared with those receiving A2 beta-casein milk. Additionally, a statistically significant positive association between abdominal pain and stool consistency was observed when participants consumed the A1 but not the A2 diet. Further studies of the role of A1 beta-casein in milk intolerance are needed.

  11. NMR Spectroscopic Analysis on the Chiral Recognition of Noradrenaline by {beta}-Cyclodextrin ({beta}-CD) and Carboxymethyl- {beta}-cyclodextrin (CM- {beta}-CD)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Hoo; Yi, Dong Heui; Jung, Seun Ho [Konkuk University, Seoul (Korea, Republic of)

    2004-02-15

    {beta}-CD and CM-{beta}-CD as chiral NMR shift agents were used to resolve the enantiomers of noradrenaline (NA). The stoichiometry of each complex formed between the CDs and the enantiomers of NA was found to be 1 : 1 through the continuous variation plots. The binding constants (K) of the complexes were determined from 1H NMR titration curves. This result indicated that both {beta}-CD and CM-{beta}-CD formed the complexes with the S (+)-NA more preferentially than its R(.)-enantiomer. The K values for the complexes with {beta}-CD (KS(+) = 537 M{sup -1} and K{sub R}({sub -}) = 516 M{sup -1}) was larger than those with CM-{beta}-CD (K{sub S}({sub +}) = 435 M{sup -1} and K{sub R}({sub -}) = 313 M{sup -1}), however, enantioselectivity ({alpha}) of S({sub +})- and R(-)-NA to CM-{beta}-CD ({alpha} = 1.38) was larger than that to {beta}-CD ({alpha} = 1.04), indicating that CM-{beta}-CD was the better chiral NMR solvating agents for the recognition of the enantiomers of NA. Two dimensional rotating frame nuclear Overhauser enhancement spectroscopy (ROESY) experiments were also performed to explain the binding properties in terms of spatial fitting of the NA molecule into the macrocyclic cavities

  12. Review of double beta experiments

    CERN Document Server

    Sarazin, Xavier

    2012-01-01

    This paper is the first part of the manuscript written in April 2012 for my academic Accreditation to supervise research. It offers a review of the double beta experimental techniques. My purpose is to detail, for each technique, the different origins of background, how they can be identified, and how they can be reduced. Advantages and limitations are discussed. This review is organized as follows. First, the question of the possible Majorana nature for the neutrino is presented and the physic of neutrinoless double beta decay is summarized. Then I begin by presenting the tracko-calo NEMO-3 and SuperNEMO experiments. I've worked on these two experiments since 15 years. So it was natural to start with them with a relatively more exhaustive description. I will then present the germanium technique. I will then review the bolometer technique. I will describe in detail the recent progress in scintillating bolometers because I think that it is one of the most promising techniques. Finally I will review the large l...

  13. Beta attenuation transmission system (BATS)

    Energy Technology Data Exchange (ETDEWEB)

    Hagan, R.C.; Fullbright, H.J.

    1977-01-01

    The beta attenuation transmission system (BATS) is an automated radiation gauge designed for quantitative measurement of component thickness in explosive detonators. The BATS was designed and built by Group M-1, the Nondestructive Testing Group, of the Los Alamos Scientific Laboratory to measure the areal thickness, in mg/cm/sup 2/, of a cylinder of high explosive (HE) enclosed within a plastic holder. The problem is to determine the density of the HE. A /sup 90/Sr source is collimated by a 0.25 x 1.59-mm slit, and the transmitted beta-particle flux is detected by a plastic scintillator, coupled to a photomultiplier tube. The detonator is transported through the radiation beam by a leadscrew, ballnut, stepping-motor combination. Continuous analog position data are available, derived from the output from a linear-actuated potentiometer attached to the scanner. A linear electrometer amplifies the detected signal, which is then integrated for a preselected time, to obtain the desired statistical accuracy. A microprocessor (..mu..P) is used to control the scanner position and to make the data readings at the assigned positions. The data are stored, and, at the completion of the scan, are processed into the desired format. The final answer is displayed to the operator or output to a peripheral device for permanent record. The characteristics of the radiation source, the collimator, the signal detection and conditioning, and the final results are described in detail. The scanner and the microprocessor control system are briefly outlined.

  14. Challenges in Double Beta Decay

    Directory of Open Access Journals (Sweden)

    Oliviero Cremonesi

    2014-01-01

    Full Text Available In the past ten years, neutrino oscillation experiments have provided the incontrovertible evidence that neutrinos mix and have finite masses. These results represent the strongest demonstration that the electroweak Standard Model is incomplete and that new Physics beyond it must exist. In this scenario, a unique role is played by the Neutrinoless Double Beta Decay searches which can probe lepton number conservation and investigate the Dirac/Majorana nature of the neutrinos and their absolute mass scale (hierarchy problem with unprecedented sensitivity. Today Neutrinoless Double Beta Decay faces a new era where large-scale experiments with a sensitivity approaching the so-called degenerate-hierarchy region are nearly ready to start and where the challenge for the next future is the construction of detectors characterized by a tonne-scale size and an incredibly low background. A number of new proposed projects took up this challenge. These are based either on large expansions of the present experiments or on new ideas to improve the technical performance and/or reduce the background contributions. In this paper, a review of the most relevant ongoing experiments is given. The most relevant parameters contributing to the experimental sensitivity are discussed and a critical comparison of the future projects is proposed.

  15. Association of heterocellular HPFH, beta(+)-thalassaemia, and delta beta(0)-thalassaemia: haematological and molecular aspects.

    OpenAIRE

    Cianetti, L; Care, A; Sposi, N M; Giampaolo, A; Calandrini, M; Petrini, M.; Massa, A.; Marinucci, M.; Mavilio, F; Ceccanti, M.

    1984-01-01

    An Italian family in which heterocellular hereditary persistence of fetal haemoglobin (HPFH) interacts with both beta(+)- and delta beta-thalassaemia is described. The index case was an 8 year old girl who was presumed to inherit both heterocellular HPFH and beta (+)-thalassaemia from her mother and delta beta-thalassaemia from her father. She was healthy and never needed blood transfusions. The possible contribution of heterocellular HPFH to the less severe expression of the compound delta b...

  16. The impact of beta-elemene on beta-tubulin of human hepatoma hepg2 cells

    Institute of Scientific and Technical Information of China (English)

    Yuqiu Mao; Liying Ban; Jielin Zhang; Li Hou; Xiaonan Cui

    2014-01-01

    Objective:The aim of this study was to investigate the impact of beta-elemene injection on the growth and beta-tubulin of human hepatocarcinoma HepG2 cells. Methods:cellproliferation was assessed by MTT assay. cellcycle distribution was detected by flow cytometry (FCM). The mRNA expression of beta-tubulin was measured by RT-PCR. West-ern blot analysis was used to determine protein expression of beta-tubulin and the polymerization of beta-tubulin. Results:Beta-elemene injection inhibited HepG2 cells proliferation in a dose-and time-dependent manner;FCM analysis indicated beta-elemene injection induced cellcycle arrested at S phase. RT-PCR and western-blot analysis showed that beta-elemene injection down-regulated beta-tubulin expression at both mRNA and protein levels, presenting a dose-dependent manner. Moreover, beta-elemene injection reduced the polymerization of microtubules in a dose-dependent manner. Conclusion:Beta-elemene injection can inhibit the proliferation of hepatoma HepG2 cells, the mechanism might be partly related to the down-regulation of beta-tubulin and inhibition of microtubular polymerization.

  17. Expressions of GSK-3beta, Beta-Catenin and PPAR-Gamma in Medulloblastoma

    Institute of Scientific and Technical Information of China (English)

    Xiong Zhang; Lu Si; Yu Li; Can Mi

    2009-01-01

    Objective: To investigate the expressions of GSK-3beta, Beta-catenin and PPAR-gamma, and their relationship in medulloblastoma, and to explore their value in clinic application.Methods: Immunohistochemical staining with SP method was conducted to determine the expressions of GSK-3beta, Beta-catenin and PPAR-gamma in 48 cases of medulloblastoma and 10 normal cerebellar tissues.Results: The rate of abnormal expressions of beta-catenin and PPAR-gamma in MB was higher than that in normal. Conversely, GSK-3beta in MB was lower than that in the normal (P<0.05). Furthermore, in medulloblastoma, beta-catenin and GSK-3beta showed a negative correlation, PPAR-gamma and beta-catenin had a positive correlation.Conclusion: Abnormal expression of beta-catenin plays a crucial role in the development of medulloblastoma. Meanwhile, PPAR-gamma and GSK-3beta which are tightly related with beta-catenin are both involved in the genesis and development of medulloblastoma.

  18. The pharmacokinetics of beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin in the rat

    NARCIS (Netherlands)

    Frijlink, H W; Visser, J; Hefting, N R; Oosting, R; Meijer, D K; Lerk, C F

    1990-01-01

    Hydroxypropyl-beta-cyclodextrin was analyzed by HPLC using postcolumn complexation with phenolphthalein and negative colorimetric detection, with a detection limit of 20 micrograms/ml. The pharmacokinetics of beta-cyclodextrin and of hydroxypropyl-beta-cyclodextrin were studied after intravenous adm

  19. Radiation-induced polymerization of {beta}(+)-pinene and synthesis of optically active {beta}(+)/{beta}(-)pinene polymers and copolymers

    Energy Technology Data Exchange (ETDEWEB)

    Cataldo, Franco, E-mail: franco.cataldo@fastwebnet.i [Lupi Chemical Research, Via Casilina 1626/A, 00133 Rome (Italy); Lilla, Edo; Ursini, Ornella [Institute of Chemical Methodologies, CNR, Via Salaria Km. 29300, Monterotondo Stazione 00016, Rome (Italy)

    2011-06-15

    Poly-{beta}(+)-pinene (pB(+)p) was synthesized with {gamma} irradiation of the monomer {beta}(+)-pinene in bulk under vacuum at 1181 kGy. Also scalemic mixtures of {beta}(+)-pinene and {beta}(-)-pinene were irradiated at 1181 kGy to obtain synthetic copolymers of pB(+)/B(-)p. For comparison also {beta}(-)-pinene was converted into poly-{beta}(-)-pinene (pB(-)p) under the identical conditions adopted for its enantiomer. Furthermore pB(+)p and pB(-)p were also synthesized by thermal processing under the action of a chemical free radical initiator. The optical rotatory dispersion (ORD) of all pBp resins synthesized were accurately studied in the spectral range comprised between 375 and 625 nm and a curious asymmetry in the ORD of pB(+)p versus the ORD of pB(-)p is reported. Furthermore, it is shown that (+)-p-menth-1-ene and (-)-p-menth-1-ene are useful as a model compounds for the pBp resins and for the explanation of the amplification of the optical activity of the {beta}(+)-pinene and {beta}(-)-pinene after their ring-opening polymerization to pB(+)p and pB(-)p. The pBp resins were studied also by FT-IR spectroscopy and by thermal analysis (TGA and DTG).

  20. Imperfect World of beta beta-decay Nuclear Data Sets

    Energy Technology Data Exchange (ETDEWEB)

    Pritychenko, B. [Brookhaven National Lab. (BNL), Upton, NY (United States). NNDC

    2015-01-03

    The precision of double-beta ββ-decay experimental half lives and their uncertainties is reanalyzed. The method of Benford's distributions has been applied to nuclear reaction, structure and decay data sets. First-digit distribution trend for ββ-decay T2v1/2 is consistent with large nuclear reaction and structure data sets and provides validation of experimental half-lives. A complementary analysis of the decay uncertainties indicates deficiencies due to small size of statistical samples, and incomplete collection of experimental information. Further experimental and theoretical efforts would lead toward more precise values of-decay half-lives and nuclear matrix elements.

  1. Beta-glucosidase I variants with improved properties

    Energy Technology Data Exchange (ETDEWEB)

    Bott, Richard R.; Kaper, Thijs; Kelemen, Bradley; Goedegebuur, Frits; Hommes, Ronaldus Wilhelmus; Kralj, Slavko; Kruithof, Paulien; Nikolaev, Igor; Van Der Kley, Wilhelmus Antonious Hendricus; Van Lieshout, Johannes Franciscus Thomas; Van Stigt Thans, Sander

    2016-09-20

    The present disclosure is generally directed to enzymes and in particular beta-glucosidase variants. Also described are nucleic acids encoding beta-glucosidase variants, compositions comprising beta-glucosidase variants, methods of using beta-glucosidase variants, and methods of identifying additional useful beta-glucosidase variants.

  2. Dosimetry of low-energy beta radiation

    Energy Technology Data Exchange (ETDEWEB)

    Borg, J.

    1996-08-01

    Useful techniques and procedures for determination of absorbed doses from exposure in a low-energy {beta} radiation field were studied and evaluated in this project. The four different techniques included were {beta} spectrometry, extrapolation chamber dosimetry, Monte Carlo (MC) calculations, and exoelectron dosimetry. As a typical low-energy {beta} radiation field a moderated spectrum from a {sup 14}C source (E{sub {beta}},{sub max} =156 keV) was chosen for the study. The measured response of a Si(Li) detector to photons (bremsstrahlung) showed fine agreement with the MC calculated photon response, whereas the difference between measured and MC calculated responses to electrons indicates an additional dead layer thickness of about 12 {mu}m in the Si(Li) detector. The depth-dose profiles measured with extrapolation chambers at two laboratories agreed very well, and it was confirmed that the fitting procedure previously reported for {sup 147}Pm depth-dose profiles is also suitable for {beta} radiation from {sup 14}C. An increasing difference between measured and MC calculated dose rates for increasing absorber thickness was found, which is explained by limitations of the EGS4 code for transport of very low-energy electrons (below 10-20 keV). Finally a study of the thermally stimulated exoelectron emission (TSEE) response of BeO thin film dosemeters to {beta} radiation for radiation fields with maximum {beta} energies ranging from 67 keV to 2.27 MeV is reported. For maximum {beta} energies below approximately 500 keV, a decrease in the response amounting to about 20% was observed. It is thus concluded that a {beta} dose higher than about 10 {mu}Gy can be measured with these dosemeters to within 0 to -20% independently of the {beta}energy for E{sub {beta}},{sub max} values down to 67 keV. (au) 12 tabs., 38 ills., 71 refs.

  3. Search for beta sup - and beta sup -beta sup - decays of sup 4 sup 8 Ca

    CERN Document Server

    Bakalyarov, A; Barabash, A; Briançon, C; Brudanin, V; Egorov, V; Hubert, F; Hubert, P; Kovalik, A; Lebedev, V I; Rukhadze, N I; Stekl, I; Umatov, V; Vylov, T D

    2002-01-01

    A sup 4 sup 8 CaCO sub 3 powder sample containing 20.18 g of sup 4 sup 8 Ca was measured for 797 h with a 400 cm sup 3 low-background HPGe detector. New limits on decays of sup 4 sup 8 Ca were obtained. For single beta transitions to sup 4 sup 8 Sc the limits are equal to 0.71x10 sup 2 sup 0 y, 1.1x10 sup 2 sup 0 y, and 0.82x10 sup 2 sup 0 y for transitions to the ground state, excited 5 sup + and 4 sup + states, respectively. The new limits on double beta decay to excited states of sup 4 sup 8 Ti are equal to 0.47x10 sup 2 sup 0 y, 1.1x10 sup 2 sup 0 y, and 0.90x10 sup 2 sup 0 y for transitions to the first 2 sup + , second 2 sup + and first 0 sup + excited states, respectively. All limits are given at the 90% CL.

  4. [Hemoglobin C -- beta-thalassemia disease and homozygous beta-thalassemia in a black African family (author's transl)].

    Science.gov (United States)

    Basset, P; Fall, M; Oudart, J L

    1975-01-01

    The study of a Malian family has allowed to prove existence of two types of beta-thalassemia genes: the beta0 gene which suppresses the synthesis of the beta chain into cis position and the beta+ gene which slows down only partially this synthesis. The difference between this two genes has been possible owing to the hemoglobin C found in this family and induced by the betaC mutated gene. The segregation of the four genes betaA, betaC, beta0 thal, and beta+ thal. has allowed to compare all the possible phenotypes deriving from the combinations by two of these allelic genes. PMID:128735

  5. Broad resonances and beta-decay

    DEFF Research Database (Denmark)

    Riisager, K.; Fynbo, H. O. U.; Hyldegaard, S.;

    2015-01-01

    Beta-decay into broad resonances gives a distorted lineshape in the observed energy spectrum. Part of the distortion arises from the phase space factor, but we show that the beta-decay matrix element may also contribute. Based on a schematic model for p-wave continuum neutron states it is argued...

  6. A proportional-scintillation counter beta spectrometer

    International Nuclear Information System (INIS)

    Using a proportional counter for coincidence gating of events in a plastic scintillator provides selective registration of beta interactions in the scintillator. This technique has been used to construct a field instrument that can selectively collect beta spectra (coincidence gating) or gamma spectra (anticoincidence gating). Associated dose rates are calculated from the spectra

  7. Localization of thymosin beta-4 in tumors

    DEFF Research Database (Denmark)

    Larsson, L. -I.; Holck, Susanne

    2007-01-01

    Overexpression of thymosin beta-4 has been linked to malignant progression but the localization of this polypeptide within tumors is incompletely known. We therefore examined breast cancers for thymosin beta-4 using immunofluorescence. Reactive cells were identified with monoclonal cell marker...... in the tumor microenvironment may modulate tumor behavior....

  8. Higher-Order Beta Matching with Solutions in Long Beta-Eta Normal Form

    DEFF Research Database (Denmark)

    Støvring, Kristian

    2006-01-01

    Higher-order matching is a special case of unification of simply-typed lambda-terms: in a matching equation, one of the two sides contains no unification variables. Loader has recently shown that higher-order matching up to beta equivalence is undecidable, but decidability of higher-order matching...... up to beta-eta equivalence is a long-standing open problem.We show that higher-order matching up to beta-eta equivalence is decidable if and only if a restricted form of higher-order matching up to beta equivalence is decidable: the restriction is that solutions must be in long beta-eta normal form....

  9. Adaptive changes in pancreatic beta cell fractional area and beta cell turnover in human pregnancy

    OpenAIRE

    Butler, A. E.; Cao-Minh, L.; Galasso, R; Rizza, R. A.; Corradin, A.; Cobelli, C; Butler, P C

    2010-01-01

    Aims/hypothesis We sought to establish the extent and basis for adaptive changes in beta cell numbers in human pregnancy. Methods Pancreas was obtained at autopsy from women who had died while pregnant (n = 18), post-partum (n = 6) or were not pregnant at or shortly before death (controls; n = 20). Pancreases were evaluated for fractional pancreatic beta cell area, islet size and islet fraction of beta cells, beta cell replication (Ki67) and apoptosis (TUNEL), and indirect markers of beta cel...

  10. Beta-conjugates of real algebraic numbers as Puiseux expansions

    CERN Document Server

    Verger-Gaugry, Jean-Louis

    2011-01-01

    The beta-conjugates of a base of numeration $\\beta > 1$, $\\beta$ being a Parry number, were introduced by Boyd, in the context of the R\\'enyi-Parry dynamics of numeration system and the beta-transformation. These beta-conjugates are canonically associated with $\\beta$. Let $\\beta > 1$ be a real algebraic number. A more general definition of the beta-conjugates of $\\beta$ is introduced in terms of the Parry Upper function $f_{\\beta}(z)$ of the beta-transformation. We introduce the concept of a germ of curve at $(0,1/\\beta) \\in \\mathbb{C}^{2}$ associated with $f_{\\beta}(z)$ and the reciprocal of the minimal polynomial of $\\beta$. This germ is decomposed into irreducible elements according to the theory of Puiseux, gathered into conjugacy classes. The beta-conjugates of $\\beta$, in terms of the Puiseux expansions, are given a new equivalent definition in this new context. If $\\beta$ is a Parry number the (Artin-Mazur) dynamical zeta function $\\zeta_{\\beta}(z)$ of the beta-transformation, simply related to $f_{\\b...

  11. Ranking Beta Sheet Topologies of Proteins

    DEFF Research Database (Denmark)

    Fonseca, Rasmus; Helles, Glennie; Winter, Pawel

    2010-01-01

    One of the challenges of protein structure prediction is to identify long-range interactions between amino acids.  To reliably predict such interactions, we enumerate, score and rank all beta-topologies (partitions of beta-strands into sheets, orderings of strands within sheets and orientations...... of paired strands) of a given protein.  We show that the beta-topology corresponding to the native structure is, with high probability, among the top-ranked. Since full enumeration is very time-consuming, we also suggest a method to deal with proteins with many beta-strands. The results reported...... in this paper are highly relevant for ab initio protein structure prediction methods based on decoy generation. The top-ranked beta-topologies can be used to find initial conformations from which conformational searches can be started. They can also be used to filter decoys by removing those with poorly...

  12. Beta cell proliferation and growth factors

    DEFF Research Database (Denmark)

    Nielsen, Jens Høiriis; Svensson, C; Møldrup, Annette;

    1999-01-01

    Formation of new beta cells can take place by two pathways: replication of already differentiated beta cells or neogenesis from putative islet stem cells. Under physiological conditions both processes are most pronounced during the fetal and neonatal development of the pancreas. In adulthood little...... cloned a novel GH/PRL stimulated rat islet gene product, Pref-1 (preadipocyte factor-1). This protein contains six EGF-like motifs and may play a role both in embryonic pancreas differentiation and in beta cell growth and function. In summary, the increasing knowledge about the mechanisms involved...... increase in the beta cell number seems to occur. In pregnancy, however, a marked hyperplasia of the beta cells is observed both in rodents and man. Increased mitotic activity has been seen both in vivo and in vitro in islets exposed to placental lactogen (PL), prolactin (PRL) and growth hormone (GH...

  13. Simultaneous beta/gamma digital spectroscopy

    Science.gov (United States)

    Farsoni, Abdollah T.

    A state-of-the-art radiation detection system for simultaneous spectroscopy of beta-particles and gamma-rays has been developed. The system utilizes a triple-layer phoswich detector and a customized Digital Pulse Processor (DPP) built in our laboratory. The DPP board was designed to digitally capture the analog signal pulses and, following several digital preprocessing steps, transfer valid pulses to the host computer for further digital processing. A MATLAB algorithm was developed to digitally discriminate beta and gamma events and reconstruct separate beta and gamma-ray energy spectra with minimum crosstalk. The spectrometer proved to be an effective tool for recording separate beta and gamma-ray spectra from mixed radiation fields. The system as a beta-gamma spectrometer will have broad-ranging applications in nuclear non-proliferation, radioactive waste management, worker safety, systems reliability, dose assessment, and risk analysis.

  14. Peripheral beta-endorphin and pain modulation.

    Science.gov (United States)

    Hartwig, A C

    1991-01-01

    Beta-endorphin is a peptide with morphine-like effects produced primarily in the anterior lobe of the pituitary gland. After its cleavage from the parent molecule, proopiomelanocortin, beta-endorphin is circulated via the blood stream to interact with specific opioid receptors located throughout the body. The peptide produces analgesia by inhibiting the firing of peripheral somatosensory fibers. It also affects other senses, such as vision, hearing, and smell. Whereas the ability to increase beta-endorphin secretion during times of surgical stress is positively correlated with amelioration of pain, the administration of exogenous opioids, such as fentanyl, reduces plasma beta-endorphin. Decreased beta-endorphin concentrations may play a role in trigeminal neuralgia, migraine headache, and rheumatoid arthritis. PMID:1814247

  15. Clusters of conserved beta cell marker genes for assessment of beta cell phenotype

    DEFF Research Database (Denmark)

    Martens, Geert A; Jiang, Lei; Hellemans, Karine H;

    2011-01-01

    The aim of this study was to establish a gene expression blueprint of pancreatic beta cells conserved from rodents to humans and to evaluate its applicability to assess shifts in the beta cell differentiated state. Genome-wide mRNA expression profiles of isolated beta cells were compared to those...... of a large panel of other tissue and cell types, and transcripts with beta cell-abundant and -selective expression were identified. Iteration of this analysis in mouse, rat and human tissues generated a panel of conserved beta cell biomarkers. This panel was then used to compare isolated versus laser capture...... microdissected beta cells, monitor adaptations of the beta cell phenotype to fasting, and retrieve possible conserved transcriptional regulators....

  16. Complement activation by the amyloid proteins A beta peptide and beta 2-microglobulin

    DEFF Research Database (Denmark)

    Nybo, Mads; Nielsen, E H; Svehag, S E

    1999-01-01

    Complement activation (CA) has been reported to play a role in the pathogenesis of Alzheimer's disease (AD). To investigate whether CA may contribute to amyloidogenesis in general, the CA potential of different amyloid fibril proteins was tested. CA induced by A beta preparations containing soluble...... protein, protofilaments and some fibrils or only fibrils in a solid phase system (ELISA) was modest with a slow kinetics compared to the positive delta IgG control. Soluble A beta induced no detectable CA in a liquid phase system (complement consumption assay) while fibrillar A beta caused CA at 200 mg....../ml and higher concentrations. Soluble beta 2-microglobulin (beta 2M) purified from peritoneal dialysates was found to be as potent a complement activator as A beta in both solid and liquid phase systems while beta 2M purified from urine exhibited lower activity, a difference which may be explained...

  17. Clusters of conserved beta cell marker genes for assessment of beta cell phenotype

    DEFF Research Database (Denmark)

    Martens, Geert A; Jiang, Lei; Hellemans, Karine H;

    2011-01-01

    of a large panel of other tissue and cell types, and transcripts with beta cell-abundant and -selective expression were identified. Iteration of this analysis in mouse, rat and human tissues generated a panel of conserved beta cell biomarkers. This panel was then used to compare isolated versus laser......The aim of this study was to establish a gene expression blueprint of pancreatic beta cells conserved from rodents to humans and to evaluate its applicability to assess shifts in the beta cell differentiated state. Genome-wide mRNA expression profiles of isolated beta cells were compared to those...... capture microdissected beta cells, monitor adaptations of the beta cell phenotype to fasting, and retrieve possible conserved transcriptional regulators....

  18. Involvement of urokinase-type plasminogen activator system in cancer: an overview.

    Science.gov (United States)

    Mekkawy, Ahmed H; Pourgholami, Mohammad H; Morris, David L

    2014-09-01

    Currently, there are several studies supporting the role of urokinase-type plasminogen activator (uPA) system in cancer. The association of uPA to its receptor triggers the conversion of plasminogen into plasmin. This process is regulated by the uPA inhibitors (PAI-1 and PAI-2). Plasmin promotes degradation of basement membrane and extracellular matrix (ECM) components as well as activation of ECM latent matrix metalloproteases. Degradation and remodeling of the surrounding tissues is crucial in the early steps of tumor progression by facilitating expansion of the tumor mass, release of tumor growth factors, activation of cytokines as well as induction of tumor cell proliferation, migration, and invasion. Hence, many tumors showed a correlation between uPA system component levels and tumor aggressiveness and survival. Therefore, this review summarizes the structure of the uPA system, its contribution to cancer progression, and the clinical relevance of uPA family members in cancer diagnosis. In addition, the review evaluates the significance of uPA system in the development of cancer-targeted therapies.

