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Sample records for 2-hour urokinase regime

  1. Molecular-specific urokinase antibodies

    Atassi, M. Zouhair (Inventor); Morrison, Dennis R. (Inventor)

    2009-01-01

    Antibodies have been developed against the different molecular forms of urokinase using synthetic peptides as immunogens. The peptides were synthesized specifically to represent those regions of the urokinase molecules which are exposed in the three-dimensional configuration of the molecule and are uniquely homologous to urokinase. Antibodies are directed against the lysine 158-isoleucine 159 peptide bond which is cleaved during activation from the single-chain (ScuPA) form to the bioactive double chain (54 KDa and 33 KDa) forms of urokinase and against the lysine 135 lysine 136 bond that is cleaved in the process of removing the alpha-chain from the 54 KDa form to produce the 33 KDa form of urokinase. These antibodies enable the direct measurement of the different molecular forms of urokinase from small samples of conditioned medium harvested from cell cultures.

  2. Conformational regulation of urokinase receptor function

    Gårdsvoll, Henrik; Jacobsen, Benedikte; Kriegbaum, Mette C;

    2011-01-01

    The urokinase-type plasminogen activator receptor (uPAR) is a glycolipid-anchored membrane protein with an established role in focalizing uPA-mediated plasminogen activation on cell surfaces. Distinct from this function, uPAR also modulates cell adhesion and migration on vitronectin-rich matrices...

  3. Thrombolytic treatment for acute ischemic cerebral stroke: intraarterial urokinase infusion vs. intravenous heparin and urokinase infusion

    To evaluate the efficacy and limitation of intra-arterial urokinase (IAUK) infusion for treatment of acute cerebral stroke. Twenty-seven acute cerebral stroke patients treated with IAUK infusion within six hours of stroke onset were reviewed. All patients showed normal initial brain findings on CT. In 21 patients, urokinase(5-15 x 105IU) was administered through a microcatheter placed into or proximal to occluded segment. Mechanical disruption of thrombus by guidewire was performed in 17 patients. Angiographic and clinical responses and complications after IAUK infusion, were evaluated and the results were compared with those of intravenous heparin(N=19) and urokinase infusion(N=19). Complete or partial angiographic recanalization of occluded segment was found in 18 patients (67%), and neurologic improvement was followed in 14 patients(52%). The degree of improvement on the stroke scale score after IAUK infusion was statistically more significant(p<0.05) than that shown after intravenous heparin and urokinase infusion. Complications after IAUK infusion were large(15%) and small amount intracerebral hemorrhage(15%), contrast leakage into brain parenchyma(11%), and gastrointestinal bleeding(4%). Between the IAVK and the intravenous urokinase infusion group, differences in extent and types of complications were statistically insignificant, but were significantly higher in those two groups than in the intravenous heparin infusion group. IAUK infusion may be effective for the treatment of acute cerebral stroke

  4. Antibodies Against Three Forms of Urokinase

    Morrison, Dennis R.; Atassi, M. Zouhair

    2007-01-01

    Antibodies that bind to preselected regions of the urokinase molecule have been developed. These antibodies can be used to measure small quantities of each of three molecular forms of urokinase that could be contained in microsamples or conditioned media harvested from cultures of mammalian cells. Previously available antibodies and assay techniques do not yield both clear distinctions among, and measurements of, all three forms. Urokinase is a zymogen that is synthesized in a single-chain form, called ScuPA, which is composed of 411 amino acid residues (see figure). ScuPA has very little enzyme activity, but it can be activated in two ways: (1) by cleavage of the peptide bond lysine 158/isoleucine 159 and the loss of lysine 158 to obtain the high molecular-weight (HMW) form of the enzyme or (2) by cleavage of the bond lysine 135/lysine 136 to obtain the low-molecular-weight (LMW) form of the enzyme. The antibodies in question were produced in mice and rabbits by use of peptides as immunogens. The peptides were selected to obtain antibodies that bind to regions of ScuPA that include the lysine 158/isoleucine 159 and the lysine 135/lysine 136 bonds. The antibodies include monoclonal and polyclonal ones that yield indications as to whether either of these bonds is intact. The polyclonal antibodies include ones that preferentially bind to the HMW or LMW forms of the urokinase molecule. The monoclonal antibodies include ones that discriminate between the ScuPA and the HMW form. A combination of these molecular-specific antibodies will enable simultaneous assays of the ScuPA, HMW, and LMW forms in the same specimen of culture medium.

  5. A composite role of vitronectin and urokinase in the modulation of cell morphology upon expression of the urokinase receptor

    Hillig, Thore; Engelholm, Lars H; Ingvarsen, Signe;

    2008-01-01

    The urokinase receptor, urokinase receptor (uPAR), is a glycosylphosphatidylinositol-anchored membrane protein engaged in pericellular proteolysis and cellular adhesion, migration, and modulation of cell morphology. A direct matrix adhesion is mediated through the binding of uPAR to vitronectin, ...

  6. Expression of urokinase receptors by human trophoblast. A histochemical and ultrastructural analysis

    Multhaupt, H A; Mazar, A; Cines, D B;

    1994-01-01

    vivo has not been examined. EXPERIMENTAL DESIGN: Immunohistochemistry and immunoelectron microscopy were used to characterize the expression of urokinase receptors by villous and extravillous trophoblast at several points in gestation. RESULTS: Urokinase receptors were expressed in a polarized fashion...

  7. Regulation of urokinase by cellular receptors and inhibitors

    Several cell types display binding sites for 125I-urokinase which in certain cases are occupied with endogenous urokinase. These sites appear to focus urokinase at cell surfaces and hence may participate in tissue matrix destruction and cell invasion. Using immunofluorescence double labeling, the author shows that the receptor-bound urokinase present on human foreskin fibroblasts and HT1080 human fibrosarcoma cells is colocalized with vinculin, an intracellular actin-binding protein that is deposited at cell to substratum focal adhesion sites. Thus, this indicates linkage of the plasminogen/plasmin system both to sites of cell adhesion and to the cytoskeleton. He furthermore reports that neither EGF, TGFβ or PDGF significantly altered the shape or intensity of the receptor-bound urokinase clusters but that thrombin, at mitogenic doses, caused a disappearance of the urokinase strands and a loss or gross alteration of the underlying focal adhesion plaques, as indicated by immunofluorescence staining for vinculin and talin, and by interference reflection microscopy. These observations suggest that thrombin may be a unique effector of cell adhesion, shape and movement. He used a quantitative in vitro invasion assay to study the role of plasminogen activator inhibitors type 1 and 2 (PAI-1, PAI-2) and protease nexin (PN1) in basement membrane (BM) invasion by 125I-iododeoxyuridine-labeled HT 1080 cells. The results obtained showed that 5 μg/ml of PAI-1, PAI-2 and PN1 preadsorbed to the BM completely blocked HT1080 invasion. On the contrary an anti-PAI-1 monoclonal antibody induced an approximately two-fold increase in invasion. 125I-fibrinogen was polymerized on the amnion BM and the fibrinolytic activity of the cells was measured under the invasion assay conditions by measuring the radioactivity in the culture medium at different time points

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

    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

  9. The significance of the serum CG level of 2 hours after meal in hyperthyroid patients

    To observe the liver condition of hyperthyroid patients with different course of disease, the levels of serum CG over night fasting and of 2 hours after meal in 132 hyperthyroid patients and 50 normal persons were measured by RIA. Hyperthyroid patients were divided into 3 groups by their different course of disease. For normal persons and the group whose course of disease within half year there was no significant difference in CG levels of fasting and 2 hours after meal. For the group whose course of disease in period of 0.5-2 years the CG level of 2 hours after meal were over the normal range (P<0.01), but no difference was found in CG level of fasting. For the group whose course of disease over 2 years, the CG levels of fasting and 2 hours after meal were all over the normal range (P<0.01, P<0.001), CG level of the 2 hours after meal was much higher. The results suggested that CG level measured 2 hours after meal was more sensitive than that after over night fasting in hyperthyroid patients with hepatocellular damage, and the damage degree paralleled to their courses of disease

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

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

    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 ...

  11. UVB increases urokinase-type plasminogen activator receptor (uPAR) expression.

    Marschall, C; Lengyel, E; Nobutoh, T; Braungart, E; Douwes, K; Simon, A; Magdolen, V; Reuning, U; Degitz, K

    1999-07-01

    Keratinocytes synthesize and secrete urokinase-type plasminogen activator, which binds to its specific receptor on keratinocytes. When bound to urokinase-type plasminogen activator receptor, urokinase-type plasminogen activator proteolytically converts surface bound plasminogen to plasmin, which in turn cleaves many extracellular components leading to pericellular proteolysis. The activation of the urokinase system has been observed during re-epithelialization of skin wounds and in lesions of the autoimmune blistering skin disease pemphigus. As pemphigus is photoinducible, we investigated the effect of ultraviolet B on urokinase-type plasminogen activator and urokinase-type plasminogen activator receptor expression in the epidermal keratinocyte cell line A431. Ultraviolet B increased cellular and secreted urokinase-type plasminogen activator protein (enzyme-linked immunosorbent assay) and urokinase-type plasminogen activator receptor cell surface expression (flow cytometry) 24 h postirradiation. Northern blot analysis indicated that ultraviolet B increased urokinase-type plasminogen activator receptor mRNA. Compared with a more rapid mRNA induction by epidermal growth factor (maximal after 4 h) the ultraviolet B response was maximal after 24 h and prolonged up to 36 h. The mRNA induction was not dependent on protein synthesis as judged by cycloheximide incubation. Ultraviolet B did not influence urokinase-type plasminogen activator receptor mRNA stability (actinomycin D incubation). A transiently transfected chloramphenicol acetyltransferase-reporter construct containing a -398/+51 urokinase-type plasminogen activator receptor promoter fragment was activated when cells were exposed to ultraviolet B. This induction was almost completely abolished by mutating a -182/-176 AP-1 binding sequence. Ultraviolet B increased the binding capacity at this AP-1 motif in electrophoretic mobility shift assays. These data identify a distinct transcriptional mechanism by which

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

    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

  13. Urokinase receptor forms in serum from non-small cell lung cancer patients

    Almasi, Charlotte Elberling; Christensen, Ib Jarle; Høyer-Hansen, Gunilla; Danø, Keld; Pappot, Helle; Dienemann, Hendrik; Muley, Thomas

    2011-01-01

    To study the prognostic impact of the different forms of the receptor for urokinase plasminogen activator (uPAR) in serum from 171 non-small cell lung cancer (NSCLC) patients.......To study the prognostic impact of the different forms of the receptor for urokinase plasminogen activator (uPAR) in serum from 171 non-small cell lung cancer (NSCLC) patients....

  14. Plasma soluble urokinase plasminogen activator receptor in children with urinary tract infection

    Wittenhagen, Per; Andersen, Jesper Brandt; Hansen, Anita; Lindholm, Lone; Rønne, Frederik Malmborg; Theil, Jørn; Tvede, Michael; Eugen-Olsen, Jesper

    2011-01-01

    In this prospective study we investigated the role of plasma levels of soluble urokinase plasminogen activator receptor (suPAR) in children with urinary tract infection.......In this prospective study we investigated the role of plasma levels of soluble urokinase plasminogen activator receptor (suPAR) in children with urinary tract infection....

  15. Purification of urokinase by combined cation exchanger and affinity chromatographic cartridges.

    Hou, K C; Zaniewski, R

    1990-02-23

    Crude urokinase from human urine processed through foam flotation and ammonium sulfate precipitation containing 720 National Health Institute Committee on Thrombolytic Agents U/mg activity was purified by an SP cation exchanger followed by a zinc-chelated affinity chromatographic cartridge. The cartridges were of a radial-flow type formed by using acrylic and cellulose composite matrices. The high rigidity of the matrix structure permits fast flow of protein solutions (liters per minute) and thus allows processing of a large volume of crude urokinase under low operating pressures. A greater than six-fold increase in specific enzyme activity of urokinase was achieved by adsorbing and eluting 1 l of a 3 mg/ml crude urokinase solution on an SP cartridge. The eluent was further purified by passing through a zinc-chelated affinity cartridge to achieve greater than a eighteen-fold increase in urokinase specific activity. This report demonstrates the combined use of a cation exchanger with zinc-chelated chromatographic cartridges in purifying urokinase on a relatively large scale. The relationship between the amount of zinc chelated in the matrix to its effect on urokinase purification is also discussed. PMID:2329161

  16. Clinical study of urokinase-bound fibrocollagenous tubes.

    Senatore, F; Bernath, F; Meisner, K

    1986-02-01

    Dacron-reinforced fibrocollagenous tubes (FCT) were synthesized from canine mongrels using the mandril-rod technique in order to develop a small diameter (i.e., 4 mm i.d.) vascular graft. They were rendered fibrinolytic by immobilizing urokinase on to the inner surface of the tubes. Urokinase-bound fibrocollagenous tubes (UK-FCT), control FCTs (i.e., no bound enzyme), Perloff grafts (Dr. Perloff, Department of Surgery, University Medical Center, Sidney Australia, has developed a mandril-derived collagenous tube from goats. Samples were implanted for comparative purposes.) and autogeneous saphenous veins, were interposed in the carotid or femoral artery in chronic studies involving 21 canine mongrels. On the basis of Doppler auscultation and palpation, the UK-FCTs were statistically more patent than other candidate prostheses. Fibrin degradation product (FDP) increased in the dogs' systemic circulation with a postoperative peak of 5 days. The host's increase in fibrinolytic activity was shown to be local to the anastamosis. A carotid arterial extracorporeal shunt was designed to evaluate acute patency. Results indicated a rapid thrombosis but no platlet or fibrin adherence to the graft surface was observed, as evidenced by scanning electron microscopy. PMID:2937788

  17. Structural investigations of recombinant urokinase growth factor-like domain.

    Beloglazova, I B; Beabealashvilli, R Sh; Gursky, Ya G; Bocharov, E V; Mineev, K S; Parfenova, E V; Tkachuk, V A

    2013-05-01

    Urokinase-type plasminogen activator (uPA) is a serine protease that converts the plasminogen zymogen into the enzymatically active plasmin. uPA is synthesized and secreted as the single-chain molecule (scuPA) composed of an N-terminal domain (GFD) and kringle (KD) and C-terminal proteolytic (PD) domains. Earlier, the structure of ATF (which consists of GFD and KD) was solved by NMR (A. P. Hansen et al. (1994) Biochemistry, 33, 4847-4864) and by X-ray crystallography alone and in a complex with the soluble form of the urokinase receptor (uPAR, CD87) lacking GPI (C. Barinka et al. (2006) J. Mol. Biol., 363, 482-495). According to these data, GFD contains two β-sheet regions oriented perpendicularly to each other. The area in the GFD responsible for binding to uPAR is localized in the flexible Ω-loop, which consists of seven amino acid residues connecting two strings of antiparallel β-sheet. It was shown by site-directed mutagenesis that shortening of the Ω-loop length by one amino acid residue leads to the inability of GFD to bind to uPAR (V. Magdolen et al. (1996) Eur. J. Biochem., 237, 743-751). Here we show that, in contrast to the above-mentioned studies, we found no sign of the β-sheet regions in GFD in our uPA preparations either free or in a complex with uPAR. The GFD seems to be a rather flexible and unstructured domain, demonstrating in spite of its apparent flexibility highly specific interaction with uPAR both in vitro and in cell culture experiments. Circular dichroism, tryptophan fluorescence during thermal denaturation of the protein, and heteronuclear NMR spectroscopy of ¹⁵N/¹³C-labeled ATF both free and in complex with urokinase receptor were used to judge the secondary structure of GFD of uPA. PMID:23848154

  18. An experimental investigation on the concentration of selective infusion of urokinase in superacute cerebral embolism in dog

    Objective: To study the effect of thrombolysis of intra-arterial infusion of different concentrations of urokinase (UK) in dogs. Methods: 25 healthy crossbreeding dogs were divided into five groups, with five dogs in each group. Every dog was injected with self-thrombus from carotids internal artery to embolize its distal part or branches. Treatment with different concentrations of UK was initiated 2 hours after setting up the model of cerebral embolism by carotids internal artery. The dose of each group was: A(control group), 0.9% physiological sodium chloride solution; B, 1200 U/ml UK; C, 6000 U/ml UK; D, 12000 U/ml UK; E, 60000 U/ml UK. Angiography and CT scannings were performed before and after thrombolysis. Pathologic examination was performed 24 hours after embolism. Results: The rate of recanalization of groups A, B were 0 but 100% for groups C, D and E, Judged by angiographies after thrombolysis, group C, D and E had significantly better reperfusion compared with group A, B(P<0.0001). Among groups C, D and E there were no significant differences but with a large bleeding in four dogs of group E after recanalization by CT scanning. Conclusions: Intra-arterial thrombolysis is an effective method to treat the superacute cerebral embolism but with a range of safe and effective concentration of UK, 6000 U/ml-12000 U/ml, reaching high rate of thrombolysis, and low rate of hemorrhage

  19. Bicyclic Peptide Inhibitor of Urokinase-Type Plasminogen Activator

    Roodbeen, Renée; Paaske, Berit; Jiang, Longguang;

    2013-01-01

    The development of protease inhibitors for pharmacological intervention has taken a new turn with the use of peptidebased inhibitors. Here, we report the rational design of bicyclic peptide inhibitors of the serine protease urokinase-type plasminogen activator (uPA), based on the established...... monocyclic peptide, upain-2. It was successfully converted to a bicyclic peptide, without loss of inhibitory properties. The aim was to produce a peptide cyclised by an amide bond with an additional stabilising across-the-ring covalent bond. We expected this bicyclic peptide to exhibit a lower entropic...... burden upon binding. Two bicyclic peptides were synthesised with affinities similar to that of upain-2, and their binding energetics were evaluated by isothermal titration calorimetry. Indeed, compared to upain-2, the bicyclic peptides showed reduced loss of entropy upon binding to uPA. We also...

  20. Urokinase and type I plasminogen activator inhibitor production by normal human hepatocytes: modulation by inflammatory agents.

    Busso, N; Nicodeme, E; Chesne, C; Guillouzo, A; Belin, D; Hyafil, F

    1994-07-01

    We examined the effects of inflammatory cytokines (interleukin-1 beta, tumor necrosis factor-alpha and transforming growth factor-beta) on the plasminogen activator system (urokinase, tissue-type plasminogen activator, type 1 plasminogen activator inhibitor) in primary cultures of human hepatocytes. We show that interleukin-1 beta and tumor necrosis factor-alpha increase urokinase-type plasminogen activator production, reinforcing the concept that increased urokinase production is associated with inflammatory processes. By contrast, the same agents (i.e., interleukin-1 beta and tumor necrosis factor-alpha) do not stimulate plasminogen activator inhibitor type 1 production. This latter observation rules out hepatocytes as a major cellular source of plasmatic plasminogen activator inhibitor type 1 during acute-phase-related responses. Among the inflammatory agents used, transforming growth factor-beta was found to be the most effective modulator of both urokinase-type plasminogen activator and plasminogen activator inhibitor type 1, inducing severalfold increases of activity of urokinase-type plasminogen activator, antigen and the corresponding mRNA and increasing plasminogen activator inhibitor type 1 antigen and mRNA levels. Urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 modulation by transforming growth factor-beta may play a critical role in hepatic pathophysiology. PMID:8020888

  1. Macroeconomic regimes

    Baele, L.T.M.; Bekaert, G.R.J.; Cho, S.; Inghelbrecht, K.; Moreno, A.

    2015-01-01

    A New-Keynesian macro-model is estimated accommodating regime-switching behavior in monetary policy and macro-shocks. A key to our estimation strategy is the use of survey-based expectations for inflation and output. Output and inflation shocks shift to the low volatility regime around 1985 and 1990

  2. Prolonged radiation damage in rat colon and urokinase expression in epithelium

    Hayashida, Masayuki; Minami, Kazunori; Okimoto, Tomoaki [Nagasaki Univ. (Japan). School of Medicine; Shichijo, Kazuko; Matsuu, Mutsumi; Nakayama, Toshiyuki; Sekine, Ichiro

    2001-12-01

    Although radiation therapy plays important role in the treatment of gynecological tumors, it may cause radiation injury as a late effect. Several recent reports show that urokinase such as urokinase type plasminogen activator (uPA) contributes to the repair of ulcerative lesions of the colon epithelium. We studied radiation induced enterocolitis using rat animal models. Seventy-two female Wistar rats were irradiated by a single fraction dose of 36 Gy at laparotomy. Histological changes and activity of urokinase system were investigated after irradiation. Ulcers were observed in irradiated field in 12 of 19 animals (63%) even at 60th week after irradiation. Urokinase expressions were observed in the margins of active ulcer. Urokinase was thought to play important role in exacerbation of ulcer formation. Expression of uPA was also observed in submucosal glands. Ischaemic changes were not observed in irradiated colon despite sclerosing vasculitis. It is suggested that uPA played reciprocal roles in radiation induced enterocolitis: healing and aggravation of ulcer. (author)

  3. Application of Molecular Modeling to Urokinase Inhibitors Development

    V. B. Sulimov

    2014-01-01

    Full Text Available Urokinase-type plasminogen activator (uPA plays an important role in the regulation of diverse physiologic and pathologic processes. Experimental research has shown that elevated uPA expression is associated with cancer progression, metastasis, and shortened survival in patients, whereas suppression of proteolytic activity of uPA leads to evident decrease of metastasis. Therefore, uPA has been considered as a promising molecular target for development of anticancer drugs. The present study sets out to develop the new selective uPA inhibitors using computer-aided structural based drug design methods. Investigation involves the following stages: computer modeling of the protein active site, development and validation of computer molecular modeling methods: docking (SOL program, postprocessing (DISCORE program, direct generalized docking (FLM program, and the application of the quantum chemical calculations (MOPAC package, search of uPA inhibitors among molecules from databases of ready-made compounds to find new uPA inhibitors, and design of new chemical structures and their optimization and experimental examination. On the basis of known uPA inhibitors and modeling results, 18 new compounds have been designed, calculated using programs mentioned above, synthesized, and tested in vitro. Eight of them display inhibitory activity and two of them display activity about 10 μM.

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

    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...

  5. Adsorption and Step Elution of Urokinase Using, Affinity Chromatography -Comparison of Data with Rate Model Simulation

    MohammadRezaAboudzadehRovais; JiawenZhu; BinWu

    2004-01-01

    A non-equilibrium chromatographic rate model was employed to simulate the affinity chromatography of urokinase. The chromatography process was developed to a yield of high purity product of urokinase from crude materials. The affinity gel used in the process was prepared by an epichlorohydrin-activation method using epichlorohydrin activated Sepharose 4B as a matrix and p-aminobenzamidine as a ligand. The chromatographic process were numerically simulated and analyzed with the aid of VERSE-LC computer simulator. Considering the basic principles, rate model with the back mixing in column inlet was utilized in simulating and studying the effect of the column inlet pattern on other parameters. Comparison of the simulation results with the experimental data showed that the rate model can be used to describe the affinity chromatography of urokinase in a fixed bed column with satisfactory accuracy.

  6. Efficacy of 2-hour post glucose insulin levels in predicting insulin resistance in polycystic ovarian syndrome with infertility

    Pikee Saxena

    2011-01-01

    Full Text Available Background : Insulin resistance (IR is central to the pathogenesis of polycystic ovarian syndrome (PCOS, but tests for determining IR are elaborate, tedious and expensive. Aims : To evaluate if "2-hour post-glucose insulin level" is an effective indicator of IR and can aid in diagnosing IR in infertile PCOS women. Settings and Design : Observational study at infertility clinic of a tertiary care center. Materials and Methods : 50 infertile women with PCOS and 20 females with tubal/male factor infertility were evaluated for the presence of IR, as defined by the fasting/2-hour post-glucose insulin levels cutoffs of >25/>41 μU/mL, respectively. The clinical, metabolic and endocrinologic profile was determined in both the groups. Statistical Analysis : Statistical analysis was performed using SPSS (Chicago, IL, USA. Results : Body mass index, post load glucose, insulin, glucose/insulin ratio, area under curve (AUC of glucose and insulin and insulinogenic index were significantly lower in the controls as compared to the PCOS group. "2-hour post-glucose insulin levels" were elevated in 88% of PCOS individuals but were normal in all females not suffering from PCOS. These levels significantly correlated with AUC of glucose and insulin, and insulinogenic index and inversely correlated with 2-hour glucose to insulin ratio (r=0.827, 0.749 and −0.732, respectively. Conclusions : "2-hour post-glucose insulin levels" appears to be a good indicator of IR. It can be a useful tool, especially in low resource setting where a single sample can confirm the diagnosis, thus reducing cost and repeat visits.

  7. Efficacy of 2-hour post glucose insulin levels in predicting insulin resistance in polycystic ovarian syndrome with infertility

    Saxena, Pikee; Prakash, Anupam; Nigam, Aruna

    2011-01-01

    BACKGROUND: Insulin resistance (IR) is central to the pathogenesis of polycystic ovarian syndrome (PCOS), but tests for determining IR are elaborate, tedious and expensive. AIMS: To evaluate if “2-hour post-glucose insulin level” is an effective indicator of IR and can aid in diagnosing IR in infertile PCOS women. SETTINGS AND DESIGN: Observational study at infertility clinic of a tertiary care center. MATERIALS AND METHODS: 50 infertile women with PCOS and 20 females with tubal/male factor infertility were evaluated for the presence of IR, as defined by the fasting/2-hour post-glucose insulin levels cutoffs of >25/>41 μU/mL, respectively. The clinical, metabolic and endocrinologic profile was determined in both the groups. STATISTICAL ANALYSIS: Statistical analysis was performed using SPSS (Chicago, IL, USA). RESULTS: Body mass index, post load glucose, insulin, glucose/insulin ratio, area under curve (AUC) of glucose and insulin and insulinogenic index were significantly lower in the controls as compared to the PCOS group. “2-hour post-glucose insulin levels” were elevated in 88% of PCOS individuals but were normal in all females not suffering from PCOS. These levels significantly correlated with AUC of glucose and insulin, and insulinogenic index and inversely correlated with 2-hour glucose to insulin ratio (r=0.827, 0.749 and –0.732, respectively). CONCLUSIONS: “2-hour post-glucose insulin levels” appears to be a good indicator of IR. It can be a useful tool, especially in low resource setting where a single sample can confirm the diagnosis, thus reducing cost and repeat visits. PMID:21772735

  8. Estuary regime

    The primary aim of this research into estuary regime is to provide engineers with an improved method of predicting the long term evolutionary effects of major engineering changes in estuaries. Of specific interest to the Department of Trade and Industry's renewable energy R and D programme is the long term impact of tidal energy barrages on estuarine morphology. It is considered that the approach being taken is the most appropriate line to follow in terms of developing an applicable estuary regime predictive capability. As a consequence it is considered that any further regime model development should be complimentary to this approach. In addition to model development there is still an enormous amount of basic research required in examining sediment transport processes within the estuarine environment. Recently developed models for predicting the motion of fluidised mud on inter-tidal and sub-tidal banks, an important process within the estuarine sediment regime, requires specific field data calibration and validation. The impacts of wave action on sediment mobility on estuarine banks is a further area requiring field measurements. It is recommended that the opportunity be taken to obtain a set of measurements at a site following construction of major engineering works to provide data for future verification of a regime model. Possibilities exist, for example, on the Tees Estuary for such measurements. (author)

  9. Activation of human pro-urokinase by unrelated proteases secreted by Pseudomonas aeruginosa : LasB and protease IV activate human pro-urokinase

    Beaufort, Nathalie; Seweryn, Paulina; De Bentzmann, Sophie; Tang, Aihua; Kellermann, Josef; Grebenchtchikov, Nicolai; Schmitt, Manfred; Sommerhoff, Christian,; Pidard, Dominique; Magdolen, Viktor

    2010-01-01

    Abstract Pathogenic bacteria, including Pseudomonas aeruginosa, interact with and engage the host plasminogen (Plg) activation system, which encompasses the urokinase(uPA)-type Plg activator, and is involved in extracellular proteolysis, including matrilysis and fibrinolysis. We hypothesized that secreted bacterial proteases might contribute to the activation of this major extracellular proteolytic system, thereby participating in bacterial dissemination. We report that LasB, a...

  10. Regime change?

    Following the 1998 nuclear tests in South Asia and later reinforced by revelations about North Korean and Iraqi nuclear activities, there has been growing concern about increasing proliferation dangers. At the same time, the prospects of radiological/nuclear terrorism are seen to be rising - since 9/11, concern over a proliferation/terrorism nexus has never been higher. In the face of this growing danger, there are urgent calls for stronger measures to strengthen the current international nuclear nonproliferation regime, including recommendations to place civilian processing of weapon-useable material under multinational control. As well, there are calls for entirely new tools, including military options. As proliferation and terrorism concerns grow, the regime is under pressure and there is a temptation to consider fundamental changes to the regime. In this context, this paper will address the following: Do we need to change the regime centered on the Treaty on the Nonproliferation of Nuclear Weapons (NPT) and the International Atomic Energy Agency (IAEA)? What improvements could ensure it will be the foundation for the proliferation resistance and physical protection needed if nuclear power grows? What will make it a viable centerpiece of future nonproliferation and counterterrorism approaches?

  11. Effects of acute and 2-hour postphysical activity on the estimation of body fat made by the bod pod.

    Harrop, Bradley J; Woodruff, Sarah J

    2015-06-01

    The Bod Pod has been found to be reliable/valid against several criterion methods, including hydrostatic weighing and dual-energy x-ray absorptiometry, and under different conditions, such as clothing, dehydrated states, and body temperature changes. However, questions remain regarding the effects of an acute bout of exercise. Therefore, the purpose was to determine the effects of an acute bout of exercise on the estimations made by the Bod Pod. Participants (15 men and 22 women) were of age 18-27 years and were currently exercising. Baseline Bod Pod measures were completed followed by a 30-minute cycling trial at 75% of maximum heart rate. Bod Pod measures were taken immediately after exercise and 2 hours after exercise. Differences between men and women were found at baseline between height (p temperature (p temperature (p affect the prediction 2 hours after exercise in women. PMID:25756324

  12. Efficacy of 2-hour post glucose insulin levels in predicting insulin resistance in polycystic ovarian syndrome with infertility

    Pikee Saxena; Anupam Prakash; Aruna Nigam

    2011-01-01

    Background : Insulin resistance (IR) is central to the pathogenesis of polycystic ovarian syndrome (PCOS), but tests for determining IR are elaborate, tedious and expensive. Aims : To evaluate if "2-hour post-glucose insulin level" is an effective indicator of IR and can aid in diagnosing IR in infertile PCOS women. Settings and Design : Observational study at infertility clinic of a tertiary care center. Materials and Methods : 50 infertile women with PCOS and 20 females with tubal/male fact...

