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Sample records for growth factor-mediated urokinase

  1. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Nandy, Debashis; Mukhopadhyay, Debabrata, E-mail: mukhopadhyay.debabrata@mayo.edu [Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, 200 First Street SW, Guggenheim 1321C, Rochester, MN 55905 (United States)

    2011-02-24

    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed.

  2. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    International Nuclear Information System (INIS)

    Nandy, Debashis; Mukhopadhyay, Debabrata

    2011-01-01

    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed

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

    International Nuclear Information System (INIS)

    Patecki, Margret; Schaewen, Markus von; Tkachuk, Sergey; Jerke, Uwe; Dietz, Rainer; Dumler, Inna; Kusch, Angelika

    2007-01-01

    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. TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition.

    Science.gov (United States)

    Zhang, Heng; Liu, Chen-Ying; Zha, Zheng-Yu; Zhao, Bin; Yao, Jun; Zhao, Shimin; Xiong, Yue; Lei, Qun-Ying; Guan, Kun-Liang

    2009-05-15

    The TAZ transcription co-activator has been shown to promote cell proliferation and to induce epithelial-mesenchymal transition. Recently we have demonstrated that TAZ is phosphorylated and inhibited by the Hippo tumor suppressor pathway, which is altered in human cancer. The mechanism of TAZ-mediated transcription is unclear. We demonstrate here that TEAD is a key downstream transcription factor mediating the function of TAZ. Disruption of TEAD-TAZ binding or silencing of TEAD expression blocked the function of TAZ to promote cell proliferation and to induce epithelial-mesenchymal transition, demonstrating TEAD as a key downstream effector of TAZ. We also identified CTGF, a gene that regulates cell adhesion, proliferation, and migration, as a direct target of TAZ and TEAD. Our study establishes a functional partnership between TAZ and TEAD under negative regulation by the Hippo signaling pathway.

  5. Vascular endothelial growth factor mediates ceramide 1-phosphate-stimulated macrophage proliferation.

    Science.gov (United States)

    Ouro, Alberto; Arana, Lide; Riazy, Maziar; Zhang, Peng; Gomez-Larrauri, Ana; Steinbrecher, Urs; Duronio, Vincent; Gomez-Muñoz, Antonio

    2017-12-15

    The bioactive sphingolipid ceramide 1-phosphate (C1P) regulates cell division in a variety of cell types including macrophages. However, the mechanisms involved in this action are not completely understood. In the present work we show that C1P stimulates the release of vascular endothelial growth factor (VEGF) in RAW264.7 macrophages, and that this growth factor is essential for stimulation of cell proliferation by C1P. The stimulation of VEGF release was dependent upon activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB-1 also known as Akt-1), and mitogen-activated protein kinase-kinase (MEK)/extracellularly regulated kinase-2 (ERK-2) pathways, as inhibition of these kinases with selective pharmacological inhibitors or with specific gene silencing siRNA, abrogated VEGF release. A key observation was that sequestration of VEGF with a neutralizing antibody, or treatment with VEGF siRNA abolished C1P-stimulated macrophage growth. Also, inhibition of the pathways involved in C1P-stimulated VEGF release inhibited the stimulation of macrophage growth by C1P. Moreover, blockade of VEGF receptor-2 (VEGFR-2), which is the primary receptor for VEGF, with the pharmacological inhibitor DMH4, or with specific VEGFR-2 siRNA, substantially inhibited C1P-stimulated cell growth. It can be concluded that stimulation of VEGF release is a key factor in the promotion of macrophage proliferation by C1P. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Functional Development of the Human Gastrointestinal Tract: Hormone- and Growth Factor-Mediated Regulatory Mechanisms

    Directory of Open Access Journals (Sweden)

    Daniel Ménard

    2004-01-01

    Full Text Available The present review focuses on the control of gastrointestinal (GI tract development. The first section addresses the differences in general mechanisms of GI development in humans versus rodents, highlighting that morphogenesis of specific digestive organs and the differentiation of digestive epithelia occur not only at different stages of ontogeny but also at different rates. The second section provides an overview of studies from the author's laboratory at the Université de Sherbrooke pertaining to the development of the human fetal small intestine and colon. While both segments share similar morphological and functional characteristics, they are nevertheless modulated by distinct regulatory mechanisms. Using the organ culture approach, the author and colleagues were able to establish that hormones and growth factors, such as glucocorticoids, epidermal growth factor, insulin and keratinocyte growth factor, not only exert differential effects within these two segments, they can also trigger opposite responses in comparison with animal models. In the third section, emphasis is placed on the functional development of human fetal stomach and its various epithelial cell types; in particular, the glandular chief cells responsible for the synthesis and secretion of gastric enzymes such as pepsinogen-5 and gastric lipase. Bearing in mind that limitations of available cell models have, until now, greatly impeded the comprehension of molecular mechanisms regulating human gastric epithelial cell functions, the last section focuses on new human gastric epithelial cell models recently developed in the author's laboratory. These models comprise a novel primary culture system of human fetal gastric epithelium including, for the first time, functional chief cells, and human gastric epithelium cell lines cloned from the parental NCI-N87 strain. These new cells lines could serve important applications in the study of pathogenic action and epithelial

  7. Hepatocyte growth factor mediates mesenchymal stem cell–induced recovery in multiple sclerosis models.

    Science.gov (United States)

    Bai, Lianhua; Lennon, Donald P; Caplan, Arnold I; DeChant, Anne; Hecker, Jordan; Kranso, Janet; Zaremba, Anita; Miller, Robert H

    2012-06-01

    Mesenchymal stem cells (MSCs) have emerged as a potential therapy for a range of neural insults. In animal models of multiple sclerosis, an autoimmune disease that targets oligodendrocytes and myelin, treatment with human MSCs results in functional improvement that reflects both modulation of the immune response and myelin repair. Here we demonstrate that conditioned medium from human MSCs (MSC-CM) reduces functional deficits in mouse MOG35–55-induced experimental autoimmune encephalomyelitis (EAE) and promotes the development of oligodendrocytes and neurons. Functional assays identified hepatocyte growth factor (HGF) and its primary receptor cMet as critical in MSC-stimulated recovery in EAE, neural cell development and remyelination. Active MSC-CM contained HGF, and exogenously supplied HGF promoted recovery in EAE, whereas cMet and antibodies to HGF blocked the functional recovery mediated by HGF and MSC-CM. Systemic treatment with HGF markedly accelerated remyelination in lysolecithin-induced rat dorsal spinal cord lesions and in slice cultures. Together these data strongly implicate HGF in mediating MSC-stimulated functional recovery in animal models of multiple sclerosis.

  8. Copper reverses cardiomyocyte hypertrophy through vascular endothelial growth factor-mediated reduction in the cell size.

    Science.gov (United States)

    Zhou, Yang; Jiang, Youchun; Kang, Y James

    2008-07-01

    Previous studies have shown that dietary copper supplementation reversed heart hypertrophy induced by pressure overload in a mouse model. The present study was undertaken to understand the cellular basis of copper-induced regression of cardiac hypertrophy. Primary cultures of neonatal rat cardiomyocytes were treated with phenylephrine (PE) at a final concentration of 100 microM in cultures for 48 h to induce cellular hypertrophy. The hypertrophied cardiomyocytes were exposed to copper sulfate at a final concentration of 5 microM in cultures for additional 24 h. This copper treatment reduced the size of the hypertrophied cardiomyocytes, as measured by flow cytometry, protein content in cells, cell volume and cardiomyocyte hypertrophy markers including beta-myosin heavy chain protein, skeletal alpha-actin, and atrial natriuretic peptide. Cell cycle analysis and cell sorting of p-histone-3 labeled cardiomyocytes indicated that cell division was not involved in the copper-induced regression of cardiomyocyte hypertrophy. Copper also inhibited PE-induced apoptosis, determined by a TUNEL assay. Because copper stimulates vascular endothelial growth factor (VEGF) production through activation of hypoxia-inducible transcription factor, an anti-VEGF antibody at a final concentration of 2 ng/ml in cultures was used and shown to blunt copper-induced regression of cell hypertrophy. Conversely, VEGF alone at a final concentration of 0.2 microg/ml reversed cell hypertrophy as the same as copper did. This study demonstrates that both copper and VEGF reduce the size of hypertrophied cardiomyocytes, and copper regression of cardiac hypertrophy is VEGF-dependent.

  9. Fibroblast growth factor-mediated proliferation of central nervous system precursors depends on endogenous production of insulin-like growth factor I

    International Nuclear Information System (INIS)

    Drago, J.; Murphy, M.; Carroll, S.M.; Harvey, R.P.; Bartlett, P.F.

    1991-01-01

    Fibroblast growth factor stimulates proliferation and subsequent differentiation of precursor cells isolated from the neuroepithelium of embryonic day 10 mice in vitro. Here we show that fibroblast growth factor-induced proliferation is dependent on the presence of insulin-like growth factors (IGFs) and that IGF-I is endogenously produced by the neuroepithelial cells. Blocking of endogenous IGF-I activity with anti-IGF-I antibodies results in complete inhibition of fibroblast growth factor-mediated proliferation and in cell death. IGF-I alone acts as a survival agent. These observations correlate with the detection of transcripts for IGF-I and basic fibroblast growth factor in freshly isolated neuroepithelium and are consistent with an autocrine action of these factors in early brain development in vivo

  10. Overexpression of Heparin-Binding Epidermal Growth Factor-Like Growth Factor Mediates Liver Fibrosis in Transgenic Mice.

    Science.gov (United States)

    Guo, Yongze; Ding, Qian; Chen, Lei; Ji, Chenguang; Hao, Huiyao; Wang, Jia; Qi, Wei; Xie, Xiaoli; Ma, Junji; Li, Aidi; Jiang, Xiaoyu; Li, Xiaotian; Jiang, Huiqing

    2017-08-01

    The role of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in liver fibrosis is not clear and is sometimes even contradictory. To clarify this role, a HB-EGF transgenic (Tg) mouse model was, for the first time, used to evaluate the functions of HB-EGF in liver fibrosis. For the in vivo study, carbon tetrachloride injection and bile duct ligation treatment were used to induce liver fibrosis in HB-EGF Tg mice and wild-type (WT) mice, respectively. Primary hepatic satellite cells (HSCs) were isolated from HB-EGF Tg and WT mice for the in vitro study. Compared with the WT mice, HB-EGF Tg mice were shown to develop more severe liver fibrosis when treated with carbon tetrachloride or bile duct ligation, with increased matrix metalloproteinases 13 activity and enhanced expression of fibrogenic genes including α-smooth muscle actin and collagen I. HB-EGF gene transfer led to an increase in proliferation and a decrease in apoptosis in primary HSCs. The ERK signaling pathway was more highly activated in primary HSCs from HB-EGF Tg mice than in those from WT mice. Our investigation confirmed the profibrotic effect of HB-EGF on the liver using a Tg mouse model. This result may contribute to the elucidation of HB-EGF as a therapeutic target in liver fibrosis. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  11. Short-term myeloid growth factor mediated expansion of bone marrow haemopoiesis studied by localized magnetic resonance proton spectroscopy

    DEFF Research Database (Denmark)

    Jensen, K E; Hansen, P B; Larsen, V A

    1994-01-01

    spectroscopy (MRS). Six patients were treated with daily subcutaneous injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF, n = 2) or granulocyte-macrophage colony-stimulating factor (rhGM-CSF, n = 4) for 5d before marrow harvest. MRS investigations were performed prior to treatment......Previously we have shown that short-term myeloid growth factor priming of haemopoiesis prior to bone marrow harvest increased the yield of myeloid progenitors in the graft. The present study is intended to investigate the expansion of haemopoiesis by volume selective proton magnetic resonance....../76 x 10(3) (range 28.4-1180.6/23.2-2850.0). MRS detected a significant increase in bone marrow 'relative water content' day 12, 1 week after myeloid growth factor treatment was stopped, from median 30.5% (range 16-45) to 79% (range 56-93). In parallel, haemopoiesis was detected in new areas of femur...

  12. Short-term myeloid growth factor mediated expansion of bone marrow haemopoiesis studied by localized magnetic resonance proton spectroscopy

    DEFF Research Database (Denmark)

    Jensen, K E; Hansen, P B; Larsen, V A

    1994-01-01

    /76 x 10(3) (range 28.4-1180.6/23.2-2850.0). MRS detected a significant increase in bone marrow 'relative water content' day 12, 1 week after myeloid growth factor treatment was stopped, from median 30.5% (range 16-45) to 79% (range 56-93). In parallel, haemopoiesis was detected in new areas of femur......Previously we have shown that short-term myeloid growth factor priming of haemopoiesis prior to bone marrow harvest increased the yield of myeloid progenitors in the graft. The present study is intended to investigate the expansion of haemopoiesis by volume selective proton magnetic resonance......-density cell proliferation rate in marrow samples increased from median 21.9 (range 4.5-31) x 10(3) cpm to 54.7 (range 13.9-94) x 10(3) cpm and the total number of myeloid progenitors enumerated as day 7/14 GM-CFUs per volume aspirated marrow increased from median 11/8 x 10(3) (range 4.0-87.5/2.2-103.0) to 64...

  13. Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Davis Rodney

    2006-07-01

    Full Text Available Abstract Background Prostate cancer cells communicate reciprocally with the stromal cells surrounding them, inside the prostate, and after metastasis, within the bone. Each tissue secretes factors for interpretation by the other. One stromally-derived factor, Hepatocyte Growth Factor (HGF, was found twenty years ago to regulate invasion and growth of carcinoma cells. Working with the LNCaP prostate cancer progression model, we found that these cells could respond to HGF stimulation, even in the absence of Met, the only known HGF receptor. The new HGF binding partner we find on the cell surface may help to clarify conflicts in the past literature about Met expression and HGF response in cancer cells. Methods We searched for Met or any HGF binding partner on the cells of the PC3 and LNCaP prostate cancer cell models, using HGF immobilized on agarose beads. By using mass spectrometry analyses and sequencing we have identified nucleolin protein as a novel HGF binding partner. Antibodies against nucleolin (or HGF were able to ameliorate the stimulatory effects of HGF on met-negative prostate cancer cells. Western blots, RT-PCR, and immunohistochemistry were used to assess nucleolin levels during prostate cancer progression in both LNCaP and PC3 models. Results We have identified HGF as a major signaling component of prostate stromal-conditioned media (SCM and have implicated the protein nucleolin in HGF signal reception by the LNCaP model prostate cancer cells. Antibodies that silence either HGF (in SCM or nucleolin (on the cell surfaces eliminate the adhesion-stimulatory effects of the SCM. Likewise, addition of purified HGF to control media mimics the action of SCM. C4-2, an LNCaP lineage-derived, androgen-independent human prostate cancer cell line, responds to HGF in a concentration-dependent manner by increasing its adhesion and reducing its migration on laminin substratum. These HGF effects are not due to shifts in the expression levels of

  14. Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells

    International Nuclear Information System (INIS)

    Tate, Amanda; Isotani, Shuji; Bradley, Michael J; Sikes, Robert A; Davis, Rodney; Chung, Leland WK; Edlund, Magnus

    2006-01-01

    Prostate cancer cells communicate reciprocally with the stromal cells surrounding them, inside the prostate, and after metastasis, within the bone. Each tissue secretes factors for interpretation by the other. One stromally-derived factor, Hepatocyte Growth Factor (HGF), was found twenty years ago to regulate invasion and growth of carcinoma cells. Working with the LNCaP prostate cancer progression model, we found that these cells could respond to HGF stimulation, even in the absence of Met, the only known HGF receptor. The new HGF binding partner we find on the cell surface may help to clarify conflicts in the past literature about Met expression and HGF response in cancer cells. We searched for Met or any HGF binding partner on the cells of the PC3 and LNCaP prostate cancer cell models, using HGF immobilized on agarose beads. By using mass spectrometry analyses and sequencing we have identified nucleolin protein as a novel HGF binding partner. Antibodies against nucleolin (or HGF) were able to ameliorate the stimulatory effects of HGF on met-negative prostate cancer cells. Western blots, RT-PCR, and immunohistochemistry were used to assess nucleolin levels during prostate cancer progression in both LNCaP and PC3 models. We have identified HGF as a major signaling component of prostate stromal-conditioned media (SCM) and have implicated the protein nucleolin in HGF signal reception by the LNCaP model prostate cancer cells. Antibodies that silence either HGF (in SCM) or nucleolin (on the cell surfaces) eliminate the adhesion-stimulatory effects of the SCM. Likewise, addition of purified HGF to control media mimics the action of SCM. C4-2, an LNCaP lineage-derived, androgen-independent human prostate cancer cell line, responds to HGF in a concentration-dependent manner by increasing its adhesion and reducing its migration on laminin substratum. These HGF effects are not due to shifts in the expression levels of laminin-binding integrins, nor can they be linked to

  15. An Anti-Urokinase Plasminogen Activator Receptor Antibody (ATN-658 Blocks Prostate Cancer Invasion, Migration, Growth, and Experimental Skeletal Metastasis In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Shafaat A. Rabbani

    2010-10-01

    Full Text Available Urokinase plasminogen activator receptor (uPAR is a multidomain protein that plays important roles in the growth, invasion, and metastasis of a number of cancers. In the present study, we examined the effects of administration of a monoclonal anti-uPAR antibody (ATN-658 on prostate cancer progression in vitro and in vivo. We examined the effect of treatment of ATN-658 on human prostate cancer cell invasion, migration, proliferation, and regulation of intracellular signaling pathways. For in vivo studies, PC-3 cells (1 x 106 were inoculated into the right flank of male Balb C nu/nu mice through subcutaneous or through intratibial route (2 x 105 of male Fox Chase severe combined immunodeficient mice to monitor the effect on tumor growth and skeletal metastasis. Treatment with ATN-658 resulted in a significant dose-dependent decrease in PC-3 cell invasion and migration without affecting cell doubling time. Western blot analysis showed that ATN-658 treatment decreased the phosphorylation of serine/threonine protein kinase B (AKT, mitogen-activated protein kinase (MAPK, and focal adhesion kinase (FAK without affecting AKT, MAPK, and FAK total protein expression. In in vivo studies, ATN-658 caused a significant decrease in tumor volume and a marked reduction in skeletal lesions as determined by Faxitron x-ray and micro-computed tomography. Immunohistochemical analysis of subcutaneous and tibial tumors showed a marked decrease in the levels of expression of pAKT, pMAPK, and pFAK, consistent with the in vitro observations. Results from these studies provide compelling evidence for the continued development of ATN-658 as a potential therapeutic agent for the treatment of prostate and other cancers expressing uPAR.

  16. A region in urokinase plasminogen receptor domain III controlling a functional association with alpha5beta1 integrin and tumor growth

    DEFF Research Database (Denmark)

    Chaurasia, Pratima; Aguirre-Ghiso, Julio; Liang, Olin D

    2006-01-01

    Highly expressed urokinase plasminogen activator receptor (uPAR) can interact with alpha5beta1 integrin leading to persistent ERK activation and tumorigenicity. Disrupting this interaction reduces ERK activity, forcing cancer cells into dormancy. We identified a site in uPAR domain III that is in......Highly expressed urokinase plasminogen activator receptor (uPAR) can interact with alpha5beta1 integrin leading to persistent ERK activation and tumorigenicity. Disrupting this interaction reduces ERK activity, forcing cancer cells into dormancy. We identified a site in uPAR domain III...

  17. Hemangiosarcoma and its cancer stem cell subpopulation are effectively killed by a toxin targeted through epidermal growth factor and urokinase receptors.

    Science.gov (United States)

    Schappa, Jill T; Frantz, Aric M; Gorden, Brandi H; Dickerson, Erin B; Vallera, Daniel A; Modiano, Jaime F

    2013-10-15

    Targeted toxins have the potential to overcome intrinsic or acquired resistance of cancer cells to conventional cytotoxic agents. Here, we hypothesized that EGFuPA-toxin, a bispecific ligand-targeted toxin (BLT) consisting of a deimmunized Pseudomonas exotoxin (PE) conjugated to epidermal growth factor and urokinase, would efficiently target and kill cells derived from canine hemangiosarcoma (HSA), a highly chemotherapy resistant tumor, as well as cultured hemangiospheres, used as a surrogate for cancer stem cells (CSC). EGFuPA-toxin showed cytotoxicity in four HSA cell lines (Emma, Frog, DD-1 and SB) at a concentration of ≤100 nM, and the cytotoxicity was dependent on specific ligand-receptor interactions. Monospecific targeted toxins also killed these chemoresistant cells; in this case, a "threshold" level of EGFR expression appeared to be required to make cells sensitive to the monospecific EGF-toxin, but not to the monospecific uPA-toxin. The IC₅₀ of CSCs was higher by approximately two orders of magnitude as compared to non-CSCs, but these cells were still sensitive to EGFuPA-toxin at nanomolar (i.e., pharmacologically relevant) concentrations, and when targeted by EGFuPA-toxin, resulted in death of the entire cell population. Taken together, our results support the use of these toxins to treat chemoresistant tumors such as sarcomas, including those that conform to the CSC model. Our results also support the use of companion animals with cancer for further translational development of these cytotoxic molecules. Copyright © 2013 UICC.

  18. Tumor cells secrete an angiogenic factor that stimulates basic fibroblast growth factor and urokinase expression in vascular endothelial cells

    NARCIS (Netherlands)

    Peverali, F.A.; Mandriota, S.J.; Ciana, P.; Marelli, R.; Quax, P.; Rifkin, D.B.; Della Valle, G.; Mignatti, P.

    1994-01-01

    Culture medium conditioned by human SK-Hep1 hepatoma cells or mouse S180 sarcoma cells rapidly up-regulates endothelial cell expression of basic fibroblast growth factor (bFGF) and induces formation of capillary-like structures by vascular endothelial cells grown on three-dimensional fibrin gels (in

  19. Selective arterial thrombolysis with urokinase

    International Nuclear Information System (INIS)

    Park, Jae Hyung; Park, Kil Sun; Chung, Jin Wook; Han, Joon Koo; Kim, Sang Joon; Kim, Dae Young

    1991-01-01

    Seven patients with thrombotic occlusions of the peripheral arteries or grafts were treated with urokinase by direct intraarterial selective infusion. During the infusion, simultaneous heparin infusion was used to reduce the frequency of thrombus formation on the infusion catheter or recurrent thrombosis. In 4 patients in whom a complete thrombolysis occurred, urokinase was infused by a high-dose transthrombus bolus technique followed by continuous infusion. There other patients, in whom thrombolysis was partially accomplished and then surgical thrombectomy was performed, were treated only by continuous urokinase infusion. Small hematomas developed at the infusion catheter entry site in 2 patients, but transfusion or operation was not required. Other significant complications were not found. Our results suggest that selective arterial infusion of urokinase with a transthrombus bolus technique can accomplish a complete arterial thrombolysis without any significant complications

  20. Enhancement of the nerve growth factor-mediated neurite outgrowth from PC12D cells by Chinese and Paraguayan medicinal plants.

    Science.gov (United States)

    Li, P; Matsunaga, K; Ohizumi, Y

    1999-07-01

    It is very important to search for natural compounds possessing nerve growth factor (NGF)-potentiating activity. Extracts of 7 Chinese and 10 Paraguayan medicinal plants were examined for their effects on the NGF-mediated neurite outgrowth from PC12D cells to evaluate their NGF-potentiating activities. In the methanol extracts, Gymmopteris rufa (LINN.) BERNH, Ruta graveolens LINN. and Picrorhiza scrophulariiflora PENNELL markedly increased the proportion of neurite-bearing cells. In the case of ethyl acetate fractions, Equisetum giganteum LINN. produced the most powerful enhancement of the proportion of the neurite-bearing cells, and the activities were in the following decreasing order: Equisetum giganteum LINN., Gymmopteris rufa (LINN.) BERNH, Ruta graveolens LINN., and Picrorhiza scrophulariiflora PENNELL. In the water fractions, Imperata cylindrica, Ginseng Radix, Gymmopteris rufa (LINN.) BERNH, Gochnatia polymorpha (LESS) CAB and Picrorhiza scrophulariiflora PENNELL caused a weak enhancement of the proportion of PC12D cells with neurites. Of all the extracts and fractions, the methanol extract of Picrorhiza scrophulariiflora PENNELL induced the longest neurites in PC12D cells. In the ethyl acetate and water fractions of Nardostachys chinensis, long neurites were observed although only a small proportion of PC12D cells had neurites. On the other hand, in the ethyl acetate fraction of Equisetum gigantheum LINN., while the length of the neurites was short, the proportion of neurite-bearing cells was largest among all the extracts and fractions.

  1. [PDGFRα Participates in Basic Fibroblast Growth Factor-mediated Recovery of Human Bone Marrow Mesenchymal Stem Cell Proliferation and Osteogenic Differentiation after Irradiation].

    Science.gov (United States)

    Dai, Kai; Yang, Zhi; Xu, Shuang-Nian; Zhang, Jian-Min; Chen, Jie-Ping

    2015-12-01

    To explore the effects of basic fibroblast growth factor (bFGF) on human bone marrow mesenchymal stem cell (hBMMSC) damaged by irradiation and its underlying mechanisms. hBMMSC was irradiated with 0, 6, 12 Gy X ray, then flow cytometry, cell counting kit-8 (CCK-8), Western blot and alizarin red staining were used to detect the effects of X ray on apoptosis, proliferation and osteogenic differentiation of hBMMSC; 0, 1, 5, 10, 20 ng/ml bFGF was added to hBMMSC irradiated with X ray for selecting the suitable bFGF reaction concentration; then the Western blot was used to detect the expression of PDGFRα so as to evaluate whether the expression of PDGFRα participated in bFGF-mediated recovery of hBMMSC proliferation and osteogenic differentiation after irradiation. The proliferation and osteogenic differentiation of hBMMSC decreased remarkably after irradiation. bFGF promoted the recovery of proliferation and osteogenic differentiation of irradiated hBMMSC compared with untreated irradiated hBMMSC (P recovery of hBMMSC proliferation and osteogenic differentiation. The damage of hBMMSC proliferation and osteogenic differentiation associates with downregulation of PDGFRα expression induced by irrediation. PDGFRα involves in repairing effect of bFGF on irradiation damage of hBMMSC.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    PA 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...

  3. Basic Fibroblast Growth Factor-Mediated Overexpression of Vascular Endothelial Growth Factor in 1F6 Human Melanoma Cells is Regulated by Activation of PI-3K and p38 MAPK

    Directory of Open Access Journals (Sweden)

    Dennis Fontijn

    2009-01-01

    Full Text Available Background: 1F6 human melanoma xenografts overexpressing either the 18 kD (18kD form or all (ALL forms of human basic fibroblast growth factor (bFGF demonstrate an abundant number of microvessels and accelerated growth. We now examined whether bFGF mediates vascular endothelial growth factor (VEGF expression.

  4. [Urokinase in the management of occluded PICC lines].

    Science.gov (United States)

    Muller, C; Jacquier, A; Varoquaux, A; Cohen, F; Louis, G; Gaubert, J Y; Moulin, G; Bartoli, J M; Vidal, V

    2010-03-01

    To determine the efficacy and safety of urokinase in the management of occluded PICC lines. A total of 587 PICC lines were placed over an 11 month period. During this period, 28 PICC lines (4.8%) became occluded: 12 occluded PICC lines were successfully managed by simple flushing with normal saline while 16 PICC lines were thrombolyzed with urokinase. After urokinase, 93.8% (15/16) of occluded PICC lines were completely patent. A single infusion of urokinase, 20,000 IU over 30 minutes, was used in all cases. No secondary occlusion or complication was noted after urokinase. Urokinase is effective and safe to restore patency to occluded PICC lines. The procedure is simple, and could be performed at the bedside by nursing staff after medical prescription. It is an alternative to over the wire PICC line exchange, that could reduce the risk of complication related to manipulations, patient discomfort and cost.

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

    International Nuclear Information System (INIS)

    Ko, Gi Young; Suh, Dae Chul; Lee, Jae Hong; Kim, Jun Hyoung; Choi, Choong Gon; Lee, Ho Kyu; Lee, Myoung Chong

    1996-01-01

    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 10 5 IU) 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

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

    DEFF Research Database (Denmark)

    Illemann, Martin; Bird, Nigel; Majeed, Ali

    2009-01-01

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

  7. Interaction of urokinase A chain with the receptor of human keratinocytes stimulates release of urokinase-like plasminogen activator

    Energy Technology Data Exchange (ETDEWEB)

    Fibbi, G.; Magnelli, L.; Pucci, M.; Del Rosso, M. (Florence Univ. (Italy))

    1990-03-01

    On the basis of a fibrinolytic assay with {sup 125}I-fibrin, zymography, and immunoprobing with anti-human urokinase antibody, the authors have observed that the in vitro established NCTC human keratinocyte cell line releases into the culture medium a 54,000-Da plasminogen activator which is indistinguishable from human urokinase. Only the early release following the washing of keratinocyte monolayers is accounted for by secretion of preformed enzyme, while late secretory events require the de novo synthesis of urokinase. The released enzyme can interact by autocriny with its own receptor present on keratinocytes. The addition to the keratinocyte culture medium of the urokinase A chain can stimulate a concentration-dependent urokinase oversecretion, which is not paralleled by oversecretion of plasminogen activator inhibitor-1. Since stimulation of urokinase production can be obtained by an A chain concentration which was previously shown to be efficient in inducing keratinocyte mobilization in an in vitro migration model system, they hypothesize that this mechanism may be important in vivo during the process of wound repair.

  8. A role for calcium in the regulation of ATP-binding cassette, sub-family C, member 3 (ABCC3) gene expression in a model of epidermal growth factor-mediated breast cancer epithelial-mesenchymal transition.

    Science.gov (United States)

    Stewart, Teneale A; Azimi, Iman; Thompson, Erik W; Roberts-Thomson, Sarah J; Monteith, Gregory R

    2015-03-13

    Epithelial-mesenchymal transition (EMT), a process implicated in cancer metastasis, is associated with the transcriptional regulation of members of the ATP-binding cassette superfamily of efflux pumps, and drug resistance in breast cancer cells. Epidermal growth factor (EGF)-induced EMT in MDA-MB-468 breast cancer cells is calcium signal dependent. In this study induction of EMT was shown to result in the transcriptional up-regulation of ATP-binding cassette, subfamily C, member 3 (ABCC3), a member of the ABC transporter superfamily, which has a recognized role in multidrug resistance. Buffering of cytosolic free calcium inhibited EGF-mediated ABCC3 increases, indicating a calcium-dependent mode of regulation. Silencing of TRPM7 (an ion channel involved in EMT associated vimentin induction) did not inhibit ABCC3 up-regulation. Silencing of the store operated calcium entry (SOCE) pathway components ORAI1 and STIM1 also did not alter ABCC3 induction by EGF. However, the calcium permeable ion channel transient receptor potential cation channel, subfamily C, member 1 (TRPC1) appears to contribute to the regulation of both basal and EGF-induced ABCC3 mRNA. Improved understanding of the relationship between calcium signaling, EMT and the regulation of genes important in therapeutic resistance may help identify novel therapeutic targets for breast cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. The urokinase receptor associated protein (uPARAP/endo180)

    DEFF Research Database (Denmark)

    Engelholm, L H; Nielsen, B S; Danø, K

    2001-01-01

    of this proteolytic system. uPARAP is a high molecular weight type-1 membrane protein, belonging to the macrophage mannose receptor protein family. On the surface of certain cells, uPARAP forms a ternary complex with the pro-form of the urokinase-type plasminogen activator (uPA) and its primary receptor (uPAR). While......The urokinase-mediated plasminogen activation system plays a central role in the extracellular proteolytic degradation reactions in cancer invasion. In this review article we discuss a number of recent findings identifying a new cellular receptor protein, uPARAP, that interacts with components...

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

    DEFF Research Database (Denmark)

    Picone, R; Kajtaniak, E L; Nielsen, Lars Søegaard

    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......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 distribution of uPA in tumor cells and tissues suggest that the uPA/uPAR interaction may be important in regulating extracellular proteolysis-dependent processes (e.g., invasion, tissue destruction). Phorbol myristate acetate (PMA), an inducer of U937 cell differentiation to macrophage-like cells, elicits...... in the affinity of the uPAR for uPA, thus uncovering another way of regulating the interaction between uPA and uPAR. In addition, the PMA treatment causes a modification of migration of the cross-linked receptor in mono- and bidimensional gel electrophoresis....

  11. Differential binding of urokinase and peptide antagonists to the urokinase receptor

    DEFF Research Database (Denmark)

    Engelholm, L H; Behrendt, N

    2001-01-01

    for the invasion of cancer cells, thus making uPAR a potential target for anti-invasive therapy based on binding antagonists. A remarkable property of the uPA-uPAR system is a pronounced species specificity in ligand recognition. We have now cloned and studied uPAR from four primate species and show that even......The urokinase plasminogen activator receptor (uPAR) is a membrane protein active in localizing the plasminogen activation cascade system on the cell surface. The resulting pericellular proteolytic activity is responsible for degradation reactions in the extracellular matrix that are needed....... These findings aid the elucidation of the structure/function relationship of uPAR and, unexpectedly, identify a structural distinction governing the binding of uPA and a very similar peptide antagonist....

  12. Platelet-derived growth factor mediates interleukin-13-induced ...

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... ... blocker or MEK inhibitor partially suppressed IL-13-induced collagen I production. Taken together, our study suggests that activation of JAK/STAT6 signal pathway and subsequent PDGF generation and resultant ERK1/2 MAPK activation mediated IL-13-induced collagen I production in airway fibroblasts.

  13. Urokinase production by electrophoretically separated cultured human embryonic kidney cells

    Science.gov (United States)

    Kunze, M. E.; Plank, L. D.; Giranda, V.; Sedor, K.; Todd, P. W.

    1985-01-01

    Urokinase is a plasminogen activator found in urine. Relatively pure preparations have been tested in Europe, Japan and the United States for the treatment of deep vein thrombosis and other dangerous blood clots. Human embryonic kidney cell cultures have been found to produce urokinase at much higher concentrations, but less than 5% of the cells in typical cultures are producers. Since human diploid cells become senescent in culture the selection of clones derived from single cells will not provide enough material to be useful, so a bulk purification method is needed for the isolation of urokinase producing cell populations. Preparative cell electrophoresis was chosen as the method, since evidence exists that human embryonic cell cultures are richly heterogeneous with respect to electrophoretic mobility, and preliminary electrophoretic separations on the Apollo-Soyuz space flight produced cell populations that were rich in urokinase production. Similarly, erythropoietin is useful in the treatment of certain anemias and is a kidney cell duct, and electrophoretically enriched cell populations producing this product have been reported. Thus, there is a clear need for diploid human cells that produce these products, and there is evidence that such cells should be separable by free-flow cell electrophoresis.

  14. The urokinase receptor as a potential target in cancer therapy

    DEFF Research Database (Denmark)

    Romer, John; Nielsen, Boye Schnack; Ploug, Michael

    2004-01-01

    The glycolipid-anchored receptor for urokinase-type plasminogen activator (uPAR) is essential for cell-surface associated plasminogen activation and is overexpressed at the invasive tumor-stromal microenvironment in many human cancers. In line with this, uPAR and uPA levels in both resected tumor...

  15. Alteplase vs. urokinase for occluded hemodialysis catheter: A randomized trial.

    Science.gov (United States)

    Pollo, Viviane; Dionízio, Danielle; Bucuvic, Edwa Maria; Castro, João Henrique; Ponce, Daniela

    2016-07-01

    Introduction Thrombosis of tunneled central venous catheters (CVC) in hemodialysis (HD) patients is common and it can lead to the elimination of vascular sites. To compare the efficacy of alteplase vs. urokinase in reestablishing adequate blood flow through completely occluded vascular catheters. Methods In this randomized study, patients with completely occluded tunneled HD catheters received 40 minutes intracatheter dwell with alteplase (1 mg/mL) or urokinase (5000 IU/mL). Primary endpoint was the proportion of patients with occluded catheters achieving post-thrombolytic blood flow of ≥250 mL/min. Safety endpoints included the incidence of hemorrhagic and infectious complications. Findings Eligible adult patients (n = 100) were treated with alteplase (n = 44) or urokinase (n = 56). The two groups were similar in gender (male: 51.8% vs. 56.8%, P = 0.35), age (60 ± 12 vs. 59 ± 13 years, P = 0.71), time on dialysis (678 ± 203 vs. 548 ± 189 days, P = 0.77), diabetes and cardiovascular disease (55.6% vs. 70.4%, P = 0.08 and 17.8% vs. 22.7%, P = 0.38, respectively), jugular vein as main vascular access (54.8% vs. 62.5%, P = 0.57), and time of CVC (278 ± 63 vs. 218 ± 59 days, P = 0.67). Primary success with alteplase and urokinase occurred in 42/44 (95%) vs. 46/56 (82%), P = 0.06. Success was not achieved after the second dose of alteplase and urokinase in 1 and 7 cases, respectively (2% vs. 12%, P = 0.075). Serious adverse effects were not observed in both groups. There was no difference between the two groups in infectious complications (P = 0.94). Discussion Alteplase and urokinase are effective thrombolytic agents for restoring HD catheter patency. Our study has revealed a likely slight superiority of alteplase over urokinase for unblocking central lines, but which has enrolled too few patients to be able to detect a difference of this size. © 2016 International Society for

  16. The urokinase plasminogen activator receptor-associated protein/endo180 is coexpressed with its interaction partners urokinase plasminogen activator receptor and matrix metalloprotease-13 during osteogenesis

    DEFF Research Database (Denmark)

    Engelholm, L H; Nielsen, B S; Netzel-Arnett, Sarah

    2001-01-01

    The urokinase plasminogen activator receptor-associated protein/Endo180 (uPARAP/Endo180) is a newly discovered member of the macrophage mannose receptor family that was reported to interact with ligand-bound urokinase plasminogen activator receptor (uPAR), matrix metalloprotease-13 (MMP-13), and ...

  17. Dynamics of urokinase receptor interaction with Peptide antagonists studied by amide hydrogen exchange and mass spectrometry

    DEFF Research Database (Denmark)

    Jørgensen, Thomas J D; Gårdsvoll, Henrik; Danø, Keld

    2004-01-01

    Using amide hydrogen exchange combined with electrospray ionization mass spectrometry, we have in this study determined the number of amide hydrogens on several peptides that become solvent-inaccessible as a result of their high-affinity interaction with the urokinase-type plasminogen activator...... receptor (uPAR). These experiments reveal that at least six out of eight amide hydrogens in a synthetic nine-mer peptide antagonist (AE105) become sequestered upon engagement in uPAR binding. Various uPAR mutants with decreased affinity for this peptide antagonist gave similar results, thereby indicating...... that deletion of the favorable interactions involving the side chains of these residues in uPAR does not affect the number of hydrogen bonds established by the main chain of the peptide ligand. The isolated growth factor-like domain (GFD) of the cognate serine protease ligand for uPAR showed 11 protected amide...

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

    DEFF Research Database (Denmark)

    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...... induce the same response. In this report, we show that both of these triggering mechanisms can be operative and that uPAR-dependent modulation of cell morphology can indeed occur independently of a direct vitronectin binding. Expression of wild-type uPAR on HEK293 cells led to pronounced vitronectin...... was restored, although this did not rescue the uPAR-vitronectin binding and adhesion capability. On the other hand, using other uPAR variants, we could show that uPAR-vitronectin adhesion is indeed capable and sufficient to induce the same morphological rearrangements. This was shown with cells expressing...

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

    DEFF Research Database (Denmark)

    Almasi, Charlotte Elberling; Christensen, Ib Jarle; Høyer-Hansen, Gunilla

    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....

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

    DEFF Research Database (Denmark)

    Wittenhagen, Per; Andersen, Jesper Brandt; Hansen, Anita

    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....

  1. Urokinase plasminogen activator cleaves its cell surface receptor releasing the ligand-binding domain

    DEFF Research Database (Denmark)

    Høyer-Hansen, G; Rønne, E; Solberg, H.

    1992-01-01

    The cellular receptor for urokinase-type plasminogen activator (uPAR) is a glycolipid-anchored three-domain membrane protein playing a central role in pericellular plasminogen activation. We have found that urokinase (uPA) can cleave its receptor between domains 1 and 2 generating a cell-associat...

  2. Soluble urokinase plasminogen activator receptor during allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Haastrup, E; Andersen, J; Ostrowski, S R

    2011-01-01

    Previous studies have found that soluble urokinase plasminogen activation receptor (suPAR) increases during inflammatory and malignant illness and elevated suPAR levels may be associated with poor clinical outcome. The purpose of this study was to investigate plasma levels of suPAR during...... to pretreatment levels. High suPAR levels at day 0 were associated with increased mortality (P = 0.011). The present study found increased suPAR levels during the conditioning in SCT patients. Further, the data indicated that increased suPAR levels may be associated with increased mortality, suggesting su...

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

    DEFF Research Database (Denmark)

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

    2003-01-01

    The reciprocal pro-enzyme activation system of plasmin, urokinase-type plasminogen activator (uPA) and their respective zymogens is a potent mechanism in the generation of extracellular proteolytic activity. Plasminogen activator inhibitor type 1 (PAI-1) acts as a negative regulator. This system...... is complicated by a poorly understood intrinsic reactivity of the uPA pro-enzyme (pro-uPA) before proteolytic activation, directed against both plasminogen and PAI-1. We have studied the integrated activation mechanism under the repression of PAI-1 in a purified system. A covalent reaction between pro...

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

    Science.gov (United States)

    Multhaupt, H A; Mazar, A; Cines, D B; Warhol, M J; McCrae, K R

    1994-09-01

    Through their ability to invade endometrium, remodel the uterine spiral arteries, and sustain placental blood fluidity, trophoblast cells play a central role in establishing and maintaining the integrity of the uteroplacental vasculature. The expression of urokinase receptors by trophoblast may facilitate these processes by focusing plasminogen activator activity to discrete sites on the cell surface and promoting the activation of cell-bound plasminogen. However, although urokinase receptors are expressed by cultured trophoblast, the expression of these receptors by trophoblast in vivo has not been examined. Immunohistochemistry and immunoelectron microscopy were used to characterize the expression of urokinase receptors by villous and extravillous trophoblast at several points in gestation. Urokinase receptors were expressed in a polarized fashion at the leading edge of migrating extravillous trophoblast cells. Receptors were also abundantly expressed during the first and second trimesters of gestation by villous trophoblast, where they were located on apical villous projections and within intracellular vacuoles, a subset of which were lysosomes. The polarized expression of urokinase receptors by invasive extravillous trophoblast cells is consistent with a role for these receptors in mediating the extent and directionality of trophoblast migration. In contrast, the expression of urokinase receptors by villous trophoblast, which are not actively invasive in vivo, may serve to facilitate the generation of plasmin at the interface of these cells with maternal plasma, thereby limiting the deposition of fibrin within the placental intervillous spaces. Diminished urokinase receptor expression by villous trophoblast at term may represent a physiologic adaptation to diminish local fibrinolysis and limit hemorrhage at parturition.

  5. Dialysis Access Graft Thrombolysis: Randomized Study of Pulse-Spray Versus Continuous Urokinase Infusion

    International Nuclear Information System (INIS)

    Goodwin, Scott C.; Arora, Lokesh C.; Razavi, Mahmood K.; Sayre, James; McNamara, Thomas O.; Yoon, Chun

    1998-01-01

    Purpose: To compare pulse-spray to continuous-infusion thrombolysis with high-dose urokinase in thrombosed dialysis access grafts. Methods: A prospective randomized controlled trial was performed. From August 1992 to September 1993, 30 thrombosed polytetrafluoroethylene (PTFE) grafts in 24 patients were included, 15 grafts in each group. The success of thrombolysis, mean time to thrombolysis, mean urokinase dose, and 60-day patency rate were evaluated. Results: In the pulse-spray group, the mean time to thrombolysis was 72 min with a mean urokinase dose of 560,000 U. The 60-day patency rate was 71%. In the continuous-infusion group, the mean infusion time to thrombolysis was 55 min with a mean dose of 479,000 U. The 60-day patency rate was 73%. Conclusion: No statistically significant difference was found between the two techniques in the mean time to thrombolysis, the mean urokinase dose used, or the 60-day patency rate

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

    DEFF Research Database (Denmark)

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

    1994-01-01

    BACKGROUND: Through their ability to invade endometrium, remodel the uterine spiral arteries, and sustain placental blood fluidity, trophoblast cells play a central role in establishing and maintaining the integrity of the uteroplacental vasculature. The expression of urokinase receptors by troph...

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

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

    DEFF Research Database (Denmark)

    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 ...

  9. Application of Molecular Modeling to Urokinase Inhibitors Development

    Directory of Open Access Journals (Sweden)

    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.