  19. Brain-derived neurotrophic factor inducing angiogenesis through modulation of matrix-degrading proteases

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Background Recent studies have proved that brain-derived neurotrophic factor (BDNF) possesses angiogenic activity in vitro and in vivo. However, the proangiogenic mechanism of BDNF has not yet been provided with enough information. To explore the proangiogenic mechanism of BDNF, we investigated the effects of BDNF on extracellular proteolytic enzymes, including matrix metalloproteinases (MMPs) and serine proteases, particularly the urokinase-type plasminogen activator (uPA)-plasmin system in human umbilical vein endothelial cells (HUVECs) model. Methods Tube formation assay was performed in vitro to evaluate the effects of BDNF on angiogenesis. The HUVECs were treated with various concentrations of BDNF (25-400 ng/ml) for different (6-48 hours), reverse transcriptase-polymerase chain reaction (RT-PCR) was used to assay MMP-2, MMP-9, TIMP-1, and TIMP-2 mRNA in HUVECs, and the conditioned medium was analyzed for MMP and uPA activity by gelatin zymography and fibrin zymography, respectively. uPA, plasminogen activator inhibitor (PAI)-1, tissue inhibitors of metalloproteinase (TIMP)-1, and TIMP-2 were quantified by western blotting analysis. Results BDNF elicited robust and elongated angiogeneis in two-dimensional cultures of HUVECs in comparison with control. The stimulation of serum-starved HUVECs with BDNF caused obvious increase in MMP-2 and MMP-9 mRNA expression and induced the pro-MMP-2 and pro-MMP-9 activation without significant differences in proliferation. However, BDNF had no effect on TIMP-1 and TIMP-2 production. BDNF increased uPA and PAI-1 production in a dose-dependent manner. Maximal activation of uPA and PAI-1 expression in HUVECs was induced by 100 ng/ml BDNF, while effects of 200 ng/ml and 400 ng/ml BDNF were slightly reduced in comparison with with those of 100 ng/ml. Protease activity for uPA was also increased by BDNF in a dose-dependent manner. BDNF also stimulated uPA and PAI-1 production beyond that in control cultures in a time

  20. uPA基因修饰骨髓源性肝干细胞移植对肝纤维化大鼠TGF-β-Smads信号通路的影响%Effect of transplantation of uPA gene-modified bone marrowderived liver stem cells on the TGF-β/Smad signal pathway in rats with liver fibrosis

    Institute of Scientific and Technical Information of China (English)

    孙超; 李定国; 陈源文; 陈颖伟; 汪保灿

    2011-01-01

    目的:探讨尿激酶型纤溶酶原激活物(uPA)基因修饰骨髓源性肝干细胞(BDLSC)移植对CC14诱导的大鼠肝组织转化生长因子-β-Smads(TGF-β-Smads)信号通路的影响.方法:采用皮下注射CC14建立大鼠肝纤维化模型.将纯系Fisher大鼠随机分为正常组、模型组、BDLSC组(尾静脉注入2×10(6)BDLSC)和BDLSC-uPA组(尾静脉注入2×10(6)AduPA转染的BDLSC),每组9只.观察各组大鼠肝功能和病理组织学变化;采用免疫组织化学法或Western blot法分别检测大鼠肝组织TGF-β1,Smad3及Smad7蛋白表达变化.结果:与模型组和BDLSC组相比,BDLSC-uPA组大鼠肝脏结缔组织增生程度减轻,假小叶形成不明显,肝功能明显改善;肝组织TGF-β1蛋白表达明显低于模型组和BDLSC组(0.1849±0.0456vs0.8202±0.0636,0.2936±0.0548,均P<0.05),而Smad3和Smad7蛋白表达无明显变化.结论:uPA基因修饰BDLSC移植可能部分通过抑制TGF-β1蛋白表达,从而发挥抗肝纤维化的作用.%AIM: To explore the effect of transplantation of urokinase-type plasminogen activator (uPA) gene-modified bone marrow-derived liver stem cells (BDLSC) on the transforming growth factor-β (TGF-β)/Smad signal pathway in rats with CC14-induced liver fibrosis. METHODS: Liver fibrosis was induced in rats by subcutaneous injection of CC14. The rats were randomly divided into control group, model group,BDLSC group (injected with 2×106 BDLSC via the tail vein), and BDLSC-uPA group(injected with 2×106 uPA-transfected BDLSC via the tail vein). Liver function and hepatic pathohistologicai changes were detected, and the expression of TGF-β1, Smad3 and Smad7 proteins was determined by immunohistochemistry or Western blot. RESULTS: In the BDLSC-uPA group, the extent of liver fibrosis was much milder, the formation of pseudolobules was less obvious, liver function was better, and the expression of TGF-β1 protein in the liver (0.1849 ± 0.0456 vs 0.8202 ± 0.0636, 0.2936 ± 0.0548, both P < 0

  1. Ellagic acid promotes A{beta}42 fibrillization and inhibits A{beta}42-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Ying [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Yang, Shi-gao; Du, Xue-ting; Zhang, Xi; Sun, Xiao-xia; Zhao, Min [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Sun, Gui-yuan, E-mail: sungy2004@sohu.com [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Liu, Rui-tian, E-mail: rtliu@tsinghua.edu.cn [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China)

    2009-12-25

    Smaller, soluble oligomers of {beta}-amyloid (A{beta}) play a critical role in the pathogenesis of Alzheimer's disease (AD). Selective inhibition of A{beta} oligomer formation provides an optimum target for AD therapy. Some polyphenols have potent anti-amyloidogenic activities and protect against A{beta} neurotoxicity. Here, we tested the effects of ellagic acid (EA), a polyphenolic compound, on A{beta}42 aggregation and neurotoxicity in vitro. EA promoted A{beta} fibril formation and significant oligomer loss, contrary to previous results that polyphenols inhibited A{beta} aggregation. The results of transmission electron microscopy (TEM) and Western blot displayed more fibrils in A{beta}42 samples co-incubated with EA in earlier phases of aggregation. Consistent with the hypothesis that plaque formation may represent a protective mechanism in which the body sequesters toxic A{beta} aggregates to render them harmless, our MTT results showed that EA could significantly reduce A{beta}42-induced neurotoxicity toward SH-SY5Y cells. Taken together, our results suggest that EA, an active ingredient in many fruits and nuts, may have therapeutic potential in AD.

  2. Evidence for Novel [beta]-Sheet Structures in Iowa Mutant [beta]-Amyloid Fibrils

    Energy Technology Data Exchange (ETDEWEB)

    Tycko, Robert; Sciarretta, Kimberly L.; Orgel, Joseph P.R.O.; Meredith, Stephen C.; (IIT); (NIH); (UC)

    2009-07-24

    Asp23-to-Asn mutation within the coding sequence of {beta}-amyloid, called the Iowa mutation, is associated with early onset, familial Alzheimer's disease and cerebral amyloid angiopathy, in which patients develop neuritic plaques and massive vascular deposition predominantly of the mutant peptide. We examined the mutant peptide, D23N-A{beta}40, by electron microscopy, X-ray diffraction, and solid-state NMR spectroscopy. D23N-A{beta}40 forms fibrils considerably faster than the wild-type peptide (k = 3.77 x 10{sup -3} min{sup -1} and 1.07 x 10{sup -4} min{sup -1} for D23N-A{beta}40 and the wild-type peptide WT-A{beta}40, respectively) and without a lag phase. Electron microscopy shows that D23N-A{beta}40 forms fibrils with multiple morphologies. X-ray fiber diffraction shows a cross-{beta} pattern, with a sharp reflection at 4.7 {angstrom} and a broad reflection at 9.4 {angstrom}, which is notably smaller than the value for WT-A{beta}40 fibrils (10.4 {angstrom}). Solid-state NMR measurements indicate molecular level polymorphism of the fibrils, with only a minority of D23N-A{beta}40 fibrils containing the in-register, parallel {beta}-sheet structure commonly found in WT-A{beta}40 fibrils and most other amyloid fibrils. Antiparallel {beta}-sheet structures in the majority of fibrils are indicated by measurements of intermolecular distances through 13C-13C and 15N-13C dipole-dipole couplings. An intriguing possibility exists that there is a relationship between the aberrant structure of D23N-A{beta}40 fibrils and the unusual vasculotropic clinical picture in these patients.

  3. Dosimetry of Low-Energy Beta Radiation

    DEFF Research Database (Denmark)

    Borg, Jette

    Useful techniques and procedures for derermination of absorbed doses from exposure in a low-energy beta radiation were studied and evaluated. The four techniques included were beta spectrometry, extrapolation chamber dosimetry, Monte Carlo (MC) calculations, and exoelectron dosimetry. As a typical...... low-energy beta radiation field a moderated spectrum from a carbon-14 source was used. The measured responce of a Si(Li) detector to photons (bremsstrahlung) showed fine agreemant with the MC calculated photon response, whereas the difference between measured and MC calculated response to electrons...

  4. Rotational beta expansion: Ergodicity and Soficness

    OpenAIRE

    Akiyama, Shigeki; Caalim, Jonathan

    2015-01-01

    We study a family of piecewise expanding maps on the plane, generated by composition of a rotation and an expansive similitude of expansion constant $\\beta$. We give two constants $B_1$ and $B_2$ depending only on the fundamental domain that if $\\beta>B_1$ then the expanding map has a unique absolutely continuous invariant probability measure, and if $\\beta>B_2$ then it is equivalent to $2$-dimensional Lebesgue measure. Restricting to a rotation generated by $q$-th root of unity $\\zeta$ with ...

  5. Falsifying Baryogenesis with Neutrinoless Double Beta Decay

    CERN Document Server

    Graf, Lukas

    2016-01-01

    We discuss the relation between lepton number violation at high and low energies, particularly, the constraints on baryogenesis models, which would be implied by an observation of neutrinoless double beta decay. The primordial baryon asymmetry can be washed out by effective lepton number violating operators triggering neutrinoless double beta decay in combination with sphaleron processes. A generic conclusion is that popular models of baryogenesis are excluded if a non-standard mechanism of neutrinoless double beta decay, i.e., other than the standard light neutrino exchange, is observed. Apart from the effective field approach, we also outline the possible extension of our arguments to a general UV-completed model.

  6. Beta-alanine synthesis in Escherichia coli.

    OpenAIRE

    Cronan, J. E.

    1980-01-01

    The enzyme, aspartate 1-decarboxylase (L-aspartate 1-carboxy-lyase; EC 4.1.1.15), that catalyzes the reaction aspartate leads to beta-alanine + CO2 was found in extracts of Escherichia coli. panD mutants of E. coli are defective in beta-alanine biosynthesis and lack aspartate 1-decarboxylase. Therefore, the enzyme functions in the biosynthesis of the beta-alanine moiety of pantothenate. The genetic lesion in these mutants is closely linked to the other pantothenate (pan) loci of E. coli K-12.

  7. Review of modern double beta decay experiments

    Science.gov (United States)

    Barabash, A. S.

    2015-10-01

    The review of modern experiments on search and studying of double beta decay processes is done. Results of the most sensitive current experiments are discussed. The main attention is paid to EXO-200, KamLAND-Zen, GERDA-I and CUORE-0 experiments. Modern values of T1/2(2ν) and best present limits on neutrinoless double beta decay and double beta decay with Majoron emission are presented. Conservative limits on effective mass of a Majorana neutrino ( at the level of ˜ 0.01-0.1 eV are discussed.

  8. Bound beta-decay: BOB

    International Nuclear Information System (INIS)

    For many years exotic decay modes of the neutron have been investigated as possible doorways to the exploration of new physics. The bound beta-decay (BOB) of the neutron into a hydrogen atom and an anti-neutrino offers a very elegant method to study neutrino helicities. However, this rare decay has not yet been observed for the free neutron, owing to the challenge of measuring a decay involving only electrically neutral particles and with an estimated branching ratio of only a few 106 of the three-body decay mode. During the past few years scientists from the TUM E18 Group have developed a novel experimental scheme which addresses all necessary problems associated with the observation of this two-body neutron decay in a very coherent way. The BOB experiment shall be installed at a tangential beam tube of a powerful research reactor such as the SR6 at the FRMII in Garching or H6-H7 beam tube at ILL. This talk will provide insights and ideas on how such an experiment is to be performed.

  9. Dopamine beta-hydroxylase deficiency

    Directory of Open Access Journals (Sweden)

    Senard Jean-Michel

    2006-03-01

    Full Text Available Abstract Dopamine beta-hydroxylase (DβH deficiency is a very rare form of primary autonomic failure characterized by a complete absence of noradrenaline and adrenaline in plasma together with increased dopamine plasma levels. The prevalence of DβH deficiency is unknown. Only a limited number of cases with this disease have been reported. DβH deficiency is mainly characterized by cardiovascular disorders and severe orthostatic hypotension. First symptoms often start during a complicated perinatal period with hypotension, muscle hypotonia, hypothermia and hypoglycemia. Children with DβH deficiency exhibit reduced ability to exercise because of blood pressure inadaptation with exertion and syncope. Symptoms usually worsen progressively during late adolescence and early adulthood with severe orthostatic hypotension, eyelid ptosis, nasal stuffiness and sexual disorders. Limitation in standing tolerance, limited ability to exercise and traumatic morbidity related to falls and syncope may represent later evolution. The syndrome is caused by heterogeneous molecular alterations of the DBH gene and is inherited in an autosomal recessive manner. Restoration of plasma noradrenaline to the normal range can be achieved by therapy with the synthetic precursor of noradrenaline, L-threo-dihydroxyphenylserine (DOPS. Oral administration of 100 to 500 mg DOPS, twice or three times daily, increases blood pressure and reverses the orthostatic intolerance.

  10. Neutron bound {beta}- decay- BOB

    Energy Technology Data Exchange (ETDEWEB)

    Gabriel, M.; Berger, M.; Emmerich, R.; Faestermann, T.; Gutsmiedl, E.; Hartmann, F.J.; Paul, S.; Ruschel, S.; Schoen, J.; Schott, W.; Schubert, U.; Trautner, A. [Physik-Department, TUM, 85748 Garching (Germany); Engels, R. [Institut fuer Kernphysik, Forschungszentrum Juelich, 52425 Juelich (Germany); Fierlinger, P. [Excellence Cluster Universe, TUM, 85748 Garching (Germany); Hertenberger, R. [Sektion Physik, LMU, 85748 Garching (Germany); Roehrmoser, R. [FRM2, TUM, 85748 Garching (Germany); Udem, T. [Max-Planck-Institut fuer Quantenphysik, 85748 Garching (Germany)

    2011-07-01

    The bound neutron {beta}-decay(BOB) into a hydrogen atom and an electron antineutrino is investigated.The hyper-fine-state population of the monoenergetic hydrogen atoms (326.3 eV) yields the neutrino left-handed-ness or a possible right-handed admixture and possible small scalar and tensor contributions to the weak force. Preexperiments to measure the BOB H(2s) atoms have been done or are being set up using ionizer and RF discharge proton sources, a Wien filter, Cs and Ar cells, a spin filter, electric counter and accelerating fields, a double focusing magnet and a solar blind PM for the Lyman-{alpha} photons. In a first experiment, the charge exchange of the H(2s) atoms into H{sup -}, offering a selective method to discriminate these states against background, is investigated. In a second step the number of background H(2s) resulting from protons interacting with the walls of the experimental setup are determined. For this a quenching E field and a solar blind PM are used.

  11. Beta cell count instead of beta cell mass to assess and localize growth in beta cell population following pancreatic duct ligation in mice.

    Directory of Open Access Journals (Sweden)

    Marie Chintinne

    Full Text Available BACKGROUND: Pancreatic-tail duct ligation (PDL in adult rodents has been reported to induce beta cell generation and increase beta cell mass but increases in beta cell number have not been demonstrated. This study examines whether PDL increases beta cell number and whether this is caused by neogenesis of small clusters and/or their growth to larger aggregates. METHODOLOGY: Total beta cell number and its distribution over small (100 µm clusters was determined in pancreatic tails of 10-week-old mice, 2 weeks after PDL or sham. PRINCIPAL FINDINGS: PDL increased total beta cell mass but not total beta cell number. It induced neogenesis of small beta cell clusters (2.2-fold higher number which contained a higher percent proliferating beta cells (1.9% Ki67+cells than sham tails (<0.2%; their higher beta cell number represented <5% of total beta cell number and was associated with a similar increase in alpha cell number. It is unknown whether the regenerative process is causally related to the inflammatory infiltration in PDL-tails. Human pancreases with inflammatory infiltration also exhibited activation of proliferation in small beta cell clusters. CONCLUSIONS/SIGNIFICANCE: The PDL model illustrates the advantage of direct beta cell counts over beta cell mass measurements when assessing and localizing beta cell regeneration in the pancreas. It demonstrates the ability of the adult mouse pancreas for neogenesis of small beta cell clusters with activated beta cell proliferation. Further studies should investigate conditions under which neoformed small beta cell clusters grow to larger aggregates and hence to higher total beta cell numbers.

  12. Energetic, Structural, and Antimicrobial Analyses of [beta]-Lactam Side Chain Recognition by [beta]-Lactamases

    Energy Technology Data Exchange (ETDEWEB)

    Caselli, E.; Powers, R.A.; Blaszczak, L.C.; Wu, C.Y.E.; Prati, F.; Shoichet, B.K. (NWU)

    2010-03-05

    Penicillins and cephalosporins are among the most widely used and successful antibiotics. The emergence of resistance to these {beta}-lactams, most often through bacterial expression of {beta}-lactamases, threatens public health. To understand how {beta}-lactamases recognize their substrates, it would be helpful to know their binding energies. Unfortunately, these have been difficult to measure because {beta}-lactams form covalent adducts with {beta}-lactamases. This has complicated functional analyses and inhibitor design. To investigate the contribution to interaction energy of the key amide (R1) side chain of {beta}-lactam antibiotics, eight acylglycineboronic acids that bear the side chains of characteristic penicillins and cephalosporins, as well as four other analogs, were synthesized. These transition-state analogs form reversible adducts with serine {beta}-lactamases. Therefore, binding energies can be calculated directly from K{sub i} values. The K{sub i} values measured span four orders of magnitude against the Group I {beta}-lactamase AmpC and three orders of magnitude against the Group II {beta}-lactamase TEM-1. The acylglycineboronic acids have K{sub i} values as low as 20 nM against AmpC and as low as 390 nM against TEM-1. The inhibitors showed little activity against serine proteases, such as chymotrypsin. R1 side chains characteristic of {beta}-lactam inhibitors did not have better affinity for AmpC than did side chains characteristic of {beta}-lactam substrates. Two of the inhibitors reversed the resistance of pathogenic bacteria to {beta}-lactams in cell culture. Structures of two inhibitors in their complexes with AmpC were determined by X-ray crystallography to 1.90 {angstrom} and 1.75 {angstrom} resolution; these structures suggest interactions that are important to the affinity of the inhibitors. Acylglycineboronic acids allow us to begin to dissect interaction energies between {beta}-lactam side chains and {beta}-lactamases. Surprisingly

  13. Synthesis of mesoporous Beta and Sn-Beta zeolites and their catalytic performances.

    Science.gov (United States)

    Jin, Junjiang; Ye, Xinxin; Li, Yongsheng; Wang, Yanqin; Li, Liang; Gu, Jinlou; Zhao, Wenru; Shi, Jianlin

    2014-06-14

    Mesoporous Beta zeolite has been successfully prepared through hydrothermal synthesis in the presence of cationic ammonium-modified chitosan as the meso-template. Through a subsequent solid-gas reaction between highly dealuminated mesoporous Beta zeolite and SnCl4 steam at an elevated temperature, mesoporous Sn-Beta has been facilely obtained. It was revealed that the addition of cationic chitosan induced the nanocrystal aggregation to particle sizes of ∼300 nm, giving rise to the intercrystalline/interparticle mesoporosity. In the Sn-implanting procedure, Sn species were demonstrated to be doped into the framework of the resulting mesoporous Beta zeolite in a tetrahedral environment without structural collapse. Due to the micro/mesoporous structures, both mesoporous Beta and Sn-Beta exhibited superior performances in α-pinene isomerization, Baeyer-Villiger oxidation of 2-adamantanone by hydrogen peroxide and the isomerization of glucose in water, respectively.

  14. Pressure phase lines and enthalpies for the. cap alpha. -. beta. and. beta. -liquid transitions in beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Abey, A.

    1984-10-31

    The effect of hydrostatic pressure on the ..cap alpha..-..beta.. and ..beta..-liquid transition temperatures in Be was measured in a gas pressure system. Differential thermal analysis was used in the pressure range from 0.1 MPa to 0.7 GPa. For the ..cap alpha..-..beta.. transition, dT/dP = 43 +- 7 K/GPa; for the ..beta..-liquid transition, dT/dP = 35 +- 7 K/GPa. Although it is possible that large systematic errors may arise from experimental procedures, our results are seriously at odds with those of other investigators. Transition enthalpies for the ..cap alpha..-..beta.. and ..beta..-liquid transitions were 1.9 +- 0.2 and 2.2 +- 0.2 kcal/g.m., respectively, at a pressure of 0.1 MPa.

  15. Systematic Risk on Istanbul Stock Exchange: Traditional Beta Coefficient Versus Downside Beta Coefficient

    Directory of Open Access Journals (Sweden)

    Gülfen TUNA

    2013-03-01

    Full Text Available The aim of this study is to test the validity of Downside Capital Asset Pricing Model (D-CAPM on the ISE. At the same time, the explanatory power of CAPM's traditional beta and D-CAPM's downside beta on the changes in the average return values are examined comparatively. In this context, the monthly data for seventy three stocks that are continuously traded on the ISE for the period 1991-2009 is used. Regression analysis is applied in this study. The research results have shown that D-CAPM is valid on the ISE. In addition, it is obtained that the power of downside beta coefficient is higher than traditional beta coefficient on explaining the return changes. Therefore, it can be said that the downside beta is superior to traditional beta in the ISE for chosen period.

  16. A comparison of enzymatic phosphorylation and phosphatidylation of beta-L- and beta-D-nucleosides.

    Science.gov (United States)

    Birichevskaya, Larisa L; Kvach, Sergei V; Sivets, Grigorii G; Kalinichenko, Elena N; Zinchenko, Anatoly I; Mikhailopulo, Igor A

    2007-04-01

    Enzymatic 5'-monophosphorylation and 5'-phosphatidylation of a number of beta-L- and beta-D-nucleosides was investigated. The first reaction, catalyzed by nucleoside phosphotransferase (NPT) from Erwinia herbicola, consisted of the transfer of the phosphate residue from p-nitrophenylphosphate (p-NPP) to the 5'-hydroxyl group of nucleoside; the second was the phospholipase D (PLD)-catalyzed transphosphatidylation of L-alpha-lecithin with a series of beta-L- and beta-D-nucleosides as the phosphatidyl acceptor resulted in the formation of the respective phospholipid-nucleoside conjugates. Some beta-L-nucleosides displayed similar or even higher substrate activity compared to the beta-D-enantiomers. PMID:17206374

  17. Expression of transforming growth factor beta (TGF beta) receptors and expression of TGF beta 1, TGF beta 2 and TGF beta 3 in human small cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Damstrup, L; Rygaard, K; Spang-Thomsen, M;

    1993-01-01

    A panel of 21 small cell lung cancer cell (SCLC) lines were examined for the presence of Transforming growth factor beta receptors (TGF beta-r) and the expression of TGF beta mRNAs. By the radioreceptor assay we found high affinity receptors to be expressed in six cell lines. scatchard analysis...... of the binding data demonstrated that the cells bound between 4.5 and 27.5 fmol mg-1 protein with a KD ranging from 16 to 40 pM. TGF beta 1 binding to the receptors was confirmed by cross-linking TGF beta 1 to the TGF beta-r. Three classes of TGF beta-r were demonstrated, type I and type II receptors with M......(r) = 65,000 and 90,000 and the betaglycan (type III) with M(r) = 280,000. Northern blotting showed expression of TGF beta 1 mRNA in ten, TGF beta 2 mRNA in two and TGF beta 3 mRNA in seven cell lines. Our results provide, for the first time, evidence that a large proportion of a broad panel of SCLC cell...

  18. Rosemary extracts improve flow-mediated dilatation of the brachial artery and plasma PAI-1 activity in healthy young volunteers

    OpenAIRE

    Sinkovic, Andreja; Suran, David; Lokar, Lidija; Fliser, Eva; Skerget, Mojca; Novak, Zoran; Knez, Zeljko

    2010-01-01

    Abstract Polyphenol antioxidants decrease the risk of atherosclerosis. Our aim was to evaluate prospectively in healthy young participants the effect of oral rosemary extracts (RE), consisting of diphenols, upon endothelial dysfunction (ED), preceding structural atherosclerosis. We prospectively studied 19 healthy young volunteers, who received oral RE (77.7 mg) for 21 days, consisting of active substances carnosol (0.97 mg), carnosic (8.60 mg) and rosmarinic acid (10.30 mg). Befor...

  19. Neutrino potential for neutrinoless double beta decay

    CERN Document Server

    Iwata, Yoritaka

    2016-01-01

    Neutrino potential for neutrinoless double beta decay is studied with focusing on its statistical property. The statistics provide a gross view of understanding amplitude of constitutional components of the nuclear matrix element.

  20. Literature in Focus Beta Beams: Neutrino Beams

    CERN Multimedia

    2009-01-01

    By Mats Lindroos (CERN) and Mauro Mezzetto (INFN Padova, Italy) Imperial Press, 2009 The beta-beam concept for the generation of electron neutrino beams was first proposed by Piero Zucchelli in 2002. The idea created quite a stir, challenging the idea that intense neutrino beams only could be produced from the decay of pions or muons in classical neutrino beams facilities or in future neutrino factories. The concept initially struggled to make an impact but the hard work by many machine physicists, phenomenologists and theoreticians over the last five years has won the beta-beam a well-earned position as one of the frontrunners for a possible future world laboratory for high intensity neutrino oscillation physics. This is the first complete monograph on the beta-beam concept. The book describes both technical aspects and experimental aspects of the beta-beam, providing students and scientists with an insight into the possibilities o...