  13. Dietary Fatty Acids Differentially Associate with Fasting Versus 2-Hour Glucose Homeostasis: Implications for The Management of Subtypes of Prediabetes.

    Guess, Nicola; Perreault, Leigh; Kerege, Anna; Strauss, Allison; Bergman, Bryan C

    2016-01-01

    Over-nutrition has fuelled the global epidemic of type 2 diabetes, but the role of individual macronutrients to the diabetogenic process is not well delineated. We aimed to examine the impact of dietary fatty acid intake on fasting and 2-hour plasma glucose concentrations, as well as tissue-specific insulin action governing each. Normoglycemic controls (n = 15), athletes (n = 14), and obese (n = 23), as well as people with prediabetes (n = 10) and type 2 diabetes (n = 11), were queried about their habitual diet using a Food Frequency Questionnaire. All subjects were screened by an oral glucose tolerance test (OGTT) and studied using the hyperinsulinemic/euglycemic clamp with infusion of 6,62H2-glucose. Multiple regression was performed to examine relationships between dietary fat intake and 1) fasting plasma glucose, 2) % suppression of endogenous glucose production, 3) 2-hour post-OGTT plasma glucose, and 4) skeletal muscle insulin sensitivity (glucose rate of disappearance (Rd) and non-oxidative glucose disposal (NOGD)). The %kcal from saturated fat (SFA) was positively associated with fasting (β = 0.303, P = 0.018) and 2-hour plasma glucose (β = 0.415, P<0.001), and negatively related to % suppression of hepatic glucose production (β = -0.245, P = 0.049), clamp Rd (β = -0.256, P = 0.001) and NOGD (β = -0.257, P = 0.001). The %kcal from trans fat was also negatively related to clamp Rd (β = -0.209, P = 0.008) and NOGD (β = -0.210, P = 0.008). In contrast, the %kcal from polyunsaturated fat (PUFA) was negatively associated with 2-hour glucose levels (β = -0.383, P = 0.001), and positively related to Rd (β = 0.253, P = 0.007) and NOGD (β = 0.246, P = 0.008). Dietary advice to prevent diabetes should consider the underlying pathophysiology of the prediabetic state. PMID:26999667

  14. Dietary Fatty Acids Differentially Associate with Fasting Versus 2-Hour Glucose Homeostasis: Implications for The Management of Subtypes of Prediabetes

    Guess, Nicola; Perreault, Leigh; Kerege, Anna; Strauss, Allison; Bergman, Bryan C.

    2016-01-01

    Over-nutrition has fuelled the global epidemic of type 2 diabetes, but the role of individual macronutrients to the diabetogenic process is not well delineated. We aimed to examine the impact of dietary fatty acid intake on fasting and 2-hour plasma glucose concentrations, as well as tissue-specific insulin action governing each. Normoglycemic controls (n = 15), athletes (n = 14), and obese (n = 23), as well as people with prediabetes (n = 10) and type 2 diabetes (n = 11), were queried about their habitual diet using a Food Frequency Questionnaire. All subjects were screened by an oral glucose tolerance test (OGTT) and studied using the hyperinsulinemic/euglycemic clamp with infusion of 6,62H2-glucose. Multiple regression was performed to examine relationships between dietary fat intake and 1) fasting plasma glucose, 2) % suppression of endogenous glucose production, 3) 2-hour post-OGTT plasma glucose, and 4) skeletal muscle insulin sensitivity (glucose rate of disappearance (Rd) and non-oxidative glucose disposal (NOGD)). The %kcal from saturated fat (SFA) was positively associated with fasting (β = 0.303, P = 0.018) and 2-hour plasma glucose (β = 0.415, P<0.001), and negatively related to % suppression of hepatic glucose production (β = -0.245, P = 0.049), clamp Rd (β = -0.256, P = 0.001) and NOGD (β = -0.257, P = 0.001). The %kcal from trans fat was also negatively related to clamp Rd (β = -0.209, P = 0.008) and NOGD (β = -0.210, P = 0.008). In contrast, the %kcal from polyunsaturated fat (PUFA) was negatively associated with 2-hour glucose levels (β = -0.383, P = 0.001), and positively related to Rd (β = 0.253, P = 0.007) and NOGD (β = 0.246, P = 0.008). Dietary advice to prevent diabetes should consider the underlying pathophysiology of the prediabetic state. PMID:26999667

  15. Characterization of human endothelial cell urokinase-type plasminogen activator receptor protein and messenger RNA

    Barnathan, E S; Kuo, A; Karikó, K;

    1990-01-01

    Human umbilical vein endothelial cells in culture (HUVEC) express receptors for urokinase-type plasminogen activators (u-PA). The immunochemical nature of this receptor and its relationship to u-PA receptors expressed by other cell types is unknown. Cross-linking active site-blocked u-PA to HUVEC...

  16. The urokinase receptor (uPAR) facilitates clearance of Borrelia burgdorferi

    J.W.R. Hovius; M.F. Bijlsma; G.J.W. van der Windt; W.J. Wiersinga; B.J.D. Boukens; J. Coumou; A. Oei; R. de Beer; A.F. de Vos; C. van 't Veer; A.P. van Dam; P. Wang; E. Fikrig; M.M. Levi; J.J.T.H. Roelofs; T. van der Poll

    2009-01-01

    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

  17. Tissue plasminogen activator and urokinase plasminogen activator in human epileptogenic pathologies

    A.M. Iyer; E. Zurolo; K. Boer; J.C. Baayen; F. Giangaspero; A. Arcella; G.C. Di Gennaro; V. Esposito; W.G.M. Spliet; P.C. van Rijen; D. Troost; J.A. Gorter; E. Aronica

    2010-01-01

    A growing body of evidence demonstrates the involvement of plasminogen activators (PAs) in a number of physiologic and pathologic events in the CNS. Induction of both tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) has been observed in different experimental models of ep

  18. Superselective Urokinase Infusion Therapy for Dorsalis Pedis Artery Occlusion in Buerger's Disease

    Occlusion of the proximal left dorsalis pedis artery (DPA) in a patient with Buerger's disease was treated by continuous urokinase intraarterial infusion using a microcatheter. Recanalization of the DPA and healing of a toe ulcer were achieved. The patient remains asymptomatic during a 4-year follow-up

  19. Regulation of urokinase receptors in monocytelike U937 cells by phorbol ester phorbol myristate acetate

    Picone, R; Kajtaniak, E L; Nielsen, L S;

    1989-01-01

    A specific surface receptor for urokinase plasminogen activator (uPA) recognizes the amino-terminal growth factor-like sequence of uPA, a region independent from and not required for the catalytic activity of this enzyme. The properties of the uPA receptor (uPAR) and the localization and distribu...

  20. The human receptor for urokinase plasminogen activator. NH2-terminal amino acid sequence and glycosylation variants

    Behrendt, N; Rønne, E; Ploug, M;

    1990-01-01

    The receptor for human urokinase-type plasminogen activator (u-PA) was purified from phorbol 12-myristate 13-acetate-stimulated U937 cells by temperature-induced phase separation of detergent extracts, followed by affinity chromatography with immobilized diisopropyl fluorophosphate-treated u-PA. ...

  1. The ligand-binding domain of the cell surface receptor for urokinase-type plasminogen activator

    Behrendt, N; Ploug, M; Patthy, L;

    1991-01-01

    The purified urokinase plasminogen activator receptor (u-PAR) was cleaved into two fragments by mild chymotrypsin treatment. The smaller fragment (apparent Mr 16,000) possessed the ligand-binding capability, as shown by chemical cross-linking analysis. This fragment constituted the NH2-terminal p...

  2. Competition Regime

    Danilo Icaza Ortiz

    2013-01-01

    This paper is a review of the competition regime works of various authors, published under the auspices of the University of the Hemispheres and the Corporation for Studies and Publications. Analyzes the structure, the general concepts, case law taken for development. Includes comments on the usefulness of this work for the study of competition law and the contribution to the lawyers who want to practice in this branch of economic law.

  3. Competition Regime

    Danilo Icaza Ortiz

    2013-01-01

    Full Text Available This paper is a review of the competition regime works of various authors, published under the auspices of the University of the Hemispheres and the Corporation for Studies and Publications. Analyzes the structure, the general concepts, case law taken for development. Includes comments on the usefulness of this work for the study of competition law and the contribution to the lawyers who want to practice in this branch of economic law.

  4. Cloning and expression of the receptor for human urokinase plasminogen activator, a central molecule in cell surface, plasmin dependent proteolysis

    Roldan, A L; Cubellis, M V; Masucci, M T;

    1990-01-01

    The surface receptor for urokinase plasminogen activator (uPAR) has been recognized in recent years as a key molecule in regulating plasminogen mediated extracellular proteolysis. Surface plasminogen activation controls the connections between cells, basement membrane and extracellular matrix, an...

  5. Urokinase-type plasminogen activator receptor as a predictor of poor outcome in patients with systemic inflammatory response syndrome

    Wu, Xiao-Ling; Long, Ding; Yu, Li; Yang, Jun-hui; Zhang, Yuan-chao; Geng, Feng

    2013-01-01

    BACKGROUND: Urokinase-type plasminogen activator (uPA) and urokinase-type plasminogen activator receptor (uPAR) are known as important factors, which mediate a variety of functions in terms of vascular homeostasis, inflammation and tissue repair. However, their role in systemic inflammatory response syndrome (SIRS) has been less well studied. This study aimed to test the hypothesis that the abnormalities of fibrinolysis and degradation of extracellular matrix mediated by uPA and uPAR are dire...

  6. Effect of urokinase on the proliferation of primary cultures of human prostatic cells

    The effects of exogenously added urokinase type plasminogen activator, tissue type plasminogen activator, plasmin and thrombin on the proliferation of primary cultures of cells derived from prostatic hyperplasia or prostatic carcinomas were investigated by measuring the incorporation of 3H-thymidine into the cultures. Addition of urokinase type plasminogen activator (1.35 x 10(-9) M) or thrombin (10(-7) M) to the culture medium caused a two-fold increase of 3H-thymidine incorporation, regardless of the origin of the prostatic cells. Tissue type plasminogen activator did not alter the rate of 3H-thymidine incorporation, whereas plasmin caused a 25% decrease of 3H-thymidine incorporation in all cultures

  7. Arterial thrombotic occlusions following percutaneous catheterization in infants and children: local thrombolytic therapy with urokinase

    Six cases of right external iliac and common femoral arterial thrombotic occlusions following transfemoral cardiac catheterization were found among the 117 infants and children with congenital heart disease. Physical findings of arterial thrombosis were lower extremity coldness and absence of femoral pulse, which appeared just after cardiac catheterization. Transcatheter local intrathrombotic infusion of Urokinase were done with 50000 IU bolus doses and 40000-50000 IU/h running doses. All 6 cases showed complete thrombolysis and re-establishment of femoral circulation. Three cases developed bleeding from arterial puncture sites, and were subsequently controlled properly by compression. No other complication was found. Our results suggest that local thrombolytic therapy with Urokinase is effective treatment method without significant complication for the infants and children with fresh thrombotic occlusions following cardiac catheterization and angiography

  8. Dictyostelium discoideum: a model for testing novel inhibitors of urokinase-type plasminogen activator

    Thompson, Elinor

    2013-01-01

    The social amoeba Dictyostelium discoideum is a useful non-animal eukaryote for testing novel compounds and dissecting cell regulatory molecular networks. We used this model organism to investigate the effect of a series of arylboronic acids and pinacol esters on development, chemotaxis and viability. These compounds were studied in parallel by collaborators for serine protease and urokinase-type plasminogen activator (uPA) inhibition, both in vitro and in vivo. In those biochemical assays, t...

  9. Rapid neural regulation of muscle urokinase-like plasminogen activator as defined by nerve crush.

    Hantaï, D; Rao, J. S.; Festoff, B W

    1990-01-01

    Muscle plasminogen activators (PAs), such as urokinase-like PA and, to a lesser extent, tissue PA, increase dramatically after denervation induced by axotomy. The PA/plasmin system has also been implicated in degradation of specific components of the muscle fiber basement membrane after local activation of plasminogen. These results suggest that neural regulation of muscle extracellular matrix metabolism accompanies or precedes regeneration after injury and is mediated by activation of PAs. I...

  10. Anterograde Intra-Arterial Urokinase Injection for Salvaging Fibular Free Flap

    Dae-Sung Lee

    2013-05-01

    Full Text Available We present a case of a 57-year-old male patient who presented with squamous cell carcinoma on his mouth floor with cervical and mandibular metastases. Wide glossectomy with intergonial mandibular ostectomy, and sequential reconstruction using fibular osteomyocutaneous free flap were planned. When the anastomosis between the peroneal artery of the fibular free flap and the right lingual artery was performed, no venous flow was observed at the vena comitans. Then re-anastomosis followed by topical application of papaverine and lidocaine was attempted. However, the blood supply was not recovered. Warm saline irrigation over 30 minutes was also useless. Microvascular thromboses of donor vessels were clinically suspected, so a solution of 100,000 units of urokinase was infused once through a 26-gauge angiocatheter inserted into the recipient artery just at the arterial anastomotic site, until the solution gushed out through the flap vena comitans. Immediately after the application of urokinase, arterial flow and venous return were restored. There were no complications during the follow-up period of 11 months. We believe that vibrating injuries from the reciprocating saw during osteotomies and flap insetting might be the cause of microvascular thromboses. The use of urokinase may provide a viable option for the treatment of suspicious intraoperative arterial thrombosis.

  11. Urokinase Separation from Cell Culture Broth of a Human Kidney Cell Line

    Vibha Bansal, Pradip K. Roychoudhury, Ashok Kumar

    2007-01-01

    Full Text Available A single step ion-exchange chromatography on a sulfo-propyl (SP- Sepharose column was performed to separate both the high molecular weight (HMW- and low molecular weight (LMW- forms of enzymatically active urokinase type plasminogen activator from human kidney (HT1080 cell culture media. The level of urokinase secreted by the cell line reached to about 145 Plough units/ml culture broth within 48 h of cultivation. The conditioned cell culture media was applied directly to the column without any prior concentration steps. Polyacrylamide gel electrophoresis of the column eluates in the presence of sodium dodecyl sulphate showed that the cell line secretes three forms of two-chain high molecular weight (HMW urokinase of molecular weights (Mr 64,000, 60,900 and 55,000. In addition, two low molecular weight (LMW forms of Mr 22,000 and 20,000; proteolytic cleavage products of HMW, were also found. The HMW and LMW forms had intrinsic plasminogen dependent proteolytic activity as judged by zymographic analysis. The specific activity of the pooled peak fractions increased (approximately 93-fold to values as high as 1481 Plough units/ mg protein. Both HMW as well as LMW forms were obtained in significantly high yields.

  12. Evaluation of intracoronary administration of urokinase and tirofiban in treating acute myocardial infarction with massive thrombus

    Objective: To assess the safety and efficacy of intracoronary administration of both urokinase and tirofiban for the treatment of acute myocardial infarction (AMI) with massive thrombus during emergency percutaneous coronary intervention in AMI patients. Methods: During the period of June 2008 June 2009 percutaneous coronary intervention was carried out in 85 patients with AMI, of whom seven patients showed high-burden thrombus in the infarct-related artery (IRA). Intracoronary infusion with urokinase and tirofiban was performed. During hospitalization and follow-up period the TIMI flow grade and myocardial perfusion were determined, side-effects of the drugs and major adverse cardiac events were observed, and cardiac color Doppler ultrasonography was employed for follow-up checkups. The clinical data were analyzed and therapeutic results were evaluated. Results: After stent deployment neither 'no-reflow' nor 'slow flow' phenomenon was observed and the grade of IRA flow was improved to TIMI 2-3 grade. During hospitalization no major adverse cardiac events such as death,re-infarction, target vessel revascularization, etc. occurred, and severe bleeding complications didn't occur either. During the follow-up period of 3-9 months, no major adverse cardiac events developed and the cardiac color Doppler ultrasonography showed that the left ventricle had an excellent performance in all cases. Conclusion: During emergency percutaneous coronary intervention for patients with AMI, intracoronary administration of both urokinase and tirofiban is safe and effective for AMI patients with massive thrombus. (authors)

  13. Urokinase perfusion prevents intrahepatic ischemic-type biliary lesion in donor livers

    Ren Lang; Qiang He; Zhong-Kui Jin; Dong-Dong Han; Da-Zhi Chen

    2009-01-01

    AIM: To evaluate whether urokinase perfusion of non-heart-beating cadaveric donor livers reduces the incidence of intrahepatic ischemic-type biliary lesions (IITBLs). METHODS: A prospective study was conducted to investigate potential microthrombosis in biliary microcirculation when non-heart-beating cadaveric livers were under warm or cold ischemic conditions. The experimental group included 140 patients who underwent liver transplantation during the period of January 2006 to December 2007, and survived for more than 1 year. The control group included 220 patients who received liver transplantation between July 1999 and December 2005 and survived for more than 1 year. In the experimental group, the arterial system of the donor liver was perfused twice with urokinase during cold perfusion and after trimming of the donor liver. The incidence of IITBLs was compared between the two groups. RESULTS: In the control group, the incidence of IITBLs was 5.9% (13/220 cases) after 3-11 mo of transplantation. In the experimental group, two recipients (1.4%) developed IITBLs at 3 and 6 mo after transplantation, respectively. The difference in the incidence between the two groups was statistically significant ( P < 0.05). CONCLUSION: Double perfusion of cadaveric livers from non-heart-beating donors with urokinase may reduce the incidence of IITBLs.

  14. Flushing the liver with urokinase before transplantation does not prevent nonanastomotic biliary strictures.

    Pietersen, Lars C; den Dulk, A Claire; Braat, Andries E; Putter, Hein; Korkmaz, Kerem Sebib; Baranski, Andre G; Schaapherder, Alexander F M; Dubbeld, Jeroen; van Hoek, Bart; Ringers, Jan

    2016-04-01

    The aim of the present study was to assess whether flushing the donor liver with urokinase immediately before implantation reduces the incidence of nonanastomotic biliary strictures (NASs) after liver transplantation, without causing increased blood loss, analyzed as a historical cohort study. Between January 2005 and October 2012, all liver (re-)transplantations were included. Of the 185 liver transplant recipients included, 63 donor livers between January 2010 and October 2012 received urokinase (study group), whereas the donor liver of 122 consecutive recipients, who served as a historical control group, between January 2005 and January 2010 did not receive urokinase. Basic donor (Eurotransplant donor risk index) and recipient (age, body mass index, laboratory Model for End-Stage Liver Disease score) characteristics did not significantly differ in both groups. Thirty-three recipients developed NASs: 22 in the control group (18%) and 11 (17.5%) in the study group (P = 0.68). Analyzed separately for donation after circulatory death (P = 0.42) or donation after brain death (P = 0.89), there was no difference between the groups in incidence of NAS. Of all the recipients developing NAS, 7 (21%) needed retransplantation and all others were treated conservatively. Autologous blood transfusion requirements did not differ significantly between both groups (P = 0.91), whereas interestingly, more heterologous blood transfusions were needed in the control group (P blood loss. Liver Transplantation 22 420-426 2016 AASLD. PMID:26600096

  15. Analysis of multi-factors affecting symptomatic intracranial hemorrhage in intraarterial thrombolysis with urokinase for acute ischemic stroke

    Objective: To explore the causes and preventive measures of symptomatic intracranial hemorrhage in 217 patients with acute cerebral ischemic stroke treated with local intra-arterial urokinase. Methods: From February 1999 to June 2004, 217 patients were treated for acute ischemic stroke with local intra-arterial urokinase in our hospital. Factors associated with symptomatic intracranial hemorrhage of intra-arterial thrombolysis were analyzed by Stepwise logistic regression to identify some factors relating the prediction symptomatic intracranial hemorrhage. Results: Symptomatic intracranial hemorrhage occurred in 8 cases (3.7%). Predictors of the symptomatic intracranial hemorrhage were the elevated systolic blood pressure before therapy (odds ratio, 1.096; 95% CI, 1.006 to 1.194) and urokinase (UK) treatment (odds ratio, 1.068 ; 95% CL, 1.053 to 1.247). Risk of secondary symptomatic intracranial hemorrhage was increased with elevated systolic blood pressure. Other factors like age, initial treating time, NIHSS, diabetes and collateral circulation did not predict the symptomatic intracranial hemorrhage respectively. Conclusions: Predictors of symptomatic intracranial hemorrhage after local intra-arterial infusion of urokinase for acute ischemic stroke were the elevated systolic blood pressure before therapy and urokinase (UK) treatment. (authors)

  16. Correlation of 2 hour, 4 hour, 8 hour and 12 hour urine protein with 24 hour urinary protein in preeclampsia.

    Savita Rani Singhal

    2014-09-01

    Full Text Available To find shortest and reliable time period of urine collection for determination of proteinuria.It is a prospective study carried out on 125 pregnant women with preeclampsia after 20 weeks of gestation having urine albumin >1 using dipstick test. Urine was collected in five different time intervals in colors labeled containers with the assistance of nursing staff; the total collection time was 24 hours. Total urine protein of two-hour, four-hour, eight-hour, 12-hour and 24-hour urine was measured and compared with 24-hour collection. Data was analyzed using the Pearson correlation coefficient.There was significant correlation (p value < 0.01 in two, four, eight and 12-hour urine protein with 24-urine protein, with correlation coefficient of 0.97, 0.97, 0.96 and 0.97, respectively. When a cut off value of 25 mg, 50 mg. 100 mg, and 150 mg for urine protein were used for 2-hour, 4-hours, 8-hour and 12-hour urine collection, a sensitivity of 92.45%, 95.28%, 91.51%, and 96.23% and a specificity of 68.42%, 94.74%, 84.21% and 84.21% were obtained, respectively.Two-hour urine proteins can be used for assessment of proteinuria in preeclampsia instead of gold standard 24-hour urine collection for early diagnosis and better patient compliance.

  17. Targeting the autolysis loop of urokinase-type plasminogen activator with conformation-specific monoclonal antibodies

    Bøtkjær, Kenneth Alrø; Fogh, Sarah; Bekes, Erin C;

    2011-01-01

    Tight regulation of serine proteases is essential for their physiological function, and unbalanced states of protease activity have been implicated in a variety of human diseases. One key example is the presence of uPA (urokinase-type plasminogen activator) in different human cancer types...... to harbour the epitopes for three conformation-specific monoclonal antibodies, two with a preference for the zymogen form pro-uPA, and one with a preference for active uPA. All three antibodies were shown to have overlapping epitopes, with three common residues being crucial for all three antibodies...

  18. Characterization of human endothelial cell urokinase-type plasminogen activator receptor protein and messenger RNA

    Barnathan, E S; Kuo, A; Karikó, K; Rosenfeld, L; Murray, S C; Behrendt, N; Rønne, E; Weiner, D; Henkin, J; Cines, D B

    1990-01-01

    Human umbilical vein endothelial cells in culture (HUVEC) express receptors for urokinase-type plasminogen activators (u-PA). The immunochemical nature of this receptor and its relationship to u-PA receptors expressed by other cell types is unknown. Cross-linking active site-blocked u-PA to HUVEC...... endothelial cell cDNA library using the polymerase chain reaction (PCR) and oligonucleotide primers corresponding to the DNA sequence of the receptor cloned from transformed human fibroblasts (Roldan et al, EMBO J 9:467, 1990). The size of the cDNA (approximately 1,054 base pairs, bp) and the presence of a...

  19. Interconversion of Active and Inactive Conformations of Urokinase-Type Plasminogen Activator

    Liu, Zhuo; Kromann-Hansen, Tobias; Lund, Ida K;

    2012-01-01

    The catalytic activity of serine proteases depends on a salt-bridge between the amino group of residue 16 and the side chain of Asp194. The salt-bridge stabilizes the oxyanion hole and the S1 specificity pocket of the protease. Some serine proteases exist in only partially active forms, in which...... the amino group of residue 16 is exposed to the solvent. Such a partially active state is assumed by a truncated form of the murine urokinase-type plasminogen activator (muPA), consisting of residues 16-243. Here we investigated the allosteric interconversion between partially active states and the...

  20. Urokinase-type plasminogen activator receptor (uPAR) as a promising new imaging target

    Persson, Morten; Kjaer, Andreas

    2013-01-01

    Urokinase-type plasminogen activator receptor (uPAR) has been shown to be of special importance during cancer invasion and metastasis. However, currently, tissue samples are needed for measurement of uPAR expression limiting the potential as a clinical routine. Therefore, non-invasive methods are...... the cell surface. Due to the importance of uPAR in cancer invasion and metastasis, a number of high-affinity ligands have been identified during the last decades. These ligands have recently been used as starting point for the development of a number of ligands for imaging of uPAR using various...

  1. Synthesis of New Ligands of Urokinase Receptor and New Urotensin-II Derivatives

    Yousif, Ali Munaim

    2015-01-01

    Unit 1: The urokinase-type plasminogen activator receptor (uPAR) is involved in the regulation of cell migration. The uPAR is formed by three domains connected by short linker region. The Ser88-Arg-Ser- Arg-Tyr92 is the minimum chemotactic sequence of uPAR required to induce the same intracellular signaling as result of its binding with formyl peptide receptor (FPRs). With aim to perform a SAR study on this sequence we have synthesized a large peptide library using phosphorylated ...

  2. Urokinase Expression by Tumor Suppressor Protein p53: A Novel Role in mRNA Turnover

    Shetty, Praveenkumar; Velusamy, Thirunavukkarasu; Bhandary, Yashodhar P.; Shetty, Rashmi S.; Liu, Ming-Cheh; Shetty, Sreerama

    2008-01-01

    Lung carcinoma (H1299) cells deficient in p53 (p53−/−) express large amounts of urokinase-type plasminogen activator (uPA) protein and uPA mRNA, and exhibit slower degradation of uPA mRNA than that of p53-expressing nonmalignant Beas2B human airway epithelial cells. Expression of p53 protein in H1299 cells, upon transfection with p53 cDNA, suppressed basal as well as uPA-induced expression of uPA protein in both conditioned media and cell lysates, and decreased the level of steady-state uPA m...

  3. Soluble Urokinase Plasminogen Activator Receptor Levels in Tuberculosis Patients at High Risk for Multidrug Resistance

    Tri Yudani Mardining Raras; Triwahju Astuti; Iin Noor Chozin

    2012-01-01

    The soluble urokinase plasminogen activator receptor (suPAR) has been shown to be a strong prognostic biomarker for tuberculosis (TB). In the present study, the profiles of plasma suPAR levels in pulmonary TB patients at high risk for multidrug resistance were analyzed and compared with those in multidrug resistant (MDR)-TB patients. Forty patients were prospectively included, consisting of 10 MDR-TB patients and 30 TB patients at high risk for MDR, underwent clinical assesment. Plasma suPAR ...

  4. Combination of irradiation, carcinostatics, and urokinase for the treatment of uterine cervical carcinoma

    In the treatment of carcinoma of the cervix uteri, histological changes were studied by dividing patients into 2 groups. One group was treated with radio-therapy and the other was treated with radiotherapy combined with chemotherapy, using antineoplastic agents which were used alone or in combination with urokinase. In regard to radiotherapy alone, Linac 10 MeV x-ray, 60Co-teletherapy, and radium contiguous irradiation were evaluated, and marked changes in cancerous parenchyma were seen with irradiation over 3000 rad. Irradiation of 3000 rad caused destruction of cancer cells, separation of the cells, inclusion of the focus, necrosis of hyalinization, and infiltration of neutrophils and lymphocytes. Approximately 4000 rad caused hyperplasia of the interstitial connective tissues, in addition to the above-mentioned changes. Approximately 5000 rad caused destruction and disappearance of cancer tissues, and approximately 6000 rad caused disappearance of the cancer cells which were then only connective or necrostic tissues. When radiotherapy was combined with BLM and FAMT therapies, degenerative changes were observed in many cases with irradiation of 1200 - 2400 mgh of radium or 1000 - 3000 rad of Linac or 60Co. The addition of urokinase tended to further accelerate the degeneration begun by BLM therapy. (Tsunoda, M.)

  5. Urokinase receptor cleavage correlates with tumor volume in a transgenic mouse model of breast cancer

    Thurison, Tine; Almholt, Kasper; Gårdsvoll, Henrik;

    2015-01-01

    The urokinase plasminogen activator system plays a key role in tissue degradation during cancer invasion. The linker region between domains I and II of the intact, three domain urokinase receptor uPAR(I-III) is highly susceptible to proteolytic cleavage and the resulting cleaved uPAR forms are...... strong prognostic biomarkers in several types of cancer, i.e., high levels of the cleaved uPAR forms indicate poor survival. To better understand the role of uPAR cleavage in cancer, we have designed immunoassays for specific quantification of intact mouse uPAR [muPAR(I-III)] and mouse uPAR domain I [mu......PAR(I)]. The level of muPAR(I) is significantly increased in mammary tumor-bearing mice compared to controls and, notably, there is a strong correlation to tumor volume. In contrast, the tumor volume is only weakly correlated to the level of intact muPAR(I-III), indicating that cleavage of muPAR is a more...

  6. Soluble urokinase receptor levels in plasma during 5 years of highly active antiretroviral therapy in HIV-1-infected patients

    Ostrowski, Sisse R; Katzenstein, Terese L; Piironen, Timo;

    2004-01-01

    High blood levels of the soluble urokinase receptor (suPAR) strongly predict increased mortality in human immunodeficiency virus-1 (HIV-1)-infected patients. This study investigated the plasma concentration of suPAR in 29 treatment-naive HIV-1-infected patients during 5 years treatment with highl...

  7. Expression of urokinase plasminogen activator, its receptor and type-1 inhibitor in malignant and benign prostate tissue

    Usher, Pernille Autzen; Thomsen, Ole Frøkjær; Iversen, Peter; Johnsen, Morten; Brünner, Nils; Høyer-Hansen, Gunilla; Andreasen, Peter; Danø, Keld; Nielsen, Boye Schnack

    2005-01-01

    The plasminogen activation (PA) cascade participates in degradation of extracellular matrix during cancer invasion. We have studied the expression of urokinase-type plasminogen activator (uPA) mRNA, uPA receptor (uPAR) mRNA and immunoreactivity, and type-1 plasminogen activator inhibitor (PAI-1) ...

  8. The plasma level of soluble urokinase receptor is elevated in patients with Streptococcus pneumoniae bacteraemia and predicts mortality

    Wittenhagen, p; Kronborg, Gitte; Nielsen, H; Obel, N; Pedersen, SS; Eugen-Olsen, Jesper; Weis, Nina Margrethe

    2004-01-01

    This multicentre prospective study was conducted to investigate whether the level of the soluble form of urokinase-type plasminogen activator receptor (suPAR) is elevated during pneumococcal bacteraemia and is of predictive value in the early stage of the disease. Plasma levels of suPAR were incr...