  10. Studies on urokinase (UK) therapy of thromboembolic diseases

    International Nuclear Information System (INIS)

    Wakayama, Ryuji; Satake, Kisaburo; Hisamatsu, Tokugoro; Fukase, Masaichi

    1974-01-01

    In order to determine the urokinase (UK) concentration in blood, a radioimmunoassay method was developed, in which a radioactive material labeled with 125 I-Na was used. In this method, the movement of UK in blood and the relationship between the UK concentration and fibrinolytic activity were studied with the following results: 1) The concentration of UK in normal human blood was found to be 6.84 +- 2.53 PKU early in the morning with an apparent daily rythmic fluctuation in concentration. 2) With an intravenous drip of 20,000 to 30,000 PKU, the UK concentration increased 6 to 8 PKU/ml above the early morning value, then in one to two hours it returned to the previous value once again. In some of the cases, a slight, transient decrease occurred. 3) Following the UK drip, UK concentration in the blood and fibrinolytic activity varied in a parallel fashion. Plasminogen and antiplasmin levels were not altered by administration of only 20,000 to 30,000 PKU of UK. Fibrinogen was lowered, but the fluctuation was within the physiological range. (S. Oyama)

  11. Role of the urokinase-fibrinolytic system in epithelial-mesenchymal transition during lung injury.

    Science.gov (United States)

    Marudamuthu, Amarnath Satheesh; Bhandary, Yashodhar Prabhakar; Shetty, Shwetha Kumari; Fu, Jian; Sathish, Venkatachalem; Prakash, Ys; Shetty, Sreerama

    2015-01-01

    Alveolar type II epithelial (ATII) cell injury precedes development of pulmonary fibrosis. Mice lacking urokinase-type plasminogen activator (uPA) are highly susceptible, whereas those deficient in plasminogen activator inhibitor (PAI-1) are resistant to lung injury and pulmonary fibrosis. Epithelial-mesenchymal transition (EMT) has been considered, at least in part, as a source of myofibroblast formation during fibrogenesis. However, the contribution of altered expression of major components of the uPA system on ATII cell EMT during lung injury is not well understood. To investigate whether changes in uPA and PAI-1 by ATII cells contribute to EMT, ATII cells from patients with idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease, and mice with bleomycin-, transforming growth factor β-, or passive cigarette smoke-induced lung injury were analyzed for uPA, PAI-1, and EMT markers. We found reduced expression of E-cadherin and zona occludens-1, whereas collagen-I and α-smooth muscle actin were increased in ATII cells isolated from injured lungs. These changes were associated with a parallel increase in PAI-1 and reduced uPA expression. Further, inhibition of Src kinase activity using caveolin-1 scaffolding domain peptide suppressed bleomycin-, transforming growth factor β-, or passive cigarette smoke-induced EMT and restored uPA expression while suppressing PAI-1. These studies show that induction of PAI-1 and inhibition of uPA during fibrosing lung injury lead to EMT in ATII cells. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  12. Managing dysfunctional central venous access devices: a practical approach to urokinase thrombolysis.

    Science.gov (United States)

    Kumwenda, Mick; Dougherty, Lisa; Spooner, Helen; Jackson, Victoria; Mitra, Sandip; Inston, Nicholas

    2018-01-25

    Tunnelled central venous access devices (CVADs) are defined as any intravenous multipurpose catheters placed within the central veins for use in haemodialysis and administration of blood products or chemotherapy in oncology and haematological conditions. Frequent complications include thrombosis and catheter-related infection, which may lead to significant adverse patient outcomes. Once thrombosis is suspected correction should be attempted empirically with thrombolytic agents. Commonly available thrombolytic agents in the UK include urokinase (Syner-Kinase) and alteplase (Cathflo). It is well recognised that urokinase usage differs widely and concerns were raised by clinicians about the variation of dose regimens nationally. The objective of the CVAD Focus Group was to address this issue and offer guidance in the management of suspected thrombosis of CVAD with urokinase using two algorithms for renal and non-renal dysfunctional CVAD and to audit prospectively the outcomes of intervention.

  13. The soluble urokinase plasminogen activator receptor and its fragments in venous ulcers

    DEFF Research Database (Denmark)

    Ahmad, Anwar; Saha, Prakash; Evans, Colin

    2015-01-01

    OBJECTIVE: Activation of proteolytic mechanisms at the cell surface through the activity of urokinase-type plasminogen activator (uPA) bound to its receptor, uPAR, is an important process in wound healing. The soluble forms of uPAR (suPAR and its fragments I, II, and III) have nonproteolytic...

  14. Soluble Urokinase-Type Plasminogen Activator Receptor Levels in Patients With Schizophrenia

    DEFF Research Database (Denmark)

    Nielsen, Jimmi; Røge, Rasmus; Pristed, Sofie Gry

    2015-01-01

    BACKGROUND: The etiology of schizophrenia remains largely unknown but alterations in the immune system may be involved. In addition to the psychiatric symptoms, schizophrenia is also associated with up to 20 years reduction in life span. Soluble urokinase-type plasminogen activator receptor (suPA...

  15. A sensitive bioimmunoassay for thrombin-cleaved two-chain urokinase-type plasminogen activator (abstract)

    NARCIS (Netherlands)

    Braat, E.A.M.; Nauland, U.; Dooijewaard, G.; Rijken, P.C.

    1996-01-01

    Thrombin cleaves single-chain urokinase-type plasminogen activator (scu-PA) into a virtually inactive two-chain form (tcu-PA/T). Little is known about the physiological importance of tcu-PA/T. To examine the occurrence of tcu-PA/T in vivo, we developed a sensitive and specific bioimmunoassay (BIA)

  16. Physical exercise induces enhancement of urokinase-type plasminogen activator (u-PA) levels in plasma

    NARCIS (Netherlands)

    Dooijewaard, G.; Boer, A.de; Turion, P.N.C.; Cohen, A.F.; Breimer, D.D.; Kluft, C.

    1991-01-01

    The enhancement of the blood fibrinolytic potential by physical exercise is generally attributed to the release of tissue-type plasminogen activator (t-PA) from the vessel wall. In this study we have investigated the possible contribution of urokinase-type plasminogen activator (u-PA). Six healthy

  17. Adsorption behavior of Urokinase by the polypropylene film with amine, hydroxylamine and polyol groups

    International Nuclear Information System (INIS)

    Lee, Kwang-Pill; Kang, Hae-Jeong; Joo, Duck-Lae; Choi, Seong-Ho

    2001-01-01

    For the purpose of the recovery of urokinase, the polypropylene (PP) films were modified by radiation-induced grafting of glycidylmethacrylate (GMA) and subsequent chemical modification of epoxy group of poly-GMA graft chains. The physical and chemical properties of the irradiated PP film, GMA-grafted PP film and the PP films modified with trimethylamine (TMA), hydroxylamine (HA), diethanolamine (DEA), and tri(hydroxymethyl)aminomethane (THMAM) were investigated by IR, SEM, and XPS. The adsorption of urokinase for the PP films modified with TMA, HA, DEA, and THMAM group were examined under various conditions of the functional group content, pH value and salt. It increased with increasing the content of functional group. The adsorption behavior of the PP films modified for different functional groups was in the following order: TMA>DEA>THMAM>HA. The adsorption of urokinase by the PP films with various functional groups at pH=7.4 were higher than that at pH=9.0. In TMA, DEA, and THMAM groups, the adsorption of urokinase without salts was also higher than those with salts. (author)

  18. Peptide antagonists of the human urokinase receptor and method for selecting them

    DEFF Research Database (Denmark)

    2006-01-01

    A novel set of inhibitors of the binding interaction between human urokinase plasminogen activator (uPA) and its cell surface receptor (uPAR) has been developed. The inhibitors comprise of peptide fragments, monomeric or in multiple copies attached to a common scaffold, in which the amino acid se...... are antagonistic....

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

    DEFF Research Database (Denmark)

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

    1994-01-01

    are not actively invasive in vivo, may serve to facilitate the generation of plasmin at the interface of these cells with maternal plasma, thereby limiting the deposition of fibrin within the placental intervillous spaces. Diminished urokinase receptor expression by villous trophoblast at term may represent...

  20. Inactivation of single-chain urokinase-type plasminogen activator by thrombin in human subjects

    NARCIS (Netherlands)

    Braat, E. A.; Levi, M. [=Marcel M.; Bos, R.; Haverkate, F.; Lassen, M. R.; de Maat, M. P.; Rijken, D. C.

    1999-01-01

    Thrombin cleaves single-chain urokinase-type plasminogen activator (scu-PA) into a virtually inactive two-chain form (tcu-PA/T), a process that may protect a blood clot from early fibrinolysis. It is not known under what circumstances tcu-PA/T can be generated in vivo. We have studied the occurrence

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

    DEFF Research Database (Denmark)

    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...

  2. Structure and ligand interactions of the urokinase receptor (uPAR)

    DEFF Research Database (Denmark)

    Kjaergaard, Magnus; Hansen, Line V.; Jacobsen, Benedikte

    2008-01-01

    The urokinase-type plasminogen activator receptor (uPAR or CD87) is a glycolipid-anchored membrane glycoprotein, which is responsible for focalizing plasminogen activation to the cell surface through its high-affinity binding to the serine protease uPA. This tight interaction (KD less than 1 nM) ...

  3. Soluble Urokinase Plasminogen Activator Receptor for Risk Prediction in Patients Admitted with Acute Chest Pain

    DEFF Research Database (Denmark)

    Lyngbæk, Stig; Andersson, Charlotte; Marott, Jacob L

    2013-01-01

    Plasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) predict mortality in several clinical settings, but the long-term prognostic importance of suPAR in chest pain patients admitted on suspicion of non-ST-segment elevation acute coronary syndrome (NSTEACS) is uncertain....

  4. Quantitation of the receptor for urokinase plasminogen activator by enzyme-linked immunosorbent assay

    DEFF Research Database (Denmark)

    Rønne, E; Behrendt, N; Ploug, M

    1994-01-01

    Binding of the urokinase plasminogen activator (uPA) to a specific cell surface receptor (uPAR) plays a crucial role in proteolysis during tissue remodelling and cancer invasion. An immunosorbent assay for the quantitation of uPAR has now been developed. This assay is based on two monoclonal anti...

  5. Activity of Nanobins Targeted to the Urokinase Plasminogen Activator System

    Science.gov (United States)

    Hankins, Patrick Leon

    While innovations in nanotechnology have resulted in numerous medical advancements for the treatment of cancer, there remains an urgent unmet need for safe and efficient molecular platforms that facilitate the delivery of potent therapeutics to solid tumors. Nanoscale formulations help to overcome the poor bioavailability and systemic organ toxicity associated with many small molecule drugs. Of these nanoparticle drug delivery systems, the greatest clinical successes to date have employed simple nanoscale lipid bilayer assemblies which encase large payloads of chemotherapeutic. While the nanobin platform we have developed has seen initial success through the passive accumulation into tumors, actively targeting nanobins to tumor specific antigens has the potential to increase the therapeutic index of these nanoparticle drugs. We have identified the urokinase plasminogen activator (uPA) and its cell surface bound receptor (uPAR) as ideal targets for drug delivery due to their selective overexpression in metastatic cancers and their important role in tumor progression. From a panel of monoclonal antibodies targeted to uPA and uPAR, we have selected ATN291 and ATN658 as lead candidates for nanobin targeting based on their tumor cell binding and ability to be internalized by cells. A novel method of conjugating antibodies to liposomes was developed for our nanobin platform that preserves the high binding affinity and specificity of these antibodies. We evaluated these uPA- and uPAR-targeted nanobins in several xenograft tumor models and found that they were well-tolerated over a wide range of doses and demonstrated significantly increased antitumor efficacy over untargeted nanobins in multiple tumor types. Preliminary studies suggest that uPA-targeted nanobins are readily internalized by tumor cells, and we believe this is the mechanism for their increased antitumor effect. A method for radiolabeling nanobins with gallium-67 was developed, and preliminary SPECT

  6. Half-life of single-chain urokinase-type plasminogen activator (scu-PA) and two-chain urokinase-type plasminogen activator (tcu-PA) in patients with acute myocardial infarction.

    Science.gov (United States)

    Köhler, M; Sen, S; Miyashita, C; Hermes, R; Pindur, G; Heiden, M; Berg, G; Mörsdorf, S; Leipnitz, G; Zeppezauer, M

    1991-04-01

    The pharmacokinetics of urokinase (two-chain urokinase-type plasminogen activator, tcu-PA) and single-chain urokinase-type plasminogen activator (scu-PA) were studied in 20 patients with acute myocardial infarction (AMI). Ten consecutive patients received 2.5 million units tcu-PA by bolus injection within 5 min during the first 6 h after AMI (group I). Ten further consecutive patients received 250,000 U tcu-PA within 5 min, followed by 4.5 million U scu-PA by intravenous infusion over 40 min (group II). An enzyme immunoassay was developed for urokinase antigen determinations, and a fibrin plate assay for determinations of fibrinolytic activity was applied. Using a 3-compartment model, in group I 98% of urokinase antigen were cleared with a half-life of 60.8 min. After scu-PA, urokinase antigen was cleared with half-lives (area under the curve in parentheses) of 6.9 min (74.8%), 26.5 min (23.6%), and 329.7 min (2.2%). The half-disappearance times of fibrinolytic activity were 18 and 8 min in group I and II, respectively. A more pronounced decrease of plasminogen was observed after tcu-PA.

  7. Regions involved in binding of urokinase-type-1 inhibitor complex and pro-urokinase to the endocytic alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein. Evidence that the urokinase receptor protects pro-urokinase against binding to the endocytic receptor.

    Science.gov (United States)

    Nykjaer, A; Kjøller, L; Cohen, R L; Lawrence, D A; Garni-Wagner, B A; Todd, R F; van Zonneveld, A J; Gliemann, J; Andreasen, P A

    1994-10-14

    The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2MR/LRP) binds several ligands, including complex between the two chain urokinase-type plasminogen activator (uPA) and type-1 plasminogen activator inhibitor (PAI-1), and the single chain zymogen pro-urokinase (pro-uPA). We have used truncated variants of uPA and PAI-1 as well as Fab fragments of monoclonal antibodies with known epitopes to identify regions in the uPA.PAI-1 complex and in pro-uPA involved in binding to alpha 2MR/LRP.uPA.PAI-1 complex bound with high affinity (EC50 about 0.4 nM) via contacts in the PAI-1 moiety as well as the uPA serine proteinase domain and the uPAA chain. Pro-uPA bound with lower affinity (EC50 about 10 nM), and efficient binding to alpha 2MR/LRP was dependent on contact with both the A chain and the serine proteinase domain. We analyzed the effect of complex formation with the urokinase receptor since this is the primary target for binding of uPA.PAI-1 and pro-uPA at the cell surface, and since it has been demonstrated that urokinase receptor-bound uPA.PAI-1 complex is internalized following interaction with alpha 2 MR/LRP (Nykjaer, A., Petersen, C. M., Møller, B., Jensen, P.H., Moestrup, S.K., Holtet, T.L., Etzerodt M., Thøgersen, H.C., Munch, M., Andreasen, P.A., and Gliemann, J. (1992) J. Biol. Chem. 267, 14543-14546). Soluble recombinant urokinase receptor blocked the binding of pro-uPA to alpha 2MR/LRP but caused only a slight reduction in the affinity for binding of uPA.PAI-1. Moreover, pro-uPA bound to the urokinase receptor at the cell surface was not internalized and degraded unless activated to uPA and complexed with PAI-1. We conclude that pro-uPA is protected against degradation via alpha 2MR/LRP when bound to uPAR due to shielding of a binding contact in the A chain, whereas the affinity of uPAR-bound uPA.PAI-1 complex for binding to alpha 2MR/LRP remains sufficient to allow rapid internalization and degradation.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    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 partia......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 partially by mRNA stabilization of inhibitor of apoptosis proteins, most prominently the X-linked inhibitor of apoptosis protein (XIAP). The antiapoptotic activity of uPA was dependent on its protease activity, the presence of uPA receptor (uPAR) and low-density lipoprotein receptor-related protein (LRP...

  9. Effect of purified, soluble urokinase receptor on the plasminogen-prourokinase activation system

    DEFF Research Database (Denmark)

    Behrendt, N; Danø, K

    1996-01-01

    The extracellular proteolytic pathway mediated by the urokinase plasminogen activator (uPA) is a cascade system, initiated by activation of the zymogen, pro-uPA. Pro-uPA as well as uPA binds to the cellular uPA receptor (uPAR) which has a central function in cell-dependent acceleration of the cas......The extracellular proteolytic pathway mediated by the urokinase plasminogen activator (uPA) is a cascade system, initiated by activation of the zymogen, pro-uPA. Pro-uPA as well as uPA binds to the cellular uPA receptor (uPAR) which has a central function in cell-dependent acceleration...

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

    Directory of Open Access Journals (Sweden)

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

    International Nuclear Information System (INIS)

    Qiao Qianlin; Zhou Shi; Wang Xuejian; Wu Qinghua; Song Jie

    2005-01-01

    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)

  12. Pharmacokinetics and pharmacodynamics of saruplase, an unglycosylated single-chain urokinase-type plasminogen activator, in patients with acute myocardial infarction

    NARCIS (Netherlands)

    Koster, R. W.; Cohen, A. F.; Hopkins, G. R.; Beier, H.; Günzler, W. A.; van der Wouw, P. A.

    1994-01-01

    We examined in patients with acute myocardial infarction (AMI) the pharmacokinetics of saruplase, an unglycosylated, single chain, urokinase-type plasminogen activator (rscu-PA) by measuring urokinase-type plasminogen activator (u-PA) antigen and total u-PA activity, its conversion to active

  13. The psychological aftermath of bereavement : Risk factors, mediating processes, and intervention

    NARCIS (Netherlands)

    Van der Houwen, H.K.

    2009-01-01

    In this dissertation some of the major facets associated with the psychological effects of bereavement were the subject of investigation: risk factors, mediating processes and intervention. Previous research on risk factors is limited because of a number of methodological shortcomings: a focus on

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

    LENUS (Irish Health Repository)

    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.

  15. INDUCTION AND/OR MAINTENANCE OF TUMOR DORMANCY BY DISRUPTION OF UROKINASE PLASMINOGEN ACTIVATOR RECEPTOR-INTEGRIN INTERACTION

    DEFF Research Database (Denmark)

    2010-01-01

    The present invention relates to a method of inducing cancer cells into dormancy and treating cancer in a subject. This method involves administering to a subject an effective amount of a compound that disrupts interaction between urokinase plasminogen activator receptor and integrin, thereby...... including cancer cells into dormancy and treating cancer in the subject. Also disclosed is a method of disrupting interaction between integrin and urokinase plasminogen activator receptor on cancer cells. The present invention also relates to a method of screening for compounds effective in inducing tumor...... dormancy and treating cancer in a subject....

  16. Rational targeting of the urokinase receptor (uPAR): development of antagonists and non-invasive imaging probes

    DEFF Research Database (Denmark)

    Kriegbaum, Mette Camilla; Persson, Morten; Haldager, L

    2011-01-01

    In the last two decades, the urokinase-type plasminogen activator receptor (uPAR) has been implicated in a number of human pathologies such as cancer, bacterial infections, and paroxysmal nocturnal hemoglobinuria. The primary function of this glycolipid-anchored receptor is to focalize uPA-mediat......In the last two decades, the urokinase-type plasminogen activator receptor (uPAR) has been implicated in a number of human pathologies such as cancer, bacterial infections, and paroxysmal nocturnal hemoglobinuria. The primary function of this glycolipid-anchored receptor is to focalize u...

  17. Association between polymorphism at 3 ׳UTR of urokinase gene and risk of calcium

    Directory of Open Access Journals (Sweden)

    S. Morovvati

    2016-06-01

    Full Text Available Background: Kidney stone is a common multifactorial disease in Iran. Environmental and genetic factors including single nucleotide polymorphism (SNP affect the incidence of kidney stones. Objective: The aim of this study was to determine the association of +4065 T/C polymorphism at 3′untranslated region (3'UTR of urokinase gene and calcium kidney stones. Methods: This case-control study was conducted on 70 patients with history of calcium kidney stones as case group and 70 healthy subjects as control group in the Baqiyatallah hospital in 2013. The polymorphism was assessed using the Allele Specific PCR (AS-PCR method. Allele and genotype frequencies of the two groups were compared using 2x2 contingency tables. Hardy-Weinberg equilibrium was compared between the two groups using Chi-square test. Findings: Of 70 cases, 10 (15% were heterozygous and 24 (34% were homozygous for the polymorphism. Of 70 controls, 25 (35% were heterozygous for the polymorphism. The frequency of mutant T allele was 41% in the case group and 18% in the control group. The frequency of mutant C allele was 59% in the case group and 82% in the control group. The risk of calcium kidney stones in carriers of the mutant allele was 1.7 times higher than non-carriers (OR: 1.7. Conclusion: With regards to the results, it seems that there is a significant association between the polymorphism at 3 ׳UTR of urokinase gene and formation of calcium kidney stones. Urokinase gene polymorphism may be introduced as a candidate gene involved in calcium stone formation.

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

    DEFF Research Database (Denmark)

    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...... part of the intact receptor, probably including the whole sequence 1-87, and contained N-linked carbohydrate. After detergent phase separation in the Triton X-114 system, the fragment was present in the water phase where its binding activity could be demonstrated in the absence of the rest...

  19. Jet and ultrasonic nebulization of single chain urokinase plasminogen activator (scu-PA)

    DEFF Research Database (Denmark)

    Münster, Anna-Marie; Bendstrup, E; Jensen, J.I.

    2000-01-01

    locally by nebulization in a recombinant zymogen form as single chain urokinase plasminogen activator (scu-PA). We aimed to characterize the particle size distribution, drug output, and enzymatic activity of scu-PA after nebulization with a Ventstream jet nebulizer (Medic-Aid, Bognor Regis, UK) and a Syst......'AM DP-100 ultrasonic nebulizer (Pulmolink, Kent, UK). The particle size distribution was measured with a laser diffraction method and the drug output was determined by collection on filters. The amount of protein on the filters was determined with the Lowry method, and the enzymatic activity after...... in terms of particle size distribution and preservation of fibrinolytic activity....

  20. Structure and ligand interactions of the urokinase receptor (uPAR)

    DEFF Research Database (Denmark)

    Kjaergaard, Magnus; Hansen, Line V.; Jacobsen, Benedikte

    2008-01-01

    The urokinase-type plasminogen activator receptor (uPAR or CD87) is a glycolipid-anchored membrane glycoprotein, which is responsible for focalizing plasminogen activation to the cell surface through its high-affinity binding to the serine protease uPA. This tight interaction (KD less than 1 n...... on disulfide connectivities, and they adopt a characteristic three-finger fold. Interestingly, the gene for uPAR is localized in a cluster of 6 homologous genes encoding proteins with multiple LU-domains. The structural biology of uPAR will be reviewed with special emphasis on its multidomain composition...

  1. The urokinase receptor and its structural homologue C4.4A in human cancer

    DEFF Research Database (Denmark)

    Jacobsen, B; Ploug, M

    2008-01-01

    The urokinase-type plasminogen activator receptor (uPAR) and its structural homologue C4.4A are multidomain members of the Ly6/uPAR/alpha-neurotoxin protein domain family. Both are glycosylphosphatidylinositol-anchored membrane glycoproteins encoded by neighbouring genes located on chromosome 19q13...... in a number of human cancers including colon adenocarcinoma and pulmonary squamous cell carcinoma. Targeting uPAR in experimental animal models has also provided promising results regarding the interference with pathogenic plasminogen activation. In the case of C4.4A, very recent data have demonstrated...

  2. Soluble Urokinase Plasminogen Activator Receptor as a Marker for Use of Antidepressants

    DEFF Research Database (Denmark)

    Haastrup, Eva; Grau, Katrine; Eugen-Olsen, Jesper

    2014-01-01

    OBJECTIVES: Inflammation is involved in the pathogenesis of depression. A few cross-sectional population-based studies have found that depression is associated with increased levels of inflammatory markers. Soluble urokinase plasminogen activation receptor (suPAR) is known to be a stable marker...... for inflammation. We investigated the bidirectional association between suPAR levels and use of antidepressants. METHODS: suPAR level was measured in 9305 blood donors and analysed in relation to 5-years follow-up data on purchase of antidepressants and hospital diagnoses of depression from a nationwide Danish...

  3. The psychological aftermath of bereavement : Risk factors, mediating processes, and intervention

    OpenAIRE

    Van der Houwen, H.K.

    2009-01-01

    In this dissertation some of the major facets associated with the psychological effects of bereavement were the subject of investigation: risk factors, mediating processes and intervention. Previous research on risk factors is limited because of a number of methodological shortcomings: a focus on only one or a few factors (which increases the chances of reporting spurious results) and reliance on use of a single measure of bereavement outcome. We avoided these pitfalls by simultaneously exami...

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    The uPAR and its ligand uPA are expressed by both osteoblasts and osteoclasts. Their function in bone remodeling is unknown. We report that uPAR-lacking mice display increased BMD, increased osteogenic potential of osteoblasts, decreased osteoclasts formation, and altered cytoskeletal reorganizat......The uPAR and its ligand uPA are expressed by both osteoblasts and osteoclasts. Their function in bone remodeling is unknown. We report that uPAR-lacking mice display increased BMD, increased osteogenic potential of osteoblasts, decreased osteoclasts formation, and altered cytoskeletal...... 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 u......PAR and produce urokinase (uPA). The purpose of this study was to investigate the role of uPAR in bone remodeling. MATERIALS AND METHODS: In vivo studies were performed in uPAR knockout (KO) and wildtype (WT) mice on a C57Bl6/SV129 (75:25) background. Bone mass was analyzed by pQCT. Excised tibias were subjected...

  5. Plasma levels of intact and cleaved urokinase receptor decrease in HIV-1-infected patients initiating highly active antiretroviral therapy

    DEFF Research Database (Denmark)

    Ostrowski, S R; Katzenstein, T L; Pedersen, M

    2006-01-01

    Elevated blood levels of soluble urokinase receptor (suPAR) measured by ELISA decrease in human immunodeficiency virus-1 (HIV-1)-infected patients initiating highly active antiretroviral therapy (HAART). As the suPAR ELISA measures both three- and two-domain suPAR [suPAR(I-III), suPAR(II-III)] an...

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

    DEFF Research Database (Denmark)

    Perch, M; Kofoed, P; Fischer, TK

    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...... an important association between suPAR and acute malaria infection in humans....

  7. Rational targeting of the urokinase receptor (uPAR): development of antagonists and non-invasive imaging probes

    DEFF Research Database (Denmark)

    Kriegbaum, M C; Persson, M; Haldager, L

    2011-01-01

    In the last two decades, the urokinase-type plasminogen activator receptor (uPAR) has been implicated in a number of human pathologies such as cancer, bacterial infections, and paroxysmal nocturnal hemoglobinuria. The primary function of this glycolipid-anchored receptor is to focalize uPA-mediat...

  8. A sensitive bioimmunoassay for thrombin-cleaved two-chain urokinase-type plasminogen activator in human body fluids

    NARCIS (Netherlands)

    Braat, E.A.M.; Nauland, U.; Dooijewaard, G.; Rijken, D.C.

    1996-01-01

    Thrombin cleaves single-chain urokinase-type plasminogen activator (scu-PA) into a two-chain form (tcu-PA/T), which is virtually inactive in plasminogen activator assays. Little is known about the physiological importance of tcu-PA/T. To examine the occurrence of tcu-PA/T in vivo, we developed a

  9. The inactivation of single-chain urokinase-type plasminogen activator by thrombin in a plasma milieu : effect of thrombomodulin

    NARCIS (Netherlands)

    Braat, E.A.M.; Los, P.; Rijken, D.C.

    1998-01-01

    Thrombin cleaves single-chain urokinase-type plasminogen activator (scu- PA) into a virtually inactive two-chain form (tcu-PA/T), a process which may contribute to the maintenance of a fresh blood clot. We have examined the inactivation of scu-PA by thrombin in a plasma milieu to get more insight in

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

    DEFF Research Database (Denmark)

    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...

  11. Extracellular collagenases and the endocytic receptor, urokinase plasminogen activator receptor-associated protein/Endo180, cooperate in fibroblast-mediated collagen degradation

    DEFF Research Database (Denmark)

    Madsen, Daniel H; Engelholm, Lars H; Ingvarsen, Signe

    2007-01-01

    The collagens of the extracellular matrix are the most abundant structural proteins in the mammalian body. In tissue remodeling and in the invasive growth of malignant tumors, collagens constitute an important barrier, and consequently, the turnover of collagen is a rate-limiting process in these......The collagens of the extracellular matrix are the most abundant structural proteins in the mammalian body. In tissue remodeling and in the invasive growth of malignant tumors, collagens constitute an important barrier, and consequently, the turnover of collagen is a rate-limiting process...... in these events. A recently discovered turnover route with importance for tumor growth involves intracellular collagen degradation and is governed by the collagen receptor, urokinase plasminogen activator receptor-associated protein (uPARAP or Endo180). The interplay between this mechanism and extracellular...... of large collagen fragments. First, we show that collagen that has been pre-cleaved by a mammalian collagenase is taken up much more efficiently than intact, native collagen by uPARAP/Endo180-positive cells. Second, we demonstrate that this preference is governed by the acquisition of a gelatin...

  12. In vitro activity of probiotic Lactobacillus reuteri against gastric cancer progression by downregulation of urokinase plasminogen activator/urokinase plasminogen activator receptor gene expression.

    Science.gov (United States)

    Rasouli, Bahareh Sadat; Ghadimi-Darsajini, Ali; Nekouian, Reza; Iragian, Gholam-Reza

    2017-01-01

    Gastric cancer (GC) is the third leading cause of cancer death, and most patients represent metastatic phenotype at the time of diagnosis. Urokinase plasminogen activator (uPA) system is well known for its critical roles in cancer cells invasion since uPA/uPA receptor (uPAR) overexpresses in several cancers. Subsequently, suppression of uPA/uPAR gene expression improves patients overall survival and prevents cancer progression. The aim of the current study was to investigate possible effects of live Lactobacillus reuteri as a probiotic in inhibition of GC cells proliferation and invasion. Human gastric adenocarcinoma epithelial cell line (AGS) cells were treated with different ratios of live L. reuteri and were incubated for 24, 48, and 72 h. Viability of cancer cells was measured with 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay, and the effects of L. reuteri on uPA/uPAR gene expression were assessed by real-time polymerase chain reaction. Our results showed that L. reuteri inhibits cell proliferation significantly in dose-dependent manner. Expressions of uPA and uPAR were downregulated followed by co-incubation of AGS cells and live L. reuteri compared to untreated-based line level. This study provides strong support in the role of L. reuteri in suppression of GC cell invasion by downregulation of pathways which is involved in extracellular matrix degradation such as uPA and uPAR.

  13. Motivational factors mediating the association between acculturation and participation in sport among young Turkish and Moroccan women in the Netherlands

    NARCIS (Netherlands)

    Hosper, Karen; Nierkens, Vera; van Valkengoed, Irene; Stronks, Karien

    2008-01-01

    Objective. Acculturation of migrant women has been associated with increased participation in physical activity, including participation in sport. We assessed which motivational factors mediate this association among Turkish and Moroccan migrant women in the Netherlands. Methods. Data were available

  14. Soluble urokinase-type plasminogen activator receptor forms in plasma as markers of atherosclerotic plaque vulnerability

    DEFF Research Database (Denmark)

    Olson, Fredrik J; Thurison, Tine; Ryndel, Mikael

    2009-01-01

    OBJECTIVES:: To test if circulating forms of the soluble urokinase-type plasminogen activator receptor (suPAR) are potential biomarkers of plaque vulnerability. DESIGN AND METHODS:: Plasma concentrations of suPAR(I-III), suPAR(II-III) and uPAR(I) were measured by time-resolved fluorescence...... immunoassays in Caucasian patients operated for symptomatic carotid atherosclerosis (n=255). Local suPAR release from plaques into the circulation was assessed in plasma passing retrogradely over the plaque in the carotid artery, collected during surgery (n=7). RESULTS:: The suPAR(I-III) (P=0.03) and su......PAR(II-III) (P=0.006) concentrations were higher after ischemic strokes and transient ischemic attacks, i.e., clinical subgroups associated with poorer prognosis and a less stable plaque phenotype, than after amaurosis fugax. Slightly elevated suPAR(I-III) levels were found in plasma from the carotid lesion...

  15. Targeting of peptide conjugated magnetic nanoparticles to urokinase plasminogen activator receptor (uPAR) expressing cells

    DEFF Research Database (Denmark)

    Hansen, Line; Larsen, Esben Kjær Unmack; Nielsen, Erik Holm

    2013-01-01

    Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted...... towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor...... patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific targeting peptide onto polyethylene glycol (PEG) coated USPIO nanoparticles by click chemistry resulted in a five times higher uptake in vitro in a uPAR positive cell line compared...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    Kim, Tae-Dong; Song, Kyoung-Sub; Li, Ge; Choi, Hoon; Park, Hae-Duck; Lim, Kyu; Hwang, Byung-Doo; Yoon, Wan-Hee

    2006-01-01

    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

  18. Soluble urokinase plasminogen activator receptor: a risk factor for carotid plaque, stroke, and coronary artery disease.

    Science.gov (United States)

    Persson, Margaretha; Östling, Gerd; Smith, Gustav; Hamrefors, Viktor; Melander, Olle; Hedblad, Bo; Engström, Gunnar

    2014-01-01

    Recent studies indicate that the urokinase system could have an important role in atherogenesis and plaque rupture. The relationships among the soluble urokinase plasminogen activator receptor (suPAR), carotid plaque, and incidence of ischemic stroke and coronary artery disease (CAD) events were studied in a prospective cohort. Occurrence of carotid plaque and plasma levels of suPAR were assessed in 5166 men and women, aged 45 to 68 years, participating in the Malmö Diet and Cancer study. Incidences of ischemic stroke and CAD were monitored during a mean follow-up of 15 years. Subjects with carotid plaque had significantly higher levels of suPAR compared with those without carotid plaque. suPAR was associated with increased incidence of ischemic stroke (hazard ratio [HR] for third versus first tertile, 1.50; 95% confidence interval [CI], 1.06-2.11) and CAD (HR, 1.55; 95% CI, 1.13-2.13) after adjustment for risk factors. The risk factor-adjusted HR for ischemic stroke was 2.21 (95% CI, 1.52-3.22) in subjects with carotid plaque and high suPAR (ie, third tertile) and 1.51 (95% CI, 1.05-2.17) in subjects with carotid plaque and low suPAR compared with those without carotid plaque and low suPAR (reference). High levels of suPAR significantly increased the risk of ischemic stroke and CAD in subjects with carotid plaque. suPAR is associated with increased occurrence of carotid plaque and increased incidence of ischemic stroke and CAD. Presence of both elevated levels of suPAR and carotid plaque increases the risk of ischemic stroke in an additive way.

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

  20. Epigenetic Aberrations Are Not Specific to Transcription Factor-Mediated Reprogramming

    Directory of Open Access Journals (Sweden)

    Ulf Tiemann

    2016-01-01

    Full Text Available Somatic cells can be reprogrammed to pluripotency using different methods. In comparison with pluripotent cells obtained through somatic nuclear transfer, induced pluripotent stem cells (iPSCs exhibit a higher number of epigenetic errors. Furthermore, most of these abnormalities have been described to be intrinsic to the iPSC technology. Here, we investigate whether the aberrant epigenetic patterns detected in iPSCs are specific to transcription factor-mediated reprogramming. We used germline stem cells (GSCs, which are the only adult cell type that can be converted into pluripotent cells (gPSCs under defined culture conditions, and compared GSC-derived iPSCs and gPSCs at the transcriptional and epigenetic level. Our results show that both reprogramming methods generate indistinguishable states of pluripotency. GSC-derived iPSCs and gPSCs retained similar levels of donor cell-type memory and exhibited comparable numbers of reprogramming errors. Therefore, our study demonstrates that the epigenetic abnormalities detected in iPSCs are not specific to transcription factor-mediated reprogramming.

  1. Soluble urokinase plasminogen activator receptor is a marker of dysmetabolism in HIV-infected patients receiving highly active antiretroviral therapy

    DEFF Research Database (Denmark)

    Andersen, Ove; Eugen-Olsen, Jesper; Kofoed, Kristian

    2008-01-01

    Circulating soluble urokinase plasminogen activator receptor (suPAR) reflects the immune and pro-inflammatory status of the HIV-infected patient. Highly active antiretroviral therapy (HAART) suppresses suPAR. Independent of the immune response to HAART, suPAR remains elevated in some HIV-infected......Circulating soluble urokinase plasminogen activator receptor (suPAR) reflects the immune and pro-inflammatory status of the HIV-infected patient. Highly active antiretroviral therapy (HAART) suppresses suPAR. Independent of the immune response to HAART, suPAR remains elevated in some HIV...... fluctuate. In conclusion, suPAR may reflect the metabolic status of the HIV-infected patient on HAART, thus linking low-grade inflammation, immune constitution, lipid and glucose metabolism, and fat redistribution. Circadian suPAR concentration appeared stable, suggesting that sampling schedule does...

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

    DEFF Research Database (Denmark)

    Botha, Shani; Fourie, Carla M T; Schutte, Rudolph

    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......-cause mortality. We determined whether suPAR, CRP and IL-6 are predictive of both all-cause and cardiovascular mortality in a black population, highly burdened by cardiovascular disease and HIV infection. METHODS: We included 1425 black South Africans, of which 208 died within five years after baseline data...

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

    DEFF Research Database (Denmark)

    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....

  4. Two-color cytofluorometry and cellular properties of the urokinase receptor associated with a human metastatic carcinomatous cell line

    International Nuclear Information System (INIS)

    Takahashi, K.; Gojobori, T.; Tanifuji, M.

    1991-01-01

    Purified human urokinase was labeled with either fluorescein isothiocyanate or iodine-125 and used as a probe for binding to the human metastatic carcinomatous cell line, Detroit 562. Cytofluorometry showed that the ligand bound preferentially to cells that had been exposed to acidic pH. The binding was competitive and decreased after mild tryptic digestion. The bound ligand could be removed by restoration of the cells to a low pH. Therefore, the cells had specific binding sites. The bound urokinase was involved in the breakdown of fibrin. Two-color cytofluorometric maps were constructed by counterstaining with propidium iodide. Results suggested that there were different cell populations that had different numbers of receptors and amounts of DNA. We cloned cells and found that single clones had homogeneous levels of receptors with different dissociation constants (from 10(-13) to 10(-11) mol/mg protein) for different clones. Cells of one clone, C5, which had high levels of receptor production, moved characteristically on a glass substratum coated with gold particles and reacted with wheat germ agglutinin, but not with concanavalin A. The receptors were found together with adhesion proteins at the sites where the cells adhered to the substrate. These results and the data obtained by zymography of the cellular proteins suggested that the urokinase-type plasminogen activators were bound to the receptors. The membrane-associated activator may stimulate local proteolysis, facilitating the migration of the tumor cell across the substrate

  5. Two-color cytofluorometry and cellular properties of the urokinase receptor associated with a human metastatic carcinomatous cell line

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, K.; Gojobori, T.; Tanifuji, M. (Shimane Medical Univ., Izumo (Japan))

    1991-02-01

    Purified human urokinase was labeled with either fluorescein isothiocyanate or iodine-125 and used as a probe for binding to the human metastatic carcinomatous cell line, Detroit 562. Cytofluorometry showed that the ligand bound preferentially to cells that had been exposed to acidic pH. The binding was competitive and decreased after mild tryptic digestion. The bound ligand could be removed by restoration of the cells to a low pH. Therefore, the cells had specific binding sites. The bound urokinase was involved in the breakdown of fibrin. Two-color cytofluorometric maps were constructed by counterstaining with propidium iodide. Results suggested that there were different cell populations that had different numbers of receptors and amounts of DNA. We cloned cells and found that single clones had homogeneous levels of receptors with different dissociation constants (from 10(-13) to 10(-11) mol/mg protein) for different clones. Cells of one clone, C5, which had high levels of receptor production, moved characteristically on a glass substratum coated with gold particles and reacted with wheat germ agglutinin, but not with concanavalin A. The receptors were found together with adhesion proteins at the sites where the cells adhered to the substrate. These results and the data obtained by zymography of the cellular proteins suggested that the urokinase-type plasminogen activators were bound to the receptors. The membrane-associated activator may stimulate local proteolysis, facilitating the migration of the tumor cell across the substrate.

  6. Methods of MicroRNA Promoter Prediction and Transcription Factor Mediated Regulatory Network.

    Science.gov (United States)

    Zhao, Yuming; Wang, Fang; Chen, Su; Wan, Jun; Wang, Guohua

    2017-01-01

    MicroRNAs (miRNAs) are short (~22 nucleotides) noncoding RNAs and disseminated throughout the genome, either in the intergenic regions or in the intronic sequences of protein-coding genes. MiRNAs have been proved to play important roles in regulating gene expression. Hence, understanding the transcriptional mechanism of miRNA genes is a very critical step to uncover the whole regulatory network. A number of miRNA promoter prediction models have been proposed in the past decade. This review summarized several most popular miRNA promoter prediction models which used genome sequence features, or other features, for example, histone markers, RNA Pol II binding sites, and nucleosome-free regions, achieved by high-throughput sequencing data. Some databases were described as resources for miRNA promoter information. We then performed comprehensive discussion on prediction and identification of transcription factor mediated microRNA regulatory networks.

  7. Identification and characterization of the murine cell surface receptor for the urokinase-type plasminogen activator

    DEFF Research Database (Denmark)

    Solberg, H; Løber, D; Eriksen, J

    1992-01-01

    Cell-binding experiments have indicated that murine cells on their surface have specific binding sites for mouse urokinase-type plasminogen activator (u-PA). In contrast to the human system, chemical cross-linking studies with an iodinated ligand did not yield any covalent adducts in the murine...... system, but in ligand-blotting analysis, two mouse u-PA-binding proteins could be visualized. To confirm that these proteins are the murine counterpart of the human u-PA receptor (u-PAR), a peptide was derived from the murine cDNA clone assigned to represent the murine u-PAR due to cross......-blotting analysis. Binding of mouse u-PA to its receptor showed species specificity in ligand-blotting analysis, since mouse u-PA did not bind to human u-PAR and human u-PA did not bind to mouse u-PAR. The apparent M(r) of mouse u-PAR varied between different mouse cell lines and ranged over M(r) 45...

  8. Urokinase-type plasminogen activator: a new target for male contraception?

    Science.gov (United States)

    Qin, Ying; Han, Yan; Xiong, Cheng-Liang; Li, Hong-Gang; Hu, Lian; Zhang, Ling

    2015-01-01

    Urokinase-type plasminogen activator (uPA) is closely related to male reproduction. With the aim of investigating the possibility for uPA as a potential contraceptive target, in the present work, Kunming male mice were immunized by human uPA subcutaneous injection at three separate doses for 3 times. Then the potency of the anti-human uPA antibody in serum was analyzed, and mouse fertility was evaluated. Serum antibody titers for human uPA in immunized groups all reached 1:10,240 or higher levels by enzyme linked immunosorbent assay, and mating experiments revealed that pregnancy rates and the mean number of embryos implanted after mating declined obviously (P male mice. Sperm function tests suggested that the sperm concentration, sperm viability, sperm motility, and in vitro fertilization rate for the cauda epididymis sperm in uPA-immunized groups were lower than those in the controls (P male mice could effectively reduce their fertility, and uPA could become a new target for immunocontraception in male contraceptive development.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  10. Terminalia catappa attenuates urokinase-type plasminogen activator expression through Erk pathways in Hepatocellular carcinoma.

    Science.gov (United States)

    Yeh, Chao-Bin; Yu, Yung-Luen; Lin, Chiao-Wen; Chiou, Hui-Ling; Hsieh, Ming-Ju; Yang, Shun-Fa

    2014-04-30

    The survival rate of malignant tumors, and especially hepatocellular carcinoma (HCC), has not improved primarily because of uncontrolled metastasis. In our previous studies, we have reported that Terminalia catappa leaf extract (TCE) exerts antimetastasis effects on HCC cells. However, the molecular mechanisms of urokinase-type plasminogen activator (u-PA) in HCC metastasis have not been thoroughly investigated, and remain poorly understood. The activities and protein levels of u-PA were determined by casein zymography and western blotting. Transcriptional levels of u-PA were detected by real-time PCR and promoter assays. We found that treatment of Huh7 cells with TCE significantly reduced the activities, protein levels and mRNA levels of u-PA. A chromatin immunoprecipitation (ChIP) assay showed that TCE inhibited the transcription protein of nuclear factors SP-1 and NF-κB. TCE also did inhibit the effects of u-PA by reducing the phosphorylation of ERK1/2 pathway. These results show that u-PA expression may be a potent therapeutic target in the TCE-mediated suppression of HCC metastasis.

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

    DEFF Research Database (Denmark)

    Thurison, Tine; Almholt, Kasper; Gårdsvoll, Henrik

    2015-01-01

    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 specific...... marker for cancer than increased expression of muPAR per se. The levels of the muPAR forms are dramatically affected by in vivo challenge with a urokinase -blocking antibody, demonstrating a functional role of uPA in uPAR cleavage. The levels of the muPAR forms are, however, unaffected by u......PA-deficiency, suggesting that redundant proteases maintains the task of cleaving uPAR(I-III) when uPA is absent. Our findings emphasize the significance of the cleaved uPAR forms as cancer biomarkers. The strong correlation between muPAR(I) and the tumor volume in our experimental setup may motivate investigations...

  12. Soluble Urokinase Plasminogen Activator Receptor as a Marker for Use of Antidepressants

    Science.gov (United States)

    Haastrup, Eva; Grau, Katrine; Eugen-Olsen, Jesper; Thorball, Christian; Kessing, Lars Vedel; Ullum, Henrik

    2014-01-01

    Objectives Inflammation is involved in the pathogenesis of depression. A few cross-sectional population-based studies have found that depression is associated with increased levels of inflammatory markers. Soluble urokinase plasminogen activation receptor (suPAR) is known to be a stable marker for inflammation. We investigated the bidirectional association between suPAR levels and use of antidepressants. Methods suPAR level was measured in 9305 blood donors and analysed in relation to 5-years follow-up data on purchase of antidepressants and hospital diagnoses of depression from a nationwide Danish register. Results For men and women without prior use of antidepressants we found a significantly higher risk for incident use of antidepressants with higher suPAR values. For men, the risk of first use of antidepressants increased by 72% from the 1st to the 4th quartile (HR = 1.72, 95% CI: 1.11–2.69). For women, it increased by 108% from the 1st to the 4th quartile (HR = 2.08, 95% CI: 1.45–2.98). Previous use of antidepressants was also significantly associated with higher suPAR levels (p = 0.002). Conclusions High suPAR levels are associated with an increased risk for both previous and future use of antidepressants in healthy men and women. High suPAR are also associated with increased risk for a hospital diagnosis of depression. PMID:25329298

  13. Inhibition of receptor-bound urokinase by plasminogen-activator inhibitors

    DEFF Research Database (Denmark)

    Ellis, Vincent John; Wun, T C; Behrendt, N

    1990-01-01

    Urokinase-type plasminogen activator (uPA) binds to a specific receptor on various cell types, the bound molecule retaining its enzymatic activity against plasminogen. We have now investigated whether receptor-bound uPA also retains the ability to react with and be inhibited by plasminogen...... activator inhibitors (PAI-1 and PAI-2). uPA bound to its receptor on human U937 monocyte-like cells was inhibited by PAI-1 (in its active form in the presence of vitronectin fragments) with an association rate constant of 4.5 x 10(6) M-1 s-1, which was 40% lower than that obtained for uPA in solution (7.9 x...... 10(6) M-1 s-1). The inhibition of uPA by PAI-2 was decreased to a similar extent by receptor binding, falling from 5.3 x 10(5) to 3.3 x 10(5) M-1 s-1. Stimulation of U937 cells with phorbol 12-myristate 13-acetate was accompanied by a further reduction in receptor-bound uPA inhibition by PAI-1...