  1. Probing neutrinoless double beta decay with SNO+

    CERN Document Server

    Arushanova, Evelina

    2015-01-01

    Probing neutrinoless double beta decay is one of the primary goals for SNO+, SNOLAB's multi-purpose neutrino detector. In order to achieve this goal the SNO detector has been adapted so that it can be filled with Te-loaded liquid scintillator. During the initial double beta phase the target loading is 0.3% natural Te, which equates to $\\sim790$ kg of double beta isotope. Estimating the sensitivity to neutrinoless double beta decay requires a well understood background model. For SNO+ this is provided by a comprehensive study considering all possible background contributions, whether they originate from within the liquid scintillator cocktail, the surrounding parts of the detector or other irreducible backgrounds. Given these considerations, for five years running in the initial phase, the expected sensitivity is $T_{1/2}^{0\

  2. Review of modern double beta decay experiments

    Energy Technology Data Exchange (ETDEWEB)

    Barabash, A. S., E-mail: barabash@itep.ru [Institute of Theoretical and Experimental Physics (NRC ”Kurchatov Institute”), B. Cheremushkinskaya 25, Moscow (Russian Federation)

    2015-10-28

    The review of modern experiments on search and studying of double beta decay processes is done. Results of the most sensitive current experiments are discussed. The main attention is paid to EXO-200, KamLAND-Zen, GERDA-I and CUORE-0 experiments. Modern values of T{sub 1/2}(2ν) and best present limits on neutrinoless double beta decay and double beta decay with Majoron emission are presented. Conservative limits on effective mass of a Majorana neutrino (〈m{sub ν}〉 < 0.46 eV) and a coupling constant of Majoron to neutrino (〈g{sub ee}〉 < 1.3 · 10{sup −5}) are obtained. Prospects of search for neutrinoless double beta decay in new experiments with sensitivity to 〈m{sub ν}〉 at the level of ∼ 0.01-0.1 eV are discussed.

  3. Beta decay of highly charged ions

    International Nuclear Information System (INIS)

    Ion storage rings and ion traps provide the very first opportunity to address nuclear beta decay under conditions prevailing in hot stellar plasmas during nucleosynthesis, i.e. at high atomic charge states. Experiments are summarized that were performed in this field during the last decade at the ion storage-cooler ring ESR in Darmstadt. Special emphasis is given to the first observation of bound-state beta decay, where the created electron remains bound in an inner orbital of the daughter atom. The impact of this specific 'stellar' decay mode for s-process nucleosynthesis as well as for nuclear 'eon clocks' is outlined. Finally, a new technique, single-ion decay spectroscopy, is presented, where one observes two-body beta decay characteristics (i.e. orbital electron capture or bound-state beta decay) of highly charged, single ions for well-defined nuclear and atomic quantum states of both the mother - and the daughter - ion.

  4. Solid-state NMR analysis of the {beta}-strand orientation of the protofibrils of amyloid {beta}-protein

    Energy Technology Data Exchange (ETDEWEB)

    Doi, Takashi [Graduate School of Science, Kyoto University, Kyoto 606-8502 (Japan); Masuda, Yuichi, E-mail: masuda@mail.pharm.tohoku.ac.jp [Graduate School of Science, Kyoto University, Kyoto 606-8502 (Japan); Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578 (Japan); Irie, Kazuhiro [Graduate School of Agriculture, Kyoto University, Kyoto 606-8502 (Japan); Akagi, Ken-ichi; Monobe, Youko; Imazawa, Takayoshi [Section of Laboratory Equipment, Division of Biomedical Research, National Institute of Biomedical Innovation, Osaka 567-0085 (Japan); Takegoshi, K. [Graduate School of Science, Kyoto University, Kyoto 606-8502 (Japan)

    2012-11-30

    Highlights: Black-Right-Pointing-Pointer The supramolecular structure of A{beta}42 protofibrils was analyzed by solid-state NMR. Black-Right-Pointing-Pointer The Ala-21 residue in the A{beta}42 protofibrils is included in a slightly disordered {beta}-strand. Black-Right-Pointing-Pointer The A{beta}42 protofibrils do not form intermolecular in-register parallel {beta}-sheets. -- Abstract: Alzheimer's disease (AD) is caused by abnormal deposition (fibrillation) of a 42-residue amyloid {beta}-protein (A{beta}42) in the brain. During the process of fibrillation, the A{beta}42 takes the form of protofibrils with strong neurotoxicity, and is thus believed to play a crucial role in the pathogenesis of AD. To elucidate the supramolecular structure of the A{beta}42 protofibrils, the intermolecular proximity of the Ala-21 residues in the A{beta}42 protofibrils was analyzed by {sup 13}C-{sup 13}C rotational resonance experiments in the solid state. Unlike the A{beta}42 fibrils, an intermolecular {sup 13}C-{sup 13}C correlation was not found in the A{beta}42 protofibrils. This result suggests that the {beta}-strands of the A{beta}42 protofibrils are not in an in-register parallel orientation. A{beta}42 monomers would assemble to form protofibrils with the {beta}-strand conformation, then transform into fibrils by forming intermolecular parallel {beta}-sheets.

  5. Genetic counselling in the beta-thalassaemias

    OpenAIRE

    Ioannides, Adonis S.

    2013-01-01

    The beta-thalassaemias are very important genetic disorders of haemoglobin synthesis and are amongst the commonest monogenic disorders. In view of the severity of beta-thalassaemia major, a number of screening programmes have been developed aimed at reducing the number of individuals born with the condition. Genetic counsellingplays a vital role in this process supporting the successful implementation of screening and delineating available options to at risk individuals. This review assesses ...

  6. Searches for neutrinoless double beta decay

    Science.gov (United States)

    Schwingenheuer, Bernhard

    2012-07-01

    Neutrinoless double beta decay is a lepton number violating process whose observation would also establish that neutrinos are their own anti-particles. There are many experimental efforts with a variety of techniques. Some (EXO, Kamland-Zen, GERDA phase I and CANDLES) started take data in 2011 and EXO has reported the first measurement of the half life for the double beta decay with two neutrinos of 136Xe. The sensitivities of the different proposals are reviewed.

  7. Searches for neutrinoless double beta decay

    CERN Document Server

    Schwingenheuer, B

    2012-01-01

    Neutrinoless double beta decay is a lepton number violating process whose observation would also establish that neutrinos are their own anti-particles. There are many experimental efforts with a variety of techniques. Some (EXO, Kamland-Zen, GERDA phase I and CANDLES) started take data in 2011 and EXO has reported the first measurement of the half life for the double beta decay with two neutrinos of $^{136}$Xe. The sensitivities of the different proposals are reviewed.

  8. Peripheral beta-endorphin and pain modulation.

    OpenAIRE

    Hartwig, A. C.

    1991-01-01

    Beta-endorphin is a peptide with morphine-like effects produced primarily in the anterior lobe of the pituitary gland. After its cleavage from the parent molecule, proopiomelanocortin, beta-endorphin is circulated via the blood stream to interact with specific opioid receptors located throughout the body. The peptide produces analgesia by inhibiting the firing of peripheral somatosensory fibers. It also affects other senses, such as vision, hearing, and smell. Whereas the ability to increase ...

  9. Unexpected pattern of beta-globin mutations in beta-thalassaemia patients from northern Portugal

    OpenAIRE

    Cabeda, J.; Correia, C.; Estevinho, A.; Simões, C.; Amorim, M; L. Pinho; Justiça, B

    1999-01-01

    We characterized the genetic nature of beta-thalassaemia in northern Portugal. Of the 164 patients studied three were beta-thalassaemia major cases (one IVS-1-6/beta degrees 39 and two homozygous IVS-1-110). The analysis of the frequency of each mutation in the families revealed that the codon 6(-A) mutation was unexpectedly frequent (40%) and associated with the beta-globin haplotype E, and not with the usual European and North African CD6(-A) haplotypes. In contrast, the frequency of IVS-1-...

  10. Isotope Effects in the Bonds of beta-CrOOH and beta-CrOOD

    DEFF Research Database (Denmark)

    Nørlund Christensen, A.; Hansen, P.; Lehmann, M. S.

    1976-01-01

    Samples of orthorhombic chromium oxide hydroxide, beta -CrOOH, and the deuterated compound, beta -CrOOD, were prepared hydrothermally. The crystal structures were determined by powder profile refinement technique using neutron diffraction data. Unit cells are: beta -CrOOH: a equals 4. 862(2) A, b...... equals 4. 298(a) A, c equals 2. 995(1) A; beta -CrOOD: a equals 4. 873(5) A, b equals 4. 332(7) A, c equals 2. 963(2) A, with Z equals 2. The space group is P2//1nm or Pnnm....

  11. Toward beta cell replacement for diabetes.

    Science.gov (United States)

    Johannesson, Bjarki; Sui, Lina; Freytes, Donald O; Creusot, Remi J; Egli, Dieter

    2015-04-01

    The discovery of insulin more than 90 years ago introduced a life-saving treatment for patients with type 1 diabetes, and since then, significant progress has been made in clinical care for all forms of diabetes. However, no method of insulin delivery matches the ability of the human pancreas to reliably and automatically maintain glucose levels within a tight range. Transplantation of human islets or of an intact pancreas can in principle cure diabetes, but this approach is generally reserved for cases with simultaneous transplantation of a kidney, where immunosuppression is already a requirement. Recent advances in cell reprogramming and beta cell differentiation now allow the generation of personalized stem cells, providing an unlimited source of beta cells for research and for developing autologous cell therapies. In this review, we will discuss the utility of stem cell-derived beta cells to investigate the mechanisms of beta cell failure in diabetes, and the challenges to develop beta cell replacement therapies. These challenges include appropriate quality controls of the cells being used, the ability to generate beta cell grafts of stable cellular composition, and in the case of type 1 diabetes, protecting implanted cells from autoimmune destruction without compromising other aspects of the immune system or the functionality of the graft. Such novel treatments will need to match or exceed the relative safety and efficacy of available care for diabetes.

  12. Neoclassical transport in high {beta} tokamaks

    Energy Technology Data Exchange (ETDEWEB)

    Cowley, S.C.

    1992-12-01

    Neoclassical, transport in high {beta} large aspect ratio tokamaks is calculated. The variational method introduced by Rosenbluth, et al., is used to calculate the full Onsager matrix in the banana regime. These results are part of a continuing study of the high {beta} large aspect ratio equilibria introduced in Cowley, et al. All the neoclassical coefficients are reduced from their nominal low {beta} values by a factor ({var_epsilon}/q{sup 2}{beta}){sup {1/2}} II. This factor is the ratio of plasma volume in the boundary layer to the volume in the core. The fraction of trapped particles on a given flux surface (f{sub t}) is also reduced by this factor so that {approximately} {sub ({var_epsilon}}/q{sup 2}{beta}){sup {1/2}}. Special attention is given to the current equation, since this is thought to be relevant at low 3 and therefore may also be relevant at high {beta}. The bootstrap current term is found to exceed the actual current by a factor of the square root of the aspect ratio.

  13. Possible errors in assay for beta-glycosidase activity.

    OpenAIRE

    Chadwick, R W; Allison, J C; Talley, D L; George, S.E.

    1995-01-01

    Cecal homogenates were assayed for the enzymes beta-glucosidase, beta-glucuronidase, and beta-galactosidase. Anaerobic incubation with the addition of excess 3,4-dichloronitrobenzene, a substrate for nitroreductase, significantly increased the detection of the beta-glycosidase enzymes' activities.

  14. Continuous and Jump Betas: Implications for Portfolio Diversification

    Directory of Open Access Journals (Sweden)

    Vitali Alexeev

    2016-06-01

    Full Text Available Using high-frequency data, we decompose the time-varying beta for stocks into beta for continuous systematic risk and beta for discontinuous systematic risk. Estimated discontinuous betas for S&P500 constituents between 2003 and 2011 generally exceed the corresponding continuous betas. We demonstrate how continuous and discontinuous betas decrease with portfolio diversification. Using an equiweighted broad market index, we assess the speed of convergence of continuous and discontinuous betas in portfolios of stocks as the number of holdings increase. We show that discontinuous risk dissipates faster with fewer stocks in a portfolio compared to its continuous counterpart.

  15. Transforming growth factor-beta inhibition reduces progression of early choroidal neovascularization lesions in rats: P17 and P144 peptides.

    Directory of Open Access Journals (Sweden)

    Javier Zarranz-Ventura

    Full Text Available The purpose of this study was to assess the effects of transforming growth factor beta (TGF-β inhibitor peptides (P17 & P144 on early laser-induced choroidal neovascularization (LI-CNV lesions in rats, two weeks after laser CNV induction. Seventy-one Long Evans rats underwent diode laser application in an established LI-CNV model. Baseline fluorescein angiography (FA was performed 14 days following laser procedure, and treatments were administered 16 days post-laser application via different administration routes. Intravenous groups included control (IV-Control, P17 (IV-17, and P144 (IV-144 groups, whereas intravitreal groups included P17 (IVT-17, P144 (IVT-144, and a mixture of both peptides (IVT-17+144 (with fellow eyes receiving vehicle alone. CNV evolution was assessed using FA performed weekly for four weeks after treatment. Following sacrifice, VEGF, TGF-β, COX-2, IGF-1, PAI-1, IL-6, MMP-2, MMP-9, and TNF-α gene expression was assessed using RT-PCR. VEGF and p-SMAD2 protein levels were also assessed by western-blot, while MMP-2 activity was assessed with gelatin zymography. Regarding the FA analysis, the mean CNV area was lower from the 3(rd week in IVT-17 and IVT-144 groups, and also from the 2(nd week in IVT-17+144. Biochemical analysis revealed that gene expression was lower for VEGF and COX-2 genes in IV-17 and IV-144 groups, VEGF gene in IVT-17+144 group and MMP-2 gene in IVT-17 and IVT-144 groups. VEGF protein expression was also decreased in IV-17, IV-144, IVT-17 and IVT-144, whereas pSMAD-2 levels were lower in IV-17, IV-144 and IVT-17+144 groups. Zymogram analysis revealed decreased MMP-2 activity in IV-17, IV-144, IVT-17 and IVT-144 groups. These data suggest that the use of TGF-β inhibitor peptides (P17 & P144 decrease the development of early CNV lesions by targeting different mediators than those typically affected using current anti-angiogenic therapies. Its potential role in the treatment of early CNV appears promising

  16. Rheumatoid factors from patients with rheumatoid arthritis react with Des-Lys58-beta 2m, modified beta 2-microglobulin

    DEFF Research Database (Denmark)

    Williams, R C; Nissen, Mogens Holst; Malone, C C

    1993-01-01

    -cleaved beta 2m and Des-Lys58-beta 2m) appeared to parallel the previously determined beta 2m single amino acid specificities, in that RF showing strong reactivity with Lysine 58 also showed a significant diminished reactivity with the Des-Lys58-beta 2m lacking the critical lysine residue. The present...

  17. beta-adrenoceptor density in chronic infarcted myocardium : a subtype specific decrease of beta(1)-adrenoceptor density

    NARCIS (Netherlands)

    Anthonio, RL; Brodde, OE; van Veldhuisen, DJ; Crijns, HJGM; van Gilst, WH

    2000-01-01

    beta-adrenoceptor density is altered in different cardiac diseases. In heart failure beta-adrenoceptor density is down regulated but in acute myocardial ischemia beta-adrenoceptor density is up regulated. In hearts with myocardial infarction total beta-adrenoceptor density is decreased shortly after

  18. Characterization of beta-R1, a gene that is selectively induced by interferon beta (IFN-beta) compared with IFN-alpha.

    Science.gov (United States)

    Rani, M R; Foster, G R; Leung, S; Leaman, D; Stark, G R; Ransohoff, R M

    1996-09-13

    We report preliminary characterization of a gene designated beta-R1, which is selectively expressed in response to interferon beta (IFN-beta) compared with IFN-alpha. In human astrocytoma cells, beta-R1 was induced to an equivalent extent by 10 IU/mL IFN-beta or 2500 IU/mL IFN-alpha2. To address the mechanism of this differential response, we analyzed induction of the beta-R1 gene in fibrosarcoma cells and derivative mutant cells lacking components required for signaling by type I IFNs. beta-R1 was readily induced by IFN-beta in the parental 2fTGH cell line, but not by recombinant IFN-alpha2, IFN-alpha Con1, or a mixture of IFN-alpha subtypes. IFN-alpha8 induced beta-R1 weakly. beta-R1 was not induced by IFN-beta in mutant cell lines U2A, U3A, U4A, and U6A, which lack, respectively, p48, STAT1, JAK1, and STAT2. U5A cells, which lack the Ifnar 2.2 component of the IFN-alpha and -beta receptor, also failed to express beta-R1. U1A cells are partially responsive to IFN-beta and IFN-alpha8 but lacked beta-R1 expression, indicating that TYK2 protein is essential for induction of this gene. Taken together, these results suggest that the expression of beta-R1 in response to type I IFN requires IFN-stimulated gene factor 3 plus an additional component, which is more efficiently formed on induction by IFN-beta compared with IFN-alpha.

  19. Genetic analysis of beta1 integrin "activation motifs" in mice

    DEFF Research Database (Denmark)

    Czuchra, Aleksandra; Meyer, Hannelore; Legate, Kyle R;

    2006-01-01

    /beta tails, leading to tail separation and integrin activation. We analyzed mice in which we mutated the tyrosines of the beta1 tail and the membrane-proximal aspartic acid required for the salt bridge. Tyrosine-to-alanine substitutions abolished beta1 integrin functions and led to a beta1 integrin...... and the membrane-proximal salt bridge between alpha and beta1 tails have no apparent function under physiological conditions in vivo....

  20. Beta-Negative Binomial Process and Poisson Factor Analysis

    OpenAIRE

    Zhou, Mingyuan; Hannah, Lauren; Dunson, David; Carin, Lawrence

    2011-01-01

    A beta-negative binomial (BNB) process is proposed, leading to a beta-gamma-Poisson process, which may be viewed as a "multi-scoop" generalization of the beta-Bernoulli process. The BNB process is augmented into a beta-gamma-gamma-Poisson hierarchical structure, and applied as a nonparametric Bayesian prior for an infinite Poisson factor analysis model. A finite approximation for the beta process Levy random measure is constructed for convenient implementation. Efficient MCMC computations are...

  1. Beta Gyres in Global Analysis Fields

    Institute of Scientific and Technical Information of China (English)

    Sun-Hee KIM; H.Joe KWON; R.L.ELSBERRY

    2009-01-01

    A three-component decomposition is applied to global analysis data to show the existence of a beta gyre,which causes Tropical Cyclone (TC) to drift from a large-scale environmental steering current.Analyses from the Global Data Assimilation and Prediction System (GDAPS) of the Korea Meteorological Administration (KMA),the Global Forecast System (GFS) of NCEP,and the Navy Operational Global Atmospheric Prediction System (NOGAPS) are used in this study.The structure of the beta gyre obtained in our analyses is in good agreement with the theoretical structure,with a cyclonic circulation to the southwest of the TC center,an anticyclonic circulation to the northeast,and a ventilation flow directed northwestward near the center.The circulation of the beta gyre is strongest at the 850-hPa level where the cyclonically swirling primary circulation is strongest,and decreases with height,in a pyramid shape similar to the primary circulation.The individual structure of the beta gyre is case- and model-dependent.At a certain analysis time,one model may clearly reveal a well-defined beta gyre,but the other models may not.Within one model,the beta gyre may be well defined at some analysis times,but not at other times.The structure of the beta gyre in the analysis field is determined by the nature of the vortex initialization scheme and the model behavior during the 6-h forecast in the operational data assimilation cycle.

  2. Beta-adrenoceptors in obstetrics and gynecology.

    Science.gov (United States)

    Modzelewska, Beata

    2016-01-01

    One hundred and twenty years after the description of extracts from the adrenal medulla, the use of beta-blockers and beta-agonists evolved from antianginal drugs and tocolytics to ligand-directed signaling. Beta-blockers in the fields of obstetrics and gynecology have so far been limited to the consideration of continuing treatment of disorders of the cardiovascular system and other dysfunctions that started before pregnancy. Studies in recent years have shown that beta-adrenoceptor signaling might be crucial in carcinogenesis and metastasis, apoptosis and anoikis. On the other hand, the use of beta-adrenoceptor agonists in tocolysis is, as yet, the primary method for inhibiting premature uterine contractions. Unfortunately, the efficacy of current pharmacological treatment for the management of preterm labor is regularly questioned. Moreover, studies related to non-pregnant myometrium performed to date indicate that the rhythmic contractions of the uterus are required for menstruation and have an important role in human reproduction. In turn, abnormal uterine contractility has been linked to dysmenorrhea, a condition associated with painful uterine cramping. The benefits of the use of beta2-adrenoceptor agonists in dysmenorrhea are still unclear and should be balanced against a wide range of adverse effects recognized with this class of medication. The ideal tocolytic agent is one which is effective for the pregnant or non-pregnant woman but has no side effects on either the woman or the baby. Looking to the future with both caution and hope, the potential metamorphosis of beta3-adrenoceptor agonists from experimental tools into therapeutic drugs for tocolysis warrants attention.

  3. Oligomerization and toxicity of A{beta} fusion proteins

    Energy Technology Data Exchange (ETDEWEB)

    Caine, Joanne M., E-mail: Jo.Caine@csiro.au [CSIRO Materials Science and Engineering and the Preventive Health Flagship, Parkville, Victoria (Australia); Bharadwaj, Prashant R. [CSIRO Materials Science and Engineering and the Preventive Health Flagship, Parkville, Victoria (Australia); Centre for Excellence for Alzheimer' s Disease Research and Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Western Australia (Australia); Sankovich, Sonia E. [CSIRO Materials Science and Engineering and the Preventive Health Flagship, Parkville, Victoria (Australia); Ciccotosto, Giuseppe D. [The Department of Pathology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010 (Australia); Streltsov, Victor A.; Varghese, Jose [CSIRO Materials Science and Engineering and the Preventive Health Flagship, Parkville, Victoria (Australia)

    2011-06-10

    Highlights: {yields} We expressed amyloid-{beta} (A{beta}) peptide as a soluble maltose binding protein fusion (MBP-A{beta}42 and MBP-A{beta}16). {yields} The full length A{beta} peptide fusion, MBP-A{beta}42, forms oligomeric species as determined by SDS-PAGE gels, gel filtration and DLS. {yields} The MBP-A{beta}42, but not MBP-A{beta}16 or MBP alone, is toxic to both yeast and mammalian cells as determined by toxicity assays. -- Abstract: This study has found that the Maltose binding protein A{beta}42 fusion protein (MBP-A{beta}42) forms soluble oligomers while the shorter MBP-A{beta}16 fusion and control MBP did not. MBP-A{beta}42, but neither MBP-A{beta}16 nor control MBP, was toxic in a dose-dependent manner in both yeast and primary cortical neuronal cells. This study demonstrates the potential utility of MBP-A{beta}42 as a reagent for drug screening assays in yeast and neuronal cell cultures and as a candidate for further A{beta}42 characterization.

  4. Conformation, molecular packing and field effect mobility of regioregular beta,beta'-dihexylsexithiophiophene

    DEFF Research Database (Denmark)

    Kiriy, N.; Kiriy, A.; Bocharova, V.;

    2004-01-01

    ) V-1 s(-1), which is considerably less than the FEM of alpha,omega-DH6T. To understand the reason for such poor macroscopic electrical properties, the conformation and the molecular packing of beta,beta'-DH6T were systematically studied by means of UV-vis spectroscopy, scanning electron microscopy...

  5. Detrimental effects of beta-blockers in COPD - A concern for nonselective beta-blockers

    NARCIS (Netherlands)

    van der Woude, HJ; Zaagsma, J; Postma, DS; Winter, TH; van Hulst, M; Aalbers, R

    2005-01-01

    Introduction: beta-Blockers are known to worsen FEV1 and airway hyperresponsiveness (AHR) in patients with asthma. Both characteristics determine the outcome of COPD, a disease with frequent cardiac comorbidity requiring beta-blocker treatment. Design: A double-blind, placebo-controlled, randomized,

  6. BETA SPECTRA. I. Negatrons spectra; ESPECTROS BETA. I. Espectros simples de negatrones

    Energy Technology Data Exchange (ETDEWEB)

    Grau Malonda, A.; Garcia-Torano, E.

    1978-07-01

    Using the Fermi theory of beta decay, the beta spectra for 62 negatrons emitters have been computed introducing a correction factor for unique forbidden transitions. These spectra are plotted vs. energy, once normal i sed, and tabulated with the related Fermi functions. The average and median energies are calculated. (Author)

  7. Mrp2 is essential for estradiol-17 beta(beta-D-glucuronide)-induced cholestasis in rats

    NARCIS (Netherlands)

    Huang, LY; Smit, JW; Meijer, DKF; Vore, M

    2000-01-01

    The present study evaluates the roles of the multidrug resistance-1 P-glycoprotein, Mdr1a/1b, the bile salt export pump (Bsep), and the multidrug resistance-associated protein-2 (Mrp2) in mediating cholestasis induced by estradiol-17 beta(beta-D-glucuronide) (E(2)17G). Administration of [H-3]E(2)17G

  8. Regulation of glycogen synthase kinase-3{beta} (GSK-3{beta}) after ionizing radiation; Regulation der Glykogen Synthase Kinase-3{beta} (GSK-3{beta}) nach ionisierender Strahlung

    Energy Technology Data Exchange (ETDEWEB)

    Boehme, K.A.

    2006-12-15

    Glycogen Synthase Kinase-3{beta} (GSK-3{beta}) phosphorylates the Mdm2 protein in the central domain. This phosphorylation is absolutely required for p53 degradation. Ionizing radiation inactivates GSK-3{beta} by phosphorylation at serine 9 and in consequence prevents Mdm2 mediated p53 degradation. During the work for my PhD I identified Akt/PKB as the kinase that phosphorylates GSK-3{beta} at serine 9 after ionizing radiation. Ionizing radiation leads to phosphorylation of Akt/PKB at threonine 308 and serine 473. The PI3 Kinase inhibitor LY294002 completely abolished Akt/PKB serine 473 phosphorylation and prevented the induction of GSK-3{beta} serine 9 phosphorylation after ionizing radiation. Interestingly, the most significant activation of Akt/PKB after ionizing radiation occurred in the nucleus while cytoplasmic Akt/PKB was only weakly activated after radiation. By using siRNA, I showed that Akt1/PKBa, but not Akt2/PKB{beta}, is required for phosphorylation of GSK- 3{beta} at serine 9 after ionizing radiation. Phosphorylation and activation of Akt/PKB after ionizing radiation depends on the DNA dependent protein kinase (DNA-PK), a member of the PI3 Kinase family, that is activated by free DNA ends. Both, in cells from SCID mice and after knockdown of the catalytic subunit of DNA-PK by siRNA in osteosarcoma cells, phosphorylation of Akt/PKB at serine 473 and of GSK-3{beta} at serine 9 was completely abolished. Consistent with the principle that phosphorylation of GSK-3 at serine 9 contributes to p53 stabilization after radiation, the accumulation of p53 in response to ionizing radiation was largely prevented by downregulation of DNA-PK. From these results I conclude, that ionizing radiation induces a signaling cascade that leads to Akt1/PKBa activation mediated by DNA-PK dependent phosphorylation of serine 473. After activation Akt1/PKBa phosphorylates and inhibits GSK-3{beta} in the nucleus. The resulting hypophosphorylated form of Mdm2 protein is no longer

  9. Neutrinoless double beta decay from lattice QCD

    CERN Document Server

    Nicholson, Amy; Chang, Chia Cheng; Clark, M A; Joo, Balint; Kurth, Thorsten; Rinaldi, Enrico; Tiburzi, Brian; Vranas, Pavlos; Walker-Loud, Andre

    2016-01-01

    While the discovery of non-zero neutrino masses is one of the most important accomplishments by physicists in the past century, it is still unknown how and in what form these masses arise. Lepton number-violating neutrinoless double beta decay is a natural consequence of Majorana neutrinos and many BSM theories, and many experimental efforts are involved in the search for these processes. Understanding how neutrinoless double beta decay would manifest in nuclear environments is key for understanding any observed signals. In these proceedings we present an overview of a set of one- and two-body matrix elements relevant for experimental searches for neutrinoless double beta decay, describe the role of lattice QCD calculations, and present preliminary lattice QCD results.