  9. The liberated domain I of urokinase plasminogen activator receptor--a new tumour marker in small cell lung cancer

    Almasi, Charlotte E; Drivsholm, Lars; Pappot, Helle;

    2013-01-01

    The prognosis of small cell lung cancer (SCLC) remains poor with a 5-year survival rate of 4-6%. In non-small cell lung cancer (NSCLC), high levels of intact and cleaved forms of the receptor for urokinase plasminogen activator (uPAR) are significantly associated with short overall survival. Our...

  10. The Heparin-Induced Thrombocytopenia and Thrombosis Syndrome: Treatment with Intraarterial Urokinase and Systemic Platelet Aggregation Inhibitors

    We report a case of the heparin-induced thrombocytopenia and thrombosis syndrome presenting with acute ischemia of a lower limb. The patient was successfully treated by withdrawal of heparin products, intraarterial urokinase, and platelet anti-aggregation therapy consisting of Dextran and aspirin

  11. Plasminogen activation by receptor-bound urokinase. A kinetic study with both cell-associated and isolated receptor

    Ellis, V; Behrendt, N; Danø, K

    1991-01-01

    The specific cellular receptor for urokinase-type plasminogen activator (uPA) is found on a variety of cell types and has been postulated to play a central role in the mediation of pericellular proteolytic activity. We have studied the kinetics of plasminogen (Plg) activation catalyzed by uPA spe...

  12. Cellular receptor for urokinase plasminogen activator. Carboxyl-terminal processing and membrane anchoring by glycosyl-phosphatidylinositol

    Ploug, M; Rønne, E; Behrendt, N;

    1991-01-01

    The cellular receptor for human urokinase-type plasminogen activator (u-PAR) is shown by several independent criteria to be a true member of a family of integral membrane proteins, anchored to the plasma membrane exclusively by a COOH-terminal glycosyl-phosphatidylinositol moiety. 1) Amino acid a...

  13. A conserved TATA-less proximal promoter drives basal transcription from the urokinase-type plasminogen activator receptor gene

    Soravia, E; Grebe, A; De Luca, P;

    1995-01-01

    The urokinase-type plasminogen activator receptor (uPAR) focuses at the cell surface the activation of pro-uPA and, hence, the formation of plasmin, thus enhancing directional extracellular proteolysis. To characterize the transcriptional regulatory mechanisms that control receptor expression, we...

  14. Aberrant glomerular filtration of urokinase-plasminogen activator in nephrotic syndrome leads to amiloride-sensitive plasminogen activation in urine

    Stæhr, Mette; Buhl, Kristian Bergholt; Andersen, René F;

    2015-01-01

    In nephrotic syndrome, aberrant glomerular filtration of plasminogen and conversion to active plasmin in pre-urine is thought to activate proteolytically ENaC and contribute to sodium retention and edema. The ENaC blocker amiloride is an off-target inhibitor of urokinase-type plasminogen activator...

  15. Genetic association of urokinase-type plasminogen activator gene rs2227564 site polymorphism with sporadic Alzheimer's disease in the Han Chinese population

    Xuelian Ji; Longfei Jia; Jianping Jia; Li Qi

    2012-01-01

    A missense C/T polymorphism in exon 6 (the NCBI rsID is rs2227564) of the urokinase-type plasminogen activator gene has been identified as a possible hot spot for Alzheimer's disease risk.The present study analyzed urokinase-type plasminogen gene polymorphisms of rs2227564 with sporadic Alzheimer's disease by PCR-restriction fragment length polymorphism.Results showed that CC,CT and TT genotype distribution frequencies had significant differences between sporadic Alzheimer's disease patients and healthy controls.In-depth analysis of the association between urokinase-type plasminogen gene rs2227564 polymorphisms and sporadic Alzheimer's disease indicated that people with the C-positive genotype CC + CT were at a higher risk for developing sporadic Alzheimer's disease.These results support the contribution of the polymorphisms of rs2227564 in the urokinase-type plasminogen gene to the pathogenesis of sporadic Alzheimer's disease in the Han Chinese population.

  16. Urokinase plasminogen activator receptor affects bone homeostasis by regulating osteoblast and osteoclast function

    Furlan, Federico; Galbiati, Clara; Jørgensen, Niklas R;

    2007-01-01

    reorganization in mature osteoclasts. INTRODUCTION: Urokinase receptor (uPAR) is actively involved in the regulation of important cell functions, such as proliferation, adhesion, and migration. It was previously shown that the major players in bone remodeling, osteoblasts and osteoclasts, express uPAR and...... to mechanical tests. UPAR KO calvaria osteoblasts were characterized by proliferation assays, RT-PCR for important proteins secreted during differentiation, and immunoblot for activator protein 1 (AP-1) family members. In vitro osteoclast formation was tested with uPAR KO bone marrow monocytes in the...... osteoblasts showed a proliferative advantage with no difference in apoptosis, higher matrix mineralization, and earlier appearance of alkaline phosphatase (ALP). Surface RANKL expression at different stages of differentiation was not altered. AP-1 components, such as JunB and Fra-1, were upregulated in u...

  17. Urokinase mediates endothelial cell survival via induction of the X-linked inhibitor of apoptosis protein

    Prager, Gerald W; Mihaly, Judit; Brunner, Patrick M;

    2008-01-01

    factor kappaB (NF-kappaB) p52 activation. Indeed, blocking NF-kappaB activation by using specific NF-kappaB inhibitors abolished uPA-induced cell survival as it blocked uPA-induced XIAP up-regulation. Furthermore, down-regulating XIAP expression by small interfering RNA (siRNA) significantly reduced u......Urokinase-type plasminogen activator (uPA) additionally elicits a whole array of pro-angiogenic responses, such as differentiation, proliferation, and migration. In this study, we demonstrate that in endothelial cells uPA also protects against apoptosis by transcriptional up-regulation and......PA-dependent endothelial cell survival. This mechanism is also important for VEGF-induced antiapoptosis because VEGF-dependent up-regulation of XIAP was found defective in uPA(-/-) endothelial cells. This led us to conclude that uPA is part of a novel NF-kappaB-dependent cell survival pathway....

  18. Effects of urokinase-type plasminogen activator in the acquisition, expression and reinstatement of cocaine-induced conditioned-place preference

    Bahi, Amine; Kusnecov, Alexander W; Dreyer, Jean-Luc

    2008-01-01

    Cocaine and many other psychostimulants strongly induce urokinase-type plasminogen activator (uPA) expression in the mesolimbic dopaminergic pathway, which plays a major role in drug-mediated behavioral plasticity [Bahi A, Boyer F, Gumy C, Kafri T, Dreyer JL. In vivo gene delivery of urokinase-type plasminogen activator with regulatable lentivirus induces behavioral changes in chronic cocaine administration. Eur J Neurosci 2004;20:3473–88; Bahi A, Boyer F, Kafri T, Dreyer JL. Silencing urokin...

  19. The superoxide scavenger TEMPOL induces urokinase receptor (uPAR expression in human prostate cancer cells

    Francis Joseph

    2006-06-01

    Full Text Available Abstract There is little understanding of the effect that reactive oxygen metabolites have on cellular behavior during the processes of invasion and metastasis. These oxygen metabolites could interact with a number of targets modulating their function such as enzymes involved in basement membrane dissolution, adhesion molecules involved in motility or receptors involved in proliferation. We investigated the effect of increased scavenging of superoxide anions on the expression of the urokinase receptor (uPAR in PC-3M human prostate cancer cells. Urokinase receptor is a GPI-linked cell surface molecule which mediates multiple functions including adhesion, proliferation and pericellular proteolysis. Addition of the superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (TEMPOL to PC-3M cultures stimulated expression of uPAR protein peaking between 48 and 72 hours. Cell surface expression of the uPAR was also increased. Surprisingly, uPAR transcript levels increased only slightly and this mild increase did not coincide with the striking degree of protein increase. This disparity indicates that the TEMPOL effect on uPAR occurs through a post-transcriptional mechanism. TEMPOL presence in PC-3M cultures reduced intracellular superoxide-type species by 75% as assayed by NBT dye conversion; however this reduction significantly diminished within hours following TEMPOL removal. The time gap between TEMPOL treatment and peak uPAR protein expression suggests that reduction of reactive oxygen metabolites in prostate cancer cells initiates a multistep pathway which requires several hours to culminate in uPAR induction. These findings reveal a novel pathway for uPAR regulation involving reactive oxygens such as superoxide anion.

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

    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

  1. Outcome evaluation of intra-arterial infusion of urokinase for acute ischemic stroke

    To evaluate the results of intra-arterial urokinase thrombolysis in cases of acute ischemic stroke and to define the factors affecting prognosis. Forty-eight patients with angiographically proven occlusion of the intracranial arteries were treated with local intra-arterial infusion of urokinase within six hours of the onset of symptoms. Neurologic status was evaluated on admission and on discharge using the NIH (National Institute of Health) stroke scale score (SSS). When the SSS decreased by at least four points, this was considered indicative of an improved clinical outcome. Complete recanalization was achieved in 17/48 patients (35%), including 8 of 13 (62%) with occlusion of the vertebrobasilar artery (VBA), 9 of 20 (45%) with occlusion of the middle cerebral artery (MCA), and none of 15 with occlusion of the internal carotid artery (ICA). Neurologic status improved in 12 (60%) of patients with MCA occlusion, in five (38%) of those with VBA occlusion and in three (20%) of those with ICA occlusion (p less than 0.005). Patients in whom occluded MCA was completely recanalized showed greater clinical improvement than those with partial or no recanalization (p less than 0.05). The overall mortality rate was 21%, 43% (9/21) in patients in whom CT revealed signs of early infarct, but only 4% (1/27) in those without this sign (p less than 0.05). The mortality rate of patients with parenchymal hematoma (4/5) was higher than that of those with hemorrhagic infarct (3/9) or without hemorrhage (3/34) (p less than 0.005). In patients in whom occluded MCA was completely recanalized, the clinical outcome was better, while patients with VBA occlusion did not benefit from recanalization. The presence on CT scans of signs of early infarct and of parenchymal hematoma after thrombolysis correlated with a high mortality rate. (author)

  2. Outcome evaluation of intra-arterial infusion of urokinase for acute ischemic stroke

    Shi, Hai Bin [First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Suh, Dae Chul; Lim, Soo Mee [Asan Medical Center, College of Medicine, University of Ulsan, Seoul (Korea, Republic of); And Others

    2000-06-01

    To evaluate the results of intra-arterial urokinase thrombolysis in cases of acute ischemic stroke and to define the factors affecting prognosis. Forty-eight patients with angiographically proven occlusion of the intracranial arteries were treated with local intra-arterial infusion of urokinase within six hours of the onset of symptoms. Neurologic status was evaluated on admission and on discharge using the NIH (National Institute of Health) stroke scale score (SSS). When the SSS decreased by at least four points, this was considered indicative of an improved clinical outcome. Complete recanalization was achieved in 17/48 patients (35%), including 8 of 13 (62%) with occlusion of the vertebrobasilar artery (VBA), 9 of 20 (45%) with occlusion of the middle cerebral artery (MCA), and none of 15 with occlusion of the internal carotid artery (ICA). Neurologic status improved in 12 (60%) of patients with MCA occlusion, in five (38%) of those with VBA occlusion and in three (20%) of those with ICA occlusion (p less than 0.005). Patients in whom occluded MCA was completely recanalized showed greater clinical improvement than those with partial or no recanalization (p less than 0.05). The overall mortality rate was 21%, 43% (9/21) in patients in whom CT revealed signs of early infarct, but only 4% (1/27) in those without this sign (p less than 0.05). The mortality rate of patients with parenchymal hematoma (4/5) was higher than that of those with hemorrhagic infarct (3/9) or without hemorrhage (3/34) (p less than 0.005). In patients in whom occluded MCA was completely recanalized, the clinical outcome was better, while patients with VBA occlusion did not benefit from recanalization. The presence on CT scans of signs of early infarct and of parenchymal hematoma after thrombolysis correlated with a high mortality rate. (author)

  3. The Prognostic Significance of Soluble Urokinase Plasminogen Activator Receptor in Acute Myeloid Leukemia

    Nergiz Erkut

    2016-05-01

    Full Text Available Objective: The soluble urokinase plasminogen activator receptor (suPAR is a soluble form of the urokinase plasminogen activator receptor expressed in various immune and cancer cells. The levels of suPAR have been demonstrated to correlate with prognosis in various cancers. This study was intended to investigate serum suPAR levels and their effect on prognosis in patients with acute myeloid leukemia (AML. Materials and Methods: Thirty newly diagnosed patients with AML and 29 healthy individuals were enrolled. Serum suPAR levels were analyzed by enzyme-linked immunosorbent assay. Results: Serum suPAR levels were significantly higher in patients with AML than in healthy individuals (9±5.9 ng/mL and 2.4±1.4 ng/mL, respectively; p<0.001. Positive correlation was determined between suPAR levels and white blood cell counts (p<0.01. Serum suPAR levels were lower in patients who achieved complete response than in patients not achieving complete response (5.5±2.2 ng/mL and 12±6.6 ng/mL, respectively; p<0.001. The median overall survival was longer in patients with serum suPAR levels below 6.71 ng/mL than in those with serum suPAR levels above 6.71 ng/mL (12.6±13.2 months and 1.71±0.6 months, respectively; p=0.02. Multivariate Cox regression analysis showed that suPAR had independent prognostic value (95% confidence interval: 1.029-6.259; p<0.05 in AML. Conclusion: Serum suPAR levels can be used as a prognostic marker in AML.

  4. Activation of human pro-urokinase by unrelated proteases secreted by Pseudomonas aeruginosa.

    Beaufort, Nathalie; Seweryn, Paulina; de Bentzmann, Sophie; Tang, Aihua; Kellermann, Josef; Grebenchtchikov, Nicolai; Schmitt, Manfred; Sommerhoff, Christian P; Pidard, Dominique; Magdolen, Viktor

    2010-06-15

    Pathogenic bacteria, including Pseudomonas aeruginosa, interact with and engage the host plasminogen (Plg) activation system, which encompasses the urokinase (uPA)-type Plg activator, and is involved in extracellular proteolysis, including matrilysis and fibrinolysis. We hypothesized that secreted bacterial proteases might contribute to the activation of this major extracellular proteolytic system, thereby participating in bacterial dissemination. We report that LasB, a thermolysin-like metalloprotease secreted by Ps. aeruginosa, converts the human uPA zymogen into its active form (kcat=4.9 s-1, Km=8.9 microM). Accordingly, whereas the extracellular secretome from the LasB-expressing pseudomonal strain PAO1 efficiently activates pro-uPA, the secretome from the isogenic LasB-deficient strain PDO240 is markedly less potent in pro-uPA activation. Still, both secretomes induce some metalloprotease-independent activation of the human zymogen. The latter involves a serine protease, which we identified via both recombinant protein expression in Escherichia coli and purification from pseudomonal cultures as protease IV (PIV; kcat=0.73 s-1, Km=6.2 microM). In contrast, neither secretomes nor the pure proteases activate Plg. Along with this, LasB converts Plg into mini-Plg and angiostatin, whereas, as reported previously, it processes the uPA receptor, inactivates the plasminogen activator inhibitor 1, and activates pro-matrix metalloproteinase 2. PIV does not target these factors at all. To conclude, LasB and PIV, although belonging to different protease families and displaying quite different substrate specificities, both activate the urokinase-type precursor of the Plg activation cascade. Direct pro-uPA activation, as also reported for other bacterial proteases, might be a frequent phenomenon that contributes to bacterial virulence. PMID:20337595

  5. The receptor for urokinase regulates TLR2 mediated inflammatory responses in neutrophils.

    Gang Liu

    Full Text Available The urokinase-type plasminogen activator receptor (uPAR, a glycosylphosphatidylinositol (GPI anchored membrane protein, regulates urokinase (uPA protease activity, chemotaxis, cell-cell interactions, and phagocytosis of apoptotic cells. uPAR expression is increased in cytokine or bacteria activated cell populations, including macrophages and monocytes. However, it is unclear if uPAR has direct involvement in the response of inflammatory cells, such as neutrophils and macrophages, to Toll like receptor (TLR stimulation. In this study, we found that uPAR is required for optimal neutrophil activation after TLR2, but not TLR4 stimulation. We found that the expression of TNF-α and IL-6 induced by TLR2 engagement in uPAR-/- neutrophils was less than that in uPAR+/+ (WT neutrophils. Pretreatment of neutrophils with PI-PLC, which cleaves GPI moieties, significantly decreased TLR2 induced expression of TNF-α in WT neutrophils, but demonstrated only marginal effects on TNF-α expression in PAM treated uPAR-/- neutrophils. IκB-α degradation and NF-κB activation were not different in uPAR-/- or WT neutrophils after TLR2 stimulation. However, uPAR is required for optimal p38 MAPK activation after TLR2 engagement. Consistent with the in vitro findings that uPAR modulates TLR2 engagement induced neutrophil activation, we found that pulmonary and systemic inflammation induced by TLR2, but not TLR4 stimulation is reduced in uPAR-/- mice compared to WT counterparts. Therefore, our data suggest that neutrophil associated uPAR could be a potential target for treating acute inflammation, sepsis, and organ injury related to severe bacterial and other microbial infections in which TLR2 engagement plays a major role.

  6. Interleukin-6 infusion during human endotoxaemia inhibits in vitro release of the urokinase receptor from peripheral blood mononuclear cells

    Ostrowski, S R; Plomgaard, P; Fischer, C P;

    2005-01-01

    Leucocyte expression of the urokinase receptor [urokinase-type plasminogen activator receptor (uPAR)] is regulated by inflammatory mediators. This study investigated the in vivo effect of endotoxin, interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha on uPAR-release in vivo and in vitro in...... humans. Healthy subjects received intravenous endotoxin injection [high-dose, 2 ng/kg (n=8) and low-dose, 0.06 ng/kg (n=7)], coadministration of 0.06 ng/kg endotoxin and 3 h recombinant human (rh)IL-6 infusion (n=7) or 3 h infusion of rhIL-6 (n=6), rhTNF-alpha (n=6) or NaCl (n=5). Soluble uPAR (su...

  7. Quantitative PET of human urokinase-type plasminogen activator receptor with 64Cu-DOTA-AE105

    Persson, Morten; Madsen, Jacob; Østergaard, Søren;

    2012-01-01

    Expression levels of the urokinase-type plasminogen activator receptor (uPAR) represent an established biomarker for poor prognosis in a variety of human cancers. The objective of the present study was to explore whether noninvasive PET can be used to perform a quantitative assessment of expressi...... levels of uPAR across different human cancer xenograft models in mice and to illustrate the clinical potential of uPAR PET in future settings for individualized therapy.......Expression levels of the urokinase-type plasminogen activator receptor (uPAR) represent an established biomarker for poor prognosis in a variety of human cancers. The objective of the present study was to explore whether noninvasive PET can be used to perform a quantitative assessment of expression...

  8. In vivo gene delivery of urokinase-type plasminogen activator with regulatable lentivirus induces behavioural changes in chronic cocaine administration

    Bahi, Amine; Boyer, Frederic; Gumy, Christèle; Kafri, Tal; Dreyer, Jean-Luc

    2005-01-01

    Serine proteases play a key function in extracellular processes affecting central nervous system plasticity. Recently, the role of extracellular proteolytic processes in regulating synaptic structure and function has been described. However, to date direct evidence linking extracellular serine protease activity with drug-related behavioural changes has not been documented. Importantly, in a screening for genes induced after drug treatment we found that urokinase plasminogen-type activator (uP...

  9. Localization of urokinase-type plasminogen activator in stromal cells in adenocarcinomas of the colon in humans.

    Grøndahl-Hansen, J.; Ralfkiaer, E; Kirkeby, L. T.; P. Kristensen; Lund, L. R.; Danø, K

    1991-01-01

    Human colon adenocarcinomas and adjacent normal colon tissues were stained immunohistochemically with three different monoclonal antibodies and one preparation of polyclonal antibodies against each of the two plasminogen activators, uPA (urokinase type) and tPA (tissue type). The staining patterns seen with the respective sets of antibodies were identical. In all of 10 cases, staining for uPA in the normal colon tissue was confined to scattered fibroblastlike cells in the lamina propria. Othe...

  10. Urokinase-targeted recombinant bacterial protein toxins-a rationally designed and engineered anticancer agent for cancer therapy

    Yizhen LIU; Shi-Yan LI

    2009-01-01

    Urokinase-targeted recombinant bacterial protein toxins are a sort of rationally designed and engineered anticancer recombinant fusion proteins representing a novel class of agents for cancer therapy.Bacterial protein toxins have long been known as the primary virulence factor(s) for a variety of pathogenic bacteria and are the most powerful human poisons.On the other hand,it has been well documented that urokinase-type plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR),making up the uPA system,are overexpressed in a variety of human tumors and tumor cell lines.The expression of uPA system is highly correlated with tumor invasion and metastasis.To exploit these characteristics in the design of tumor cell-selective cytotoxins,two prominent bacterial protein toxins,i.e.,the diphtheria toxin and anthrax toxin are deliberately engineered through placing a sequence targeted specifically by the uPA system to form anticancer recombinant fusion proteins.These uPA system-targeted bacterial protein toxins are activated selectively on the surface of uPA systemexpressing tumor cells,thereby killing these cells.This article provides a review on the latest progress in the exploitation of these recombinant fusion proteins as potent tumoricidal agents.It is perceptible that the strategies for cancer therapy are being innovated by this novel therapeutic approach.

  11. Exchange Rate Regime Choice

    2006-01-01

    The choice of an adequate exchange rate regime proves to be a highly sensitive field within which the economic authorities present and confirm themselves. The advantages and disadvantages of fixed and flexible exchange rate regimes, which have been quite relativized from the conventional point of view, together with simultaneous, but not synchronised effects of structural and external factors, remain permanently questioned throughout a complex process of exchange rate regime decision making. ...

  12. 纳米尿激酶的性状研究%Characterization of urokinase chitosan nanoparticles

    金海将; 张皓; 张柏根; 孙敏莉

    2011-01-01

    背景:尿激酶半衰期短,需持续大量给药,并发症也不小,故有必要研制具有缓释作用的溶栓药物.目的:了解包载尿激酶的水溶性壳聚糖纳米粒子的性状.方法:将壳聚糖和三聚磷酸钠以离子凝集法制备尿激酶纳米粒子后,用透射电镜观察其形态,采用粒径仪测纳米粒子粒径,酶标仪比色法测粒子包封率,纳米粒子冻干法测其载药量,并检测体内外纳米粒子缓释特性.结果与结论:当壳聚糖、三聚磷酸钠、尿激酶的质量比为7∶1∶1时,不仅溶液稳定,形成的纳米粒子粒径小,而且包封率和载药量均合适.制备出包封率最高达94.8%的尿激酶纳米粒子,载药量为14.5%,此时平均粒径236 nm,透射电镜观察示粒子形态较规则,呈球形;粒子具有较好的缓释性能;表明将尿激酶包被于纳米粒子中,避免了消化酶的直接作用,延长了半衰期,不仅在体内能保持较长时间的活性,而且具有明显的缓释效果.%BACKGROUND: Because urokinase has a short half-life, and has a sustained large dose, resulting in in negligible complications,it is necessary to develops low- release thrombolytic drugs .OBJECTIVE: To study the characterization of urokinase chitosan nanoparticles.METHODS: The nanoparticles were prepared via the self-assembly of chitosan and sodium tripolyphosphate. Themorphololywas observed by transmission electron microscopy (TEM). Particle size was measured with particle size instrument Theencapsulation efficiency was tested by ELISA Reader. Drug loading efficiency was measured by the way of weighing lyophiizedpowder. Release characteristics of the nanoparticles were investigated both in vitro and in vivo.RESULT SAND CONCLUSION: When the mass ratio of chitosan, sodium trip olyphosph ate, and ur ok in as was 7:1:1, the solutionwas stable, the nanoparticle size was small, and drug encapsulation efficiency and loading efficiency were appropriate. When thehighest encapsulation

  13. Increased expression of urokinase plasminogen activator and its cognate receptor in human seminomas

    The urokinase plasminogen activating system (uPAS) is implicated in neoplastic progression and high tissue levels of uPAS components correlate with a poor prognosis in different human cancers. Despite that, relative few studies are available on the expression and function of the uPAS components in human seminomas. In the present study we characterized the expression of the urokinase plasminogen activator (uPA), its cognate receptor (uPAR) and the uPA inhibitors PAI-1 and PAI-2 in normal human testis and seminomas. The expression of the above genes was evaluated by means of quantitative RT-PCR, western blot, zymographic analysis and immunohistochemistry. Quantitative RT-PCR analysis of 14 seminomas demonstrated that uPA and uPAR mRNAs were, with respect to control tissues, increased in tumor tissues by 3.80 ± 0.74 (p < 0.01) and 6.25 ± 1.18 (p < 0.01) fold, respectively. On the other hand, PAI-1 mRNA level was unchanged (1.02 ± 0.24 fold), while that of PAI-2 was significantly reduced to 0.34 ± 0.18 (p < 0.01) fold. Western blot experiments performed with protein extracts of three seminomas and normal tissues from the same patients showed that uPA protein levels were low or undetectable in normal tissues and induced in tumor tissues. On the same samples, zymographic analysis demonstrated increased uPA activity in tumor tissue extracts. Western blot experiments showed that also the uPAR protein was increased in tumor tissues by 1.83 ± 0.15 fold (p < 0.01). The increased expression of uPA and uPAR was further confirmed by immunohistochemical staining performed in 10 seminomas and autologous uninvolved peritumoral tissues. Finally, variation in the mRNA level of PAI-1 significantly correlated with tumor size. We demonstrated the increased expression of uPA and uPAR in human seminomas with respect to normal testis tissues, which may be relevant in testicular cancer progression

  14. Sustainable urban regime adjustments

    Quitzau, Maj-Britt; Jensen, Jens Stissing; Elle, Morten;

    2013-01-01

    The endogenous agency that urban governments increasingly portray by making conscious and planned efforts to adjust the regimes they operate within is currently not well captured in transition studies. There is a need to acknowledge the ambiguity of regime enactment at the urban scale. This direc...

  15. Thrombolysis for treating deep venous thrombosis by high-dose urokinase: the usefulness of preventive placement of inferior vena cava filter

    Objective: To investigate the feasibility and efficacy of high-dose urokinase thrombolysis for treating lower limb deep venous thrombosis (DVT) after inferior vena cava (IVC) filter placement. Methods: Thirteen patients of venographically proved DVT underwent preventive IVC filter placement for thrombolysis by high-dose urokinase. Antegrade infusion of high-dose urokinase was performed via the dorsalis pedis vein of the involved lower limb. The total dose of urokinase was 9 000 000 ∼ 16 000 000 units, and the procedure of thrombolysis was performed in ICU ward where the patients were closely monitored clinically and laboratorially. Results: A total of 13 IVC filters were successfully deployed without disposition and migration. The therapeutic effects were divided into four scales as follows: complete disappearance of the venous thrombosis and clinically asymptomatic (n = 2); remarkable recovery characterized by markedly improved clinical symptoms and venographically proved patent lumen in which the diameter was larger than 70% (n = 9); effective treatment indicating improved symptoms to some degrees and venographically proved patent lumen in which the diameter was smaller than 70% ( n = 2); and ineffective treatment (n = 0). No pulmonary embolism and hemorrhage occurred during the procedure of thrombolysis. Conclusion: High-dose urokinase for treating DVT is safe and effective after preventive placement of IVC filter

  16. Soluble Urokinase Receptors in Focal Segmental Glomerulosclerosis: A Review on the Scientific Point of View

    Saleem, Moin A.; Meijers, Björn

    2016-01-01

    Focal segmental glomerulosclerosis (FSGS) is one of the primary glomerular disorders in both children and adults which can progress to end-stage renal failure. Although there are genetic and secondary causes, circulating factors have also been regarded as an important factor in the pathogenesis of FSGS, because about 40% of the patients with FSGS have recurrence after renal transplantation. Soluble urokinase-type plasminogen activator receptor (suPAR) is a soluble form of uPAR, which is a membrane-bound protein linked to GPI in various immunologically active cells, including podocytes. It has recently been suggested as a potential circulating factor in FSGS by in vitro podocyte experiments, in vivo mice models, and human studies. However, there have also been controversies on this issue, because subsequent studies showed conflicting results. suPAR levels were also increased in patients with other glomerular diseases and were inversely correlated with estimated glomerular filtration rate. Nevertheless, there has been no balanced review on this issue. In this review, we compare the conflicting data on the involvement of suPAR in the pathogenesis of FSGS and shed light on interpretation by taking into account many points and the potential variables and confounders influencing serum suPAR levels.