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    PAR and produce urokinase (uPA). The purpose of this study was to investigate the role of uPAR in bone remodeling. MATERIALS AND METHODS: In vivo studies were performed in uPAR knockout (KO) and wildtype (WT) mice on a C57Bl6/SV129 (75:25) background. Bone mass was analyzed by pQCT. Excised tibias were subjected......The uPAR and its ligand uPA are expressed by both osteoblasts and osteoclasts. Their function in bone remodeling is unknown. We report that uPAR-lacking mice display increased BMD, increased osteogenic potential of osteoblasts, decreased osteoclasts formation, and altered cytoskeletal...... of macrophage-colony stimulating factor (M-CSF) and RANKL. Phalloidin staining in osteoclasts served to study actin ring and podosome formation. RESULTS: pQCT revealed increased bone mass in uPAR-null mice. Mechanical tests showed reduced load-sustaining capability in uPAR KO tibias. uPAR KO osteoblasts showed...

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

    Directory of Open Access Journals (Sweden)

    Andreas Kronbichler

    2016-01-01

    Full Text Available 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.

  16. Data on the regulation of moesin and merlin by the urokinase receptor (uPAR: Model explaining distal activation of integrins by uPAR

    Directory of Open Access Journals (Sweden)

    Bernard Degryse

    2017-12-01

    Full Text Available The data presented herein are connected to our research article (doi: 10.1016/j.biocel.2017.04.012 [1], in which we investigated the functional connections between the urokinase receptor (uPAR, and the ezrin/radixin/moesin (ERM proteins, moesin and merlin [1]. Firstly, a model of action is proposed that enlightens how uPAR regulates distal integrins. In addition, data show the effects of expressing wild-type moesin or permanently active T558D mutant of moesin on angiogenesis and morphology of human aortic endothelial cells (HAEC. Additional data compare the effects of urokinase (uPA, the main ligand of uPAR on the same cells. Lastly, we provide technical data demonstrating the effects of specific siRNA for moesin and merlin on moesin and merlin expression, respectively. Keywords: Urokinase receptor, Moesin, Merlin, Angiogenesis, siRNA

  17. Plasminogen-independent initiation of the pro-urokinase activation cascade in vivo. Activation of pro-urokinase by glandular kallikrein (mGK-6) in plasminogen-deficient mice

    DEFF Research Database (Denmark)

    List, K; Jensen, Ole Nørregaard; Bugge, T H

    2000-01-01

    The plasminogen activation (PA) system is involved in the degradation of fibrin and various extracellular matrix proteins, taking part in a number of physiological and pathological tissue remodeling processes including cancer invasion. This system is organized as a classical proteolytic cascade......, and as for other cascade systems, understanding the physiological initiation mechanism is of central importance. The attempts to identify initiation routes for activation of the proform of the key enzyme urokinase-type plasminogen activator (pro-uPA) in vivo have been hampered by the strong activator potency...

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

    DEFF Research Database (Denmark)

    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...... with aberrant filtration of uPA across the injured glomerular barrier. Amiloride inhibits urine uPA activity which attenuates plasminogen activation and urine protease activity in vivo. Urine uPA is a relevant target for amiloride in vivo....

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...... data were collected from 5,538 participants in the Danish population-based Inter99 study. Their suPAR levels were measured using a sandwich enzyme-linked immunosorbent assay. In the final adjusted model, smoking and morbid obesity were strongly associated with higher suPAR levels (P

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

    DEFF Research Database (Denmark)

    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...... 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...

  1. Expression and activity of the urokinase plasminogen activator system in canine primary brain tumors

    Directory of Open Access Journals (Sweden)

    Rossmeisl JH

    2017-04-01

    Full Text Available John H Rossmeisl,1–3 Kelli Hall-Manning,4 John L Robertson,1,3,5 Jamie N King,1,2 Rafael V Davalos,3,5 Waldemar Debinski,3 Subbiah Elankumaran6,† 1Veterinary and Comparative Neuro-Oncology Laboratory, 2Department of Small Animal Clinical Sciences, 3The Brain Tumor Center of Excellence, Wake Forest Baptist Medical Center Comprehensive Cancer Center, Winston-Salem, NC, 4Virginia Tech Animal Laboratory Services, Virginia-Maryland College of Veterinary Medicine, 5Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Virginia Tech, 6Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA, USA†The authors regret to advise of the passing of Dr Subbiah Elankumaran prior to publicationBackground: The expression of the urokinase plasminogen activator receptor (uPAR, a glycosylphosphatidylinositol-anchored protein family member, and the activity of its ligand, urokinase-type plasminogen activator (uPA, have been associated with the invasive and metastatic potentials of a variety of human brain tumors through their regulation of extracellular matrix degradation. Domesticated dogs develop naturally occurring brain tumors that share many clinical, phenotypic, molecular, and genetic features with their human counterparts, which has prompted the use of the dogs with spontaneous brain tumors as models to expedite the translation of novel brain tumor therapeutics to humans. There is currently little known regarding the role of the uPA system in canine brain tumorigenesis. The objective of this study was to characterize the expression of uPAR and the activity of uPA in canine brain tumors as justification for the development of uPAR-targeted brain tumor therapeutics in dogs.Methods: We investigated the expression of uPAR in 37 primary canine brain tumors using immunohistochemistry, Western blotting, real

  2. The urokinase-system in tumor tissue stroma of the breast and breast cancer cell invasion.

    Science.gov (United States)

    Hildenbrand, Ralf; Schaaf, Antonela

    2009-01-01

    The urokinase-system has been implicated in tumor spread. The serine protease urokinase-type plasminogen activator (uPA), its receptor (uPAR) and its inhibitor (PAI-1) are involved in the control of extracellular turnover, cell migration, invasion, cell signalling, proliferation, apoptosis and angiogenesis leading to a variety of different responses, under both physiological and pathological conditions. uPA and PAI-1 were the first novel tumor biological factors to be validated at the highest level of evidence regarding their clinical utility in breast cancer. However, it is unclear whether it is their (relative) levels in the tumor stroma or in the tumor cells themselves that is the most relevant to patients outcome. This is the first study in which tumor cells and stromal tissue of invasive breast carcinomas were separated by laser capture microdissection followed by ELISA-based determination of the uPA, uPAR and PAI-1 levels. In addition, we localized uPA, uPAR and PAI-1 distribution in invasive breast cancer (n=30) and in ductal carcinoma in situ (DCIS, n=30) by immunohistochemistry and in situ hybridization. We have demonstrated that no significant differences between uPA, uPAR and PAI-1 levels in tumor stroma only, tumor cells only and not separated breast cancer tissue exist (p>0.05). Our results suggest that similar expression levels of these factors in both compartments and in not separated breast cancer tissue may have the same impact on the clinical behavior of breast cancer. These results are an important issue for practical use of tissue sampling. For using uPA and PAI-1 levels as prognostic and predictive factors in breast cancer the quantity of tumor stroma in the tumor tissue specimen is not relevant for assessment patients outcome. Our results were confirmed by immunohistochemistry and in situ hybridization analysis showing that in nearly all cases of invasive carcinomas and DCIS fibroblasts as well as macrophages strongly express uPA, uPAR and PAI

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

    Directory of Open Access Journals (Sweden)

    Joppe W R Hovius

    2009-05-01

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

  4. Interleukin-33 induces urokinase in human endothelial cells--possible impact on angiogenesis.

    Science.gov (United States)

    Stojkovic, S; Kaun, C; Heinz, M; Krychtiuk, K A; Rauscher, S; Lemberger, C E; de Martin, R; Gröger, M; Petzelbauer, P; Huk, I; Huber, K; Wojta, J; Demyanets, S

    2014-06-01

    Urokinase-type plasminogen activator (u-PA) plays a pivotal role in extracellular proteolysis and is thought to be critically involved in the modulation of angiogenesis. Interleukin (IL)-33 is a member of the IL-1 cytokine family, which is thought to act as danger signal that is released from cells after injury. IL-33 is involved in the pathogenesis of various inflammatory diseases and previously was shown to induce angiogenesis and inflammatory activation of endothelial cells. We investigated the impact of IL-33 on u-PA in endothelial cells as a new possible function for IL-33. We could demonstrate that IL-33 upregulated u-PA mRNA expression and protein production in human coronary artery and human umbilical vein endothelial cells in a time- and concentration-dependent manner via interaction with its receptor ST2 and activation of the nuclear factor-κB pathway but independent of autocrine IL-1-induced effects. The hydroxymethylglutaryl-coenzyme A reductase inhibitor simvastatin abrogated the IL-33-induced increase in u-PA, thus providing further evidence for pleiotropic effects of statins. IL-33 induced u-PA-dependent capillary-like tube formation and vessel sprouting. In human carotid atherosclerotic plaques (n = 16), u-PA mRNA positively correlated with IL-33 mRNA expression (r = 0.780, P < 0.001). Furthermore, IL-33 and u-PA protein were detected in endothelial cells in these samples using fluorescence immunohistochemistry. We hypothesize that IL-33, representing a danger signal that is released after tissue damage, in addition to its role in the inflammatory activation of endothelial cells, is involved in u-PA-driven angiogenesis, a process that has been shown before to be linked to inflammation in various pathologies. © 2014 International Society on Thrombosis and Haemostasis.

  5. Imaging the urokinase plasminongen activator receptor in preclinical breast cancer models of acquired drug resistance.

    Science.gov (United States)

    LeBeau, Aaron M; Sevillano, Natalia; King, Mandy L; Duriseti, Sai; Murphy, Stephanie T; Craik, Charles S; Murphy, Laura L; VanBrocklin, Henry F

    2014-01-01

    Subtype-targeted therapies can have a dramatic impact on improving the quality and quantity of life for women suffering from breast cancer. Despite an initial therapeutic response, cancer recurrence and acquired drug-resistance are commonplace. Non-invasive imaging probes that identify drug-resistant lesions are urgently needed to aid in the development of novel drugs and the effective utilization of established therapies for breast cancer. The protease receptor urokinase plasminogen activator receptor (uPAR) is a target that can be exploited for non-invasive imaging. The expression of uPAR has been associated with phenotypically aggressive breast cancer and acquired drug-resistance. Acquired drug-resistance was modeled in cell lines from two different breast cancer subtypes, the uPAR negative luminal A subtype and the uPAR positive triple negative subtype cell line MDA-MB-231. MCF-7 cells, cultured to be resistant to tamoxifen (MCF-7 TamR), were found to significantly over-express uPAR compared to the parental cell line. uPAR expression was maintained when resistance was modeled in triple-negative breast cancer by generating doxorubicin and paclitaxel resistant MDA-MB-231 cells (MDA-MB-231 DoxR and MDA-MB-231 TaxR). Using the antagonistic uPAR antibody 2G10, uPAR was imaged in vivo by near-infrared (NIR) optical imaging and (111)In-single photon emission computed tomography (SPECT). Tumor uptake of the (111)In-SPECT probe was high in the three drug-resistant xenografts (> 46 %ID/g) and minimal in uPAR negative xenografts at 72 hours post-injection. This preclinical study demonstrates that uPAR can be targeted for imaging breast cancer models of acquired resistance leading to potential clinical applications.

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

    Science.gov (United States)

    Botkjaer, Kenneth A; Fogh, Sarah; Bekes, Erin C; Chen, Zhuo; Blouse, Grant E; Jensen, Janni M; Mortensen, Kim K; Huang, Mingdong; Deryugina, Elena; Quigley, James P; Declerck, Paul J; Andreasen, Peter A

    2011-08-15

    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, with high levels correlating with a poor prognosis. This observation has stimulated efforts into finding new principles for intervening with uPA's activity. In the present study we characterize the so-called autolysis loop in the catalytic domain of uPA as a potential inhibitory target. This loop was found 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, demonstrating a direct link between conformational changes of the autolysis loop and the creation of a catalytically mature active site. All three antibodies are potent inhibitors of uPA activity, the two pro-uPA-specific ones by inhibiting conversion of pro-uPA to active uPA and the active uPA-specific antibody by shielding the access of plasminogen to the active site. Furthermore, using immunofluorescence, the conformation-specific antibodies mAb-112 and mAb-12E6B10 enabled us to selectively stain pro-uPA or active uPA on the surface of cultured cells. Moreover, in various independent model systems, the antibodies inhibited tumour cell invasion and dissemination, providing evidence for the feasibility of pharmaceutical intervention with serine protease activity by targeting surface loops that undergo conformational changes during zymogen activation. © The Authors Journal compilation © 2011 Biochemical Society

  7. Factors mediating the effects of a depression intervention on functional disability in older African Americans.

    Science.gov (United States)

    Gitlin, Laura N; Szanton, Sarah L; Huang, Jin; Roth, David L

    2014-12-01

    To determine factors mediating the effects of a depression intervention for older African Americans on functional disability and, secondarily, whether functional improvements mediate intervention effects on depressive symptoms. Structural equation modeling to examine mediators in a secondary analysis of a randomized trial with 4-month follow-up. Philadelphia region. Community-dwelling African Americans (≥55) with depressive symptoms living in an urban area (N = 208). Up to 10 one-hour sessions over 4 months conducted by licensed social workers who provided care management, referrals and linkages, stress reduction techniques, depression knowledge and symptom recognition, and behavioral activation techniques. Main outcome was self-reported functional difficulty level for 18 basic activities. Mediators included depression severity (Patient Health Questionnaire), depression knowledge and symptom recognition, behavioral activation, and anxiety. At 4 months, the intervention had positive effects on functional difficulty and all mediators (P intervention's effect on functional disability. Enhancing behavioral activation and decreasing anxiety were not found to mediate improvements in functional disability. The two significant mediators jointly explained 62.5% of the intervention's total effect on functional disability. Functional improvement was not found to mediate the intervention's effect on depressive symptoms. This multicomponent depression intervention for African Americans has an effect on functional disability that is driven primarily by enhancing symptom recognition and decreasing depressive symptoms. Reduction of functional difficulties did not account for improvements in depressive symptoms. Nonpharmacological treatments for depressive symptoms that enhance symptom recognition in older African Americans can also reduce their functional difficulties with daily living activities. © 2014, Copyright the Authors Journal compilation © 2014, The American

  8. Chemical genomic-based pathway analyses for epidermal growth factor-mediated signaling in migrating cancer cells.

    Directory of Open Access Journals (Sweden)

    Shigeyuki Magi

    Full Text Available To explore the diversity and consistency of the signaling pathways that regulate tumor cell migration, we chose three human tumor cell lines that migrated after treatment with EGF. We then quantified the effect of fifteen inhibitors on the levels of expression or the phosphorylation levels of nine proteins that were induced by EGF stimulation in each of these cell lines. Based on the data obtained in this study and chemical-biological assumptions, we deduced cell migration pathways in each tumor cell line, and then compared them. As a result, we found that both the MEK/ERK and JNK/c-Jun pathways were activated in all three migrating cell lines. Moreover, GSK-3 and p38 were found to regulate PI3K/Akt pathway in only EC109 cells, and JNK was found to crosstalk with p38 and Fos related pathway in only TT cells. Taken together, our analytical system could easily distinguish between the common and cell type-specific pathways responsible for tumor cell migration.

  9. Short-term myeloid growth factor mediated expansion of bone marrow haemopoiesis studied by localized magnetic resonance proton spectroscopy

    DEFF Research Database (Denmark)

    Jensen, K E; Hansen, P B; Larsen, V A

    1994-01-01

    -density cell proliferation rate in marrow samples increased from median 21.9 (range 4.5-31) x 10(3) cpm to 54.7 (range 13.9-94) x 10(3) cpm and the total number of myeloid progenitors enumerated as day 7/14 GM-CFUs per volume aspirated marrow increased from median 11/8 x 10(3) (range 4.0-87.5/2.2-103.0) to 64...

  10. Comparison of the inhibition of urokinase-type plasminogen activator (u-PA) activity by monoclonal antibodies specific for u-PA as assessed by different assays

    NARCIS (Netherlands)

    Boheemen, P.A. van; Hoogen, N.M. van den; Koolwijk, N.

    1995-01-01

    Six murine monoclonal antibodies (MAbs) specific for urokinase-type plasminogen activator (u-PA) were tested for their ability to inhibit u-PA activity in three different assays with respect to amidolytic activity, plasminogen activation and fibrinolytic activity. Two of the MAbs were able to

  11. A new assay for measurement of the liberated domain I of the urokinase receptor in plasma improves the prediction of survival in colorectal cancer

    DEFF Research Database (Denmark)

    Thurison, Tine; Lomholt, Anne F; Rasch, Morten G

    2010-01-01

    The liberated domain I of the urokinase plasminogen activator receptor [uPAR(I)] is a significant prognostic marker in lung and ovarian cancer, although the uPAR(I) concentration is below the limit of quantification (LOQ) in a substantial proportion of patient samples (Lung Cancer 2005;48:349-55;...

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

    DEFF Research Database (Denmark)

    Jiang, Longguang; Zhao, Baoyu; Xu, Peng

    2015-01-01

    Abstract 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...

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

    DEFF Research Database (Denmark)

    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...

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

    DEFF Research Database (Denmark)

    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...

  15. Domain interplay in the urokinase receptor. Requirement for the third domain in high affinity ligand binding and demonstration of ligand contact sites in distinct receptor domains

    DEFF Research Database (Denmark)

    Behrendt, N; Ronne, E; Dano, K

    1996-01-01

    The urokinase plasminogen activator receptor (uPAR) is a membrane protein comprised of three extracellular domains. In order to study the importance of this domain organization in the ligand-binding process of the receptor we subjected a recombinant, soluble uPAR (suPAR) to specific proteolytic...

  16. Cell-induced potentiation of the plasminogen activation system is abolished by a monoclonal antibody that recognizes the NH2-terminal domain of the urokinase receptor

    DEFF Research Database (Denmark)

    Rønne, E; Behrendt, N; Ellis, V

    1991-01-01

    We have raised four monoclonal antibodies recognizing different epitopes within the human cell-surface receptor for urokinase-type plasminogen activator (u-PA). One of these antibodies completely abolishes the potentiation of plasmin generation observed upon incubation of the zymogens pro...

  17. The serum level of soluble urokinase receptor is elevated in tuberculosis patients and predicts mortality during treatment: a community study from Guinea-Bissau

    DEFF Research Database (Denmark)

    Eugen-Olsen, Jesper; Gustafson, P; Sidenius, N

    2002-01-01

    OBJECTIVE: To investigate whether the serum level of soluble urokinase plasminogen activator receptor (suPAR) carries prognostic information in individuals infected with Mycobacterium tuberculosis. DESIGN: suPAR was measured by ELISA in 262 individuals at the time of enrolment into a cohort based...

  18. Urokinase-type plasminogen activator receptor plays a role in neutrophil migration during lipopolysaccharide-induced peritoneal inflammation but not during Escherichia coli-induced peritonitis

    NARCIS (Netherlands)

    Renckens, Rosemarijn; Roelofs, Joris J. T. H.; Florquin, Sandrine; van der Poll, Tom

    2006-01-01

    BACKGROUND: Urokinase-type plasminogen activator receptor (uPAR) is expressed on many different cells, including leukocytes. uPAR has been implicated to play a role in neutrophil migration to sites of inflammation. METHODS: To determine the role that uPAR plays in neutrophil recruitment in response

  19. Circulating soluble urokinase plasminogen activator receptor levels and peripheral arterial disease outcomes.

    Science.gov (United States)

    Samman Tahhan, Ayman; Hayek, Salim S; Sandesara, Pratik; Hajjari, Jamal; Hammadah, Muhammad; O'Neal, Wesley T; Kelli, Heval M; Alkhoder, Ayman; Ghasemzadeh, Nima; Ko, Yi-An; Aida, Hiroshi; Gafeer, Mohamad Mazen; Abdelhadi, Naser; Mohammed, Kareem Hosny; Patel, Keyur; Arya, Shipra; Reiser, Jochen; Vaccarino, Viola; Sperling, Laurence; Quyyumi, Arshed

    2017-09-01

    Circulating soluble urokinase plasminogen activator receptor (suPAR) is a marker of immune activation associated with atherosclerosis. Whether suPAR levels are associated with prevalent peripheral arterial disease (PAD) and its adverse outcomes remains unknown and is the aim of the study. SuPAR levels were measured in 5810 patients (mean age 63 years, 63% male, 77% with obstructive coronary artery disease [CAD]) undergoing cardiac catheterization. The presence of PAD (n = 967, 17%) was classified as carotid (36%), lower/upper extremities (30%), aortic (15%) and multisite disease (19%). Multivariable logistic and Cox regression models were used to determine independent predictors of prevalent PAD and outcomes including all-cause death, cardiovascular death and PAD-related events after adjustment for age, gender, race, body mass index, smoking, diabetes, hypertension, hyperlipidemia, renal function, heart failure history, and obstructive CAD. Plasma suPAR levels were 22.5% (p < 0.001) higher in patients with PAD compared to those without PAD. Plasma suPAR was higher in patients with more extensive PAD (≥2 compared to single site) p < 0.001. After multivariable adjustment, suPAR was associated with prevalent PAD; odds ratio (OR) for highest compared to lowest tertile of 2.0, 95% CI (1.6-2.5) p < 0.001. In Cox survival analyses adjusted for clinical characteristics and medication regimen, suPAR (in the highest vs. lowest tertile) remained an independent predictor of all-cause death [HR 3.1, 95% CI (1.9-5.3)], cardiovascular death [HR 3.5, 95% CI (1.8-7.0)] and PAD-related events [HR = 1.8, 95% CI (1.3-2.6) p < 0.001 for all]. Plasma suPAR level is predictive of prevalent PAD and of incident cardiovascular and PAD-related events. Whether SuPAR measurement can help screen, risk stratify, or monitor therapeutic responses in PAD requires further investigation. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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

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

    DEFF Research Database (Denmark)

    Ellis, V; Behrendt, N; Danø, K

    1991-01-01

    importance for the efficient activation of Plg by receptor-bound uPA. Plasmin generated in the cell-surface Plg activation system described here was also observed to be protected from its principal physiological inhibitor alpha-2-antiplasmin. Together, these data demonstrate that the cell surface constitutes......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 u.......67 microM, below the physiological Plg concentration of 2 microM. A concomitant 6-fold reduction in kcat resulted in an increase in the overall catalytic efficiency, kcat/Km, of 5.7-fold. This high affinity Plg activation was abolished in the presence of a Plg-binding antagonist. In contrast to intact...

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

    DEFF Research Database (Denmark)

    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......: 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...... of arterial stiffness (pulse wave velocity ≥10 m s(-1) ). Analyses were adjusted for gender, age, systolic blood pressure, estimated glomerular filtration rate, UAER, glycated haemoglobin (HbA1c ), total cholesterol, body mass index, C-reactive protein, antihypertensive treatment and smoking. RESULTS: Soluble...

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

    DEFF Research Database (Denmark)

    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...

  4. Soluble urokinase receptor is elevated in cerebrospinal fluid from patients with purulent meningitis and is associated with fatal outcome

    DEFF Research Database (Denmark)

    Ostergaard, Christian; Benfield, Thomas; Lundgren, Jens D

    2004-01-01

    The urokinase-type plasminogen activator system has been suggested to play a pathophysiological role in brain damage. The aim of this study was to evaluate CSF levels of suPAR in 183 patients clinically suspected of having meningitis on admission. Of these, 54 patients were found to have purulent...... meningitis, 63 had lymphocytic meningitis, 12 had encephalitis, and 54 patients were suspected of, but had no evidence of, meningitis. There was a significant difference in suPAR levels among patient groups (Kruskal Wallis test, p ... infection (purulent meningitis: median suPAR 2.41 microg/l (range 0.12-35), lymphocytic meningitis: 1.10 microg/l (0.15-5.31), and encephalitis (1.77 microg/l (0.17-11.7)) than in patients without meningitis (0.64 microg/l (0-5.34) (Dunn's multiple comparison test, p

  5. Involvement of urokinase receptor in the cross-talk between human hematopoietic stem cells and bone marrow microenvironment

    DEFF Research Database (Denmark)

    Selleri, Carmine; Montuori, Nunzia; Salvati, Annamaria

    2016-01-01

    Hematopoietic stem cells (HSCs) reside in bone marrow (BM) and can be induced to mobilize into the circulation for transplantation. Homing and lodgement into BM of transplanted HSCs are the first critical steps in their engraftment and involve multiple interactions between HSCs and the BM...... Culture (LTC)-Initiating Cells (ICs) and in the release of clonogenic progenitors from LTCs of CD34+ HSCs. Further, suPAR increases adhesion and survival of CD34+ KG1 AML cells, whereas uPAR84-95 increases their proliferation.Thus, circulating DIIDIII-suPAR, strongly increased in HSC mobilization...... microenvironment.uPAR is a three domain receptor (DIDIIDIII) which binds urokinase, vitronectin, integrins. uPAR can be cleaved and shed from the cell surface generating full-length and cleaved soluble forms (suPAR and DIIDIII-suPAR). DIIDIII-suPAR can bind fMLF receptors through the SRSRY sequence (residues 88...

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

    International Nuclear Information System (INIS)

    Song, Jae Min; Yoon, Woong; Kim, Jae Kyu; Seo, Jeong Jin; Heo, Sook Hee; Park, Jin Gyoon; Jeong, Yoon Yeon; Kang, Heoung Keun

    2002-01-01

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. [Transradial approach for transcatheter selective superior mesenteric artery urokinase infusion therapy in patients with acute extensive portal and superior mesenteric vein thrombosis].

    Science.gov (United States)

    Wang, Yan; Wang, Mao-qiang; Liu, Feng-yong; Wang, Zhi-jun; Duan, Feng; Song, Peng

    2012-06-05

    To evaluate the feasibility and efficacy of urokinase infusion therapy via a transradial approach for transcatheter superior mesenteric artery (SMA) in patients with acute extensive portal and superior mesenteric venous thrombosis. During a period of 8 years, 47 patients with acute extensive thrombosis of portal vein (PV) and superior mesenteric veins (SMV) received urokinase infusion therapy by transcatheter selective SMA via radial artery. Their mean age was 44 ± 13 years (range: 19 - 65). Through radial sheath, a 5F catheter was placed into SMA and subsequently the infusion of urokinase was given for 5 - 11 days (mean: 7.1 ± 2.5). Adequate anticoagulation was initiated during treatment, throughout hospitalization and post-discharge. Follow-up contrast-enhanced computed tomography (CT) was performed in each patient every 3 days and before the removal of infusion catheter. Termination of urokinase infusion therapy was decided on the basis of clinical and radiographic findings. Technical success was achieved in all patients. Two patients had worsening abdominal pain, developed the signs of peritonitis at 24 hours after interventional treatment and underwent eventual laparotomy with the resection of necrotic bowel. Substantial clinical improvement was observed in 45 (95.7%) of them after the procedure. Minor complications at the radial puncture site were observed in 7 patients (14.9%) and infusion therapy continued. Follow-up CT scans at pre-discharge demonstrated a nearly complete disappearance of PV-SMV thrombosis in 29 patients (64.4%) and partial recanalization of PV-SMV thrombosis in 16 patients (35.6%). They were discharged at 9 - 20 days (mean: 12 ± 6) post-admission. The mean post-discharge duration of follow-up was 48 ± 20 months. Recurrent episodes of PV and SMV thrombosis were observed in 2 (4.4%) patients at 6 months and 5 years respectively post-discharge and they were treated successfully with urokinase infusion. The transcatheter SMA urokinase

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

    Directory of Open Access Journals (Sweden)

    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

  10. Association of Serum Soluble Urokinase Receptor Levels With Progression of Kidney Disease in Children.

    Science.gov (United States)

    Schaefer, Franz; Trachtman, Howard; Wühl, Elke; Kirchner, Marietta; Hayek, Salim S; Anarat, Ali; Duzova, Ali; Mir, Sevgi; Paripovic, Dusan; Yilmaz, Alev; Lugani, Francesca; Arbeiter, Klaus; Litwin, Mieczyslaw; Oh, Jun; Matteucci, Maria Chiara; Gellermann, Jutta; Wygoda, Simone; Jankauskiene, Augustina; Klaus, Günter; Dusek, Jiri; Testa, Sara; Zurowska, Aleksandra; Caldas Afonso, Alberto; Tracy, Melissa; Wei, Changli; Sever, Sanja; Smoyer, William; Reiser, Jochen

    2017-11-06

    Conventional methods to diagnose and monitor chronic kidney disease (CKD) in children, such as creatinine level and cystatin C-derived estimated glomerular filtration rate (eGFR) and assessment of proteinuria in spot or timed urine samples, are of limited value in identifying patients at risk of progressive kidney function loss. Serum soluble urokinase receptor (suPAR) levels strongly predict incident CKD stage 3 in adults. To determine whether elevated suPAR levels are associated with renal disease progression in children with CKD. Post hoc analysis of 2 prospectively followed up pediatric CKD cohorts, ie, the ESCAPE Trial (1999-2007) and the 4C Study (2010-2016), with serum suPAR level measured at enrollment and longitudinal eGFR measured prospectively. In the 2 trials, a total of 898 children were observed at 30 (ESCAPE Trial; n = 256) and 55 (4C Study; n = 642) tertiary care hospitals in 13 European countries. Renal diagnoses included congenital anomalies of the kidneys and urinary tract (n = 637 [70.9%]), tubulointerstitial nephropathies (n = 92 [10.2%]), glomerulopathies (n = 69 [7.7%]), postischemic CKD (n = 42 [4.7%]), and other CKD (n = 58 [6.5%]). Total follow-up duration was up to 7.9 years, and median follow-up was 3.1 years. Analyses were conducted from October 2016 to December 2016. Serum suPAR level was measured at enrollment, and eGFR was measured every 2 months in the ESCAPE Trial and every 6 months in the 4C Study. The primary end point of CKD progression was a composite of 50% eGFR loss, eGFR less than 10 mL/min/1.73 m2, or initiation of renal replacement therapy. The primary end point in this study was renal survival, defined as a composite of 50% loss of GFR that persisted for at least 1 month, the start of renal replacement therapy, or an eGFR less than 10 mL/min/1.73 m2. Of the 898 included children, 560 (62.4%) were male, and the mean (SD) patient age at enrollment was 11.9 (3.5) years. The mean (SD) eGFR was 34

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

    International Nuclear Information System (INIS)

    Sasaki, Hiroshi; Klotz, Laurence H.; Sugar, Linda M.; Kiss, Alexander; Venkateswaran, Vasundara

    2015-01-01

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

  12. Regulation of DNA methylation in human breast cancer. Effect on the urokinase-type plasminogen activator gene production and tumor invasion.

    Science.gov (United States)

    Guo, Yongjing; Pakneshan, Pouya; Gladu, Julienne; Slack, Andrew; Szyf, Moshe; Rabbani, Shafaat A

    2002-11-01

    Urokinase-type plasminogen activator (uPA) is a member of the serine protease family and can break down various components of the extracellular matrix to promote growth, invasion, and metastasis of several malignancies including breast cancer. In the current study we examined the role that the DNA methylation machinery might be playing in regulating differential uPA gene expression in breast cancer cell lines. uPA mRNA is expressed in the highly invasive, hormone-insensitive human breast cancer cell line MDA-MB-231 but not in hormone-responsive cell line MCF-7. Using methylation-sensitive PCR, we show that 90% of CpG dinucleotides in the uPA promoter are methylated in MCF-7 cells, whereas fully demethylated CpGs were detected in MDA-MB-231 cells. uPA promoter activity, which is directly regulated by the Ets-1 transcription factor, is inhibited by methylation as determined by uPA promoter-luciferase reporter assays. We then tested whether the state of expression and methylation of the uPA promoter correlates with the global level of DNA methyltransferase and demethylase activities in these cell lines. We show that maintenance DNA methyltransferase activity is significantly higher in MCF-7 cells than in MDA-MB-231 cells, whereas demethylase activity is higher in MDA-MB-231 cells. We suggest that the combination of increased DNA methyltransferase activity with reduced demethylase activity contributes to the methylation and silencing of uPA expression in MCF-7 cells. The converse is true in MDA-MB-231 cells, which represents a late stage highly invasive breast cancer. The histone deacetylase inhibitor, Trichostatin A, induces the expression of the uPA gene in MDA-MB-231 cells but not in MCF-7 cells. This supports the hypothesis that DNA methylation is the dominant mechanism involved in the silencing of uPA gene expression. Taken together, these results provide insight into the mechanism regulating the transcription of the uPA gene in the complex multistep process of

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-08-28

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

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

    OpenAIRE

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

  15. Transradial Approach for Transcatheter Selective Superior Mesenteric Artery Urokinase Infusion Therapy in Patients with Acute Extensive Portal and Superior Mesenteric Vein Thrombosis

    International Nuclear Information System (INIS)

    Wang Maoqiang; Guo Liping; Lin Hanying; Liu Fengyong; Duan Feng; Wang Zhijun

    2010-01-01

    The purpose of this investigation was to assess the feasibility and effectiveness of transradial approach for transcatheter superior mesenteric artery (SMA) urokinase infusion therapy in patients with acute extensive portal and superior mesenteric venous thrombosis. During a period of 7 years, 16 patients with acute extensive thrombosis of the portal (PV) and superior mesenteric veins (SMV) were treated by transcatheter selective SMA urokinase infusion therapy by way of the radial artery. The mean age of the patients was 39.5 years. Through the radial sheath, a 5F Cobra catheter was inserted into the SMA, and continuous infusion of urokinase was performed for 5-11 days (7.1 ± 2.5 days). Adequate anticoagulation was given during treatment, throughout hospitalization, and after discharge. Technical success was achieved in all 16 patients. Substantial clinical improvement was seen in these 16 patients after the procedure. Minor complications at the radial puncture site were observed in 5 patients, but trans-SMA infusion therapy was not interrupted. Follow-up computed tomography scan before discharge demonstrated nearly complete disappearance of PV-SMV thrombosis in 9 patients and partial recanalization of PV-SMV thrombosis in 7 patients. The 16 patients were discharged 9-19 days (12 ± 6.0 days) after admission. Mean duration of follow-up after hospital discharge was 44 ± 18.5 months, and no recurrent episodes of PV-SMV thrombosis developed during that time period. Transradial approach for transcatheter selective SMA urokinase infusion therapy in addition to anticoagulation is a safe and effective therapy for the management of patients with acute extensive PV-SMV thrombosis.

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

    Directory of Open Access Journals (Sweden)

    Lampelj Maja

    2015-12-01

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

  17. Monitoring of chemotherapy successfulness of Platina/Taxol chemotherapy protocol by using determination of serum urokinase plasminogen activator (uPA and soluble urokinase plasminogen activator receptor (suPAR in patients with ovarian carcinoma FIGO II

    Directory of Open Access Journals (Sweden)

    Dženita Ljuca

    2007-05-01

    Full Text Available In about 70% of cases, ovarian carcinoma has been diagnosed at an advanced stage. Invasion and metastasis of solid tumors request protease activity resulting in basal membrane destruction and surrounding matrix. In that process, urokinase plasminogen activator (uPA and its receptor, urokinase plasminogen activator receptor (suPAR play a key role, that via plasmin activation lead to basal membrane and matrix degradation in surrounding of the tumor, enable to its invasion and metastasis. Determination of serum concentration of those tumor markers can be useful in preoperative as well as in postoperative period. Their serum concentrations in ovarian cancer patients may help in good monitoring of remission or progression during chemotherapy treatment. In late 1950s and eariy 1960s, when it was found out that malignant ovarian tumors were chemosensitive, their chemotherapy treatment has begun. In the beginning it was used only mono-therapy, and by discovering new cytostatics it was replaced by poly-chemotherapy. Now days, in the therapy of advanced stages of ovarian carcinoma combination of cisplatine or carboplatine with paclitaxel is considering as standard treatment. Aim of this study was to determine serum uPA, suPAR and CEA in FIGO II and III patients with different histo-logical type (serous, mucinous, clear cell tumor before and after PT chemotherapy protocol during following three cycles. In this prospective study we have analyzed 17 patients with ovarian carcinoma, those have been after surgery treated by chemotherapy. Serum levels of uPA and suPAR have been determined by ELISA-test (Imubind uPA, Imubind uPAR, American Diagnostica, and CEA by OPUS Imunoassay method. Results of this study have shown that uPA, suPAR and CEA met criteria for prognostic markers for monitoring of successful-ness of platina/taxol chemotherapy protocol for serous, mucinous and clear cell tumor FIGO II and III stage of ovarian carcinoma. In case of PT chemotherapy

  18. New insights into the factors mediating the onset of puberty in sea bass.

    Science.gov (United States)

    Espigares, F; Rocha, A; Molés, G; Gómez, A; Carrillo, M; Zanuy, S

    2015-12-01

    In populations of 1-year-old male European sea bass (Dicentrarchus labrax), only large males are able to acquire for the first time a functional competence of their reproductive axis; in other words, to attain puberty. To examine the causes and mechanisms involved in the onset of puberty in this species, a size sorting sampling was carried out to obtain two experimental groups of small and large male fish exhibiting different growth rates. As expected, only large fish reached full spermiogenesis (stage V of testicular development) by the end of the experiment. Our study suggests that fish size is a permissive condition to ensure full effectiveness of the hormonal (Gnrh1, gonadotropins and sexual steroids) actions. Thus, though small fish had endocrine profiles similar to those of large fish, their amplitude was much lower, and was most likely the reason why functional competence of the reproductive axis was not achieved. Moreover, this work provides evidence of the involvement of kisspeptin and Gnrh1 systems in the onset of puberty in a marine teleost fish. It also indicates that very likely kisspeptin and Gnrh1 may regulate gonadotropins and sex steroids at specific stages of testicular development. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Montelukast Induces Apoptosis-Inducing Factor-Mediated Cell Death of Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ming-Ju Tsai

    2017-06-01

    Full Text Available Developing novel chemo-prevention techniques and advancing treatment are key elements to beating lung cancer, the most common cause of cancer mortality worldwide. Our previous cohort study showed that cysteinyl leukotriene receptor antagonists, mainly montelukast, decreased the lung cancer risk in asthma patients. In the current study, we conducted in vivo and in vitro experiments to demonstrate the inhibiting effect of montelukast on lung cancer and to investigate the underlying mechanisms. Using Lewis lung carcinoma-bearing mice, we showed that feeding montelukast significantly delayed the tumor growth in mice (p < 0.0001. Montelukast inhibited cell proliferation and colony formation and induced the cell death of lung cancer cells. Further investigation showed the down-regulation of B-cell lymphoma 2 (Bcl-2, up-regulation of Bcl-2 homologous antagonist/killer (Bak, and nuclear translocation of apoptosis-inducing factor (AIF in montelukast-treated lung cancer cells. Montelukast also markedly decreased the phosphorylation of several proteins, such as with no lysine 1 (WNK1, protein kinase B (Akt, extracellular signal-regulated kinase 1/2 (Erk1/2, MAPK/Erk kinase (MEK, and proline-rich Akt substrate of 40-kDa (PRAS40, which might contribute to cell death. In conclusion, montelukast induced lung cancer cell death via the nuclear translocation of AIF. This study confirmed the chemo-preventive effect of montelukast shown in our previous cohort study. The utility of montelukast in cancer prevention and treatment thus deserves further studies.

  20. Mechanisms of transcription factor-mediated direct reprogramming of mouse embryonic stem cells to trophoblast stem-like cells.

    Science.gov (United States)

    Rhee, Catherine; Lee, Bum-Kyu; Beck, Samuel; LeBlanc, Lucy; Tucker, Haley O; Kim, Jonghwan

    2017-09-29

    Direct reprogramming can be achieved by forced expression of master transcription factors. Yet how such factors mediate repression of initial cell-type-specific genes while activating target cell-type-specific genes is unclear. Through embryonic stem (ES) to trophoblast stem (TS)-like cell reprogramming by introducing individual TS cell-specific 'CAG' factors (Cdx2, Arid3a and Gata3), we interrogate their chromosomal target occupancies, modulation of global transcription and chromatin accessibility at the initial stage of reprogramming. From the studies, we uncover a sequential, two-step mechanism of cellular reprogramming in which repression of pre-existing ES cell-associated gene expression program is followed by activation of TS cell-specific genes by CAG factors. Therefore, we reveal that CAG factors function as both decommission and pioneer factors during ES to TS-like cell fate conversion. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  1. Transcription-factor-mediated DNA looping probed by high-resolution, single-molecule imaging in live E. coli cells.

    Directory of Open Access Journals (Sweden)

    Zach Hensel

    Full Text Available DNA looping mediated by transcription factors plays critical roles in prokaryotic gene regulation. The "genetic switch" of bacteriophage λ determines whether a prophage stays incorporated in the E. coli chromosome or enters the lytic cycle of phage propagation and cell lysis. Past studies have shown that long-range DNA interactions between the operator sequences O(R and O(L (separated by 2.3 kb, mediated by the λ repressor CI (accession number P03034, play key roles in regulating the λ switch. In vitro, it was demonstrated that DNA segments harboring the operator sequences formed loops in the presence of CI, but CI-mediated DNA looping has not been directly visualized in vivo, hindering a deep understanding of the corresponding dynamics in realistic cellular environments. We report a high-resolution, single-molecule imaging method to probe CI-mediated DNA looping in live E. coli cells. We labeled two DNA loci with differently colored fluorescent fusion proteins and tracked their separations in real time with ∼40 nm accuracy, enabling the first direct analysis of transcription-factor-mediated DNA looping in live cells. Combining looping measurements with measurements of CI expression levels in different operator mutants, we show quantitatively that DNA looping activates transcription and enhances repression. Further, we estimated the upper bound of the rate of conformational change from the unlooped to the looped state, and discuss how chromosome compaction may impact looping kinetics. Our results provide insights into transcription-factor-mediated DNA looping in a variety of operator and CI mutant backgrounds in vivo, and our methodology can be applied to a broad range of questions regarding chromosome conformations in prokaryotes and higher organisms.

  2. Cadmium exposure is associated with soluble urokinase plasminogen activator receptor, a circulating marker of inflammation and future cardiovascular disease

    International Nuclear Information System (INIS)

    Fagerberg, Björn; Borné, Yan; Barregard, Lars; Sallsten, Gerd; Forsgard, Niklas; Hedblad, Bo; Persson, Margaretha; Engström, Gunnar

    2017-01-01

    Background: Diet and smoking are the main sources of cadmium exposure in the general population. Cadmium increases the risk of cardiovascular diseases, and experimental studies show that it induces inflammation. Blood cadmium levels are associated with macrophages in human atherosclerotic plaques. Soluble urokinase-type plasminogen activator receptor (suPAR) is an emerging biomarker for cardiovascular events related to inflammation and atherosclerotic plaques. The aim was to examine whether blood cadmium levels are associated with circulating suPAR and other markers of inflammation. Methods: A population sample of 4648 Swedish middle-aged women and men was examined cross-sectionally in 1991–1994. Plasma suPAR was assessed by ELISA, leukocytes were measured by standard methods, and blood cadmium was analysed by inductively coupled plasma mass spectrometry. Prevalent cardiovascular disease, ultrasound-assessed carotid plaque occurrence, and several possible confounding factors were recorded. Results: After full adjustment for risk factors and confounding variables, a 3-fold increase in blood cadmium was associated with an 10.9% increase in suPAR concentration (p<0.001). In never-smokers, a 3-fold increase in blood cadmium was associated with a 3.7% increase in suPAR concentration (p<0.01) after full adjustment. Blood cadmium was not associated with C-reactive protein, white blood cell count and Lp-PLA2 but with neutrophil/lymphocyte ratio in one of two statistical models. Conclusions: Exposure to cadmium was associated with increased plasma suPAR in the general population, independently of smoking and cardiovascular disease. These results imply that cadmium is a possible cause for raised levels of this inflammatory marker. - Highlights: • Cadmium is a toxic proinflammatory, proatherosclerotic metal. • Soluble urokinase-type plasminogen activator receptor (suPAR) in plasma is a promising proinflammatory marker of atherosclerosis. • Blood cadmium and plasma su

  3. ELISA for complexes between urokinase-type plasminogen activator and its receptor in lung cancer tissue extracts

    DEFF Research Database (Denmark)

    de Witte, H; Pappot, H; Brünner, N

    1997-01-01

    A sandwich-type ELISA has been developed for the assessment of complexes between urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in extracts of squamous cell lung carcinomas. The assay is based on a combination of rabbit polyclonal anti-uPA antibodies and a biotinylated mouse...... anti-uPAR monoclonal antibody (MAb). The detection limit of the assay is approximately 0.5 fmol/ml. A linear dose-response is obtained with up to 40 fmol/ml of uPA:uPAR complexes, while uPA and uPAR separately do not cause any response in the ELISA. A buffer which has been used previously for optimal...... extraction of uPAR yields the highest amounts of uPA:uPAR complexes. Absorption of tumor extracts with anti-uPA or anti-uPAR MAbs results in a complete disappearance of the ELISA signal, demonstrating the specificity of the ELISA. The recovery of chemically cross-linked uPA:uPAR complexes added to tumor...

  4. Inhibition of plasmin, urokinase, tissue plasminogen activator, and C1S by a myxoma virus serine proteinase inhibitor.