  10. Estimating beta-mixing coefficients via histograms

    CERN Document Server

    McDonald, Daniel J; Schervish, Mark

    2011-01-01

    The literature on statistical learning for time series often assumes asymptotic independence or "mixing" of data sources. Beta-mixing has long been important in establishing the central limit theorem and invariance principle for stochastic processes; recent work has identified it as crucial to extending results from empirical processes and statistical learning theory to dependent data, with quantitative risk bounds involving the actual beta coefficients. There is, however, presently no way to actually estimate those coefficients from data; while general functional forms are known for some common classes of processes (Markov processes, ARMA models, etc.), specific coefficients are generally beyond calculation. We present an l1-risk consistent estimator for the beta-mixing coefficients, based on a single stationary sample path. Since mixing coefficients involve infinite-order dependence, we use an order-d Markov approximation. We prove high-probability concentration results for the Markov approximation and show...

  11. Tevatron B0 low beta tuning report

    International Nuclear Information System (INIS)

    A detailed study of the low beta insertion for the B0 experimental area has been carried out and is described below. This insertion is similar to the Type C low beta previously report, anti p Note 169, although some changes have been made to the quadrupole lengths and positions. This insertion is designated Type E. The purpose of the study was to see if it is possible to turn the insertion on in a smooth and continuous manner and tune the insertion to a value of β* of less than one meter while maintaining the overall tune of the j Tevatron to a constant value. This was found to be possible. An examination of chromaticity corrections for the Tevatron with the low beta insertion on in various configurations was also undertaken

  12. Protein-binding RNA aptamers affect molecular interactions distantly from their binding sites

    DEFF Research Database (Denmark)

    Dupont, Daniel M; Thuesen, Cathrine K; Bøtkjær, Kenneth A;

    2015-01-01

    Nucleic acid aptamer selection is a powerful strategy for the development of regulatory agents for molecular intervention. Accordingly, aptamers have proven their diligence in the intervention with serine protease activities, which play important roles in physiology and pathophysiology. Nonetheless...... potential, both binding to the serine protease urokinase-type plasminogen activator (uPA). We determine the subsequent impact of aptamer binding on the well-established molecular interactions (plasmin, PAI-1, uPAR, and LRP-1A) controlling uPA activities. One of the aptamers (upanap-126) binds to the area...... around the C-terminal α-helix in pro-uPA, while the other aptamer (upanap-12) binds to both the β-hairpin of the growth factor domain and the kringle domain of uPA. Based on the mapping studies, combined with data from small-angle X-ray scattering analysis, we construct a model for the upanap-12:pro...

  13. BETASCAN: probable beta-amyloids identified by pairwise probabilistic analysis.

    Directory of Open Access Journals (Sweden)

    Allen W Bryan

    2009-03-01

    Full Text Available Amyloids and prion proteins are clinically and biologically important beta-structures, whose supersecondary structures are difficult to determine by standard experimental or computational means. In addition, significant conformational heterogeneity is known or suspected to exist in many amyloid fibrils. Recent work has indicated the utility of pairwise probabilistic statistics in beta-structure prediction. We develop here a new strategy for beta-structure prediction, emphasizing the determination of beta-strands and pairs of beta-strands as fundamental units of beta-structure. Our program, BETASCAN, calculates likelihood scores for potential beta-strands and strand-pairs based on correlations observed in parallel beta-sheets. The program then determines the strands and pairs with the greatest local likelihood for all of the sequence's potential beta-structures. BETASCAN suggests multiple alternate folding patterns and assigns relative a priori probabilities based solely on amino acid sequence, probability tables, and pre-chosen parameters. The algorithm compares favorably with the results of previous algorithms (BETAPRO, PASTA, SALSA, TANGO, and Zyggregator in beta-structure prediction and amyloid propensity prediction. Accurate prediction is demonstrated for experimentally determined amyloid beta-structures, for a set of known beta-aggregates, and for the parallel beta-strands of beta-helices, amyloid-like globular proteins. BETASCAN is able both to detect beta-strands with higher sensitivity and to detect the edges of beta-strands in a richly beta-like sequence. For two proteins (Abeta and Het-s, there exist multiple sets of experimental data implying contradictory structures; BETASCAN is able to detect each competing structure as a potential structure variant. The ability to correlate multiple alternate beta-structures to experiment opens the possibility of computational investigation of prion strains and structural heterogeneity of amyloid

  14. beta2-Agonists at the Olympic Games.

    Science.gov (United States)

    Fitch, Kenneth D

    2006-01-01

    The different approaches that the International Olympic Committee (IOC) had adopted to beta2-agonists and the implications for athletes are reviewed by a former Olympic team physician who later became a member of the Medical Commission of the IOC (IOC-MC). Steadily increasing knowledge of the effects of inhaled beta2-agonists on health, is concerned with the fact that oral beta2-agonists may be anabolic, and rapid increased use of inhaled beta2-agonists by elite athletes has contributed to the changes to the IOC rules. Since 2001, the necessity for athletes to meet IOC criteria (i.e., that they have asthma and/or exercise-induced asthma [EIA]) has resulted in improved management of athletes. The prevalence of beta2-agonist use by athletes mirrors the known prevalence of asthma symptoms in each country, although athletes in endurance events have the highest prevalence. The age-of-onset of asthma/EIA in elite winter athletes may be atypical. Of the 193 athletes at the 2006 Winter Olympics who met th IOC's criteria, only 32.1% had childhood asthma and 48.7% of athletes reported onset at age 20 yr or older. These findings lead to speculation that years of intense endurance training may be a causative factor in bronchial hyperreactivity. The distinction between oral (prohibited in sports) and inhaled salbutamol is possible, but athletes must be warned that excessive use of inhaled salbutamol can lead to urinary concentrations similar to those observed after oral administration. This article provides justification that athletes should provide evidence of asthma or EIA before being permitted to use inhaled beta2-agonists. PMID:17085798

  15. A New Step up,a Double-digit Reward

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    A detailed report on the performance of China garment exports and imports in 2005 Surfing on the waves of the RMB revaluation, the unstableness of raw material prices and the trade disagreements with the EU and US, the hardworking China garment and accessory industry got its repayment of $75.52 billion for foreign trade in 2005, hiked 19.6% against 2004. Garment and accessory exports made 73.88 billion US dollar and $1.62 billion in imports, it also achieved US 72.2 billion of trade surplus and took up more than half of the share in the entire China textile foreign trade value in 2005.

  16. Beta/gamma test problems for ITS

    International Nuclear Information System (INIS)

    The Integrated Tiger Series of Coupled Electron/Photon Monte Carlo Transport Codes (ITS 3.0, PC Version) was used at Oak Ridge National Laboratory (ORNL) to compare with and extend the experimental findings of the beta/gamma response of selected health physics instruments. In order to assure that ITS gives correct results, several beta/gamma problems have been tested. ITS was used to simulate these problems numerically, and results for each were compared to the problem's experimental or analytical results. ITS successfully predicted the experimental or analytical results of all tested problems within the statistical uncertainty inherent in the Monte Carlo method

  17. Helicity and nuclear $\\beta$ decay correlations

    CERN Document Server

    Hong, Ran; García, Alejandro

    2016-01-01

    We present simple derivations of nuclear $\\beta$-decay correlations with an emphasis on the special role of helicity. This provides a good opportunity to teach students about helicity and chirality in particle physics through exercises using simple aspects of quantum mechanics. In addition, this paper serves as an introduction to nuclear $\\beta$-decay correlations from both a theoretical and experimental vantage. This article can be used to introduce students to ongoing experiments searching for hints of new physics in the low-energy precision frontier.

  18. Volume Effects in Discrete beta functions

    CERN Document Server

    Liu, Yuzhi; Zou, Haiyuan

    2011-01-01

    We calculate discrete beta functions corresponding to the two-lattice matching for the 2D O(N) models and Dyson's hierarchical model. We describe and explain finite-size effects such as the appearance of a nontrivial infrared fixed point that goes to infinity at infinite volume or the merging of an infrared and an ultraviolet fixed point. We present extensions of the RG flows to the complex coupling plane. We discuss the possibility of constructing a continuous beta function from the discrete one by using functional conjugation methods. We briefly discuss the relevance of these findings for the search of nontrivial fixed points in multiflavor lattice gauge theory models.

  19. Population screening for beta-thalassaemia.

    Science.gov (United States)

    Flatz, S D; Flatz, G

    1980-09-01

    The graphic recording of time to 50% haemolysis in a glycerine-saline solution is a simple, reproducible method of determining erythrocyte osmotic fragility. Studies on a normal population yielded an upper limit of normal of 90 s. In 250 healthy males from Northern Thailand all 19 with beta-thalassaemia minor had abnormal osmotic indices, and the value of the test was confirmed in beta-thalassaemia heterozygotes in Europe. Of 23 patients with iron deficiency 18 had abnormal osmotic indices. However, this is not thought likely to be a significant source of false positives in the screening of populations at risk of haemoglobinopathies but in whom iron deficiency is rare.

  20. Survey instrument response to beta radiations

    International Nuclear Information System (INIS)

    Available survey instruments do not have the beta measurement characteristics needed for accurate dose rate assessments. Such instruments have severe angular and energy dependence. In addition, beta measurements often require corrections for the source geometry response of the detector to permit accurate assessments. Studies were performed to characterize present instruments and to determine optimum characteristics for a field instrument. Results of the studies were used to specify and procure an instrument with improved characteristics. The purpose of this paper is to describe the results of the studies and the design of the instrument

  1. Survey instrument response to beta radiations

    International Nuclear Information System (INIS)

    Available survey instruments do not have the beta measurement characteristics needed for accurate dose rate assessments. Such instruments have severe angular and energy dependence. In addition, beta measurements often require corrections for the source geometry response of the detector to permit accurate assessments. Studies were performed to characterize present instruments and to determine optimum characteristics for a field instrument. Results of the studies were used to specify and procure an instrument with improved characteristics. The purpose of this paper is to describe the results of the studies and the design of the instrument. 6 refs., 6 figs., 4 tabs

  2. Why search for double beta decay?

    International Nuclear Information System (INIS)

    Searching for neutrinoless double beta decay is the only known practical method for trying to determine whether neutrinos are their own antiparticles. The theoretical motivation for supposing that they may indeed be their own antiparticles is described. The reason that it is so difficult to ascertain experimentally whether they are or are not is explained, as is the special sensitivity of neutrinoless double beta decay. The potential implications of the observation of this reaction for neutrino mass and for the physics of neutrinos is discussed

  3. Supermultiplet of $\\beta-$deformations from twistors

    CERN Document Server

    Milián, Segundo P

    2016-01-01

    We consider the supermultiplet of linearized beta-deformation of $\\mathcal{N}=4$ Super Yang-Mills(SYM). It was previously studied on the gravitational side. We study the supermultiplet of beta-deformations on the field theory side and we compare two finite-dimensional representations of $psl(4|4,\\bf{R})$ algebra. We show that they are related by an intertwining operator. We develop a twistor-based approach which could be useful for studying other finite-dimensional and nonunitary representations in AdS/CFT correspondence.

  4. Symmetry violations in nuclear and neutron $\\beta$ decay

    CERN Document Server

    Vos, K K; Timmermans, R G E

    2015-01-01

    The role of $\\beta$ decay as a low-energy probe of physics beyond the Standard Model is reviewed. Traditional searches for deviations from the Standard Model structure of the weak interaction in $\\beta$ decay are discussed in the light of constraints from the LHC and the neutrino mass. Limits on the violation of time-reversal symmetry in $\\beta$ decay are compared to the strong constraints from electric dipole moments. Novel searches for Lorentz symmetry breaking in the weak interaction in $\\beta$ decay are also included, where we discuss the unique sensitivity of $\\beta$ decay to test Lorentz invariance. We end with a roadmap for future $\\beta$-decay experiments.

  5. Transforming growth factor-beta (TGF-beta) and programmed cell death in the vertebrate retina.

    Science.gov (United States)

    Duenker, Nicole

    2005-01-01

    Programmed cell death (PCD) is a precisely regulated phenomenon essential for the homeostasis of multicellular organisms. Developmental systems, particularly the nervous system, have provided key observations supporting the physiological role of PCD. We have recently shown that transforming growth factor-beta (TGF-beta) plays an important role in mediating ontogenetic PCD in the nervous system. As part of the central nervous system the developing retina serves as an ideal model system for investigating apoptotic processes during neurogenesis in vivo as it is easily accessible experimentally and less complex due to its limited number of different neurons. This review summarizes data indicating a pivotal role of TGF-beta in mediating PCD in the vertebrate retina. The following topics are discussed: expression of TGF-beta isoforms and receptors in the vertebrate retina, the TGF-beta signaling pathway, functions and molecular mechanisms of PCD in the nervous system, TGF-beta-mediated retinal apoptosis in vitro and in vivo, and interactions of TGF-beta with other pro- and anti-apoptotic factors.

  6. Nuclear Matrix Elements for the $\\beta\\beta$ Decay of the $^{76}$Ge

    CERN Document Server

    Brown, B A; Horoi, M

    2015-01-01

    The nuclear matrix elements for two-neutrino double-beta (2 n$\\beta\\beta$ ) and zero-neutrino double-beta (0 n$\\beta\\beta$) decay of 76 Ge are evaluated in terms of the configuration interaction (CI), quasiparticle random phase approximation (QRPA) and interacting boson model (IBM) methods. We show that the decomposition of the matrix elements in terms of interemediate states in 74 Ge is dominated by ground state of this nucleus. We consider corrections to the CI results that arise from configurations admixtures involving orbitals out-side of the CI configuration space by using results from QRPA, many-body-perturbation theory, and the connections to related observables. The CI two-neutrino matrix element is reduced due to the inclusion of spin-orbit partners, and to many-body correlations connected with Gamow-Teller beta decay. The CI zero-neutrino matrix element for the heavy neutrino is enhanced due to particle-particle correlations that are connected with the odd-even oscillations in the nuclear masse...

  7. Human liver alcohol dehydrogenase. 1. The primary structure of the beta 1 beta 1 isoenzyme.

    Science.gov (United States)

    Hempel, J; Bühler, R; Kaiser, R; Holmquist, B; de Zalenski, C; von Wartburg, J P; Vallee, B; Jörnvall, H

    1984-12-17

    Determination of the amino acid sequence of the beta 1 subunit from the class I (pyrazole-sensitive) human liver alcohol dehydrogenase isoenzyme beta 1 beta 1 revealed a 373-residue structure differing at 48 positions (including a gap) from that of the subunit of the well studied horse liver alcohol dehydrogenase EE isoenzyme. The structure deduced is compatible with known differences in composition, ultraviolet absorbance, electrophoretic mobility and catalytic properties between the horse and human enzymes. All zinc-liganding residues of the horse E subunit are strictly conserved in the human beta 1 subunit, despite an earlier report of a mutation involving Cys-46. This residue therefore remains conserved in all known alcohol dehydrogenase structures. However, the total cysteine content of the beta 1 structure is raised from 14 in the subunit of the horse enzyme to 15 by a Tyr----Cys exchange. Most exchanges are on the surface of the molecule and of a well conserved nature. Substitutions close to the catalytic centre are of interest to explain the altered substrate specificity and different catalytic activity of the beta 1 homodimer. Functionally, a Ser----Thr exchange at position 48 appears to be of special importance, since Thr-48 in beta 1 instead of Ser-48 in the horse enzyme can restrict available space. Four other substitutions also line the active-site pocket, and appear to constitute partly compensated exchanges. PMID:6391920

  8. Topical beta-Blockers and Mortality

    NARCIS (Netherlands)

    Muskens, Rogier P. H. M.; Wolfs, Roger C. W.; Wittenian, Jacqueline C. M.; Hofman, Albert; de Jong, Paulus T. V. M.; Stricker, Bruno H. C.; Jansonius, Nomdo M.

    2008-01-01

    Purpose: To study the associations between long-term and short-term use of topical beta-blockers and mortality. Design: Prospective population-based cohort study. Participants: To examine long-term effects, 3842 participants aged 55 years and older were recruited. To examine short-term effects, 484

  9. Semiconductor detectors and double beta decay

    International Nuclear Information System (INIS)

    The underlying theory of double beta decay is discussed as well as some experimental observations. A class of second generation 76Ge detector experiments is then discussed. The design and physics considerations involved in the system used by LBL are explained, particularly the means of rejecting background activity. 24 references, 18 figures, 3 tables

  10. Herwig++ 2.0beta Release Note

    OpenAIRE

    Gieseke, Stefan; Grellscheid, D.; Ribon, Alberto; Richardson, P.; Seymour, Michael H.; Stephens, Phil; Webber, Bryan R

    2006-01-01

    A new release of the Monte Carlo program Herwig++ (version 2.0beta) is now available. The main new feature is the extension of the program to include simple hadron-hadron processes including the initial-state parton shower.

  11. Average beta measurement in EXTRAP T1

    International Nuclear Information System (INIS)

    Beginning with the ideal MHD pressure balance equation, an expression for the average poloidal beta, ΒΘ, is derived. A method for unobtrusively measuring the quantities used to evaluate ΒΘ in Extrap T1 is described. The results if a series of measurements yielding ΒΘ as a function of externally applied toroidal field are presented. (author)

  12. Characterization of a Commercial Silicon Beta Cell

    Energy Technology Data Exchange (ETDEWEB)

    Foxe, Michael P. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hayes, James C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Mayer, Michael F. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); McIntyre, Justin I. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Sivels, Ciara B. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Suarez, Rey [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-03-31

    Silicon detectors are of interest for the verification of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) due to their enhanced energy resolution compared to plastic scintillators beta cells. Previous work developing a figure-of-merit (FOM) for comparison of beta cells suggests that the minimum detectable activity (MDA) could be reduced by a factor of two to three with the use of silicon detectors. Silicon beta cells have been developed by CEA (France) and Lares Ltd. (Russia), with the PIPSBox developed by CEA being commercially available from Canberra for approximately $35k, but there is still uncertainty about the reproducibility of the capabilities in the field. PNNL is developing a high-resolution beta-gamma detector system in the shallow underground laboratory, which will utilize and characterize the operation of the PIPSBox detector. Throughout this report, we examine the capabilities of the PIPSBox as developed by CEA. The lessons learned through the testing and use of the PIPSBox will allow PNNL to strategically develop a silicon detector optimized to better suit the communities needs in the future.

  13. Multiple nerve palsies in beta thalassaemia major.

    OpenAIRE

    Lamabadusuriya, S. P.

    1989-01-01

    A patient with beta thalassaemia major is described who developed a lower motor neurone facial nerve palsy on the left side, together with a phrenic nerve palsy on the same side, during the course of the illness. This complication has not been reported before in haemoglobinopathies.

  14. Association behavior of native beta-lactoglobulin

    DEFF Research Database (Denmark)

    Verheul, M.; Pedersen, J.S.; Roefs, S.P.F.M.;

    1999-01-01

    The association behavior of beta-lactoglobulin has been studied by small-angle neutron scattering as a function of protein concentration, temperature, pH, and NaCl concentration of the solution. By indirect Fourier transformation of the spectra, pair-distance distribution functions for the variou...

  15. Sources of beta cells inside the pancreas.

    Science.gov (United States)

    De Groef, Sofie; Staels, Willem; Van Gassen, Naomi; Lemper, Marie; Yuchi, Yixing; Sojoodi, Mozhdeh; Bussche, Leen; Heremans, Yves; Leuckx, Gunter; De Leu, Nico; Van de Casteele, Mark; Baeyens, Luc; Heimberg, Harry

    2016-09-01

    The generation of beta(-like) cells to compensate for their absolute or relative shortage in type 1 and type 2 diabetes is an obvious therapeutic strategy. Patients first received grafts of donor islet cells over 25 years ago, but this procedure has not become routine in clinical practice because of a donor cell shortage and (auto)immune problems. Transplantation of differentiated embryonic and induced pluripotent stem cells may overcome some but not all the current limitations. Reprogramming exocrine cells towards functional beta(-like) cells would offer an alternative abundant and autologous source of beta(-like) cells. This review focuses on work by our research group towards achieving such a source of cells. It summarises a presentation given at the 'Can we make a better beta cell?' symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Amin Ardestani and Kathrin Maedler, DOI: 10.1007/s00125-016-3892-9 , and by Heiko Lickert and colleagues, DOI: 10.1007/s00125-016-3949-9 ) and a commentary by the Session Chair, Shanta Persaud (DOI: 10.1007/s00125-016-3870-2 ). PMID:27053238

  16. beta-decay of O-13

    NARCIS (Netherlands)

    Knudsen, HH; Fynbo, HOU; Borge, MJG; Boutami, R; Dendooven, P; Diget, CA; Eronen, T; Fox, S; Fraile, LM; Fulton, B; Huikary, J; Jeppesen, HB; Jokinen, AS; Jonson, B; Kankainen, A; Moore, [No Value; Nieminen, A; Nyman, G; Penttila, H; Riisager, K; Rinta-Antila, S; Tengblad, O; Wang, Y; Wilhelmsen, K; Aysto, J

    2005-01-01

    The beta decay of O-13 has been studied at the IGISOL facility of the Jyvaskyla accelerator centre (Finland). By developing a low-energy isotope-separated beam of O-13 and using a modern segmented charged-particle detector array an improved measurement of the delayed proton spectrum was possible. Pr

  17. Beta-glucuronidase-mediated drug release

    NARCIS (Netherlands)

    Boven, E; Scheeren, HW; Haisma, HJ; Pinedo, HM

    2002-01-01

    The selective activation of a relatively non-toxic prodrug by an enzyme present only in the tumour should enhance the drug concentration at the tumour site and result in a better anti-tumour effect and a reduction in systemic toxicity as compared to conventional chemotherapy. beta-Glucuronidase is s

  18. LHC dijet constraints on double beta decay

    CERN Document Server

    Helo, J C

    2015-01-01

    We use LHC dijet data to derive constraints on neutrinoless double beta decay. Upper limits on cross sections for the production of "exotic" resonances, such as a right-handed W boson or a diquark, can be converted into lower limits on the double beta decay half-life for fixed choices of other parameters. Constraints derived from run-I data are already surprisingly strong and complementary to results from searches using same-sign dileptons plus jets. For the case of the left-right symmetric model, in case no new resonance is found in future runs of the LHC and assuming $g_L=g_R$, we estimate a lower limit on the double beta decay half-live larger than $10^{27}$ ys can be derived from future dijet data, except in the window of relatively light right-handed neutrino masses in the range $0.5$ MeV to $50$ GeV. Part of this mass window will be tested in the upcoming SHiP experiment. We also discuss current and future limits on possible scalar diquark contributions to double beta decay that can be derived from dije...

  19. Frameshift mutation events in beta-glucosidases.

    Science.gov (United States)

    Rojas, Antonio; Garcia-Vallvé, Santiago; Montero, Miguel A; Arola, Lluís; Romeu, Antoni

    2003-09-18

    Compensated frameshift mutation is a modification of the reading frame of a gene that takes place by way of various molecular events. It appears to be a widespread event that is only observed when homologous amino acid and nucleodotide sequences are compared. To identify these mutation events, the sequence analysis rationale was based on the search for short regions that would have much lower degrees of conservation in protein, but not in DNA, in well-conserved beta-glucosidase families. We have restricted our study to a seed set of sequences of O-glycoside hydrolase families 1 and 3. We found compensated frameshift mutation in the family of 1 beta-glucosidases for the Erwinia herbicola, Cellulomonas fimi, and (non-cyanogenic) Trifolium repens gene sequences, and in the family of 3 beta-glucosidases for the Clostridium thermocellum and Clostridium stercorarium gene sequences. By computational treatment, the observed mutation events in the gene frameshifting sub-sequence have been neutralised. Each nucleotide insertion must be eliminated and each nucleotide deletion must be substituted by the symbol N (any nucleotide). When the frameshifting fragments of the amino acid sequences were substituted by the computationally neutralised subsequences, the beta-glucosidase alignments were improved. We also discuss the structural implications of the compensated frameshift mutations events. PMID:14527732

  20. Three loop QCD MOM beta-functions

    CERN Document Server

    Gracey, J A

    2011-01-01

    We present the full expressions for the QCD beta-function in the MOMggg, MOMq and MOMh renormalization schemes at three loops for an arbitrary colour group in the Landau gauge. The results for all three schemes are in very good agreement with the SU(3) numerical estimates provided by Chetyrkin and Seidensticker.

  1. Binding capacity of a barley beta-D-glucan to the beta-glucan recognition molecule dectin-1.

    Science.gov (United States)

    Tada, Rui; Adachi, Yoshiyuki; Ishibashi, Ken-ichi; Tsubaki, Kazufumi; Ohno, Naohito

    2008-02-27

    To clarify whether barley beta-glucans exhibit their biological effects via binding to dectin-1, a pivotal receptor for beta-1,3-glucan, the structure of barley beta-glucan E70-S (BBG-70) was unambiguously investigated by NMR spectroscopy and studied for its binding capacity and specificity to dectin-1 by ELISA. NMR spectroscopy confirmed that BBG-70 contains two different linkage glucans, namely, alpha-glucan and beta-glucan, which are not covalently attached to one another. Beta-glucan within BBG-70 is a linear mixed-linkage beta-glucan composed of 1,3- and 1,4-beta-D-glucopyranose residues but does not contain the continuous 1,3-linkage. Competitive ELISA revealed that highly purified barley beta-glucan E70-S (pBBG-70) inhibits the binding of soluble dectin-1 to sonifilan (SPG), a beta-1,3-glucan, although at a concentration higher than that of SPG and laminarin. It was found that barley beta-glucan can be recognized by dectin-1, implying that barley beta-glucan might, at least in part, exhibit its biological effects via the recognition by dectin-1 of the ligand sugar structure, which may be formed by 1,3-beta- and 1,4-beta-glucosyl linkage. PMID:18205312

  2. Universality in Chiral Random Matrix Theory at $\\beta =1$ and $\\beta =4$

    CERN Document Server

    Sener, M K

    1998-01-01

    In this paper the kernel for spectral correlation functions of the invariant chiral random matrix ensembles with real ($\\beta =1$) and quaternion real ($\\beta = 4$) matrix elements is expressed in terms of the kernel of the corresponding complex Hermitean random matrix ensembles ($\\beta=2$). Such identities are exact in case of a Gaussian probability distribution and, under certain smoothness assumptions, they are shown to be valid asymptotically for an arbitrary finite polynomial potential. They are proved by means of a construction proposed by Brézin and Neuberger. Microscopic universality for all three chiral ensembles then follows from universal behavior for $\\beta =2$ both at the hard edge (shown by Akemann, Damgaard, Magnea and Nishigaki) and at the soft edge of the spectrum (shown by Kanzieper and Freilikher).