  17. Endovascular Treatment of Left Iliofemoral Deep Vein Thrombosis Using Urokinase Thrombolysis and Adjunctive Aspiration Thrombectomy

    Suh, Sang Hyun; Lee, Do Yun; Won, Jong Yun [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2010-02-15

    To evaluate the efficacy of adjunctive aspiration thrombectomy for the treatment of iliofemoral deep vein thrombosis (DVT). 24 patients (9 males and 15 females; mean age, 53 years), treated by aspiration thrombectomy were enrolled in this study. The day after undergoing urokinase (UK) thrombolysis, any residual thrombus over a long segment was treated by aspiration thrombectomy using a 12 Fr long sheath. Residual short-segment (< 10 cm) iliac vein thrombus and/or stenosis were treated with a stent. The evaluation of venous patency was conducted by color Doppler ultrasonography, venography and/or computed tomography. The technical and clinical success rates were 100% and 92%, respectively. Twenty-three patients were treated by UK thrombolysis and iliac stent. The overall patency rate at 1, 2 and 3 years was 85%, 82% and 81%, respectively. Over the course of the follow-up period, occlusion was observed in 4 cases (1 acute and 3 chronic cases). Periprocedural complication occurred in 4 cases (17%) in the form of a minimal hematoma or pain on the puncture site as well as a case of pulmonary embolism at one month after treatment. The adjunctive aspiration thrombectomy with conventional thrombolysis and stent placement can be an effective and safe method in the treatment of left iliofemoral DVT

  18. Endovascular Treatment of Left Iliofemoral Deep Vein Thrombosis Using Urokinase Thrombolysis and Adjunctive Aspiration Thrombectomy

    To evaluate the efficacy of adjunctive aspiration thrombectomy for the treatment of iliofemoral deep vein thrombosis (DVT). 24 patients (9 males and 15 females; mean age, 53 years), treated by aspiration thrombectomy were enrolled in this study. The day after undergoing urokinase (UK) thrombolysis, any residual thrombus over a long segment was treated by aspiration thrombectomy using a 12 Fr long sheath. Residual short-segment (< 10 cm) iliac vein thrombus and/or stenosis were treated with a stent. The evaluation of venous patency was conducted by color Doppler ultrasonography, venography and/or computed tomography. The technical and clinical success rates were 100% and 92%, respectively. Twenty-three patients were treated by UK thrombolysis and iliac stent. The overall patency rate at 1, 2 and 3 years was 85%, 82% and 81%, respectively. Over the course of the follow-up period, occlusion was observed in 4 cases (1 acute and 3 chronic cases). Periprocedural complication occurred in 4 cases (17%) in the form of a minimal hematoma or pain on the puncture site as well as a case of pulmonary embolism at one month after treatment. The adjunctive aspiration thrombectomy with conventional thrombolysis and stent placement can be an effective and safe method in the treatment of left iliofemoral DVT

  19. The modified pulse-spray method using Urokinase in subacute and chronic thrombotic arterial occlusion

    To evaluate the effectiveness and safety of the modified pulse-spray method using Urokinase(UK) in subacute and chronic thrombotic arterial occlusion. Modified pulse-spray methods using UK were performed in seven patients with subacute (1 week-1month) to chronic (1month-5years) occlusive symptoms such as limb pain, claudication and impotence. Angiographic examination revealed thrombotic occlusion of the aorta, common iliac arteries, brachial arterio-venous hemodialysis graft and femoro-popliteal bypass graft. The patients underwent thrombolysis using modified pulse-spray and additional constant infusion of UK. In the presence of underlying stenosis or organized clots, balloon angioplasty or stent placement was performed. Complete lysis was obtained in five of seven patients. For initial lysis, the mean dose of UK was 420,000 units, and the mean modified pulse-spray time was 50 minutes. Mean total dose of UK and mean total time for complete lysis were 800,000 units and 161 minutes, respectively. Thrombolysis of the femoro-popliteal bypass graft failed due to severe occlusion of the distal anastomosis. Partial lysis was achieved in one patient with aorto-illac occlusion, but further thrombolysis was stopped due to bleeding at the puncture site. The modified pulse-spray method using UK is effective in treating subacute and chronic arterial thrombotic occlusion. It augments the speed, safety and efficacy of thrombolysis. When underlying stenosis or organized clots remain after thrombolysis, ballon angioplasty or stent placement would be helpful

  20. [Preparation of novel magnetic dextran affinity adsorbents and their application to purify urokinase].

    Dong, Y S; Liang, F; Yu, X Y; Guo, L A; Chang, J H

    2001-01-01

    The reverse phase suspension and embedment technique were adopted to prepare magnetic dextran microsphere (MDMS). The dispersion medium was mixture of some organic solvents. Span-80 was used as stabilizer. The aqueous dextran with magnetic fluid was suspended in dispersion medium with epichlorohydrin as cross-linking reagent. The mixture was stirred for 30 minutes at room temperature and then heated at 70 degrees C for 4 hours, MDMS was thus obtained. MDMS was activated by epichlorohydrin on which 6-aminohexanoic acid, glycine or ethylene diamine was bonded as spacers. Then it was coupled with p-aminobenzamide, L-arginine methyl ester or guanidohexanoic acid and five magnetic affinity adsorbents were prepared. The MDMS was polydisperse particles with the size of 50-300 meshes and the content of Fe3O4 was about 6.2 per cent in the MDMS. Influence of some parameters such as viscosity and density of organic phase, the volume ratio of organic and aqueous phase, the quantity of surfactant and stirring speed on preparing MDMS was studied. Magnetic affinity adsorbents were used to purify crude urokinase in a bath mode and the effect of coupling reagents and ligands on results of purification was discussed. The bioactivity recovery was 40.0 to 60.7 per cent, the purification-fold was between 14.9 and 32.8, and the adsorptive capacity varies from 89 mg to 121 mg per milliliter of adsorbent. PMID:12541840

  1. Intra-Carotid Urokinase thrombolytic therapy in acute cerebral infarction: a preliminary study

    We conducted a pilot study to evaluate the possibility that the intraarterial thrombolytic therapy might lead to recanalization of the acutely occluded cerebral arteries and subsequent clinical improvement in patients with acute cerebral infarction. Mean time from the onset of symptoms to the start of treatment and mean dosage of thrombolytic agent, Urokinase, were 6.4 hours and 1,260,000 units, respectively. Seven of 12 cases (58%) with acute cerebral infarction demonstrated successful recanalization. Neurological evaluation at one week and three months after the onset of symptoms suggested better outcome in the cases with recanalization. Repeat CT scan at 24 hours and one week after the procedure demonstrated the evidence of hemorrhagic infarction in the infarcted territories in five cases (41%), but clinical deteriorations were observed in only 2 cases. Though statistical analysis could not be done because the limited number of cases, these results suggest that the intraarterial thrombolytic therapy had a role in the management of acute cerebral infarction

  2. EXPRESSION AND SIGNIFICANCE OF UROKINASE-TYPE PLASMINOGEN ACTIVATOR IN BREAST CANCER

    XIAO Jiping; ZHANG Guangde; XIA Wenhua; CHENG Deji

    1999-01-01

    Objective: To study the expression and clinical significance of urokinase-type plasminogen activator (uPA) in breast cancer. Methods: Applying streptavidin-biotin complex (SABC) immunohistochemical technique, expression of uPA was studied in 100 patients with primary breast cancer. Results: There were 55 patients with high uPA expression, and 45 with lower expression. There was significant correlation between uPA expression and TNM stage, lymph node status, and the tumor size. Neither age, menopausal status, nor ER status was significantly related with level of uPA expression. The patients with high expression of uPA had significantly shorter disease-free survival (DFS)and overall survival (OS) than did those with low expression of uPA. Univariate analysis showed that uPA as a prognostic factor was of similar magnitude to lymph node status and TNM stage, but stronger than that of ER status and tumor size. UPA was an independent prognostic factor affecting disease-free survival and overall survival. Conclusion: uPA appears to be a strong and independent biologic marker for predicting prognosis of breast cancer.

  3. Tyk2 mediates effects of urokinase on human vascular smooth muscle cell growth

    The urokinase (uPA)/uPA receptor (uPAR) system plays a role in the response of the vessel wall to injury, presumably by modulating vascular smooth muscle cell (VSMC) functional behaviour. The Jak/Stat signaling pathway has been implicated to mediate the uPA/uPAR-directed cell migration and proliferation in VSMC. We have therefore investigated the underlying molecular mechanisms, which remained not completely understood. In particular, we aimed at identification of the kinase involved in the signaling cascade leading to Stat1 phosphorylation by uPA and its impact on VSMC growth. We performed expression in VSMC of kinase-deficient mutant forms of the Janus kinases Jak1 and Tyk2 and used different cell culture models imitating the response to vascular injury. We provide evidence that Tyk2, but not Jak1, mediates uPA-induced Stat1 phosphorylation and VSMC growth inhibition and suggest a novel function for Tyk2 as an important modulator of the uPA-directed VSMC functional behaviour at the place of injury

  4. Aggregation and retention of human urokinase type plasminogen activator in the yeast endoplasmic reticulum

    Smirnov Vladimir N

    2002-10-01

    Full Text Available Abstract Background Secretion of recombinant proteins in yeast can be affected by their improper folding in the endoplasmic reticulum and subsequent elimination of the misfolded molecules via the endoplasmic reticulum associated protein degradation pathway. Recombinant proteins can also be degraded by the vacuolar protease complex. Human urokinase type plasminogen activator (uPA is poorly secreted by yeast but the mechanisms interfering with its secretion are largely unknown. Results We show that in Hansenula polymorpha overexpression worsens uPA secretion and stimulates its intracellular aggregation. The absence of the Golgi modifications in accumulated uPA suggests that aggregation occurs within the endoplasmic reticulum. Deletion analysis has shown that the N-terminal domains were responsible for poor uPA secretion and propensity to aggregate. Mutation abolishing N-glycosylation decreased the efficiency of uPA secretion and increased its aggregation degree. Retention of uPA in the endoplasmic reticulum stimulates its aggregation. Conclusions The data obtained demonstrate that defect of uPA secretion in yeast is related to its retention in the endoplasmic reticulum. Accumulation of uPA within the endoplasmic reticulum disturbs its proper folding and leads to formation of high molecular weight aggregates.

  5. Leukemia inhibitory factor promote trophoblast invasion via urokinase-type plasminogen activator receptor in preeclampsia.

    Zheng, Qin; Dai, Kuixing; Cui, Xinyuan; Yu, Ming; Yang, Xuesong; Yan, Bin; Liu, Shuai; Yan, Qiu

    2016-05-01

    Preeclampsia is a pregnancy-related syndrome which can cause perinatal mortality and morbidity. Inadequate invasion by trophoblast cells may lead to poor perfusion of the placenta, even result in preeclampsia. Understanding the molecular mechanisms underlying placentation facilitates the better intervention of preeclampsia. Urokinase-type plasminogen activator receptor (uPAR) is involved in the physiological and pathological processes. Leukemia inhibitory factor (LIF) is an important regulator in the establishment of pregnancy. However, the expression of uPAR in preeclamptic patients and its relationship with LIF remains unclear. In the current study, we found that the level of uPAR was relatively lower in the placentas from preeclamptic patients as compared with normal pregnant women. LIF promoted trophoblast cell outgrowth by upregulating uPAR in an explants culture, and LIF also enhanced migration and invasion potential through uPAR in trophoblast JAR and JEG-3 cell lines, and with increased gelatinolytic activities of matrix metalloproteinase 2 (MMP-2). The effect of LIF and uPAR on trophoblast migration and invasion was mediated by PI3K/AKT signaling pathway. Our data indicates the roles of LIF in promoting trophoblast migration and invasion through uPAR and suggest that abnormal expression of uPAR might be associated with the etiology of preeclampsia. PMID:27133045

  6. Identification of a Novel Nucleus Protein Involved in the Regulation of Urokinase in 95D Cells

    Chang TONG; Li TAN; Ping LI; Yun-Song ZHU

    2005-01-01

    The urokinase-type plasminogen activator (uPA) plays an important role in cellular invasion.By using the downstream part of a 74 bp DNA region called the cooperation mediator (COM) of the uPA promoter as a bait sequence in the yeast one-hybrid screen, a gene called PBK1 was previously cloned from the cDNA library of the 95D lung cancer cell strain. In this study, the intracellular distribution of PBK1 was studied by using the transient transfection of pEGFP-C3-PBK1, and PBK1 was found to be localized in the nucleus. Co-transfection of pEGFP-C3-PBK1 and the deletion mutants of the pGL3-uPA promoter indicated that PBK1 can increase the uPA promoter activity by about 25% and this effect is uPA enhancer-dependent.Western blotting and Enzyme-linked immunoadsordent assay further confirmed that PBK1 can upregulate the expression of uPA. Our results suggest that PBK1 is involved in the regulation of uPA expression, which might provide a new clue to further understanding the regulation mechanism of uPA expression.

  7. Exchange rate regime choice

    Beker Emilija

    2006-01-01

    Full Text Available The choice of an adequate exchange rate regime proves to be a highly sensitive field within which the economic authorities present and confirm themselves. The advantages and disadvantages of fixed and flexible exchange rate regimes, which have been quite relativized from the conventional point of view, together with simultaneous, but not synchronized effects of structural and external factors, remain permanently questioned throughout a complex process of exchange rate regime decision making. The paper reflects the attempt of critical identification of the key exchange rate performances with emphasis on continuous non-uniformity and (uncertainty of shelf life of a relevant choice.

  8. Structure, function and expression on blood and bone marrow cells of the urokinase-type plasminogen activator receptor, uPAR

    Plesner, T; Behrendt, N; Ploug, M

    1997-01-01

    Several important functions have been assigned to the receptor for urokinase-type plasminogen activator, uPAR. As implied by the name, uPAR was first identified as a high affinity cellular receptor for urokinase plasminogen activator (uPA). It mediates the binding of the zymogen, pro-uPA, to the...... shown that urokinase-type plasminogen activator (uPAR) is expressed as a differentiation antigen on cells of the myelomonocytic lineage and as an activation antigen on monocytes and T lymphocytes. Neutrophils contain intracellular reservoirs of uPAR that are translocated to the plasma membrane upon...... activation, and neutrophils from patients with the rare blood disease paroxysmal nocturnal hemoglobinuria (PNH) that fail to express glycosyl-phosphatidylinositol-anchored proteins including uPAR, show a very significantly reduced transmigration over an endothelial barrier. Cell-associated plasminogen...

  9. Cytokines in cerebrospinal fluid of neurosyphilis patients: Identification of Urokinase plasminogen activator using antibody microarrays.

    Lu, Ping; Zheng, Dao-Cheng; Fang, Chang; Huang, Jin-Mei; Ke, Wu-Jian; Wang, Liu-Yuan; Zeng, Wei-Ying; Zheng, He-Ping; Yang, Bin

    2016-04-15

    Little is known regarding protein responses to syphilis infection in cerebrospinal fluid (CSF) of patients presenting with neurosyphilis. Protein and antibody arrays offer a new opportunity to gain insights into global protein expression profiles in these patients. Here we obtained CSF samples from 46 syphilis patients, 25 of which diagnosed as having central nervous system involvement based on clinical and laboratory findings. The CSF samples were then analyzed using a RayBioH L-Series 507 Antibody Array system designed to simultaneously analyze 507 specific cytokines. The results indicated that 41 molecules showed higher levels in patients with neurosyphilis in comparison with patients without neural involvement. For validation by single target ELISA, we selected five of them (MIP-1a, I-TAC/CXCL11, Urokinase plasminogen activator [uPA], and Oncostatin M) because they have previously been found to be involved in central nervous system (CNS) disorders. The ELISA tests confirmed that uPA levels were significantly higher in the CSF of neurosyphilis patients (109.1±7.88pg/ml) versus patients without CNS involvement (63.86±4.53pg/ml, p<0.0001). There was also a clear correlation between CSF uPA levels and CSF protein levels (p=0.0128) as well as CSF-VDRL titers (p=0.0074) used to diagnose neurosyphilis. No significant difference between the two groups of patients, however, was found in uPA levels in the serum, suggesting specific activation of the inflammatory system in the CNS but not the periphery in neurosyphilis patients. We conclude that measurements of uPA levels in CSF may be an additional parameter for diagnosing neurosyphilis. PMID:27049560

  10. Hypoxia stimulates urokinase receptor expression through a heme protein-dependent pathway.

    Graham, C H; Fitzpatrick, T E; McCrae, K R

    1998-05-01

    Hypoxia underlies a number of biologic processes in which cellular migration and invasion occur. Because earlier studies have shown that the receptor for urokinase-type plasminogen activator (uPAR) may facilitate such events, we studied the effect of hypoxia on the expression of uPAR by first trimester human trophoblasts (HTR-8/SVneo) and human umbilical vein endothelial cells (HUVEC). Compared with control cells cultured under standard conditions (20% O2), HTR-8/SVneo cells and HUVEC cultured in 1% O2 expressed more uPAR, as determined by flow cytometric and [125I]-prourokinase ligand binding analyses. Increased uPAR expression paralleled increases in uPAR mRNA. The involvement of a heme protein in the hypoxia-induced expression of uPAR was suggested by the observations that culture of cells with cobalt chloride, or sodium 4, 5-dihydroxybenzene-1,3-disulfonate (Tiron), an iron-chelating agent, also stimulated uPAR expression, and that the hypoxia-induced uPAR expression was inhibited by adding carbon monoxide to the hypoxic atmosphere. Culture of HTR-8/SVneo cells with vascular endothelial growth factor (VEGF) did not increase uPAR mRNA levels, suggesting that the hypoxia-mediated effect on uPAR expression by these cells did not occur through a VEGF-dependent mechanism. The functional importance of these findings is suggested by the fact that HTR-8/SVneo cells cultured under hypoxia displayed higher levels of cell surface plasminogen activator activity and greater invasion through a reconstituted basement membrane. These results suggest that hypoxia may promote cellular invasion by stimulating the expression of uPAR through a heme protein-dependent pathway. PMID:9558386

  11. World Nonproliferation Regime

    Ouyang Liping; Wu Xingzuo

    2007-01-01

    2006 witnessed an intense struggle between nuclear proliferation and nonproliferation. Iran's nuclear issue and North Korea's nuclear test have cast a deep shadow over the current international nonproliferation regime. The international contest for civil nuclear development became especially fierce as global energy prices went up. Such a situation , to some extent, accelerated the pace of nuclear proliferation. Furthermore, the existing international nonproliferation regime, based upon the Nuclear Nonproliferation Treaty (NPT), was affected by loopholes, and the U.S. failed in its ambition to unite other forces to mend fences. The international community needs to come up with a comprehensive and long-term strategy to meet the demand for an effective future nonproliferation regime in a healthy nuclear order.

  12. Dimagrire in regime mediatico

    Boutaud, Jean-Jacques

    2012-01-01

    publication en italien : BOUTAUD Jean-Jacques, « Dimagrire in regime mediatico », Dietetica e semiotica. Regimi di Senso, a cura di Dario Mangano e Gianfranco Marrone, Mimesis Edizioni, Milano, 2013, p. 19-38 Il titolo può leggersi in molti modi. Per esempio: dietetica e semiotica sono due regimi di senso, uno alimentare e l'altro comunicativo, con pari dignità, dunque da paragonare fra loro. Oppure: grazie alla semiotica la dietetica appare, non più come un regime alimentare, ma come un r...

  13. Discrimination of different forms of the murine urokinase plasminogen activator receptor on the cell surface using monoclonal antibodies

    Rasch, M.G.; Pass, J.; Illemann, M.;

    2008-01-01

    The urokinase plasminogen activator receptor (uPAR) is a versatile three-domain GPI-anchored protein, which binds urokinase plasminogen activator (uPA) and thereby focalises plasminogen activation on the cell surface. Generation of a proteolytic potential is essential in both normal physiological...... murine monocyte macrophage-like P388D.1 cells, we have now generated and characterised two high-affinity murine mAbs, mR3 and mR4, raised against murine uPAR. mR3 was found to recognise an epitope located in domain I of uPAR. Surface plasmon resonance analyses and cell binding studies revealed that this...... mAb was able to bind preformed complexes of murine pro-uPA and murine uPAR. In contrast, mR4 recognises domains II-III in uPAR and does not bind preformed pro-uPA-uPAR complexes in similar analyses. Immunofluorescence microscopy of P388D.1 cells revealed that mR3 stained the cells equally well in...

  14. Soluble urokinase plasminogen activator receptor as a prognostic marker of all-cause and cardiovascular mortality in a black population

    Botha, Shani; Fourie, Carla M T; Schutte, Rudolph; Eugen-Olsen, Jesper; Pretorius, Ronel; Schutte, Aletta E

    2015-01-01

    BACKGROUND: Elevated inflammatory markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) are well-known risk factors for cardiovascular mortality. The less familiar marker, soluble urokinase plasminogen activator receptor (suPAR), is known to predict cancer, infections and all-cause mo......BACKGROUND: Elevated inflammatory markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) are well-known risk factors for cardiovascular mortality. The less familiar marker, soluble urokinase plasminogen activator receptor (suPAR), is known to predict cancer, infections and all.......39, 95% CI 1.17-1.65) predicted all-cause mortality, while only suPAR (HR 1.40, 95% CI 1.04-1.87) and IL-6 (HR 1.61,95% CI 1.10-2.35) predicted cardiovascular mortality. The prognostic value of suPAR was independent of IL-6 and CRP (P≤0.015). CONCLUSION: SuPAR predicted both all-cause and cardiovascular...

  15. The tyrosine phosphatase SHP-2 controls urokinase-dependent signaling and functions in human vascular smooth muscle cells

    The urokinase (uPA)/urokinase receptor (uPAR) multifunctional system is an important mediator of functional behaviour of human vascular smooth muscle cells (VSMC). uPAR associates with platelet-derived growth factor receptor β (PDGFR-β), which serves as a transmembrane adaptor for uPAR in VSMC, to transduce intracellular signaling and initiate functional changes. The precise and rapid propagation of these signaling cascades demands both strict and flexible regulatory mechanisms that remain unexplored. We provide evidence that the tyrosine phosphatase SHP-2 mediates these processes. uPA regulated SHP-2 phosphorylation, catalytic activity, and its co-localization and association with the PDGFR-β. Active PDGFR-β was required for the uPA-induced SHP-2 phosphorylation. uPAR-directed STAT1 pathway was disturbed in cells expressing SHP-2 inactive mutant. Both, cell proliferation and migration were impaired in VSMC with downregulated SHP-2. Elucidating the underlying mechanisms, we found that uPA induced SHP-2 recruitment to lipid rafts. Disruption of rafts abolished uPA-related control of SHP-2 phosphorylation, its association with PDGFR-β and finally the VSMC functional responses. Our results demonstrate that SHP-2 plays an important role in uPA-directed signaling and functional control of human VSMC and suggest that this phosphatase might contribute to the pathogenesis of the uPA-related vascular remodeling

  16. High plasma levels of intact and cleaved soluble urokinase receptor reflect immune activation and are independent predictors of mortality in HIV-1-infected patients

    Ostrowski, Sisse Rye; Piironen, Timo; Høyer-Hansen, Gunilla;

    2005-01-01

    BACKGROUND: High blood levels of soluble urokinase receptor (suPAR) measured by enzyme-linked immunoassay (ELISA) (bulk measurement of 3-domain and 2-domain suPAR [suPAR(I-III), suPAR(II-III)], and suPAR(I-III) ligand complexes) strongly predict mortality in HIV-1-infected patients. This study in...

  17. High plasma levels of intact and cleaved soluble urokinase receptor reflect immune activation and are independent predictors of mortality in HIV-1-infected patients

    Ostrowski, Sisse Rye; Piironen, Timo; Høyer-Hansen, Gunilla;

    2005-01-01

    High blood levels of soluble urokinase receptor (suPAR) measured by enzyme-linked immunoassay (ELISA) (bulk measurement of 3-domain and 2-domain suPAR [suPAR(I-III), suPAR(II-III)], and suPAR(I-III) ligand complexes) strongly predict mortality in HIV-1-infected patients. This study investigated p...

  18. Presence of urokinase plasminogen activator, its inhibitor and receptor in small cell lung cancer and non-small cell lung cancer

    Pappot, H.; Pfeiffer, P.; Grøndahl Hansen, J.; Skov, B.G.

    1997-01-01

    Spreading of cancer cells is dependent on the combined action of several proteolytic enzymes, such as serine proteases, comprising the urokinase pathway of plasminogen activation. Previous studies of lung cancer indicate that expression, localization and prognostic impact of the components of the...

  19. Elevated soluble urokinase receptor values in CSF, age and bacterial meningitis infection are independent and additive risk factors of fatal outcome

    Tzanakaki, G; Paparoupa, M; Kyprianou, M;

    2012-01-01

    The aim of the present study was to evaluate the potential role of cerebrospinal fluid soluble urokinase receptor (suPAR) level, infection and age as risk factors for fatal outcome in patients suspected of having meningitis and/or bacteraemia on admission to hospital. A total of 545 cerebrospinal...

  20. Prognostic value of plasma soluble urokinase plasminogen activator receptor (suPAR) in Danish patients with recurrent epithelial ovarian cancer (REOC)

    Begum, Farah Diba; Høgdall, Estrid V S; Riisbo, Rikke;

    2006-01-01

    The level of the soluble urokinase plasminogen activator receptor (suPAR) is elevated in tumour tissue from several types of cancer. This is the first study aiming to predict the prognosis for survival by the use of a pre-chemotherapeutic plasma suPAR value in 71 patients with recurrent epithelial...

  1. A 55,000-60,000 Mr receptor protein for urokinase-type plasminogen activator. Identification in human tumor cell lines and partial purification

    Nielsen, L S; Kellerman, G M; Behrendt, N;

    1988-01-01

    The iodinated Mr approximately equal to 15,000 amino-terminal fragment (ATF) of the urokinase-type plasminogen activator (u-PA) molecule bound specifically to the cell surface of all of seven cultured human tumor cell lines studied. Cross-linking of iodinated ATF to the cell surface using a bifun...

  2. Urokinase receptor mRNA level and gene transcription are strongly and rapidly increased by phorbol myristate acetate in human monocyte-like U937 cells

    Lund, L R; Rønne, E; Roldan, A L;

    1991-01-01

    We have studied the effect of the tumor promotor phorbol myristate acetate (PMA) on the level of mRNA for the receptor for urokinase-type plasminogen activator (u-PAR) in the human monocyte-like cell line U937. PMA causes an early increase in the u-PAR mRNA level which reaches a maximal 50-fold e...

  3. Radiation-Induced Hypomethylation Triggers Urokinase Plasminogen Activator Transcription in Meningioma Cells

    Kiran Kumar Velpula

    2013-02-01

    Full Text Available Our previous studies have shown the role of radiation-induced urokinase plasminogen activator (uPA expression in the progression of meningioma. In the present study, we investigated whether modulation of DNA methylation profiles could regulate uPA expression. Initially, radiation treatment was found to induce hypomethylation in meningioma cells with a decrease in DNA (cytosine-5-methyltransferase 1 (DNMT1 and methyl-CpG binding domain protein (MBD expression. However, oxidative damage by H2O2 or pretreatment of irradiated cells with N-acetyl cysteine (NAC did not show any influence on these proteins, thereby indicating a radiation-specific change in the methylation patterns among meningioma cells. Further, we identified that hypomethylation is coupled to an increase in uPA expression in these cells. Azacytidine treatment induced a dose-dependent surge of uPA expression, whereas pre-treatment with sodium butyrate inhibited radiation-induced uPA expression, which complemented our prior results. Methylation-specific polymerase chain reaction on bisulfite-treated genomic DNA revealed a diminished methylation of uPA promoter in irradiated cells. Transfection with small hairpin RNA (shRNA-expressing plasmids targeting CpG islands of the uPA promoter showed a marked decline in uPA expression with subsequent decrease in invasion and proliferation of meningioma cells. Further, radiation treatment was found to recruit SP1 transcription factor, which was abrogated by shRNA treatment. Analysis on signaling events demonstrated the activation of MAP kinase kinase (MEK-extracellular signal-regulated kinase (ERK in radiation-treated cells, while U0126 (MEK/ERK inhibitor blocked hypomethylation, recruitment of SP1, and uPA expression. In agreement with our in vitro data, low DNMT1 levels and high uPA were found in intracranial tumors treated with radiation compared to untreated tumors. In conclusion, our data suggest that radiation-mediated hypomethylation

  4. Soluble urokinase-type plasminogen activator receptor is a novel biomarker predicting acute exacerbation in COPD

    Gumus A

    2015-02-01

    Full Text Available Aziz Gumus,1 Nejat Altintas,2 Halit Cinarka,1 Aynur Kirbas,3 Muge Haziroglu,1 Mevlut Karatas,1 Unal Sahin1 1Department of Pulmonary Medicine, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey; 2Department of Pulmonary Medicine, School of Medicine, Namik Kemal University, Tekirdag, Turkey; 3Department of Clinical Biochemistry, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey Background: Chronic obstructive pulmonary disease (COPD is a chronic inflammatory condition, and progresses with acute exacerbations. (AE. During AE, levels of acute phase reactants such as C-reactive protein (CRP and inflammatory cells in the circulation increase. Soluble urokinase-type plasminogen activator receptor (suPAR levels increase in acute viral and bacterial infections and in diseases involving chronic inflammation. The purpose of this study was to investigate the effectiveness of suPAR in predicting diagnosis of AE of COPD (AE-COPD and response to treatment. Methods: The study population consisted of 43 patients diagnosed with AE-COPD and 30 healthy controls. suPAR, CRP, and fibrinogen levels were measured on the first day of hospitalization and on the seventh day of treatment. Results: We found that fibrinogen (P<0.001, CRP (P<0.001, and suPAR (P<0.001 were significantly higher in patients with AE-COPD than in healthy controls. Fibrinogen (P<0.001, CRP (P=0.001, and suPAR (P<0.001 were significantly decreased by the seventh day of treatment. However, the area under receiver operator characteristic curve showed that suPAR is superior to CRP and fibrinogen in distinguishing AE-COPD. There was a correlation between fibrinogen, CRP, and suPAR. However, only fibrinogen was a powerful predictor of suPAR in multiple linear regression. In multiple logistic regression, only suPAR and fibrinogen were strong predictors of AE-COPD (P=0.002 and P=0.014, respectively. Serum suPAR was negatively correlated with forced expiratory volume in 1

  5. The “Lipid Accumulation Product” Is Associated with 2-Hour Postload Glucose Outcomes in Overweight/Obese Subjects with Nondiabetic Fasting Glucose

    Malavazos, Alexis Elias; Cereda, Emanuele; Ermetici, Federica; Caccialanza, Riccardo; Briganti, Silvia; Rondanelli, Mariangela; Morricone, Lelio

    2015-01-01

    “Lipid accumulation product” (LAP) is a continuous variable based on waist circumference and triglyceride concentration previously associated with insulin resistance. We investigated the accuracy of LAP in identifying oral glucose tolerance test (OGTT) abnormalities and compared it to the homeostasis model assessment of insulin resistance (HOMA-IR) in a population of overweight/obese outpatients presenting with nondiabetic fasting glucose. We studied 381 (male: 23%) adult (age: 18–70 years) overweight/obese Caucasians (body mass index: 36.9 ± 5.4 Kg/m2) having fasting plasma glucose < 7.0 mmol/L. OGTT was used to diagnose unknown glucose tolerance abnormalities: impaired glucose tolerance (IGT) and type-2 diabetes mellitus (T2-DM). According to OGTT 92, subjects had an IGT and 33 were diagnosed T2-DM. Logistic regression analysis detected a significant association for both LAP and HOMA-IR with single (IGT and T2-DM) and composite (IGT + T2-DM) abnormal glucose tolerance conditions. However, while the association with diabetes was similar between LAP and HOMA-IR, the relationship with IGT and composite outcomes by models including LAP was significantly superior to those including HOMA-IR (P = 0.006 and P = 0.007, resp.). LAP seems to be an accurate index, performing better than HOMA-IR, for identifying 2-hour postload OGTT outcomes in overweight/obese patients with nondiabetic fasting glucose. PMID:25792981

  6. The “Lipid Accumulation Product” Is Associated with 2-Hour Postload Glucose Outcomes in Overweight/Obese Subjects with Nondiabetic Fasting Glucose

    Alexis Elias Malavazos

    2015-01-01

    Full Text Available “Lipid accumulation product” (LAP is a continuous variable based on waist circumference and triglyceride concentration previously associated with insulin resistance. We investigated the accuracy of LAP in identifying oral glucose tolerance test (OGTT abnormalities and compared it to the homeostasis model assessment of insulin resistance (HOMA-IR in a population of overweight/obese outpatients presenting with nondiabetic fasting glucose. We studied 381 (male: 23% adult (age: 18–70 years overweight/obese Caucasians (body mass index: 36.9 ± 5.4 Kg/m2 having fasting plasma glucose < 7.0 mmol/L. OGTT was used to diagnose unknown glucose tolerance abnormalities: impaired glucose tolerance (IGT and type-2 diabetes mellitus (T2-DM. According to OGTT 92, subjects had an IGT and 33 were diagnosed T2-DM. Logistic regression analysis detected a significant association for both LAP and HOMA-IR with single (IGT and T2-DM and composite (IGT + T2-DM abnormal glucose tolerance conditions. However, while the association with diabetes was similar between LAP and HOMA-IR, the relationship with IGT and composite outcomes by models including LAP was significantly superior to those including HOMA-IR (P=0.006 and P=0.007, resp.. LAP seems to be an accurate index, performing better than HOMA-IR, for identifying 2-hour postload OGTT outcomes in overweight/obese patients with nondiabetic fasting glucose.