    Science.gov (United States)

    Lomas, D A; Evans, D L; Upton, C; McFadden, G; Carrell, R W

    1993-01-05

    The myxoma and malignant rabbit fibroma poxviruses are lethal tumorigenic viruses of rabbits whose virulence is modulated by the production of a virus-encoded secreted serine proteinase inhibitor, SERP-1. This viral protein was detected in medium harvested from myxoma and malignant rabbit fibroma virus-infected cells, and its inhibitory profile has been characterized by gel and kinetic analysis. SERP-1 forms complexes with and inhibits the human fibrinolytic enzymes plasmin, urokinase, and two-chain tissue-type plasminogen activator (association rate constants 3.4 x 10(4), 4.3 x 10(4), and 3.6 x 10(4) M-1 s-1 respectively). It is also able to inhibit C1S, the first enzyme in the complement cascade with an association rate constant which was unaffected by the addition of heparin (1.3 x 10(3) M-1 s-1). SERP-1 acts as a substrate for and is cleaved by thrombin, porcine trypsin, human neutrophil elastase, porcine pancreatic elastase, thermolysin, subtilisin, bovine alpha-chymotrypsin, and factor Xa. Incubation with kallikrein and cathepsin G had no effect. The structure of SERP-1 has been modeled on other members of the serpin family which revealed the characteristic serpin architecture apart from the absence of the D-helix. Structural analysis and kinetic assays demonstrate that the absence of this region does not prevent inhibitory activity and furthermore allow the identification of cysteine residues involved in internal and intermolecular disulfide bonding.

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

    International Nuclear Information System (INIS)

    Shin, Sung Wook; Do, Young Soo; Park, Hong Seok and others

    1998-01-01

    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

  6. Soluble urokinase-type plasminogen activator receptor (suPAR) and interleukin-6 levels in hyperemesis gravidarum.

    Science.gov (United States)

    Desdicioglu, Raziye; Yildirim, Melahat; Kocaoglu, Gulcan; Demir Cendek, Busra; Avcioglu, Gamze; Tas, Emre Erdem; Sengul, Ozlem; Erel, Ozcan; Yavuz, Ayse Filiz

    2017-10-09

    The aim was to compare serum soluble urokinase-type plasminogen activator receptor (suPAR) levels as well as interleukin-6 levels (IL-6) in pregnant women with hyperemesis gravidarum (HG) and asymptomatic pregnant women. Our study population consists of voluntary first trimester-pregnant women who applied to the outpatient clinic of the department of obstetrics and gynecology of Ankara Ataturk Training and Research Hospital. Between February and May 2016, 60 pregnant women were included in our prospective study. Serum suPAR and IL-6 levels were evaluated with the ELISA method. Twenty-nine pregnant women with HG and 31 asymptomatic pregnant women were included in the study. Serum suPAR level in the HG group was measured as 0.36 ± 0.56 ng/ml, whereas this level in the healthy pregnant control group was measured as 0.15 ± 0.15 ng/ml (p hyperemesis gravidarum. Copyright © 2017. Published by Elsevier Taiwan LLC.

  7. Urokinase-Type Plasminogen Activator Receptor Transcriptionally Controlled Adenoviruses Eradicate Pancreatic Tumors and Liver Metastasis in Mouse Models12

    Science.gov (United States)

    Huch, Meritxell; Gros, Alena; José, Anabel; González, Juan Ramon; Alemany, Ramon; Fillat, Cristina

    2009-01-01

    Treatment options for pancreatic cancer have shown limited success mainly owing to poor selectivity for pancreatic tumor tissue and to a lack of activity in the tumor. In this study, we describe the ability of the urokinase-type plasminogen activator receptor (uPAR) promoter to efficiently and selectively target pancreatic tumors and metastases, which enables the successful management of pancreatic cancer. We have generated a replication-defective reporter adenovirus, AduPARLuc, and a conditionally replicating adenovirus, AduPARE1A, and we have studied the selectivity and antitumoral efficacy in pancreatic tumors and metastases. Toxicity was studied on intravascular delivery. We demonstrate that the uPAR promoter is highly active in pancreatic tumors but very weak in normal tissues. Tumor specificity is evidenced by a 100-fold increase in the tumor-to-liver ratio and by selective targeting of liver metastases (P < .001). Importantly, the AduPARE1A maintains the oncolytic activity of the wild-type virus, with reduced toxicity, and exhibits significant antitumoral activity (25% tumor eradication) and prolonged survival in pancreatic xenograft models (P < .0001). Furthermore, upon intravascular delivery, we demonstrate complete eradication of liver metastasis in 33% of mice, improving median survival (P = 5.43 x 10-5). The antitumoral selective activity of AduPARE1A shows the potential of uPAR promoter-based therapies in pancreatic cancer treatment. PMID:19484141

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

    DEFF Research Database (Denmark)

    Wittenhagen, P; Kronborg, G; Weis, N

    2004-01-01

    .05). In multivariate analysis, only suPAR remained a significant predictor of death (mortality rate of 13 for suPAR levels of > 10 ng/mL; 95% CI: 1.1-158). The increase in suPAR levels may reflect increased expression by vascular or inflammatory cells in the setting of pneumococcal sepsis. This plasma protein may......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...... increased significantly (median 5.5; range 2.4-21.0 ng/mL) in 141 patients with pneumococcal bacteraemia, compared to 31 healthy controls (median 2.6, range 1.5-4.0 ng/mL, p 0.001). Furthermore, suPAR levels were elevated significantly in patients who died from the infection (n = 24) compared to survivors...

  9. Urokinase receptor derived peptides as potent inhibitors of the formyl peptide receptor type 1-triggered cell migration.

    Science.gov (United States)

    Yousif, Ali Munaim; Ingangi, Vincenzo; Merlino, Francesco; Brancaccio, Diego; Minopoli, Michele; Bellavita, Rosa; Novellino, Ettore; Carriero, Maria Vincenza; Carotenuto, Alfonso; Grieco, Paolo

    2018-01-01

    The receptor for the urokinase-type plasminogen activator (uPAR) is a widely recognized master regulator of cell migration. We and others have previously documented that the uPAR(84-95) sequence, interacts with the formyl peptide receptors (FPR)s, henceforth inducing cell migration of several cell lines, including leukocytes, and the synthetic shorter peptide (Ser 88 -Arg-Ser-Arg-Tyr 92 , SRSRY) retains chemotactic activity in vitro and in vivo. Recently, we have developed the head-to-tail cyclic analog [SRSRY], a new potent and stable inhibitor of monocyte trafficking. This prompted us to develop novel cyclic and linear analogs of [SRSRY] with the aim to broaden the knowledge about structure-activity relationships of peptide [SRSRY]. Herein we report their synthesis, effects on cell migration, conformational and docking analyses which served to envisage a new pharmacophore model for inhibitors of FPR1-triggered cell migration. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Enhanced discrimination of benign from malignant prostatic disease by selective measurements of cleaved forms of urokinase receptor in serum

    DEFF Research Database (Denmark)

    Piironen, Timo; Haese, Alexander; Huland, Hartwig

    2006-01-01

    BACKGROUND: Early detection of prostate cancer (PCa) centers on measurements of prostate-specific antigen (PSA), but current testing practices suffer from lack of specificity and generate many unnecessary prostate biopsies. Soluble urokinase plasminogen activator receptor (uPAR) is present in blood...... total PSA (tPSA), free PSA (fPSA), intact uPAR [uPAR(I-III)], intact uPAR + cleaved uPAR domains II+III [uPAR(I-III) + uPAR(II-III)], and cleaved uPAR domain I [uPAR(I)] in sera from 224 men with and 166 men without PCa. We assessed differences in serum concentrations between the PCa and noncancer...... groups within the entire cohort and in men with tPSA concentrations of 2-10 microg/L. The diagnostic accuracy of individual analytes and analyte combinations was explored by logistic regression and ROC analyses and evaluations of sensitivity and specificity pairs. RESULTS: Serum uPAR(I) and u...

  11. Clinical outcomes of transcatheter selective superior mesenteric artery urokinase infusion therapy vs transjugular intrahepatic portosystemic shunt in patients with cirrhosis and acute portal vein thrombosis.

    Science.gov (United States)

    Jiang, Ting-Ting; Luo, Xiao-Ping; Sun, Jian-Ming; Gao, Jian

    2017-11-07

    To compare the outcomes of transcatheter superior mesenteric artery (SMA) urokinase infusion and transjugular intrahepatic portosystemic shunt (TIPS) for acute portal vein thrombosis (PVT) in cirrhosis. From January 2013 to December 2014, patients with liver cirrhosis and acute symptomatic PVT who met the inclusion criteria were randomly assigned to either an SMA group or a TIPS group. The two groups accepted transcatheter selective SMA urokinase infusion therapy and TIPS, respectively. The total follow-up time was 24 mo. The primary outcome measure was the change in portal vein patency status which was evaluated by angio-computed tomography or Doppler ultrasound. Secondary outcomes were rebleeding and hepatic encephalopathy. A total of 40 patients were enrolled, with 20 assigned to the SMA group and 20 to the TIPS group. The symptoms of all patients in the two groups improved within 48 h. PVT was improved in 17 (85%) patients in the SMA group and 14 (70%) patients in the TIPS group. The main portal vein (MPV) thrombosis was significantly reduced in both groups ( P mesenteric vein (SMV) thrombosis and splenic vein (SV) thrombosis were significantly reduced ( P = 0.048 and P = 0.02), which did not occur in the TIPS group. At 6-, 12-, and 24-mo follow-up, in the SMA group and the TIPS group, the cumulative rates free of the first episode of rebleeding were 80%, 65%, and 45% vs 90%, 80%, and 60%, respectively ( P = 0.320); the cumulative rates free of the first episode of hepatic encephalopathy were 85%, 80%, and 65% vs 50%, 40%, and 35%, respectively ( P = 0.022). Transcatheter selective SMA urokinase infusion and TIPS are safe and effective for acute symptomatic PVT in cirrhosis.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  13. Serum level of soluble urokinase-type plasminogen activator receptor is a strong and independent predictor of survival in human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Sidenius, N; Sier, CFM; Ullum, H

    2000-01-01

    Human immunodeficiency virus-1 (HIV-1) infection has been shown to result in up-regulation of the urokinase-type plasminogen activator receptor (uPAR/CD87) on leukocytes in vitro and in vivo. The objective of this study was to investigate whether this up-regulation is paralleled by higher serum...... that the serum suPAR level is a novel, strong, and independent predictor of survival in HIV-1 infection. This report is the first to demonstrate an important association between the plasminogen activator system and disease progression in HIV-1 infection....

  14. The immune marker soluble urokinase plasminogen activator receptor is associated with new-onset diabetes in non-smoking women and men

    DEFF Research Database (Denmark)

    Haugaard, S B; Andersen, O; Hansen, T W

    2012-01-01

    Aim: To explore the putative association of new-onset diabetes and the soluble urokinase plasminogen activator receptor (suPAR), which is a new and stable plasma marker of immune function and low-grade inflammation. This association has been previously suggested by using the less sensitive...... International Classification of Disease system to detect incident diabetes in the Danish MONICA 10 cohort. Methods: The Danish National Diabetes Register enabled more accurate identification of incident diabetes during a median follow-up of 13.8 years in the Danish MONICA 10 cohort (n = 2353 generally healthy......-onset diabetes (P...

  15. Prognostic value of intact and cleaved forms of the urokinase plasminogen activator receptor in a retrospective study of 518 colorectal cancer patients

    DEFF Research Database (Denmark)

    Lomholt, Anne Fog; Christensen, Ib J; Høyer-Hansen, Gunilla

    2010-01-01

    The levels of the soluble urokinase plasminogen activator receptor (suPAR) in blood have been shown to correlate with prognosis in various cancers. Plasma levels of the combined suPAR forms have previously shown to be a strong prognostic marker in the present cohort of CRC patients and could...... potentially identify high-risk patients among those with early stage disease. In order to investigate whether the individual suPAR forms are stronger prognostic markers than the combined amount we measured the different uPAR forms in serum from the same cohort and evaluated their prognostic significance....

  16. In vivo evaluation of urokinase-loaded hollow nanogels for sonothrombolysis on suture embolization-induced acute ischemic stroke rat model

    OpenAIRE

    Yuming Teng; Haiqiang Jin; Ding Nan; Mengnan Li; Chenghe Fan; Yuanyuan Liu; Pu Lv; Wei Cui; Yongan Sun; Hongjun Hao; Xiaozhong Qu; Zhenzhong Yang; Yining Huang

    2018-01-01

    The urokinase-type plasminogen activator (uPA) loaded hollow nanogels (nUK) were synthesized by a one-step reaction of glycol chitosan and aldehyde capped poly (ethylene oxide). The resultant formulation is sensitive to diagnostic ultrasound (US) of 2 MHz. Herein, we evaluated the in vivo sonothrombolysis performance of the nUK on acute ischemic stroke rat model which was established by suture embolization of middle cerebral artery (MCA). Via intravenous (i.v.) administration, the experimenta...

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

    Directory of Open Access Journals (Sweden)

    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. Urokinase vs Tissue-Type Plasminogen Activator for Thrombolytic Evacuation of Spontaneous Intracerebral Hemorrhage in Basal Ganglia

    Directory of Open Access Journals (Sweden)

    Yuqian Li

    2017-08-01

    Full Text Available Spontaneous intracerebral hemorrhage (ICH is a devastating form of stroke, which leads to a high rate of mortality and poor neurological outcomes worldwide. Thrombolytic evacuation with urokinase-type plasminogen activator (uPA or tissue-type plasminogen activator (tPA has been showed to be a hopeful treatment for ICH. However, to the best of our knowledge, no clinical trials were reported to compare the efficacy and safety of these two fibrinolytics administrated following minimally invasive stereotactic puncture (MISP in patients with spontaneous basal ganglia ICH. Therefore, the authors intended here to evaluate the differential impact of uPA and tPA in a retrospective study. In the present study, a total of 86 patients with spontaneous ICH in basal ganglia using MISP received either uPA (uPA group, n = 45 or tPA (tPA group, n = 41, respectively. The clinical baseline characteristics prior to the operation were collected. In addition, therapeutic responses were assessed by the short-term outcomes within 30 days postoperation, as well as long-term outcomes at 1 year postoperation. Our findings showed that, in comparison with tPA, uPA was able to better promote hematoma evacuation and ameliorate perihematomal edema, but the differences were not statistically significant. Moreover, the long-term functional outcomes of both groups were similar, with no statistical difference. In conclusion, these results provide evidence supporting that uPA and tPA are similar in the efficacy and safety for thrombolytic evacuation in combination with MISP in patients with spontaneous basal ganglia ICH.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Ligand binding modulates the structural dynamics and activity of urokinase-type plasminogen activator: A possible mechanism of plasminogen activation.

    Directory of Open Access Journals (Sweden)

    Tobias Kromann-Hansen

    Full Text Available The catalytic activity of trypsin-like serine proteases is in many cases regulated by conformational changes initiated by binding of physiological modulators to exosites located distantly from the active site. A trypsin-like serine protease of particular interest is urokinase-type plasminogen activator (uPA, which is involved in extracellular tissue remodeling processes. Herein, we used hydrogen/deuterium exchange mass spectrometry (HDXMS to study regulation of activity in the catalytic domain of the murine version of uPA (muPA by two muPA specific monoclonal antibodies. Using a truncated muPA variant (muPA16-243, containing the catalytic domain only, we show that the two monoclonal antibodies, despite binding to an overlapping epitope in the 37s and 70s loops of muPA16-243, stabilize distinct muPA16-243 conformations. Whereas the inhibitory antibody, mU1 was found to increase the conformational flexibility of muPA16-243, the stimulatory antibody, mU3, decreased muPA16-243 conformational flexibility. Furthermore, the HDXMS data unveil the existence of a pathway connecting the 70s loop to the active site region. Using alanine scanning mutagenesis, we further identify the 70s loop as an important exosite for the activation of the physiological uPA substrate plasminogen. Thus, the data presented here reveal important information about dynamics in uPA by demonstrating how various ligands can modulate uPA activity by mediating long-range conformational changes. Moreover, the results provide a possible mechanism of plasminogen activation.

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

    International Nuclear Information System (INIS)

    Bacchiocchi, Roberta; Lo Muzio, Lorenzo; Fazioli, Francesca; Rubini, Corrado; Pierpaoli, Elisa; Borghetti, Giulia; Procacci, Pasquale; Nocini, Pier Francesco; Santarelli, Andrea; Rocchetti, Romina; Ciavarella, Domenico

    2008-01-01

    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

  2. Inflammation and psychosocial factors mediate exercise effects on sleep quality in breast cancer survivors: pilot randomized controlled trial.

    Science.gov (United States)

    Rogers, Laura Q; Fogleman, Amanda; Trammell, Rita; Hopkins-Price, Patricia; Spenner, Allison; Vicari, Sandra; Rao, Krishna; Courneya, Kerry S; Hoelzer, Karen; Robbs, Randall; Verhulst, Steven

    2015-03-01

    To improve mechanistic understanding, this pilot randomized controlled trial examined mediators of an exercise intervention effects on sleep in breast cancer survivors (BCS). Forty-six postmenopausal BCS (≤Stage II, off primary treatment) were randomized to a 3-month exercise intervention or control group. Intervention included 160 min/week of moderate intensity aerobic walking, twice weekly resistance training (resistance bands), and six discussion groups (to improve adherence). Blinded assessments at baseline and post-intervention included sleep disturbance (PSQI and PROMIS®), objective sleep quality (accelerometer), serum cytokines, accelerometer physical activity, cardiorespiratory fitness, body composition, fatigue, and psychosocial factors. Mediation was tested using Freedman-Schatzkin difference-in-coefficients tests. When compared with control, the intervention group demonstrated a significant increase in PSQI sleep duration (i.e., fewer hours of sleep/night) (d = 0.73, p = .03). Medium to large but non-significant standardized effect sizes were noted for PSQI daytime somnolence (d = -0.63, p = .05) and accelerometer latency (d = -0.49, p = .14). No statistically significant mediators were detected for PSQI sleep duration score or accelerometer latency. Daytime somnolence was mediated by tumor necrosis factor-alpha (mediated 23% of intervention effect, p sleep outcomes were noted for accelerometer physical activity, PROMIS® fatigue, exercise social support, and/or physical activity enjoyment. Inflammation and psychosocial factors may mediate or enhance sleep response to our exercise intervention. Further study is warranted to confirm our results and translate our findings into more effective interventions aimed at improving sleep quality in BCS. Copyright © 2014 John Wiley & Sons, Ltd.

  3. Reduced metastasis of transgenic mammary cancer in urokinase-deficient mice

    DEFF Research Database (Denmark)

    Almholt, Kasper; Lund, L.R.; Rygaard, Jørgen

    2005-01-01

    >7-fold in the MMTV-PymT model. We studied a cohort of 55 MMTV-PymT transgenic mice, either uPA-deficient or wild-type controls. Tumor incidence, latency, growth rate and final primary tumor burden were not significantly affected by uPA deficiency. In contrast, average lung metastasis volume...... was reduced from 1.58 mm3 in wild-type controls to 0.21 mm3 in uPA-deficient mice (p = 0.023). Tumor cell dissemination to brachial lymph nodes was also reduced from 53% (28/53) in wild-type controls to 31% (17/54) in uPA-deficient mice (p = 0.032). Mice without plasminogen display a severe pleiotropic...

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

    DEFF Research Database (Denmark)

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

    1990-01-01

    We have studied the effect of plasminogen activator inhibitors PAI-1 and PAI-2 on the binding of urokinase-type plasminogen activator (u-PA) to its receptor in the human choriocarcinoma cell line JAR. With 125I-labeled ligands in whole-cell binding assays, both uncomplexed u-PA and u-PA-inhibitor......We have studied the effect of plasminogen activator inhibitors PAI-1 and PAI-2 on the binding of urokinase-type plasminogen activator (u-PA) to its receptor in the human choriocarcinoma cell line JAR. With 125I-labeled ligands in whole-cell binding assays, both uncomplexed u-PA and u...... in an apparently intact form in the medium or was still cell associated. The degradation could be inhibited by inhibitors of vesicle transport and lysosomal hydrolases. By electron microscopic autoradiography, both 125I-u-PA and 125I-u-PA-inhibitor complexes were located over the cell membrane at 4 degrees C...

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

    International Nuclear Information System (INIS)

    Peng, P.-L.; Hsieh, Y.-S.; Wang, C.-J.; Hsu, J.-L.; Chou, F.-P.

    2006-01-01

    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

  6. Artificial exon shuffling between tissue-type plasminogen activator (t-PA) and urokinase (u-PA): a comparative study on the fibrinolytic properties of t-PA/u-PA hybrid proteins

    NARCIS (Netherlands)

    de Vries, C. [=Carlie J. M.; Veerman, H.; Blasi, F.; Pannekoek, H.

    1988-01-01

    We constructed two human tissue-type plasminogen activator/urokinase (t-PA/u-PA) hybrid cDNAs which were expressed by transfection of mouse Ltk- cells. The properties of the secreted proteins were compared with those of recombinant t-PA (rt-PA) and high molecular weight (HMW) u-PA. The hybrid

  7. Role of the low density lipoprotein receptorrelated protein (lrp) in the clearance and liver uptake of recombinant single chain urokinase-type plasminogen activator (rscu-pa) in rats

    NARCIS (Netherlands)

    Kaaden, M.E. van der; Riiken, D.C.; Kruiit, J.K.; Berkel, T. van; Kuiper, J.

    1996-01-01

    Urokinase-type plasminogen activator (u-PA) is used as a thrombolytic agent in the treatment of acute myocardial infarction. In vitro, E.coli produced rscu-PA is recognized by LRP on parenchyma! liver cells. In this study we investigated the role of LRP in the liver uptake and plasma clearance of

  8. Urokinase receptor-associated protein (uPARAP) is expressed in connection with malignant as well as benign lesions of the human breast and occurs in specific populations of stromal cells

    DEFF Research Database (Denmark)

    Schnack Nielsen, Boye; Rank, Fritz; Engelholm, Lars H

    2002-01-01

    The urokinase-type plasminogen activator (uPA) and the uPA receptor (uPAR) are key components in the plasminogen activation system, serving to promote specific events of extracellular matrix degradation in connection with tissue remodeling and cancer invasion. We recently described a new u...

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

    Directory of Open Access Journals (Sweden)

    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

  10. Tumour Microenvironments Induce Expression of Urokinase Plasminogen Activator Receptor (uPAR) and Concomitant Activation of Gelatinolytic Enzymes

    Science.gov (United States)

    Magnussen, Synnøve; Hadler-Olsen, Elin; Latysheva, Nadezhda; Pirila, Emma; Steigen, Sonja E.; Hanes, Robert; Salo, Tuula; Winberg, Jan-Olof; Uhlin-Hansen, Lars; Svineng, Gunbjørg

    2014-01-01

    Background 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. Methods 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. Results 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. Conclusions 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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    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...... proteins. Up to 20mg of intact fusion protein were expressed by stably transfected Drosophila S2 cells per liter of culture using this strategy. Purification of these secreted fusion proteins from the conditioned serum free medium of S2 cells was accompanied by an efficient one-step immunoaffinity...

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

    DEFF Research Database (Denmark)

    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...... and 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...

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

    DEFF Research Database (Denmark)

    Nielsen, Lars Søegaard; Kellerman, G M; Behrendt, N

    1988-01-01

    a bifunctional amino-reactive reagent followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography revealed with the four cell lines studied the occurrence of a single band migrating with an Mr of 70,000-75,000, indicating complex formation with an Mr of 55,000-60,000 u-PA receptor...... protein (u-PA-R). In the human monocyte cell line U937 cultivated in the presence of phorbol ester, the amount of complex was strongly increased, and a fraction of the complex had a slower electrophoretic mobility. Comparison between autoradiograms of reduced and unreduced samples suggests that u......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...

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

    DEFF Research Database (Denmark)

    Zhao, Baoyu; Gandhi, Sonu; Yuan, Cai

    2015-01-01

    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...

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

    DEFF Research Database (Denmark)

    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...... fluid samples from patients with clinically suspected meningitis were sent to the Hellenic National Meningitis Reference Laboratory. Ten of 545 (1.83%) patients died. Analysis by receiver operating characteristics (ROC) curve revealed that both suPAR and age were significant for prediction of fatal...... outcome. Patients with levels of suPAR above the cut-off values and age ≥51 years, or patients in which either Neisseria meningitis or Streptococcus pneumoniae were detected were categorized as high risk patients. The combination of the above three predictors (suPAR, age and infectious agent...

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

    DEFF Research Database (Denmark)

    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...... that the plasminogen activation system could play a role in this type of cancer during invasion. In addition a difference in the levels of the components of the plasminogen activation system in NSCLC and SCLC is found, which could contribute to the differences in biology....

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

    Science.gov (United States)

    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.

  18. A high-protein diet during hospitalization is associated with an accelerated decrease in soluble urokinase plasminogen activator receptor levels in acutely ill elderly medical patients with SIRS

    DEFF Research Database (Denmark)

    Tavenier, Juliette; Haupt, Thomas Huneck; Andersen, Aino L

    2017-01-01

    inflammation in healthy elderly. We hypothesized that nutritional support and resistance training would accelerate the resolution of inflammation in hospitalized elderly patients with SIRS. Acutely admitted patients aged >65 years with SIRS were randomized to an intervention consisting of a high-protein diet......Acute illness and hospitalization in elderly individuals are often accompanied by the systemic inflammatory response syndrome (SIRS) and malnutrition, both associated with wasting and mortality. Nutritional support and resistance training were shown to increase muscle anabolism and reduce...... (1.7 g/kg per day) during hospitalization, and daily protein supplement (18.8 g) and 3 weekly resistance training sessions for 12 weeks after discharge (Intervention, n=14), or to standard-care (Control, n=15). Plasma levels of the inflammatory biomarkers soluble urokinase plasminogen activator...

  19. Randomized comparison of intracoronary tirofiban versus urokinase as an adjunct to primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: results of the ICTUS-AMI trial.

    Science.gov (United States)

    Zhu, Tian-qi; Zhang, Qi; Ding, Feng-hua; Qiu, Jian-ping; Jin, Hui-geng; Jiang, Li; Lu, Lin; Zhang, Rui-yan; Hu, Jian; Yang, Zhen-kun; Shen, Ying; Shen, Wei-feng

    2013-08-01

    No randomized trial has been performed to compare the efficacy of an intracoronary bolus of tirofiban versus urokinase during primary percutaneous coronary intervention (PCI). We investigated whether the effects of adjunctive therapy with an intracoronary bolus of urokinase was noninferior to the effects of an intracoronary bolus of tirofiban in patients with ST-elevation myocardial infarction (STEMI) undergoing PCI. A total of 490 patients with acute STEMI undergoing primary PCI were randomized to an intracoronary bolus of tirofiban (10 µg/kg; n = 247) or urokinase (250 kU/20 ml; n = 243). Serum levels of P-selectin, von Willebrand factor (vWF), CD40 ligand (CD40L), and serum amyloid A (SAA) in the coronary sinus were measured before and after intracoronary drug administration. The primary endpoint was the rate of complete ( ≥ 70%) ST-segment resolution (STR) at 90 minutes after intervention, and the noninferiority margin was set to 15%. In the intention-to-treat analysis, complete STR was achieved in 54.4% of patients treated with an intracoronary bolus of urokinase and in 60.6% of those treated with an intracoronary bolus of tirofiban (adjusted difference: -7.0%; 95% confidence interval: -15.7% to 1.8%). The corrected TIMI frame count of the infarct-related artery was lower, left ventricular ejection fraction was higher, and the 6-month major adverse cardiac event-free survival tended to be better in the intracoronary tirofiban group. An intracoronary bolus of tirofiban resulted in lower levels of P-selectin, vWF, CD40L, and SAA in the coronary sinus compared with an intracoronary bolus of urokinase after primary PCI (P < 0.05). An intracoronary bolus of urokinase as an adjunct to primary PCI for acute STEMI is not equally effective to an intracoronary bolus of tirofiban with respect to improvement in myocardial reperfusion assessed by STR. This may be caused by less reduction in coronary circulatory platelet activation and inflammation.

  20. Perinatal and lifestyle factors mediate the association between maternal education and preschool children's weight status: the ToyBox study.

    Science.gov (United States)

    Androutsos, Odysseas; Moschonis, George; Ierodiakonou, Despo; Karatzi, Kalliopi; De Bourdeaudhuij, Ilse; Iotova, Violeta; Zych, Kamila; Moreno, Luis A; Koletzko, Berthold; Manios, Yannis

    2018-04-01

    This study aimed to explore the associations among perinatal, sociodemographic, and behavioral factors and preschool overweight/obesity. Data were collected from 7541 European preschoolers in May/June 2012. Children's anthropometrics were measured, and parents self-reported all other data via questionnaires. Level of statistical significance was set at P ≤ 0.05. Certain perinatal factors (i.e., maternal prepregnancy overweight/obesity, maternal excess gestational weight gain, excess birth weight, and "rapid growth velocity"), children's energy balance-related behaviors (i.e., high sugar-sweetened beverage consumption, increased screen time, reduced active-play time), family sociodemographic characteristics (i.e., Eastern or Southern Europe, low maternal and paternal education), and parental overweight/obesity were identified as correlates of preschoolers' overweight/obesity. Furthermore, maternal prepregnancy overweight/obesity, children's "rapid growth velocity," and increased screen time mediated by 21.2%, 12.5%, and 5.7%, respectively, the association between maternal education and preschoolers' body mass index. This study highlighted positive associations of preschooler's overweight/obesity with excess maternal prepregnancy and gestational weight gain, excess birth weight and "rapid growth velocity," Southern or Eastern European region, and parental overweight/obesity. Moreover, maternal prepregnancy overweight/obesity, children's "rapid growth velocity," and increased screen time partially mediated the association between maternal education and preschoolers' body mass index. The findings of the present study may support childhood obesity prevention initiatives, because vulnerable population groups and most specifically low-educated families should be prioritized. Among other fields, these intervention initiatives should also focus on the importance of normal prepregnancy maternal weight status, normal growth velocity during infancy, and retaining

  1. Learning as conceptual change: Factors mediating the development of preservice elementary teachers' views of nature of science

    Science.gov (United States)

    Abd-El-Khalick, Fouad; Akerson, Valarie L.

    2004-09-01

    This study assessed, and identified factors in participants' learning ecologies that mediated, the effectiveness of an explicit reflective instructional approach that satisfied conditions for learning as conceptual change on preservice elementary teachers' views of nature of science (NOS). Participants were 28 undergraduate students enrolled in an elementary science methods course. A purposively selected focus group of six participants who showed differential growth in terms of their NOS views were closely followed throughout the study. The Views of Nature of Science Questionnaire-Form B (VNOS-B) in conjunction with individual interviews was used to assess participants' views prior to and at the conclusion of the study. Other data sources included weekly reflection papers, exit interviews, and an instructor's log. Initially, the greater majority of participants held naïve views of NOS. Substantial and favorable changes in these views were evident as a result of the intervention. An examination of the development of the focus group participants' NOS views indicated that the effectiveness of the intervention was mediated by motivational, cognitive, and worldview factors. These were related to internalizing the importance and utility of teaching and learning about NOS, exhibiting a deep processing approach to learning, and viewing science and religion as two distinct rather than opposing enterprises.

  2. Repression by an auxin/indole acetic acid protein connects auxin signaling with heat shock factor-mediated seed longevity.

    Science.gov (United States)

    Carranco, Raúl; Espinosa, José Manuel; Prieto-Dapena, Pilar; Almoguera, Concepción; Jordano, Juan

    2010-12-14

    The plant hormone auxin regulates growth and development by modulating the stability of auxin/indole acetic acid (Aux/IAA) proteins, which in turn repress auxin response factors (ARFs) transcriptional regulators. In transient assays performed in immature sunflower embryos, we observed that the Aux/IAA protein HaIAA27 represses transcriptional activation by HaHSFA9, a heat shock transcription factor (HSF). We also found that HaIAA27 is stabilized in immature sunflower embryos, where we could show bimolecular fluorescence complementation interaction between native forms of HaIAA27 and HaHSFA9. An auxin-resistant form of HaIAA27 was overexpressed in transgenic tobacco seeds, leading to effects consistent with down-regulation of the ortholog HSFA9 gene, effects not seen with the native HaIAA27 form. Repression of HSFs by HaIAA27 is thus likely alleviated by auxin in maturing seeds. We show that HSFs such as HaHSFA9 are targets of Aux/IAA protein repression. Because HaHSFA9 controls a genetic program involved in seed longevity and embryonic desiccation tolerance, our findings would suggest a mechanism by which these processes can be auxin regulated. Aux/IAA-mediated repression involves transcription factors distinct from ARFs. This finding widens interpretation of auxin responses.

  3. 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

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. Renin angiotensin system blockade reduces urinary levels of soluble urokinase plasminogen activator receptor (suPAR) in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Persson, Frederik; Theilade, Simone; Eugen-Olsen, Jesper

    2016-01-01

    treatment periods were compared to placebo. Patients (n = 22) were treated for 2-month periods with either placebo, irbesartan 300 mg once daily, aliskiren 300 mg once daily or irbesartan/aliskiren combination in random order. Placebo geometric mean plasma (SEM) levels of suPAR were 3.3 ng/mL (1.1......) and urine levels were 4.0 ng/mL (1.1). None of the treatments had significant effects on plasma levels of suPAR compared to placebo. Compared to placebo, irbesartan and combination treatment decreased urinary levels of suPAR significantly (-1.3 ng/mL), while aliskiren did not. In patients with type 2......Soluble urokinase plasminogen activator receptor (suPAR) is associated with faster decline in kidney function and the pathogenesis of diabetic nephropathy. However, little is known about the impact of treatment on plasma and urinary levels of suPAR. We aimed to investigate the impact of renin...

  6. In vivo evaluation of urokinase-loaded hollow nanogels for sonothrombolysis on suture embolization-induced acute ischemic stroke rat model

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    Yuming Teng

    2018-03-01

    Full Text Available The urokinase-type plasminogen activator (uPA loaded hollow nanogels (nUK were synthesized by a one-step reaction of glycol chitosan and aldehyde capped poly (ethylene oxide. The resultant formulation is sensitive to diagnostic ultrasound (US of 2 MHz. Herein, we evaluated the in vivo sonothrombolysis performance of the nUK on acute ischemic stroke rat model which was established by suture embolization of middle cerebral artery (MCA. Via intravenous (i.v. administration, the experimental data prove a controlled release of the therapeutic protein around the clots under ultrasound stimulation, leading to enhanced thrombolysis efficiency of the nUK, evidenced from smaller infarct volume and better clinical scores when compared to the i.v. dose of free uPA no matter with or without US intervention. Meanwhile, the preservation ability of the nanogels not only prolonged the circulation duration of the protein, but also resulted in the better blood-brain barrier protection of the nUK formulation, showing no increased risk on the hemorrhagic transformation than the controls. This work suggests that the nUK is a safe sonothrombolytic formulation for the treatment of acute ischemic stroke.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    -statistic for a model based on traditional risk factors was improved from 0.72 to 0.74 (P=0.008) with the addition of suPAR. CONCLUSION: Elevated levels of plasma suPAR are associated with the presence and severity of CAD and are independent predictors of death and MI in patients with suspected or known CAD.......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...

  8. Aspirin Inhibits IKK-β-mediated Prostate Cancer Cell Invasion by Targeting Matrix Metalloproteinase-9 and Urokinase-Type Plasminogen Activator.

    Science.gov (United States)

    Shi, Chongjun; Zhang, Nini; Feng, Yang; Cao, Jiewei; Chen, Xuyi; Liu, Bin

    2017-01-01

    Aspirin has been demonstrated to possess potent chemopreventive and anticancer effects on prostate cancer. However, the more detailed molecular mechanisms of aspirin to suppress prostate cancer cell invasion have not been clearly elucidated. Transwell assays were performed to evaluate the effects of aspirin on cell invasion. Matrix metalloproteinases (MMPs) and serine proteinases activities in cell media were examined by gelatin zymography and ELISA. In addition, inhibitor of κB (IκB) kinase-β (IKK-β) phosphorylation and IKK-β kinase activity were measured to assess the effects of aspirin on IKK-β activation. We found that aspirin suppressed the invasion and attachment in human prostate cancer cells. Aspirin treatment significantly resulted in reduction of matrix metalloproteinase-9 (MMP-9) and upregulation of tissue inhibitors of metalloproteinase-1 (TIMP-1) activity, which are the proteolytic enzymes contributing to the degradation of extracellular matrix and basement membrane in cell invasion and metastasis. Our data further showed that aspirin was able to inhibit both urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) expression in the cells. In addition, aspirin treatment caused a strong decrease in nuclear factor-kappa B (NF-κB) activation, inhibitor of κB (IκB)-α phosphorylation together with translocation of NF-κB p65 to nucleus and IκB kinase (IKK)- β activation. Moreover, the inhibitory effects of aspirin on cell invasion were reversed by IKK-β overexpression, while the IKK inhibitor sensitizes the anti-invasive effect of aspirin in prostate cancer cells. The present research concluded that aspirin suppressed prostate cancer cell invasion by reducing MMP-9 activity and uPA expression through decreasing of IKK-β-mediated NF-κB activation, indicating that the ability of aspirin to inhibit cell invasion might be useful in the chemoprevention of metastatic prostate cancer. © 2017 The Author(s)Published by

  9. Aspirin Inhibits IKK-β-mediated Prostate Cancer Cell Invasion by Targeting Matrix Metalloproteinase-9 and Urokinase-Type Plasminogen Activator

    Directory of Open Access Journals (Sweden)

    Chongjun Shi

    2017-03-01

    Full Text Available Background/Aims: Aspirin has been demonstrated to possess potent chemopreventive and anticancer effects on prostate cancer. However, the more detailed molecular mechanisms of aspirin to suppress prostate cancer cell invasion have not been clearly elucidated. Methods: Transwell assays were performed to evaluate the effects of aspirin on cell invasion. Matrix metalloproteinases (MMPs and serine proteinases activities in cell media were examined by gelatin zymography and ELISA. In addition, inhibitor of κB (IκB kinase-β (IKK-β phosphorylation and IKK-β kinase activity were measured to assess the effects of aspirin on IKK-β activation. Results: We found that aspirin suppressed the invasion and attachment in human prostate cancer cells. Aspirin treatment significantly resulted in reduction of matrix metalloproteinase-9 (MMP-9 and upregulation of tissue inhibitors of metalloproteinase-1 (TIMP-1 activity, which are the proteolytic enzymes contributing to the degradation of extracellular matrix and basement membrane in cell invasion and metastasis. Our data further showed that aspirin was able to inhibit both urokinase-type plasminogen activator (uPA and plasminogen activator inhibitor-1 (PAI-1 expression in the cells. In addition, aspirin treatment caused a strong decrease in nuclear factor-kappa B (NF-κB activation, inhibitor of κB (IκB-α phosphorylation together with translocation of NF-κB p65 to nucleus and IκB kinase (IKK- β activation. Moreover, the inhibitory effects of aspirin on cell invasion were reversed by IKK-β overexpression, while the IKK inhibitor sensitizes the anti-invasive effect of aspirin in prostate cancer cells. Conclusion: The present research concluded that aspirin suppressed prostate cancer cell invasion by reducing MMP-9 activity and uPA expression through decreasing of IKK-β-mediated NF-κB activation, indicating that the ability of aspirin to inhibit cell invasion might be useful in the chemoprevention of

  10. Plasma levels of soluble urokinase-type plasminogen activator receptor (suPAR and early mortality risk among patients enrolling for antiretroviral treatment in South Africa

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    Bangani Nonzwakazi

    2007-05-01

    Full Text Available Abstract Background Serum concentrations of soluble urokinase-type plasminogen activator receptor (suPAR have a strong independent association with HIV-1-related mortality. The practical utility of plasma suPAR in assessing short-term all-cause mortality risk was evaluated in patients with advanced immunodeficiency enrolling in an antiretroviral treatment (ART programme in South Africa. Methods An enzyme-linked immunosorbent assay (ELISA was used to measure plasma concentrations of suPAR in patients at the time of enrolment to the ART programme. The association between plasma suPAR concentrations, baseline patient characteristics and cohort outcomes after 4 months of ART were determined. Results Patients (n = 293, 70% female had a median age of 33 years and were followed up for a median of 5 months from enrolment. The median CD4 cell count was 47 cells/μl (IQR = 22–72 and 38% of patients had WHO stage 4 disease. 218 (74% patients remained alive after 4 months of ART; 39 (13% died and 36 (12% were lost to the programme for other reasons. Patients who died had significantly higher plasma suPAR concentrations compared to those who either survived (P 10 suPAR concentrations were significantly associated with lower CD4 cell counts, WHO clinical stage 4 disease and male sex. In multivariate analysis to identify factors associated with death, log10 suPAR concentration was the most strongly associated variable (P Conclusion Plasma suPAR concentration was the strongest independent predictor of short-term mortality risk among patients with advanced immunodeficiency enrolling in this ART programme. However, lack of a discriminatory threshold did not permit this marker to be used to triage patients according to short-term mortality risk.

  11. Circulating intact and cleaved forms of the urokinase-type plasminogen activator receptor: biological variation, reference intervals and clinical useful cut-points.

    Science.gov (United States)

    Thurison, Tine; Christensen, Ib J; Lund, Ida K; Nielsen, Hans J; Høyer-Hansen, Gunilla

    2015-01-15

    High levels of circulating forms of the urokinase-type plasminogen activator receptor (uPAR) are significantly associated to poor prognosis in cancer patients. Our aim was to determine biological variations and reference intervals of the uPAR forms in blood, and in addition, to test the clinical relevance of using these as cut-points in colorectal cancer (CRC) prognosis. uPAR forms were measured in citrated and EDTA plasma samples using time-resolved fluorescence immunoassays. Diurnal, intra- and inter-individual variations were assessed in plasma samples from cohorts of healthy individuals. Reference intervals were determined in plasma from healthy individuals randomly selected from a Danish multi-center cross-sectional study. A cohort of CRC patients was selected from the same cross-sectional study. The reference intervals showed a slight increase with age and women had ~20% higher levels. The intra- and inter-individual variations were ~10% and ~20-30%, respectively and the measured levels of the uPAR forms were within the determined 95% reference intervals. No diurnal variation was found. Applying the normal upper limit of the reference intervals as cut-point for dichotomizing CRC patients revealed significantly decreased overall survival of patients with levels above this cut-point of any uPAR form. The reference intervals for the different uPAR forms are valid and the upper normal limits are clinically relevant cut-points for CRC prognosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Soluble urokinase-type plasminogen activator receptor (suPAR) in patients with acute pancreatitis (AP) - Progress in prediction of AP severity.

    Science.gov (United States)

    Lipinski, Michal; Rydzewska-Rosolowska, Alicja; Rydzewski, Andrzej; Cicha, Malgorzata; Rydzewska, Grazyna

    Soluble urokinase-type plasminogen activator receptor (suPAR) is a glycoprotein secreted during inflammation and infections. Moreover, increased levels of suPAR are observed after hypoxia and ischaemia. The aim of the study was to assess whether suPAR could represent a useful marker of acute pancreatitis (AP) severity. We have observed a cohort of 126 prospectively enrolled patients. Based on the presence of persistent organ failure (more than 48 h) and local complications (diagnosis of moderate AP [MSAP]), patients were classified into three groups: mild AP (MAP), moderate and severe AP (SAP). The blood samples were taken on admission for detecting suPAR concentrations. AP was considered severe in 33 patients (26.2%), MSAP was found in 37 patients (29.4%), and MAP was found in 56 patients (44,4%). The AUC for SAP predicted by suPAR was 0.993. The calculated cut-off point for prognosis SAP is 4.75 ng/mL. The BISAP score of ≥3 for detection of SAP had sensitivity and specificity of 94.6% and 63.6%, respectively. The AUC for severity predicted by BISAP amounted to 0.916. Additionally, suPAR turned out to be a good predictor of fatal AP: for the cut-off point 7.05 ng/mL, the AUC was 0.917. The AUC for death prediction in AP patients based on the BISAP score ≥3 was 0.894. suPAR concentration is a promising new diagnostic and prognostic indicator in SAP obtainable in the early stage of disease. Larger studies are recommended to evaluate this role further. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  13. A high-protein diet during hospitalization is associated with an accelerated decrease in soluble urokinase plasminogen activator receptor levels in acutely ill elderly medical patients with SIRS.

    Science.gov (United States)

    Tavenier, Juliette; Haupt, Thomas H; Andersen, Aino L; Buhl, Sussi F; Langkilde, Anne; Andersen, Jens R; Jensen, Jens-Erik B; Pedersen, Mette M; Petersen, Janne; Andersen, Ove

    2017-05-01

    Acute illness and hospitalization in elderly individuals are often accompanied by the systemic inflammatory response syndrome (SIRS) and malnutrition, both associated with wasting and mortality. Nutritional support and resistance training were shown to increase muscle anabolism and reduce inflammation in healthy elderly. We hypothesized that nutritional support and resistance training would accelerate the resolution of inflammation in hospitalized elderly patients with SIRS. Acutely admitted patients aged >65 years with SIRS were randomized to an intervention consisting of a high-protein diet (1.7 g/kg per day) during hospitalization, and daily protein supplement (18.8 g) and 3 weekly resistance training sessions for 12 weeks after discharge (Intervention, n=14), or to standard-care (Control, n=15). Plasma levels of the inflammatory biomarkers soluble urokinase plasminogen activator receptor (suPAR), interleukin-6, C-reactive protein (CRP), and albumin were measured at admission, discharge, and 4 and 13 weeks after discharge. The Intervention group had an earlier decrease in suPAR levels than the Control group: -15.4% vs. +14.5%, P=.007 during hospitalization, and -2.4% vs. -28.6%, P=.007 between discharge and 4 weeks. There were no significant effects of the intervention on the other biomarkers. All biomarkers improved significantly between admission and 13 weeks, although with different kinetics (suPAR: -22%, interleukin-6: -86%, CRP: -89%, albumin: +11%). Nutritional support during hospitalization was associated with an accelerated decrease in suPAR levels, whereas the combined nutrition and resistance training intervention after discharge did not appear to affect the inflammatory state. Our results indicate that improved nutritional care during hospitalization may accelerate recovery in acutely ill elderly medical patients. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Kim, Yeoun-Hee; Chang, Yongmin; Jung, Jae-Chang

    2012-01-01

    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.