  3. RESEARCH OF BETA AS ADEQUATE RISK MEASURE-IS BETA STILL ALIVE?

    Directory of Open Access Journals (Sweden)

    Ante Perković

    2011-02-01

    Full Text Available The capital asset pricing model (CAPM is one of the most important models in financial economics and it has a long history of theoretical and empirical investigations. The main underlying concept of the CAPM model is that assets with a high risk (high beta should earn a higher return than assets with a low risk (low beta and vice versa. The implication which can be drawn out of this is that all assets with a beta above zero bear some risk and therefore their expected return is above the return of the risk-free rate. In this research observation on monthly stock prices on Croatian stock market from January 1st 2005 until December 31st 2009 is used to form our sample. CROBEX index is used as proxy of the market portfolio. The results demonstrate that beta can not be trusted in making investment decisions and rejects the validity of the whole CAPM model on Croatian stock market.

  4. A guide to 17beta-hydroxysteroid dehydrogenases.

    Science.gov (United States)

    Adamski, J; Jakob, F J

    2001-01-22

    17beta-Hydroxysteroid dehydrogenases (17beta-HSD) are pivotal in controlling the biological potency of steroid hormones by catalyzing oxidation or reduction at position 17. Several 17beta-HSDs may as well metabolize further substrates including alcohols, bile acids, fatty acids and retinols. This review summarizes recent progress in the field of 17beta-HSD research provides an update of nomenclature. PMID:11165003

  5. Neutrinoless $\\beta\\beta$ decay nuclear matrix elements in an isotopic chain

    CERN Document Server

    Rodríguez, Tomás R

    2012-01-01

    We analyze nuclear matrix elements (NME) of neutrinoless double beta decay calculated for the Cadmium isotopes. Energy density functional methods including beyond mean field effects such as symmetry restoration and shape mixing are used. Strong shell effects are found associated to the underlying nuclear structure of the initial and final nuclei. Furthermore, we show that NME for two-neutrino double beta decay evaluated in the closure approximation, $M^{2\

  6. Interleukin-1 beta (IL-1 beta) induces thrombocytosis in mice: Possible implication of IL-6

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, H.; Ishibashi, T.; Shikama, Y.; Okano, A.; Akiyama, Y.; Uchida, T.; Maruyama, Y. (Fukushima Medical College (Japan))

    1990-12-15

    We administered recombinant human interleukin-1 beta (IL-1 beta), the common mediator of inflammation process, to C57B1/6 male mice (0.5 microgram, every 12 hours over five times) intraperitoneally and consequently induced a remarkable thrombocytosis. Day 1 was designated as the following day of the last injection in the morning. A significant thrombocytosis was observed on days 1 through 5 with a peak on day 2 (162 +/- 9 x 10(4)/mm3) compared with the control mice injected with heated IL-1 beta (101 +/- 11 x 10(4)/mm3). A striking increase in mean size of marrow megakaryocytes was noted on days 1 and 2. The incorporation of 75Se-selenomethionine into circulating platelets as a measure of platelet production was about 2.3 times higher in IL-1 beta-treated mice than in control mice. To determine which factor(s) is responsible for elicited thrombocytosis, the in vitro studies and bioassays for several hematopoietic factors were performed. IL-1 beta by itself did not stimulate megakaryocytopoiesis in vitro, suggesting that the thrombocytosis is attributed to other factor(s) via IL-1 beta stimulation. Serum colony-stimulating factor (CSF) activity after a single IL-1 beta (0.5 microgram) injection, monitored by colony assay with 10% tested serum, peaked at 3 hours. Formed colonies were mostly granulocyte (G) and granulocyte-macrophage (GM)-types, and studies using rabbit anti-mouse GM-CSF serum or using human marrow as target cells showed that the CSF activity of the tested serum consisted of, at least, GM-CSF and G-CSF. Addition of IL-3 concomitantly with the tested serum gave rise to a greater number of megakaryocytic colonies. Serum IL-3, monitored by IL-3-dependent cell line 32D clone 5, and erythropoietin activities were not detected at serum level in IL-1 beta-treated mice.

  7. Interleukin-1 beta (IL-1 beta) induces thrombocytosis in mice: Possible implication of IL-6

    International Nuclear Information System (INIS)

    We administered recombinant human interleukin-1 beta (IL-1 beta), the common mediator of inflammation process, to C57B1/6 male mice (0.5 microgram, every 12 hours over five times) intraperitoneally and consequently induced a remarkable thrombocytosis. Day 1 was designated as the following day of the last injection in the morning. A significant thrombocytosis was observed on days 1 through 5 with a peak on day 2 (162 +/- 9 x 10(4)/mm3) compared with the control mice injected with heated IL-1 beta (101 +/- 11 x 10(4)/mm3). A striking increase in mean size of marrow megakaryocytes was noted on days 1 and 2. The incorporation of 75Se-selenomethionine into circulating platelets as a measure of platelet production was about 2.3 times higher in IL-1 beta-treated mice than in control mice. To determine which factor(s) is responsible for elicited thrombocytosis, the in vitro studies and bioassays for several hematopoietic factors were performed. IL-1 beta by itself did not stimulate megakaryocytopoiesis in vitro, suggesting that the thrombocytosis is attributed to other factor(s) via IL-1 beta stimulation. Serum colony-stimulating factor (CSF) activity after a single IL-1 beta (0.5 microgram) injection, monitored by colony assay with 10% tested serum, peaked at 3 hours. Formed colonies were mostly granulocyte (G) and granulocyte-macrophage (GM)-types, and studies using rabbit anti-mouse GM-CSF serum or using human marrow as target cells showed that the CSF activity of the tested serum consisted of, at least, GM-CSF and G-CSF. Addition of IL-3 concomitantly with the tested serum gave rise to a greater number of megakaryocytic colonies. Serum IL-3, monitored by IL-3-dependent cell line 32D clone 5, and erythropoietin activities were not detected at serum level in IL-1 beta-treated mice

  8. Effect of heating rate on temperature of titanium alloy (. cap alpha. +. beta. ). -->. beta. transformaton

    Energy Technology Data Exchange (ETDEWEB)

    Gridnev, V.N.; Ivasishin, O.M.; Markovskij, P.E. (AN Ukrainskoj SSR, Kiev. Inst. Metallofiziki)

    1985-01-01

    The effect of doping of two-phase titaniums alloys and morphology of initial structure on the Tsub(t) temperature shift value of (..cap alpha..+..beta..)..--> beta.. transformation depending on heating rate is investigated. It has been found that the Tsub(t) shift occurs in the strictly determined temperature range depending on chemical alloy composition. The Tsub(t) shift is directly proportional to the Ksub(..beta..) coefficient applied as a quantitative alloying characteristic as well as a dimensional factor equal either to the plate thickness or the ..cap alpha..-phase globule diameter depending on the type of initial structure. In the limits of this temperature range the (..cap alpha..+..beta..)..--> beta..-transformation occurs completely according to the diffusion mechanism. The critical heating rate at which maximum permissible Tsub(t) value is attained and above which its stabilization is observed is determined by the same parameters - the alloy doping degree characterized by the Ksub(..beta..) coefficient and the ..cap alpha..-phase crystal dimensions in the initial structure.

  9. Mechanisms of beta-amyloid neurotoxicity : Perspectives of pharmacotherapy

    NARCIS (Netherlands)

    Harkany, T; Abraham, [No Value; Konya, C; Nyakas, C; Zarandi, M; Penke, B; Luiten, PGM

    2000-01-01

    One of the characteristic neuropathological hallmarks of Alzheimer's disease (AD) is the extracellular accumulation of beta -amyloid peptides (A beta) in neuritic plaques, Experimental data indicate that different molecular forms of A beta affect a wide array of neuronal and glial functions and ther

  10. Why Downside Beta Is Better: An Educational Example

    Science.gov (United States)

    Chong, James T.; Jennings, William P.; Phillips, G. Michael

    2013-01-01

    An educational example is presented that is an effective teaching illustration to help students understand the difference between traditional CAPM beta and downside (or down-market) beta and why downside beta is a superior measure for use in personal financial planning investment policy statements.

  11. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.

    NARCIS (Netherlands)

    Rudick, R.A.; Stuart, W.H.; Calabresi, P.A.; Confavreux, C.; Galetta, S.L.; Radue, E.W.; Lublin, F.D.; Weinstock-Guttman, B.; Wynn, D.R.; Lynn, F.; Panzara, M.A.; Sandrock, A.W.

    2006-01-01

    BACKGROUND: Interferon beta is used to modify the course of relapsing multiple sclerosis. Despite interferon beta therapy, many patients have relapses. Natalizumab, an alpha4 integrin antagonist, appeared to be safe and effective alone and when added to interferon beta-1a in preliminary studies. MET

  12. First forbidden beta decay of some strongly deformed nuclei

    NARCIS (Netherlands)

    Werf, Siebren Ysbrand van der

    1971-01-01

    In this thesis we present measurements of the shape factors of the first forbidden beta decays of the nuclei Tm^170, Re^186, Re^188 and Lu^176m. For Lu^176m, also the beta gamma directionalcorrelation was measured. In chapter I formulas for the observable quantities in first forbidden beta decay and

  13. [beta]-Lactamases in the Biochemistry and Molecular Biology Laboratory

    Science.gov (United States)

    Amador, Paula; Prudencio, Cristina; Vieira, Monica; Ferraz, Ricardo; Fonte, Rosalia; Silva, Nuno; Coelho, Pedro; Fernandes, Ruben

    2009-01-01

    [beta]-lactamases are hydrolytic enzymes that inactivate the [beta]-lactam ring of antibiotics such as penicillins and cephalosporins. The major diversity of studies carried out until now have mainly focused on the characterization of [beta]-lactamases recovered among clinical isolates of Gram-positive staphylococci and Gram-negative…

  14. Induction of beta-lactamase production in Pseudomonas aeruginosa biofilm

    DEFF Research Database (Denmark)

    Giwercman, B; Jensen, E T; Høiby, N;

    1991-01-01

    Imipenem induced high levels of beta-lactamase production in Pseudomonas aeruginosa biofilms. Piperacillin also induced beta-lactamase production in these biofilms but to a lesser degree. The combination of beta-lactamase production with other protective properties of the biofilm mode of growth...

  15. TGF-beta and BMP in breast cancer cell invasion

    NARCIS (Netherlands)

    Naber, Hildegonda Petronella Henriëtte

    2012-01-01

    TGF-beta and BMPs are members of the TGF-beta superfamily of cytokines which play an important role in a multitude of processes. In cancer, TGF-beta is known for its dual role: in early stages it inhibits cancer cell proliferation, whereas in later stages it promotes invasion and metastasis. In this

  16. 21 CFR 886.5100 - Ophthalmic beta radiation source.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ophthalmic beta radiation source. 886.5100 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Therapeutic Devices § 886.5100 Ophthalmic beta radiation source. (a) Identification. An ophthalmic beta radiation source is a device intended to apply...

  17. Beta-glucuronidase-mediated drug release.

    Science.gov (United States)

    de Graaf, Michelle; Boven, Epie; Scheeren, Hans W; Haisma, Hidde J; Pinedo, Herbert M

    2002-01-01

    The selective activation of a relatively non-toxic prodrug by an enzyme present only in the tumour should enhance the drug concentration at the tumour site and result in a better anti-tumour effect and a reduction in systemic toxicity as compared to conventional chemotherapy. beta-Glucuronidase is such an enzyme. It is normally expressed in the lysosomes of cells. In larger tumours, however, high levels of the enzyme are present in necrotic areas. Several glucuronide prodrugs have been synthesised that can be activated by beta-glucuronidase. They are relatively non-toxic due to their hydrophilic nature, which prevents them from entering cells and thus from contact with lysosomal beta-glucuronidase. The main problem of glucuronide prodrugs for clinical use is their fast renal clearance. Special attention should be paid to the development of new less hydrophilic prodrugs with slower clearance, as this would result in a prolonged exposure to beta-glucuronidase at the site of the tumour and a reduction of the amount of prodrug needed. A number of interesting anthracyclin-based glucuronide prodrugs have been synthesised and have shown favourable therapeutic effects compared to treatment with the parent drug. The tumoural levels of beta-glucuronidase can even be enhanced by two-step approaches, in which exogenous enzyme is targeted to the tumour by an antibody (ADEPT) or by the gene encoding the enzyme in transduced tumour cells (GDEPT). The ADEPT and GDEPT approaches in combination with glucuronide prodrugs have shown enhanced efficacy in experimental tumour models. Further improvement of ADEPT and GDEPT is warranted to optimise the tumour uptake and retention of antibody-enzyme fusion proteins and the efficiency and safety of current gene delivery methods. In conclusion, it is clear that glucuronide prodrugs hold promise for future use in the treatment of cancer in patients as monotherapy. Enhancement of the therapeutic effects of glucuronide prodrugs, also in patients

  18. Correlation between metastatic potential and variants from colorectal tumor cell line HT-29

    Institute of Scientific and Technical Information of China (English)

    Min Wang; Ilka Vogel; Holger Kalthoff

    2003-01-01

    AIM: To evaluate the relationship between uPA, PAI-1,CEA, PI3K and metastatic potential in three colorectal tumor cell lines.METHODS: Metastatic model in nude rats was established by variants HT-29c and HT-29d cell lines and the metastatic potential of two tumor cell variants was compared.Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) were determined using ELISA in colorectal carcinoma WiDr, HT29 and HT-29d cell lines with different metastatic potentials.Expression of carcinoembryonic antigen (CEA) and phosphoinositide 3-kinase (PI3-Kinase) was analyzed using immunohistochemistry (IHC) in these cell lines in vitro and in vivo. CEA expression was compared using fluorescence activated cell sorter (FACS)in vitro.RESULTS: The number of HT-29d cells arrested in liver dramatically decreased within the initial 24 hours after injection. The taking rate of liver metastases in the variant HT-29d increased as compared with parental HT-29 cells (70 % versus 50 %) and a variant HT-29b cells (70 % versus 60 %), and extensive organs were synchronously involved in metastases. The uPA concentration of variant HT-29d cell line was significantly higher than that of the non-metastatic WiDr and the low metastatic HT-29 cell lines. The variant HT-29d cells produced stronger PI3-kinase expression as compared with the non-metastatic WiDr cells and the low metastatic HT-29 cellsin vivo.CONCLUSION: The selected variant HT-29d cell exhibited an enhanced metastatic potential. The level of uPA and PAI-1 is positively correlated with the metastatic capacity of tumor cells. The expression of PI3-kinase correlates with tumor development and metastasis.

  19. Beta-hypergeometric probability distribution on symmetric matrices

    OpenAIRE

    Hassairi, Abdelhamid; Masmoudi, Mouna

    2012-01-01

    Some remarkable properties of the beta distribution are based on relations involving independence between beta random variables such that a parameter of one among them is the sum of the parameters of an other (see (1.1) et (1.2) below). Asci, Letac and Piccioni \\cite{6} have used the real beta-hypergeometric distribution on $ \\reel$ to give a general version of these properties without the condition on the parameters. In the present paper, we extend the properties of the real beta to the beta...

  20. Beta-lactamases of Mycobacterium tuberculosis and Mycobacterium kansasii.

    Science.gov (United States)

    Segura, C; Salvadó, M

    1997-09-01

    Re-emergence of infectious diseases caused by mycobacteria as well as the emergence of multiresistant strains of Mycobacterium has promoted the research on the use of beta-lactames in the treatment of such diseases. Mycobacteria produce beta-lactamases: M. tuberculosis produces a wide-spectrum beta-lactamase whose behaviour mimicks those of Gram-negative bacteria. M. kansasii produces also beta-lactamase which can be inhibited by clavulanic acid. An overview on beta-lactamases from both species is reported.

  1. Comparative evaluation of a new beta-lactamase inhibitor, YTR 830, combined with different beta-lactam antibiotics against bacteria harboring known beta-lactamases.

    OpenAIRE

    Gutmann, L; Kitzis, M D; Yamabe, S; Acar, J F

    1986-01-01

    YTR 830, a new beta-lactamase inhibitor, combined with amoxicillin or carbenicillin, showed a synergistic effect similar to that observed with clavulanic acid, and generally better than that with sulbactam, against strains harboring chromosome-encoded penicillinases and broad-spectrum beta-lactamases or plasmid-determined beta-lactamases. With ampicillin, YTR 830 showed the best synergistic activity of the inhibitors against Proteus morganii, Citrobacter freundii, and Enterobacter cloacae and...

  2. Bactericidal interactions of a beta-lactam and beta-lactamase inhibitors in experimental Pseudomonas aeruginosa endocarditis caused by a constitutive overproducer of type Id beta-lactamase.

    OpenAIRE

    Bayer, A S; Selecky, M; Babel, K; Hirano, L; Yih, J; Parr, T R

    1987-01-01

    We investigated the in vitro and in vivo effects of a combination of a beta-lactam (ceftazidime) and a beta-lactamase inhibitor (dicloxacillin) to synergistically kill a ceftazidime-resistant variant, Pseudomonas aeruginosa PA-48, which overproduces type Id cephalosporinase constitutively. In vitro, dicloxacillin plus ceftazidime exerted bactericidal synergy at approximately 10(5) CFU/ml of inoculum (but not at approximately 10(7)-CFU inoculum), whereas other beta-lactamase inhibitors (sulbac...

  3. Genetic counselling in the beta-thalassaemias

    Directory of Open Access Journals (Sweden)

    Adonis S. Ioannides

    2013-03-01

    Full Text Available The beta-thalassaemias are very important genetic disorders of haemoglobin synthesis and are amongst the commonest monogenic disorders. In view of the severity of beta-thalassaemia major, a number of screening programmes have been developed aimed at reducing the number of individuals born with the condition. Genetic counsellingplays a vital role in this process supporting the successful implementation of screening and delineating available options to at risk individuals. This review assesses the contribution of genetic counsellingat each stage of this process in the context of new diagnostic techniques and therapeutic options and discusses some of the more challenging aspects such as genotype/ phenotype correlation and coinheritance of other genetic conditions or genetic modifiers.

  4. Beta-plane turbulence: experiments with altimetry

    CERN Document Server

    Zhang, Y

    2013-01-01

    Results from a new series of experiments on flows generated by an electromagnetic method in a rotating tank with topographic beta-effect are presented. The velocity fields are measured by the Altimetric Imaging Velocimetry. The turbulent flows observed in the experiments develop zonal jets which are latent in a stationary forced-dissipative regime of the flow but become prominent in the decaying flow. The two-dimensional energy spectra of the flows exhibit the development of anisotropy towards zonal motions. The experiments demonstrate dual turbulent cascade with energy and enstrophy ranges. The frequency-wavenumber spectra reveal the presence of Rossby waves at low wavenumbers which are excited by the turbulent motions. The experimental results are compared with available theory of beta-plane turbulence.

  5. The NEXT double beta decay experiment

    Science.gov (United States)

    Laing, A.; NEXT Collaboration

    2016-05-01

    NEXT (Neutrino Experiment with a Xenon TPC) is a neutrinoless double-beta (ββ0v) decay experiment at Laboratorio Subterraneo de Canfranc (LSC). It is an electroluminescent Time Projection Chamber filled with high pressure 136Xe gas with separated function capabilities for calorimetry and tracking. Energy resolution and background suppression are the two key features of any neutrinoless double beta decay experiment. NEXT has both good energy resolution (LSC. It will validate the NEXT background rate expectations and will make first measurements of the two neutrino ββ2v mode of 136Xe. Furthermore, the NEXT technique can be extrapolated to the tonne scale, thus allowing the full exploration of the inverted hierarchy of neutrino masses. These proceedings review NEXT R&D results, the status of detector commissioning at LSC and the NEXT physics case.

  6. Source preparations for alpha and beta measurements

    Energy Technology Data Exchange (ETDEWEB)

    Holm, E. [Risoe National Lab., Roskilde (Denmark)

    2001-01-01

    Regarding alpha particle emitters subject for environmental studies, electrodeposition or co-precipitation as fluorides are the most common methods. For electro deposition stainless steel is generally used as cathode material but also other metals such as Ni, Ag, and Cu showed promising results. The use of other anode material than platinum, such as graphite should be investigated. For other purposes such as optimal resolution other more sophisticated methods are used but often resulting in poorer recovery. For beta particle emitters the type of detection system will decide the source preparation. Similar methods as for alpha particle emitters, electrodeposition or precipitation techniques can be used. Due to the continuous energy distribution of the beta pulse height distribution a high resolution is not required. Thicker sources from the precipitates or a stable isotopic carrier can be accepted but correction for absorption in the source must be done. (au)

  7. Search for Neutrinoless Double-Beta Decay

    CERN Document Server

    Tornow, Werner

    2014-01-01

    After the pioneering work of the Heidelberg-Moscow (HDM) and International Germanium Experiment (IGEX) groups, the second round of neutrinoless double-$\\beta$ decay searches currently underway has or will improve the life-time limits of double-$\\beta$ decay candidates by a factor of two to three, reaching in the near future the $T_{1/2} = 3 \\times 10^{25}$ yr level. This talk will focus on the large-scale experiments GERDA, EXO-200, and KamLAND-Zen, which have reported already lower half-life time limits in excess of $10^{25}$ yr. Special emphasis is given to KamLAND-Zen, which is expected to approach the inverted hierarchy regime before future 1-ton experiments probe completely this life-time or effective neutrino-mass regime, which starts at $\\approx 2 \\times 10^{26}$ yr or $\\approx 50$ meV.

  8. Numerical models for high beta magnetohydrodynamic flow

    International Nuclear Information System (INIS)

    The fundamentals of numerical magnetohydrodynamics for highly conducting, high-beta plasmas are outlined. The discussions emphasize the physical properties of the flow, and how elementary concepts in numerical analysis can be applied to the construction of finite difference approximations that capture these features. The linear and nonlinear stability of explicit and implicit differencing in time is examined, the origin and effect of numerical diffusion in the calculation of convective transport is described, and a technique for maintaining solenoidality in the magnetic field is developed. Many of the points are illustrated by numerical examples. The techniques described are applicable to the time-dependent, high-beta flows normally encountered in magnetically confined plasmas, plasma switches, and space and astrophysical plasmas. 40 refs

  9. Autoradiographic localization of beta-adrenoreceptors in rat uterus

    Energy Technology Data Exchange (ETDEWEB)

    Tolszczuk, M.; Pelletier, G.

    1988-12-01

    The inhibitory effects of catecholamines on uterine smooth muscle are known to be mediated through beta-adrenergic receptors. To investigate further the distribution of these receptors in the rat uterus, we utilized in vitro autoradiography using ( SVI)-cyanopindolol (CYP), a specific beta-receptor ligand that has equal activity for both beta 1- and beta 2-receptor subtypes. The specificity of the labeling and the characterization of receptor subtypes in different cell types were achieved by displacement of radioligand with increasing concentrations of zinterol, a beta-adrenergic agonist with preferential affinity for the beta 2-adrenoreceptor subtype, and practolol, a beta-adrenergic antagonist that binds preferentially to the beta 1-subtype. Quantitative estimation of ligand binding was performed by densitometry. It was shown that the vast majority of beta-adrenoreceptors were of the beta 2-subtype and were found in high concentration not only in the myometrium but also in the endometrial and serosal epithelia. Specific labeling was also observed in glandular elements. These results suggest that beta-adrenoreceptors might be involved in different functions in the uterus.

  10. Urokinase-type Plasminogen Activator-like Proteases in Teleosts Lack Genuine Receptor-binding Epidermal Growth Factor-like Domains*

    Science.gov (United States)

    Bager, René; Kristensen, Thomas K.; Jensen, Jan K.; Szczur, Agnieszka; Christensen, Anni; Andersen, Lisbeth M.; Johansen, Jesper S.; Larsen, Niels; Baatrup, Erik; Huang, Mingdong; Ploug, Michael; Andreasen, Peter A.

    2012-01-01

    Plasminogen activation catalyzed by urokinase-type plasminogen activator (uPA) plays an important role in normal and pathological tissue remodeling processes. Since its discovery in the mid-1980s, the cell membrane-anchored urokinase-type plasminogen activator receptor (uPAR) has been believed to be central to the functions of uPA, as uPA-catalyzed plasminogen activation activity appeared to be confined to cell surfaces through the binding of uPA to uPAR. However, a functional uPAR has so far only been identified in mammals. We have now cloned, recombinantly produced, and characterized two zebrafish proteases, zfuPA-a and zfuPA-b, which by several criteria are the fish orthologs of mammalian uPA. Thus, both proteases catalyze the activation of fish plasminogen efficiently and both proteases are inhibited rapidly by plasminogen activator inhibitor-1 (PAI-1). But zfuPA-a differs from mammalian uPA by lacking the exon encoding the uPAR-binding epidermal growth factor-like domain; zfuPA-b differs from mammalian uPA by lacking two cysteines of the epidermal growth factor-like domain and a uPAR-binding sequence comparable with that found in mammalian uPA. Accordingly, no zfuPA-b binding activity could be found in fish white blood cells or fish cell lines. We therefore propose that the current consensus of uPA-catalyzed plasminogen activation taking place on cell surfaces, derived from observations with mammals, is too narrow. Fish uPAs appear incapable of receptor binding in the manner known from mammals and uPA-catalyzed plasminogen activation in fish may occur mainly in solution. Studies with nonmammalian vertebrate species are needed to obtain a comprehensive understanding of the mechanism of plasminogen activation. PMID:22733817

  11. Endopeptidase-Mediated Beta Lactam Tolerance

    OpenAIRE

    Dörr, Tobias; Davis, Brigid M.; Waldor, Matthew K.

    2015-01-01

    In many bacteria, inhibition of cell wall synthesis leads to cell death and lysis. The pathways and enzymes that mediate cell lysis after exposure to cell wall-acting antibiotics (e.g. beta lactams) are incompletely understood, but the activities of enzymes that degrade the cell wall (‘autolysins’) are thought to be critical. Here, we report that Vibrio cholerae, the cholera pathogen, is tolerant to antibiotics targeting cell wall synthesis. In response to a wide variety of cell wall- acting ...