  7. Complex regimes of synchronization

    Yeldesbay, Azamat

    2014-01-01

    Synchronization is a fundamental phenomenon in nature. It can be considered as a general property of self-sustained oscillators to adjust their rhythm in the presence of an interaction. In this work we investigate complex regimes of synchronization phenomena by means of theoretical analysis, numerical modeling, as well as practical analysis of experimental data. As a subject of our investigation we consider chimera state, where due to spontaneous symmetry-breaking of an initially ho...

  8. Combined use of serum adiponectin and tumor necrosis factor-alpha receptor 2 levels was comparable to 2-hour post-load glucose in diabetes prediction.

    Yu-Cho Woo

    Full Text Available BACKGROUND: Adipose tissue inflammation and dysregulated adipokine secretion are implicated in obesity-related insulin resistance and type 2 diabetes. We evaluated the use of serum adiponectin, an anti-inflammatory adipokine, and several proinflammatory adipokines, as biomarkers of diabetes risk and whether they add to traditional risk factors in diabetes prediction. METHODS: We studied 1300 non-diabetic subjects from the prospective Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS. Serum adiponectin, tumor necrosis factor-alpha receptor 2 (TNF-α R2, interleukin-6 (IL-6, adipocyte-fatty acid binding protein (A-FABP and high-sensitivity C-reactive protein (hsCRP were measured in baseline samples. RESULTS: Seventy-six participants developed diabetes over 5.3 years (median. All five biomarkers significantly improved the log-likelihood of diabetes in a clinical diabetes prediction (CDP model including age, sex, family history of diabetes, smoking, physical activity, hypertension, waist circumference, fasting glucose and dyslipidaemia. In ROC curve analysis, "adiponectin + TNF-α R2" improved the area under ROC curve (AUC of the CDP model from 0.802 to 0.830 (P = 0.03, rendering its performance comparable to the "CDP + 2-hour post-OGTT glucose" model (AUC = 0.852, P = 0.30. A biomarker risk score, derived from the number of biomarkers predictive of diabetes (low adiponectin, high TNF-α R2, had similar performance when added to the CDP model (AUC = 0.829 [95% CI: 0.808-0.849]. CONCLUSIONS: The combined use of serum adiponectin and TNF-α R2 as biomarkers provided added value over traditional risk factors for diabetes prediction in Chinese and could be considered as an alternative to the OGTT.

  9. Risk Factors Associated with Serum Levels of the Inflammatory Biomarker Soluble Urokinase Plasminogen Activator Receptor in a General Population

    Haupt, Thomas H; Kallemose, Thomas; Ladelund, Steen;

    2014-01-01

    .001). An unhealthy diet and alcohol abstinence in men were also associated with higher suPAR levels. Physical activity in leisure time had a modest impact on suPAR levels in univariate analysis, but not in the final adjusted model. In conclusion, smoking and morbid obesity were strongly associated with higher serum...... suPAR levels in this general population. Diet and alcohol consumption also seemed to impact suPAR levels. Lifestyle changes are likely to affect suPAR since ex-smokers had suPAR levels comparable to those of never-smokers.......The soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of mortality risk in various patient populations. However, little is known about the implications of lifestyle for suPAR levels in the general population. Lifestyle, demographic, and cardiovascular disease (CVD) risk factor...

  10. The urokinase receptor (uPAR) and the uPAR-associated protein (uPARAP/Endo180)

    Behrendt, Niels

    2004-01-01

    processes involve a highly organized interplay between proteases and their cellular binding sites as well as specific substrates and internalization receptors. This review article is focused on two components, the urokinase plasminogen activator receptor (uPAR) and the uPAR-associated protein (uPARAP, also......The breakdown of the barriers formed by extracellular matrix proteins is a pre-requisite for all processes of tissue remodeling. Matrix degradation reactions take part in specific physiological events in the healthy organism but also represent a crucial step in cancer invasion. These degradation...... designated Endo180), that are considered crucially engaged in matrix degradation. uPAR and uPARAP have highly diverse functions, but on certain cell types they interact with each other in a process that is still incompletely understood. uPAR is a glycosyl-phosphatidylinositol-anchored glycoprotein on the...

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

    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...... patients with low PAI-1 and high uPA-PAI-1 complex (HR = 3.06, p = 0.01). This is the first investigation of the prognostic impact of uPA-PAI-1 complex in a tumor type other than breast cancer, showing low levels of uPA-PAI-1 complex in combination with high levels of PAI-1 to be associated with poor...

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

    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 to...... sandwich ELISA method. RESULTS: Both uPA and PAI-1 were independent of classical histopathological parameters as well as of microvessel density and vascular pattern. Using death within the first 5 years as endpoint, neither of the factors were prognostic markers in univariate analysis, however......, significantly higher levels of uPA and PAI-1 were seen in tumours with an angiogenic vascular pattern. In multivariate analysis, high disease stage (P<0.0001), adenocarcinoma (P=0.007), old age (P=0.02), and presence of an angiogenic pattern (P=0.05) were identified as independent markers of death within 5...

  13. Soluble urokinase receptor levels in plasma during 5 years of highly active antiretroviral therapy in HIV-1-infected patients

    Ostrowski, Sisse R; Katzenstein, Terese L; Piironen, Timo;

    2004-01-01

    High blood levels of the soluble urokinase receptor (suPAR) strongly predict increased mortality in human immunodeficiency virus-1 (HIV-1)-infected patients. This study investigated the plasma concentration of suPAR in 29 treatment-naive HIV-1-infected patients during 5 years treatment with highly...... active antiretroviral therapy (HAART). Plasma suPAR decreased after introducing HAART, most pronounced during the first treatment year. The change in plasma suPAR was independent of changes in viral replication and CD4+ cells but it was strongly correlated with plasma levels of the soluble TNF receptor...... II. Compared with healthy individuals, plasma suPAR and sTN-FrII was increased in untreated patients. After initiating HAART, plasma sTNFrII remained increased whereas plasma suPAR decreased to a level comparable with healthy individuals. The present data indicate that the circulating suPAR level is...

  14. Soluble urokinase plasminogen activator receptor levels are elevated and associated with complications in patients with type 1 diabetes

    Theilade, S; Lyngbaek, S; Hansen, T W;

    2015-01-01

    OBJECTIVES: Soluble urokinase plasminogen activator receptor (suPAR) is a marker of inflammation and endothelial dysfunction. We investigated the associations between suPAR and diabetes, including diabetes duration and complications, in patients with type 1 diabetes. DESIGN, SETTING AND SUBJECTS...... diabetes and is associated with diabetes duration and complications independent of other risk factors. suPAR is a potential novel risk marker for the management of diabetes.......: From 2009 to 2011, 667 patients with type 1 diabetes and 51 nondiabetic control subjects were included in a cross-sectional study at Steno Diabetes Center, Gentofte, Denmark. suPAR levels were measured with an enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: The investigated diabetic...

  15. Preclinical evaluation of a urokinase plasminogen activator receptor-targeted nanoprobe in rhesus monkeys

    Chen Y

    2015-10-01

    Full Text Available Yushu Chen,1 Li Gong,2 Ning Gao,3 Jichun Liao,1 Jiayu Sun,1 Yuqing Wang,1 Lei Wang,1 Pengjin Zhu,1 Qing Fan,1 Yongqiang Andrew Wang,4 Wen Zeng,2 Hui Mao,3 Lily Yang,5 Fabao Gao11Molecular Imaging Center, Department of Radiology, West China Hospital, Sichuan University, Chengdu, 2Sichuan Primed Bio-Tech Group Co, Ltd, Chengdu, People’s Republic of China; 3Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, 4Ocean NanoTech, LLC, San Diego, CA, 5Department of Surgery, Emory University School of Medicine, Atlanta, GA, USAPurpose: To translate a recombinant peptide containing the amino-terminal fragment (ATF of urokinase plasminogen activator receptor-targeted magnetic iron oxide (IO nanoparticles (uPAR-targeted human ATF-IONPs into clinical applications, we conducted a pilot study to evaluate the toxicity and pharmacokinetics of this nanoparticle in normal rhesus monkeys.Methods: We assessed the changes in the following: magnetic resonance imaging (MRI signals from pretreatment stage to 14 days posttreatment, serum iron concentrations from 5 minutes posttreatment to 12 weeks posttreatment, routine blood examination and serum chemistry analysis results from pretreatment stage to 12 weeks after administration, and results of staining of the liver with Perls’ Prussian Blue and hematoxylin–eosin at 24 hours and 3 months posttreatment in two rhesus monkeys following an intravenous administration of the targeted nanoparticles either with a polyethylene glycol (ATF-PEG-IONP or without a PEG (ATF-IONP coating.Results: The levels of alkaline phosphatase, alanine transaminase, and direct bilirubin in the two monkeys increased immediately after the administration of the IONPs but returned to normal within 20 days and stayed within the normal reference range 3 months after the injection. The creatinine levels of the two monkeys stayed within the normal range during the study. In addition, red blood cells

  16. Influential factors of clinical outcome of local intra-arterial thrombolysis using urokinase in patients with hyperacute ischemic stroke

    To evaluate the clinical outcome and other relevant factors in cases where local intra-arterial thrombolysis (LIT) is used for the treatment of hyperacute ischemic stroke. Forty-eight hyperacute ischemic stroke patients were treated by LIT, using urokinase, within six hours of ictus, and for evaluation of their neurological status, the national institutes of health stroke scale (NIHSS) score was used. Angiography recanalization was classified according to Mori recanalization grades. Three months after LIT, the outcome was assessed by clinical examination using the modified rankin scale (good outcome: RS=0-3; poor outcome: RS=4-6). In all patients, the findings of pre- and post- LIT CT, and angiography, as well as neurological status and hemorrhagic complications, were also analysed. Thirty-three patients had occlusions of the middle cerebral artery (MCA), and 15, of the internal carotid artery (ICA). The NIHSS score averaged 16.9 at the onset of therapy and 13.5 at 24 hours later. Successful recanalization (Mori grade 3,4) was achieved in 28 (58.3%) of 48 patients, but in 20 (41.7%) the attempt failed. Twenty-two (45.8%) of the 48 patients had a good outcome, but in (54.2%) the outcome was poor. Thirteen (40.6%) of 32 patients with MCA occlusions and 13 (81.2%) of 16 with ICA occlusions had a poor outcome. Eight patients (16.7%) died. Overall, hemorrhages occured in 20 (41.7%) of 48 patients, with symptomatic hemorrhage in ten. Five (50%) of these ten died. LIT using urokinase for hyperacute ischemic stroke is feasible; patients with MCA occlusions had better outcomes than those with ICA occlusions. Hemorrhagic complications of LIT were frequent, and in cases of symptomatic hemorrhage a fatal outcome may be expected

  17. Influential factors of clinical outcome of local intra-arterial thrombolysis using urokinase in patients with hyperacute ischemic stroke

    Song, Jae Min; Yoon, Woong; Kim, Jae Kyu; Seo, Jeong Jin; Heo, Sook Hee; Park, Jin Gyoon; Jeong, Yoon Yeon; Kang, Heoung Keun [Chonam University Hospital, Kwangju (Korea, Republic of)

    2002-10-01

    To evaluate the clinical outcome and other relevant factors in cases where local intra-arterial thrombolysis (LIT) is used for the treatment of hyperacute ischemic stroke. Forty-eight hyperacute ischemic stroke patients were treated by LIT, using urokinase, within six hours of ictus, and for evaluation of their neurological status, the national institutes of health stroke scale (NIHSS) score was used. Angiography recanalization was classified according to Mori recanalization grades. Three months after LIT, the outcome was assessed by clinical examination using the modified rankin scale (good outcome: RS=0-3; poor outcome: RS=4-6). In all patients, the findings of pre- and post- LIT CT, and angiography, as well as neurological status and hemorrhagic complications, were also analysed. Thirty-three patients had occlusions of the middle cerebral artery (MCA), and 15, of the internal carotid artery (ICA). The NIHSS score averaged 16.9 at the onset of therapy and 13.5 at 24 hours later. Successful recanalization (Mori grade 3,4) was achieved in 28 (58.3%) of 48 patients, but in 20 (41.7%) the attempt failed. Twenty-two (45.8%) of the 48 patients had a good outcome, but in (54.2%) the outcome was poor. Thirteen (40.6%) of 32 patients with MCA occlusions and 13 (81.2%) of 16 with ICA occlusions had a poor outcome. Eight patients (16.7%) died. Overall, hemorrhages occured in 20 (41.7%) of 48 patients, with symptomatic hemorrhage in ten. Five (50%) of these ten died. LIT using urokinase for hyperacute ischemic stroke is feasible; patients with MCA occlusions had better outcomes than those with ICA occlusions. Hemorrhagic complications of LIT were frequent, and in cases of symptomatic hemorrhage a fatal outcome may be expected.

  18. Construction, Expression, and Characterization of a Recombinant Annexin B1-Low Molecular Weight Urokinase Chimera in Escherichia coli

    Hong-Li YAN; Wei-Ting WANG; Yan HE; Zhuan-You ZHAO; Yuan-Jian GAO; Yi ZHANG; Shu-Han SUN

    2004-01-01

    To produce a thrombi-targeting plasminogen activator,low molecular weight single-chain urokinase gene(scuPA32k)was spliced with the full-length cDNA of annexin B 1 gene(anxB1)by overlap extension method.The fused gene anxBlscuPA was ligated into pET28a vector,transformed into E.coli BL21-RIL,and then induced to express under the control of T7 promoter.The AnxB 1ScuPA protein expressed amounted to 22% of the total bacterial proteins.The product was refolded,and then purified by using DEAE Sepharose fast flow ion-exchange column and Superdex S-200 gel-filtration column.HPLC analysis revealed that the final purity is about 95%.The specific activity ofAnxB 1ScuPA,measured as amidolytic activity,reached 100,000 IU/mg.It had a similar S2444 catalytic efficiency(kcat/Km)to ScuPA32k,and also showed high activated-platelet membrane-binding activity and anticoagulant activity,indicating that the chimera fully retained the components of enzymatic and membrane-binding activities of the parent molecules.In vivo test revealed that,the dogs administered with AnxB 1ScuPA had less reperfusion time,higher reperfusion ratio,and less bleeding effects than those with urokinase.These findings indicated that AnxB 1ScuPAmight have advantages over current available thrombolytic agents.

  19. Reduced release of intact and cleaved urokinase receptor in stimulated whole-blood cultures from human immunodeficiency virus-1-infected patients

    Ostrowski, S R; Piironen, T; Høyer-Hansen, G;

    2005-01-01

    The blood levels of the soluble forms of the urokinase receptor (suPAR) are increased in human immunodeficiency virus (HIV)-1-infected patients. This study investigated whether the release of urokinase-type plasminogen activator receptor (uPAR) in whole-blood cultures was affected by HIV infection...... controls, whereas the correlation was weaker to leucocytes and nonexisting to circulating suPAR levels in HIV patients. These findings demonstrate that HIV infection affects stimulated and spontaneous uPAR release in whole-blood cultures. Given that high blood levels of suPAR in HIV patients are linked to....... The release of different uPAR forms in whole-blood cultures incubated 24 h with or without phytohemagglutinin and lipopolysaccharide was analysed in 47 HIV patients and 19 controls. suPAR was measured by enzyme-linked immunosorbent assay (ELISA) (bulk-suPAR) and three different time...

  20. Phorbol ester induces the biosynthesis of glycosylated and nonglycosylated plasminogen activator inhibitor 2 in high excess over urokinase-type plasminogen activator in human U-937 lymphoma cells

    1987-01-01

    The tumor-promoting phorbol ester PMA induces changes in the histiocytic human lymphoma cell line U-937 akin to cellular differentiation (Ralph, P., N. Williams, M. A. S. Moore, and P. B. Litcofsky, 1982, Cell. Immunol., 71:215-223) and concomitantly stimulates the biosynthesis of plasminogen activator inhibitor 2 (PAI 2) and of urokinase-type plasminogen activator (u-PA). PAI 2 is found in a nonglycosylated intracellular and a glycosylated secreted form. The former appears to be identical to...

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

    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.

  2. Interleukin-1ß-induced expression of the urokinase-type plasminogen activator receptor and its co-localization with MMPs in human articular chondrocytes

    Schwab, W.; Schulze-Tanzil, G.; Mobasheri, A; Dressler, J.; Kotzsch, M.; Shakibaei, M.

    2004-01-01

    The urokinase-type plasminogen activator receptor (uPAR) plays a critical role in cartilage degradation during osteoarthritis as it regulates pericellular proteolysis mediated by serine proteinases. Another important family of proteinases responsible for ECM destruction in arthritis are the matrix metalloproteinases (MMPs). MMPs are regulated by IL- 1ß, a cytokine that plays a pivotal role in pathogenesis of osteoarthritis. This study was undertaken to address ...

  3. Soluble urokinase-type plasminogen activator receptor levels in patients with burn injuries and inhalation trauma requiring mechanical ventilation: an observational cohort study

    Backes, Yara; van der Sluijs, Koenraad F; Tuip de Boer, Anita M; Hofstra, Jorrit Jan; Vlaar, Alexander PJ; Determann, Rogier M; Knape, Paul; David P Mackie; Schultz, Marcus J.

    2011-01-01

    Introduction Soluble urokinase-type plasminogen activator receptor (suPAR) has been proposed as a biologic marker of fibrinolysis and inflammation. The aim of this study was to investigate the diagnostic and prognostic value of systemic and pulmonary levels of suPAR in burn patients with inhalation trauma who need mechanical ventilation. Methods suPAR was measured in plasma and nondirected lung-lavage fluid of mechanically ventilated burn patients with inhalation trauma. The samples were obta...

  4. In vivo effects of urease-producing bacteria involved with the pathogenesis of infection-induced urolithiasis on renal urokinase and sialidase activity.

    du Toit, P J; van Aswegen, C H; Nel, J A; Steyn, P L; Ligthelm, A J; du Plessis, D J

    1995-01-01

    Many hypotheses have been proposed for renal stone formation. It has been argued that with infection-induced renal stones the hydrolysis of urea by bacterial urease increases urinary pH, with consequent stone formation. Unfortunately, this theory is not applicable to the micro-organisms that do not produce urease (e.g. Escherichia coli). It has been recently reported that E. coli reduces the urinary urokinase activity of male rats, but does not influence the urinary sialidase activity. This study has now been expanded to the urease-producing bacteria Proteus mirabilis, Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa and Micrococcus luteus. Subcutaneous injections with these bacteria were found to significantly (P urease-producing mammalian skin bacterium, M. luteus, was, however, the exception (P = 0.1079). In contrast to S. epidermidis, P. aeruginosa and M. luteus (P mirabilis and S. aureus had no effect on renal sialidase activity (P Proteus species are predominant in infection-induced renal stones. According to the urokinase-sialidase hypothesis, a decrease in urinary urokinase activity should increase the uromucoid levels, whilst no effect on the urinary sialidase activity should favour conversion of urinary uromucoid to mineralizable matrix. These conditions may lead to renal stone formation. An increase in urinary pH resulting from urease-producing micro-organisms will increase salt precipitation on the uromucoid. It is thus concluded that urease-producing bacteria may play a double role in renal stone formation. PMID:8839391

  5. The human urokinase-plasminogen activator gene (PLAU) is located on chromosome 10q24 centromeric to the HOX11 gene

    Stein, P.M.; Stass, S.A.; Kagan, J. (Univ. of Texas, Houston (United States))

    1993-04-01

    Urokinase-plasminogen activator is one of two soluble serine proteases that are produced by humans and that convert plasminogen, an inactive proenzyme present in plasma and other extracellular fluids, to plasmin, a protease with broad substrate specificities. Its activity is involved in processes requiring localized extracellular proteolysis such as fibrinolysis, tissue remodeling, and cell migration. Increased production of urokinase has been associated with cancer metastases. The gene for urokinase-plasminogen activator, PLAU, was mapped to chromosome 10q24-qter. By employing somatic cell genetics, polymerase chain reaction (PCR), and Southern blot analysis, the authors assign PLAU to chromosome 10q24. Human chromosome segment 10q23-q25 contains the genes for terminal deoxynucleotidyltransferase, cytochrome P450IIC, glutamic-oxaloacetic transaminase, and plasma retinol binding protein, which form a syntenic group on murine chromosome 19. It is therfore of interest that PLAU and glutamate dehydrogenase, which are on murine chromosome 14, also map in or close to this region of human chromosome 10.

  6. Political Regimes and Economic Growth

    Carlos Pinho

    2009-12-01

    Full Text Available Are political regimes drivers of economic growth? While political institutions are influenced by economic development, they are in turn a key determinant of the development process. This study builds in the Neoclassical Growth theory to identify the influence of political regimes on economic development through a panel data sample of 170 countries from 1960 to 2000. Results suggest that once fixed effects are considered, the positive relationship between income per capita and political regimes measured by different democracy variables disappears.

  7. Cigarette Smoke and the Induction of Urokinase Plasminogen Activator Receptor In Vivo: Selective Contribution of Isoforms to Bronchial Epithelial Phenotype.

    Portelli, Michael A; Stewart, Ceri E; Hall, Ian P; Brightling, Christopher E; Sayers, Ian

    2015-08-01

    The urokinase plasminogen activator receptor (uPAR) gene (PLAUR) has been identified as an asthma susceptibility gene, with polymorphisms within that gene being associated with baseline lung function, lung function decline, and lung function in a smoking population. Soluble cleaved uPAR (scuPAR), a molecule identified as a marker of increased morbidity and mortality in a number of diseases, has been shown to be elevated in the airways of patients with asthma and in patients with chronic obstructive pulmonary disease. However, the functionality of soluble receptor isoforms and their relationship with an important initiator for obstructive lung disease, cigarette smoke, remains undefined. In this study, we set out to determine the effect of cigarette smoke on soluble uPAR isoforms, its regulatory pathway and the resultant effect on bronchial epithelial cell function. We identified a positive association between cigarette pack-years and uPAR expression in the airway bronchial epithelium of biopsies from patients with asthma (n = 27; P = 0.0485). In vitro, cigarette smoke promoted cleavage of uPAR from the surface of bronchial epithelial cells (1.5× induction; P bronchial epithelial cells. This suggests that cigarette smoke elevates soluble receptor isoforms in bronchial epithelial cells through direct (cleavage) and indirect (messenger RNA expression) means. These findings provide further insight into how cigarette smoke may influence changes in the airways of importance to airway remodeling and obstructive lung disease progression. PMID:25490122

  8. Prognostic significance of circulating intact and cleaved forms of urokinase plasminogen activator receptor in inoperable chemotherapy treated cholangiocarcinoma patients

    Grunnet, M; Christensen, I J; Lassen, U;

    2014-01-01

    determine if pre-treatment serum levels of uPAR forms and a decrease in levels during chemotherapy are predictive of survival in patients with inoperable cholangiocarcinoma. DESIGN AND METHODS: Patients with inoperable cholangiocarcinoma were consecutively included in the training set (n=108). A test set......PAR(I-III)+uPAR(II-III) after 2cycles of chemotherapy was associated with poor survival (HR=1.79, 95% CI:1.08-2.97, p=0.023, n=57). This predictor, however, was not significant in the test set (p=0.21, 26 events in 27 patients). CONCLUSION: The baseline level of uPAR(I-III)+uPAR(II-III) is a predictor of survival in inoperable......BACKGROUND: High levels of intact and cleaved forms of the urokinase-type plasminogen activator receptor (uPAR) in both tissue and blood are associated with poor survival in several cancer diseases. The prognostic significance of uPAR in cholangiocarcinoma is unknown. The aims of this study were to...

  9. Structure-based Engineering of Species Selectivity in the Interaction Between Urokinase and its Receptor: Implication for Preclinical Cancer Therapy

    The high affinity interaction between the urokinase-type plasminogen activator (uPA) and its glycolipid-anchored receptor (uPAR) is decisive for cell surface-associated plasminogen activation. Because plasmin activity controls fibrinolysis in a variety of pathological conditions, including cancer and wound healing, several intervention studies have focused on targeting the uPA · uPAR interaction in vivo. Evaluations of such studies in xenotransplanted tumor models are, however, complicated by the pronounced species selectivity in this interaction. We now report the molecular basis underlying this difference by solving the crystal structure for the murine uPA · uPAR complex and demonstrate by extensive surface plasmon resonance studies that the kinetic rate constants for this interaction can be swapped completely between these orthologs by exchanging only two residues. This study not only discloses the structural basis required for a successful rational design of the species selectivity in the uPA · uPAR interaction, which is highly relevant for functional studies in mouse models, but it also suggests the possible development of general inhibitors that will target the uPA · uPAR interaction across species barriers.

  10. Interventional recanalization of artificial arteriovenous fistula and graft for hemodialysis: angioplasty and pulsed-spray thrombolysis with Urokinase

    To evaluate the effectiveness of percutaneous transluminal angioplasty (PTA) and pul-sed-spray pharmaco-mechanical thrombolysis (PSPMT) using urokinase for the management of insufficient hemodialysis access. Between September 1996 and May 1998, 21 insufficient hemodialysis accesses were treated in 16 patients(3 artificial arteriovenous fistulae, AVF; and 13 arteriovenous graft, AVG). PTA and PSPMT were performed in 6 and 15 cases, respectively, and success and long-term patency rates were evaluated. The overall success rate of PTA and PSPMT for insufficient hemodialysis access was 76. 2%(16/21). The success rates of PTA and PSPMT were 83.3%(5/6) and 73.3%(11/15), respectively. The primary patency rates of PSPMT were 69±12.8% at 6 months and 38±18.6% at 12 months. One of the two initially successful PTAs had been patent for 7 months, and the second PTA was performed at that time due to venous stenosis. The other was patent for 15 months throughout the follow-up period. PTA and PSPMT are effective primary methods for the treatment of insufficient hemodialysis access;success and patency rates were high, and the procedures can be performed repeatedly.=20

  11. Serum levels of soluble urokinase plasminogen activator receptor is associated with parasitemia in children with acute Plasmodium falciparum malaria infection

    Perch, M; Kofoed, Pe; Fischer, Torge; Có, F; Rombo, L; Aaby, P; Eugen-Olsen, J

    2004-01-01

    Serum levels of soluble urokinase plasminogen activator receptor (suPAR) are significantly elevated and of prognostic value in patients suffering from serious infectious diseases such as HIV and tuberculosis. Our objective was to investigate suPAR levels during symptomatic malaria infection and 7...... days after treatment. Children younger than 6 years who presented with fever or other symptoms compatible with malaria were enrolled. Blood films and samples were collected on day 0 and day 7. Twenty-five children were allocated to each of three groups according to the amount of Plasmodium falciparum...... group 1 after 7 days of treatment. All became malaria negative in their blood slides and all decreased in suPAR level to median 3.48 ng/mL (IQR: 3.08-3.91) (P <0.0001). Group 2 consisted of 25 children with 1-20 parasites in their blood slide. The suPAR level was median 2.91 ng/mL (IQR: 2.27-4.40) and...

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

    Pappot, Helle; Pedersen, Anders N; Brünner, Nils; Christensen, Ib Jarle

    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...... patients with low PAI-1 and high uPA-PAI-1 complex (HR = 3.06, p = 0.01). This is the first investigation of the prognostic impact of uPA-PAI-1 complex in a tumor type other than breast cancer, showing low levels of uPA-PAI-1 complex in combination with high levels of PAI-1 to be associated with poor...... for the prognostic impact of PAI-1 on survival. Standard clinical parameters were available and the patients had a median survival time of 25 months. An ELISA established to measure preformed uPA-PAI-1 complexes was applied to the tumor extracts and previously measured data on uPA and PAI-1 levels...

  13. Comparative study of intraarterial and intravenous thrombolysis with urokinase in canine models of acute pulmonary arterial embolism

    Objective: To evaluate the efficiency and safety of intraarterial thrombolysis with urokinase (UK)in canine models of acute pulmonary arterial embolism. Methods: 24 Canine models of selective acute pulmonary artery embolism with autologous blood clot were divided randomly into 3 groups(each with 8 dogs): intraarterial thrombolytic group (10 000 u/kg of UK infused in 30 rain), intravenous thrombolytic group (20 000 u/kg of UK infused in 2 h) and control group (100 ml of saline infused in 2 h). The value of pulmonary arterial mean pressure (PAMP), blood gas analysis (PaO2 and PaCO2), coagulation index(PT and APTT)and D-dimer were tested at 2 h, 4 h after the thrombolytic procedure and pulmonary arterial angiography was repeated. Results: Comparing the levels of PAMP, PaO2 and D-dimer, showed significant difference in the 3 groups (P2 and blood supply restores more rapidly than the intravenous one. (authors)

  14. Catheter-Directed Thrombolysis with a Continuous Infusion of Low-Dose Urokinase for Non-Acute Deep Venous Thrombosis of the Lower Extremity

    Gao, Binbin; Zhang, Jingyong; Wu, Xuejun; Han, Zonglin; Zhou, Hua; Dong, Dianning; Jin, Xing [Shandong Provincial Hospital, Shandong University, Ji' nan (China)

    2011-02-15

    We wanted to evaluate the feasibility of catheter-directed thrombolysis with a continuous infusion of low-dose urokinase for treating non-acute (less than 14 days) deep venous thrombosis of the lower extremity. The clinical data of 110 patients who were treated by catheter-directed thrombolysis with a continuous infusion of low-dose urokinase for lower extremity deep venous thrombosis was analysed. Adjunctive angioplasty or/and stenting was performed for the residual stenosis. Venous recanalization was graded by pre- and posttreatment venography. Follow-up was performed by clinical evaluation and Doppler ultrasound. A total of 112 limbs with deep venous thrombosis with a mean symptom duration of 22.7 days (range: 15-38 days) were treated with a urokinase infusion (mean: 3.5 million IU) for a mean of 196 hours. After thrombolysis, stent placement was performed in 25 iliac vein lesions and percutaneous angioplasty (PTA) alone was done in fi ve iliac veins. Clinically significant recanalization was achieved in 81% (90 of 112) of the treated limbs: complete recanalization was achieved in 28% (31 of 112) and partial recanalization was achieved in 53% (59 of 112). Minor bleeding occurred in 14 (13%) patients, but none of the patients suffered from major bleeding or symptomatic pulmonary embolism. During followup (mean: 15.2 months, range: 3-24 months), the veins were patent in 74 (67%) limbs. Thirty seven limbs (32%) showed progression of the stenosis with luminal narrowing more than 50%, including three with rethrombosis, while one revealed an asymptomatic iliac vein occlusion: 25 limbs (22%) developed mild post-thrombotic syndrome, and none had severe post-thrombotic syndrome. Valvular reflux occurred in 24 (21%) limbs. Catheter-directed thrombolysis with a continuous infusion of low-dose urokinase combined with adjunctive iliac vein stenting is safe and effective for removal of the clot burden and for restoration of the venous flow in patients with non-acute lower

  15. 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

    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...