  15. Diagnostic accuracy of soluble urokinase plasminogen activator receptor (suPAR) for prediction of bacteremia in patients with systemic inflammatory response syndrome.

    Science.gov (United States)

    Hoenigl, Martin; Raggam, Reinhard B; Wagner, Jasmin; Valentin, Thomas; Leitner, Eva; Seeber, Katharina; Zollner-Schwetz, Ines; Krammer, Werner; Prüller, Florian; Grisold, Andrea J; Krause, Robert

    2013-02-01

    Soluble urokinase plasminogen activator receptor (suPAR) serum concentrations have recently been described to reflect the severity status of systemic inflammation. In this study, the diagnostic accuracy of suPAR, C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) to predict bacteremia in patients with systemic inflammatory response syndrome (SIRS) was compared. A total of 132 patients with SIRS were included. In 55 patients blood cultures had resulted positive (study group 1, Gram positive bacteria: Staphylococcus aureus and Streptococcus spp., n=15; study group 2, Gram-negative bacteria, n=40) and 77 patients had negative blood culture results (control group, n=77). Simultaneously with blood cultures suPAR, CRP, PCT, IL-6 and white blood count (WBC) were determined. SuPAR values were significantly higher in study group 1 (median 8.11; IQR 5.78-15.53; p=0.006) and study group 2 (median 9.62; IQR 6.52-11.74; p<0.001) when compared with the control group (median 5.65; IQR 4.30-7.83). ROC curve analysis revealed an AUC of 0.726 for suPAR in differentiating SIRS patients with bacteremia from those without. The biomarkers PCT and IL-6 showed comparable results. Regarding combinations of biomarkers multiplying suPAR, PCT and IL-6 was most promising and resulted in an AUC value of 0.804. Initial suPAR serum concentrations were significantly higher (p=0.028) in patients who died within 28 days than in those who survived. No significant difference was seen for PCT, IL-6 and CRP. In conclusion, suPAR, IL-6 and PCT may contribute to predicting bacteremia in SIRS patients. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  16. Urokinase-type plasminogen activator (uPA) stimulates triglyceride synthesis in Huh7 hepatoma cells via p38-dependent upregulation of DGAT2.

    Science.gov (United States)

    Paland, Nicole; Gamliel-Lazarovich, Aviva; Coleman, Raymond; Fuhrman, Bianca

    2014-11-01

    The liver is the central organ of fatty acid and triglyceride metabolism. Oxidation and synthesis of fatty acids and triglycerides is under the control of peroxisome-proliferator-activated receptors (PPAR) α. Impairment of these receptors' function contributes to the accumulation of triglycerides in the liver resulting in non-alcoholic fatty liver disease. Urokinase-type plasminogen activator (uPA) was shown to regulate gene expression in the liver involving PPARγ transcriptional activity. In this study we questioned whether uPA modulates triglyceride metabolism in the liver, and investigated the mechanisms involved in the observed processes. Huh7 hepatoma cells were incubated with increasing concentrations of uPA for 24 h uPA dose-dependently increased the cellular triglyceride mass, and this effect resulted from increased de novo triglyceride synthesis mediated by the enzyme diglyceride acyltransferase 2 (DGAT2). Also, the amount of free fatty acids was highly up regulated by uPA through activation of the transcription factor SREBP-1. Chemical activation of PPARα further increased uPA-stimulated triglyceride synthesis, whereas inhibition of p38, an upstream activator of PPARα, completely abolished the stimulatory effect of uPA on both triglyceride synthesis and DGAT2 upregulation. The effect of uPA on triglyceride synthesis in Huh7 cells was mediated via binding to its receptor, the uPAR. In vivo studies in uPAR(-/-) mice demonstrated that no lipid droplets were observed in their livers compared to C57BL/6 mice and the triglyceride levels were significantly lower. This study presents a new biological function of the uPA/uPAR system in the metabolism of triglycerides and might present a new target for an early therapeutic intervention for NAFLD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Inflammation and uPAR-Expression in Colorectal Liver Metastases in Relation to Growth Pattern and Neo-adjuvant Therapy

    DEFF Research Database (Denmark)

    Eefsen, R L; Engelholm, L; Alpizar-Alpizar, W

    2015-01-01

    Proteolytic activity and inflammation in the tumour microenvironment affects cancer progression. In colorectal cancer (CRC) liver metastases it has been observed that three different immune profiles are present, as well as proteolytic activity, determined by the expression of urokinase-type plasm......Proteolytic activity and inflammation in the tumour microenvironment affects cancer progression. In colorectal cancer (CRC) liver metastases it has been observed that three different immune profiles are present, as well as proteolytic activity, determined by the expression of urokinase......-type plasminogen activator (uPAR).The main objectives of this study were to investigate uPAR expression and the density of macrophages (CD68) and T cells (CD3) as markers of inflammation in resected CRC liver metastases, where patients were neo-adjuvantly treated with chemotherapy with or without the angiogenesis...... inhibitor bevacizumab. Chemonaive patients served as a control group. The markers were correlated to growth patterns (GP) of liver metastases, i.e. desmoplastic, pushing and replacement GP. It was hypothesised that differences in proteolysis and inflammation could reflect tumour specific growth and therapy...

  18. Nicotine stimulates urokinase-type plasminogen activator receptor expression and cell invasiveness through mitogen-activated protein kinase and reactive oxygen species signaling in ECV304 endothelial cells

    International Nuclear Information System (INIS)

    Khoi, Pham Ngoc; Park, Jung Sun; Kim, Nam Ho; Jung, Young Do

    2012-01-01

    Urokinase-type plasminogen activator receptor (uPAR) expression is elevated during inflammation, tissue remodeling and in many human cancers. This study investigated the effect of nicotine, a major alkaloid in tobacco, on uPAR expression and cell invasiveness in ECV304 endothelial cells. Nicotine stimulated uPAR expression in a dose-dependent manner and activated extracellular signal-regulated kinases-1/2 (Erk-1/2), c-Jun amino-terminal kinase (JNK) and p38 mitogen activated protein kinase (MAPK). Specific inhibitors of MEK-1 (PD98059) and JNK (SP600125) inhibited the nicotine-induced uPAR expression, while the p38 MAPK inhibitor SB203580 did not. Expression vectors encoding dominant negative MEK-1 (pMCL-K97M) and JNK (TAM67) also prevented nicotine-induced uPAR promoter activity. The intracellular hydrogen peroxide (H 2 O 2 ) content was increased by nicotine treatment. The antioxidant N-acetylcysteine prevented nicotine-activated production of reactive oxygen species (ROS) and uPAR expression. Furthermore, exogenous H 2 O 2 increased uPAR mRNA expression. Deleted and site-directed mutagenesis demonstrated the involvement of the binding sites of transcription factor nuclear factor-kappaB (NF-κB) and activator protein (AP)-1 in the nicotine-induced uPAR expression. Studies with expression vectors encoding mutated NF-κB signaling molecules and AP-1 decoy confirmed that NF-κB and AP-1 were essential for the nicotine-stimulated uPAR expression. MAPK (Erk-1/2 and JNK) and ROS functioned as upstream signaling molecules in the activation of AP-1 and NF-κB, respectively. In addition, ECV304 endothelial cells treated with nicotine displayed markedly enhanced invasiveness, which was partially abrogated by uPAR neutralizing antibodies. The data indicate that nicotine induces uPAR expression via the MAPK/AP-1 and ROS/NF-κB signaling pathways and, in turn, stimulates invasiveness in human ECV304 endothelial cells. -- Highlights: ► Endothelial cells treated with nicotine

  19. Nicotine stimulates urokinase-type plasminogen activator receptor expression and cell invasiveness through mitogen-activated protein kinase and reactive oxygen species signaling in ECV304 endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Khoi, Pham Ngoc; Park, Jung Sun; Kim, Nam Ho; Jung, Young Do, E-mail: ydjung@chonnam.ac.kr

    2012-03-01

    Urokinase-type plasminogen activator receptor (uPAR) expression is elevated during inflammation, tissue remodeling and in many human cancers. This study investigated the effect of nicotine, a major alkaloid in tobacco, on uPAR expression and cell invasiveness in ECV304 endothelial cells. Nicotine stimulated uPAR expression in a dose-dependent manner and activated extracellular signal-regulated kinases-1/2 (Erk-1/2), c-Jun amino-terminal kinase (JNK) and p38 mitogen activated protein kinase (MAPK). Specific inhibitors of MEK-1 (PD98059) and JNK (SP600125) inhibited the nicotine-induced uPAR expression, while the p38 MAPK inhibitor SB203580 did not. Expression vectors encoding dominant negative MEK-1 (pMCL-K97M) and JNK (TAM67) also prevented nicotine-induced uPAR promoter activity. The intracellular hydrogen peroxide (H{sub 2}O{sub 2}) content was increased by nicotine treatment. The antioxidant N-acetylcysteine prevented nicotine-activated production of reactive oxygen species (ROS) and uPAR expression. Furthermore, exogenous H{sub 2}O{sub 2} increased uPAR mRNA expression. Deleted and site-directed mutagenesis demonstrated the involvement of the binding sites of transcription factor nuclear factor-kappaB (NF-κB) and activator protein (AP)-1 in the nicotine-induced uPAR expression. Studies with expression vectors encoding mutated NF-κB signaling molecules and AP-1 decoy confirmed that NF-κB and AP-1 were essential for the nicotine-stimulated uPAR expression. MAPK (Erk-1/2 and JNK) and ROS functioned as upstream signaling molecules in the activation of AP-1 and NF-κB, respectively. In addition, ECV304 endothelial cells treated with nicotine displayed markedly enhanced invasiveness, which was partially abrogated by uPAR neutralizing antibodies. The data indicate that nicotine induces uPAR expression via the MAPK/AP-1 and ROS/NF-κB signaling pathways and, in turn, stimulates invasiveness in human ECV304 endothelial cells. -- Highlights: ► Endothelial cells

  20. In IgA Nephropathy, Glomerulosclerosis Is Associated with Increased Urinary CD80 Excretion and Urokinase-Type Plasminogen Activator Receptor-Positive Podocyturia

    Directory of Open Access Journals (Sweden)

    Hernán Trimarchi

    2017-05-01

    Full Text Available Background: Podocyturia may determine the evolution to podocytopenia, glomerulosclerosis, and renal failure. According to the Oxford classification of IgA nephropathy (IgAN, the S1 lesion describes glomerulosclerosis. Urokinase-type plasminogen activator receptor (uPAR participates in podocyte attachment, while CD80 increases in glomerulosclerosis. We measured uPAR-positive urinary podocytes and urinary CD80 (uCD80 in controls and in IgAN subjects with M1E0S0T0 and M1E0S1T0 Oxford scores to assess a potential association between podocyturia, inflammation, and glomerulosclerosis. Methods: The groups were as follows: controls (G1, n = 20 and IgAN group (G2, n = 39, subdivided into M1E0S0T0 (G2A, n = 21 and M1E0S1T0 (G2B, n = 18. Among the included variables, we determined uPAR-positive podocytes/gram of urinary creatinine (gUrCr and uCD80 ng/gUrCr. Biopsies with interstitial fibrosis and tubular atrophy <10% were included. Results: Groups were not different in age and gender; urinary protein-creatinine (uP/C ratio, Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI equation, uPAR-positive podocytes/gUrCr, and uCD80 were significantly increased in G2 versus G1. G2A and G2B were not different in age, gender, hypertension, and follow-up. G2B displayed significantly higher uP/C, uPAR-positive podocytes, uCD80, and lower CKD-EPI versus G2A. Strong significant correlations were encountered between uCD80 and podocyturia in G2A and G2B. However, when G1 was compared to G2A and G2B separately, the differences with respect to uP/C, uPAR-positive podocytes, and podocyturia were significantly stronger versus G2B than versus G2A. Conclusions: IgAN presents elevated uCD80 excretion and uPAR-positive podocyturia, while CD80 correlates with podocyturia. Glomerulosclerosis (S1 at the time of biopsy is associated with higher uP/C, lower renal function, increased uPAR-positive podocyturia, and CD80 excretion, and is independent of M1. In IgAN, uPAR may

  1. Intact and cleaved forms of the urokinase receptor enhance discrimination of cancer from non-malignant conditions in patients presenting with symptoms related to colorectal cancer.

    Science.gov (United States)

    Lomholt, A F; Høyer-Hansen, G; Nielsen, H J; Christensen, I J

    2009-09-15

    Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality in developed countries. It is known that early detection results in improved survival, and consequently there is a need for improved diagnostic tools in CRC. The plasma level of soluble urokinase plasminogen activator receptor (suPAR) was proposed as a marker in CRC patients. This study was undertaken to evaluate the individual molecular forms of suPAR as discriminators in a group of patients undergoing endoscopical examination following symptoms related to colorectal cancer. In a case-control study comprising 308 patients undergoing endoscopical examination following CRC-related symptoms, 77 CRC patients with adenocarcinoma were age and gender matched to: 77 patients with adenomas; 77 with other non-malignant findings, and 77 with no findings. The different uPAR forms were measured in citrate plasma collected before endoscopical examination, using three different Time Resolved - Fluorescence Immuno Assays (TR-FIA's). All soluble uPAR forms were found to be significantly higher in cancer patients than in patients presenting with other non-malignant findings; uPAR(I) P=0.0006, suPAR(I-III) P<0.0001 and suPAR(I-III)+(II-III) P<0.0001, whereas no significant difference was found when performing similar comparisons for patients presenting with adenomas. The odds ratio (OR) for the comparison of uPAR(I) in patients with CRC to subjects with other non-malignant findings was 3.44 (95% CI:1.86-6.37). CRC patients had a mean elevated level of 20.9% (95% CI:10.2-32.6) for suPAR(I-III) and 18.5% (95% CI:9.0-28.8) for suPAR(I-III)+(II-III) compared with subjects with non-malignant findings. The findings confirm reports on increased uPAR expression in cancer patients and in particular elevated levels of suPAR in blood from CRC patients and indicate that suPAR levels in blood are increasing during carcinogenesis. Although none of the measured uPAR forms were cancer specific, our findings suggest

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

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yeoun-Hee [Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Chang, Yongmin [Department of Molecular Medicine, Kyungpook National University College of Medicine, Kyungpook National University, 200 Dongduk-Ro Jung-Gu, Daegu 700-714 (Korea, Republic of); Jung, Jae-Chang, E-mail: jcjung@knu.ac.kr [Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu 702-701 (Korea, Republic of)

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer Staurosporine mediates stimulation of RGC differentiation in vitro cultured retinal neuroblasts. Black-Right-Pointing-Pointer Staurosporine mediates uPA activation during RGC differentiation in vitro. Black-Right-Pointing-Pointer Inhibition of uPA blocks the staurosporine mediated RGC differentiation both in vitro and in ovo. Black-Right-Pointing-Pointer 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

  3. Exploiting subsite S1 of trypsin-like serine proteases for selectivity: potent and selective inhibitors of urokinase-type plasminogen activator.

    Science.gov (United States)

    Mackman, R L; Katz, B A; Breitenbucher, J G; Hui, H C; Verner, E; Luong, C; Liu, L; Sprengeler, P A

    2001-11-08

    A nonselective inhibitor of trypsin-like serine proteases, 2-(2-hydroxybiphenyl-3-yl)-1H-indole-5-carboxamidine (1) (Verner, E.; Katz, B. A.; Spencer, J.; Allen, D.; Hataye, J.; Hruzewicz, W.; Hui, H. C.; Kolesnikov, A.; Li, Y.; Luong, C.; Martelli, A.; Radika. K.; Rai, R.; She, M.; Shrader, W.; Sprengeler, P. A.; Trapp, S.; Wang, J.; Young, W. B.; Mackman, R. L. J. Med. Chem. 2001, 44, 2753-2771) has been optimized through minor structural changes on the S1 binding group to afford remarkably selective and potent inhibitors of urokinase-type plasminogen activator (uPA). The trypsin-like serine proteases(1) that comprise drug targets can be broadly categorized into two subfamilies, those with Ser190 and those with Ala190. A single-atom modification, for example, replacement of hydrogen for chlorine at the 6-position of the 5-amidinoindole P1 group on 1, generated up to 6700-fold selectivity toward the Ser190 enzymes and against the Ala190 enzymes. The larger chlorine atom displaces a water molecule (H(2)O1(S1)) that binds near residue 190 in all the complexes of 1, and related inhibitors, in uPA, thrombin, and trypsin. The water molecule, H(2)O1(S1), in both the Ser190 or Ala190 enzymes, hydrogen bonds with the amidine N1 nitrogen of the inhibitor. When it is displaced, a reduction in affinity toward the Ala190 enzymes is observed due to the amidine N1 nitrogen of the bound inhibitor being deprived of a key hydrogen-bonding partner. In the Ser190 enzymes the affinity is maintained since the serine hydroxyl oxygen O gamma(Ser190) compensates for the displaced water molecule. High-resolution crystallography provided evidence for the displacement of the water molecule and validated the design rationale. In summation, a novel and powerful method for engineering selectivity toward Ser190 proteases and against Ala190 proteases without substantially increasing molecular weight is described.

  4. Prognostic significance of urokinase plasminogen activator and plasminogen activator inhibitor-1 mRNA expression in lymph node- and hormone receptor-positive breast cancer

    Directory of Open Access Journals (Sweden)

    Krause Alexander

    2006-08-01

    Full Text Available Abstract Background One of the most thoroughly studied systems in relation to its prognostic relevance in patients with breast cancer, is the plasminogen activation system that comprises of, among others, the urokinase Plasminogen Activator (uPA and its main inhibitor, the Plasminogen Activator Inhibitor-1 (PAI-1. In this study, we investigated the prognostic value of uPA and PAI-1 at the mRNA level in lymph node- and hormone receptor-positive breast cancer. Methods The study included a retrospective series of 87 patients with hormone-receptor positive and axillary lymph node-positive breast cancer. All patients received radiotherapy, adjuvant anthracycline-based chemotherapy and five years of tamoxifen treatment. The median patient age was 54 and the median follow-up time was 79 months. Distant relapse occurred in 30 patients and 22 patients died from breast cancer during follow-up. We investigated the prognostic value of uPA and PAI-1 at the mRNA level as measured by real-time quantitative RT-PCR. Results uPA and PAI-1 gene expression was not found to be correlated with any of the established clinical and pathological factors. Metastasis-free Survival (MFS and Breast Cancer specific Survival (BCS were significantly shorter in patients expressing high levels of PAI-1 mRNA (p PAI-1 mRNA appeared to be the strongest prognostic factor for MFS (Hazard Ratio (HR = 10.12; p = 0.0002 and for BCS (HR = 13.17; p = 0.0003. Furthermore, uPA gene expression was not significantly associated neither with MFS (p = 0.41 nor with BCS (p = 0.19. In a Cox-multivariate regression analysis, uPA expression did not demonstrate significant independent prognostic value. Conclusion These findings indicate that high PAI-1 mRNA expression represents a strong and independent unfavorable prognostic factor for the development of metastases and for breast cancer specific survival in a population of hormone receptor- and lymph node-positive breast cancer patients.

  5. Prognostic significance of urokinase plasminogen activator and plasminogen activator inhibitor-1 mRNA expression in lymph node- and hormone receptor-positive breast cancer

    International Nuclear Information System (INIS)

    Leissner, Philippe; Verjat, Thibault; Bachelot, Thomas; Paye, Malick; Krause, Alexander; Puisieux, Alain; Mougin, Bruno

    2006-01-01

    One of the most thoroughly studied systems in relation to its prognostic relevance in patients with breast cancer, is the plasminogen activation system that comprises of, among others, the urokinase Plasminogen Activator (uPA) and its main inhibitor, the Plasminogen Activator Inhibitor-1 (PAI-1). In this study, we investigated the prognostic value of uPA and PAI-1 at the mRNA level in lymph node- and hormone receptor-positive breast cancer. The study included a retrospective series of 87 patients with hormone-receptor positive and axillary lymph node-positive breast cancer. All patients received radiotherapy, adjuvant anthracycline-based chemotherapy and five years of tamoxifen treatment. The median patient age was 54 and the median follow-up time was 79 months. Distant relapse occurred in 30 patients and 22 patients died from breast cancer during follow-up. We investigated the prognostic value of uPA and PAI-1 at the mRNA level as measured by real-time quantitative RT-PCR. uPA and PAI-1 gene expression was not found to be correlated with any of the established clinical and pathological factors. Metastasis-free Survival (MFS) and Breast Cancer specific Survival (BCS) were significantly shorter in patients expressing high levels of PAI-1 mRNA (p < 0.0001; p < 0.0001; respectively). In Cox multivariate analysis, the level of PAI-1 mRNA appeared to be the strongest prognostic factor for MFS (Hazard Ratio (HR) = 10.12; p = 0.0002) and for BCS (HR = 13.17; p = 0.0003). Furthermore, uPA gene expression was not significantly associated neither with MFS (p = 0.41) nor with BCS (p = 0.19). In a Cox-multivariate regression analysis, uPA expression did not demonstrate significant independent prognostic value. These findings indicate that high PAI-1 mRNA expression represents a strong and independent unfavorable prognostic factor for the development of metastases and for breast cancer specific survival in a population of hormone receptor- and lymph node-positive breast cancer

  6. Decreased Hepatocyte Growth Factor (HGF) and Gamma Aminobutyric Acid (GABA) in Individuals with Obsessive-Compulsive Disorder (OCD).

    Science.gov (United States)

    Russo, Anthony J; Pietsch, Stefanie C

    2013-01-01

    There is support for the role of gamma aminobutyric acid (GABA) in the etiology of mood disorders. Recent research has shown that hepatocyte growth factor (HGF) modulates GABAergic inhibition and seizure susceptibility. This study was designed to determine and correlate plasma levels of HGF and GABA as well as symptom severity in individuals with obsessive-compulsive disorder (OCD). Plasma from 15 individuals with OCD (9 males, 6 females;, mean age 38.7 years) and 17 neurotypical controls (10 males, 7 females; mean age 35.2 years) was assessed for HGF, GABA, urokinase plasminogen activator (uPA), and urokinase plasminogen activator receptor (uPAR) concentration using enzyme-linked immunosorbest assays ELISAs. Symptom severity was assessed in these OCD individuals and compared with HGF and GABA concentrations. In this preliminary study, individuals with OCD had significantly decreased HGF levels, decreased plasma levels of GABA and decreased uPA. We found that both uPA and uPAR levels correlate with HGF. Both low uPA and low uPAR levels correlate with high symptom severity in individuals with OCD. Low GABA levels in OCD individuals also correlate with high symptom severity. These results demonstrate a preliminary association between HGF, GABA, uPA levels, and OCD and suggest that plasma GABA and uPA levels are related to symptom severity in individuals with OCD.

  7. The pro-inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is associated with incident type 2 diabetes among overweight but not obese individuals with impaired glucose regulation

    DEFF Research Database (Denmark)

    Heraclides, A; Jensen, T M; Rasmussen, S S

    2013-01-01

    Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION) and for whom data on suPAR, BMI and smoking were available. Logistic regression analysis was used to estimate the odds for incident type 2 diabetes per twofold increase in suPAR levels. Interactions between both smoking and body......Recent evidence links the soluble urokinase plasminogen activator receptor (suPAR), a stable biomarker of systemic immune activation, to several chronic diseases, including type 2 diabetes. suPAR is also associated with adiposity and smoking. We hypothesised that this biomarker would be linked...... to incident type 2 diabetes in individuals with impaired glucose regulation and that this association would be modified by smoking and body weight status. The study included 1,933 participants with impaired glucose regulation, who were drawn from the Danish arm of the Anglo-Danish-Dutch Study of Intensive...

  8. Flavonol-enriched fraction from Vaccinium macrocarpon fruit inhibits matrix metalloproteinase-2, matrix metalloproteinase-9 and urokinase-type plasminogen activator expression in human prostate cancer cells in vitro

    Directory of Open Access Journals (Sweden)

    James MacPhee

    2014-11-01

    Full Text Available Background: Prostate cancer, amongst other cancer types has a genetic and environmental component, which can contribute to prostate cancer development and progression. Vaccinum macrocarpon (American cranberry is a botanical that contains several phytochemicals which have been suggested to play a role in preventing cardiovascular disease, cancer, and urinary tract infections as well as in the maintenance of oral health. Context and purpose of this study: This investigation evaluated the effects of a flavonolenriched fraction (FL from the American cranberry (Vaccinium macrocarpon containing quercetin and myricetin glycosides on matrix metalloproteinase (MMP and urokinase-type plasminogen activator (uPA activities and their associated regulatory proteins in DU145 human prostate cancer cells in vitro. Results: A flavonol-enriched fraction (FL was prepared from Vaccinium macrocarpon berries and the effect of this fraction on prostate cancer cell behaviour was assessed using biochemical and molecular approaches including cytotoxicity assays and Western blot analysis to determine protein expression. Cranberry FL decreased cellular viability of DU145 cells at a concentration of 25 ug/ml by 20% after 6 hours of treatment. Further investigations determined that associated with this cytotoxicity, cranberry FL decreases matrix metalloproteinase (MMP ( specifically MMP-2 and MMP-9 activity and urokinase plasminogen activator (uPA activity through effects on specific temporal MMP regulators and uPA regulators and by affecting either the phosphorylation status and/or expression of specific MAP kinase, PI-3 kinase, NF-kB and AP-1 pathway associated proteins. Conclusion: This study demonstrates, for the first time, the ability of Vaccinium macrocarpon flavonols to modulate cellular pathways associated with migration, invasion, and proliferation, suggesting that cranberry (Vaccinium macrocarpon is a viable candidate for further research as a natural product that

  9. Growth of Murine Splenic Tissue Is Suppressed by Lymphotoxin β-Receptor Signaling (LTβR) Originating from Splenic and Non-Splenic Tissues

    DEFF Research Database (Denmark)

    Milićević, Novica M; Nohroudi, Klaus; Schmidt, Friederike

    2016-01-01

    LTβR signaling. Two-dimensional differential gel electrophoresis and subsequent mass spectrometry of stromal splenic tissue was applied to screen for potential factors mediating the LTβR dependent suppressive activity. Thus, LTβR dependent growth suppression is involved in regulating the size...

  10. SlDREB2, a tomato dehydration-responsive element-binding 2 transcription factor, mediates salt stress tolerance in tomato and Arabidopsis.

    Science.gov (United States)

    Hichri, Imène; Muhovski, Yordan; Clippe, André; Žižková, Eva; Dobrev, Petre I; Motyka, Vaclav; Lutts, Stanley

    2016-01-01

    To counter environmental cues, cultivated tomato (Solanum lycopersicum L.) has evolved adaptive mechanisms requiring regulation of downstream genes. The dehydration-responsive element-binding protein 2 (DREB2) transcription factors regulate abiotic stresses responses in plants. Herein, we isolated a novel DREB2-type regulator involved in salinity response, named SlDREB2. Spatio-temporal expression profile together with investigation of its promoter activity indicated that SlDREB2 is expressed during early stages of seedling establishment and in various vegetative and reproductive organs of adult plants. SlDREB2 is up-regulated in roots and young leaves following exposure to NaCl, but is also induced by KCl and drought. Its overexpression in WT Arabidopsis and atdreb2a mutants improved seed germination and plant growth in presence of different osmotica. In tomato, SlDREB2 affected vegetative and reproductive organs development and the intronic sequence present in the 5' UTR drives its expression. Physiological, biochemical and transcriptomic analyses showed that SlDREB2 enhanced plant tolerance to salinity by improvement of K(+) /Na(+) ratio, and proline and polyamines biosynthesis. Exogenous hormonal treatments (abscisic acid, auxin and cytokinins) and analysis of WT and 35S::SlDREB2 tomatoes hormonal contents highlighted SlDREB2 involvement in abscisic acid biosynthesis/signalling. Altogether, our results provide an overview of SlDREB2 mode of action during early salt stress response. © 2015 John Wiley & Sons Ltd.

  11. Recanalization rate and clinical outcome of intravenous tissue plasminogen activator at 0.6 mg/kg and intra-arterial urokinase in acute ischemic stroke with large vessel occlusion

    International Nuclear Information System (INIS)

    Nakashima, Kazuya; Ohnishi, Hideyuki; Taomoto, Katsushi

    2008-01-01

    We evaluated the recanalization rate and clinical outcome of intravenous tissue plasminogen activator (t-PA) and intra-arterial urokinase (PTA) in acute ischemic stroke with large vessel occlusion. The recanalization of the occlusion site and the ischemic change were evaluated with pre-and post-treated MRI and MR angiography (MRA). Total recanalization rates after the intravenous (IV) t-PA and the PTA therapy were 35.6 and 21.9%, respectively. These rates were 50.0 and 16.7% in the distal middle cerebral artery (MCA), 52.6 and 25.0% in the proximal MCA, 6.3 and 5.3% in the internal carotid artery (ICA), 25.0 and 26.3% in the basilar artery (BA), respectively. The rates of the symptomatic intracerebral hemorrhage after IV t-PA and PTA were 0 and 5.2%, respectively. The proportion of modified Rankin Scale (mRS) of 0 to 1 at 3 months after treatments were 17.4% in IV t-PA and 12.5% in PTA. Our results indicated better recanalization rate and outcome of MCA with t-PA than that of PTA. However, the recanalization rate of ICA and BA were very poor in both t-PA and PTA as yet. It is necessary to investigate newly strategies and/or modality for ICA and BA occlusion. (author)

  12. Vasodilator-Stimulated Phosphoprotein (VASP) depletion from breast cancer MDA-MB-231 cells inhibits tumor spheroid invasion through downregulation of Migfilin, β-catenin and urokinase-plasminogen activator (uPA).

    Science.gov (United States)

    Gkretsi, Vasiliki; Stylianou, Andreas; Stylianopoulos, Triantafyllos

    2017-03-15

    A hallmark of cancer cells is their ability to invade surrounding tissues and form metastases. Cell-extracellular matrix (ECM)-adhesion proteins are crucial in metastasis, connecting tumor ECM with actin cytoskeleton thus enabling cells to respond to mechanical cues. Vasodilator-stimulated phosphoprotein (VASP) is an actin-polymerization regulator which interacts with cell-ECM adhesion protein Migfilin, and regulates cell migration. We compared VASP expression in MCF-7 and MDA-MB-231 breast cancer (BC) cells and found that more invasive MDA-MB-231 cells overexpress VASP. We then utilized a 3-dimensional (3D) approach to study metastasis in MDA-MB-231 cells using a system that considers mechanical forces exerted by the ECM. We prepared 3D collagen I gels of increasing concentration, imaged them by atomic force microscopy, and used them to either embed cells or tumor spheroids, in the presence or absence of VASP. We show, for the first time, that VASP silencing downregulated Migfilin, β-catenin and urokinase plasminogen activator both in 2D and 3D, suggesting a matrix-independent mechanism. Tumor spheroids lacking VASP demonstrated impaired invasion, indicating VASP's involvement in metastasis, which was corroborated by Kaplan-Meier plotter showing high VASP expression to be associated with poor remission-free survival in lymph node-positive BC patients. Hence, VASP may be a novel BC metastasis biomarker. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Stomagenesis versus myogenesis: Parallels in intrinsic and extrinsic regulation of transcription factor mediated specialized cell-type differentiation in plants and animals.

    Science.gov (United States)

    Putarjunan, Aarthi; Torii, Keiko U

    2016-05-01

    Although the last common unicellular ancestor of plants and animals diverged several billion years ago, and while having developed unique developmental programs that facilitate differentiation and proliferation specific to plant and animal systems, there still exists a high degree of conservation in the logic regulating these developmental processes within these two seemingly diverse kingdoms. Stomatal differentiation in plants involves a series of orchestrated cell division events mediated by a family of closely related bHLH transcription factors (TFs) to create a pair of mature guard cells. These TFs are in turn regulated by a number of upstream signaling components that ultimately function to achieve lineage specific differentiation and organized tissue patterning on the plant epidermis. The logic involved in the specification of the myogenic differentiation program in animals is intriguingly similar to stomatal differentiation in plants: Closely-related myogenic bHLHs, known as MRFs (Myogenic Regulatory Factors) provide lineage specificity essential for cell-fate determination. These MRFs, similar to the bHLHs in plants, are regulated by several upstream signaling cascades that succinctly regulate each differentiation step, leading to the production of mature muscle fibers. This review aims at providing a perspective on the emerging parallels in the logic employed by key bHLH transcription factors and their upstream signaling components that function to precisely regulate key cell-state transition events in the stomatal as well as myogenic cell lineages. © 2016 The Authors. Development, Growth & Differentiation published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Developmental Biologists.

  14. Changes in soluble factor-mediated CD8+ cell-derived antiviral activity in cynomolgus macaques infected with simian immunodeficiency virus SIVmac251: relationship to biological markers of progression.

    Science.gov (United States)

    Dioszeghy, Vincent; Benlhassan-Chahour, Kadija; Delache, Benoit; Dereuddre-Bosquet, Nathalie; Aubenque, Celine; Gras, Gabriel; Le Grand, Roger; Vaslin, Bruno

    2006-01-01

    Cross-sectional studies have shown that the capacity of CD8+ cells from human immunodeficiency virus (HIV)-infected patients and simian immunodeficiency virus (SIV) SIVmac-infected macaques to suppress the replication of human and simian immunodeficiency viruses in vitro depends on the clinical stage of disease, but little is known about changes in this antiviral activity over time in individual HIV-infected patients or SIV-infected macaques. We assessed changes in the soluble factor-mediated noncytolytic antiviral activity of CD8+ cells over time in eight cynomolgus macaques infected with SIVmac251 to determine the pathophysiological role of this activity. CD8+ cell-associated antiviral activity increased rapidly in the first week after viral inoculation and remained detectable during the early phase of infection. The net increase in antiviral activity of CD8+ cells was correlated with plasma viral load throughout the 15 months of follow-up. CD8+ cells gradually lost their antiviral activity over time and acquired virus replication-enhancing capacity. Levels of antiviral activity correlated with CD4+ T-cell counts after viral set point. Concentrations of beta-chemokines and interleukin-16 in CD8+ cell supernatants were not correlated with this antiviral activity, and alpha-defensins were not detected. The soluble factor-mediated antiviral activity of CD8+ cells was neither cytolytic nor restricted to major histocompatibility complex. This longitudinal study strongly suggests that the increase in noncytolytic antiviral activity from baseline and the maintenance of this increase over time in cynomolgus macaques depend on both viral replication and CD4+ T cells.

  15. Changes in Soluble Factor-Mediated CD8+ Cell-Derived Antiviral Activity in Cynomolgus Macaques Infected with Simian Immunodeficiency Virus SIVmac251: Relationship to Biological Markers of Progression†

    Science.gov (United States)

    Dioszeghy, Vincent; Benlhassan-Chahour, Kadija; Delache, Benoit; Dereuddre-Bosquet, Nathalie; Aubenque, Celine; Gras, Gabriel; Le Grand, Roger; Vaslin, Bruno

    2006-01-01

    Cross-sectional studies have shown that the capacity of CD8+ cells from human immunodeficiency virus (HIV)-infected patients and simian immunodeficiency virus (SIV) SIVmac-infected macaques to suppress the replication of human and simian immunodeficiency viruses in vitro depends on the clinical stage of disease, but little is known about changes in this antiviral activity over time in individual HIV-infected patients or SIV-infected macaques. We assessed changes in the soluble factor-mediated noncytolytic antiviral activity of CD8+ cells over time in eight cynomolgus macaques infected with SIVmac251 to determine the pathophysiological role of this activity. CD8+ cell-associated antiviral activity increased rapidly in the first week after viral inoculation and remained detectable during the early phase of infection. The net increase in antiviral activity of CD8+ cells was correlated with plasma viral load throughout the 15 months of follow-up. CD8+ cells gradually lost their antiviral activity over time and acquired virus replication-enhancing capacity. Levels of antiviral activity correlated with CD4+ T-cell counts after viral set point. Concentrations of β-chemokines and interleukin-16 in CD8+ cell supernatants were not correlated with this antiviral activity, and α-defensins were not detected. The soluble factor-mediated antiviral activity of CD8+ cells was neither cytolytic nor restricted to major histocompatibility complex. This longitudinal study strongly suggests that the increase in noncytolytic antiviral activity from baseline and the maintenance of this increase over time in cynomolgus macaques depend on both viral replication and CD4+ T cells. PMID:16352548

  16. Vasodilator-Stimulated Phosphoprotein (VASP) depletion from breast cancer MDA-MB-231 cells inhibits tumor spheroid invasion through downregulation of Migfilin, β-catenin and urokinase-plasminogen activator (uPA)

    Energy Technology Data Exchange (ETDEWEB)

    Gkretsi, Vasiliki; Stylianou, Andreas; Stylianopoulos, Triantafyllos, E-mail: tstylian@ucy.ac.cy

    2017-03-15

    A hallmark of cancer cells is their ability to invade surrounding tissues and form metastases. Cell-extracellular matrix (ECM)-adhesion proteins are crucial in metastasis, connecting tumor ECM with actin cytoskeleton thus enabling cells to respond to mechanical cues. Vasodilator-stimulated phosphoprotein (VASP) is an actin-polymerization regulator which interacts with cell-ECM adhesion protein Migfilin, and regulates cell migration. We compared VASP expression in MCF-7 and MDA-MB-231 breast cancer (BC) cells and found that more invasive MDA-MB-231 cells overexpress VASP. We then utilized a 3-dimensional (3D) approach to study metastasis in MDA-MB-231 cells using a system that considers mechanical forces exerted by the ECM. We prepared 3D collagen I gels of increasing concentration, imaged them by atomic force microscopy, and used them to either embed cells or tumor spheroids, in the presence or absence of VASP. We show, for the first time, that VASP silencing downregulated Migfilin, β-catenin and urokinase plasminogen activator both in 2D and 3D, suggesting a matrix-independent mechanism. Tumor spheroids lacking VASP demonstrated impaired invasion, indicating VASP’s involvement in metastasis, which was corroborated by Kaplan-Meier plotter showing high VASP expression to be associated with poor remission-free survival in lymph node-positive BC patients. Hence, VASP may be a novel BC metastasis biomarker. - Highlights: • More invasive MDA-MB-231 overexpress VASP compared to MCF-7 breast cancer cells. • We prepared 3D collagen I gels of increasing concentration and characterized them. • VASP silencing downregulated Migfilin, β-catenin and uPA both in 2D and 3D culture. • Tumor spheroids lacking VASP demonstrated impaired invasion. • Kaplan-Meier plotter shows association of high VASP expression with poor survival.

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

    International Nuclear Information System (INIS)

    Herszényi, László; Farinati, Fabio; Cardin, Romilda; István, Gábor; Molnár, László D; Hritz, István; De Paoli, Massimo; Plebani, Mario; Tulassay, Zsolt

    2008-01-01

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

  18. Dioscorea nipponica Attenuates Migration and Invasion by Inhibition of Urokinase-Type Plasminogen Activator through Involving PI3K/Akt and Transcriptional Inhibition of NF-[Formula: see text]B and SP-1 in Hepatocellular Carcinoma.

    Science.gov (United States)

    Hsieh, Ming-Ju; Yeh, Chao-Bin; Chiou, Hui-Ling; Hsieh, Ming-Chang; Yang, Shun-Fa

    2016-01-01

    High mortality and morbidity rates for hepatocellular carcinoma (HCC) in Taiwan primarily result from uncontrolled tumor metastasis. In our previous studies, we have reported that Dioscorea nipponica Makino extract (DNE) has anti-metastasis effects on human oral cancer cells. However, the effect of DNE on hepatoma metastasis have not been thoroughly investigated and remains poorly understood. To determine the effects of DNE on the migration and invasion in HCC cells we used a wound healing model, Boyden chamber assays, gelatin/casein zymography and Western blotting. Transcriptional levels of matrix metalloproteinase-9 (MMP-9) and urokinase-type plasminogen activator (u-PA) were detected by real-time PCR and promoter assays. In this study, DNE treatment significantly inhibited the migration/invasion capacities of Huh7 cell lines. The results of gelatin/casein zymography and Western blotting revealed that the activities and protein levels of the MMP-9 and u-PA were inhibited by DNE. Tests of the mRNA levels, real-time PCR, and promoter assays evaluated the inhibitory effects of DNE on u-PA expression in human hepatoma cells. A chromatin immunoprecipitation (ChIP) assay showed not only that DNE inhibits u-PA expression, but also the inhibitory effects were associated with the down-regulation of the transcription factors of NF-[Formula: see text]B and SP-1 signaling pathways. Western blot analysis also showed that DNE inhibits PI3K and phosphorylation of Akt. In conclusion, these results show that u-PA expression may be a potent therapeutic target in the DNE-mediated suppression of HCC invasion/migration. DNE may have potential use as a chemo-preventive agent against liver cancer metastasis.

  19. Low-molecular-weight fractions of Alcalase hydrolyzed egg ovomucin extract exert anti-inflammatory activity in human dermal fibroblasts through the inhibition of tumor necrosis factor-mediated nuclear factor κB pathway.

    Science.gov (United States)

    Sun, Xiaohong; Chakrabarti, Subhadeep; Fang, Jun; Yin, Yulong; Wu, Jianping

    2016-07-01

    Ovomucin is a mucin-like protein from egg white with a variety of biological functions. We hypothesized that ovomucin-derived peptides might exert anti-inflammatory activity. The specific objectives were to test the anti-inflammatory activities of different ovomucin hydrolysates and its various fractions in human dermal fibroblasts, and to understand the possible molecular mechanisms. Three ovomucin hydrolysates were prepared and desalted; only the desalted Alcalase hydrolysate showed anti-inflammatory activity. Desalting of ovomucin hydrolysate enriched the proportion of low-molecular-weight (MW) peptides. Indeed, ultrafiltration of this hydrolysate displayed comparable anti-inflammatory activity in dermal fibroblasts, indicating the responsible role of low-MW bioactive peptides in exerting the beneficial biological function. The anti-inflammatory activity of low-MW peptides was regulated through the inhibition of tumor necrosis factor-mediated nuclear factor κ-light-chain-enhancer of activated B cells activity. Our study demonstrated that both peptide composition and MW distribution play important roles in anti-inflammatory activity. The low-MW fractions prepared from ovomucin Alcalase hydrolysate may have potential applications for maintenance of dermal health and treatment of skin diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Growth Disorders

    Science.gov (United States)

    ... problem or disease. The pituitary gland makes growth hormone, which stimulates the growth of bone and other tissues. Children who have too little ... gland tumor, which is not cancer. Too much growth hormone can cause gigantism in children, where their bones and their body grow too much. In adults, ...

  1. Analysis of a two-domain binding site for the urokinase-type plasminogen activator-plasminogen activator inhibitor-1 complex in low-density-lipoprotein-receptor-related protein.

    Science.gov (United States)

    Andersen, O M; Petersen, H H; Jacobsen, C; Moestrup, S K; Etzerodt, M; Andreasen, P A; Thøgersen, H C

    2001-07-01

    The low-density-lipoprotein-receptor (LDLR)-related protein (LRP) is composed of several classes of domains, including complement-type repeats (CR), which occur in clusters that contain binding sites for a multitude of different ligands. Each approximately 40-residue CR domain contains three conserved disulphide linkages and an octahedral Ca(2+) cage. LRP is a scavenging receptor for ligands from extracellular fluids, e.g. alpha(2)-macroglobulin (alpha(2)M)-proteinase complexes, lipoprotein-containing particles and serine proteinase-inhibitor complexes, like the complex between urokinase-type plasminogen activator (uPA) and the plasminogen activator inhibitor-1 (PAI-1). In the present study we analysed the interaction of the uPA-PAI-1 complex with an ensemble of fragments representing a complete overlapping set of two-domain fragments accounting for the ligand-binding cluster II (CR3-CR10) of LRP. By ligand blotting, solid-state competition analysis and surface-plasmon-resonance analysis, we demonstrate binding to multiple CR domains, but show a preferential interaction between the uPA-PAI-1 complex and a two-domain fragment comprising CR domains 5 and 6 of LRP. We demonstrate that surface-exposed aspartic acid and tryptophan residues at identical positions in the two homologous domains, CR5 and CR6 (Asp(958,CR5), Asp(999,CR6), Trp(953,CR5) and Trp(994,CR6)), are critical for the binding of the complex as well as for the binding of the receptor-associated protein (RAP) - the folding chaperone/escort protein required for transport of LRP to the cell surface. Accordingly, the present work provides (1) an identification of a preferred binding site within LRP CR cluster II; (2) evidence that the uPA-PAI-1 binding site involves residues from two adjacent protein domains; and (3) direct evidence identifying specific residues as important for the binding of uPA-PAI-1 as well as for the binding of RAP.

  2. The relationship of entrepreneurial traits, skill, and motivation to subsequent venture growth.

    Science.gov (United States)

    Baum, J Robert; Locke, Edwin A

    2004-08-01

    Previous research on entrepreneurship as well as goal, social-cognitive, and leadership theories has guided hypotheses regarding the relationship between entrepreneurial traits and skill (passion, tenacity, and new resource skill) and situationally specific motivation (communicated vision, self-efficacy, and goals) to subsequent venture growth. Data from 229 entrepreneur-chief executive officers and 106 associates in a single industry were obtained in a 6-year longitudinal study. Structural equation modeling revealed a web of relationships that impact venture growth. Goals, self-efficacy, and communicated vision had direct effects on venture growth, and these factors mediated the effects of passion, tenacity, and new resource skill on subsequent growth. Furthermore, communicated vision and self-efficacy were related to goals, and tenacity was related to new resource skill. (c) 2004 APA

  3. Growth theory and 'green growth'

    NARCIS (Netherlands)

    Smulders, S.; Toman, M.; Withagen, C.A.A.M.