  12. Beta-Thalassaemia types in southern Sardinia.

    OpenAIRE

    Cao, A; Furbetta, M; Ximenes, A; Angius, A; Rosatelli, C; Tuveri, T; Scalas, M T; Falchi, A M; Maccioni, L; Melis, M A; R. Galanello

    1981-01-01

    In this study the prevalence of the different beta-thalassaemia types in southern Sardinia was investigated by cellulose acetate and agar gel electrophoresis or globin chain synthesis analysis on column chromatography or both in (1) all the patients (347) presenting with thalassaemia major or intermedia at our haematology service from 1976 to 1979, and (2) a group of 82 patients with transfusion-dependent thalassaemia major randomly chosen from 236 under our care. Apart from six subjects with...

  13. Risk adjusted equity valuation and accounting betas

    OpenAIRE

    Pope, P F; Wang, P.

    2000-01-01

    In this paper we develop a general equity valuation model where abnormal earnings, back value, the discount factor and interest rates evolve stochastically. Focusing on the dynamics of abnormal earnings, we demonstrate the back value, abnormal earnings, "other information" and two risk adjustment terms are sufficient for valuation when pricing kernel risk is attributable to a single market factor. The risk adjustment terms depend on accounting betas reflecting the covariances between abnormal...

  14. Tables of double beta decay data

    International Nuclear Information System (INIS)

    A compilation of experimental data on double beta decay is presented. The tables contain the most stringent known experimental limits or positive results of 2β transitions of 69 natural nuclides to ground and excited states of daughter nuclei for different channels (2β-; 2β+; εβ+; 2ε) and modes (0ν; 2ν; 0νM) of decay. (authors). 189 refs., 9 figs., 3 tabs

  15. SPL and Beta Beams to the Frejus

    CERN Document Server

    Mezzetto, M

    2005-01-01

    Physics potential of a conventional neutrino beam generated by the 2.2 GeV, 4MW, Superconducting Proton Linac and of a Beta Beam fired to a gigantic water Ccaronerenkov detector hosted below Frejus, 130 km away from CERN, are briefly summarized. theta/sub 13/ sensitivity could be improved by up to 3 orders of magnitude with respect to the present experimental limit and a first sensitive search for leptonic CP violation could be performed.

  16. Precision mass measurements utilizing beta endpoints

    CERN Document Server

    Moltz, D M; Kern, B D; Noma, H; Ritchie, B G; Toth, K S

    1981-01-01

    A technique for precise determination of beta endpoints with an intrinsic germanium detector has been developed. The energy calibration is derived from gamma -ray photopeak measurements. This analysis procedure has been checked with a /sup 27/Si source produced in a (p, n) reaction on a /sup 27/Al target and subsequently applied to mass separated samples of /sup 76/Rb, /sup 77/Rb and /sup 78/Rb. Results indicate errors <50 keV are obtainable. (29 refs).

  17. Beta Beams for Precision Measurements of Neutrino Oscillation Parameters

    CERN Document Server

    Wildner, E; Hansen, C; De Melo Mendonca, T; Stora, T; Damjanovic, S; Payet, J; Chancé, A; Zorin, V; Izotov, I; Rasin, S; Sidorov, A; Skalyga, V; De Angelis, G; Prete, G; Cinausero, M; Kravchuk, V; Gramegna, F; Marchi, T; Collazuol, G; Mezzetto, M; Delbar, T; Loiselet, M; Keutgen, T; Mitrofanov, S; Burt, G; Dexter, A; Lamy, T; Latrasse, L; Marie-Jeanne, M; Sortais, P; Thuillier, T; Debray, F; Trophime, C; Hass, M; Hirsh, T; Berkovits, D; Stahl, A; Vardaci, E; Di Nitto, A; Brondi, A; La Rana, G; Moro, R; De Rosa, G; Palladino, V

    2012-01-01

    Neutrino oscillations have implications for the Standard Model of particle physics. The CERN Beta Beam has outstanding capabilities to contribute to precision measurements of the parameters governing neutrino oscillations. The FP7 collaboration EUROnu (2008-2012) is a design study that will review three facilities (Super-Beams, Beta Beams and Neutrino Factories) and perform a cost assessment that, coupled with the physics performance, will give means to the European research authorities to make decisions on future European neutrino oscillation facilities. ”Beta Beams” produce collimated pure electron (anti)neutrinos by accelerating beta active ions to high energies and having them decay in a storage ring. Using existing machines and infrastructure is an advantage for the cost evaluation; however, this choice is also constraining the Beta Beams. Recent work to make the Beta Beam facility a solid option will be described: production of Beta Beam isotopes, the 60 GHz pulsed ECR source development, integratio...

  18. Reinvestigation of the beta-decay of {sup 110}Mo

    Energy Technology Data Exchange (ETDEWEB)

    Wang, J.C.; Dendooven, P.; Hankonen, S.; Huikari, J.; Jokinen, A.; Kolhinen, V.S.; Lhersonneau, G.; Nieminen, A.; Peraejaervi, K.; Rinta-Antila, S.; Aeystoe, J. [Department of Physics, University of Jyvaeskylae, FIN-40351, Jyvaeskylae (Finland)

    2004-01-01

    The beta-decay of the neutron-rich nucleus {sup 110}Mo, separated by the IGISOL on-line mass separator from other fission products, has been investigated by using beta-gamma and gamma-gamma coincidence techniques. The decay scheme of {sup 110}Mo has been revised, including 3 new excited states and 7 new {gamma} transitions in {sup 110}Tc. The {beta}-feedings were measured and log ft values and B(GT) values were deduced based on a Q{sub {beta}}-value from systematics. Three excited 1{sup +} states in {sup 110}Tc fed by spin-flip allowed-unhindered beta transitions were identified. The deduced beta-decay strengths are compared with the Gamow-Teller strength distribution obtained from a macroscopic-microscopic calculation. The role of the asymptotic quantum numbers in the context of the allowed beta-decay is discussed. (orig.)

  19. Simulation in double-beta decay experiments

    International Nuclear Information System (INIS)

    A detailed understanding of background radiation sources is a key to interpretation and enhanced sensitivity of double-beta decay experiments. Improvement of several techniques will be discussed. An implementation of the EGS4 code was developed to improve the accuracy of detector simulations, in particular for a 100Mo double-beta decay experiment. The efficiency modification due to the angular dependence of the 539 keV - 590 keV gamma-ray coincidence was successfully determined. The success of the 100Mo effort led to the modeling of uranium-thorium backgrounds found in an electroformed copper shield built for a 76Ge experiment. The large copper mass increased our sensitivity to contaminants present in copper produced this way, and led to changes in our cryostat electroforming technique. The original goal was the determination of the 210Pb content of the 450 year old lead shield previously used in 71Ge two-neutrino double-beta decay measurements. The results pertaining to low background materials and fabrication techniques will also be discussed

  20. Beta decay properties from a statistical model

    International Nuclear Information System (INIS)

    The present work assumes that any intrinsic structure in the nuclei involved is not important. Only spin, parity, and energy are considered. Quantities such as half-life, average beta energy, or average gamma energy can be obtained by integrals over the beta strength function weighted by kinematic and other factors. The beta strength function is proportional to the level density multiplied by a reduced transition probability. Delayed neutron emission is calculated by assuming that the daughter is a compound nucleus which then statistically decays as in the Hauser-Feshbach approach. Using the ENDF/B-V fission product file which contains 877 nuclei, energy-dependent reduced transition probabilities were found for allowed 0+ → 1+ transitions (50 cases) and for other allowed transitions (over 600 cases), corresponding to log ft values of 4.3 and 5.6 respectively. No dependence on either transition energy or on mass was found. A reduced transition probability corresponding to log ft of 7.1 was used for first forbidden transitions. Some results are presented and discussed

  1. Effects of calcium impurity on phase relationship, ionic conductivity and microstructure of Na$^{+}$-$\\beta/beta"$-alumina solid electrolyte

    Indian Academy of Sciences (India)

    SUNG-TAE LEE; DAE-HAN LEE; SANG-MIN LEE; SANG-SOO HAN; SANG-HYUNG LEE; SUNG-KI LIM

    2016-06-01

    Ca-doped Na$^{+}$-$\\beta/beta"$-alumina was synthesized using a solid-state reaction. The changes in the properties of Na$^{+}$-$\\beta/beta"$-alumina resulting from the presence of Ca impurity were studied. Ca (0–5 wt%) was added to the respective samples, which were then sintered. The specimens were characterized using X-ray diffraction, scanningelectron microscopy, densimetry and impedance analysis. In the sintered specimens, the $\\beta"$-alumina phase fraction decreased as Ca content increased, whereas the relative sintered density increased. The surface morphology of Cadoped Na$^{+}$-$\\beta/beta"$-alumina specimens showed a Ca-rich layer, which was the main cause of increase in the specificresistance.

  2. A Novel Dimeric Inhibitor Targeting Beta2GPI in Beta2GPI/Antibody Complexes Implicated in Antiphospholipid Syndrome

    Energy Technology Data Exchange (ETDEWEB)

    A Kolyada; C Lee; A De Biasio; N Beglova

    2011-12-31

    {beta}2GPI is a major antigen for autoantibodies associated with antiphospholipid syndrome (APS), an autoimmune disease characterized by thrombosis and recurrent pregnancy loss. Only the dimeric form of {beta}2GPI generated by anti-{beta}2GPI antibodies is pathologically important, in contrast to monomeric {beta}2GPI which is abundant in plasma. We created a dimeric inhibitor, A1-A1, to selectively target {beta}2GPI in {beta}2GPI/antibody complexes. To make this inhibitor, we isolated the first ligand-binding module from ApoER2 (A1) and connected two A1 modules with a flexible linker. A1-A1 interferes with two pathologically important interactions in APS, the binding of {beta}2GPI/antibody complexes with anionic phospholipids and ApoER2. We compared the efficiency of A1-A1 to monomeric A1 for inhibition of the binding of {beta}2GPI/antibody complexes to anionic phospholipids. We tested the inhibition of {beta}2GPI present in human serum, {beta}2GPI purified from human plasma and the individual domain V of {beta}2GPI. We demonstrated that when {beta}2GPI/antibody complexes are formed, A1-A1 is much more effective than A1 in inhibition of the binding of {beta}2GPI to cardiolipin, regardless of the source of {beta}2GPI. Similarly, A1-A1 strongly inhibits the binding of dimerized domain V of {beta}2GPI to cardiolipin compared to the monomeric A1 inhibitor. In the absence of anti-{beta}2GPI antibodies, both A1-A1 and A1 only weakly inhibit the binding of pathologically inactive monomeric {beta}2GPI to cardiolipin. Our results suggest that the approach of using a dimeric inhibitor to block {beta}2GPI in the pathological multivalent {beta}2GPI/antibody complexes holds significant promise. The novel inhibitor A1-A1 may be a starting point in the development of an effective therapeutic for antiphospholipid syndrome.

  3. The beta strength function structure in \\beta + decay of lutecium, thulium and cesium isotopes

    CERN Document Server

    Alkhazov, G D; Naumov, Yu V; Orlov, S Yu; Vitman, V D

    1981-01-01

    The spectra of total gamma -absorption in the decays of some lutetium, thulium and cesium isotopes have been measured. The probabilities for level population in the decay of the isotopes have been determined. The deduced beta strength functions reveal pronounced structure. Calculations of the strength functions using the Saxon-Woods potential and the residual Gamow-Teller interaction are presented. It is shown that in beta /sup +/ decay of light thulium and cesium isotopes the strength function comprises more than 70% of the Gamow-Teller excitations with mu /sub tau /=+1. This result is the first direct observation of the Gamov-Teller resonance in beta /sup +/ decay of nuclei with T/sub z/>0. (21 refs).

  4. Beta-decay rate and beta-delayed neutron emission probability of improved gross theory

    Science.gov (United States)

    Koura, Hiroyuki

    2014-09-01

    A theoretical study has been carried out on beta-decay rate and beta-delayed neutron emission probability. The gross theory of the beta decay is based on an idea of the sum rule of the beta-decay strength function, and has succeeded in describing beta-decay half-lives of nuclei overall nuclear mass region. The gross theory includes not only the allowed transition as the Fermi and the Gamow-Teller, but also the first-forbidden transition. In this work, some improvements are introduced as the nuclear shell correction on nuclear level densities and the nuclear deformation for nuclear strength functions, those effects were not included in the original gross theory. The shell energy and the nuclear deformation for unmeasured nuclei are adopted from the KTUY nuclear mass formula, which is based on the spherical-basis method. Considering the properties of the integrated Fermi function, we can roughly categorized energy region of excited-state of a daughter nucleus into three regions: a highly-excited energy region, which fully affect a delayed neutron probability, a middle energy region, which is estimated to contribute the decay heat, and a region neighboring the ground-state, which determines the beta-decay rate. Some results will be given in the presentation. A theoretical study has been carried out on beta-decay rate and beta-delayed neutron emission probability. The gross theory of the beta decay is based on an idea of the sum rule of the beta-decay strength function, and has succeeded in describing beta-decay half-lives of nuclei overall nuclear mass region. The gross theory includes not only the allowed transition as the Fermi and the Gamow-Teller, but also the first-forbidden transition. In this work, some improvements are introduced as the nuclear shell correction on nuclear level densities and the nuclear deformation for nuclear strength functions, those effects were not included in the original gross theory. The shell energy and the nuclear deformation for

  5. In vitro proliferation of adult human beta-cells.

    Directory of Open Access Journals (Sweden)

    Sabine Rutti

    Full Text Available A decrease in functional beta-cell mass is a key feature of type 2 diabetes. Glucagon-like peptide 1 (GLP-1 analogues induce proliferation of rodent beta-cells. However, the proliferative capacity of human beta-cells and its modulation by GLP-1 analogues remain to be fully investigated. We therefore sought to quantify adult human beta-cell proliferation in vitro and whether this is affected by the GLP-1 analogue liraglutide.Human islets from 7 adult cadaveric organ donors were dispersed into single cells. Beta-cells were purified by FACS. Non-sorted cells and the beta-cell enriched ("beta-cells" population were plated on extracellular matrix from rat (804G and human bladder carcinoma cells (HTB9 or bovine corneal endothelial ECM (BCEC. Cells were maintained in culture+/-liraglutide for 4 days in the presence of BrdU.Rare human beta-cell proliferation could be observed either in the purified beta-cell population (0.051±0.020%; 22 beta-cells proliferating out of 84'283 beta-cells counted or in the non-sorted cell population (0.055±0.011%; 104 proliferating beta-cells out of 232'826 beta-cells counted, independently of the matrix or the culture conditions. Liraglutide increased human beta-cell proliferation on BCEC in the non-sorted cell population (0.082±0.034% proliferating beta-cells vs. 0.017±0.008% in control, p<0.05.These results indicate that adult human beta-cell proliferation can occur in vitro but remains an extremely rare event with these donors and particular culture conditions. Liraglutide increases beta-cell proliferation only in the non-sorted cell population and only on BCEC. However, it cannot be excluded that human beta-cells may proliferate to a greater extent in situ in response to natural stimuli.

  6. Thymosin beta 4 and thymosin beta 10 expression in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    W. Theunissen

    2014-03-01

    Full Text Available Thymosin beta 4 (Tβ4 and thymosin beta 10 (Tβ10 are two members of the beta-thymosin family involved in many cellular processes such as cellular motility, angiogenesis, inflammation, cell survival and wound healing. Recently, a role for beta-thymosins has been proposed in the process of carcinogenesis as both peptides were detected in several types of cancer. The aim of the present study was to investigate the expression pattern of Tβ4 and Tβ10 in hepatocellular carcinoma (HCC. To this end, the expression pattern of both peptides was analyzed in liver samples obtained from 23 subjects diagnosed with HCC. Routinely formalin-fixed and paraffin-embedded liver samples were immunostained by indirect immunohistochemistry with polyclonal antibodies to Tβ4 and Tβ10. Immunoreactivity for Tβ4 and Tβ10 was detected in the liver parenchyma of the surrounding tumor area. Both peptides showed an increase in granular reactivity from the periportal to the periterminal hepatocytes. Regarding HCC, Tβ4 reactivity was detected in 7/23 cases (30% and Tβ10 reactivity in 22/23 (97% cases analyzed, adding HCC to human cancers that express these beta-thymosins. Intriguing finding was seen looking at the reactivity of both peptides in tumor cells infiltrating the surrounding liver. Where Tβ10 showed a strong homogeneous expression, was Tβ4 completely absent in cells undergoing stromal invasion. The current study shows expression of both beta-thymosins in HCC with marked differences in their degree of expression and frequency of immunoreactivity. The higher incidence of Tβ10 expression and its higher reactivity in tumor cells involved in stromal invasion indicate a possible major role for Tβ10 in HCC progression.

  7. Systematic Risk on Istanbul Stock Exchange: Traditional Beta Coefficient Versus Downside Beta Coefficient

    OpenAIRE

    Gülfen TUNA; Vedat Ender TUNA

    2013-01-01

    The aim of this study is to test the validity of Downside Capital Asset Pricing Model (D-CAPM) on the ISE. At the same time, the explanatory power of CAPM's traditional beta and D-CAPM's downside beta on the changes in the average return values are examined comparatively. In this context, the monthly data for seventy three stocks that are continuously traded on the ISE for the period 1991-2009 is used. Regression analysis is applied in this study. The research results have shown that D-CAPM i...

  8. BETA. A code for {beta}{sub eff} measurement and analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Yuichi; Okajima, Shigeaki; Sakurai, Takeshi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1999-03-01

    The code BETA has been developed to calculate the following reactor physics parameters which are used for the {beta}{sub eff} measurement and analysis; Diven factor, Spatial correction factor (g-factor) for neutron correlation experiment, Adjoint weighted g-factor, Fission rate integrated in whole reactor and Adjoint weighted fission rate integrated in whole reactor: The code also calculates the effective delayed neutron fraction with different evaluated delayed neutron data. These parameters are calculated with using the forward and adjoint fluxes given by SLAROM, POPLARS or TWOTRAN-II. This report describes the input data and job control statements instructions, file requirements and sample input output data. (author)

  9. The effects of beta-carotene and vitamin E on erythrocytes lipid peroxidation in beta-thalassemia patients

    Directory of Open Access Journals (Sweden)

    Soleiman Mahjoub

    2007-12-01

    Full Text Available BACKGROUND: Thalassemia is the most common hereditary disease in the world. Thalassemic erythrocytes are exposed to higher oxidative stress and lipid peroxidation. The aim of this study was to investigate the effects of beta-carotene and vitamin E on erythrocytes lipid peroxidation in beta-thalassemia patients.
    METHODS: A prospective double-blind, placebo-controlled study of the effect of beta-carotene and vitamin E on lipid peroxidation in erythrocytes membranes was performed on 120 beta-thalassemia major patients in four groups. The patients were supplemented for 4 weeks as follows: group 1 with beta-carotene (13 mg/day, group 2 with vitamin E (550 mg/day, group 3 with beta-carotene plus vitamin E and group 4 with placebo. We prepared all capsules for 4 roups in the same shape and color. Measurements of serum beta-carotene and vitamin E were performed by high performance
    liquid chromatography. After preparation of ghost cells from blood specimens, malondialdehyde (MDA was determined as index of lipid peroxidation in erythrocytes membranes before and after treatment. RESULTS: The levels of serum beta-carotene and vitamin E were significantly lower and MDA concentrations in erythrocytes membranes were significantly higher in beta-thalassemia patients compared to controls (P<0.001. In groups that treated with vitamin supplements for 4-weeks, lipid peroxidation rates were significantly reduced after treatment (P<0.001, but in placebo group there was not significant difference (P>0.05.
    CONCLUSIONS: Our findings provide evidence that an oral treatment with beta-carotene and vitamin E can significantly reduce lipid peroxidation of erythrocytes membranes and could be useful in management of beta-thalassemia major patients. KEYWORDS: Beta-thalassemia major, beta-carotene, vitamin E, malondialdehyde, lipid peroxidation.

  10. Dopaminergic and beta-adrenergic effects on gastric antral motility

    DEFF Research Database (Denmark)

    Bech, K; Hovendal, C P; Gottrup, F;

    1984-01-01

    bethanechol or pentagastrin inducing motor activity patterns as in the phase III of the MMC and the digestive state respectively. The stimulated antral motility was dose-dependently inhibited by dopamine. The effect was significantly blocked by specifically acting dopaminergic blockers, while alpha- and beta......-adrenergic blockers were without any significant effects. Dose-response experiments with bethanechol and dopamine showed inhibition of a non-competitive type. Isoprenaline was used alone and in conjunction with selective blockade of beta 1- and beta 2-receptors during infusion of bethanechol which induces a pattern...... similar to phase III in the migrating myoelectric complex. The stimulated antral motility was dose-dependently inhibited by isoprenaline. The effect could be significantly blocked by propranolol (beta 1 + beta 2-adrenoceptor blocker) and by using in conjunction the beta 1-adrenoceptor blocker practolol...

  11. Fracture risk in perimenopausal women treated with beta-blockers

    DEFF Research Database (Denmark)

    Rejnmark, Lars; Vestergaard, Peter; Kassem, Moustapha;

    2004-01-01

    beta2-Adrenergic receptors have been identified on human osteoblastic and osteoclastic cells, raising the question of a sympathetic regulation of bone metabolism. We investigated effects of treatment with beta-adrenergic receptor antagonists (beta-blockers) on bone turnover, bone mineral density...... (BMD), and fracture risk. Within the Danish Osteoporosis Prevention Study (DOPS) a population based, comprehensive cohort study of 2016 perimenopausal women, associations between treatment with beta-blockers and bone turnover and BMD were assessed in a cross-sectional design at the start of study....... Moreover, in a nested case-control design, fracture risk during the subsequent 5 years was assessed in relation to treatment with beta-blockers at baseline. Multiple regression- and logistic regression-analyses were performed. Treatment with beta-blockers was associated with a threefold increased fracture...

  12. Chlamydia pneumoniae Promotes Dysfunction of Pancreatic Beta Cells

    Science.gov (United States)

    Rodriguez, Annette R.; Plascencia-Villa, Germán; Witt, Colleen M.; Yu, Jieh-Juen; José-Yacamán, Miguel; Chambers, James P.; Perry, George; Guentzel, M. Neal; Arulanandam, Bernard P.

    2015-01-01

    The human pathogen Chlamydia pneumoniae has been implicated in chronic inflammatory diseases including type 2 diabetes. Therefore, we designed a study to evaluate pancreatic beta cells and mast cells during chlamydial infection. Our study revealed that C. pneumoniae infected mast cells significantly (p< 0.005) decreased beta cell ATP and insulin production, in contrast to uninfected mast cells co-cultured with beta cells. Infected mast cells exhibited pyknotic nuclei and active caspase-3 and caspase-1 expression. Additionally, ex vivo analyses of tissues collected from C. pneumoniae infected mice showed increased interleukin-1β production in splenocytes and pancreatic tissues as was observed with in vitro mast cell-beta cell co-cultures during C. pneumoniae infection. Notably, infected mast cells promoted beta cell destruction. Our findings reveal the negative effect of C. pneumoniae on mast cells, and the consequential impact on pancreatic beta cell function and viability. PMID:25863744

  13. Distribution of beta-amyloid in the canine brain.

    Science.gov (United States)

    Hou, Y; White, R G; Bobik, M; Marks, J S; Russell, M J

    1997-03-01

    The distribution of amyloid-beta protein (A beta) in the canine brain was demonstrated by immunochemistry on serially sectioned tissues from 10 aged mixed breed dogs. Summation of quantitative data and relegation to anatomical sites for the 10 dogs showed A beta to be widely distributed in the cortex and hippocampus while completely absent in the brain stem and cerebellum. The highest density of A beta was in the dentate gyrus of the hippocampus. Cortical areas exhibiting the greatest A beta deposition were the posterior and medial suprasylvius gyrus and the proreus gyrus of the frontal lobe. Unlike humans the canine entorhinal cortex, amygdala, basal ganglia and olfactory bulbs were rarely affected. This suggested that the highly developed olfactory pathways of the canine are generally spared from A beta deposition. PMID:9141082

  14. Purification and properties of beta-galactosidase from Aspergillus nidulans.

    Science.gov (United States)

    Díaz, M; Pedregosa, A M; de Lucas, J R; Torralba, S; Monistrol, I F; Laborda, F

    1996-12-01

    Beta-Galactosidase from mycelial extract of Aspergillus nidulans has been purified by substrate affinity chromatography and used to obtain anti-beta-galactosidase polyclonal antibodies. A. nidulans growing in lactose as carbon source synthesizes one active form of beta-galactosidase which seems to be a multimeric enzyme of 450 kDa composed of monomers with 120 and 97 kDa. Although the enzyme was not released to the culture medium, some enzymatic activity was detected in a cell-wall extract, thus suggesting that it can be an extracellular enzyme. Beta-Galactosidase of A. nidulans is a very unstable enzyme with an optimum pH value of 7.5 and an optimum temperature of 30 degrees C. It was only active against beta-galactoside substrates like lactose and p-nitrophenyl-beta-D-galactoside (PNPG).

  15. Chiral Two-body Currents and Neutrinoless Double Beta Decay

    Energy Technology Data Exchange (ETDEWEB)

    Menendez, Javier [Institut fuer Kernphysik, Technische Universitaet Darmstadt, 64289 Darmstadt (Germany); ExtreMe Matter Institute EMMI, GSI Helmholtzzentrum fuer Schwerionenforschung GmbH, 64291 Darmstadt (Germany)

    2011-12-16

    The nuclear matrix elements (NMEs) of neutrinoless double-beta (0{nu}{beta}{beta}) decay are studied using weak currents derived in the framework of chiral effective field theory. Apart from the standard one-body (1b) currents, it is shown that two-body (2b) currents contribute to weak processes. The normal-ordered 1b part of 2b currents modifies the Gamow-Teller (GT){sigma}{tau}{sup -} part of the 1b current, contributing to the well-known quenching of GT single-{beta} decays. The momentum-transfer dependence of the quenching due to 2b currents is also predicted. Therefore, including 2b currents allows to address, microscopically, the problem of the axial weak coupling (g{sub A}) value, which is the biggest uncertainty in the 0{nu}{beta}{beta} decay NME calculations for all available methods.