  16. Mapping the topographic epitope landscape on the urokinase plasminogen activator receptor (uPAR) by surface plasmon resonance and X-ray crystallography

    Baoyu Zhao; Sonu Gandhi; Cai Yuan; Zhipu Luo; Rui Li; Henrik Gårdsvoll; Valentina de Lorenzi; Nicolai Sidenius; Mingdong Huang; Michael Ploug

    2015-01-01

    The urokinase-type plasminogen activator receptor (uPAR or CD87) is a glycolipid-anchored membrane protein often expressed in the microenvironment of invasive solid cancers and high levels are generally associated with poor patient prognosis (Kriegbaum et al., 2011 [1]). uPAR is organized as a dynamic modular protein structure composed of three homologous Ly6/uPAR domains (LU).This internally flexible protein structure of uPAR enables an allosteric regulation of the interactions with its two ...

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

    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.

  18. Proteomic Identification of LASP-1 Down-regulation After RNAi Urokinase Silencing in Human Hepatocellular Carcinoma Cells

    Alessandro Salvi

    2009-02-01

    Full Text Available In human hepatocellular carcinoma (HCC, the high expression of urokinase-type plasminogen activator (uPA is an unfavorable prognostic factor and a therapeutic target. To identify the downstream effects of uPA silencing by RNA interference, we studied proteome modifications of uPA-inhibited SKHep1C3 cells, an HCC-derived cell line. The study with two-dimensional difference gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight-mass spectrometry showed Lim and SH3 protein 1 (LASP-1, cytokeratin 1 (CK-1, cytokeratin 10 (CK-10, and heterogeneous nuclear ribonucleoprotein H1 down-modulation after uPA inhibition. LASP-1, CK-1, and CK-10 are involved in cytoskeleton dynamics as heterogeneous nuclear ribonucleoprotein H1 takes part in the mRNA processing and stability. We first confirmed the proteomic data by Western blot and immunoflorescence and then explored the link between uPA and LASP-1. The ectopic expression of uPA and LASP-1 supported the proteomic results and showed that uPA up-regulation increased LASP-1 expression and that both were implicated in SKHep1C3 motility. siRNA LASP-1 inhibition showed that LASP-1 was involved in actin microfilaments organization of SKHep1C3 cells. The disruption of the actin microfilaments after LASP-1 depletion increased uPA secretion and SKHep1C3 motility. Our results would suggest the hypothesis that uPA and LASP-1 expression may be coordinated in HCC-derived cells. In summary, the proteomic identification of a set of uPA downstream proteins provides new insight into the function of uPA in HCC cells.

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

    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

  20. Prognostic value analysis of urokinase-type plasminogen activator receptor in oral squamous cell carcinoma: an immunohistochemical study

    Oral squamous cell carcinoma (OSCC) represents the most common oral malignancy. Despite recent advances in therapy, up to 50% of the cases have relapse and/or metastasis. There is therefore a strong need for the identification of new biological markers able to predict the clinical behaviour of these lesions in order to improve quality of life and overall survival. Among tumour progression biomarkers, already known for their involvement in other neoplasia, a crucial role is ascribed to the urokinase-type plasminogen activator receptor (uPAR), which plays a multiple role in extracellular proteolysis, cell migration and tissue remodelling not only as a receptor for the zymogen pro-uPA but also as a component for cell adhesion and as a chemoattractant. The purpose of this study was to gain information on the expression of uPAR in OSCC and to verify whether this molecule can have a role as a prognostic/predictive marker for this neoplasia. In a retrospective study, a cohort of 189 OSCC patients was investigated for uPAR expression and its cellular localization by immunohistochemistry. As standard controls, 8 normal oral mucosal tissues free of malignancy, obtained from patients with no evidence or history of oral cavity tumours, were similarly investigated. After grouping for uPAR expression, OSCCs were statistically analyzed for the variables age, gender, histological grading (G), tumour size, recurrence, TNM staging and overall survival rate. In our immunohistochemical study, 74 cases (39.1%) of OSCC showed a mostly cytoplasmic positivity for uPAR, whereas 115 were negative. uPAR expression correlated with tumour differentiation grade and prognosis: percentage of positive cases was the greatest in G3 (70.4%) and patients positives for uPAR expression had an expectation of life lower than those for uPAR negatives. The results obtained in this study suggest a role of uPAR as a potential biomarker useful to identify higher risk subgroups of OSCC patients

  1. The evaluation of the cardiac function and the effect of urokinase therapy in patients with AMI in ICU

    The cardiac function and the effect of therapy in patients with acute myocardial infarction (AMI) were assessed in 61 patients by analysis of Tl-scintigraphy and Tc-HSA gated pool study in our ICU. Nineteen of them were treated with intravenous Urokinase (UK) within 6 hours from onset. The other 36 patients without UK treatment served as a control group. Significant correlation was recognized between Tl-defect ratio calculated by the circumferential profile curve and peak-CPK levels with a correlation coefficient of 0.578. Significant correlation (r=-0.674) was found between Tl-defect ratio and LVEF. Cardiac function, Tl-defect ratio and peak-CPK levels were compared among patients with antero-septal AMI, inferior AMI and posterior AMI. Significant reductions of LVEF (37.2+-11.7 %) were observed in antero-septal AMI, while RVEF (43.0+-10.0 %) showed significant decreases in inferior AMI. In addition, Tl-defect ratio (3.36+-1.97) and peak-CPK levels in antero-septal AMI were significant higher than those in iferior AMI and posterior AMI. The UK group showed a significant increase of LVEF as compared with the control group in patients with antero-septal AMI. In patients with inferior AMI, no significant differences were observed between UK and control group in LVEF, RVEF and Tl-defect ratio. We have demonstrated that a combination of Tl-scintigraphy and Tc-HSA gated pool study are useful techniques especially when performed in ICU, to evaluate the cardiac function and the effect of thrombolysis therapy and thus greatly contribute to the primary care of AMI cases. (author)

  2. MULTILATERAL DIPLOMACY AND INTERNATIONAL REGIMES

    BENEA Ciprian-Beniamin

    2014-12-01

    Full Text Available The history of diplomacy can by divided in three main periods: one is that of occasional diplomacy peculiar to Middle Ages, while other belong to permane diplomacy, peculiar to modern times. But this one can be divided in two parts, too: one with a bilateral character, previos to 1st World War, and one with a multilateral character, manifested especially after the end on 1st World War. This third type is the focus of present paper. And it cannot be separated from the newly international constructs: international regimes, and international organizations. International instritutions the area where international regimes are belonging to – are legal constructs which provide the formal (and legal framework for continous negotiations. They are the most visible part of the new diplomacy – the one which has a permanent character, and it has an more open face. Anyway, the most important connection has to do with the international institutions, international regimes, and multilateral international negotiations. In the era of the new diplomacy, they all have a permanent character. International institutions help international negotiations carring on; while in their turn, they provide the base for international regimes’ creation, and especially for their evolution. The international regimes’ evolution is an inseparable part of a permanent international framework. And if there is missing a permanent international framework (international organization connected to a specific regime, this regime is a difuse one, its members have only informal relations among them, while they survey each other, looking at their behavior, but they don’t have a formal relationship among them, which could help them solving their future common interests, and protect them from their common fears. International regimes are very important in the era when evrithing touches, and influences everything. In the same time, the complexity of our present world can be successfully

  3. Cloud regimes as phase transitions

    Stechmann, Samuel N.; Hottovy, Scott

    2016-06-01

    Clouds are repeatedly identified as a leading source of uncertainty in future climate predictions. Of particular importance are stratocumulus clouds, which can appear as either (i) closed cells that reflect solar radiation back to space or (ii) open cells that allow solar radiation to reach the Earth's surface. Here we show that these clouds regimes -- open versus closed cells -- fit the paradigm of a phase transition. In addition, this paradigm characterizes pockets of open cells as the interface between the open- and closed-cell regimes, and it identifies shallow cumulus clouds as a regime of higher variability. This behavior can be understood using an idealized model for the dynamics of atmospheric water as a stochastic diffusion process. With this new conceptual viewpoint, ideas from statistical mechanics could potentially be used for understanding uncertainties related to clouds in the climate system and climate predictions.

  4. Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2

    Berberine, a compound isolated from medicinal herbs, has been reported with many pharmacological effects related to anti-cancer and anti-inflammation capabilities. In this study, we observed that berberine exerted a dose- and time-dependent inhibitory effect on the motility and invasion ability of a highly metastatic A549 cells under non-cytotoxic concentrations. In cancer cell migration and invasion process, matrix-degrading proteinases are required. A549 cell treated with berberine at various concentrations showed reduced ECM proteinases including matrix metalloproteinase-2 (MMP2) and urokinase-plasminogen activator (u-PA) by gelatin and casein zymography analysis. The inhibitory effect is likely to be at the transcriptional level, since the reduction in the transcripts levels was corresponding to the proteins. Moreover, berberine also exerted its action via regulating tissue inhibitor of metalloproteinase-2 (TIMP-2) and urokinase-plasminogen activator inhibitor (PAI). The upstream mediators of the effect involved c-jun, c-fos and NF-κB, as evidenced by reduced phosphorylation of the proteins. These findings suggest that berberine possesses an anti-metastatic effect in non-small lung cancer cell and may, therefore, be helpful in clinical treatment

  5. Urokinase plasminogen receptor and the fibrinolytic complex play a role in nerve repair after nerve crush in mice, and in human neuropathies.

    Cristina Rivellini

    Full Text Available Remodeling of extracellular matrix (ECM is a critical step in peripheral nerve regeneration. In fact, in human neuropathies, endoneurial ECM enriched in fibrin and vitronectin associates with poor regeneration and worse clinical prognosis. Accordingly in animal models, modification of the fibrinolytic complex activity has profound effects on nerve regeneration: high fibrinolytic activity and low levels of fibrin correlate with better nerve regeneration. The urokinase plasminogen receptor (uPAR is a major component of the fibrinolytic complex, and binding to urokinase plasminogen activator (uPA promotes fibrinolysis and cell movement. uPAR is expressed in peripheral nerves, however, little is known on its potential function on nerve development and regeneration. Thus, we investigated uPAR null mice and observed that uPAR is dispensable for nerve development, whereas, loss of uPAR affects nerve regeneration. uPAR null mice showed reduced nerve repair after sciatic nerve crush. This was a consequence of reduced fibrinolytic activity and increased deposition of endoneurial fibrin and vitronectin. Exogenous fibrinolysis in uPAR null mice rescued nerve repair after sciatic nerve crush. Finally, we measured the fibrinolytic activity in sural nerve biopsies from patients with peripheral neuropathies. We showed that neuropathies with defective regeneration had reduced fibrinolytic activity. On the contrary, neuropathies with signs of active regeneration displayed higher fibrinolytic activity. Overall, our results suggest that enforced fibrinolysis may facilitate regeneration and outcome of peripheral neuropathies.

  6. Friction Regimes in the Lubricants Solid-State Regime

    Schipper, D.J.; Maathuis, O.; Dowson, D.; Taylor, C.M.; Childs, T.H.C.; Dalmaz, G.

    1995-01-01

    Friction measurements were performed in the lubricant's solid-state regime to study the transition from full-film lubrication, in which the separation is maintained by a solidified lubricant, to mixed lubrication. Special attention is paid to the influence of temperature (inlet viscosity) and roughn

  7. The Choice of Monetary Regime

    Østrup, Finn

    comparisonbetween monetary regimes suggests that welfare is highest under nominalincome targeting where the nominal income target is determined to bring aboutprice stability.Keywords: Monetary regimes; fiscal policy; monetary non-neutrality.JEL classicification: E42, E61, E62.......The article examines how government spending is determined in a closedeconomy where the nominal wage is pre-set through contracts and the wage settershave perfect foresight regarding subsequent policy decisions. The monetaryregime affects government spending because: (i) with a pre-set nominal wage...

  8. On the regimes of premixing

    Angelini, S.; Theofanous, T.G.; Yuen, W.W. [California Univ., Santa Barbara, CA (United States). Center for Risk Studies and Safety

    1998-01-01

    The conditions of the MAGICO-2000 experiment are extended to more broadly investigate the regimes of premixing, and the corresponding internal structures of mixing zones. With the help of the data and numerical simulations using the computer code PM-ALPHA, we can distinguish extremes of behavior dominated by inertia and thermal effects - we name these the inertia and thermal regimes, respectively. This is an important distinction that should guide future experiments aimed at code verification in this area. Interesting intermediate behaviors are also delineated and discussed. (author)

  9. Postoperative blood loss reduction in computer-assisted surgery total knee replacement by low dose intra-articular tranexamic acid injection together with 2-hour clamp drain: a prospective triple-blinded randomized controlled trial

    Paphon Sa-ngasoongsong

    2011-10-01

    Full Text Available A high-dose local tranexamic acid has been introduced in total knee arthroplasty for bleeding control. We are not sure about the systemic absorption and side effects. The aim of this study was to evaluate the effect of low dosage of intra-articular tranexamic acid injection combined with 2-hour clamp drain in minimally bleeding computer-assisted surgery total knee replacement (CAS-TKR. A prospective randomized controlled trial was conducted in a total of 48 patients underwent CAS-TKR. The patients were randomly assigned to receive either of a mixed intra-articular solution of tranexamic acid 250 mg with physiologic saline (TXA group, or physiologic saline (control group and then followed by clamp drain for 2 hours. Postoperative blood loss was measured by three different methods as drainage volume, total hemoglobin loss and calculated total blood loss. Transfusion requirement and postoperative complications were recorded. All patients were screened for deep vein thrombosis and the functional outcomes were evaluated at 6 months after surgery. The mean postoperative drainage volume, total hemoglobin loss and calculated total blood loss in TXA group were 308.8 mL, 2.1 g/dL and 206.3 mL compared to 529.0 mL, 3.0 g/dL and 385.1 mL in the control group (P=0.0003, 0.0005 and <0.0001 respectively. Allogenic blood transfusion was needed for one patient (4.2% in TXA group and for eight patients (33.3% in the control group. Postoperative knee scores were not significantly different between groups. No deep vein thrombosis, infection or wound complication was detected in both groups. In this study, low dose intra-articular tranexamic acid injection combined with 2-hour clamping drain was effective for reducing postoperative blood loss and transfusion requirement in CAS-TKR without significant difference in postoperative complications or functional outcomes.

  10. Postoperative blood loss reduction in computer-assisted surgery total knee replacement by low dose intra-articular tranexamic acid injection together with 2-hour clamp drain: a prospective triple-blinded randomized controlled trial

    Sa-ngasoongsong, Paphon; Channoom, Thanaphot; Kawinwonggowit, Viroj; Woratanarat, Patarawan; Chanplakorn, Pongsthorn; Wibulpolprasert, Bussanee; Wongsak, Siwadol; Udomsubpayakul, Umaporn; Wechmongkolgorn, Supaporn; Lekpittaya, Nantaporn

    2011-01-01

    A high-dose local tranexamic acid has been introduced in total knee arthroplasty for bleeding control. We are not sure about the systemic absorption and side effects. The aim of this study was to evaluate the effect of low dosage of intra-articular tranexamic acid injection combined with 2-hour clamp drain in minimally bleeding computer-assisted surgery total knee replacement (CAS-TKR). A prospective randomized controlled trial was conducted in a total of 48 patients underwent CAS-TKR. The patients were randomly assigned to receive either of a mixed intra-articular solution of tranexamic acid 250 mg with physiologic saline (TXA group), or physiologic saline (control group) and then followed by clamp drain for 2 hours. Postoperative blood loss was measured by three different methods as drainage volume, total hemoglobin loss and calculated total blood loss. Transfusion requirement and postoperative complications were recorded. All patients were screened for deep vein thrombosis and the functional outcomes were evaluated at 6 months after surgery. The mean postoperative drainage volume, total hemoglobin loss and calculated total blood loss in TXA group were 308.8 mL, 2.1 g/dL and 206.3 mL compared to 529.0 mL, 3.0 g/dL and 385.1 mL in the control group (P=0.0003, 0.0005 and <0.0001 respectively). Allogenic blood transfusion was needed for one patient (4.2%) in TXA group and for eight patients (33.3%) in the control group. Postoperative knee scores were not significantly different between groups. No deep vein thrombosis, infection or wound complication was detected in both groups. In this study, low dose intra-articular tranexamic acid injection combined with 2-hour clamping drain was effective for reducing postoperative blood loss and transfusion requirement in CAS-TKR without significant difference in postoperative complications or functional outcomes. PMID:22053253

  11. Postoperative blood loss reduction in computer-assisted surgery total knee replacement by low dose intra-articular tranexamic acid injection together with 2-hour clamp drain: a prospective triple-blinded randomized controlled trial

    Paphon Sa-ngasoongsong; Thanaphot Channoom; Viroj Kawinwonggowit; Patarawan Woratanarat; Pongsthorn Chanplakorn; Bussanee Wibulpolprasert; Siwadol Wongsak; Umaporn Udomsubpayakul; Supaporn Wechmongkolgorn; Nantaporn Lekpittaya

    2011-01-01

    A high-dose local tranexamic acid has been introduced in total knee arthroplasty for bleeding control. We are not sure about the systemic absorption and side effects. The aim of this study was to evaluate the effect of low dosage of intra-articular tranexamic acid injection combined with 2-hour clamp drain in minimally bleeding computer-assisted surgery total knee replacement (CAS-TKR). A prospective randomized controlled trial was conducted in a total of 48 patients underwent CAS-TKR. The pa...

  12. Nova Scotia's offshore royalty regime

    Oil production from the Hibernia project in Newfoundland's offshore began in December 1997. It is estimated that by 2010 some 30 per cent of Canada's light oil production and as much as 5-10 per cent of its natural gas production will originate from offshore Newfoundland and Nova Scotia. The current level of investment in east coast offshore petroleum developments is the result of the magnitude of discovered and undiscovered petroleum resources in the region. Advances in offshore petroleum technology also contributed to lower development costs. Another reason for increased investment has been an efficient and predictable regulatory environment and government policies. Nova Scotia's royalty regimes and the evolution of royalty regimes for the Sable Offshore Energy project were discussed. The Offshore Petroleum Royalty Act gives Nova Scotia the ability to establish a royalty regime through regulations, or to enter into royalty agreements on a project by project basis, or to use a mix of both agreement and regulation. The philosophy underlying Nova Scotia's royalty regime is to find the right balance between industry and government's share of project revenues

  13. Tumour microenvironments induce expression of urokinase plasminogen activator receptor (uPAR and concomitant activation of gelatinolytic enzymes.

    Synnøve Magnussen

    Full Text Available The urokinase plasminogen activator receptor (uPAR is associated with poor prognosis in oral squamous cell carcinoma (OSCC, and increased expression of uPAR is often found at the invasive tumour front. The aim of the current study was to elucidate the role of uPAR in invasion and metastasis of OSCC, and the effects of various tumour microenvironments in these processes. Furthermore, we wanted to study whether the cells' expression level of uPAR affected the activity of gelatinolytic enzymes.The Plaur gene was both overexpressed and knocked-down in the murine OSCC cell line AT84. Tongue and skin tumours were established in syngeneic mice, and cells were also studied in an ex vivo leiomyoma invasion model. Soluble factors derived from leiomyoma tissue, as well as purified extracellular matrix (ECM proteins, were assessed for their ability to affect uPAR expression, glycosylation and cleavage. Activity of gelatinolytic enzymes in the tissues were assessed by in situ zymography.We found that increased levels of uPAR did not induce tumour invasion or metastasis. However, cells expressing low endogenous levels of uPAR in vitro up-regulated uPAR expression both in tongue, skin and leiomyoma tissue. Various ECM proteins had no effect on uPAR expression, while soluble factors originating from the leiomyoma tissue increased both the expression and glycosylation of uPAR, and possibly also affected the proteolytic processing of uPAR. Tumours with high levels of uPAR, as well as cells invading leiomyoma tissue with up-regulated uPAR expression, all displayed enhanced activity of gelatinolytic enzymes.Although high levels of uPAR are not sufficient to induce invasion and metastasis, the activity of gelatinolytic enzymes was increased. Furthermore, several tumour microenvironments have the capacity to induce up-regulation of uPAR expression, and soluble factors in the tumour microenvironment may have an important role in the regulation of posttranslational

  14. Plasma levels of soluble urokinase-type plasminogen activator receptor associate with the clinical severity of acute Puumala hantavirus infection.

    Tuula K Outinen

    Full Text Available OBJECTIVES: Urokinase-type plasminogen activator receptor is a multifunctional glycoprotein, the expression of which is increased during inflammation. It is known to bind to β3-integrins, which are elementary for the cellular entry of hantaviruses. Plasma soluble form of the receptor (suPAR levels were evaluated as a predictor of severe Puumala hantavirus (PUUV infection and as a possible factor involved in the pathogenesis of the disease. DESIGN: A single-centre prospective cohort study. SUBJECTS AND METHODS: Plasma suPAR levels were measured twice during the acute phase and once during the convalescence in 97 patients with serologically confirmed acute PUUV infection using a commercial enzyme-linked immunosorbent assay (ELISA. RESULTS: The plasma suPAR levels were significantly higher during the acute phase compared to the control values after the hospitalization (median 8.7 ng/ml, range 4.0-18.2 ng/ml vs. median 4.7 ng/ml, range 2.4-12.2 ng/ml, P<0.001. The maximum suPAR levels correlated with several variables reflecting the severity of the disease. There was a positive correlation with maximum leukocyte count (r = 0.475, p<0.001, maximum plasma creatinine concentration (r = 0.378, p<0.001, change in weight during the hospitalization (r = 0.406, p<0.001 and the length of hospitalization (r = 0.325, p = 0.001, and an inverse correlation with minimum platelet count (r = -0.325, p = 0.001 and minimum hematocrit (r = -0.369, p<0.001. CONCLUSION: Plasma suPAR values are markedly increased during acute PUUV infection and associate with the severity of the disease. The overexpression of suPAR possibly activates β3-integrin in PUUV infection, and thus might be involved in the pathogenesis of the disease.

  15. Plasma Levels of Soluble Urokinase-Type Plasminogen Activator Receptor Associate with the Clinical Severity of Acute Puumala Hantavirus Infection

    Outinen, Tuula K.; Tervo, Laura; Mäkelä, Satu; Huttunen, Reetta; Mäenpää, Niina; Huhtala, Heini; Vaheri, Antti; Mustonen, Jukka; Aittoniemi, Janne

    2013-01-01

    Objectives Urokinase-type plasminogen activator receptor is a multifunctional glycoprotein, the expression of which is increased during inflammation. It is known to bind to β3-integrins, which are elementary for the cellular entry of hantaviruses. Plasma soluble form of the receptor (suPAR) levels were evaluated as a predictor of severe Puumala hantavirus (PUUV) infection and as a possible factor involved in the pathogenesis of the disease. Design A single-centre prospective cohort study. Subjects and Methods Plasma suPAR levels were measured twice during the acute phase and once during the convalescence in 97 patients with serologically confirmed acute PUUV infection using a commercial enzyme-linked immunosorbent assay (ELISA). Results The plasma suPAR levels were significantly higher during the acute phase compared to the control values after the hospitalization (median 8.7 ng/ml, range 4.0–18.2 ng/ml vs. median 4.7 ng/ml, range 2.4–12.2 ng/ml, P<0.001). The maximum suPAR levels correlated with several variables reflecting the severity of the disease. There was a positive correlation with maximum leukocyte count (r = 0.475, p<0.001), maximum plasma creatinine concentration (r = 0.378, p<0.001), change in weight during the hospitalization (r = 0.406, p<0.001) and the length of hospitalization (r = 0.325, p = 0.001), and an inverse correlation with minimum platelet count (r = −0.325, p = 0.001) and minimum hematocrit (r = −0.369, p<0.001). Conclusion Plasma suPAR values are markedly increased during acute PUUV infection and associate with the severity of the disease. The overexpression of suPAR possibly activates β3-integrin in PUUV infection, and thus might be involved in the pathogenesis of the disease. PMID:23990945

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

    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.

  17. Friction Regimes in the Lubricants Solid-State Regime

    Schipper, D.J.; Maathuis, O.; Dowson, D; Taylor, C.M.; Childs, T.H.C.; Dalmaz, G.

    1995-01-01

    Friction measurements were performed in the lubricant's solid-state regime to study the transition from full-film lubrication, in which the separation is maintained by a solidified lubricant, to mixed lubrication. Special attention is paid to the influence of temperature (inlet viscosity) and roughness on this transition. The friction measurements showed that in the lubricants solid-state region three lubrication modes can be distinguished: A) full-film lubrication; separation is maintained b...

  18. The Concept of Truth Regime

    Lorna Weir

    2008-07-01

    Full Text Available “Truth regime” is a much used but little theorized concept, with the Foucauldian literature presupposing that truth in modernity is uniformly scientific/quasi-scientific and enhances power. I argue that the forms of truth characteristic of our present are wider than Foucault recognized, their relations to power more various, and their historicity more complex. The truth regime of advanced modernity is characterized by multiple, irreducible truth formulae that co-exist and sometimes vie for dominance. A truth formula stabilizes a network of elements: a relation between representation and presentation (words and things, truth and non-truth, and the place of the subject in discourse. Our contemporary truth regime comprises radically heterogeneous truthful knowledges – science, governance, religion/politics, and common culture – that have distinct histories and relations to power.

  19. The emerging climate change regime

    The emerging climate change regime--with the UN Framework Convention on Climate Change (FCCC) at its core--reflects the substantial uncertainties, high stakes and complicated politics of the greenhouse warming issue. The regime represents a hedging strategy. On the one hand, it treats climate change as a potentially serious problem, and in response, creates a long-term, evolutionary process to encourage further research, promote national planning, increase public awareness, and help create a sense of community among states. But it requires very little by way of substantive--and potentially costly--mitigation or adaptation measures. Although the FCCC parties have agreed to negotiate additional commitments, substantial progress is unlikely without further developments in science, technology, and public opinion. The FCCC encourages such developments, and is capable of evolution and growth, should the political will to take stronger international action emerge. 120 refs., 3 tabs

  20. Demystifying optimal dynamic treatment regimes.

    Moodie, Erica E M; Richardson, Thomas S; Stephens, David A

    2007-06-01

    A dynamic regime is a function that takes treatment and covariate history and baseline covariates as inputs and returns a decision to be made. Murphy (2003, Journal of the Royal Statistical Society, Series B 65, 331-366) and Robins (2004, Proceedings of the Second Seattle Symposium on Biostatistics, 189-326) have proposed models and developed semiparametric methods for making inference about the optimal regime in a multi-interval trial that provide clear advantages over traditional parametric approaches. We show that Murphy's model is a special case of Robins's and that the methods are closely related but not equivalent. Interesting features of the methods are highlighted using the Multicenter AIDS Cohort Study and through simulation. PMID:17688497

  1. Disclosure regimes and corporate governance

    Wüstemann, Jens

    2004-01-01

    As there is a strong relationship of disclosure regimes and corporate governance the internationally varying distribution of information rights can be interpreted as a function of different systems of corporate governance. A disclosure system comprises all legally recognized information claims that a system of corporate governance or a financial system furnishes financial contracting parties with: Both public disclosure and disclosure via private information channels may serve value-relevant ...

  2. The EU Commission consultation regime

    Quittkat, Christine; Finke, Barbara

    2008-01-01

    "The present consultation regime of the European Commission is marked by the role the Commission assigns to non-governmental actors or civil society organisations (CSOs). The Commission's documents on its policy of consultation and cooperation with external non-governmental actors reveal that a reflective approach has emerged during the 1980s, referring to a more elaborate concept of 'good governance'. The gradual extension is most noticeable in the change of terminology, from ‘consultation’ ...

  3. Contrasting Monetary Regimes in Africa

    Patrick Honohan; Stephen A. O'Connell

    1997-01-01

    In post-independence sub-Saharan Africa, institutional arrangements for monetary policy have taken a variety of forms, although the historical evolution of many African financial systems has been similar. This paper identifies five different regimes and examines how they evolved over time. It focuses on how the alternative institutional arrangements have influenced the performance of monetary policy under fiscal pressure, and concludes that, although the trend appears to be toward more flexib...

  4. The International Climate Change Regime

    Yamin, Farhana; Depledge, Joanna

    2005-01-01

    Aimed at the increasing number of policy-makers, stakeholders, researchers, and other professionals working on climate change, this volume presents a detailed description and analysis of the international regime established in 1992 to combat the threat of global climate change. It provides a comprehensive accessible guide to a high-profile area of international law and politics, covering not only the obligations and rights of countries, but ongoing climate negotiations as well.

  5. Monetary regimes in open economies

    Korpos, A.

    2006-01-01

    This thesis presents a two-country open economy framework for the analysis of strategic interactions among monetary authorities and wage bargaining institutions. From this perspective, the thesis investigates the economic consequences of replacing flexible and fixed exchange rate regimes with a monetary union, such as the European Economic and Monetary Union. It shows that fixing a currency creates a flatter Phillips curve and increases the aggressiveness of wage demands by labor unions. Comp...

  6. Exchange Rate Regimes and Location

    Ricci, Luca Antonio

    1997-01-01

    This paper investigates the effects of fixed versus flexible exchange rate regimes on location choices of firms and on the degree of specialization of countries. In a two-country two-differentiated-good monetary model, demand, supply, and monetary shocks arise after wages are set and prices are optimally chosen. The exchange rate performs then an adjustment role for firms located in the country relatively specialized in the good they produce, but it constitutes a factor of disturbance for the...