    2014-01-01

    The relatively new and still amorphous concept of 'green growth' can be understood as a call for balancing longer-term investments in sustaining environmental wealth with nearer-term income growth to reduce poverty. We draw on a large body of economic theory available for providing insights on such

  4. Eyelid Growths

    Science.gov (United States)

    ... of the Eyelids and Tears Blepharitis Blepharospasm Canaliculitis Chalazion and Stye (Hordeolum) Dacryocystitis Dacryostenosis Entropion and Ectropion ... mimic other eye disorders (such as blepharitis and chalazion ), so a doctor usually biopsies any growths that ...

  5. Population growth and economic growth.

    Science.gov (United States)

    Narayana, D L

    1984-01-01

    This discussion of the issues relating to the problem posed by population explosion in the developing countries and economic growth in the contemporary world covers the following: predictions of economic and social trends; the Malthusian theory of population; the classical or stationary theory of population; the medical triage model; ecological disaster; the Global 2000 study; the limits to growth; critiques of the Limits to Growth model; nonrenewable resources; food and agriculture; population explosion and stabilization; space and ocean colonization; and the limits perspective. The Limits to Growth model, a general equilibrium anti-growth model, is the gloomiest economic model ever constructed. None of the doomsday models, the Malthusian theory, the classical stationary state, the neo-Malthusian medical triage model, the Global 2000 study, are so far reaching in their consequences. The course of events that followed the publication of the "Limits to Growth" in 1972 in the form of 2 oil shocks, food shock, pollution shock, and price shock seemed to bear out formally the gloomy predictions of the thesis with a remarkable speed. The 12 years of economic experience and the knowledge of resource trends postulate that even if the economic pressures visualized by the model are at work they are neither far reaching nor so drastic. Appropriate action can solve them. There are several limitations to the Limits to Growth model. The central theme of the model, which is overshoot and collapse, is unlikely to be the course of events. The model is too aggregative to be realistic. It exaggerates the ecological disaster arising out of the exponential growth of population and industry. The gross underestimation of renewable resources is a basic flaw of the model. The most critical weakness of the model is its gross underestimation of the historical trend of technological progress and the technological possiblities within industry and agriculture. The model does correctly emphasize

  6. Conformational regulation of urokinase receptor function

    DEFF Research Database (Denmark)

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

    2011-01-01

    PA per se into the hydrophobic ligand binding cavity of uPAR that modulates the function of this receptor. Based on these data, we now propose a model in which the inherent interdomain mobility in uPAR plays a major role in modulating its function. Particularly one uPAR conformation, which is stabilized...

  7. Urokinase plasminogen activator receptor, plasminogen activator ...

    African Journals Online (AJOL)

    Breast cancer is one of the most important leading causes of cancer deathin the less developed countries.The identification of markers that could assist in diagnosis, evaluation of therapeutic response, detection of recurrence and metastasis is a useful tool. The present study is undertaken to provide insights about the role of ...

  8. Tenascin C promiscuously binds growth factors via its fifth fibronectin type III-like domain.

    Directory of Open Access Journals (Sweden)

    Laura De Laporte

    Full Text Available Tenascin C (TNC is an extracellular matrix protein that is upregulated during development as well as tissue remodeling. TNC is comprised of multiple independent folding domains, including 15 fibronectin type III-like (TNCIII domains. The fifth TNCIII domain (TNCIII5 has previously been shown to bind heparin. Our group has shown that the heparin-binding fibronectin type III domains of fibronectin (FNIII, specifically FNIII12-14, possess affinity towards a large number of growth factors. Here, we show that TNCIII5 binds growth factors promiscuously and with high affinity. We produced recombinant fragments of TNC representing the first five TNCIII repeats (TNCIII1-5, as well as subdomains, including TNCIII5, to study interactions with various growth factors. Multiple growth factors of the platelet-derived growth factor (PDGF family, the fibroblast growth factor (FGF family, the transforming growth factor beta (TGF-β superfamily, the insulin-like growth factor binding proteins (IGF-BPs, and neurotrophins were found to bind with high affinity to this region of TNC, specifically to TNCIII5. Surface plasmon resonance was performed to analyze the kinetics of binding of TNCIII1-5 with TGF-β1, PDGF-BB, NT-3, and FGF-2. The promiscuous yet high affinity of TNC for a wide array of growth factors, mediated mainly by TNCIII5, may play a role in multiple physiological and pathological processes involving TNC.

  9. Nerve Growth Factor in Cancer Cell Death and Survival

    International Nuclear Information System (INIS)

    Molloy, Niamh H.; Read, Danielle E.; Gorman, Adrienne M.

    2011-01-01

    One of the major challenges for cancer therapeutics is the resistance of many tumor cells to induction of cell death due to pro-survival signaling in the cancer cells. Here we review the growing literature which shows that neurotrophins contribute to pro-survival signaling in many different types of cancer. In particular, nerve growth factor, the archetypal neurotrophin, has been shown to play a role in tumorigenesis over the past decade. Nerve growth factor mediates its effects through its two cognate receptors, TrkA, a receptor tyrosine kinase and p75 NTR , a member of the death receptor superfamily. Depending on the tumor origin, pro-survival signaling can be mediated by TrkA receptors or by p75 NTR . For example, in breast cancer the aberrant expression of nerve growth factor stimulates proliferative signaling through TrkA and pro-survival signaling through p75 NTR . This latter signaling through p75 NTR promotes increased resistance to the induction of cell death by chemotherapeutic treatments. In contrast, in prostate cells the p75 NTR mediates cell death and prevents metastasis. In prostate cancer, expression of this receptor is lost, which contributes to tumor progression by allowing cells to survive, proliferate and metastasize. This review focuses on our current knowledge of neurotrophin signaling in cancer, with a particular emphasis on nerve growth factor regulation of cell death and survival in cancer

  10. Phosphorylated hepatocyte growth factor receptor/c-Met is associated with tumor growth and prognosis in patients with bladder cancer: correlation with matrix metalloproteinase-2 and -7 and E-cadherin.

    Science.gov (United States)

    Miyata, Yasuyoshi; Sagara, Yuji; Kanda, Shigeru; Hayashi, Tomayoshi; Kanetake, Hiroshi

    2009-04-01

    Hepatocyte growth factor receptor/c-Met is associated with malignant aggressiveness and survival in various cancers including bladder cancer. Although phosphorylation of hepatocyte growth factor receptor/c-Met is essential for its function, the pathologic significance of phosphorylated hepatocyte growth factor receptor/c-Met in bladder cancer remains elusive. We investigated the clinical significance of its expression, and its correlation with cancer cell progression-related molecules. The expression levels of 2 tyrosine residues of hepatocyte growth factor receptor/c-Met (pY1234/1235 and pY1349) were examined immunohistochemically in 133 specimens with nonmetastatic bladder cancer. We also investigated their correlation with matrix metalloproteinase-1, -2, -7, and -14; urokinase-type plasminogen activator; E-cadherin; CD44 standard, variant 3, and variant 6; and vascular endothelial growth factor. Expression of phosphorylated hepatocyte growth factor receptor/c-Met was detected in cancer cells, but was rare in normal urothelial cells. Although hepatocyte growth factor receptor/c-Met, pY1234/1235 hepatocyte growth factor receptor/c-Met, and pY1349 hepatocyte growth factor receptor/c-Met were associated with pT stage, multivariate analysis identified pY1349 hepatocyte growth factor receptor/c-met expression only as a significant factor for high pT stage. Expression of pY1349 hepatocyte growth factor receptor/c-Met was a marker of metastasis and (P = .001) and cause-specific survival (P = .003). Expressions of matrix metalloproteinase-2, matrix metalloproteinase-7, and E-cadherin correlated with pY1349 hepatocyte growth factor receptor/c-Met expression. Our results demonstrated that pY1349 hepatocyte growth factor receptor/c-Met plays an important role in tumor development, and its expression is a significant predictor of metastasis and survival of patients with bladder cancer. The results suggest that these activities are mediated, at least in part, by matrix

  11. growth conditions

    Directory of Open Access Journals (Sweden)

    Martin Fuchs

    1998-01-01

    Full Text Available We consider the obstacle problem {minimize????????I(u=?OG(?udx??among functions??u:O?Rsuch?that???????u|?O=0??and??u=F??a.e. for a given function F?C2(O¯,F|?O<0 and a bounded Lipschitz domain O in Rn. The growth properties of the convex integrand G are described in terms of a N-function A:[0,8?[0,8 with limt?8¯A(tt-2<8. If n=3, we prove, under certain assumptions on G,C1,8-partial regularity for the solution to the above obstacle problem. For the special case where A(t=tln(1+t we obtain C1,a-partial regularity when n=4. One of the main features of the paper is that we do not require any power growth of G.

  12. Growth hormone deficiency - children

    Science.gov (United States)

    ... childhood. The pediatrician will most often draw the child's growth curve on a growth chart . Children with growth ... Most cases are not preventable. Review your child's growth chart ... child's growth rate, evaluation by a specialist is recommended.

  13. CT-Detected Growth of Coronary Artery Calcification in Asymptomatic Middle-Aged Subjects and Association With 15 Biomarkers

    DEFF Research Database (Denmark)

    Diederichsen, Søren Zöga; Grønhøj, Mette Hjortdal; Mickley, Hans

    2017-01-01

    , vitamin D3, parathyroid hormone, osteoprotegerin), lipid metabolism (triglyceride, high- and low-density lipoprotein, total cholesterol), inflammation (C-reactive protein, soluble urokinase-type plasminogen activator receptor), kidney function (creatinine, cystatin C, urate), and myocardial necrosis...

  14. Growth Factor Receptors and Apoptosis Regulators: Signaling Pathways, Prognosis, Chemosensitivity and Treatment Outcomes of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Siddik Sarkar

    2009-01-01

    Full Text Available Biomarkers of breast cancer are necessary for prognosis and prediction to chemotherapy. Prognostic biomarkers provide information regarding outcome irrespective of therapy, while predictive biomarkers provide information regarding response to therapy. Candidate prognostic biomarkers for breast cancers are growth factor receptors, steroid receptors, Ki-67, cyclins, urokinase plasminogen activator, p53, p21, pro- and anti-apoptotic factors, BRCA1 and BRCA2. But currently, the predictive markers are Estrogen and Progesterone receptors responding to endocrine therapy, and HER-2 responding to herceptin. But there are numerous breast cancer cases, where tamoxifen is ineffective even after estrogen receptor positivity. This lead to search of new prognostic and predictive markers and the number of potential markers is constantly increasing due to proteomics and genomics studies. However, most biomarkers individually have poor sensitivity or specificity, or other clinical value. It can be resolved by studying various biomarkers simultaneously, which will help in better prognosis and increasing sensitivity for chemotherapeutic agents. This review is focusing on growth factor receptors, apoptosis markers, signaling cascades, and their correlation with other associated biomarkers in breast cancers. As our knowledge regarding molecular biomarkers for breast cancer increases, prognostic indices will be developed that combine the predictive power of individual molecular biomarkers with specific clinical and pathologic factors. Rigorous comparison of these existing as well as emerging markers with current treatment selection is likely to see an escalation in an era of personalized medicines to ensure the breast cancer patients receive optimal treatment. This will also solve the treatment modalities and complications related to chemotherapeutic regimens.

  15. Insulin-Like Growth Factor-1 Inscribes a Gene Expression Profile for Angiogenic Factors and Cancer Progression in Breast Epithelial Cells

    Directory of Open Access Journals (Sweden)

    J.S. Oh

    2002-01-01

    Full Text Available Activation of the insulin-like growth factor-1 receptor (IGF-11R by IGF-1 is associated with the risk and progression of many types of cancer, although despite this it remains unclear how activated IGF-1 R contributes to cancer progression. In this study, gene expression changes elicited by IGF-1 were profiled in breast epithelial cells. We noted that many genes are functionally linked to cancer progression and angiogenesis. To validate some of the changes observed, the RNA and/or protein was confirmed for c-fos, cytochrome P4501Al, cytochrome P450 1131, interleukin-1 beta, fas ligand, vascular endothelial growth factor, and urokinase plasminogen activator. Nuclear proteins were also temporally monitored to address how gene expression changes were regulated. We found that IGF-1 stimulated the nuclear translocation of phosphorylated AKT, hypoxic-inducible factor-1 alpha, and phosphorylated cAMP-responsive element-binding protein, which correlated with temporal changes in gene expression. Next, the promoter regions of IGF-1-regulated genes were searched in silico. The promoters of genes that clustered together had similar regulatory regions. In summary, IGF-1 inscribes a gene expression profile relevant to cancer progression, and this study provides insight into the mechanism(s whereby some of these changes occur.

  16. THE INDIAN GROWTH MIRACLE AND ENDOGENOUS GROWTH

    OpenAIRE

    Jakob B. Madsen; Shishir Saxena; James B. Ang

    2008-01-01

    Using over half a century of R&D data for India, this paper examines the extent to which India's recent growth experience can be explained by R&D, international R&D spillovers, catch-up to the technology frontier and financial liberalization. Furthermore, the paper also tests whether any of the competing second-generation endogenous growth theories can explain India's growth experience. The findings provide support for Schumpeterian growth theory and indicate that the recent high growth rates...

  17. Step-Growth Polymerization.

    Science.gov (United States)

    Stille, J. K.

    1981-01-01

    Following a comparison of chain-growth and step-growth polymerization, focuses on the latter process by describing requirements for high molecular weight, step-growth polymerization kinetics, synthesis and molecular weight distribution of some linear step-growth polymers, and three-dimensional network step-growth polymers. (JN)

  18. Multiphasic growth curve analysis.

    NARCIS (Netherlands)

    Koops, W.J.

    1986-01-01

    Application of a multiphasic growth curve is demonstrated with 4 data sets, adopted from literature. The growth curve used is a summation of n logistic growth functions. Human height growth curves of this type are known as "double logistic" (n = 2) and "triple logistic" (n = 3) growth curves (Bock

  19. Beta-type transforming growth factor specifies organizational behavior in vascular smooth muscle cell cultures.

    Science.gov (United States)

    Majack, R A

    1987-07-01

    In culture, vascular smooth muscle cells (SMC) grow in a "hill-and-valley" (multilayered) pattern of organization. We have studied the growth, behavioral organization, and biosynthetic phenotype of rat aortic SMC exposed to purified platelet-derived growth regulatory molecules. We show that multilayered growth is not a constitutive feature of cultured SMC, and that beta-type transforming growth factor (TGF-beta) is the primary determinant of multilayered growth and the hill-and-valley pattern of organization diagnostic for SMC in culture. TGF-beta inhibited, in a dose-dependent manner, the serum- or platelet-derived growth factor-mediated proliferation of these cells in two-dimensional culture, but only when cells were plated at subconfluent densities. The ability of TGF-beta to inhibit SMC growth was inversely correlated to plating cell density. When SMC were plated at monolayer density (5 X 10(4) cells/cm2) to allow maximal cell-to-cell contact, TGF-beta potentiated cell growth. This differential response of SMC to TGF-beta may contribute to the hill-and-valley pattern of organization. Unlike its effect on other cell types, TGF-beta did not enhance the synthesis of fibronectin or its incorporation into the extracellular matrix. However, the synthesis of a number of other secreted proteins was altered by TGF-beta treatment. SMC treated with TGF-beta for 4 or 8 h secreted markedly enhanced amounts of an Mr 38,000-D protein doublet whose synthesis is known to be increased by heparin (another inhibitor of SMC growth), suggesting metabolic similarities between heparin- and TGF-beta-mediated SMC growth inhibition. The data suggest that TGF-beta may play an important and complex regulatory role in SMC proliferation and organization during development and after vascular injury.

  20. Genomic growth hormone, growth hormone receptor and ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-07-20

    Jul 20, 2009 ... Genomic growth hormone, growth hormone receptor and transforming growth factor β-3 gene polymorphism in breeder hens of Mazandaran native fowls. Babak Enayati and Ghodrat Rahimi-Mianji*. Laboratory for Molecular Genetics and Animal Biotechnology, Department of Animal Sciences, Faculty of ...

  1. Growth hormone suppression test

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003376.htm Growth hormone suppression test To use the sharing features on this page, please enable JavaScript. The growth hormone suppression test determines whether growth hormone production is ...

  2. Over-expression of thymosin beta 4 promotes abnormal tooth development and stimulation of hair growth.

    Science.gov (United States)

    Cha, Hee-Jae; Philp, Deborah; Lee, Soo-Hyun; Moon, Hye-Sung; Kleinman, Hynda K; Nakamura, Takashi

    2010-01-01

    Thymosin beta 4 has multi-functional roles in cell physiology. It accelerates wound healing, hair growth and angiogenesis, and increases laminin-5 expression in corneal epithelium. Furthermore, thymosin beta 4 stimulates tumor growth and metastasis by induction of cell migration and vascular endothelial growth factor-mediated angiogenesis. Using a construct on the skin-specific keratin-5 promoter, we have developed thymosin beta 4 over-expressing transgenic mice to further study its functional roles. Thymosin beta 4 in adult skin and in embryonic stages of the transgenic mouse was analyzed by both Western blot and immunohistochemistry. The over-expression of thymosin beta 4 was observed especially around hair follicles and in the teeth in the transgenic mice. We examined the phenotype of the thymosin beta 4 over-expressing mice. Hair growth was accelerated. In addition, the transgenic mice had abnormally-shaped white teeth and dull incisors. We found that the expression of laminin-5 was up-regulated in the skin of the transgenic mice. We conclude that thymosin beta 4 has an important physiological role in hair growth and in tooth development.

  3. Growth factors and kinases in glioblastoma growth

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Peña-Ortiz

    2016-10-01

    Full Text Available Glioblastoma multiforme (GBM is the most aggressive type of brain cancer, having the highest invasion, migration, proliferation, and angiogenesis rates. Several signaling pathways are involved in the regulation of these processes including growth factors and their tyrosine kinase receptors, such as vascular endothelial growth factor (VEGF, transforming growth factor beta (TGFβ, fibroblast growth factor (FGF, platelet-derived growth factor (PDGF, and insulin-like growth factor–I (IGF–I. Different kinases and regulators also participate in signaling pathways initiated by growth factors, such as mitogen-activated kinases (MAPK, protein kinases C (PKC, phosphatidylinositol-3 kinases (PI3K, protein kinase B (PKB or Akt, glycogen synthase kinase 3β (GSK3β, the mTOR complex, and Bcl-2. In this review, we will focus on the role of these proteins as possible therapeutic targets in GBM.

  4. RA-XII inhibits tumour growth and metastasis in breast tumour-bearing mice via reducing cell adhesion and invasion and promoting matrix degradation.

    Science.gov (United States)

    Leung, Hoi-Wing; Zhao, Si-Meng; Yue, Grace Gar-Lee; Lee, Julia Kin-Ming; Fung, Kwok-Pui; Leung, Ping-Chung; Tan, Ning-Hua; Lau, Clara Bik-San

    2015-11-23

    Cancer cells acquire invasive ability to degrade and adhere to extracellular matrix (ECM) and migrate to adjacent tissues. This ultimately results metastasis. Hence, the present study investigated the in vitro effects of cyclopeptide glycoside, RA-XII on cell adhesion, invasion, proliferation and matrix degradation, and its underlying mechanism in murine breast tumour cells, 4T1. The effect of RA-XII on tumour growth and metastasis in 4T1-bearing mice was also investigated. Our results showed that RA-XII inhibited tumour cell adhesion to collagen, fibronectin and laminin, RA-XII also reduced the expressions of vascular cell adhesion molecule, intracellular adhesion molecule and integrins, and integrin binding. In addition, RA-XII significantly inhibited breast tumour cell migration via interfering cofilin signaling and chemokine receptors. The activities of matrix metalloproteinase-9 and urokinase-type of plasminogen activator, and the expressions of ECM-associated proteinases were attenuated significantly by RA-XII. Furthermore, RA-XII induced G1 phase arrest and inhibited the expressions of cyclins and cyclin-dependent kinases. RA-XII inhibited the expressions of molecules in PI3K/AKT, NF-kappaB, FAK/pSRC, MAPK and EGFR signaling. RA-XII was also shown to have anti-tumour, anti-angiogenic and anti-metastatic activities in metastatic breast tumour-bearing mice. These findings strongly suggested that RA-XII is a potential anti-metastatic agent for breast cancer.

  5. Population growth and economic growth: a reconsideration.

    Science.gov (United States)

    Yip, C K; Zhang, J

    1996-01-01

    The relationship between population growth and development has long been a controversial topic in the economic development literature. Early work by Hoover and Coale and more recent work by Blanchet suggest that high fertility suppresses per capita income growth. However, recent work by Kelley and Srinivasan are ambivalent about such a neo-Malthusian relationship between population growth and economic growth. The authors examine these conflicting positions. They emphasize that the rates of both population growth and income growth are endogenous variables within a general equilibrium framework. An endogenous growth model with endogenous fertility is then developed. It is found that when all exogenous variables are controlled for, there exists an inverse relation between population growth and economic growth. However, when some exogenous factors change, such as an improvement in technological progress, the relation becomes ambiguous. This suggests that the conflicting findings in the literature may be because of the presence of substantial heterogeneity in unobserved variables across countries and over time in cross-country panel data sets.

  6. Inhibition of metastasis, angiogenesis, and tumor growth by Chinese herbal cocktail Tien-Hsien Liquid

    Directory of Open Access Journals (Sweden)

    Sun Andy

    2010-04-01

    Full Text Available Abstract Background Advanced cancer is a multifactorial disease that demands treatments targeting multiple cellular pathways. Chinese herbal cocktail which contains various phytochemicals may target multiple dys-regulated pathways in cancer cells and thus may provide an alternative/complementary way to treat cancers. Previously we reported that the Chinese herbal cocktail Tien-Hsien Liguid (THL can specifically induce apoptosis in various cancer cells and have immuno-modulating activity. In this study, we further evaluated the anti-metastatic, anti-angiogenic and anti-tumor activities of THL with a series of in vitro and in vivo experiments. Methods The migration and invasion of cancer cells and endothelial cells was determined by Boyden chamber transwell assays. The effect of THL on pulmonary metastasis was done by injecting CT-26 colon cancer cells intravenously to syngenic mice. The in vitro and in vivo microvessel formation was determined by the tube formation assay and the Matrigel plug assay, respectively. The in vivo anti-tumor effect of THL was determined by a human MDA-MB-231 breast cancer xenograft model. The expression of metalloproteinase (MMP-2, MMP-9, and urokinase plasminogen activator (uPA was measured by gelatin zymography. The expression of HIF-1α and the phosphorylation of ERK1/2 were determined by Western blot. Results THL inhibited the migration and invasion ability of various cancer cells in vitro, decreased the secretion of MMP-2, MMP-9, and uPA and the activity of ERK1/2 in cancer cells, and suppressed pulmonary metastasis of CT-26 cancer cells in syngenic mice. Moreover, THL inhibited the migration, invasion, and tube formation of endothelial cells in vitro, decreased the secretion of MMP-2 and uPA in endothelial cells, and suppressed neovascularization in Matrigel plugs in mice. Besides its inhibitory effect on endothelial cells, THL inhibited hypoxia-induced HIF-1α and vascular endothelial growth factor-A expression

  7. Inhibition of metastasis, angiogenesis, and tumor growth by Chinese herbal cocktail Tien-Hsien Liquid

    International Nuclear Information System (INIS)

    Chia, Jean-San; Du, Jia-Ling; Hsu, Wei-Bin; Sun, Andy; Chiang, Chun-Pin; Wang, Won-Bo

    2010-01-01

    Advanced cancer is a multifactorial disease that demands treatments targeting multiple cellular pathways. Chinese herbal cocktail which contains various phytochemicals may target multiple dys-regulated pathways in cancer cells and thus may provide an alternative/complementary way to treat cancers. Previously we reported that the Chinese herbal cocktail Tien-Hsien Liguid (THL) can specifically induce apoptosis in various cancer cells and have immuno-modulating activity. In this study, we further evaluated the anti-metastatic, anti-angiogenic and anti-tumor activities of THL with a series of in vitro and in vivo experiments. The migration and invasion of cancer cells and endothelial cells was determined by Boyden chamber transwell assays. The effect of THL on pulmonary metastasis was done by injecting CT-26 colon cancer cells intravenously to syngenic mice. The in vitro and in vivo microvessel formation was determined by the tube formation assay and the Matrigel plug assay, respectively. The in vivo anti-tumor effect of THL was determined by a human MDA-MB-231 breast cancer xenograft model. The expression of metalloproteinase (MMP)-2, MMP-9, and urokinase plasminogen activator (uPA) was measured by gelatin zymography. The expression of HIF-1α and the phosphorylation of ERK1/2 were determined by Western blot. THL inhibited the migration and invasion ability of various cancer cells in vitro, decreased the secretion of MMP-2, MMP-9, and uPA and the activity of ERK1/2 in cancer cells, and suppressed pulmonary metastasis of CT-26 cancer cells in syngenic mice. Moreover, THL inhibited the migration, invasion, and tube formation of endothelial cells in vitro, decreased the secretion of MMP-2 and uPA in endothelial cells, and suppressed neovascularization in Matrigel plugs in mice. Besides its inhibitory effect on endothelial cells, THL inhibited hypoxia-induced HIF-1α and vascular endothelial growth factor-A expression in cancer cells. Finally, our results show that THL

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

    International Nuclear Information System (INIS)

    Jiang, Jiahua; Jedinak, Andrej; Sliva, Daniel

    2011-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-11-18

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

  10. Transcription factor mediated control of anthocyanin biosynthesis in vegetative tissues

    NARCIS (Netherlands)

    Outchkourov, N.S.; Karlova, R.B.; Hölscher, Matthijs; Schrama, Xandra; Blilou, I.; Jongedijk, E.J.; Diez Simon, C.; Dijk, van A.D.J.; Bosch, H.J.; Hall, R.D.; Beekwilder, M.J.

    2018-01-01

    Plants accumulate secondary metabolites to adapt to environmental conditions. These compounds, here exemplified by the purple-colored anthocyanins, are accumulated upon high temperatures, UV-light, drought, and nutrient deficiencies, and may contribute to tolerance to these stresses. Producing

  11. Small Molecules Facilitate Single Factor-Mediated Hepatic Reprogramming

    Directory of Open Access Journals (Sweden)

    Kyung Tae Lim

    2016-04-01

    Full Text Available Recent studies have shown that defined factors could lead to the direct conversion of fibroblasts into induced hepatocyte-like cells (iHeps. However, reported conversion efficiencies are very low, and the underlying mechanism of the direct hepatic reprogramming is largely unknown. Here, we report that direct conversion into iHeps is a stepwise transition involving the erasure of somatic memory, mesenchymal-to-epithelial transition, and induction of hepatic cell fate in a sequential manner. Through screening for additional factors that could potentially enhance the conversion kinetics, we have found that c-Myc and Klf4 (CK dramatically accelerate conversion kinetics, resulting in remarkably improved iHep generation. Furthermore, we identified small molecules that could lead to the robust generation of iHeps without CK. Finally, we show that Hnf1α supported by small molecules is sufficient to efficiently induce direct hepatic reprogramming. This approach might help to fully elucidate the direct conversion process and also facilitate the translation of iHep into the clinic.

  12. Small Molecules Facilitate Single Factor-Mediated Hepatic Reprogramming.

    Science.gov (United States)

    Lim, Kyung Tae; Lee, Seung Chan; Gao, Yimeng; Kim, Kee-Pyo; Song, Guangqi; An, Su Yeon; Adachi, Kenjiro; Jang, Yu Jin; Kim, Jonghun; Oh, Kyoung-Jin; Kwak, Tae Hwan; Hwang, Seon In; You, Jueng Soo; Ko, Kinarm; Koo, Seung-Hoi; Sharma, Amar Deep; Kim, Jong-Hoon; Hui, Lijian; Cantz, Tobias; Schöler, Hans R; Han, Dong Wook

    2016-04-26

    Recent studies have shown that defined factors could lead to the direct conversion of fibroblasts into induced hepatocyte-like cells (iHeps). However, reported conversion efficiencies are very low, and the underlying mechanism of the direct hepatic reprogramming is largely unknown. Here, we report that direct conversion into iHeps is a stepwise transition involving the erasure of somatic memory, mesenchymal-to-epithelial transition, and induction of hepatic cell fate in a sequential manner. Through screening for additional factors that could potentially enhance the conversion kinetics, we have found that c-Myc and Klf4 (CK) dramatically accelerate conversion kinetics, resulting in remarkably improved iHep generation. Furthermore, we identified small molecules that could lead to the robust generation of iHeps without CK. Finally, we show that Hnf1α supported by small molecules is sufficient to efficiently induce direct hepatic reprogramming. This approach might help to fully elucidate the direct conversion process and also facilitate the translation of iHep into the clinic. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Factors mediating the depression in the adult obese outpatients

    Directory of Open Access Journals (Sweden)

    Gudelj-Rakić Jelena

    2007-01-01

    Full Text Available Introduction: The prevalence of obesity is rising to epidemic proportions at the alarming rate in both developed and underdeveloped countries around the world. Current prevalence data from individual national studies suggest that the obesity prevalence in the European countries ranges from 10% to 20% for men, and 10% to 25% for women. Health consequences of obesity imply both a number of fatal and non-fatal health problems (out of which the most common are cardiovascular problems, non-insulin dependent diabetes mellitus, cancers, and also a wide spectrum of psychological consequences from diminished self-esteem to clinical depression. Causal relationship between obesity and many chronic diseases is evidence- based. At the same time, there are marked differences in research data regarding causal obesity-depression relationship. Several studies have found no direct association between obesity and depression, while in others the prevalence of depression in obese patients was up to 50%. Gender, obesity grade, socioeconomic status and asking for professional help are named as moderators and mediators of this relationship. Among recommended screening methods, BDI-II is the most frequently used in the adult outpatient departments. Objective The aim of the study was to determine possible risk factors of depression in adult obese patients treated for obesity. Gender, obesity and education level as well as marital status were analyzed as possible moderators of depression-obesity relationship. Method The research included 267 patients, 38.0±14.6 years of age, who referred to the Outpatient Nutrition Department for dietetic consultation or nutritional medical therapy. Nutritional status was assessed by BMI (kg/mІ, calculated from measured values of body weight and height according to WHO recommendations. An estimate of the existence and/or depression level was investigated by Beck Depression Inventory - self administered questionnaire recommended for use in Serbian population. Results The results revealed higher average BDI score values in obese patients (F(267,1=6.014, p=0.015 in comparison to their non-obese counterparts. In addition, the percentage of depressive obese patients was significantly higher (55.1%, χ2 (267.1=22.64, p<0.001. There was significant correlation of BMI and BDI scores (r=0.246, p<0.001. The number of women with depression was significantly higher in comparison to men (χ2 (267.1=4.261, p=0.039.Women also had higher average BDI score (p = 0.003. MANOVA showed that BDI score was influenced by gender (F(267.1=8.936, p=0.030 and nutritional status ( F(267.1=6.115, p=0.014, but combined effect of the abovementioned moderators was not significant. Conclusion Depression is ten times more frequent in obese patients undergoing the obesity treatment vs. general population and, therefore, screening for depression is needed. Special attention should be paid to women and more obese patients due to higher incidence of depression in these groups.

  14. Macrophage Migration Inhibitory Factor Mediates PAR-Induced Bladder Pain.

    Directory of Open Access Journals (Sweden)

    Dimitrios E Kouzoukas

    Full Text Available Macrophage migration inhibitory factor (MIF, a pro-inflammatory cytokine, is constitutively expressed in urothelial cells that also express protease-activated receptors (PAR. Urothelial PAR1 receptors were shown to mediate bladder inflammation. We showed that PAR1 and PAR4 activator, thrombin, also mediates urothelial MIF release. We hypothesized that stimulation of urothelial PAR1 or PAR4 receptors elicits release of urothelial MIF that acts on MIF receptors in the urothelium to mediate bladder inflammation and pain. Thus, we examined the effect of activation of specific bladder PAR receptors on MIF release, bladder pain, micturition and histological changes.MIF release was measured in vitro after exposing immortalized human urothelial cells (UROtsa to PAR1 or PAR4 activating peptides (AP. Female C57BL/6 mice received intravesical PAR1- or PAR4-AP for one hour to determine: 1 bladder MIF release in vivo within one hour; 2 abdominal hypersensitivity (allodynia to von Frey filament stimulation 24 hours after treatment; 3 micturition parameters 24 hours after treatment; 4 histological changes in the bladder as a result of treatment; 5 changes in expression of bladder MIF and MIF receptors using real-time RT-PCR; 6 changes in urothelial MIF and MIF receptor, CXCR4, protein levels using quantitative immunofluorescence; 7 effect of MIF or CXCR4 antagonism.PAR1- or PAR4-AP triggered MIF release from both human urothelial cells in vitro and mouse urothelium in vivo. Twenty-four hours after intravesical PAR1- or PAR4-AP, we observed abdominal hypersensitivity in mice without changes in micturition or bladder histology. PAR4-AP was more effective and also increased expression of bladder MIF and urothelium MIF receptor, CXCR4. Bladder CXCR4 localized to the urothelium. Antagonizing MIF with ISO-1 eliminated PAR4- and reduced PAR1-induced hypersensitivity, while antagonizing CXCR4 with AMD3100 only partially prevented PAR4-induced hypersensitivity.Bladder PAR activation elicits urothelial MIF release and urothelial MIF receptor signaling at least partly through CXCR4 to result in abdominal hypersensitivity without overt bladder inflammation. PAR-induced bladder pain may represent an interesting pre-clinical model of Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS where pain occurs without apparent bladder injury or pathology. MIF is potentially a novel therapeutic target for bladder pain in IC/PBS patients.

  15. Factors mediating the restoration of structurally degraded soils

    DEFF Research Database (Denmark)

    Arthur, Emmanuel; Moldrup, Per; Schjønning, Per

    Soil structure is essential for sustained provision of ecosystem services such as water filtering and storage, waste disposal, carbon sequestration and many more. Structural degradation/disaggregation of soils emanating from human activities such as mining, grading and filling interferes...... with the ability of soils to perform these functions. The present study examines the roles of clay mineralogy, native organic matter, and exogenous organic material on the restoration of structurally degraded soils. Totally seven soils from Denmark and Ghana - five soils dominated by illites, one kaolinitic soil......, and one smectitic soil were sieved to 2 mm, and half of each soil amended with ground rape, packed in lysimeters, and incubated in the field for 20 months to monitor structure regeneration. During and after the incubation period, soil structure indicators and microbial activity were assessed. During...

  16. Growth Factor Liberation and DPSC Response Following Dentine Conditioning.

    Science.gov (United States)

    Sadaghiani, L; Gleeson, H B; Youde, S; Waddington, R J; Lynch, C D; Sloan, A J

    2016-10-01

    Liberation of the sequestrated bioactive molecules from dentine by the action of applied dental materials has been proposed as an important mechanism in inducing a dentinogenic response in teeth with viable pulps. Although adhesive restorations and dentine-bonding procedures are routinely practiced, clinical protocols to improve pulp protection and dentine regeneration are not currently driven by biological knowledge. This study investigated the effect of dentine (powder and slice) conditioning by etchants/conditioners relevant to adhesive restorative systems on growth factor solubilization and odontoblast-like cell differentiation of human dental pulp progenitor cells (DPSCs). The agents included ethylenediaminetetraacetic acid (EDTA; 10%, pH 7.2), phosphoric acid (37%, pH pH 1.5), and polyacrylic acid (25%, pH 3.9). Growth factors were detected in dentine matrix extracts drawn by EDTA, phosphoric acid, and citric acid from powdered dentine. The dentine matrix extracts were shown to be bioactive, capable of stimulating odontogenic/osteogenic differentiation as observed by gene expression and phenotypic changes in DPSCs cultured in monolayer on plastic. Polyacrylic acid failed to solubilize proteins from powdered dentine and was therefore considered ineffective in triggering a growth factor-mediated response in cells. The study went on to investigate the effect of conditioning dentine slices on growth factor liberation and DPSC behavior. Conditioning by EDTA, phosphoric acid, and citric acid exposed growth factors on dentine and triggered an upregulation in genes associated with mineralized differentiation, osteopontin, and alkaline phosphatase in DPSCs cultured on dentine. The cells demonstrated odontoblast-like appearances with elongated bodies and long extracellular processes extending on dentine surface. However, phosphoric acid-treated dentine appeared strikingly less populated with cells, suggesting a detrimental impact on cell attachment and growth when

  17. Growth hormone stimulation test

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003377.htm Growth hormone stimulation test To use the sharing features on this page, please enable JavaScript. The growth hormone (GH) stimulation test measures the ability of the ...

  18. Measuring multifactor productivity growth

    Czech Academy of Sciences Publication Activity Database

    Wölfl, A.; Hájková, Dana

    -, 2007/5 (2007), s. 1-45 Institutional research plan: CEZ:AV0Z70850503 Keywords : multifactor productivity growth * GDP growth * measuring Subject RIV: AH - Economics http://www.oecd.org/dataoecd/61/17/39522985.pdf

  19. CDC Child Growth Charts

    Data.gov (United States)

    U.S. Department of Health & Human Services — CDC child growth charts consist of a series of percentile curves that illustrate the distribution of selected body measurements in U.S. children. Pediatric growth...

  20. Toddler Growth and Development

    Science.gov (United States)

    ... time, his or her physical growth and motor development will slow, but you can expect to see ... Schedule of Well-Child Care Visits . ​​ Toddler Growth & Development Physical Skills Walks alone Pulls toys behind when ...

  1. Growth uncertainty and risksharing

    OpenAIRE

    Stefano Athanasoulis; Eric Van Wincoop

    1997-01-01

    How large are potential benefits from global risksharing? In order to answer this question we propose a new methodology that is closely connected with the empirical growth literature. We obtain estimates of residual risk (growth uncertainty) at various horizons from regressions of country-specific growth in deviation from world growth on a wide set of variables in the information set. Since this residual risk can be entirely hedged through risksharing, we use it to obtain a measure of the pot...

  2. [Population Growth and Development].

    Science.gov (United States)

    Clausen, A. W.

    Rapid population growth as a central development problem, the proper domain of government in reducing population growth, and effective measures which can be taken to reduce fertility are examined. Rapid population growth puts a brake on development because it exacerbates the difficult choice between higher consumption now and the investment needed…

  3. Urban tree growth modeling

    Science.gov (United States)

    E. Gregory McPherson; Paula J. Peper

    2012-01-01

    This paper describes three long-term tree growth studies conducted to evaluate tree performance because repeated measurements of the same trees produce critical data for growth model calibration and validation. Several empirical and process-based approaches to modeling tree growth are reviewed. Modeling is more advanced in the fields of forestry and...

  4. Corrupt Bureaucracy and Growth

    OpenAIRE

    Djumashev, Ratbek

    2006-01-01

    In this paper, we analyze implications of corruption on growth. We extend existing growth models by incorporating ubiquitous corruption as a by-product of the public sector. Corruption affects both taxation and public good provision, and therefore causes income redistribution and inefficiencies in the public sector. These effects of corruption lead to lower growth through distortions of investment incentives and resources allocation.

  5. Plant Growth Promoting Rhizobacteria

    Indian Academy of Sciences (India)

    IAS Admin

    Plant Growth Promoting Rhizobacteria (PGPR) are a group of bacteria that enhances plant growth and yield via various plant growth promoting substances as well as biofertilizers. Given the negative environmental impact of artificial fertiliz- ers and their increasing costs, the use of beneficial soil micro- organisms such as ...

  6. STAT6 expression in glioblastoma promotes invasive growth

    Directory of Open Access Journals (Sweden)

    Silva Corinne M

    2011-05-01

    Full Text Available Abstract Background Glioblastoma (GBM is a highly aggressive malignant primary brain tumor, characterized by rapid growth, diffuse infiltration of cells into both adjacent and remote brain regions, and a generalized resistance to currently available treatment modalities. Recent reports in the literature suggest that Signal Transducers and Activators of Transcription (STATs play important roles in the regulation of GBM pathophysiology. Methods STAT6 protein expression was analyzed by Western blotting in GBM cell lines and by immunohistochemistry in a tissue microarray (TMA of glioma patient tissues. We utilized shRNA against STAT6 to investigate the effects of prolonged STAT6 depletion on the growth and invasion of two STAT6-positive GBM cell lines. Cell proliferation was assessed by measuring 3H-Thymidine uptake over time. Invasion was measured using an in vitro transwell assay in which cells invade through a type IV collagen matrix toward a chemoattractant (Fetal Bovine Serum. Cells were then stained and counted. Kaplan-Meyer survival curves were generated to show the correlation between STAT6 gene expression and patient survival in 343 glioma patients and in a subset of patients with only GBM. Gene expression microarray and clinical data were acquired from the Rembrandt 1 public data depository (https://caintegrator.nci.nih.gov/rembrandt/. Lastly, a genome-wide expression microarray analysis was performed to compare gene expression in wild-type GBM cells to expression in stable STAT6 knockdown clones. Results STAT6 was expressed in 2 GBM cell lines, U-1242MG and U-87MG, and in normal astrocytes (NHA but not in the U-251MG GBM cell line. In our TMA study, STAT6 immunostaining was visible in the majority of astrocytomas of all grades (I-IV but not in normal brain tissue. In positive cells, STAT6 was localized exclusively in the nuclei over 95% of the time. STAT6-deficient GBM cells showed a reduction in 3H-Thymidine uptake compared to the wild

  7. Green growth in fisheries

    DEFF Research Database (Denmark)

    Nielsen, Max; Ravensbeck, Lars; Nielsen, Rasmus

    2014-01-01

    harming the environment. Fishery is an environment-dependent sector and it has been argued that there is no potential for green growth in the sector owing to global overexploitation, leaving no scope for production growth. The purpose of this paper is to explain what green growth is and to develop...... a conceptual framework. Furthermore, the aim is to show that a large green growth potential actually exists in fisheries and to show how this potential can be achieved. The potential green growth appears as value-added instead of production growth. The potential can be achieved by reducing overcapacity......, investing in the rebuilding of fish stocks and a coordinated regulation of marine activities that interact with fisheries. Incentive-based regulation of fisheries that counterbalances services of the ecosystems is an important instrument to achieve green growth....

  8. Lung growth and development.

    Science.gov (United States)

    Joshi, Suchita; Kotecha, Sailesh

    2007-12-01

    Human lung growth starts as a primitive lung bud in early embryonic life and undergoes several morphological stages which continue into postnatal life. Each stage of lung growth is a result of complex and tightly regulated events governed by physical, environmental, hormonal and genetic factors. Fetal lung liquid and fetal breathing movements are by far the most important determinants of lung growth. Although timing of the stages of lung growth in animals do not mimic that of human, numerous animal studies, mainly on sheep and rat, have given us a better understanding of the regulators of lung growth. Insight into the genetic basis of lung growth has helped us understand and improve management of complex life threatening congenital abnormalities such as congenital diaphragmatic hernia and pulmonary hypoplasia. Although advances in perinatal medicine have improved survival of preterm infants, premature birth is perhaps still the most important factor for adverse lung growth.

  9. Anti-metastatic and anti-tumor growth effects of Origanum majorana on highly metastatic human breast cancer cells: inhibition of NFκB signaling and reduction of nitric oxide production.

    Directory of Open Access Journals (Sweden)

    Yusra Al Dhaheri

    Full Text Available BACKGROUND: We have recently reported that Origanummajorana exhibits anticancer activity by promoting cell cycle arrest and apoptosis of the metastatic MDA-MB-231 breast cancer cell line. Here, we extended our study by investigating the effect of O. majorana on the migration, invasion and tumor growth of these cells. RESULTS: We demonstrate that non-cytotoxic concentrations of O. majorana significantly inhibited the migration and invasion of the MDA-MB-231 cells as shown by wound-healing and matrigel invasion assays. We also show that O. majorana induce homotypic aggregation of MDA-MB-231 associated with an upregulation of E-cadherin protein and promoter activity. Furthermore, we show that O. majorana decrease the adhesion of MDA-MB-231 to HUVECs and inhibits transendothelial migration of MDA-MB-231 through TNF-α-activated HUVECs. Gelatin zymography assay shows that O. majorana suppresses the activities of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9. ELISA, RT-PCR and Western blot results revealed that O. majorana decreases the expression of MMP-2, MMP-9, urokinase plasminogen activator receptor (uPAR, ICAM-1 and VEGF. Further investigation revealed that O. majorana suppresses the phosphorylation of IκB, downregulates the nuclear level of NFκB and reduces Nitric Oxide (NO production in MDA-MB-231 cells. Most importantly, by using chick embryo tumor growth assay, we also show that O. majorana promotes inhibition of tumor growth and metastasis in vivo. CONCLUSION: Our findings identify Origanummajorana as a promising chemopreventive and therapeutic candidate that modulate breast cancer growth and metastasis.

  10. Growth rates made easy.

    Science.gov (United States)

    Hall, Barry G; Acar, Hande; Nandipati, Anna; Barlow, Miriam

    2014-01-01

    In the 1960s-1980s, determination of bacterial growth rates was an important tool in microbial genetics, biochemistry, molecular biology, and microbial physiology. The exciting technical developments of the 1990s and the 2000s eclipsed that tool; as a result, many investigators today lack experience with growth rate measurements. Recently, investigators in a number of areas have started to use measurements of bacterial growth rates for a variety of purposes. Those measurements have been greatly facilitated by the availability of microwell plate readers that permit the simultaneous measurements on up to 384 different cultures. Only the exponential (logarithmic) portions of the resulting growth curves are useful for determining growth rates, and manual determination of that portion and calculation of growth rates can be tedious for high-throughput purposes. Here, we introduce the program GrowthRates that uses plate reader output files to automatically determine the exponential portion of the curve and to automatically calculate the growth rate, the maximum culture density, and the duration of the growth lag phase. GrowthRates is freely available for Macintosh, Windows, and Linux. We discuss the effects of culture volume, the classical bacterial growth curve, and the differences between determinations in rich media and minimal (mineral salts) media. This protocol covers calibration of the plate reader, growth of culture inocula for both rich and minimal media, and experimental setup. As a guide to reliability, we report typical day-to-day variation in growth rates and variation within experiments with respect to position of wells within the plates.