  16. Double-beta decay in deformed nuclei

    International Nuclear Information System (INIS)

    A brief review of theoretical results for the double-beta decay and the double-electron capture in heavy deformed nuclei is presented. The ββ half life of 160Gd is evaluated using an extended version of the pseudo SU(3) model. While the 2ν mode is forbidden when the most probable occupations are considered, states with different occupation numbers can be mixed through the pairing interaction. The amount of this mixing is calculated using perturbation theory. The possibility of observing the ββ decay in 160Gd is discussed for both the 2ν and 0ν modes. (author)

  17. MHD stable high beta spheromak equilibrium

    International Nuclear Information System (INIS)

    Recent observations of a pressure driven mode in CTX indicate that its performance is being limited by the low beta stability requirements typical of conventional spheromak designs. Improved designs with higher beat limits therefore have the potential to dramatically increase the temperature and lifetime of CTX and other spheromak experiments. This paper describes the results of an optimization study examining radically different geometries, but all with minimum energy current profiles which can easily be created experimentally and should be automatically stable to all ideal and resistive current drive modes. 2 refs., 3 figs

  18. Microbial degradation of poly-beta-hydroxyalkanoates.

    Science.gov (United States)

    Mas-Castellà, J; Lafuente, R; Urmeneta, J; Goodwin, S; Guerrero, R

    1994-01-01

    The search for new materials that are not hazardous to the environment has become a major issue in our society, engaged as it is in the attainment of sustainable development. Poly-beta-hydroxyalkanoates (PHA), produced exclusively by prokaryotes, can be used as thermoplastics and are fully biodegradable and innocuous to the environment. Biodegradability testing has quantified the capacity of microorganisms to degrade such new chemical compounds, particularly polyhydroxyalkanoates. Standardized tests may also discover new microorganisms and environmental conditions that accelerate biodegradation. We evaluate various techniques used to assess the biodegradability of PHA, and which may also be applied to test other kinds of polymers.

  19. The Beta-MANOVA Ensemble with General Covariance

    OpenAIRE

    Dubbs, Alexander; Edelman, Alan

    2013-01-01

    We find the joint generalized singular value distribution and largest generalized singular value distributions of the $\\beta$-MANOVA ensemble with positive diagonal covariance, which is general. This has been done for the continuous $\\beta > 0$ case for identity covariance (in eigenvalue form), and by setting the covariance to $I$ in our model we get another version. For the diagonal covariance case, it has only been done for $\\beta = 1,2,4$ cases (real, complex, and quaternion matrix entries...

  20. Marginal versus average beta of equity under corporate taxation

    OpenAIRE

    Lund, Diderik

    2009-01-01

    Even for fully equity-financed firms there may be substantial effects of taxation on the after-tax cost of capital. Among the few studies of these effects, even fewer identify all effects correctly. When marginal investment is taxed together with inframarginal, marginal beta differs from average if there are investmentrelated deductions like depreciation. To calculate asset betas, one should not only "unlever" observed equity betas, but "untax" and "unaverage" them. Risky tax claims are value...

  1. Osmotic fragility test in heterozygotes for alpha and beta thalassaemia.

    OpenAIRE

    Maccioni, L; Cao, A

    1985-01-01

    This study shows that the combination of heterozygous beta thalassaemia and deletion heterozygous (-alpha/alpha alpha) or homozygous (-alpha/-alpha) alpha+ thalassaemia may result in the production of erythrocytes which have normal mean volume and haemoglobinisation but decreased osmotic fragility. Based on this finding and previous studies, which have shown that beta thalassaemia screening by the osmotic fragility test may miss a significant proportion of beta thalassaemia heterozygotes, we ...

  2. Pharmacokinetics of sex steroids in patients with beta thalassaemia major.

    OpenAIRE

    Katz, M; De Sanctis, V.; Vullo, C; Wonke, B; McGarrigle, H. H.; Bagni, B

    1993-01-01

    AIMS--To assess the pharmacokinetics of oral, intramuscular, or transdermal hormone replacement in patients with beta thalassaemia major. METHODS--Oral (testosterone undecanoate 40 mg) and intramuscular (testosterone propionate 15 mg, phenylpropionate 30 mg, isocaproate 30 mg and decanoate 50 mg) testosterone and transdermal (17 beta oestradiol 25 micrograms and 50 micrograms) oestradiol were evaluated in 21 male (16-29 years) and 11 female (19-26 years) patients with beta thalassaemia major ...

  3. Bootstrap transition to high beta equilibrium in helical system

    International Nuclear Information System (INIS)

    It is shown theoretically and computationally that helical magnetic field, produced by continuous winding helical coils and without the toroidal coil, can sustain MHD stable high beta plasma. Pressure driven toroidal current (bootstrap current) cancels the external magnetic field and reduces the MHD potential energy, depending on the plasma beta values. Ramp-up of heating power input induces bootstrap transition to higher beta plasmas with flat-top pressure profiles. Helical pitch parameter dependence of MHD stability is analyzed. (author)

  4. Mitochondrial function in normal and diabetic beta-cells

    OpenAIRE

    Maechler, Pierre; Wollheim, Claes

    2001-01-01

    The aetiology of type 2, or non-insulin-dependent, diabetes mellitus has been characterized in only a limited number of cases. Among these, mitochondrial diabetes, a rare subform of the disease, is the consequence of pancreatic beta-cell dysfunction caused by mutations in mitochondrial DNA, which is distinct from the nuclear genome. The impact of such mutations on beta-cell function reflects the importance of mitochondria in the control of insulin secretion. The beta-cell mitochondria serve a...

  5. New Insights in the Amyloid-Beta Interaction with Mitochondria

    OpenAIRE

    Carlos Spuch; Saida Ortolano; Carmen Navarro

    2012-01-01

    Biochemical and morphological alterations of mitochondria may play an important role in the pathogenesis of Alzheimer’s disease (AD). Particularly, mitochondrial dysfunction is a hallmark of amyloid-beta-induced neuronal toxicity in Alzheimer’s disease. The recent emphasis on the intracellular biology of amyloid-beta and its precursor protein (APP) has led researchers to consider the possibility that mitochondria-associated and mitochondrial amyloid-beta may directly cause neurotoxicity. Both...

  6. Cyclic beta-glucans of members of the family Rhizobiaceae.

    OpenAIRE

    Breedveld, M. W.; Miller, K. J.

    1994-01-01

    Cyclic beta-glucans are low-molecular-weight cell surface carbohydrates that are found almost exclusively in bacteria of the Rhizobiaceae family. These glucans are major cellular constituents, and under certain culture conditions their levels may reach up to 20% of the total cellular dry weight. In Agrobacterium and Rhizobium species, these molecules contain between 17 and 40 glucose residues linked solely by beta-(1,2) glycosidic bonds. In Bradyrhizobium species, the cyclic beta-glucans are ...

  7. Proceedings of the Department of Energy workshop on beta measurements

    International Nuclear Information System (INIS)

    Participants discussed current practices, efforts to upgrade the quality of beta measurements, and initiatives necessary to improve the measurement and control of beta doses. This proceedings includes papers presented at the workshop, transcripts of panel and open discussions, and documentation of question and answer sessions. The information exchange resulting from this meeting is expected to provide a clearer focus on the problems of beta measurements

  8. Influence of. beta. -phase unhomogeneity on titanium martensite structure

    Energy Technology Data Exchange (ETDEWEB)

    Gridnev, V.N.; Ivasishin, O.M.; Markovskij, P.E.; Oshkaderov, S.P.; Svechnikov, V.L. (AN Ukrainskoj SSR, Kiev. Inst. Metallofiziki)

    Martensite structure is studied, formed by the hardening of unhomogeneous ..beta..-solid solution, its concentration unhomogeneity being formed under accelerated heating while hardening. It is established that changes in morphology and crystal geometry of martensite are observed with hardening temperature increasing. The concentration unhomogeneity of ..beta..-phase may lead to the simultaneous existence of various types of martensite together with the increased quantity of the residual ..beta..-phase.

  9. Interactions between Polymyxa betae and plant systemic defense ways

    OpenAIRE

    Desoignies, Nicolas; Schramme, Florence; Legrève, Anne; Vienna Interntational Plant Conference Association - Plant Diseases and resistance mechanisms

    2013-01-01

    Polymyxa betae is the vector of Beet necrotic yellow vein virus (BNYVV), the causal agent of sugar beet rhizomania disease. Because of the widespread use of cultivars partially resistant to BNYVV, resistance breaking BNYVV isolates have been reported. In order to develop alternative control strategies, we investigated interactions between P. betae and plant defenses. A first set of bioassays was conducted in order to assess P. betae infection after the elicitation of inducible defenses in sug...

  10. Evaluation of the instrument correction factors need in beta dosimetry

    International Nuclear Information System (INIS)

    A wide variety of portable survey instruments using Geiger-Mueller (GM) detectors, ionization chambers, or scintillation detectors exists for the measurement of gamma dose rates. Generally, the same instruments are used for beta monitoring, but the beta response of these instruments has been secondary to their development, calibration, and use; information on the beta response is difficult to obtain and seldom provided by the manufacturer. This paper summarizes observations on energy, angular, and source-geometry response of survey instruments

  11. Proceedings of the Department of Energy workshop on beta measurements

    Energy Technology Data Exchange (ETDEWEB)

    Swinth, K.L.; Vallario, E.J.

    1987-09-01

    Participants discussed current practices, efforts to upgrade the quality of beta measurements, and initiatives necessary to improve the measurement and control of beta doses. This proceedings includes papers presented at the workshop, transcripts of panel and open discussions, and documentation of question and answer sessions. The information exchange resulting from this meeting is expected to provide a clearer focus on the problems of beta measurements.

  12. Labeled ALPHA4BETA2 ligands and methods therefor

    Energy Technology Data Exchange (ETDEWEB)

    Mukherjee, Jogeshwar; Pichika, Ramaiah; Potkin, Steven; Leslie, Frances; Chattopadhyay, Sankha

    2013-02-19

    Contemplated compositions and methods are employed to bind in vitro and in vivo to an .alpha.4.beta.2 nicotinic acetylcholine receptor in a highly selective manner. Where such compounds are labeled, compositions and methods employing such compounds can be used for PET and SPECT analysis. Alternatively, and/or additionally contemplated compounds can be used as antagonists, partial agonists or agonists in the treatment of diseases or conditions associated with .alpha.4.beta..beta.2 dysfunction.

  13. ADAM12-mediated focal adhesion formation is differently regulated by beta1 and beta3 integrins

    DEFF Research Database (Denmark)

    Thodeti, Charles Kumar; Frohlich, Camilla; Nielsen, Christian Kamp;

    2005-01-01

    ADAM12, adisintegrin and metalloprotease, has been demonstrated to be upregulated in human malignant tumors and to accelerate the malignant phenotype in a mouse model for breast cancer. ADAM12 is a substrate for beta1 integrins and may affect tumor and stromal cell behavior through its binding to...

  14. Sizeable beta-strength in 31Ar (beta 3p) decay

    DEFF Research Database (Denmark)

    T. Koldste, G.; Blank, B.; J. G. Borge, M.;

    2014-01-01

    We present for the first time precise spectroscopic information on the recently discovered decay mode beta-delayed 3p-emission. The detection of the 3p events gives an increased sensitivity to the high energy part of the Gamow-Teller strength distribution from the decay of 31Ar revealing that as ...

  15. Noncovalent Interaction Energies in Covalent Complexes: TEM-1 beta-Lactamase and beta-Lactams

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiaojun; Minasov, George; Shoichet, Brian K. (NWU)

    2010-03-08

    The class A {beta}-lactamase TEM-1 is a key bacterial resistance enzyme against {beta}-lactam antibiotics, but little is known about the energetic bases for complementarity between TEM-1 and its inhibitors. Most inhibitors form a covalent adduct with the catalytic Ser70, making the measurement of equilibriumconstants, and hence interaction energies, technically difficult. This study evaluates noncovalent interactions withincovalent complexes by examining the differential stability of TEM-1 and its inhibitor adducts. The thermal denaturation of TEM-1 follows a two-state, reversible model with a melting temperature (T{sub m}) of 51.6 C and a van't Hoff enthalpy of unfolding ({Delta}H{sub VH}) of 146.2 kcal/mol at pH 7.0. The stability of the enzyme changes on forming an inhibitor adduct. As expected, some inhibitors stabilize TEM-1; transition-state analogues increase the T{sub m} by up to 3.7 C(1.7 kcal/mol). Surprisingly, all {beta}-lactam covalent acyl-enzyme complexes tested destabilize TEM-1 significantly relative to the apoenzyme. For instance, the clinically used inhibitor clavulanic acid and the {beta}-lactamase-resistant {beta}-lactams moxalactam and imipenem destabilize TEM-1 by over 2.6 C (1.2 kcal/mol) in their covalent adducts. Based on the structure of the TEM-1/imipenem complex (Maveyraud et al., J Am Chem Soc 1998;120:9748-52), destabilization by moxalactam and imipenem is thought to be caused by a steric clash between the side-chain of Asn132 and the 6(7)-{alpha} group of these {beta}-lactams. To test this hypothesis, the mutant enzyme N132A was made. In contrast with wild-type, the covalent complexes between N132A and both imipenem and moxalactam stabilize the enzyme, consistent with the hypothesis. To investigate the structural bases of this dramatic change instability, the structure of N132A/imipenem was determined by X-ray crystallography. In the complex with N132A, imipenemadopts a very different conformation from that observed in the wild

  16. Properties of a commercial extrapolation chamber in beta radiation fields

    International Nuclear Information System (INIS)

    A commercial extrapolation chamber (PTW, Germany) was tested in different beta radiation fields and its properties investigated. Its usefulness for beta radiation calibration and dosimetry was demonstrated. The Beta Secondary Standard setup of the IPEN calibration laboratory was utilized. This system, developed by the Physikalisch-Tecknische Bundesanstalt, Brunswick (Germany) and manufactured by Buchler and Co., consists of a source stand, a control unit with timer and four interchangeable beta sources: 90Sr-90Y (1850 and 74 MBq), 204Tl (18,5 MBq) ionization current detection. The variable volume ionization chamber of cylindrical form is provided with different collecting electrodes of tissue equivalent material and Mylar entrance windows of different thickesses

  17. Isolation and characterization of chicken and turkey beta 2-microglobulin

    DEFF Research Database (Denmark)

    Skjødt, K; Welinder, K G; Crone, M;

    1986-01-01

    Chicken and turkey beta 2-m were isolated from citrated plasma in sequential use of three chromatographic steps: affinity chromatography, gel filtration chromatography and anion-exchange chromatography. The purified protein was identified as beta 2-m by reaction with a beta 2-m specific monoclonal...... antibody and by the ability to recombine with the chicken MHC class I heavy chain. The purity was estimated by SDS-PAGE and IEF. The pI was between 5.1 and 5.3 for chicken beta 2-m and 4.7 and 4.8 for turkey beta 2-m, which fact is reflected in their different electrophoretic mobilities in agarose gel...... (turkey migrates in the alpha and chicken migrates in the beta region). The mol. wt of both chicken and turkey beta 2-m was 14,500 estimated by SDS-PAGE whereas calculations based on the amino acid compositions gave mol. wts of 11,000. EM280 was 15.9 for chicken beta 2-m and 16.4 for turkey beta 2-m...

  18. Interaction between {beta}-Lapachone and Ionizing Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Eun Kyung; Song, Si Yeol; Shin, Seong Soo; Lee, Sang Wook; Ahn, Seung Do; Kim, Jong Hoon [College of Medicine, University of Ulsan, Seoul (Korea, Republic of); Park, Heon Joo [College of Medicine, Inha University, Incheon (Korea, Republic of); Song, Chang Won [University of Minnesota Medical School, Minneapolis (United States)

    2006-07-01

    {beta}-Lapachone (3,4-dihydro-2,2-dimethyl-2Hnaphtho[ 1,2-b]pyran-5,6-dione)({beta}-lap) was originally isolated from the bark of the Lapacho tree growing in South America (1). This drug has attracted considerable interest in recent years because of its potent cytotoxicity against various cancer cell lines through a mechanism that works independent of the cell cycle of p53 status. Interestingly, {beta}-lap has been reported to react synergistically with Taxol, mitomycin C, genistein, and ionizing radiation (IR) (2-3) in vitro against cultured cancer cells. It has also been reported that {beta}-lap inhibits the repair of potentially lethal radiation damage by converting repairable single-stranded DNA breaks into repair-resistant, double-stranded DNA breaks. Thus {beta}- lap has been thought to act as a radiation sensitizer by inhibiting DNA damage repair. In the present study, we observed that IR sensitizes cancer cells to {beta}-lap. It thus appeared that the synergistic interaction of IR and {beta}-lap in killing cancer cells was due to an increase in cellular susceptibility to {beta}-lap, probably in addition to {beta}-lap. induced radiosensitization.

  19. Imaging the Beta-cell mass: why and how

    DEFF Research Database (Denmark)

    Saudek, Frantisek; Brogren, Carl-Henrik; Manohar, Srirang

    2008-01-01

    Diabetes is a disorder characterized by beta-cell loss or exhaustion and insulin deficiency. At present, knowledge is lacking on the underlying causes and for the therapeutic recovery of the beta-cell mass. A better understanding of diabetes pathogenesis could be obtained through exact monitoring...... that the tracer specifically bound to the beta-cell surface and could be detected by nuclear imaging. In the near future, these promising findings may offer a new way to monitor the beta-cell mass in vivo under disease and therapy conditions so that we can learn more about diabetes pathogenesis and options...

  20. International society of sports nutrition position stand: Beta-Alanine.

    Science.gov (United States)

    Trexler, Eric T; Smith-Ryan, Abbie E; Stout, Jeffrey R; Hoffman, Jay R; Wilborn, Colin D; Sale, Craig; Kreider, Richard B; Jäger, Ralf; Earnest, Conrad P; Bannock, Laurent; Campbell, Bill; Kalman, Douglas; Ziegenfuss, Tim N; Antonio, Jose

    2015-01-01

    The International Society of Sports Nutrition (ISSN) provides an objective and critical review of the mechanisms and use of beta-alanine supplementation. Based on the current available literature, the conclusions of the ISSN are as follows: 1) Four weeks of beta-alanine supplementation (4-6 g daily) significantly augments muscle carnosine concentrations, thereby acting as an intracellular pH buffer; 2) Beta-alanine supplementation currently appears to be safe in healthy populations at recommended doses; 3) The only reported side effect is paraesthesia (tingling), but studies indicate this can be attenuated by using divided lower doses (1.6 g) or using a sustained-release formula; 4) Daily supplementation with 4 to 6 g of beta-alanine for at least 2 to 4 weeks has been shown to improve exercise performance, with more pronounced effects in open end-point tasks/time trials lasting 1 to 4 min in duration; 5) Beta-alanine attenuates neuromuscular fatigue, particularly in older subjects, and preliminary evidence indicates that beta-alanine may improve tactical performance; 6) Combining beta-alanine with other single or multi-ingredient supplements may be advantageous when supplementation of beta-alanine is high enough (4-6 g daily) and long enough (minimum 4 weeks); 7) More research is needed to determine the effects of beta-alanine on strength, endurance performance beyond 25 min in duration, and other health-related benefits associated with carnosine. PMID:26175657

  1. Beta 2-Microglobulin clearance as measured by radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Woo, J.; Floyd, M.; Longley, M.A.; Cannon, D.C.

    1980-07-01

    We describe a radioimmunoassay for beta 2-microglobulin (beta 2 mu) in serum and urine. We incubated aliquots of diluted samples at room temperature for 1 h with /sup 125/I-labeled beta 2 mu and a rabbit antiserum monospecific for human beta 2 mu, and separated the phases by the double-antibody technique. The logit-log transformed dose-response curve was linear in the range 2 to 64 ng, equivalent to 0.5 to 16 mg/L of serum and 0.5 to 320 mg/L of urine. Assay sensitivity was 2.4 ng of beta 2 mu. Validation studies included tests of precision, accuracy, antibody specificity, and parallelism of the dose-response curves for standard and unknown. In a study of 25 normal individuals, serum and urine beta 2 mu ranged from 1.1 to 2.3 mg/L and 40 to 360 micrograms/24 h; the clearance of beta 2 mu was 8 to 130 microL/min. In 21 renal allograft recipients tested one to five weeks after transplantation, serum and urine beta 2 mu ranged from 3.9 to 15.6 mg/L and 7.2 to 611 mg/24 h; beta 2 mu clearance was 0.60 to 33.3 mL/min. Values for both serum and urine correlated well with severity of allograft rejection.

  2. Microstructures of duplex (beta + gamma) silver-tin alloys.

    Science.gov (United States)

    Abbott, J R; Miller, D R; Netherway, D J

    1985-05-01

    The microstructures of (beta + gamma) silver-tin alloys are especially influenced by both homogenization temperature and subsequent heat treatment. When the alloy is cooled from homogenization temperatures above approximately 200 degrees C, lenticular regions of the ordered orthorhombic gamma phase precipitate from within the disordered h.c.p. beta phase on three structurally equivalent planes, (1210), (1120), and (2110), to form a Widmanstatten structure. When the duplex alloys were homogenized at temperatures below approximately 200 degrees C, where the beta/(beta + gamma) phase boundary is vertical, these structures were not observed. PMID:3858310

  3. Beta-endorphin in genetically hypoprolactinemic rat: IPL nude rat

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, H.; Sabbagh, I.; Abou-Samra, A.B.; Bertrand, J.

    1986-01-20

    Beta-endorphin has been reported to regulate not only stress- and suckling-induced but also basal prolactin secretion. In the aim to better evaluate the endogenous beta-endorphin-prolactin interrelation, the authors measured beta-endorphin levels in a new rat strain, genetically hypoprolactinemic and characterized by a total lack of lactation: IPL nude rat. Beta-endorphin was measured using a specific anti-h-..beta.. endorphin in plasma and extracts of anterior and neurointermediate lobes of the pituitary, hypothalamus and brain. Pituitary extracts were also chromatographed on Sephadex G50 column. Results obtained showed that in IPL nude females on diestrus and males, the beta-endorphin contents of the neurointermediate lobe was significantly lower than in normal rats, while the values found in the other organs and plasma were similar. However, elution pattern of the anterior pituitary extracts from male rats showed greater immunoactivity eluting as I/sup 125/ h-beta-endorphin than in normal rat; this was not the case for the female rat. These results are consistent with a differential regulation of beta-endorphin levels of anterior and neurointermediate lobe by catecholamines. Moreover they suggest that PRL secretion was more related to neurointermediate beta-endorphin. 40 references, 2 figures, 4 tables.

  4. Latency and activation in the control of TGF-beta

    Science.gov (United States)

    Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

    1996-01-01

    The biological activity of the transforming growth factor-beta's (TGF-beta)3 is tightly controlled by their persistence in the extracellular compartment as latent complexes. Each of the three mammalian isoform genes encodes a product that is cleaved intracellularly to form two polypeptides, each of which dimerizes. Mature TGF-beta, a 24 kD homodimer, is noncovalently associated with the 80 kD latency-associated peptide (LAP). LAP is a fundamental component of TGF-beta that is required for its efficient secretion, prevents it from binding to ubiquitous cell surface receptors, and maintains its availability in a large extracellular reservoir that is readily accessed by activation. This latent TGF-beta complex (LTGF-beta) is secreted by all cells and is abundant both in circulating forms and bound to the extracellular matrix. Activation describes the collective events leading to the release of TGF-beta. Despite the importance of TGF-beta regulation of growth and differentiation in physiological and malignant tissue processes, remarkably little is known about the mechanisms of activation in situ. Recent studies of irradiated mammary gland reveal certain features of TGF-beta 1 activation that may shed light on its regulation and potential roles in the normal and neoplastic mammary gland.

  5. Ubuntu 6.10 Edgy Beta 1发布

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    近日,Ubuntu项目发布Ubuntu 6.10 Edgy Eft Beta 1版本,Edgy Eft Beta 1包含新的2.6.17版本内核、Xorg 7.1、GNOME 2.16正式版、新的Firefox浏览器Firefox2.0 Beta2、OpenOffice.org2.0.4RC2版本、聊天软件Gaim的新版本2.0 Beta3.1和新的init系统。

  6. Design, synthesis, and evaluation of 2 beta-alkenyl penam sulfone acids as inhibitors of beta-lactamases.

    Science.gov (United States)

    Richter, H G; Angehrn, P; Hubschwerlen, C; Kania, M; Page, M G; Specklin, J L; Winkler, F K

    1996-09-13

    A general method for synthesis of 2 beta-alkenyl penam sulfones has been developed. The new compounds inhibited most of the common types of beta-lactamase. The level of activity depended very strongly on the nature of the substituent in the 2 beta-alkenyl group. The inhibited species formed with the beta-lactamase from Citrobacter freundii 1205 was sufficiently stable for X-ray crystallographic studies. These, together with UV absorption spectroscopy and studies of chemical degradation, suggested a novel reaction mechanism for the new inhibitors that might account for their broad spectrum of action. The (Z)-2 beta-acrylonitrile penam sulfone Ro 48-1220 was the most active inhibitor from this class of compound. The inhibitor enhanced the action of, for example, ceftriaxone against a broad selection of organisms producing beta-lactamases. The organisms included strains of Enterobacteriaceae that produce cephalosporinases, which is an exceptional activity for penam sulfones.

  7. Vaccinia virus recombinants expressing an 11-kilodalton beta-galactosidase fusion protein incorporate active beta-galactosidase in virus particles.

    Science.gov (United States)

    Huang, C; Samsonoff, W A; Grzelecki, A

    1988-10-01

    Recombinant plasmids in which vaccinia virus transcriptional regulatory sequences were fused to the Escherichia coli lacZ gene were constructed for insertion of the lacZ gene into the vaccinia virus genome. beta-Galactosidase (beta-gal) was found in some purified recombinant vaccinia virions. By enzyme activity, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and microscopic techniques, the evidence suggested that beta-gal accounted for 5% of the total protein in the virion. These recombinant viruses were constructed so that a portion of the coding sequences of a late vaccinia virus structural polypeptide was fused to the amino terminus of beta-gal to produce the fusion protein. Removal of the coding sequences resulted in the complete loss of beta-gal activity. This demonstrated that a vaccinia virus DNA segment from a late structural gene is responsible for the incorporation of beta-gal into the virion.

  8. Beta-thalassaemia trait: haematological parameters

    International Nuclear Information System (INIS)

    Thalassaemia syndromes are a group of hereditary disorders characterised by a genetic deficiency in the synthesis of --globin genes. The objective of this study was to determine the haematological features -thalassaemia trait (BTT), and to determine the sensitivity of Mean Corpuscular Volume (MCV), Mean Corpuscular Haemoglobin (MCH) and -thalassaemia trait. Methods: A descriptive study was conducted in Hayatabad Medical Complex, Peshawar from May 2009 to May 2010 with 203 subjects having BTT. Blood samples were collected in EDTA anti-coagulated tubes. RBC indices were taken as part of complete blood count (CBC) by haematology analyser, and Haemoglobin (Hb) electrophoresis was done to determine the HbA2 percentage. The data was collected and analyzed on statistical software for demographic details, RBC indices and HBA2 levels. Results: Out of 203 patients, 92 (45%) were males and 111 (55%) were females. Most patients tested were in the 15-45 year age group. One-hundred-sixty (79%) patients had anaemia. MCV was lower than 76 fl in all the cases. Mean MCV was 59.1 fl. MCH was low, the mean MCH being 19.3 g/dl. MCH <26 gave sensitivity of 99% in detecting BTT. We calculated MI for these cases and found out that it was <12 in 75% of cases and <15 in 197 (97%). Conclusion: Beta-thalassaemia traits present with a microcytic hypochromic blood picture, detected on simple haematology analysers as low MCV and MCH and MI which provide a beta- thalassaemia trait. (author)

  9. A background free double beta decay experiment

    CERN Document Server

    Giomataris, Ioannis

    2010-01-01

    We present a new detection scheme for rejecting backgrounds in neutrino less double beta decay experiments. It relies on the detection of Cherenkov light emitted by electrons in the MeV region. The momentum threshold is tuned to reach a good discrimination between background and good events. We consider many detector concepts and a range of target materials. The most promising is a high-pressure 136Xe emitter for which the required energy threshold is easily adjusted. Combination of this concept and a high pressure Time Projection Chamber could provide an optimal solution. A simple and low cost effective solution is to use the Spherical Proportional Counter that provides two delayed signals from ionization and Cherenkov light. In solid-state double beta decay emitters, because of their higher density, the considered process is out of energy range. An alternative solution could be the development of double decay emitters with lower density by using for instance the aerogel technique. It is surprising that a te...