  7. Presence of urokinase plasminogen activator, its inhibitor and receptor in small cell lung cancer and non-small cell lung cancer

    Pappot, H.; Pfeiffer, P.; Grøndahl Hansen, J.;

    1997-01-01

    Spreading of cancer cells is dependent on the combined action of several proteolytic enzymes, such as serine proteases, comprising the urokinase pathway of plasminogen activation. Previous studies of lung cancer indicate that expression, localization and prognostic impact of the components of the...... plasminogen activation system differ in the different non-small cell lung cancer (NSCLC) types, whereas the expression of the components in small cell lung cancer (SCLC) has only sparingly been investigated. In the present study we investigate the presence of the components of the plasminogen activation...... the clinical parameters. This is the first report of a study using a quantitative method to compare levels of the components of the plasminogen activation system in tissue extracts from the two major lung cancer groups. The study shows that uPA, PAI-1 and uPAR are present in SCLC-tissue, suggesting...

  8. Targeting tumor cell invasion and dissemination in vivo by an aptamer that inhibits urokinase-type plasminogen activator through a novel multifunctional mechanism

    Botkjaer, Kenneth A; Deryugina, Elena I; Dupont, Daniel Miotto;

    2012-01-01

    Data accumulated over the latest two decades have established that the serine protease urokinase-type plasminogen activator (uPA) is a potential therapeutic target in cancer. When designing inhibitors of the proteolytic activity of serine proteases, obtaining sufficient specificity is problematic......, because the topology of the proteases' active sites are highly similar. In an effort to generate highly specific uPA inhibitors with new inhibitory modalities, we isolated uPA-binding RNA aptamers by screening a library of 35 nucleotides long 2'-fluoro-pyrimidine RNA molecules using a version of human pro......-uPA lacking the epidermal growth factor-like and kringle domains as bait. One pro-uPA-binding aptamer sequence, referred to as upanap-126, proved to be highly specific for human uPA. Upanap-126 delayed the proteolytic conversion of human pro-uPA to active uPA, but did not inhibit plasminogen activation...

  9. Distinctive binding modes and inhibitory mechanisms of two peptidic inhibitors of urokinase-type plasminogen activator with isomeric P1 residues

    Jiang, Longguang; Zhao, Baoyu; Xu, Peng;

    2015-01-01

    Two isomeric piperidine derivatives (meta and para isomers) were used as arginine mimics in the P1 position of a cyclic peptidic inhibitor (CPAYSRYLDC) of urokinase-type plasminogen activator. The two resulting cyclic peptides showed vastly different affinities (~70 fold) to the target enzyme. X......-ray crystal structure analysis showed that the two P1 residues were inserted into the S1 specificity pocket in indistinguishable manners. However, the rest of the peptides bound in entirely different ways on the surface of the enzyme, and the two peptides have different conformations, despite the highly...... similar sequence. These results demonstrate how the subtle difference in P1 residue can dictate the exosite interactions and the potencies of peptidic inhibitors, and highlight the importance of P1 residue for protease inhibition. This study provides important information for the development of peptidic...

  10. Anti-Urokinase Receptor Antisense Oligonucleotide (uPAR-aODN) to Prevent and Cure Long-Term Space Exploration-Related Retinal Pathological Angiogenesis

    Lazzarano, Stefano; Lulli, Matteo; Fibbi, Gabriella; Margheri, Francesca; Papucci, Laura; Serrati, Simona; Witort, Ewa; Chilla, Anastasia; Lapucci, Andrea; Donnini, Martino; Quaglierini, Paolo; Romiti, Alice; Specogna, Rebecca; Del Rosso, Mario; Capaccioli, Sergio

    2008-06-01

    Angiogenesis underlies a variety of physiological processes and its possible deregulation during long term space exploration needs to be investigated. Angiogenesis is a multistep process of new blood capillary formation, where degradation of the extracellular matrix (ECM) by proteolytic enzymes, including uPA (urokinase plasminogen activator) and opening the way to migration of endothelial cells (EC), is critical. Plasminogen activation system regulates angiogenesis by both uPA-driven ECM degradation and uPA receptor (uPAR). Microgravity and low dose irradiations promote tissue neoangiogeenesis and neovascularization is often common occurence in ophthalmologic pathologies. We have designed and patented the uPAR antisense oligonucleotide (aODN) and evaluated its antiangiogenetic activity by EC cellular migration and capillary morphogenesis assays. The uPAR aODN treatment caused a 75% inhibition of human microvascular EC migration and a complete inhibition of capillary morphogenesis, suggesting its therapeutic application to prevent neoangiogenesis-related ophthalmologic pathologies during space exploration.

  11. Soluble Urokinase Plasminogen Activator Receptor Level Is an Independent Predictor of the Presence and Severity of Coronary Artery Disease and of Future Adverse Events

    Eapen, Danny J; Manocha, Pankaj; Ghasemzedah, Nima;

    2014-01-01

    INTRODUCTION: Soluble urokinase plasminogen activator receptor (suPAR) is an emerging inflammatory and immune biomarker. Whether suPAR level predicts the presence and the severity of coronary artery disease (CAD), and of incident death and myocardial infarction (MI) in subjects with suspected CAD......, is unknown. METHODS AND RESULTS: We measured plasma suPAR levels in 3367 subjects (67% with CAD) recruited in the Emory Cardiovascular Biobank and followed them for adverse cardiovascular (CV) outcomes of death and MI over a mean 2.1±1.1 years. Presence of angiographic CAD (≥50% stenosis in ≥1...... coronary artery) and its severity were quantitated using the Gensini score. Cox's proportional hazard survival and discrimination analyses were performed with models adjusted for established CV risk factors and C-reactive protein levels. Elevated suPAR levels were independently associated with the presence...

  12. A new tagging system for production of recombinant proteins in Drosophila S2 cells using the third domain of the urokinase receptor

    Gårdsvoll, Henrik; Hansen, Line V; Jørgensen, Thomas J D;

    2007-01-01

    chromatography procedure using the immobilized anti-uPAR monoclonal antibody R2. An optional enterokinase cleavage site is included between the various recombinant proteins and the linker region of the tag, which enables generation of highly pure preparations of tag-free recombinant proteins. Using this system......The use of protein fusion tag technology greatly facilitates detection, expression and purification of recombinant proteins, and the demands for new and more effective systems are therefore expanding. We have used a soluble truncated form of the third domain of the urokinase receptor as a...... convenient C-terminal fusion partner for various recombinant extracellular human proteins used in basic cancer research. The stability of this cystein-rich domain, which structure adopts a three-finger fold, provides an important asset for its applicability as a fusion tag for expression of recombinant...

  13. Soluble urokinase plasminogen activator receptor (suPAR) is a novel, independent predictive marker of myocardial infarction in HIV-1-infected patients

    Rasmussen, Line Jee Hartmann; Knudsen, A; Katzenstein, T L;

    2016-01-01

    OBJECTIVES: Patients infected with HIV are at increased risk of myocardial infarction (MI). Increased plasma levels of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) have been associated with increased risk of cardiovascular diseases (CVD), including MI in the......, gender, duration of antiretroviral therapy (ART), smoking and no known CVD. suPAR was measured in the four plasma samples available for each patient at different time-points; 1, Before initiation of ART; 2, 3 months after initiation of ART; 3, 1 year before the case's MI; and 4, The last sample available...... before the case's MI. RESULTS: In unadjusted conditional regression analysis, higher levels of suPAR were associated with a significant increase in risk of MI at all time-points. Patients in the third and fourth suPAR quartiles had a three- to 10-fold higher risk of MI compared to patients in the lowest...

  14. Plasma soluble urokinase-type plasminogen activator receptor level is independently associated with coronary microvascular function in patients with non-obstructive coronary artery disease

    Mekonnen, Girum; Corban, Michel T; Hung, Olivia Y;

    2015-01-01

    BACKGROUND: Soluble urokinase-type plasminogen activator receptor (suPAR) is a novel biomarker released from leukocytes and endothelial cells that has been associated with atherosclerotic cardiovascular disease. We hypothesized that plasma suPAR level is an independent predictor of coronary...... microvascular function. METHODS: Coronary blood flow velocity and plasma suPAR levels were evaluated in patients with non-obstructive coronary artery disease. Coronary flow reserve (CFR) was calculated as the ratio of hyperemic to basal average peak blood flow velocity and coronary microvascular dysfunction was...... defined as CFR ≤ 2.0 in the setting of a fractional flow reserve value of ≥0.75. Plasma suPAR levels were measured using ELISA technique. The association between suPAR and CFR was investigated using univariate and multivariate regression analyses. RESULTS: In 66 patients, 47% were men, 26% had diabetes...

  15. Urokinase-type Plasminogen Activator-like Proteases in Teleosts Lack Genuine Receptor-binding Epidermal Growth Factor-like Domains*

    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

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

    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.

  17. Bacterial endotoxin enhances colorectal cancer cell adhesion and invasion through TLR-4 and NF-kappaB-dependent activation of the urokinase plasminogen activator system.

    Killeen, S D

    2009-05-19

    Perioperative exposure to lipopolysaccharide (LPS) is associated with accelerated metastatic colorectal tumour growth. LPS directly affects cells through Toll-like receptor 4 (TLR-4) and the transcription factor NF-kappaB. The urokinase plasminogen activator (u-PA) system is intimately implicated in tumour cell extracellular matrix (ECM) interactions fundamental to tumour progression. Thus we sought to determine if LPS directly induces accelerated tumour cell ECM adhesion and invasion through activation of the u-PA system and to elucidate the cellular pathways involved. Human colorectal tumour cell lines were stimulated with LPS. u-PA concentration, u-PA activity, active u-PA, surface urokinase plasminogen activator receptor (u-PAR) and TLR-4 expression were assessed by ELISA, colorimetric assay, western blot analysis and flow cytometry respectively. In vitro tumour cell vitronectin adhesion and ECM invasion were analysed by vitronectin adhesion assay and ECM invasion chambers. u-PA and u-PAR function was inhibited with anti u-PA antibodies or the selective u-PA inhibitors amiloride or WXC-340, TLR-4 by TLR-4-blocking antibodies and NF-kappaB by the selective NF-kappaB inhibitor SN-50. LPS upregulates u-PA and u-PAR in a dose-dependent manner, enhancing in vitro tumour cell vitronectin adhesion and ECM invasion by >40% (P<0.01). These effects were ameliorated by u-PA and u-PAR inhibition. LPS activates NF-kappaB through TLR-4. TLR-4 and NF-kappaB inhibition ameliorated LPS-enhanced u-PA and u-PAR expression, tumour cell vitronectin adhesion and ECM invasion. LPS promotes tumour cell ECM adhesion and invasion through activation of the u-PA system in a TLR-4- and NF-kappaB-dependent manner.

  18. Transcriptional Regulation of Urokinase-type Plasminogen Activator Receptor by Hypoxia-Inducible Factor 1 Is Crucial for Invasion of Pancreatic and Liver Cancer

    Peter Büchler

    2009-02-01

    Full Text Available Angioinvasion is critical for metastasis with urokinase-type plasminogen activator receptor (uPAR and tumor hypoxia-activated hypoxia-inducible factor 1 (HIF-1 as key players. Transcriptional control of uPAR expression by HIF has never been reported. The aim of the present study, therefore, was to test whether tumor hypoxia-induced HIF expression may be linked to transcriptional activation of uPAR and dependent angioinvasion. We used human pancreatic cancer cells and a model of parental and derived HIF-1β-deficient mouse liver cancer cell lines and performed Northern blot analysis, nuclear runoff assays, electrophoretic mobility shift assay, polymerase chain reaction-generated deletion mutants, luciferase assays, Matrigel invasion assays, and in vivo angioinvasion assays in the chorioallantoic membrane of fertilized chicken eggs. Urokinase-type plasminogen activator receptor promoter analysis resulted in four putative HIF binding sites. Hypoxia strongly induced de novo transcription of uPAR mRNA. With sequential deletion mutants of the uPAR promoter, it was possible to identify one HIF binding site causing a nearly 200-fold increase in luciferase activity. Hypoxia enhanced the number of invading tumor cells in vitro and in vivo. In contrast, HIF-1β-deficient cells failed to upregulate uPAR expression, to activate luciferase activity, and to invade on hypoxia. Taken together, we show for the first time that uPAR is under transcriptional control of HIF and that this is important for hypoxia-induced metastasis.

  19. Mapping the topographic epitope landscape on the urokinase plasminogen activator receptor (uPAR by surface plasmon resonance and X-ray crystallography

    Baoyu Zhao

    2015-12-01

    Full Text Available The urokinase-type plasminogen activator receptor (uPAR or CD87 is a glycolipid-anchored membrane protein often expressed in the microenvironment of invasive solid cancers and high levels are generally associated with poor patient prognosis (Kriegbaum et al., 2011 [1]. uPAR is organized as a dynamic modular protein structure composed of three homologous Ly6/uPAR domains (LU.This internally flexible protein structure of uPAR enables an allosteric regulation of the interactions with its two principal ligands: the serine protease urokinase-type plasminogen activator (uPA and the provisional matrix protein vitronectin (Vn (Mertens et al., 2012; Gårdsvoll et al., 2011; Madsen et al., 2007 [2–4]. The data presented here relates to the non-covalent trapping of one of these biologically relevant uPAR-conformations by a novel class of monoclonal antibodies (Zhao et al., 2015 [5] and to the general mapping of the topographic epitope landscape on uPAR. The methods required to achieve these data include: (1 recombinant expression and purification of a uPAR-hybrid protein trapped in the desired conformation [patent; WO 2013/020898 A12013]; (2 developing monoclonal antibodies with unique specificities using this protein as antigen; (3 mapping the functional epitope on uPAR for these mAbs by surface plasmon resonance with a complete library of purified single-site uPAR mutants (Zhao et al., 2015; Gårdsvoll et al., 2006 [5,6]; and finally (4 solving the three-dimensional structures for one of these mAbs by X-ray crystallography alone and in complex with uPAR [deposited in the PDB database as 4QTH and 4QTI, respectively].

  20. Mapping the topographic epitope landscape on the urokinase plasminogen activator receptor (uPAR) by surface plasmon resonance and X-ray crystallography.

    Zhao, Baoyu; Gandhi, Sonu; Yuan, Cai; Luo, Zhipu; Li, Rui; Gårdsvoll, Henrik; de Lorenzi, Valentina; Sidenius, Nicolai; Huang, Mingdong; Ploug, Michael

    2015-12-01

    The urokinase-type plasminogen activator receptor (uPAR or CD87) is a glycolipid-anchored membrane protein often expressed in the microenvironment of invasive solid cancers and high levels are generally associated with poor patient prognosis (Kriegbaum et al., 2011 [1]). uPAR is organized as a dynamic modular protein structure composed of three homologous Ly6/uPAR domains (LU).This internally flexible protein structure of uPAR enables an allosteric regulation of the interactions with its two principal ligands: the serine protease urokinase-type plasminogen activator (uPA) and the provisional matrix protein vitronectin (Vn) (Mertens et al., 2012; Gårdsvoll et al., 2011; Madsen et al., 2007 [2-4]). The data presented here relates to the non-covalent trapping of one of these biologically relevant uPAR-conformations by a novel class of monoclonal antibodies (Zhao et al., 2015 [5]) and to the general mapping of the topographic epitope landscape on uPAR. The methods required to achieve these data include: (1) recombinant expression and purification of a uPAR-hybrid protein trapped in the desired conformation [patent; WO 2013/020898 A12013]; (2) developing monoclonal antibodies with unique specificities using this protein as antigen; (3) mapping the functional epitope on uPAR for these mAbs by surface plasmon resonance with a complete library of purified single-site uPAR mutants (Zhao et al., 2015; Gårdsvoll et al., 2006 [5,6]); and finally (4) solving the three-dimensional structures for one of these mAbs by X-ray crystallography alone and in complex with uPAR [deposited in the PDB database as 4QTH and 4QTI, respectively]. PMID:26504891

  1. Visibility regimes in mediatized publicness

    Samuel Mateus

    2014-12-01

    Full Text Available Considering the relationship between politics, media and publicness, this paper ponders the consequences of visibility in the political field. Identifying some of its existing regimes, it will posit that today visibility plays an ambivalent function to politics: it can simultaneously operate as a synoptic monitoring and control of politicians; and at the same time it may stand as an opportunity to build a charismatic leadership. In fact, political visibilities are now negotiated between the boundaries of private and public realms, and they can take the form of a risk, or an opportunity to build on a charismatic leadership.

  2. Alberta oil sands royalty regime

    The long term objective of the Oil Sands Business Unit of Alberta Energy is to pave the way for Alberta's bitumen production to reach 3 million barrels per day by 2020. This presentation described the national government's role in resource development. It was emphasized that since the Crown is the owner of the oil sands resource, it would benefit by providing strategic leadership and by generating a larger royalty base. The oil sands fiscal regime was described with reference to generic royalty, risk sharing, investment, and project economics. Business rule principles were also outlined along with criteria for project expansions. Both upstream and downstream challenges and opportunities were listed. 4 figs

  3. Twentieth century monetary regimes in Canadian perspective

    Harley, C. Knick

    2001-01-01

    Three monetary regimes - the gold standard, a regime of 'socialism in many countries' and the post-Bretton Woods regime - and difficult transitions between them have shaped the economic history of the twentieth century. The regimes consisted of coherent sets of government policies and equally importantly, the publics expectations about policy and each made different decisions about which of the trilemma of policy goals - fixed exchange rates, domestic policy independence and integrated capita...

  4. Accommodating human values in the climate regime

    Cook, Rosalind; Tauschinsky, Eljalill

    2008-01-01

    The climate regime addresses one of the most important challenges facing humankind today. However, while the environmental and economic sides of the problem are well represented, it lacks the inclusion of social and human aspects. The human rights regime, in contrast, is a regime which has been esta

  5. Measuring the effectiveness of international environmental regimes

    Helm, C.; Sprinz, D.F.

    1999-05-01

    While past research has emphasized the importance of international regimes for international governance, systematic assessments of regime effects are missing. This article derives a standardized measurement concept for the effectiveness of international environmental regimes by developing an operational rational choice calculus to evaluate actual policy simultaneously against a non-regime counterfactual and a collective optimum. Subsequently, the empirical feasibility of the measurement instrument is demonstrated by way of two international treaties regulating transboundary air pollution in Europe. The results demonstrate that the regimes indeed show positive effects - but fall substantially short of the collective optima. (orig.)

  6. Regime Jumps in Electricity Prices

    Electricity prices are known to be very volatile and subject to frequent jumps due to system breakdown, demand shocks, and inelastic supply. As many international electricity markets are in some state of deregulation, more and more participants in these markets are exposed to these stylised facts. Appropriate pricing, portfolio, and risk management models should incorporate these facts. Authors have introduced stochastic jump processes to deal with the jumps, but we argue and show that this specification might lead to problems with identifying the true mean-reversion within the process. Instead, we propose using a regime jump model that disentangles mean-reversion from jump behaviour. This model resembles more closely the true price path of electricity prices

  7. Accommodating human values in the climate regime

    Rosalind Cook

    2008-12-01

    Full Text Available The climate regime addresses one of the most important challenges facing humankind today. However, while the environmental and economic sides of the problem are well represented, it lacks the inclusion of social and human aspects. The human rights regime, in contrast, is a regime which has been established precisely to implement human values. This article ex-plains the problems of climate change in terms of human values and argues that some proce-dures from the human rights regime offer possibilities for improvement. It is submitted that through the inclusion of human rights instruments, such as individual communication, pro-gressive realisation and authoritative interpretation, the inclusion of human values into the climate regime will be facilitated. This article presents these instruments and discusses their potential for inclusion in the climate regime.

  8. Propagation Regime of Iron Dust Flames

    Tang, Francois-David; Goroshin, Samuel; Higgins, Andrew J.

    2012-01-01

    A flame propagating through an iron-dust mixture can propagate in two asymptotic regimes. When the characteristic time of heat transfer between particles is much smaller than the characteristic time of particle combustion, the flame propagates in the continuum regime where the heat released by reacting particles can be modelled as a space-averaged function. In contrast, when the characteristic time of heat transfer is much larger than the particle reaction time, the flame can no longer be treated as a continuum due to dominating effects associated with the discrete nature of the particle reaction. The discrete regime is characterized by weak dependence of the flame speed on the oxygen concentration compared to the continuum regime. The discrete regime is observed in flames propagating through an iron dust cloud within a gas mixture containing xenon, while the continuum regime is obtained when xenon is substituted with helium.

  9. US Forest Service LANDFIRE Historical Fire Regimes

    US Forest Service, Department of Agriculture — Historical fire regimes, intervals, and vegetation conditions are mapped using the Vegetation Dynamics Development Tool (VDDT). These data support fire and...

  10. Crustal stress regime in Italy

    M. Cesaro

    1997-06-01

    Full Text Available In order to obtain a reliable map of the present-day stress field in Italy, needed to better understand the active tectonic processes and to contribute to the assessment of seismic hazard, in 1992 we started to collect and analyze new data from borehole breakouts in deep oil and geothermal wells and focal mechanisms of earthquakes (2.5 < M <5 occurred in Italy between 1988 and 1995. From about 200 deep wells and 300 focal mechanisms analyzed to date, we infer that: the internal (SW sector of the Northern Apenninic arc is extending with minimum compressional stress (Shmin oriented ? ENE, while the external front is thrusting over the Adriatic foreland (Shmin ? NW-SE. The entire Southern Apennine is extending in NE direction (from the Tyrrhenian margin to the Apulian foreland and compression (in the foredeep is no longer active at the outer (NE thrust front. Between these two arcs, an abrupt change in the tectonic regime is detected with directions of horizontal stress changing by as much as 90º in the external front, around latitude 430N. Along the Ionian side of the Calabrian arc the stress directions inferred from breakouts and focal mechanisms are scattered with a hint of rotation from N-S Shmin close to the Southern Apennines, to ~ E-W directions in the Messina Strait. In Sicily, a NW-SE direction of SHmax is evident in the Hyblean foreland, parallel to the direction of plate motion between Africa and Europe. A more complex pattern of stress directions is observed in the thrust belt zone, with rotations from the regional trend (NW í directed SHmax to NE oriented SHmax. A predominant NW direction of SHmax is also detected in mainland Sicily from earthquake focal mechanisms, but no well data are available in this region. In the northern part of Sicily (Aeolian Islands a ~N-S direction of SHmax is observed.

  11. Phorbol ester induces the biosynthesis of glycosylated and nonglycosylated plasminogen activator inhibitor 2 in high excess over urokinase-type plasminogen activator in human U-937 lymphoma cells

    Genton, C.; Kruithof, E.K.; Schleuning, W.D.

    1987-03-01

    The tumor-promoting phorbol ester PMA induces changes in the histiocytic human lymphoma cell line U-937 akin to cellular differentiation and concomitantly stimulates the biosynthesis of plasminogen activator inhibitor 2 (PAI 2) and of urokinase-type plasminogen activator (u-PA). PAI 2 is found in a nonglycosylated intracellular and a glycosylated secreted form. The former appears to be identical to PAI 2 previously purified from placental extracts and large-scale U-937 cell cultures. The sixfold increase of PAI 2 antigen measured 24 h after PMA treatment in cell extracts and conditioned media is accompanied by an equal increase of active PAI 2 mRNA, whereas the 6 to 13-fold increase of u-PA antigen in the same samples is associated with only a 1.5-fold mRNA increase. The increase of PAI 2, but not of u-PA, biosynthesis requires transcription. A 50-fold molar excess of PAI 2 over u-PA is found in both extracts and conditioned media of PMA-treated cells. PAI 2 represents at least 0.3% of total de novo synthesized protein 24 h after induction with PMA. Thus, PAI 2, but not u-PA, is an abundant product of this precursor analogue of the mononuclear phagocyte lineage, and might represent a new marker for monocyte/macrophage differentiation.

  12. Camptothecin induces urokinase-type plasminogen activator gene-expression in human RC-K8 malignant lymphoma and H69 small cell lung cancer cells.

    Shibakura M

    2002-10-01

    Full Text Available We previously reported that anthracyclines, which could generate reactive oxygen species (ROS, could induce the urokinase-type plasminogen activator (uPA gene expression in human RC-K8 malignant lymphoma cells and in H69 small cell lung cancer (SCLC cells. In screening other uPA-inducible anti-cancer agents, we found that camptothecin (CPT and its derivative, SN38, could induce uPA in RC-K8 and H69 cells. CPT and SN38, which are also used for the treatment of lymphoma and SCLC, significantly increased the uPA accumulation in the conditioned media of both cells in a dose-dependent manner. The maximum induction of uPA mRNA levels was observed 24 h after stimulation. Pretreatment with pyrrolidine dithiocarbamate (PDTC, an anti-oxidant, inhibited the CPT-induced uPA mRNA expression. Thus, CPT induces uPA through gene expression, and, therefore, CPT may influence the tumor-cell biology by up-regulating the uPA/plasmin system.

  13. Short-Term Catheter-Directed Thrombolysis with Low-Dose Urokinase Followed by Aspiration Thrombectomy for Treatment of Symptomatic Lower Extremity Deep Venous Thrombosis

    Jung, Se Hee; Lim, Nam Yeul; Song, Jang Hyeon [Dept. of Radiology, Chonnam National University Hospital, Gwangju (Korea, Republic of); Kim, Jae Kyu; Lim, Jae Hoon [Dept. of Radiology, Hospital, Ulsan University School of Medicine, Gweangju (Korea, Republic of); Chang, Nam Kyu [Dept. of Radiology, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of); Choi, Soo Jin Na; Chung, Sang Young [Dept. of Radiology, Chonnam National University Hospital, Chonnam National University School of Medicine, Gwangju (Korea, Republic of)

    2011-10-15

    To evaluate the venous patency in patients treated by catheter-directed thrombolysis with low-dose urokinase (UK) for symptomatic lower extremity deep venous thrombosis (DVT). Eighty-nine consecutive patients (46 women and 43 men; mean age, 58.1 years), treated by catheter-directed thrombolysis with low-dose UK were included in this study. Immediate venous patency was evaluated in terms of technical success (successful restoration of antegrade in-line flow in the treated vein with residual stenosis rate of less than 30%) and clinical success (significant reduction of clinical symptoms before hospital discharge). Late venous patency was evaluated in terms of primary patency rate and clinical success. Immediate technical success was achieved in all patients and immediate clinical success in 80 (90%) patients. There was no major systemic bleeding complication. The primary patency rate at 6 months and 12 months was 84% and 79%, respectively. Fifty-six (63%) patients were asymptomatic after a median clinical follow-up of 18 months, eleven (12%) patients improved moderately, seven (8%) patients remained unchanged, and fifteen (17%) patients had no clinical follow-up. Short-term catheter-directed thrombolysis with low-dose UK can be an effective, safe method to manage DVT of the lower extremities.

  14. Short-Term Catheter-Directed Thrombolysis with Low-Dose Urokinase Followed by Aspiration Thrombectomy for Treatment of Symptomatic Lower Extremity Deep Venous Thrombosis

    To evaluate the venous patency in patients treated by catheter-directed thrombolysis with low-dose urokinase (UK) for symptomatic lower extremity deep venous thrombosis (DVT). Eighty-nine consecutive patients (46 women and 43 men; mean age, 58.1 years), treated by catheter-directed thrombolysis with low-dose UK were included in this study. Immediate venous patency was evaluated in terms of technical success (successful restoration of antegrade in-line flow in the treated vein with residual stenosis rate of less than 30%) and clinical success (significant reduction of clinical symptoms before hospital discharge). Late venous patency was evaluated in terms of primary patency rate and clinical success. Immediate technical success was achieved in all patients and immediate clinical success in 80 (90%) patients. There was no major systemic bleeding complication. The primary patency rate at 6 months and 12 months was 84% and 79%, respectively. Fifty-six (63%) patients were asymptomatic after a median clinical follow-up of 18 months, eleven (12%) patients improved moderately, seven (8%) patients remained unchanged, and fifteen (17%) patients had no clinical follow-up. Short-term catheter-directed thrombolysis with low-dose UK can be an effective, safe method to manage DVT of the lower extremities.

  15. Distribution of trichloroacetic acid precipitated radioactivity in rabbits after intravenous injection of 125I-labelled single-chain human recombinant urokinase-type plasminogen activator

    Objective: To study tissue distribution profiles of trichloroacetic acid (TCA) precipitated radioactivity in rabbits following intravenous injection of 125I-labelled single-chain human recombinant urokinase-type plasminogen activator (125I-rh-sc-uPA). Methods: 125I-rh-su-uPA was prepared by Iodogen method and was purified by Saphacryl HR S-200. The radio-chemical purity was measured by reverse phase high performance liquid chromatography (RP-HPLC). Biological activity of labelled protein was measured by thrombolytic activity on fibrin plate. Results: The identification of 125I-rh-sc-uPA revealed that it was a 94.4% radio-chemically purified thrombolytic active protein. The AUC of radioactivity gradients in tissues and other specimens were as follows: kidney>urine>plasma>liver>spleen>adrenal gland>bone marrow>heart>urinary bladder>lungs>gonad>small intestinal wall>fat>lymph node>gall bladder>thymus gland>intestinal content>muscle>brain>feces in colon. Conclusion: The highest TCA precipitated radioactivity was found in plasma following I.V. of 125I-rh-u-PA, which might be favorable for the drug action. The main excretion route was urinary system

  16. The diagnostic value of soluble urokinase plasminogen activator receptor compared with C-reactive protein and procalcitonin in children with febrile neutropenia.