  11. City Population Growth and Economic Growth

    DEFF Research Database (Denmark)

    Freire-Gibb, L. Carlos

    2008-01-01

    This article looks at the relationship between city population growth (intimately related to population proximity), and economic development. The hypothesis is that wherever dynamic and inclusive networks exist, there are more opportunities for economic development in this place. When these types...... of networks choose a tool (project, policy) to implement in the city, success will be more likely. Furthermore, virtuous circles will arise. The author gives an overview of two historical cases in urban growth, in Europe (1200-1800) and the U.S.A. (1800 to today)....

  12. New thrombopoietic growth factors

    OpenAIRE

    Kuter, David J.

    2007-01-01

    Although development of first-generation thrombopoietic growth factors (recombinant human thrombopoietin [TPO] and pegylated recombinant human megakaryocyte growth and development factor [PEG-rHuMGDF]) was stopped due to development of antibodies to PEG-rHuMGDF, nonimmunogenic second-generation thrombopoietic growth factors with unique pharmacologic properties have been developed. TPO peptide mimetics contain TPO receptor-activating peptides inserted into complementarity-determining regions o...

  13. Incentives and Earnings Growth

    DEFF Research Database (Denmark)

    Frederiksen, Anders

    2013-01-01

    The career prospects of newly recruited employees differ substantially within an organization. The stars experience considerable growth in earnings; others can hardly maintain their entry salaries. This article sheds light on the mechanisms generating the observed heterogeneity in earnings growth...... by investigating the effects that explicit short-run incentives and implicit incentives have on earnings growth. The model’s predictions are tested using personnel records from a large bank and are found to be consistent with the observed earnings growth during the first half of the employees’ careers....

  14. FDI- Economic Growth Nexus

    DEFF Research Database (Denmark)

    Bujac, Andreea Ioana; Corado Cretu, Emanuel

    2017-01-01

    Conducting a systematic literature review on the topic of FDI and Economic Growth and investigating this relationship, along with the determinants of an economy that attract FDI and the externalities resulting from Foreign activities, it is found that FDI does have a positive effect on a host...... country’s economic growth but only with the preexistence of certain determinants which facilitate the absorption capacity of the host country on reaping the spillover effects (externalities) of FDI. Lastly, a framework was built to illustrate the interaction between FDI, Determinants and condition...... of the host economy, barriers to growth, economic growth and externalities....

  15. Optimising growth in phenylketonuria

    DEFF Research Database (Denmark)

    Dokoupil, Katharina; Gokmen-Ozel, Hulya; Lammardo, Anna Maria

    2012-01-01

    . Protein requirements in dietary management of PKU are met mostly from Phe-free protein substitutes with the intake of natural protein restricted to patient tolerance. Several reports have suggested that growth in early childhood in PKU is sub-optimal, relative to non-PKU control groups or reference...... populations. We reviewed the literature searching for evidence regarding PKU and growth as well as possible links between dietary management of PKU and growth. The search retrieved only limited evidence on the effect of PKU and its dietary management on growth. Physical development in PKU remains an under...

  16. Smart Growth and Transportation

    Science.gov (United States)

    Describes the relationship between smart growth and transportation, focusing smart and sustainable street design, transit-oriented development, parking management, sustainable transportation planning, and related resources.

  17. Deregulation, economic growth and growth acceleration

    Czech Academy of Sciences Publication Activity Database

    Stankov, Petar

    -, č. 424 (2010), s. 1-42 ISSN 1211-3298 R&D Projects: GA MŠk LC542 Institutional research plan: CEZ:MSM0021620846 Keywords : deregulation * economic growth * origins of institutional change Subject RIV: AH - Economics http://www.cerge-ei.cz/pdf/wp/Wp424.pdf

  18. Governance and growth revisited

    NARCIS (Netherlands)

    Seldadyo, H.; de Haan, J.; Pandu Nugroho, E.

    2007-01-01

    Recent studies yield diverging outcomes on the governance-growth relationship. In this paper we construct a new index of governance using a latent variable approach and test whether this index is related to growth with varying samples of countries and different conditioning variables. The results

  19. Nutrition and growth

    Energy Technology Data Exchange (ETDEWEB)

    Forbes, G.B.

    1977-07-01

    Longitudinal growth data on children who developed obesity during childhood reveal a distinct tendency for height gain to accelerate coincident with or after the onset of excessive weight gain. The magnitude of the relative height increment is related to the degree of overweight. Overnutrition accelerates growth, just as undernutrition retards it.

  20. Employment without Growth

    DEFF Research Database (Denmark)

    Nørgaard, Jørgen

    Employment is a central argument for economic growth in the Western world. But environmental problems like global warming points towards limits to growth. The presentation outlines the history of what has lead to this dilemma. Fortunately citizens attitudes now points towards a preference for less...

  1. Empowering growth in Pakistan?

    NARCIS (Netherlands)

    K.A. Siegmann (Karin Astrid); H. Majid (Hadia)

    2014-01-01

    textabstractPakistan's Vision 2025 connects a policy commitment to greater gender equality with inclusive growth. It prioritises a "good quality of life and high living standard for all citizens across regions, gender" and to "achieve an annual average growth rate of 7 to 8 per cent that is

  2. Pubertal growth in diabetics.

    OpenAIRE

    Stewart-Brown, S L; Lee, T J; Savage, D C

    1985-01-01

    Mean values for two variables of the pubertal growth spurt, peak height velocity and age at peak velocity, of children attending the diabetic clinic in Bristol are reported. The growth spurt was normal both in timing and intensity in boys, but the peak velocity was reduced and age at peak velocity more variable among girls.

  3. Globalization, Growth and Poverty

    International Development Research Centre (IDRC) Digital Library (Canada)

    research. Older and Poorer? How sharing among generations could improve wellbeing. TOWARD INCLUSIVE GROWTH. Around the world, the age of the entire population is changing. These changes will affect economic growth and equity across generations. In. 190 countries, the fastest-growing age group is working-age ...

  4. Synthetic growth reference charts

    NARCIS (Netherlands)

    Hermanussen, Michael; Stec, Karol; Aßmann, Christian; Meigen, Christof; Van Buuren, Stef

    2016-01-01

    Objectives: To reanalyze the between-population variance in height, weight, and body mass index (BMI), and to provide a globally applicable technique for generating synthetic growth reference charts. Methods: Using a baseline set of 196 female and 197 male growth studies published since 1831, common

  5. Growth Modulation in Achondroplasia.

    Science.gov (United States)

    McClure, Philip K; Kilinc, Eray; Birch, John G

    2017-09-01

    Achondroplasia is the most common skeletal dysplasia with a rate of nearly 1/10,000. The development of lower extremity deformity is well documented, and various modes of correction have been reported. There are no reports on the use of growth modulation to correct angular deformity in achondroplasia. Medical Records from 1985 to 2015 were reviewed for the diagnosis of achondroplasia and growth modulation procedures. Patients who had been treated for angular deformity of the legs by growth modulation were identified. A detailed analysis of their medical record and preoperative and final lower extremity radiographs was completed. Four patients underwent growth modulation procedures, all to correct existing varus deformity of the legs. Three of the 4 patients underwent bilateral distal femoral and proximal tibial growth modulation. The remaining patient underwent tibial correction only. Two of the 4 patients had a combined proximal fibular epiphysiodesis. All limbs had some improvement of alignment; however, 1 patient went on to bilateral osteotomies. Only 1 limb corrected to a neutral axis with growth modulation alone at last follow-up, initial implantation was done before 5 years of age. Growth modulation is an effective means for deformity correction in the setting of achondroplasia. However implantation may need to be done earlier than would be typical for patients without achondroplasia. Osteotomy may still be required after growth modulation for incomplete correction.

  6. Globalization, Growth and Poverty

    International Development Research Centre (IDRC) Digital Library (Canada)

    supply foreign-owned firms have gained in productivity as foreign firms made efforts to increase supplier efficiency. Also, they find that local firms, especially in Brazil, have positive (but small) vertical spillovers as they have turned to export markets. TOWARD INCLUSIVE GROWTH. Since the 1990s, growth in Argentina and ...

  7. Growth Plate Injuries

    Science.gov (United States)

    ... cause any lasting problems for your child or teen. Growth plates are areas of growing tissues that cause ... are replaced by solid bone. Who gets them? Growth plate injuries happen to children and teens. This injury happens twice as often in boys ...

  8. Growth hormone test

    Science.gov (United States)

    ... children it is called gigantism . Too little growth hormone can cause a slow or flat rate of growth in children . In adults it can cause changes in energy, muscle mass, cholesterol levels, and bone strength. The GH test may also be used ...

  9. Aid Effectiveness on Growth

    DEFF Research Database (Denmark)

    Doucouliagos, Hristos; Paldam, Martin

    The AEL (aid effectiveness literature) is econo¬metric studies of the macroeconomic effects of development aid. It contains about 100 papers of which 68 are reduced form estimates of theeffect of aid on growth in the recipient country. The raw data show that growth is unconnected to aid......, but the AEL has put so much structure on the data that all results possible have emerged. The present meta study considers both the best-set of the 68 papers and the all-set of 543 regressions published. Both sets have a positive average aid-growth elasticity, but it is small and insignificant: The AEL has...... betweenstudies is real. In particular, the aid-growth association is stronger for Asian countries, and the aid-growth association is shown to have been weaker in the 1970s....

  10. Cavitation cloud growth

    International Nuclear Information System (INIS)

    Bonnin, J.

    1977-01-01

    The cavitation cloud growth in a pipeline submitted to a steep pressure drop (passage of a negative surge) is due to the simultaneous growth of a great number of homogeneous nuclei, thus producing a cloud of cavitation bubbles whose diameters become rapidly of the same order as their distances. Though their growth are independent at the beginning of the phenomenon, interactions take place when they become relatively close, due either to a change in the system planimetry, or to the interlocking of mass diffusion (gaseous cavitation) or heat (vaporous cavitation) boundary layers. After having examined known solutions to the problem of an unique bubble growth, and their possible use in case of interaction, the limits of the unique bubble growth are pointed out to conclude in favour of a preferential geometric limit, occuring near the minimum of the perturbation celerity in the mixture [fr

  11. Aid and Growth

    DEFF Research Database (Denmark)

    Arndt, Channing; Jones, Edward Samuel; Tarp, Finn

    The micro-macro paradox has been revived. Despite broadly positive evaluations at the micro and meso-levels, recent literature has turned decidedly pessimistic with respect to the ability of foreign aid to foster economic growth. Policy implications, such as the complete cessation of aid to Africa......, are being drawn on the basis of fragile evidence. This paper first assesses the aid-growth literature with a focus on recent contributions. The aid-growth literature is then framed, for the first time, in terms of the Rubin Causal Model, applied at the macroeconomic level. Our results show that aid has...... a positive and statistically significant causal effect on growth over the long run with point estimates at levels suggested by growth theory. We conclude that aid remains an important tool for enhancing the development prospects of poor nations....

  12. Growth in pinnipeds.

    Science.gov (United States)

    McLaren, I A

    1993-02-01

    This review presents summary figures of, and fits growth curves to, data on body lengths (as standard length, SL, whenever possible) of pinnipeds at ages estimated to O.I y. (1) Generalized von Bertalanffy (vB) growth curves are fitted to most data: Lx = L infinity (I - ea(x-x0)b, Lx is length at age x, x0 is the origin of the curve (here chosen a priori as time of initiation of embryonic growth), L infinity is asymptotic length, a (which is negative) determines rate of approach to the asymptote, and b influences the 'shape' of the approach. (2) No single monotonic growth equation suffices for growth in length, which is linear before birth and remains so during early life. The vB equation is only suitable to describe mean lengths of newborns, and animals one or more years old. (3) Also, for males of polygynous species, two functions are needed to account for accelerated growth at puberty. Generally a Gompertz equation is adequate for adult males of these species. (4) The fitted growth equations permit statistical comparisons of sizes and growth rates, as well as of individual variability (as growth-curve residuals), among populations and species. (5) For the following species (including different populations when available), the reliability of data is assessed and parameters of growth curves are presented (with sexes separated where significantly different): walrus, California and Steller sea lions, Antarctic, subantarctic and northern fur seals, Hawaiian monk seal, crabeater, Weddell and Leopard seals, southern and northern elephant seals, bearded, hooded, ringed, Baikal, Caspian, spotted, harbour, harp, ribbon and grey seals. (6) Some novel findings pertain to individual species as follows. Although the Pacific walrus is generally stated to be the larger subspecies, females from Hudson Bay and males from Foxe Basin, in the eastern Canadian Arctic, may be as long as those from the Bering Sea. Although female Weddell seals have been assumed to grow larger than

  13. Environment and Growth

    DEFF Research Database (Denmark)

    Horii, Ryo; Ikefuji, Masako

    . In a less developed country, this link, which we call “limits to growth,” emerges as the “poverty-environment trap,” which explains the persistent international inequality both in terms of income and environment. This link also threatens the sustainability of the world’s economic growth, particularly when...... the emission of greenhouse gases raises the risk of natural disasters. Stronger environmental policies are required to overcome this link. While there is a trade-off between the environment and growth in the short run, we show that an appropriate policy can improve both in the long run....

  14. Aid and Growth

    DEFF Research Database (Denmark)

    Tarp, Finn; Mekasha, Tseday Jemaneh

    2013-01-01

    Recent litterature in the meta-analysis category where results from a range of studies are brought together throws doubt on the ability of foreign aid to foster economic growth and development. This article assesses what meta-analysis has to contribute to the litterature on the effectiveness...... of foreign aid in terms of growth impact. We re-examine key hypotheses, and find that the effect of aid on growth is positive and statistically significant. This significant effect is genuine, and not an artefact of publication selection. We also show why our results differ from those published elsewhere....

  15. Aid and Growth

    DEFF Research Database (Denmark)

    Mekasha, Tseday Jemaneh; Tarp, Finn

    Some recent literature in the meta-analysis category where results from a range of studies are brought together throws doubt on the ability of foreign aid to foster economic growth and development. This paper assesses what meta-analysis has to say about the effectiveness of foreign aid in terms...... of the growth impact. We re-examine key hypotheses, and find that the effect of aid on growth is positive and statistically significant. This significant effect is genuine, and not an artefact of publication selection. We also show why our results differ from those published elsewhere....

  16. Biofuels, poverty, and growth

    DEFF Research Database (Denmark)

    Arndt, Channing; Benfica, Rui; Tarp, Finn

    2010-01-01

    Mozambique's annual economic growth by 0.6 percentage points and reduces the incidence of poverty by about 6 percentage points over a 12-year phase-in period. Benefits depend on production technology. An outgrower approach to producing biofuels is more pro-poor, due to the greater use of unskilled labor......This paper assesses the implications of large-scale investments in biofuels for growth and income distribution. We find that biofuels investment enhances growth and poverty reduction despite some displacement of food crops by biofuels. Overall, the biofuel investment trajectory analyzed increases...

  17. Modeling Urban Fire Growth,

    Science.gov (United States)

    Nuclear explosion damage, *Explosion effects, *Fires, *Flame propagation, Growth (General), Area coverage, Ignition, Combustion, Casualties...Computerized simulation, Predictions, Countermeasures, Fire suppression, Damage assessment, Urban areas, Vulnerability, Data acquisition, Methodology, Symposia

  18. Normal growth and development

    Science.gov (United States)

    A child's growth and development can be divided into four periods: Infancy Preschool years Middle childhood years Adolescence Soon after birth, an infant normally loses about 5% to 10% of their birth weight. By about age ...

  19. Plant Growth Promoting Rhizobacteria

    Indian Academy of Sciences (India)

    IAS Admin

    PGPR genera exhibiting plant growth promoting activity are: Pseudomonas, Azospirillum, Azotobacter, Bacillus, Burkholdaria,. Enterobacter, Rhizobium, Erwinia, Mycobacterium, Mesorhizo- bium, Flavobacterium, etc. This article presents perspectives on the role of PGPR in agriculture sustainability. Jay Shankar Singh is an.

  20. Environmentally Sustainable Economic Growth

    Directory of Open Access Journals (Sweden)

    Stelian Brad

    2016-05-01

    Full Text Available Economic growth and sustainable development are important issues for social prosperity. Sustainable development strives for moderate and responsible use within the economic activity of the limited resources of our planet, whereas economic growth does not limit the resource exploitation and energy, being mainly focused on productivity increase. From this perspective, both conceptual and operational contradictions occur between the two pillars of prosperity. This paper looks to these contradictions and proposes some streams of intervention such as economic growth and environmental sustainability to operate in harmony. A structured framework for innovative problem solving is considered in this respect. Results of this research show that it is possible to induce smart measures in the economic system for directing businesses towards new paradigms where economic growth is possible without negative effects on environmental sustainability.

  1. Growth of dopamine crystals

    Energy Technology Data Exchange (ETDEWEB)

    Patil, Vidya, E-mail: vidya.patil@ruparel.edu; Patki, Mugdha, E-mail: mugdha.patki@ruparel.edu [D. G. Ruparel College, Senapati Bapat Marg, Mahim, Mumbai – 400 016 (India)

    2016-05-06

    Many nonlinear optical (NLO) crystals have been identified as potential candidates in optical and electro-optical devices. Use of NLO organic crystals is expected in photonic applications. Hence organic nonlinear optical materials have been intensely investigated due to their potentially high nonlinearities, and rapid response in electro-optic effect compared to inorganic NLO materials. There are many methods to grow organic crystals such as vapor growth method, melt growth method and solution growth method. Out of these methods, solution growth method is useful in providing constraint free crystal. Single crystals of Dopamine have been grown by evaporating the solvents from aqueous solution. Crystals obtained were of the size of orders of mm. The crystal structure of dopamine was determined using XRD technique. Images of crystals were obtained using FEG SEM Quanta Series under high vacuum and low KV.

  2. Floods and Mold Growth

    Science.gov (United States)

    Mold growth may be a problem after flooding. Excess moisture in the home is cause for concern about indoor air quality primarily because it provides breeding conditions for pests, molds and other microorganisms.

  3. Plant Growth Promoting Rhizobacteria

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 18; Issue 3. Plant Growth Promoting Rhizobacteria - Potential Microbes for Sustainable Agriculture. Jay Shankar Singh. General Article Volume 18 Issue 3 March 2013 pp 275-281 ...

  4. Planar elliptic growth

    Energy Technology Data Exchange (ETDEWEB)

    Mineev, Mark [Los Alamos National Laboratory

    2008-01-01

    The planar elliptic extension of the Laplacian growth is, after a proper parametrization, given in a form of a solution to the equation for areapreserving diffeomorphisms. The infinite set of conservation laws associated with such elliptic growth is interpreted in terms of potential theory, and the relations between two major forms of the elliptic growth are analyzed. The constants of integration for closed form solutions are identified as the singularities of the Schwarz function, which are located both inside and outside the moving contour. Well-posedness of the recovery of the elliptic operator governing the process from the continuum of interfaces parametrized by time is addressed and two examples of exact solutions of elliptic growth are presented.

  5. Mapping Inclusive Growth

    OpenAIRE

    Raquel Almeida Ramos; Rafael Ranieri; Jan-Willem Lammes

    2013-01-01

    Since its emergence around the turn of the century the concept of inclusive growth has been substantially debated by researchers and practitioners, has increasingly gained space in domestic and international political circles, has inspired the design of and generated projects and policies, and has impacted the views and the lives of many people. While the conceptual debate and the practical application of various definitions of inclusive growth have taken place simultaneously, they have recen...

  6. ECONOMIC GROWTH AND POVERTY,

    Science.gov (United States)

    The problems of poverty in the United States, and their resolution, are inextricably connected with the nature of the economic growth process and its...economic deprivation, but the adjustments required by growth have left in their wake new pockets of poverty . In the future, one of the key variables...that will determine how rapidly we can eliminate poverty in the United States will be the rate of increase in average incomes. And one of the key

  7. Armenia's Economic Growth Sustainability

    OpenAIRE

    Hayakawa, Tatsuji

    2015-01-01

    Armenia enjoyed 15 years of uninterrupted high economic growth prior to the global financial crisis in 2009. Investment, particularly in the mining and metallurgy sectors, played a key role as a driver of economic growth. Remittances,mostly from Russia, had an effect in sustaining consumption and boosting construction. Armenia has shown some weaknesses in the external sector, due to demands for natural gas, mineral products, machinery, and equipment. Armenia's exports and FDI suffer from the ...

  8. Inflation, volatility and growth

    OpenAIRE

    Ruth Judson; Athanasios Orphanides

    1996-01-01

    This paper re-examines the relationship between inflation, inflation volatility and growth using cross-country panel data for the past 30 years. With regard to the level of inflation, we find that in contrast to current findings which are based on cross-sectional time-average regression comparisons, exploiting the time dimension of the data reveals a strong negative correlation between inflation and income growth for all but very low inflation countries. To examine the role of inflation uncer...

  9. FGF growth factor analogs

    Energy Technology Data Exchange (ETDEWEB)

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

    2012-07-24

    The present invention provides a fibroblast growth factor heparin-binding analog of the formula: ##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y and Z are as defined, pharmaceutical compositions, coating compositions and medical devices including the fibroblast growth factor heparin-binding analog of the foregoing formula, and methods and uses thereof.

  10. Entrepreneurship, Information, and Growth

    Science.gov (United States)

    Bunten, Devin; Weiler, Stephan; Weiler, Stephan; Zahran, Sammy

    2016-01-01

    We examine the contribution to economic growth of entrepreneurial “marketplace information” within a regional endogenous growth framework. Entrepreneurs are posited to provide an input to economic growth through the information revealed by their successes and failures. We empirically identify this information source with the regional variation in establishment births and deaths, which create geographic information asymmetries that influence subsequent entrepreneurial activity and economic growth. We find that local establishment birth and death rates are significantly and positively correlated with subsequent entrepreneurship for US counties. To account for the potential endogeneity caused by forward-looking entrepreneurs, we utilize instruments based on historic mining activity. We find that the information spillover component of local establishment birth and death rates have significant positive effects on subsequent entrepreneurship and employment growth for US counties and metropolitan areas. With the help of these intruments, we show that establishment births have a positive and significant effect on future employment growth within all counties, and that in line with the information hypothesis, local establishment death rates have a similar positive effect within metropolitan counties. PMID:27516625

  11. Bacterial growth kinetics

    International Nuclear Information System (INIS)

    Boonkitticharoen, V.; Ehrhardt, J.C.; Kirchner, P.T.

    1989-01-01

    Quantitative measurement of bacterial growth may be made using a radioassay technique. This method measures, by scintillation counting, the 14 CO 2 derived from the bacterial metabolism of a 14 C-labeled substrate. Mathematical growth models may serve as reliable tools for estimation of the generation rate constant (or slope of the growth curve) and provide a basis for evaluating assay performance. Two models, i.e., exponential and logistic, are proposed. Both models yielded an accurate fit to the data from radioactive measurement of bacterial growth. The exponential model yielded high precision values of the generation rate constant, with an average relative standard deviation of 1.2%. Under most conditions the assay demonstrated no changes in the slopes of growth curves when the number of bacteria per inoculation was changed. However, the radiometric assay by scintillation method had a growth-inhibiting effect on a few strains of bacteria. The source of this problem was thought to be hypersensitivity to trace amounts of toluene remaining on the detector

  12. Entrepreneurship, Information, and Growth.

    Science.gov (United States)

    Bunten, Devin; Weiler, Stephan; Weiler, Stephan; Zahran, Sammy

    2015-09-01

    We examine the contribution to economic growth of entrepreneurial "marketplace information" within a regional endogenous growth framework. Entrepreneurs are posited to provide an input to economic growth through the information revealed by their successes and failures. We empirically identify this information source with the regional variation in establishment births and deaths, which create geographic information asymmetries that influence subsequent entrepreneurial activity and economic growth. We find that local establishment birth and death rates are significantly and positively correlated with subsequent entrepreneurship for US counties. To account for the potential endogeneity caused by forward-looking entrepreneurs, we utilize instruments based on historic mining activity. We find that the information spillover component of local establishment birth and death rates have significant positive effects on subsequent entrepreneurship and employment growth for US counties and metropolitan areas. With the help of these intruments, we show that establishment births have a positive and significant effect on future employment growth within all counties, and that in line with the information hypothesis, local establishment death rates have a similar positive effect within metropolitan counties.

  13. Cell-surface acceleration of urokinase-catalyzed receptor cleavage

    DEFF Research Database (Denmark)

    Høyer-Hansen, G; Ploug, M; Behrendt, N

    1997-01-01

    relative to the reaction in solution. The time course of uPA-catalyzed cleavage of cell-bound uPAR was studied using U937 cells stimulated with phorbol 12-myristate 13-acetate. Only 30 min was required for 10 nM uPA to cleave 50% of the cell-bound uPAR. This uPA-catalyzed cleavage reaction was inhibited...

  14. Bicyclic peptide inhibitor of urokinase-type plasminogen activator

    DEFF Research Database (Denmark)

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

    2013-01-01

    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...

  15. The urokinase receptor associated protein (uPARAP/endo180)

    DEFF Research Database (Denmark)

    Engelholm, L H; Nielsen, B S; Danø, K

    2001-01-01

    the biological consequences of this reaction have not yet been verified experimentally, a likely event is ligand internalization because uPARAP is a constitutively recycling internalization receptor. uPARAP also binds at least one component, collagen type V, in the extracellular matrix meshwork, pointing...

  16. Endogenous growth and the environment

    NARCIS (Netherlands)

    Withagen, C.A.A.M.; Vellinga, N.

    2001-01-01

    This paper examines the relationship between environmental policy and growth, from the perspective of endogenous growth theory. In particular three standard endogenous growth models are supplemented with environmental issues, such as pollution and exhaustibility of natural resources. It is found

  17. EFFECTS OF GROWTH HORMONE ON THE ONTOGENETIC ALLOMETRY OF CRANIOFACIAL BONES

    Science.gov (United States)

    Gonzalez, Paula N.; Kristensen, Erika; Morck, Douglas W.; Boyd, Steven; Hallgrímsson, Benedikt

    2014-01-01

    Organism size is controlled by interactions between genetic and environmental factors mediated by hormones with systemic and local effects. As changes in size are usually not isometric, a considerable diversity in shape can be generated through modifications in the patterns of ontogenetic allometry. In this study we evaluated the role of timing and dose of growth hormone (GH) release on growth and correlated shape changes in craniofacial bones. Using a longitudinal study design, we analyzed GH deficient mice treated with GH supplementation commencing pre- and post-puberty. We obtained 3D in vivo micro-CT images of the skull between 21 and 60 days of age and used geometric morphometrics to analyze size and shape changes among control and GH deficient treated and non-treated mice. The variable levels of circulating GH altered the size and shape of the adult skull, and influenced the cranial base, vault, and face differently. While cranial base synchondroses and facial sutures were susceptible to either the direct or indirect effect of GH supplementation, its effect was negligible on the vault. Such different responses support the role of intrinsic growth trajectories of skeletal components in controlling the modifications induced by systemic factors. Contrary to the expected, the timing of GH treatment did not have an effect on catch-up growth. GH levels also altered the ontogenetic trajectories by inducing changes in their location and extension in the shape space, indicating that differences arose before 21 days and were further accentuated by a truncation of the ontogenetic trajectories in GHD groups. PMID:25098638

  18. Rapid population growth.

    Science.gov (United States)

    1972-01-01

    At the current rate of population growth, world population by 2000 is expected to reach 7 billion or more, with developing countries accounting for some 5.4 billion, and economically advanced nations accounting for 1.6 billion. 'Population explosion' is the result of falling mortality rates and continuing high birth rates. Many European countries, and Japan, have already completed what is termed as demographic transition, that is, birth rates have fallen to below 20 births per 1000 population, death rates to 10/1000 population, and annual growth rates are 1% or less; annual growth rates for less developed countries ranged from 2 to 3.5%. Less developed countries can be divided into 3 groups: 1) countries with both high birth and death rates; 2) countries with high birth rates and low death rates; and 3) countries with intermediate and declining birth rates and low death rates. Rapid population growth has serious economic consequences. It encourages inequities in income distribution; it limits rate of growth of gross national product by holding down level of savings and capital investments; it exerts pressure on agricultural production and land; and it creates unemployment problems. In addition, the quality of education for increasing number of chidren is adversely affected, as high proportions of children reduce the amount that can be spent for the education of each child out of the educational budget; the cost and adequacy of health and welfare services are affected in a similar way. Other serious consequences of rapid population growth are maternal death and illness, and physical and mental retardation of children of very poor families. It is very urgent that over a billion births be prevented in the next 30 years to reduce annual population growth rate from the current 2% to 1% per year.

  19. The Growth Delusion

    Directory of Open Access Journals (Sweden)

    Bob Lloyd

    2009-08-01

    Full Text Available Concern for the environment and a move towards “sustainable development” has assisted progress in a wide range of renewable energy technologies in recent years. The science suggests that a transition from fossil fuels to sustainable sources of energy in a time frame commensurate with the demise of the fossil fuels and prevention of runaway climate change is needed. However, while the movement towards sustainable energy technologies is underway, the World does not want to give up the idea of continuing economic growth. In recent times the financial collapse of October 2008 has given rise to yet another set of pleas from corporations and politicians alike to restart the growth machine. The transition to renewable energy technologies will be difficult to achieve as nowhere within existing economic and political frameworks are the limits to when growth will be curtailed being set. It is possible that the irrational insistence on endless growth as a non negotiable axiom, by a large proportion of the world’s population, may in fact be akin to the similarly irrational belief, by a similarly large proportion of the world’s population, that a supernatural being controls our existence and destiny. The irrationality of religion has recently been examined by Richard Dawkins in “The God Delusion”. Dawkins’ book is used as a starting point to investigate similarities between a belief in God and a belief in continuous growth.

  20. Tools for measuring academic growth.

    Science.gov (United States)

    Kingsbury, G Gage; McCall, Martha; Hauser, Carl

    2009-01-01

    Growth measurement and growth modeling have gained substantial interest in the last few years with the development of new statistical procedures and policy decisions such as the incorporation of growth into No Child Left Behind. The current study investigates the following four aspects of growth measurement: a) issues in the development of vertical scales to measure growth; b) design of instruments to measure academic growth; c) techniques for modeling individual student growth, and d) uses of growth information in a classroom. Measuring growth has always been a daunting task, but the development of measurement tools such as the Rasch model and computerized adaptive testing position us well to obtain high-quality data with which to measure and model the growth of an individual student across a course of study. This growth information, in norm-referenced and standards-referenced form, should enhance educators' ability to enrich student learning.

  1. Developing principles of growth

    DEFF Research Database (Denmark)

    Neergaard, Helle; Fleck, Emma

    of the principles of growth among women-owned firms. Using an in-depth case study methodology, data was collected from women-owned firms in Denmark and Ireland, as these countries are similar in contextual terms, e.g. population and business composition, dominated by micro, small and medium-sized enterprises......Although it has been widely recognized that the growth of women-owned businesses is central to wealth creation, innovation and economic development; limited attention has been devoted to understanding small business growth from a female perspective.This research seeks to develop an understanding....... Extending on principles put forward in effectuation theory, we propose that women grow their firms according to five principles which enable women’s enterprises to survive in the face of crises such as the current financial world crisis....

  2. Urban growth management

    DEFF Research Database (Denmark)

    Jørgensen, Gertrud; Alexander Sick Nielsen, Thomas; Grünfelder, Julien

    2011-01-01

    urban growth and curb urban sprawl in a wider sense. Methodology The main methodology of the paper is a desk-research based review of policy options supplemented with field study and interviews in selected cased study regions. This paper consists of two parts. The first part is based on literature...... there are contradictions in the evidence presented in the literature, we believe that it may be safely said that urban growth management policies have an influence on urban growth under certain preconditions including: sufficient time for implementation and continuity of efforts; choice of appropriate policy measures......, and finally urban attractivity policies. Effective regional bodies are needed to deal with urban expansion and peri-urbanisation at a relevant scale; European rural and agricultural policies makes up the main ‘policy complex’ targeting the non-urban area including its land uses; while lastly leverage of urban...

  3. Unsustainable growth, unsustainable capitalism

    DEFF Research Database (Denmark)

    Næss, Petter

    2006-01-01

    This article argues that there is a fundamental contradiction between a profit-oriented economic system and long-term environmental sustainability. The 'solutions' that are proposed by mainstream environmental economists as well as their 'ecological economy' colleagues do not solve the central...... problems, but serve to further highlight the difficulties of changing capitalism towards sustainability. In a profit-oriented economy, capital accumulation is a prime driving force, and non-growth for the economy at large tends to result in serious economic and social crises. On the other hand, a de......-coupling of economic growth from resource depletion and environmental degradation is possible only within certain sectors or product types and within relatively short time perspectives. The assumptions of mainstream economists about infinite economic growth (and infinite dematerialisation) represent a false ontology...

  4. Secular trends in growth.

    Science.gov (United States)

    Fudvoye, Julie; Parent, Anne-Simone

    2017-06-01

    Human adult height has been increasing world-wide for a century and a half. The rate of increase depends on time and place of measurement. Final height appears to have reached a plateau in Northern European countries but it is still increasing in southern European countries as well as Japan. While mean birth length has not changed recently in industrialized countries, the secular trend finally observed in adult height mostly originates during the first 2 years of life. Secular trend in growth is a marker of public health and provides insights into the interaction between growth and environment. It has been shown to be affected by income, social status, infections and nutrition. While genetic factors cannot explain such rapid changes in average population height, epigenetic factors could be the link between growth and environment. Copyright © 2017. Published by Elsevier Masson SAS.

  5. The double Laplacian growth

    International Nuclear Information System (INIS)

    Loutsenko, I.; Yermolayeva, O.

    2008-06-01

    The dynamics of the idealized Laplacian growth (or the Hele-Shaw problem) can be approximated by the Poiselle flow which in appropriate units takes the form of the Darcy law. In this paper we account for the liquid inertia in the Hele-Shaw problem at zero surface tension limit. The Laplace dynamics for the pressure is extended here with one more for the velocity potential for which we call this growth process the Double Laplacian. The application of the conformal mappings technique leads to doubled dynamics for both the conformal map and the complex potential, which is presented in the paper for the radial and the planar growth. We apply the stability analysis and discuss the integrability for the stated problem. (author)

  6. Moral Personality Growth

    Directory of Open Access Journals (Sweden)

    Jana Kalin

    1998-12-01

    Full Text Available Learning in terms of personality growth is a life-long process, just as personality growth itself is a life-long process. Kalin presents a number of psychological theories and their impact on moral development - which is an integral part of personality growth. The paper further treats the formation and changing of beliefs, and the role of education in the two processes. Great emphasis is put on cognitive theories; Kalin explains those formulated by L. Kohlberg and J. Rest. In discussing the process of shaping and changing one's views, special emphasis is put on the environment, or rather the social group an individual belongs to, and on the influence of personality traits and experience. The paper juxtaposes the influence - strengths and weaknesses - of the psychology of persuasion and education on forming and changing one's views, taken into consideration that views consist of cognitive, emotive and conative dimensions.

  7. Inequality, Tolerance, and Growth

    DEFF Research Database (Denmark)

    Bjørnskov, Christian

    2004-01-01

    This paper argues for the importance of individuals' tolerance of inequality for economic growth. By using the political ideology of governments as a measure of revealed tolerance of inequality, the paper shows that controlling for ideology improves the accuracy with which the effects of inequali...... are measured. Results show that inequality reduces growth but more so in societies where people perceive it as being relatively unfair. Further results indicate that legal quality and social trust are likely transmission channels for the effects of inequality....

  8. Inequality, Tolerance, and Growth

    DEFF Research Database (Denmark)

    Bjørnskov, Christian

    This paper argues for the importance of individuals' tolerance of inequality for economic growth. By using the political ideology of governments as a measure of revealed tolerance of inequality, the paper shows that controlling for ideology improves the accuracy with which the effects of inequali...... are measured. Results show that inequality reduces growth but more so in societies where people perceive it as being relatively unfair. Further results indicate that legal quality and social trust are likely transmission channels for the effects of inequality....

  9. Stochastic ontogenetic growth model

    Science.gov (United States)

    West, B. J.; West, D.

    2012-02-01

    An ontogenetic growth model (OGM) for a thermodynamically closed system is generalized to satisfy both the first and second law of thermodynamics. The hypothesized stochastic ontogenetic growth model (SOGM) is shown to entail the interspecies allometry relation by explicitly averaging the basal metabolic rate and the total body mass over the steady-state probability density for the total body mass (TBM). This is the first derivation of the interspecies metabolic allometric relation from a dynamical model and the asymptotic steady-state distribution of the TBM is fit to data and shown to be inverse power law.

  10. Theoretical Grounds of Economic Growth

    Directory of Open Access Journals (Sweden)

    Hasan Alp ÖZEL

    2012-06-01

    Full Text Available Economic growth bears importance for any country with different levels of development. It is seen that various theories of economic growth give a different importance to technological development and human capital. Theories of economic growth referred to as exogenous economic growth theories, which assume technological development and human capital as determinants of economic growth and propose that they are not affected by economic variables, consider them as the main determinants of economic growth in the long run While these models support technological development as the main source of economic growth in the long run, they have deficiencies in explaining the sources of technological development. These deficiencies are overcome by endogenous growth theories. Endogenous growth theories consider technological development as a variable that is affected by the decisions of economic units and internalize them. The aim of this study is to explain the thoretical grounds of exogenous and endogenous economic growth theories and stress the differences based on their nature.

  11. Dynamic Urban Growth Models

    Science.gov (United States)

    1979-12-01

    In the report the concept of 'order by fluctuation,' that has appeared recently in physico-chemical and biological systems, is applied to the description of urban growth. It is shown that fluctuations play a vital role in the evolutionary process of ...

  12. The Bacterial Growth Curve.

    Science.gov (United States)

    Paulton, Richard J. L.

    1991-01-01

    A procedure that allows students to view an entire bacterial growth curve during a two- to three-hour student laboratory period is described. Observations of the lag phase, logarithmic phase, maximum stationary phase, and phase of decline are possible. A nonpathogenic, marine bacterium is used in the investigation. (KR)

  13. Betting on Growth.

    Science.gov (United States)

    Spoor, Dana L.

    1997-01-01

    Discusses how the Clark County School District (Las Vegas) is able to successfully manage approximately 8% student enrollment growth per year along with one new building opening on an average of every 15 days. Examines managing new facility construction, making provisions for new technology, and using portable buildings to accommodate student…

  14. Consumption growth accounting

    NARCIS (Netherlands)

    Dietzenbacher, Erik; de Groot, Olaf J.; Los, Bart

    The methodology in this paper combines an input-output structural decomposition approach with the supply-side perspective of mainstream growth accounting. In explaining the intertemporal change in consumption per worker, three sets of effects are distinguished. First, contributions due to several

  15. From Dormancy to Growth.

    Science.gov (United States)

    Malan, Riki

    Inhibitors of growth in education and training in South Africa include the past isolation from the rest of the world, failure to keep up with the rapid development of explosion of knowledge, compulsory dependency on bureaucracy, and disregard of the diverse needs of learners. Various initiatives have been undertaken that reflect the enormous need…

  16. Crystal growth and crystallography

    Science.gov (United States)

    Chernov, A. A.

    1998-01-01

    Selected topics that may be of interest for both crystal-structure and crystal-growth communities are overviewed. The growth of protein crystals, along with that of some other compounds, is one of the topics, and recent insights into related phenomena are considered as examples of applications of general principles. The relationship between crystal growth shape and structure is reviewed and an attempt to introduce semiquantitative characterization of binding for proteins is made. The concept of kinks for complex structures is briefly discussed. Even at sufficiently low supersaturations, the fluctuation of steps may not be sufficient to implement the Gibbs-Thomson law if the kink density is low enough. Subsurface ordering of liquids and growth of rough interfaces from melts is discussed. Crystals growing in microgravity from solution should be more perfect if they preferentially trap stress-inducing impurities, thus creating an impurity-depleted zone around themselves. Evidently, such a zone is developed only around the crystals growing in the absence of convection. Under terrestrial conditions, the self-purified depleted zone is destroyed by convection, the crystal traps more impurity and grows stressed. The stress relief causes mosaicity. In systems containing stress-inducing but poorly trapped impurities, the crystals grown in the absence of convection should be worse than those of their terrestrial counterparts.

  17. Globalization, Growth and Poverty

    International Development Research Centre (IDRC) Digital Library (Canada)

    One-pagers are a publication of IDRC's “Globalization, Growth and Poverty” Program Initiative, and are based on findings from the GGP -supported projects referenced in the footnotes. The authors of the work cited are not responsible for the contents of GGP One-pagers. This One-pager was prepared by Edgard Rodriguez.

  18. Rejuveniles and Growth

    DEFF Research Database (Denmark)

    Barnett, Richard C.; Bhattacharya, Joydeep

    Rejuveniles are "people who cultivate tastes and mind-sets tradi- tionally associated with those younger than themselves." (Noxon, 2006) In this paper, we study a standard AK growth model of overlapping generations populated by rejuve- niles. For our purposes, rejuveniles are old agents who deriv...

  19. Growth and Environmental Quality

    Science.gov (United States)

    Gordon, Larry J.

    1976-01-01

    The author suggests that numbers and distribution of people should be given highest priority in dealing with environmental quality. If population problems are solved, then other environmental problems will be prevented or solved. New Mexico, contends the author, must determine the balance between growth and quality of life. (MR)

  20. Coordinate green growth

    NARCIS (Netherlands)

    Alkemade, F.; Hekkert, M.P.

    2010-01-01

    Green economic growth needs a shared sense of direction if it is to lead to a more sustainable future under climate change. Studies on green innovation and societal transformation show that uncoordinated initiatives are unlikely to be an effective way “to get the ball rolling and to ‘learn

  1. Plant growth promoting rhizobacterium

    Science.gov (United States)

    Doktycz, Mitchel John; Pelletier, Dale A.; Schadt, Christopher Warren; Tuskan, Gerald A.; Weston, David

    2015-08-11

    The present invention is directed to the Pseudomonas fluorescens strain GM30 deposited under ATCC Accession No. PTA-13340, compositions containing the GM30 strain, and methods of using the GM30 strain to enhance plant growth and/or enhance plant resistance to pathogens.

  2. Time for Growth

    DEFF Research Database (Denmark)

    Boerner, Lars; Severgnini, Battista

    This paper studies the impact of the early adoption of one of the most important high-technology machines in history, the public mechanical clock, on long-run growth in Europe. We avoid endogeneity by considering the relationship between the adoption of clocks with two sets of instruments: distance...

  3. Aid and sectoral growth

    DEFF Research Database (Denmark)

    Selaya, Pablo; Thiele, Rainer

    2010-01-01

    This article examines empirically the proposition that aid to poor countries is detrimental for external competitiveness, giving rise to Dutch disease type effects. At the aggregate level, aid is found to have a positive effect on growth. A sectoral decomposition shows that the effect is (i) sign...

  4. Globalization, Growth and Poverty

    International Development Research Centre (IDRC) Digital Library (Canada)

    One-pagers are a publication of IDRC's “Globalization, Growth and Poverty” Program Initiative, and are based on findings from the GGP-supported projects referenced in the footnotes. Readers are encouraged to consult the Project output cited. The authors of the work cited are not responsible for the contents of GGP ...

  5. Supporting Inclusive Growth

    International Development Research Centre (IDRC) Digital Library (Canada)

    msandilands

    2010-10-27

    Oct 27, 2010 ... United Nations Development Programme. WRC. Women's Rights and Citizenship ... The goal of the Supporting Inclusive Growth (SIG) program is to support rigorous and policy-oriented research that ... Exploring synergies with IDRC's Environmental Economics program and other lead players outside the ...

  6. Economic growth, globalization and trade

    OpenAIRE

    Leitão, Nuno Carlos

    2012-01-01

    The purpose of this article is to investigate the relationship between economic growth, globalization and trade. The manuscript uses the assumptions of the economic growth exogenous and endogenous models. It introduces new proxies for explain the economic growth as in intra-industry trade, foreign direct investment and globalization index. The results indicate that economic growth is a dynamic process. The intra-industry has a positive impact on economic growth. This paper confirms relevant t...

  7. Epidermal growth factor and growth in vivo

    International Nuclear Information System (INIS)

    Rhodes, J.A.

    1986-01-01

    Epidermal growth factor (EGF) causes a dose-dependent thickening of the epidermis in suckling mice. The cellular mechanisms underlying this thickening were analyzed by measuring the effect of EGF on the cell-cycle. Neonatal mice were given daily injections of either 2ug EGF/g body weight/day or an equivalent volume of saline, and on the seventh day received a single injection of 3 H-thymidine. At various times the mice were perfused with fixative; 1um sections of skin were stained with a modification of Harris' hematoxylin and were autoradiographed. The sections were analyzed using three methods based on the dependence on time after injection of 3 H-thymidine of: frequency of labelled mitoses, labelling index, and reciprocal grains/nucleus. It was found that EGF caused a two-fold increase in the cell production rate. The effect of exogenous EGF on the morphology of gastric mucosa and incisors of suckling mice was also studied. The gastric mucosa appeared thicker in EGF-treated animals, but the effect was not statistically significant. In contrast to its effect on epidermis and gastric mucosa, EGF caused a significant, dose-dependent decrease in the size of the incisors. Because the mouse submandibular salivary gland is the major source of EGF the effect of sialoadenectomy on female reproductive functions was examined. Ablation of the submandibular gland had no effect on: length of estrus cycle, ability of the female to produce litters, length of the gestation period, litter size, and weight of the litter at birth. There was also no effect on survival of the offspring or on age at which the eyelids separated

  8. On Growth and Form

    Science.gov (United States)

    Maartens, Aidan

    2017-12-01

    D'Arcy Thompson was born in 1860, trained in Edinburgh and Cambridge, and held positions in Dundee and St Andrews, where he worked until his death in 1948. On Growth and Form , his classic work on the mathematical patterns and physical rules underlying biological forms, was first published in 1917. To learn more about the book's context, we met Matthew Jarron, Curator of Museum Services at the University of Dundee, in the University's D'Arcy Thompson Zoology Museum. Surrounded by specimens, many of which were collected by Thompson himself, we discussed the legacy of On Growth and Form and the life of the man behind it. © 2017. Published by The Company of Biologists Ltd.