  10. Exchange effects in double beta decay

    International Nuclear Information System (INIS)

    Over the past decade there has been very impressive progress in the laboratory study of double beta decay with very precise limits on 0-neutrino decay in /sup 76/Ge, the imminent prospect of the observation of 2-neutrino decay in /sup 100/Mo and the first laboratory observation of 2-neutrino decay in /sup 82/Se. For the last case, the laboratory rate is in essential agreement with geochemical results and in reasonable agreement with theoretical predictions based on a full shell model calculation. The motivation underlying the resurgence of interest in double beta decay is the hope that the observation of, or limits on the 0-neutrino mode will provide information about the nature of the neutrino. This clearly requires confidence in the nuclear matrix elements involved in the transition. The shell model calculations do not agree well with the geochemical values for /sup 130/Te, which has led to a spate of papers offering specific fixes for the problem. In this contribution we shall not comment on any of the specific nuclear calculations, rather we make some remarks which should be relevant to any model calculation. 11 refs., 1 tab

  11. Neutrinoless double beta decay search with SNO+

    Directory of Open Access Journals (Sweden)

    Lozza V.

    2014-01-01

    Full Text Available The SNO+ experiment is the follow up of SNO. The detector is located 2 km underground in the Vale Canada Ltd.’s Creighton Mine near Sudbury, Ontario, Canada. The active volume of the detector consists of 780 tonnes of Linear Alkyl Benzene (LAB in an acrylic vessel of 12 m diameter, surrounded by about 9500 PMTs. The main goal of the SNO+ experiment is the search for neutrinoless double beta decay of 130Te. With an initial loading of 0.3% of natural tellurium (nearly 800 kg of 130Te, it is expected to reach a sensitivity on the effective Majorana neutrino mass of about 100 meV after several years of data taking. Designed as a general purpose neutrino experiment, other exciting physical goals can be explored, like the measurement of reactor neutrino oscillations and geo-neutrinos in a geologically-interesting location, watch of supernova neutrinos and studies of solar neutrinos. A first commissioning phase with water filled detector will start at the end of 2013, while the double beta decay phase will start in 2015.

  12. Apoptosis of beta cells in diabetes mellitus.

    Science.gov (United States)

    Anuradha, Rachakatla; Saraswati, Mudigonda; Kumar, Kishore G; Rani, Surekha H

    2014-11-01

    Diabetes mellitus is a multifactorial metabolic disorder characterized by hyperglycemia. Apoptosis in beta cells has been observed in response to diverse stimuli, such as glucose, cytokines, free fatty acids, leptin, and sulfonylureas, leading to the activation of polyol, hexosamine, and diacylglycerol/protein kinase-C (DAG/PKC) pathways that mediate oxidative and nitrosative stress causing the release of different cytokines. Cytokines induce the expression of Fas and tumor necrosis factor-alpha (TNF-α) by activating the transcription factor, nuclear factor-κb, and signal transducer and activator of transcription 1 (STAT-1) in the β cells in the extrinsic pathway of apoptosis. Cytokines produced in beta cells also induce proapoptotic members of the intrinsic pathway of apoptosis. The genetic alterations in apoptosis signaling machinery and the pathogenesis of diabetes include Fas, FasL, Akt, caspases, calpain-10, and phosphatase and tensin homolog (Pten). The other gene products that are involved in diabetes are nitric oxide synthase-2 (NOS2), small ubiquitin-like modifier (SUMO), apolipoprotein CIII (ApoCIII), forkhead box protein O1 (FOXO1), and Kruppel-like zinc finger protein Gli-similar 3 (GLIS3). The gene products having antiapoptotic nature are Bcl-2 and Bcl-XL. Epigenetic mechanisms play an important role in type I and type II diabetes. Further studies on the apoptotic genes and gene products in diabetics may be helpful in pharmacogenomics and individualized treatment along with antioxidants targeting apoptosis in diabetes. PMID:25093391

  13. STIS Coronagraphic Observations of Beta Pictoris

    CERN Document Server

    Heap, S R; Lanz, T M; Cornett, R H; Hubeny, I; Maran, S P; Woodgate, B E; Heap, Sara R.; Lindler, Don J.; Lanz, Thierry M.; Cornett, Robert H.; Hubeny, Ivan; Maran, Stephen P.; Woodgate, Bruce

    1999-01-01

    We present new coronagraphic images of Beta Pictoris obtained with the Space Telescope Imaging Spectrograph (STIS) in September 1997. The high-resolution images (0.1") clearly detect the circumstellar disk as close as 0.75" to the star, corresponding to a projected radius of 15 AU. The images define the warp in the disk with greater precision and at closer radii to Beta Pic than do previous observations. They show that the warp can be modelled by the projection of two components: the main disk, and a fainter component, which is inclined to the main component by 4-5 degrees, and which extends only as far as ~4" from the star. We interpret the main component as arising primarily in the outer disk and the tilted component as defining the inner region of the disk. The observed properties of the warped inner disk are inconsistent with a driving force from stellar radiation. However, warping induced by the gravitational potential of one or more planets is consistent with the data. Using models of planet-warped disk...

  14. A POTENTIAL MECHANISM OF BREAKTHROUGH BLEEDING ASSOCIATED WITH PROGESTIN: INVOLVEMENT IN ALTERATION OF ENDOMETRIAL ENDOTHELIAL CELLS

    Institute of Scientific and Technical Information of China (English)

    Gui-hua Sha; Shou-qing Lin

    2008-01-01

    Objective To explore the potential mechanism of breakthrough bleeding associated with progestin with in vitro methods.Methods The isolation and culture of human endometrial endothelial cells (HEECs) was performed with themethod established in our laboratory. The content and activity of urokinase-type plasminogen activator (uPA) and the content of plasminogen activator inhibitor-1 ( PAI-1 ) in cell supernatants after incubated with different concentrations of progesterone (0-5 μmol/L) and 17β-estradiol (0, 0.1, or 1 nmol/L) were measured by method of ELISA. Apoptosis rate of HEECs was measured by flow eytometry. Viable cell count was measured by MTr.Results The increased level of progesterone (0.5-5 μmol/L) combined with 17β-estmdiol elevated content and activity of uPA while the production of PAI-1 remained unchanged. The apoptosis of HEECs was inhibited along with the increment of total viable cell counts at higher ooneenwations of progesterone with 17β-estradiol.Conclusion The inhibition of apoptosis and increased content and activity of uPA may contribute to the occurrence of irregular bleeding associated with progestin use to some extent.

  15. Endocrine expression of the active form of TGF-beta1 in the TGF-beta1 null mice fails to ameliorate lethal phenotype.

    Science.gov (United States)

    Longenecker, Glenn; Thyagarajan, Tamizchelvi; Nagineni, Chandrasekharam N; Flanders, Kathleen C; Factor, Valentina; Miller, Georgina; Ward, Jerrold M; Nalca, Aysegul; Rangnekar, Vivek M; Thorgeirsson, Snorri; Kulkarni, Ashok B

    2002-04-01

    TGF-beta1 null mice die by 3 to 4 weeks of age due to a severe autoimmune-mediated multifocal inflammation resulting in multi-organ failure. To assess the therapeutic potential of circulating levels of active TGF-beta1, we generated mice with endocrine expression of active TGF-beta1 on a TGF-beta1 null background (TGF-beta1 (-/-/TG)) by crossing TGF-beta1(+/-) mice with transgenic mice (TG) that express recombinant TGF-beta1 specifically in the liver and secrete it in the blood. The TGF-beta1 (-/-/TG) mice exhibit a survival profile similar to the TGF-beta1 (-/-) mice indicating a failure to rescue the lethal phenotype. However, serum TGF-beta1 levels in the TGF-beta1 (-/-/TG) mice were restored to near normal levels with expression in all the tissues, notably in the kidney and spleen. Histopathology showed reduced inflammation in the target tissues, especially in the heart. Interestingly, unlike TGF-beta1 (-/-) mice, the TGF-beta1 (-/-/TG) mice have glomerulonephritis in their kidneys similar to the TG mice. Thus, the phenotype of TGF-beta1 (-/-/TG) animal model indicates the potential role of circulating active-TGF-beta1 in reducing inflammation, but its failure to rescue lethality in TGF-beta1 null mice indicates a critical autocrine role of TGF-beta1.

  16. Cdk4 regulates recruitment of quiescent beta-cells and ductal epithelial progenitors to reconstitute beta-cell mass.

    Directory of Open Access Journals (Sweden)

    Ji-Hyeon Lee

    Full Text Available Insulin-producing pancreatic islet beta cells (beta-cells are destroyed, severely depleted or functionally impaired in diabetes. Therefore, replacing functional beta-cell mass would advance clinical diabetes management. We have previously demonstrated the importance of Cdk4 in regulating beta-cell mass. Cdk4-deficient mice display beta-cell hypoplasia and develop diabetes, whereas beta-cell hyperplasia is observed in mice expressing an active Cdk4R24C kinase. While beta-cell replication appears to be the primary mechanism responsible for beta-cell mass increase, considerable evidence also supports a contribution from the pancreatic ductal epithelium in generation of new beta-cells. Further, while it is believed that majority of beta-cells are in a state of 'dormancy', it is unclear if and to what extent the quiescent cells can be coaxed to participate in the beta-cell regenerative response. Here, we address these queries using a model of partial pancreatectomy (PX in Cdk4 mutant mice. To investigate the kinetics of the regeneration process precisely, we performed DNA analog-based lineage-tracing studies followed by mathematical modeling. Within a week after PX, we observed considerable proliferation of islet beta-cells and ductal epithelial cells. Interestingly, the mathematical model showed that recruitment of quiescent cells into the active cell cycle promotes beta-cell mass reconstitution in the Cdk4R24C pancreas. Moreover, within 24-48 hours post-PX, ductal epithelial cells expressing the transcription factor Pdx-1 dramatically increased. We also detected insulin-positive cells in the ductal epithelium along with a significant increase of islet-like cell clusters in the Cdk4R24C pancreas. We conclude that Cdk4 not only promotes beta-cell replication, but also facilitates the activation of beta-cell progenitors in the ductal epithelium. In addition, we show that Cdk4 controls beta-cell mass by recruiting quiescent cells to enter the cell

  17. The Promiscuity of [beta]-Strand Pairing Allows for Rational Design of [beta]-Sheet Face Inversion

    Energy Technology Data Exchange (ETDEWEB)

    Makabe, Koki; Koide, Shohei (UC)

    2009-06-17

    Recent studies suggest the dominant role of main-chain H-bond formation in specifying {beta}-sheet topology. Its essentially sequence-independent nature implies a large degree of freedom in designing {beta}-sheet-based nanomaterials. Here we show rational design of {beta}-sheet face inversions by incremental deletions of {beta}-strands from the single-layer {beta}-sheet of Borrelia outer surface protein A. We show that a {beta}-sheet structure can be maintained when a large number of native contacts are removed and that one can design large-scale conformational transitions of a {beta}-sheet such as face inversion by exploiting the promiscuity of strand-strand interactions. High-resolution X-ray crystal structures confirmed the success of the design and supported the importance of main-chain H-bonds in determining {beta}-sheet topology. This work suggests a simple but effective strategy for designing and controlling nanomaterials based on {beta}-rich peptide self-assemblies.

  18. Effects of amphetamine and beta-endorphin fragments on maze performance in rats

    NARCIS (Netherlands)

    Bohus, B; de Boer, S.F.

    1990-01-01

    Fragments of beta-endorphin and amphetamine cause similar effects in some tests of maze behavior in rats. The present study served to compare the influence of amphetamine and two beta-endorphin fragments [beta-endorphin (beta E)-(2-9) and beta E-(2-16)] on maze behavior in more detail. In Experiment

  19. Role for DNA polymerase beta in response to ionizing radiation.

    NARCIS (Netherlands)

    Vermeulen, C.; Verwijs-Janssen, M.; Cramers, P.; Begg, A.C.; Vens, C.

    2007-01-01

    Evidence for a role of DNA polymerase beta in determining radiosensitivity is conflicting. In vitro assays show an involvement of DNA polymerase beta in single strand break repair and base excision repair of oxidative damages, both products of ionizing radiation. Nevertheless the lack of DNA polymer

  20. Search for neutrinoless double beta decay with DCBA

    International Nuclear Information System (INIS)

    A project called DCBA (Drift Chamber Beta-ray Analyzer) is in progress at KEK in order to search for the events of neutrinoless double beta decay. For investigating technical problems, a test apparatus called DCBA-T has been constructed. The preliminary results of its engineering run are described together with the simulation studies of backgrounds originating from 214Bi and 208Tl

  1. Reversal of haemochromatotic cardiomyopathy in beta thalassaemia by chelation therapy.

    OpenAIRE

    Politi, A; M. Sticca; Galli, M

    1995-01-01

    Haemochromatotic cardiomyopathy is the main cause of morbidity and mortality in patients with beta thalassaemia major. Once congestive heart failure develops most patients die in a few months. Congestive heart failure was reversed and echocardiographic findings were restored to normal in a 24 year old woman with beta thalassaemia who resumed treatment with chelation therapy (desferrioxamine).

  2. Definition of $\\tan\\beta$ beyond tree-level

    OpenAIRE

    Yamada, Youichi

    1996-01-01

    We study the relation between different renormalization schemes for the parameter $\\tan\\beta$ in the Minimal Supersymmetric Standard Model. The contributions of the third-generation quark-squark loops to the differences between $\\tan\\beta$'s in several schemes are discussed. Their numerical differences are typically within several %.

  3. Response of ionization chamber based pocket dosimeter to beta radiation.

    Science.gov (United States)

    Kumar, Munish; Gupta, Anil; Pradhan, S M; Bakshi, A K; Chougaonkar, M P; Babu, D A R

    2013-12-01

    Quantitative estimate of the response of ionization chamber based pocket dosimeters (DRDs) to various beta sources was performed. It has been established that the ionization chamber based pocket dosimeters do not respond to beta particles having energy (Emax)1 MeV, the DRDs exhibit measureable response and the values are ~8%, ~14% and ~27% per mSv for natural uranium, (90)Sr/(90)Y and (106)Ru/(106)Rh beta sources respectively. As the energy of the beta particles increases, the response also increases. The response of DRDs to beta particles having energy>1 MeV arises due to the fact that the thickness of the chamber walls is less than the maximum range of beta particles. This may also be one of the reasons for disparity between doses measured with passive/legal dosimeters (TLDs) and DRDs in those situations in which radiation workers are exposed to mixed field of gamma photons and beta particles especially at uranium processing plants, nuclear (power and research) reactors, waste management facilities and fuel reprocessing plants etc. The paper provides the reason (technical) for disparity between the doses recorded by TLDs and DRDs in mixed field of photons and beta particles.

  4. beta-Catenin regulates airway smooth muscle contraction

    NARCIS (Netherlands)

    Jansen, Sepp R.; Van Ziel, Anna M.; Baarsma, Hoeke A.; Gosens, Reinoud

    2010-01-01

    Jansen SR, Van Ziel AM, Baarsma HA, Gosens R. beta-Catenin regulates airway smooth muscle contraction. Am J Physiol Lung Cell Mol Physiol 299: L204-L214, 2010. First published May 14, 2010; doi:10.1152/ajplung.00020.2010.-beta-Catenin is an 88-kDa member of the armadillo family of proteins that is a

  5. Role of IL-1beta in type 2 diabetes

    DEFF Research Database (Denmark)

    Dinarello, Charles A; Donath, Marc Y; Mandrup-Poulsen, Thomas

    2010-01-01

    To understand the role of inflammation as the fundamental cause of type 2 diabetes and specifically to examine the contribution of IL-1beta.......To understand the role of inflammation as the fundamental cause of type 2 diabetes and specifically to examine the contribution of IL-1beta....

  6. Library Book Circulation and the Beta-Binomial Distribution.

    Science.gov (United States)

    Gelman, E.; Sichel, H. S.

    1987-01-01

    Argues that library book circulation is a binomial rather than a Poisson process, and that individual book popularities are continuous beta distributions. Three examples demonstrate the superiority of beta over negative binomial distribution, and it is suggested that a bivariate-binomial process would be helpful in predicting future book…

  7. Induction of beta-galactosidase in Streptomyces violaceus.

    Science.gov (United States)

    Sanchez, J; Hardisson, C

    1979-07-01

    Synthesis of beta-galactosidase by Streptomyces violaceus was induced by D-galactose and L-arabinose, and to a lesser extent by lactose, D-arabinose, and methyl-beta-D-galactopyranoside. The synthesis of the enzyme was linear and started to increase 2--3 h after induction by galactose, reaching a maximum after 5--7 h. The highest level of specific activity was observed in 2% galactose, with an increase of 45 times over the basal level in glycerol. Isopropyl-beta-D-thiogalactopyranoside (IPTG) and methyl-beta-D-thiogalactopyranoside (TMG) inhibited induction by D-galactose, but did not influence enzymatic activity. Cellular extracts hydrolyzed O-nitrophenyl-beta-D-galactopyranoside, but did not significantly hydrolyze lactose, melibiose, p-nitrophenyl-alpha-D-galactopyranoside, p-nitrophenyl-beta-D-fucoside, or p-nitrophenyl-beta-D-glucopyranoside. Rifampicin and chloramphenicol inhibited beta-galactosidase synthesis in non-preinduced and in preinduced cells. The inhibition by chloramphenicol was reversible. PMID:113072

  8. Novel Beta-Gamma Coincidence Measurements Using Phoswich Detectors

    International Nuclear Information System (INIS)

    The PNNL has developed an Automated Radio-xenon Sampler/Analyzer (ARSA) for the CTBT to measure four radio-xenon isotopes using a beta-gamma coincidence counting detector. A novel method to measure beta-gamma coincidences using a phoswich detector with state-of-the-art pulse shape discrimination techniques has been investigated

  9. Closing in on Mass Production of Mature Human Beta Cells.

    Science.gov (United States)

    Kieffer, Timothy J

    2016-06-01

    Human pluripotent stem cell differentiation protocols based on mimicking developmental pathways are getting close to generating fully fledged pancreatic endocrine cells, including insulin-producing beta cells. However, challenges remain in identifying pathways to trigger the attainment of robust glucose responsiveness that occurs postnatally in beta cells. PMID:27257758

  10. Overview of total beta activity index and beta rest in surface waters of the Spanish rivers; Vision general del indice de actividad beta total y beta resto en las aguas superficiales de los rios espanoles

    Energy Technology Data Exchange (ETDEWEB)

    Pujol, L.; Payeras, J.; Pablo, M. A. de

    2013-07-01

    This work aims to give an overview of the index of total beta activity and the activity index beta rest in surface waters of the main Spanish rivers. These indices are a parameter over water quality that CEDEX comes determined by order of the Ministry of Agriculture, Food and Environment, in water policy. (Author)

  11. Free infinite divisibility for beta distributions and related ones

    OpenAIRE

    Hasebe, Takahiro

    2013-01-01

    We prove that many of beta, beta prime, gamma, inverse gamma, Student t- and ultraspherical distributions are freely infinitely divisible, but some of them are not. The latter negative result follows from a local property of probability density functions. Moreover, we show that the Gaussian, many of ultraspherical and Student t-distributions have free divisibility indicator 1.

  12. Geographical patterns in the beta diversity of China's woody plants

    DEFF Research Database (Denmark)

    Wang, Zhiheng; Fang, Jingyun; Tang, Zhiyao;

    2012-01-01

    Beta diversity (i.e. species turnover rate across space) is fundamental for understanding mechanisms controlling large-scale species richness patterns. However, the influences on beta diversity are still a matter of debate. In particular, the relative role of environmental and spatial processes (e...

  13. Proliferation of sorted human and rat beta cells

    DEFF Research Database (Denmark)

    Parnaud, G; Bosco, D; Berney, T;

    2008-01-01

    The aim of the study was to determine whether purified beta cells can replicate in vitro and whether this is enhanced by extracellular matrix (ECM) and growth factors.......The aim of the study was to determine whether purified beta cells can replicate in vitro and whether this is enhanced by extracellular matrix (ECM) and growth factors....

  14. Plasma transforming growth factor beta levels in breast cancer patients

    NARCIS (Netherlands)

    Sminia, P; Barten, AD; Van Waarde, MAWH; Vujaskovic, Z; Van Tienhoven, G

    1998-01-01

    We investigated whether the concentration of circulating transforming growth factor beta (TGF beta) yields diagnostic value in breast cancer. Blood was collected from twenty stage I and II breast cancer patients both prior to treatment and after surgical excision of the tumour. Both latent and activ

  15. Beta-glucosidases and nucleic acids encoding same

    DEFF Research Database (Denmark)

    2012-01-01

    and pharmaceuticals. Several enzymes of the newly identified strain are efficient in degradation of lignocellulosic biomasses. In particular one enzyme has been identified and characterised as having improved beta-glucosidase activity. The identified beta-glucosidase has improved thermal stability, while maintaining...

  16. Symmetry violations in nuclear and neutron beta decay

    NARCIS (Netherlands)

    Vos, K. K.; Wilschut, H. W.; Timmermans, R. G. E.

    2015-01-01

    The role of beta decay as a low-energy probe of physics beyond the standard model is reviewed. Traditional searches for deviations from the standard model structure of the weak interaction in beta decay are discussed in light of constraints from the Large Hadron Collider and the neutrino mass. Limit

  17. TGF-{beta}-stimulated aberrant expression of class III {beta}-tubulin via the ERK signaling pathway in cultured retinal pigment epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Eun Jee [Department of Ophthalmology, National Health Insurance Corporation Ilsan Hospital, Gyeonggi-do (Korea, Republic of); Chun, Ji Na; Jung, Sun-Ah [Konyang University Myunggok Medical Research Institute, Kim' s Eye Hospital, Konyang University College of Medicine, Seoul (Korea, Republic of); Cho, Jin Won [Department of Biology, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Lee, Joon H., E-mail: joonhlee@konyang.ac.kr [Konyang University Myunggok Medical Research Institute, Kim' s Eye Hospital, Konyang University College of Medicine, Seoul (Korea, Republic of)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer TGF-{beta} induces aberrant expression of {beta}III in RPE cells via the ERK pathway. Black-Right-Pointing-Pointer TGF-{beta} increases O-GlcNAc modification of {beta}III in RPE cells. Black-Right-Pointing-Pointer Mature RPE cells have the capacity to express a neuron-associated gene by TGF-{beta}. -- Abstract: The class III {beta}-tubulin isotype ({beta}{sub III}) is expressed exclusively by neurons within the normal human retina and is not present in normal retinal pigment epithelial (RPE) cells in situ or in the early phase of primary cultures. However, aberrant expression of class III {beta}-tubulin has been observed in passaged RPE cells and RPE cells with dedifferentiated morphology in pathologic epiretinal membranes from idiopathic macular pucker, proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Transforming growth factor-{beta} (TGF-{beta}) has been implicated in dedifferentiation of RPE cells and has a critical role in the development of proliferative vitreoretinal diseases. Here, we investigated the potential effects of TGF-{beta} on the aberrant expression of class III {beta}-tubulin and the intracellular signaling pathway mediating these changes. TGF-{beta}-induced aberrant expression and O-linked-{beta}-N-acetylglucosamine (O-GlcNac) modification of class III {beta}-tubulin in cultured RPE cells as determined using Western blotting, RT-PCR and immunocytochemistry. TGF-{beta} also stimulated phosphorylation of ERK. TGF-{beta}-induced aberrant expression of class III {beta}-tubulin was significantly reduced by pretreatment with U0126, an inhibitor of ERK phosphorylation. Our findings indicate that TGF-{beta} stimulated aberrant expression of class III {beta}-tubulin via activation of the ERK signaling pathway. These data demonstrate that mature RPE cells have the capacity to express a neuron-associated gene in response to TGF-{beta} stimulation and provide useful information

  18. DNA polymerase-beta is expressed early in neurons of Alzheimer's disease brain and is loaded into DNA replication forks in neurons challenged with beta-amyloid

    NARCIS (Netherlands)

    A. Copani; J.J.M. Hoozemans; F. Caraci; M. Calafiore; E.S. van Haastert; R. Veerhuis; A.J.M. Rozemuller; E. Aronica; M.A. Sortino; F. Nicoletti

    2006-01-01

    Cultured neurons exposed to synthetic beta-amyloid (A beta) fragments reenter the cell cycle and initiate a pathway of DNA replication that involves the repair enzyme DNA polymerase-beta (DNA pol-beta) before undergoing apoptotic death. In this study, by performing coimmunoprecipitation experiments

  19. Molecular cloning and phylogenetic analysis of integrins alpha v beta 1 and alpha v beta 6 of one-humped camel (Camelus dromedarius)

    DEFF Research Database (Denmark)

    Du, Junzheng; Larska, Magdalena Larska; Chang, Huiyun;

    2010-01-01

    , and 787 amino acids, respectively. The dromedary camel integrin alpha v, beta 1, and beta 6 subunit shares common structural and functional elements with their counterparts from the other species. Phylogenetic trees showed that the dromedary camel alpha v, beta 1, and beta 6 were clustered...

  20. Fluxon Modeling of Low-Beta Plasmas

    CERN Document Server

    DeForest, C E; Forest, Craig E. De; Kankelborg, Charles C.

    2006-01-01

    We have developed a new, quasi-Lagrangian approach for numerical modeling of magnetohydrodynamics in low to moderate $\\beta$ plasmas such as the solar corona. We introduce the concept of a ``fluxon'', a discretized field line. Fluxon models represent the magnetic field as a skeleton of such discrete field lines, and interpolate field values from the geometry of the skeleton where needed, reversing the usual direction of the field line transform. The fluxon skeleton forms the grid for a collection of 1-D Eulerian models of plasma along individual flux tubes. Fluxon models have no numerical resistivity, because they preserve topology explicitly. Our prototype code, \\emph{FLUX}, is currently able to find 3-D nonlinear force-free field solutions with a specified field topology, and work is ongoing to validate and extend the code to full magnetohydrodynamics. FLUX has significant scaling advantages over conventional models: for ``magnetic carpet'' models, with photospheric line-tied boundary conditions, FLUX simul...