    Sirinoglu, Melis; Soysal, Ahmet; Karaaslan, Ayşe; Kepenekli Kadayifci, Eda; Cinel, Ismail; Koç, Ahmet; Tokuç, Gülnur; Yaman, Ali; Haklar, Goncagül; Şirikçi, Önder; Turan, Serap; Altınkanat Gelmez, Gülşen; Söyletir, Güner; Bakır, Mustafa

    2016-04-01

    The aim of the present study was to determine the diagnostic value of soluble urokinase plasminogen activator receptor (suPAR) in pediatric patients with febrile neutropenia. A prospective case-control study was performed. Patients included 29 children with febrile neutropenia (FN) and 27 control subjects without any infection or immunosuppressive condition. Blood samples were obtained on the day of admission and on the 4th to 7th days of the hospital stay. The median (minimum-maximum) serum levels of suPAR obtained on the first day of the admission were 2.08 (0.93-9.42) and 2.22 (1.08-5.13) ng/mL for the FN group and the control group, respectively. The median serum levels of suPAR in the FN and control groups were not significantly different (P = .053). The mean serum suPAR level was significantly higher in nonsurvivors than in survivors in the FN group (P < .05). In the FN group, the area under the receiver operating characteristics curve (AUCROC) for suPAR was 0.546, but no optimum cutoff value, sensitivity, specificity, negative predictive value (NPV), or positive predictive value (PPV) was obtained. We conclude that suPAR is not useful as a diagnostic biomarker in children with febrile neutropenia; however, persistent high serum suPAR level may predict mortality in FN in children. PMID:27057782

  17. Extracellular Matrix Biomarker, Fibulin-1, Is Closely Related to NT-proBNP and Soluble Urokinase Plasminogen Activator Receptor in Patients with Aortic Valve Stenosis (The SEAS Study)

    Kruger, Ruan; Rasmussen, Lars M; Argraves, William S;

    2014-01-01

    BACKGROUND: Fibulin-1, a circulating extracellular matrix glycoprotein, has been associated with arterial disease and elevated N-terminal prohormone B-type natriuretic peptide (NT-proBNP) in diabetes. Soluble urokinase plasminogen activator receptor (suPAR), a marker of inflammation, has been...... associated with subclinical atherosclerosis. Therefore, we aimed to explore the interplay between these biomarkers and mild to moderate aortic valve stenosis (AS). METHODS: In 374 patients with mild to moderate AS, we investigated the relationship of fibulin-1 with NT-proBNP, levels of suPAR and the degree...... of AS at baseline and after one and four years of treatment with Simvastatin 40 mg and Ezetimibe 10 mg or placebo. RESULTS: During treatment, fibulin-1 became more closely associated with NT-proBNP (βyear0 = 0.10, p = 0.08, βyear1 = 0.16, p = 0.005, βyear4 = 0.22, p

  18. TISSUE INHIBITOR OF METALLOPROTEINASE 1, MATRIX METALLOPROTEINASE 9, ALPHA-1 ANTITRYPSIN, METALLOTHIONEIN AND UROKINASE TYPE PLASMINOGEN ACTIVATOR RECEPTOR IN SKIN BIOPSIES FROM PATIENTS AFFECTED BY AUTOIMMUNE BLISTERING DISEASES

    Ana Maria Abreu Velez

    2013-07-01

    Full Text Available Introduction: Proteinases and proteinase inhibitors have been described to play a role in autoimmune skin blistering diseases. We studied skin lesional biopsies from patients affected by several autoimmune skin blistering diseases for proteinases and proteinase inhibitors. Methods: We utilized immunohistochemistry to evaluate biopsies for alpha-1-antitrypsin, human matrix metalloproteinase 9 (MMP9, human tissue inhibitor of metalloproteinases 1 (TIMP-1, metallothionein and urokinase type plasminogen activator receptor (uPAR. We tested 30 patients affected by endemic pemphigus, 30 controls from the endemic area, and 15 normal controls. We also tested 30 biopsies from patients with bullous pemphigoid (BP, 20 with pemphigus vulgaris (PV, 8 with pemphigus foliaceus, and 14 with dermatitis herpetiformis (DH. Results: Contrary to findings in the current literature, most autoimmune skin blistering disease biopsies were negative for uPAR and MMP9. Only some chronic patients with El Bagre-EPF were positive to MMP9 in the dermis, in proximity to telocytes. TIMP-1 and metallothionein were positive in half of the biopsies from BP patients at the basement membrane of the skin, within several skin appendices, in areas of dermal blood vessel inflammation and within dermal mesenchymal-epithelial cell junctions.

  19. Synergies between nonproliferation regimes: A pragmatic approach

    Full text: With the recent progress in establishing international nonproliferation regimes, the question of synergies between different verification and monitoring regimes is becoming more acute. Three multilateral and universal nonproliferation organisations covering safeguards on civil nuclear materials, nuclear testing, and chemical weapons are up and running. A regime on biological weapons is under negotiation. Several regional organisations concerned with monitoring nonproliferation commitments in the nuclear field are in place; others are being established. Past discussions on synergies between these regimes have suffered from being too far-reaching. These discussions often have not reflected adequately the political difficulties of cooperation between regimes with different membership, scope and institutional set-up. This paper takes a pragmatic look at exploiting synergies and identifies some potential and real overlaps in the work between different verification regimes. It argues for a bottom-up approach and identifies building blocks for collaboration between verification regimes. By realising such, more limited potential for cooperation, the ground could be prepared for exploiting other synergies between these regimes. (author)

  20. Capacitance densitometer for flow regime identification

    Shipp, Jr., Roy L.

    1978-01-01

    This invention relates to a capacitance densitometer for determining the flow regime of a two-phase flow system. A two-element capacitance densitometer is used in conjunction with a conventional single-beam gamma densitometer to unambiguously identify the prevailing flow regime and the average density of a flowing fluid.

  1. LOW DOSE MAGNESIUM SULPHATE REGIME FOR ECLAMPSIA

    Bangal V

    2009-09-01

    Full Text Available Pre- eclampsia is one of the commonest medical complications seen during pregnancy. It contributes significantly to maternal and perinatal morbidity and mortality. Dr.J.A.Pritchard in 1955, introduced magnesium sulphate for control of convulsions in eclampsia and is used worldwide. Considering the low body mass index of indian women, a low dose magnesium sulphate regime has been introduced by some authors. Present study was carried out at tertiary care centre in rural area. Fifty cases of eclampsia were randomly selected to find out the efficacy of low dose magnesium sulphate regime to control eclamptic convulsions. Maternal and perinatal outcome and magnesium toxicity were analyzed. It was observed that 86% cases responded to initial intravenous dose of 4 grams of 20% magnesium sulphate . Eight percent cases, who got recurrence of convulsion, were controlled by additional 2 grams of 20% magnesium sulphate. Six percent cases required shifting to standard Pritchard regime, as they did not respond to low dose magnesium sulphate regime. The average total dose of magnesium sulphate required for control of convulsions was 20 grams ie. 54.4% less than that of standard Pritchard regime. The maternal and perinatal morbidity and mortality in the present study werecomparable to those of standard Pritchard regime. The study did not find a single case of magnesium related toxicity with low dose magnesium sulphate regime. Low dose magnesium sulphate regime was found to be safe and effective in eclampsia.

  2. Explaining the Transition Between Exchange Rate Regimes

    Masson, Paul; RUGE-MURCIA, Francisco J.

    2003-01-01

    This paper studies the transition between exchange rate regimes using a Markov chain model with time-varying transition probabilities. The probabilities are parameterized as nonlinear functions of variables suggested by the currency crisis and optimal currency area literature. Results using annual data indicate that inflation, and to a lesser extent, output growth and trade openness help explain the exchange rate regime transition dynamics.

  3. LEGAL MATRIMONIAL REGIME IN B&H

    Boris Krešić

    2011-12-01

    Full Text Available Matrimonial regime between spouses or between extramarital partners, and between parents and children is regulated by the Family Law Act of Bosnia and Herzegovina Federation, hereinafter FLA B&HF (SG FBiH 35/05, 41/05, Family Law Act of the Republic of Srpska, hereinafter FLA RS (SG RS”54/02, 41/08 and the Family Law Act of Brčko District, hereinafter FLA BD (SG RS, 66/07. Legal rules used for the regulation of the matrimonial regime between spouses, as well as between spouses and third parties make matrimonial regime (Ponjavić, 2005, p. 361. Matrimonial regime between spouses in family legislation in Bosnia and Herzegovina (B&H is regulated in two following ways: as legal matrimonial regime and as contract matrimonial regime. Legal regime is the one which applies on spouses if not arranged otherwise prior to contracting marriage or during marriage. In this paper the author indicates the differences between the legal matrimonial regimes of the two entities as well as those between the entities and Brčko District of Bosnia and Herzegovina.

  4. Strengthening the nuclear non-proliferation regime

    Although the nuclear non-proliferation regime has enjoyed considerable success, today the regime has never been under greater threat. Three states have challenged the objectives of the NPT, and there is a technology challenge - the spread of centrifuge enrichment technology and know-how. A major issue confronting the international community is, how to deal with a determined proliferator? Despite this gloomy scenario, however, the non-proliferation regime has considerable strengths - many of which can be developed further. The regime comprises complex interacting and mutually reinforcing elements. At its centre is the NPT - with IAEA safeguards as the Treaty's verification mechanism. Important complementary elements include: restraint in the supply and the acquisition of sensitive technologies; multilateral regimes such as the CTBT and proposed FMCT; various regional and bilateral regimes; the range of security and arms control arrangements outside the nuclear area (including other WMD regimes); and the development of proliferation-resistant technologies. Especially important are political incentives and sanctions in support of non-proliferation objectives. This paper outlines some of the key issues facing the non-proliferation regime

  5. The Association between HbA1c, Fasting Glucose, 1-Hour Glucose and 2-Hour Glucose during an Oral Glucose Tolerance Test and Cardiovascular Disease in Individuals with Elevated Risk for Diabetes

    Lind, Marcus; Tuomilehto, Jaakko; Uusitupa, Matti; Nerman, Olle; Eriksson, Johan; Ilanne-Parikka, Pirjo; Keinänen-Kiukaanniemi, Sirkka; Peltonen, Markku; Pivodic, Aldina; Lindström, Jaana

    2014-01-01

    Objective To determine the association between HbA1c, fasting plasma glucose (FPG), 1-hour (1 hPG) and 2-hour (2 hPG) glucose after an oral glucose tolerance test (OGTT) and cardiovascular disease in individuals with elevated risk for diabetes. Design We studied the relationship between baseline, updated mean and updated (last) value of HbA1c, FPG, 1 hPG and 2 hPG after an oral 75 g glucose tolerance test (OGTT) and acute CVD events in 504 individuals with impaired glucose tolerance (IGT) at baseline enrolled in the Finnish Diabetes Prevention Study. Setting Follow-up of clinical trial. Participants 504 individuals with IGT were followed with yearly evaluations with OGTT, FPG and HbA1c. Main Outcome Measure Relative risk of CVD. Results Over a median follow-up of 9.0 years 34 (6.7%) participants had a CVD event, which increased to 52 (10.3%) over a median follow-up of 13.0 years when including events that occurred among participants following a diagnosis of diabetes. Updated mean HbA1c, 1 hPG and 2 hPG, HR per 1 unit SD of 1.57 (95% CI 1.16 to 2.11), p = 0.0032, 1.51 (1.03 to 2.23), p = 0.036 and 1.60 (1.10 to 2.34), p = 0.014, respectively, but not FPG (p = 0.11), were related to CVD. In analyses of the last value prior to the CVD event the same three glycaemic measurements were associated with the CVD events, with HRs per 1 unit SD of 1.45 (1.06 to 1.98), p = 0.020, 1.55 (1.04 to 2.29), p = 0.030 and 2.19 (1.51 to 3.18), pdiabetes onset updated 2 hPG (p = 0.003) but not updated mean HbA1c (p = 0.08) was related to CVD. Conclusions and Relevance Current 2 hPG level in people with IGT is associated with increased risk of CVD. This supports its use in screening for prediabetes and monitoring glycaemic levels of people with prediabetes. PMID:25285769

  6. Feasibility of a dual regime gyrotron

    The design concept of a 42/84 GHz, 500 kW, CW, dual-regime gyrotron for ECRH of plasma in an experimental Tokamak will be presented in this paper. Operation at 42 GHz is fundamental where as that in 84 GHz will be second harmonic so that a similar guidance system will be retained for dual regime operation. In this paper, the mode competition and mode selection procedures are presented for such a dual regime operation. Cold cavity design and self-consistent calculations will be carried out for power and efficiencies. (author)

  7. Framing of regimes and transition strategies

    Jensen, Jens Stissing

    2012-01-01

    This article suggests that transition strategies are always formulated in the context of specific representations of the regime and the challenges it faces. It is argued that the framing of a regime affects the envisioning of transition strategies. An analysis of the current development agenda for...... the housing construction sector in Denmark reveals the relevance and impacts of different regime framings. It is proposed that the ability to cope with framing issues as situated and political processes is at the core of the governance of transitions....

  8. The nuclear marketplace and the nonproliferation regime

    The development and acceptance of the international nonproliferation regime has been one of the most remarkable achievements of the postwar era. The nonproliferation regime has developed incrementally over time, often in spite of the inability of the two superpowers to come to grips with their own arms race. States otherwise zealous to protect their sovereignty have accepted international constraints on that same sovereignty where nuclear power is concerned. The challenge to the nonproliferation regime, then, is both serious and multifaceted. There is no single or overriding source of that regime's problems, nor is there a single solution. Rolling back the NNPA and ''letting the US nuclear industry compete'' make for a good slogan but will not change the seriousness of the nonproliferation challenge

  9. The Two Regimes of Postwar Shipping

    Iversen, Martin Jes; Tenold, Stig

    2014-01-01

    the bargaining that accompanied the shift from the national regime to the competitive regime. Specifically, we show that the new regime primarily accommodated the interests of private actors such as shipping companies, rather than the interests of the authorities and the trade unions.......The aim of this article is to illustrate the most important changes in the regulatory framework of the shipping sector from the 1960s to 2010, and to analyse the basis for, and effects of, these changes. In order to explain how the transformation has occurred, we use two traditional maritime...... nations—Denmark and Norway—as case studies. First, we introduce the two regimes of Danish and Norwegian shipping: ‘the national regime’ from the early 1960s to the mid-1970s; and ‘the competitive regime’, which was fully established by the middle of the 1990s and still persists. Then, we briefly sketch...

  10. FLOW REGIMES BELOW AERATORS FOR DISCHARGE TUNNELS

    MA Fei; WU Jian-hua

    2012-01-01

    The flow regimes below an aerator influence directly the air entrainment and the cavitation damage control.Based on the theoretical considerations,the experiments of the aerator for a discharge tunnel were conducted,and the relationships between the flow regime and hydraulic and geometric parameters were investigated.The results showed that,there are two kinds of threshold values for the flow regime conversions.One is Fr1-2 standing for the conversion from the fully filled cavity to the partially filled cavity,and the other is Fr2-3 which shows the change from the partially filled cavity to the net air cavity.Two empirical expressions were obtained for the conversions of the flow regimes,which can be used in the designs of the aerators.

  11. Earth Regime Network Evolution Study (ERNESt)

    Menrad, Bob

    2016-01-01

    Speaker and Presenter at the Lincoln Laboratory Communications Workshop on April 5, 2016 at the Massachusetts Institute of Technology Lincoln Laboratory in Lexington, MA. A visual presentation titled Earth Regimes Network Evolution Study (ERNESt).

  12. The international climate regime: towards consolidation collapse

    This article deals with the different modalities that exist to manage a problem of collective action in the field of climate negotiation. It uses two concepts of the International Political Economy (IPE): the concept of International Regime (IR) and the concept of Hegemony and / or Leadership. The course the international negotiation has taken between 1992 (Rio Convention) and march 2001 (the US rejection of the Kyoto Protocol of 1997) leads us, first, to question the conditions of existence as well as the viability of a non-hegemonic International Regime (Part One). Then, we discuss the perspectives for the 'post - Kyoto' era. After having examined the preferences of the three most active actors in the negotiation (USA, Europe, G77 + China) combined with the leadership capacities they possess, we identify three scenarios for the future: i) anarchy, ii) an international regime under the American hegemony, iii) an international regime under the European leadership (Part Two). (author)

  13. What is the economy of Ancien Regime?

    Jean-Yves Grenier

    2012-01-01

    The aim of this article is to describe the main features of the Ancien Regime economy and develop a “political economy” of European societies, particularly the French, during the central period of modernity (XVII-XVIII centuries

  14. Molecular motors in conservative and dissipative regimes

    Perez-Carrasco, R.; Sancho, J. M.

    2011-10-01

    We present a theoretical study of a rotatory molecular motor under a conservative torque regime. We show that conservative and dissipative regimes present a different observable phenomenology. Our approach starts with a preliminary deterministic calculation of the motor cycle, which is complemented with stochastic simulations of a Langevin equation under a flashing ratchet potential. Finally, by using parameter values obtained from independent experimental information, our theoretical predictions are compared with experimental data of the F1-ATPase motor of the Bacillus PS3.

  15. Patent regimes and the commodification of knowledge

    Coriat, Benjamin; Weinstein, Olivier

    2011-01-01

    This paper analyses the evolution of the intellectual property regime (IPR), and more precisely the patent regime, in the USA since the 19th century. To do so, we consider intellectual property laws within the context of wider changes in capitalism, focusing on two main historical phases: firstly, the period covering the formation and development of 'corporate capitalism' dominated by large corporations and then the new phase, which opened up in the 1980s, marked by the rise to power of finan...

  16. Regime shifts and inflation uncertainty in Peru

    Paúl Castillo; Alberto Humala; Vicente Tuesta

    2012-01-01

    The link between inflation and inflation uncertainty is evaluated using Peruvian data, in a context of changing monetary policies because of regime shifts. A Markov regime-switching heteroskedasticity model that includes unobserved components is used. The model shows how periods of high (low) inflation accompany periods of high (low) short- and long-run uncertainty in inflation. The results of the model also illustrate how, during the recent period of price stability in Peru, both permanent a...

  17. Inflation in the warm and cold regimes

    Berera, Arjun

    2006-01-01

    It is now understood that inflation dynamics comes in two forms, isentropic or cold inflation and nonisentropic or warm inflation. In the former, inflation occurs without radiation production, whereas in the latter both radiation production and inflation occur concurrently. Recent, detailed, quantum field theory calculations have shown that many generic inflation models, including hybrid inflation, which were believed only to have cold inflation regimes, in fact have regimes of both warm and ...

  18. Portfolio Selection with Jumps under Regime Switching

    Lin Zhao

    2010-01-01

    Full Text Available We investigate a continuous-time version of the mean-variance portfolio selection model with jumps under regime switching. The portfolio selection is proposed and analyzed for a market consisting of one bank account and multiple stocks. The random regime switching is assumed to be independent of the underlying Brownian motion and jump processes. A Markov chain modulated diffusion formulation is employed to model the problem.

  19. Forest damage and snow avalanche flow regime

    T. Feistl; Bebi, P.; M. Christen; Margreth, S.; Diefenbach, L.; P. Bartelt

    2015-01-01

    Snow avalanches break, uproot and overturn trees causing damage to forests. The extent of forest damage provides useful information on avalanche frequency and intensity. However, impact forces depend on avalanche flow regime. In this paper, we define avalanche loading cases representing four different avalanche flow regimes: powder, intermittent, dry and wet. Using a numerical model that simulates both powder and wet snow avalanches, we study documented events with forest ...

  20. Developmental Regimes in Africa synthesis report

    Booth, D.; Dietz, A.J.; Golooba-Mutebi, F.; Fuady, A.H.; Henley, D; Kelsall, T.; Leliveld, A.H.M.; Donge, van, J.K.

    2015-01-01

    Many African countries have experienced sustained economic growth, but few have achieved the type of structural change, driven by rising productivity, that has transformed mass living standards in parts of Asia. In the Developmental Regimes in Africa Synthesis Report, editor David Booth examines how DRA research has shed new light on how developmental regimes might emerge and be sustained in Africa in the 21st century. He outlines a concept with defining features at three levels: policy conte...

  1. Improving the taxation regime for electric power

    In Norway, the present taxation regime for electric power is very complex. The power companies are currently charged with ordinary tax on profits, tax on economic rent, tax on natural resources and land tax. In addition there are the rules about licence fees, yield of power due to concession conditions, and reversion. The Norwegian Electricity Industry Association (EBL), assisted by a firm of lawyers, has proposed an improvement over the current taxation regime

  2. Regime Diagrams for K-Theory Dispersion

    Smith, Ronald B.

    2011-06-01

    In atmospheric dispersion, the "non-Gaussian" effects of gravitational settling, the vertical gradient in diffusivity and the surface deposition do not enter uniformly but rather break up parameter space into several discrete regimes. Here, we describe regime diagrams that are constructed for K-theory dispersion of effluent from a surface line source in unsheared inhomogeneous turbulence, using a previously derived Fourier-Hankel method. This K-theory formulation differs from the traditional one by keeping a non-zero diffusivity at the ground. This change allows for turbulent exchange between the canopy and the atmosphere and allows new natural length scales to emerge. The axes on the regime diagrams are non-dimensional distance defined as the ratio of downwind distance to the characteristic length scale for each effect. For each value of the ratio of settling speed to the K gradient, two to four regimes are found. Concentration formulae are given for each regime. The regime diagrams allow real dispersion problems to be categorized and the validity of end-state concentration formulae to be judged.

  3. The receptor for urokinase-plasminogen activator (uPAR) controls plasticity of cancer cell movement in mesenchymal and amoeboid migration style.

    Margheri, Francesca; Luciani, Cristina; Taddei, Maria Letizia; Giannoni, Elisa; Laurenzana, Anna; Biagioni, Alessio; Chillà, Anastasia; Chiarugi, Paola; Fibbi, Gabriella; Del Rosso, Mario

    2014-03-30

    The receptor for the urokinase plasminogen activator (uPAR) is up-regulated in malignant tumors. Historically the function of uPAR in cancer cell invasion is strictly related to its property to promote uPA-dependent proteolysis of extracellular matrix and to open a path to malignant cells. These features are typical of mesenchymal motility. Here we show that the full-length form of uPAR is required when prostate and melanoma cancer cells convert their migration style from the "path generating" mesenchymal to the "path finding" amoeboid one, thus conferring a plasticity to tumor cell invasiveness across three-dimensional matrices. Indeed, in response to a protease inhibitors-rich milieu, prostate and melanoma cells activated an amoeboid invasion program connoted by retraction of cell protrusions, RhoA-mediated rounding of the cell body, formation of a cortical ring of actin and a reduction of Rac-1 activation. While the mesenchymal movement was reduced upon silencing of uPAR expression, the amoeboid one was almost completely abolished, in parallel with a deregulation of small Rho-GTPases activity. In melanoma and prostate cancer cells we have shown uPAR colocalization with β1/β3 integrins and actin cytoskeleton, as well integrins-actin co-localization under both mesenchymal and amoeboid conditions. Such co-localizations were lost upon treatment of cells with a peptide that inhibits uPAR-integrin interactions. Similarly to uPAR silencing, the peptide reduced mesenchymal invasion and almost abolished the amoeboid one. These results indicate that full-length uPAR bridges the mesenchymal and amoeboid style of movement by an inward-oriented activity based on its property to promote integrin-actin interactions and the following cytoskeleton assembly. PMID:24681666

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

    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.

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

    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.

  6. Soluble Urokinase Receptor Levels Are Correlated with Focal Segmental Glomerulosclerosis Lesions in IgA Nephropathy: A Cohort Study from China.

    Shui-Ming Guo

    Full Text Available Soluble urokinase receptor (suPAR may be involved in the pathological mechanisms of focal segmental glomerulosclerosis (FSGS changes. However, it remains unclear whether suPAR is correlated with the FSGS-like lesions in IgA nephropathy (IgAN.We measured the plasma suPAR levels in 138 patients with IgAN, and then their clinical and pathological relationships were analyzed.We found that the plasma suPAR levels were significantly correlated with age and renal function by both univariate and multivariate analysis in our IgAN patient cohort. Female had higher plasma suPAR levels and no significant correlation was observed between plasma suPAR levels and 24-h urine protein and highly sensitive C-reaction protein with multivariate analysis. In our cohort, sixty of these IgAN patients could be diagnosed with a type of FSGS lesions. The plasma suPAR levels were higher in the IgAN patients with FSGS lesions than in the IgAN patients without FSGS lesions by univariate (P < 0.0001 and multivariate (P < 0.001 analysis adjusting for other predictor variables, which might be helpful to differentiate the pathological changes with and without FSGS lesions. And the optimal cutoff value was 1806 pg/ml in this study. The plasma suPAR concentrations were also associated with the degree of tubular atrophy/interstitial fibrosis in both univariate and multivariate analysis. In multivariate analysis, the plasma suPAR levels were correlated with the percentage of crescents, not global sclerosis and arterial lesions.Our study suggested that the plasma suPAR levels were associated with age, gender, renal function, the degree of tubular atrophy/interstitial fibrosis and the percentage of crescent formation. The plasma suPAR might be a potential predictor for the presence of FSGS pathological lesions in Chinese patients with IgAN.

  7. Staurosporine induces ganglion cell differentiation in part by stimulating urokinase-type plasminogen activator expression and activation in the developing chick retina

    Highlights: ► Staurosporine mediates stimulation of RGC differentiation in vitro cultured retinal neuroblasts. ► Staurosporine mediates uPA activation during RGC differentiation in vitro. ► Inhibition of uPA blocks the staurosporine mediated RGC differentiation both in vitro and in ovo. ► Thus, uPA may play a role in the staurosporine-mediated stimulation of RGC differentiation. -- Abstract: Here, we investigated whether staurosporine-mediated urokinase-type plasminogen activator (uPA) activation is involved in retinal ganglion cell (RGC) differentiation. Retinal cells were isolated from developing chick retinas at embryonic day 6 (E6). Relatively few control cells grown in serum-free medium started to form processes by 12 h. In contrast, staurosporine-treated cells had processes within 3 h, and processes were evident at 8 h. Immunofluorescence staining showed that Tuj-1-positive cells with shorter neurites could be detected in control cultures at 18 h, whereas numerous Tuj-1 positive ganglion cells with longer neuritic extensions were seen in staurosporine-treated cultures. BrdU-positive proliferating cells were more numerous in control cultures than in staurosporine-treated cultures, and the BrdU staining was not detected in post-mitotic Tuj-1 positive ganglion cells. Western blotting of cell lysates showed that staurosporine induced high levels of the active form of uPA. The staurosporine-induced uPA signal was localized predominantly in the soma, neurites and axons of Tuj-1-positive ganglion cells. Amiloride, an inhibitor of uPA, markedly reduced staurosporine-induced Tuj-1 staining, neurite length, neurite number, and uPA staining versus controls. In developing retinas in ovo, amiloride administration remarkably reduced the staurosporine-induced uPA staining and RGC differentiation. Taken together, our in vitro and in vivo data collectively indicate that uPA plays a role in the staurosporine-mediated stimulation of RGC differentiation.

  8. Elevated urinary levels of urokinase-type plasminogen activator receptor (uPAR) in pancreatic ductal adenocarcinoma identify a clinically high-risk group

    The urokinase plasminogen activator receptor is highly expressed and its gene is amplified in about 50% of pancreatic ductal adenocarcinomas; this last feature is associated with worse prognosis. It is unknown whether the level of its soluble form (suPAR) in urine may be a diagnostic-prognostic marker in these patients. The urinary level of suPAR was measured in 146 patients, 94 pancreatic ductal adenocarcinoma and 52 chronic pancreatitis. Urine from 104 healthy subjects with similar age and gender distribution served as controls. suPAR levels were normalized with creatinine levels (suPAR/creatinine, ng/mg) to remove urine dilution effect. Urinary suPAR/creatinine values of pancreatic ductal adenocarcinoma patients were significantly higher (median 9.8; 25th-75th percentiles 5.3-20.7) than those of either healthy donors (median 0; 0-0.5) or chronic pancreatitis patients (median 2.7; 0.9-4.7). The distribution of values among cancer patients was widespread and asymmetric, 53% subjects having values beyond the 95th percentile of healthy donors. The values of suPAR/creatinine did not correlate with tumour stage, Ca19-9 or CEA levels. Higher values correlated with poor prognosis among non-resected patients at univariate analysis; multivariate Cox regression identified high urinary suPAR/creatinine as an independent predictor of poor survival among all cancer patients (odds ratio 2.10, p = 0.0023), together with tumour stage (stage III odds ratio 2.65, p = 0.0017; stage IV odds ratio 4.61, p < 0.0001) and female gender (odds ratio 1.85, p = 0.01). A high urinary suPAR/creatinine ratio represents a useful marker for the identification of a subset of patients with poorer outcome

  9. Elevated urinary levels of urokinase-type plasminogen activator receptor (uPAR in pancreatic ductal adenocarcinoma identify a clinically high-risk group

    Brocco Giorgio

    2011-10-01

    Full Text Available Abstract Background The urokinase plasminogen activator receptor is highly expressed and its gene is amplified in about 50% of pancreatic ductal adenocarcinomas; this last feature is associated with worse prognosis. It is unknown whether the level of its soluble form (suPAR in urine may be a diagnostic-prognostic marker in these patients. Methods The urinary level of suPAR was measured in 146 patients, 94 pancreatic ductal adenocarcinoma and 52 chronic pancreatitis. Urine from 104 healthy subjects with similar age and gender distribution served as controls. suPAR levels were normalized with creatinine levels (suPAR/creatinine, ng/mg to remove urine dilution effect. Results Urinary suPAR/creatinine values of pancreatic ductal adenocarcinoma patients were significantly higher (median 9.8; 25th-75th percentiles 5.3-20.7 than those of either healthy donors (median 0; 0-0.5 or chronic pancreatitis patients (median 2.7; 0.9-4.7. The distribution of values among cancer patients was widespread and asymmetric, 53% subjects having values beyond the 95th percentile of healthy donors. The values of suPAR/creatinine did not correlate with tumour stage, Ca19-9 or CEA levels. Higher values correlated with poor prognosis among non-resected patients at univariate analysis; multivariate Cox regression identified high urinary suPAR/creatinine as an independent predictor of poor survival among all cancer patients (odds ratio 2.10, p = 0.0023, together with tumour stage (stage III odds ratio 2.65, p = 0.0017; stage IV odds ratio 4.61, p Conclusions A high urinary suPAR/creatinine ratio represents a useful marker for the identification of a subset of patients with poorer outcome.

  10. Effect of vacuum-assisted closure on the expression of urokinase-type plaminogen activator and urokinase-type plasminogen activator receptor in acute and chronic wounds healing%封闭负压引流技术对创面愈合过程纤溶酶原激活剂级联表达的影响

    李跃军; 曹大勇; 陈绍宗

    2006-01-01

    目的研究封闭负压引流技术对急慢性创面纤溶酶原激活剂(plasminogen activator,PA)级联中尿激酶型纤溶酶激活剂(urokinase-type plaminogen activator,uPA)和尿激酶型纤溶酶激活剂受体(urokinase-type plasminogen activator receptor,uPA)表达的影响.方法雄性小家猪5头,背部两侧形成急性创面,分为实验组和对照组,仅实验组动物接受封闭负压引流治疗.分别在治疗前和治疗后第1、3、6、9、12、18、25天于创缘切取标本,用兔抗人uPA和uPAR单克隆抗体按ABC程序进行免疫组织化学染色,并计算uPAA和uPAR的标记指数.人慢性创面6例,清创后进行持续封闭负压引流治疗,在治疗后第1、3、5、7天采集创面渗出液,并用ELISA法检测渗出液中uPA和uPAR的含量.结果猪急性创面在封闭负压引流治疗后uPA和uPAR均增加,在第3天达到高峰,然后急速下降,但实验组的基因表达量和染色强度均显著高于对照组.6例人慢性创面进行治疗前uPA和uPAR表达较多,随着治疗时间的延长而逐渐减少.结论封闭负压引流治疗既能上调急性创面伤口周围的表皮角质形成细胞的uPA和uPAR表达,使之迅速增殖迁移;又能通过抑制慢性创面uPA和uPAR表达,从而减少细胞外基质的降解.