  9. Growth and Poverty

    DEFF Research Database (Denmark)

    Arndt, Channing; Leyaro, Vincent; Mahrt, Kristi

    2017-01-01

    This chapter considers the evolution of welfare of the Tanzanian population using a multi-dimensional approach. It also employs a detailed economy-wide model of the Tanzanian economy to explore growth and monetary poverty reduction scenarios from 2007 to 2015. This approach permits assessment...... of the coherence of observed trends in macroeconomic variables and projects consumption poverty outcomes to 2015. In the multi-dimensional approach, we find that real gains have been achieved. On monetary poverty, our model broadly reproduces key macroeconomic features of the past eight years. We find...... that published consumption poverty reductions for 2007 to 2011/12 from the most recent assessment fall within a reasonable to optimistic range. And, the simulations generate broader based growth across the income distribution compared with the recent assessment. Looking forward, the simulations from 2012 to 2105...

  10. Unsustainable growth, unsustainable capitalism

    DEFF Research Database (Denmark)

    Næss, Petter

    2006-01-01

    problems, but serve to further highlight the difficulties of changing capitalism towards sustainability. In a profit-oriented economy, capital accumulation is a prime driving force, and non-growth for the economy at large tends to result in serious economic and social crises. On the other hand, a de...... according to which the powers and mechanisms of the natural world are considered totally controllable by humans as if they were mere epiphenomena of the human world. On the other hand, the assumptions of certain ecological economists about the possibility of steady-state capitalism disregard the relation...... between capital and surplus value, which constitutes a strong mechanism driving the capitalist economy toward limitless growth....

  11. Growth Hormone and Aging

    Science.gov (United States)

    2000-08-01

    given to children or Growth hormone (GH) is a peptide containing adolescents as substitution therapy to treat is 191 aminoacids that is secreted by the...thyroid hormones and sexual hormones time on an evident beneficial action of GH together with an appropiate nutrition , therapy has been obtained in...of GH (Tresguerres 1996) reduction in muscular and bone mass together IGFI is a peptide of 70 aminoacids that shows with an increase in body fat

  12. Analyzing growth trajectories

    Czech Academy of Sciences Publication Activity Database

    McKeague, I. W.; López-Pintado, S.; Hallin, M.; Šiman, Miroslav

    2011-01-01

    Roč. 2, č. 6 (2011), s. 322-329 ISSN 2040-1744 R&D Projects: GA MŠk(CZ) 1M06047 Institutional research plan: CEZ:AV0Z10750506 Keywords : data depth contours * growth curves * nonparametric Bayes Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 1.556, year: 2011 http://library.utia.cas.cz/separaty/2011/SI/siman-0376411.pdf

  13. Aid, Growth, and Development

    DEFF Research Database (Denmark)

    Arndt, Channing; Jones, Edward Samuel; Tarp, Finn

    This paper uses a unique panel dataset on firm-level corruption. It contains quantitative information on bribe payments by a sample of formal and informal Vietnamese firms. We show that bribe incidence is highly associated with firm-level differences in (i) visibility, (ii) sunk costs, (iii......, this premium outweighs the additional bribe cost of formalization. Formalization embodies net benefits in spite of the growth hampering effects of bribes....

  14. Old-growth Policy

    Directory of Open Access Journals (Sweden)

    Diane Vosick

    2007-12-01

    Full Text Available Most federal legislation and policies (e.g., the Wilderness Act, Endangered Species Act, National Forest Management Act fail to speak directly to the need for old-growth protection, recruitment, and restoration on federal lands. Various policy and attitudinal barriers must be changed to move beyond the current situation. For example, in order to achieve the goal of healthy old growth in frequent-fire forests, the public must be educated regarding the evolutionary nature of these ecosystems and persuaded that collaborative action rather than preservation and litigation is the best course for the future of these forests. Land managers and policy makers must be encouraged to look beyond the single-species management paradigm toward managing natural processes, such as fire, so that ecosystems fall within the natural range of variability. They must also see that, given their recent evidence of catastrophic fires, management must take place outside the wildland-urban interface in order to protect old-growth forest attributes and human infrastructure. This means that, in some wilderness areas, management may be required. Land managers, researchers, and policy makers will also have to agree on a definition of old growth in frequent-fire landscapes; simply adopting a definition from the mesic Pacific Northwest will not work. Moreover, the culture within the federal agencies needs revamping to allow for more innovation, especially in terms of tree thinning and wildland fire use. Funding for comprehensive restoration treatments needs to be increased, and monitoring of the Healthy Forest Initiative and Healthy Forest Restoration Act must be undertaken.

  15. Technology diffusion and growth

    OpenAIRE

    Erzo G. J. Luttmer

    2009-01-01

    Suppose firms are subject to decreasing returns and permanent idiosyncratic productivity shocks. Suppose also firms can only stay in business by continuously paying a fixed cost. New firms can enter. Firms with a history of relatively good productivity shocks tend to survive and others are forced to exit. This paper identifies assumptions about entry that guarantee a stationary firm size distribution and lead to balanced growth. The range of technology diffusion mechanisms that can be conside...

  16. DETERMINANTS OF ECONOMIC GROWTH

    OpenAIRE

    Bartosz Totleben

    2013-01-01

    The article is examines the impact of macroeconomic indicators, in particular: human capital, government spending, innovation, political and social stability, on economic growth. In total 12 different indicators describing the economical, political and social conditions are taken into account. The study considers 102 countries between years 1960 and 2012 and two methods of estimation are performed: generalized method of moments (GMM) and fixed effects (FE). The results show the positive impac...

  17. Geography, depreciation, and growth

    OpenAIRE

    Hsiang, SM; Jina, AS

    2015-01-01

    It has been proposed that geography influences economic growth for many reasons. Previous analyses of comparative development seem to have sidestepped the question of location-dependent depreciation. However the construction of new measures of tropical cyclone exposure enables us to consider the potential impact of this single source of capital depreciation. Using an estimate of asset destruction due to tropical cyclones, we identify the "sandcastle depreciation" rate, and find support for lo...

  18. Aid and growth regressions

    DEFF Research Database (Denmark)

    Hansen, Henrik; Tarp, Finn

    2001-01-01

    . There are, however, decreasing returns to aid, and the estimated effectiveness of aid is highly sensitive to the choice of estimator and the set of control variables. When investment and human capital are controlled for, no positive effect of aid is found. Yet, aid continues to impact on growth via...... investment. We conclude by stressing the need for more theoretical work before this kind of cross-country regressions are used for policy purposes....

  19. Facilitating post traumatic growth

    Directory of Open Access Journals (Sweden)

    Cox Helen

    2004-07-01

    Full Text Available Abstract Background Whilst negative responses to traumatic injury have been well documented in the literature, there is a small but growing body of work that identifies posttraumatic growth as a salient feature of this experience. We contribute to this discourse by reporting on the experiences of 13 individuals who were traumatically injured, had undergone extensive rehabilitation and were discharged from formal care. All participants were injured through involvement in a motor vehicle accident, with the exception of one, who was injured through falling off the roof of a house. Methods In this qualitative study, we used an audio-taped in-depth interview with each participant as the means of data collection. Interviews were transcribed verbatim and analysed thematically to determine the participants' unique perspectives on the experience of recovery from traumatic injury. In reporting the findings, all participants' were given a pseudonym to assure their anonymity. Results Most participants indicated that their involvement in a traumatic occurrence was a springboard for growth that enabled them to develop new perspectives on life and living. Conclusion There are a number of contributions that health providers may make to the recovery of individuals who have been traumatically injured to assist them to develop new views of vulnerability and strength, make changes in relationships, and facilitate philosophical, physical and spiritual growth.

  20. [Hormones and hair growth].

    Science.gov (United States)

    Trüeb, R M

    2010-06-01

    With respect to the relationship between hormones and hair growth, the role of androgens for androgenetic alopecia (AGA) and hirsutism is best acknowledged. Accordingly, therapeutic strategies that intervene in androgen metabolism have been successfully developed for treatment of these conditions. Clinical observations of hair conditions involving hormones beyond the androgen horizon have determined their role in regulation of hair growth: estrogens, prolactin, thyroid hormone, cortisone, growth hormone (GH), and melatonin. Primary GH resistance is characterized by thin hair, while acromegaly may cause hypertrichosis. Hyperprolactinemia may cause hair loss and hirsutism. Partial synchronization of the hair cycle in anagen during late pregnancy points to an estrogen effect, while aromatase inhibitors cause hair loss. Hair loss in a causal relationship to thyroid disorders is well documented. In contrast to AGA, senescent alopecia affects the hair in a diffuse manner. The question arises, whether the hypothesis that a causal relationship exists between the age-related reduction of circulating hormones and organ function also applies to hair and the aging of hair.

  1. Can Growth Be Green?

    Science.gov (United States)

    Gough, Ian

    2015-01-01

    This short article, based on a presentation at the London School of Economics, criticizes the common opinion that "green growth" offers a relatively painless - some even say pain-free - transition path for capitalist economies. After a brief summary of the daunting arithmetic entailed in combining fast decarbonization with continuing growth, the article advances 3 propositions. First, market-based carbon mitigation programs, such as carbon trading, cannot be sufficient and must be coupled with other policy pillars that foster transformative investment and widespread regulation. Second, a political economy of climate policy needs to draw on the lessons of comparative social policy research, which emphasizes the role of international pressures, interests, institutions, and ideas. Taking these into account gives a more realistic perspective on climate policy making in today's neoliberal world. Third, more radical policies on both consumption and production are called for, to ensure that carbon mitigation is not pursued at the expense of equity and social welfare. These include policies to restrain high-carbon luxury consumption and a transition toward shorter paid working time. The conclusion is that a realistic program of green growth will be immensely difficult and entail radical political change. © SAGE Publications 2015.

  2. Gambling on growth.

    Science.gov (United States)

    Feeney, A

    1990-01-01

    When the assumption is made that economic growth must be increased by 10% to accommodate population increases and to reduce poverty, the question is raised as to whether or not sustainable development is possible. The human population increased 3 times since 1900, and global economic activity has increased 7 times faster than population. Use of fossil fuels has increased by 30 times, and industrial production has increased by 50 times. The by-products of population growth and economic activity are loss of tropical rainforests; species extinction; desertification in Africa, India, and the US; toxic and radioactive pollution; and greenhouse warming and ozone depletion. The atmosphere's stability and human habitation is threatened. Sustainable development, as defined by the World Commission on Environment and Development (WCED) in "Our Common Future," is meeting present needs but not at the expense of future needs. Economic growth must proceed at different rates in different countries to close the gap between the rich and poor. Economic expansion has been criticized by the president of Negative Population Growth and the Environmental Defense Fund's coordinator of reform for the World Bank's environmental policies and Third World countries. US government response during the Reagan administration has been indifference, while support has come from the World Resources Institute, the Worldwatch Institute, the US National Wildlife Federation, and the Population Reference Bureau. Recent support has come from signers of the "G-7 Summit" and from IBM and the Dow Chemical Company. A few shared tenets are 1) that economic development is not sustainable, 2) environmental reforms are necessary to make development sustainable, 3) a trade-off is needed to increase Third World energy use, and 4) population must be stabilized. Many proposals have been offered including reducing population to 2 billion, or 40% of the current level. Reducing poverty globally is an environmentally sound

  3. Growth throughout childhood of children born growth restricted

    NARCIS (Netherlands)

    Beukers, Fenny; Rotteveel, Joost; van Weissenbruch, Mirjam M.; Ganzevoort, Wessel; van Goudoever, Johannes B.; van Wassenaer-Leemhuis, Aleid G.

    2017-01-01

    Many studies that examine growth in growth-restricted children at birth do not discriminate between fetal growth restriction (FGR) and small for gestational age (SGA). These terms however are not synonymous. In SGA, stunting and increased weight gain have been reported. We do not know if this holds

  4. Your Baby's Growth: 3 Months

    Science.gov (United States)

    ... on a standardized growth chart (there are different charts for boys and girls). Whether your baby is large, small, or medium-sized, as long as this growth pattern stays consistent over time, chances are everything is ...

  5. Market Acceptance of Smart Growth

    Science.gov (United States)

    This report finds that smart growth developments enjoy market acceptance because of stability in prices over time. Housing resales in smart growth developments often have greater appreciation than their conventional suburban counterparts.

  6. Cultural Globalization and Economic Growth

    Directory of Open Access Journals (Sweden)

    Nuno Carlos Leitão

    2013-03-01

    Full Text Available This article investigates the relationship between cultural globalization and economic growth for the Portuguese experience for the period 1995-2011. In this research we apply a static and dynamic panel data. The initial GDP per capita is negatively correlated with economic growth. This result is according to theoretical and empirical studies. This paper shows that international trade and cultural globalization promote the economic growth. As we expected the inflation has a negative impact on economic growth.

  7. Dumb Growth and the Biosphere

    OpenAIRE

    Cairns, John

    2011-01-01

    Dumb growth is defined as any growth that is unsustainable on a finite planet. Growth in population and consumption of finite resources are not sustainable practices and have already damaged the biospheric life support system in a way that is difficult to eradicate. In fact, all eight interactive global crises (human economy, climate change, exponential human population growth, ecological overshoot, biotic impoverishment and reduction of biodiversity, renewable resources depletion, energy al...

  8. Governance, Growth and Poverty Reduction

    OpenAIRE

    Mushtaq H. Khan

    2009-01-01

    Poverty reduction is a function of economic growth, income distribution and distribution changes. Governance can impact both growth and income distribution. The dominant market-enhancing governance paradigm seeks to enhance the efficiency of markets through ‘good governance’ reforms, ostensibly to trigger or sustain growth. ‘Pro-poor’ good governance reforms purport to enhance the scale and efficiency of service delivery to the poor. The good governance approach to enhancing growth is dispute...

  9. Research Award: Employment and Growth

    International Development Research Centre (IDRC) Digital Library (Canada)

    Office 2004 Test Drive User

    IDRC's Employment and Growth program supports policy-oriented research that generates new insights and options for promoting policies that facilitate inclusive growth. This is growth that enhances access of the poor to opportunities and reduces inequalities. Women's economic empowerment and youth employment are ...

  10. Economic growth and business cycles

    NARCIS (Netherlands)

    Canton, E.J.F.

    1997-01-01

    This thesis contains five essays on economic growth and business cycles. The main focus is on the interaction between economic growth and the cycle: is cyclical variability good or bad for the long-run rate of economic growth? The introduction aims to provide some empirical evidence for an

  11. Mobilizing investors for blue growth

    NARCIS (Netherlands)

    Burg, van den Sander W.K.; Stuiver, Marian; Bolman, Bas C.; Wijnen, Roland; Selnes, Trond; Dalton, Gordon

    2017-01-01

    The European Union's Blue Growth Strategy is a long term strategy to support sustainable growth in the marine and maritime sectors, aiming to contribute to innovation and economic growth (European Commission, 2012). The EU sees the financial sector as a key partner to bring about transition to

  12. Growth Hormone: Use and Abuse

    Science.gov (United States)

    ... is huma n gr owth hormone? Human growth hormone (GH) is a substance that controls your body’s growth. ... little GH, they may have health problems. Growth hormone deficiency (too little GH) and some other health problems can be treated ...

  13. PUBLIC GOODS, CORRUPTION AND GROWTH???

    OpenAIRE

    Ratbek Dzhumashev

    2006-01-01

    In this paper, we analyse implications of corruption on growth. We extend existing growth models by incorporating ubiquitous corruption as a by-product of the public sector. Corruption affects both taxation and public good provision, and therefore causes income redistribution and inefficiencies in the public sector. These effects of corruption lead to lower growth through distortions of investment incentives and resources allocation.

  14. Protein crystal growth - Growth kinetics for tetragonal lysozyme crystals

    Science.gov (United States)

    Pusey, M. L.; Snyder, R. S.; Naumann, R.

    1986-01-01

    Results are reported from theoretical and experimental studies of the growth rate of lysozyme as a function of diffusion in earth-gravity conditions. The investigations were carried out to form a comparison database for future studies of protein crystal growth in the microgravity environment of space. A diffusion-convection model is presented for predicting crystal growth rates in the presence of solutal concentration gradients. Techniques used to grow and monitor the growth of hen egg white lysozyme are detailed. The model calculations and experiment data are employed to discuss the effects of transport and interfacial kinetics in the growth of the crystals, which gradually diminished the free energy in the growth solution. Density gradient-driven convection, caused by presence of the gravity field, was a limiting factor in the growth rate.

  15. Monitoring urban growth

    DEFF Research Database (Denmark)

    Møller-Jensen, Lasse; Kofie, Richard; Yankson, Paul

    2007-01-01

    is occurring at a pace that has increased from 10 km2 per year for the period 1985-1991 to 25 km2 per year for the period 1991-2002. This development is subsequently discussed with focus on the unplanned and haphazard nature of the growth and the corresponding absence of adequate infrastructure and service......The extent of the urbanized areas of Accra is assessed from Landsat-TM satellite images for the year 2002 and compared to similar information for the years 1985 and 1991. A texture-based classification method is applied. The results show that the urbanization of the fringe areas of Accra...

  16. Translation, Quality and Growth

    DEFF Research Database (Denmark)

    Petersen, Margrethe

    The paper investigates the feasibility and some of the possible consequences of applying quality management to translation. It first gives an introduction to two different schools of translation and to (total) quality management. It then examines whether quality management may, in theory......, be applied to translation and goes on to present a case study which involves a firm in the translation industry and which illustrates quality management in practice. The paper shows that applying quality management to translation is feasible and that doing so may translate into sustained growth....

  17. Helicopter Reliability Growth Evaluation

    Science.gov (United States)

    1976-04-01

    a)A LO 44LA N4 r1i H-P 1)H CD 0 4 4J ~4J N4 N t40 4-) 1 P4 t41 0 0 0 u z 0 UN 0 010 ON r- UN 0 z 4-) o 0 N O LA 0 N- mA kID - Ln W r- 0 m 1 Y L rdO Ln...growth-c~urves. Reliability gkowth measuremenht define~d by RPM :is not sutbefor ’helicopter$. When.pgrh intensity is dha ~iged. to Alter the qrdwth ratd

  18. Dietary arginine and linear growth

    DEFF Research Database (Denmark)

    van Vught, Anneke J A H; Dagnelie, Pieter C; Arts, Ilja C W

    2013-01-01

    and slopes were defined to estimate the association between arginine intake and growth velocity, including the following covariates: sex; age; baseline height; energy intake; puberty stage at 7-year follow-up and intervention/control group. The association between arginine intake and growth velocity......The amino acid arginine is a well-known growth hormone (GH) stimulator and GH is an important modulator of linear growth. The aim of the present study was to investigate the effect of dietary arginine on growth velocity in children between 7 and 13 years of age. Data from the Copenhagen School...

  19. Carbon nanotube growth density control

    Science.gov (United States)

    Delzeit, Lance D. (Inventor); Schipper, John F. (Inventor)

    2010-01-01

    Method and system for combined coarse scale control and fine scale control of growth density of a carbon nanotube (CNT) array on a substrate, using a selected electrical field adjacent to a substrate surface for coarse scale density control (by one or more orders of magnitude) and a selected CNT growth temperature range for fine scale density control (by multiplicative factors of less than an order of magnitude) of CNT growth density. Two spaced apart regions on a substrate may have different CNT growth densities and/or may use different feed gases for CNT growth.

  20. Ion beam assisted film growth

    CERN Document Server

    Itoh, T

    2012-01-01

    This volume provides up to date information on the experimental, theoretical and technological aspects of film growth assisted by ion beams.Ion beam assisted film growth is one of the most effective techniques in aiding the growth of high-quality thin solid films in a controlled way. Moreover, ion beams play a dominant role in the reduction of the growth temperature of thin films of high melting point materials. In this way, ion beams make a considerable and complex contribution to film growth. The volume will be essential reading for scientists, engineers and students working in thi

  1. Sex dimorphism in growth.

    Science.gov (United States)

    Gasser, T; Sheehy, A; Molinari, L; Largo, R H

    2000-01-01

    While there is agreement that sex differences in height are small up to the onset of the pubertal spurt in girls, there has been some debate about the question of which, and to what extent, various growth phases contribute to the average adult sex difference of about 13 cm. There has been no consistent agreement between authors as to what extent this difference is due to the late onset of the pubertal spurt (PS) for boys and to what extent it is due to their more intense PS. In this paper, we investigate this question for the variables height, sitting and leg height, arm length, bihumeral and biiliac width. Biiliac width is a special case since both sexes have roughly the same adult size, but girls still have a shorter growing period. The gains for boys, when compared to girls, show a very different pattern across variables: for the legs, the additional growth due to the later spurt is responsible for most of the adult sex difference (64%). On the other hand, for bihumeral width and sitting height, the more intense PS contributes almost 50% to the adult sex difference. An analysis across variables indicates that increments from 1.5 to 6 years largely compensate for deviations in infant morphology from adult morphology.

  2. Probabilistic Mass Growth Uncertainties

    Science.gov (United States)

    Plumer, Eric; Elliott, Darren

    2013-01-01

    Mass has been widely used as a variable input parameter for Cost Estimating Relationships (CER) for space systems. As these space systems progress from early concept studies and drawing boards to the launch pad, their masses tend to grow substantially, hence adversely affecting a primary input to most modeling CERs. Modeling and predicting mass uncertainty, based on historical and analogous data, is therefore critical and is an integral part of modeling cost risk. This paper presents the results of a NASA on-going effort to publish mass growth datasheet for adjusting single-point Technical Baseline Estimates (TBE) of masses of space instruments as well as spacecraft, for both earth orbiting and deep space missions at various stages of a project's lifecycle. This paper will also discusses the long term strategy of NASA Headquarters in publishing similar results, using a variety of cost driving metrics, on an annual basis. This paper provides quantitative results that show decreasing mass growth uncertainties as mass estimate maturity increases. This paper's analysis is based on historical data obtained from the NASA Cost Analysis Data Requirements (CADRe) database.

  3. Springer Handbook of Crystal Growth

    CERN Document Server

    Dhanaraj, Govindhan; Prasad, Vishwanath; Dudley, Michael

    2010-01-01

    Over the years, many successful attempts have been made to describe the art and science of crystal growth. Most modern advances in semiconductor and optical devices would not have been possible without the development of many elemental, binary, ternary, and other compound crystals of varying properties and large sizes. The objective of the Springer Handbook of Crystal Growth is to present state-of-the-art knowledge of both bulk and thin-film crystal growth. The goal is to make readers understand the basics of the commonly employed growth processes, materials produced, and defects generated. Almost 100 leading scientists, researchers, and engineers from 22 different countries from academia and industry have been selected to write chapters on the topics of their expertise. They have written 52 chapters on the fundamentals of bulk crystal growth from the melt, solution, and vapor, epitaxial growth, modeling of growth processes and defects, techniques of defect characterization as well as some contemporary specia...

  4. How nations govern growth.

    Science.gov (United States)

    1984-03-02

    Officials in China admit that the killing or abondoning of baby girls stems from a government policy limiting couples to 1 child combined with an ancient preference for sons. At the same time leaders maintain that population growth is an national emergency and must be checked. And the 1-child policy remains. To enforce the policy, sterilization is compulsory for 1 parent in a 2-child family. Other reports claim that pregnant women face severe government and social pressure to have an abortion. Comunist governments are not alone in taking a forceful role in population control. In 1975 thousands of people in India were pressured to undergo "voluntary" sterilization. In many places, police and tax collectors, money in hand, "convinced" people to get sterilized. Critics recognize a horribla abuse of government powers in these population control efforts. Recognizing that the populations of the poorest nations will double in 20-30 years, 59 countries responded with some kind of population policy by 1980. These countries are spending an average of US$4.60 on population programs for each US$1 they received in UN aid. In many places, the effort is beginning to show results. A 1982 survey found that 35 countries -- with 88% of the 3rd world population -- had cut the growth of their birthrates by 5-34%. Generally, governments have chosen any of 3 ways to attack the problem: cash payments for sterilization or contraceptive use; penalties for big families; and "delayed incentives." At least 20 governments use money to convince people to have fewer babies. Some programs pay for sterilization,other for contraceptive use. All payments are low. Some governments personalize those who exceed a recommended family size. Other nations have adopted variations of the idea. Some governments, instead of paying up front cash, offer pension plans or bank accounts to limit family size. Almost all population experts believe that the mot successful programs are those which are not imposed from

  5. 2010 responsible growth report

    International Nuclear Information System (INIS)

    2010-01-01

    The report addresses several development and growth perspectives for AREVA: its integrated business model, the synergy and complementarities between nuclear and renewable energies, the sustainable development dimension of its industrial development, its sales revenue result, the reduction of its environmental footprint, its development on all continents, its balanced governance, the simplification of its capital structure, and the actions performed by its Foundation. Then, it discusses ten challenges for the company: ensuring safety and performance throughout the reactor life cycle, making the EPR reactor a standard of safety, maintaining relations based on trust with our stake holders, staying in the lead, accelerating the development of renewable energies, being a trusted partner to growing economies, being a model in mine management, promoting sustainable, effective and safe recycling of used fuel, improving performance continuously, offering development prospects to all employees. It briefly presents ten successes achieved in 2010 and indicates ten sustainable development commitments. Document in French and in English

  6. Rapid growth within India

    International Nuclear Information System (INIS)

    Hayes, D.

    2000-01-01

    The Indian government has published (in Hydrocarbon Vision 2025) its ideas for a long term strategy for its oil industry which is currently growing at an unprecedented rate. Increasing domestic production and investment in oil exploration and production overseas figure strongly in the plan. At present, India has a refining surplus but with an annual growth of 8-10%, this will disappear in the next 2-3 years. The report recommends that India should maintain 90% self-sufficiency in refining. The report sees development of the domestic oil industry as globally competitive and helping safeguard India's assets. The capability of India's refineries, current upgrading, the newer refineries and plans for new projects are all mentioned

  7. Nanowire Growth for Photovoltaics

    DEFF Research Database (Denmark)

    Holm, Jeppe Vilstrup

    consisting of a single, vertical, gallium arsenide(GaAs) nanowire grown on silicon with a radial p-i-n-junction. The average concentration was ~8, and the peak concentration was ~12. By increasing the number of junctions in solar cells, they can extract more energy per absorbed photon. In ideal multi...... of the nanowires, some of which were removed from their growth substrate and turned into single nanowire solar cells (SNWSC). The best device showed a conversion efficiency of 6.8% under 1.5AMG 1-sun illumination. In order to improve the efficiency a surface passivating shell consisting of highly doped, wide......Solar cells commercial success is based on an efficiency/cost calculation. Nanowire solar cells is one of the foremost candidates to implement third generation photo voltaics, which are both very efficient and cheap to produce. This thesis is about our progress towards commercial nanowire solar...

  8. Growth outside the core.

    Science.gov (United States)

    Zook, Chris; Allen, James

    2003-12-01

    Growth in an adjacent market is tougher than it looks; three-quarters of the time, the effort fails. But companies can change those odds dramatically. Results from a five-year study of corporate growth conducted by Bain & Company reveal that adjacency expansion succeeds only when built around strong core businesses that have the potential to become market leaders. And the best place to look for adjacency opportunities is inside a company's strongest customers. The study also found that the most successful companies were able to consistently, profitably outgrow their rivals by developing a formula for pushing out the boundaries of their core businesses in predictable, repeatable ways. Companies use their repeatability formulas to expand into any number of adjacencies. Some companies make repeated geographic moves, as Vodafone has done in expanding from one geographic market to another over the past 13 years, building revenues from $1 billion in 1990 to $48 billion in 2003. Others apply a superior business model to new segments. Dell, for example, has repeatedly adapted its direct-to-customer model to new customer segments and new product categories. In other cases, companies develop hybrid approaches. Nike executed a series of different types of adjacency moves: it expanded into adjacent customer segments, introduced new products, developed new distribution channels, and then moved into adjacent geographic markets. The successful repeaters in the study had two common characteristics. First, they were extraordinarily disciplined, applying rigorous screens before they made an adjacency move. This discipline paid off in the form of learning curve benefits, increased speed, and lower complexity. And second, in almost all cases, they developed their repeatable formulas by studying their customers and their customers' economics very, very carefully.

  9. Thermodynamics of firms' growth

    Science.gov (United States)

    Zambrano, Eduardo; Hernando, Alberto; Hernando, Ricardo; Plastino, Angelo

    2015-01-01

    The distribution of firms' growth and firms' sizes is a topic under intense scrutiny. In this paper, we show that a thermodynamic model based on the maximum entropy principle, with dynamical prior information, can be constructed that adequately describes the dynamics and distribution of firms' growth. Our theoretical framework is tested against a comprehensive database of Spanish firms, which covers, to a very large extent, Spain's economic activity, with a total of 1 155 142 firms evolving along a full decade. We show that the empirical exponent of Pareto's law, a rule often observed in the rank distribution of large-size firms, is explained by the capacity of economic system for creating/destroying firms, and that can be used to measure the health of a capitalist-based economy. Indeed, our model predicts that when the exponent is larger than 1, creation of firms is favoured; when it is smaller than 1, destruction of firms is favoured instead; and when it equals 1 (matching Zipf's law), the system is in a full macroeconomic equilibrium, entailing ‘free’ creation and/or destruction of firms. For medium and smaller firm sizes, the dynamical regime changes, the whole distribution can no longer be fitted to a single simple analytical form and numerical prediction is required. Our model constitutes the basis for a full predictive framework regarding the economic evolution of an ensemble of firms. Such a structure can be potentially used to develop simulations and test hypothetical scenarios, such as economic crisis or the response to specific policy measures. PMID:26510828

  10. International growth of neuropsychology.

    Science.gov (United States)

    Ponsford, Jennie

    2017-11-01

    Twenty-five years ago, the field of neuropsychology was well established in North America, Europe, and Australia, with less presence elsewhere. This article discusses the development of neuropsychology over the last 25 years in other regions. The growth of neuropsychology in Asia, Africa, the Middle East, Central and South America, and New Zealand is reviewed. Sources drawn on include a 2016 edition of The Clinical Neuropsychologist describing the practice of neuropsychology in 18 countries; papers on the profession of neuropsychology in Latin America (Arango-Lasprilla, Stevens, Paredes, Ardila, & Rivera, 2016), the history of neuropsychology in Asia (Lee, Wang, & Collinson, 2016), and neuropsychology in Central America (Judd, 2017); INSNET; and personal communications. There has been tremendous variability in the development of neuropsychology across these regions over the last 25 years. Obstacles to the growth of neuropsychology have included economic constraints on health care provision, limited availability of appropriate assessment and treatment methods, linguistic diversity and illiteracy, stigma toward and/or lack of awareness of neuropsychological disorders, lack of graduate training and clinical supervision, absence of accreditation of neuropsychologists as a clinical profession, poor pay, and diminished visibility of the field within the regional culture. Despite these obstacles, neuropsychological research and practice is establishing itself in these regions and has grown significantly over the last quarter century. Major challenges remain in establishing awareness of the significance of and developing culturally appropriate methods of assessing and rehabilitating cognitive aspects of brain disorders, training programs, recognition as a profession, and dedicated funding for neuropsychology positions. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  11. Brown growth, green growth, and the efficiency of urbanization

    OpenAIRE

    Quaas, Martin F.; Smulders, Sjak

    2012-01-01

    We analyze the efficiency of urbanization patterns in a stylized dynamic model of urban growth with three sectors of production. Pollution, as a force that discourages agglomeration, is caused by domestic production. We show that cities are too large and too few in number in uncoordinated equilibrium if economic growth implies increasing pollution (‘brown growth’). If, however, production becomes cleaner over time (‘green growth’) the equilibrium urbanization path reaches the efficien...

  12. SECTORAL SHARES AND ECONOMIC GROWTH

    DEFF Research Database (Denmark)

    Ahmad, Nisar; Naveed, Amjad; Naz, Amber

    2013-01-01

    believe that structural change is an unimportant side effect of the economic development. On the contrary, economists associated with the World Bank and some others posit that growth is brought about by the changes in sectoral composition. The objective of this study is to empirically test...... the relationship between sectoral shares and economic growth by using the panel data for 20 developed countries. The results of the granger causality suggest that both services and agriculture sectors do granger cause economic growth, whereas industrial sector does not granger cause growth. Reverse causality does...... not hold for any of the three sectors. The results of Barro and Non-Barro regressions along with the set of control variables have suggested that services sector is negatively affecting growth, whereas both industrial and agriculture shares are positively affect economic growth....

  13. Growth and photosynthesis of lettuce

    OpenAIRE

    Holsteijn, van, H.M.C.

    1981-01-01

    Butterhead lettuce is an important glass-house crop in the poor light period in The Netherlands. Fundamental data about the influence of temperature, light and CO 2 on growth and photosynthesis are important e.g. to facilitate selection criteria for new cultivars. In this study on lettuce emphasis has been given to light interception in the poor light period, the relationship of growth rate and relative growth rate with time, dry weight and soil cover, and to ...

  14. Linking Ethics and Economic Growth

    DEFF Research Database (Denmark)

    Foss, Nicolai Juul

    2012-01-01

    Hunt (2012) builds on his work concerning ethics and resource-advantage theory to link personal ethical standards, societal norms, and economic growth but offers few details concerning the precise mechanisms that link ethics and growth. This comment suggests a number of such mechanisms...... – for example, the influence of prevailing ethical norms on the aggregate elasticity of substitution and, therefore, total factor productivity and growth....

  15. Population growth and infant mortality

    OpenAIRE

    Fabella, Christina

    2008-01-01

    The relationship between population growth and economic outcomes is an issue of great policy significance. In the era of the Millennium Development Goals, poverty and its correlates have become the compelling issues. Economic growth may not automatically translate into reductions in poverty and its correlates (may not trickle down) if income distribution is at the same time worsening. We therefore investigate the direct effect of population growth on infant mortality for various income catego...

  16. Financing Asia’s Growth

    OpenAIRE

    Estrada, Gemma; Noland, Marcus; Park, Donghyun; Ramayandi, Arief

    2015-01-01

    Recent key challenges highlight the need to revisit Asia's financial development. These include the region's growth slowdown since the global crisis, compounded by a less benign external environment; internal structural challenges, such as population aging; and the maturing of much of the region into middle-income status. The evolving shift in the region's growth paradigm from one based primarily on investment to one based on both investment and productivity growth also underscores the urgenc...

  17. Electricity regulation and economic growth

    OpenAIRE

    Costa, M. Teresa (Maria Teresa), 1951-; Garcia-Quevedo, Jose; Trujillo-Baute, Elisa

    2018-01-01

    The main objective of this paper is to analyse the effect of electricity regulation on economic growth. Although the relationship between electricity consumption and economic growth has been extensively analysed in the empirical literature, this framework has not been used to estimate the effect of electricity regulation on economic growth. Understanding this effect is essential for the assessment of regulatory policy. Specifically, we assess the effects of two major areas of regulation, rene...

  18. Growth Pattern of Atherosclerotic Calcifications

    DEFF Research Database (Denmark)

    Larsen, Lene Lillemark; Ganz, Melanie; Dam, Erik

    2008-01-01

    We present a novel method to analyze the growth of abdominal atherosclerotic plaques based on x-ray projections. The growth analysis can aid progression monitoring in clinical trials and in population screening programs. Our results are based on a longitudinal study over 8.5 years. The annotation...... results show, for instance longitudinal growth of calcifications with a mean of 2.53 mm ($\\pm$ 1.95) in the blood flow direction and correlations with pathologically related biomarkers....

  19. Insulin-Like Growth Factor-Independent Effects of Growth Hormone on Growth Plate Chondrogenesis and Longitudinal Bone Growth.

    Science.gov (United States)

    Wu, Shufang; Yang, Wei; De Luca, Francesco

    2015-07-01

    GH stimulates growth plate chondrogenesis and longitudinal bone growth directly at the growth plate. However, it is not clear yet whether these effects are entirely mediated by the local expression and action of IGF-1 and IGF-2. To determine whether GH has any IGF-independent growth-promoting effects, we generated (TamCart)Igf1r(flox/flox) mice. The systemic injection of tamoxifen in these mice postnatally resulted in the excision of the IGF-1 receptor (Igf1r) gene exclusively in the growth plate. (TamCart)Igf1r(flox/flox) tamoxifen-treated mice [knockout (KO) mice] and their Igf1r(flox/flox) control littermates (C mice) were injected for 4 weeks with GH. At the end of the 4-week period, the tibial growth and growth plate height of GH-treated KO mice were greater than those of untreated C or untreated KO mice. The systemic injection of GH increased the phosphorylation of Janus kinase 2 and signal transducer and activator of transcription 5B in the tibial growth plate of the C and KO mice. In addition, GH increased the mRNA expression of bone morphogenetic protein-2 and the mRNA expression and protein phosphorylation of nuclear factor-κB p65 in both C and KO mice. In cultured chondrocytes transfected with Igf1r small interfering RNA, the addition of GH in the culture medium significantly induced thymidine incorporation and collagen X mRNA expression. In conclusion, our findings demonstrate that GH can promote growth plate chondrogenesis and longitudinal bone growth directly at the growth plate, even when the local effects of IGF-1 and IGF-2 are prevented. Further studies are warranted to elucidate the intracellular molecular mechanisms mediating the IGF-independent, growth-promoting GH effects.

  20. Impact of nutrients on insulin-like growth factor-I, insulin-like growth factor binding protein-3 and their ratio in African American and white males.

    Science.gov (United States)

    McGreevy, Katharine M; Hoel, Brian D; Lipsitz, Stuart R; Hoel, David G

    2007-01-01

    Higher levels of insulin-like growth factor-I (IGF-I) and lower levels of IGF binding protein-3 (IGFBP-3) have been associated with an increased risk of prostate cancer. Nutrition is known to partially regulate IGF levels and it is possible that nutritional factors mediate the impact of IGF levels on prostate cancer risk. A cross-sectional analysis of the impact of nutritional factors measured by a dietary questionnaire on plasma levels of IGF-I, IGFBP-3 and their molar ratio. Multiple linear regression analysis was used to test for effects of nutrients on IGF levels. Prostate cancer screening at the Hollings Cancer Center in Charleston, South Carolina. Ninety-five African American and 138 white males aged 33-83 years attending the screening. In whites, intakes of total, saturated and monounsaturated fats were positively associated with an increase in the molar ratio, while there was no association in African Americans. In African Americans, we found that increasing intake of calcium and dairy servings was positively associated with IGF-I levels. Increased vegetable intake was positively associated with IGFBP-3 in African Americans, while there was no effect in whites. A higher percentage of alcohol in the total diet was significantly associated with a decrease in the molar ratio and an increase in IGFBP-3 in both groups. Our results confirm previous findings of nutritional determinants of IGF levels. Additionally, we found the impact of several nutrients on IGF levels to be different in whites and African Americans, which warrants further investigation.

  1. ICT, Innovation and Productivity Growth

    DEFF Research Database (Denmark)

    Fosse, Henrik; Jacobsen, Joannes; Sørensen, Anders

    This CEBR report presents new evidence which suggests that investments in Information and Communication Technology (ICT) further productivity growth in Danish firms by stimulating innovation activities....

  2. Growth, Employment and Structural Change

    DEFF Research Database (Denmark)

    Aggarwal, Aradhna

    2016-01-01

    This paper studies the decomposition of GSDP growth per capita in Punjab via-a-vis 15 other states in India during 1993–94 and 2011–12 in terms of employment and productivity growth. Specifically, it focuses on the role of employment growth and structural change in employment on economic growth...... but structural shifts have paid off well in terms of diversification of the economy and their contribution to labour productivity especially for manufacturing. Overall employment effect had been negative but this was essentially due to contraction in the labour force; the employment rate effect turned out...

  3. Gene regulation by growth factors

    International Nuclear Information System (INIS)

    Metz, R.; Gorham, J.; Siegfried, Z.; Leonard, D.; Gizang-Ginsberg, E.; Thompson, M.A.; Lawe, D.; Kouzarides, T.; Vosatka, R.; MacGregor, D.; Jamal, S.; Greenberg, M.E.; Ziff, E.B.

    1988-01-01

    To coordinate the proliferation and differentiation of diverse cell types, cells of higher eukaryotes communicate through the release of growth factors. These peptides interact with specific transmembrane receptors of other cells and thereby generate intracellular messengers. The many changes in cellular physiology and activity that can be induced by growth factors imply that growth factor-induced signals can reach the nucleus and control gene activity. Moreover, current evidence also suggests that unregulated signaling along such pathways can induce aberrant proliferation and the formation of tumors. This paper reviews investigations of growth factor regulation of gene expression conducted by the authors' laboratory

  4. Money and Growth under Uncertainty.

    Science.gov (United States)

    ECONOMICS, UNCERTAINTY), (*MONEY, DECISION MAKING), (* BEHAVIOR , MATHEMATICAL MODELS), PRODUCTION, CONSUMPTION , EQUILIBRIUM(PHYSIOLOGY), GROWTH(PHYSIOLOGY), MANAGEMENT ENGINEERING, PROBABILITY, INTEGRAL EQUATIONS, THESES

  5. Quality, Export and Economic Growth

    DEFF Research Database (Denmark)

    Madsen, Erik Strøjer; Pedersen, Kurt

    1998-01-01

    in an international context. The paper, therefore, addresses the complicated interactions between economic growth, export performance and quality. The contribution of the paper, compared to other growth accounting research, is the inclusion of quality data, quality being a significant mirror of technological...... development. The countries covered by the research represent a wide variation in terms of economic development, from poor LDC's to the most developed industrial nations. The empirical results reveal a probable strong relationship between quality/price and export growth as well as economic growth. This new...

  6. Variations in growth pattern and predictablity of liveweight growth of ...

    African Journals Online (AJOL)

    The prediction equations results for rate of liveweight growth showed that of the four models used, the quadratic function was the best predictor of liveweight growth, as indicated by the highest and significant R2 value of 90.7 %. This was closely followed by the linear function which had a significant R2 value of 88.1 %.

  7. Corruption and economic growth with non constant labor force growth

    Science.gov (United States)

    Brianzoni, Serena; Campisi, Giovanni; Russo, Alberto

    2018-05-01

    Based on Brianzoni et al. [1] in the present work we propose an economic model regarding the relationship between corruption in public procurement and economic growth. We extend the benchmark model by introducing endogenous labor force growth, described by the logistic equation. The results of previous studies, as Del Monte and Papagni [2] and Mauro [3], show that countries are stuck in one of the two equilibria (high corruption and low economic growth or low corruption and high economic growth). Brianzoni et al. [1] prove the existence of a further steady state characterized by intermediate levels of capital per capita and corruption. Our aim is to investigate the effects of the endogenous growth around such equilibrium. Moreover, due to the high number of parameters of the model, specific attention is given to the numerical simulations which highlight new policy measures that can be adopted by the government to fight corruption.

  8. ECOLOGICAL GROWTH BOUNDARIES

    Directory of Open Access Journals (Sweden)

    Anna BLUSZCZ

    2017-01-01

    Full Text Available The trends of the society for the continuous growth, combined with the demographic changes, today have led to the important ecological problems on a global scale, which include, among others: the increased use of non-renewable natu-ral resources, an increase of the greenhouse gas emissions, contamination of soil, water, air and the progressive degra-dation of ecosystems. In the face of such serious threats the global initiatives of all countries are important to limit the results of the excessive consumption. The aim of the article is to present the methods of measurement of the consump-tion level of natural resources by the societies and the examination of relationships between the level of development of the societies and the use of resources. The popular measure – the ecological footprint – was used as a measurement method for the consumption of the today’s generations in relation to the regenerative possibilities of the natural envi-ronment. On the other hand, as the assessment method for the level of development of societies – the Human Develop-ment Index (HDI, including three basic areas: the life expectancy, GDP level per capita and education was used. The results of the research indicate that the current trend of the unlimited consumption of the highly developed countries takes place at the expense of the future generations.

  9. Ecological Growth Boundaries

    Science.gov (United States)

    Bluszcz, Anna

    2017-03-01

    The trends of the society for the continuous growth, combined with the demographic changes, today have led to the important ecological problems on a global scale, which include, among others: the increased use of non-renewable natural resources, an increase of the greenhouse gas emissions, contamination of soil, water, air and the progressive degradation of ecosystems. In the face of such serious threats the global initiatives of all countries are important to limit the results of the excessive consumption. The aim of the article is to present the methods of measurement of the consumption level of natural resources by the societies and the examination of relationships between the level of development of the societies and the use of resources. The popular measure - the ecological footprint - was used as a measurement method for the consumption of the today's generations in relation to the regenerative possibilities of the natural environment. On the other hand, as the assessment method for the level of development of societies - the Human Development Index (HDI), including three basic areas: the life expectancy, GDP level per capita and education was used. The results of the research indicate that the current trend of the unlimited consumption of the highly developed countries takes place at the expense of the future generations.

  10. Energy for growth

    International Nuclear Information System (INIS)

    McGill, S.R.

    2002-01-01

    When the 20th century began most people in the world lived on farms. When we think of subsequent developments, it is almost impossible to separate the idea of modern life from the energy-using machines that make it possible. Our world is one of cars, telephones, computers, TV sets, and the innumerable consumer products that either use energy or are made by machines that use energy. Of course, as technology has matured, we have learned to use energy more efficiently, and we expect that trend to continue. We have also widened the range of fuels that we can use, including new renewable forms of energy. But if economic development is going to continue, we are going to have to rely on our oil and gas resources for the foreseeable future. There is still an abundance of oil and gas resources, and the experience of developed countries shows that economic growth and a regard for the environment are not incompatible objectives. As always, there will be challenges. But armed with good will and sound science, we can expect to find solutions and build a better world along the way. Copyright (2002) Institution of Chemical Engineers in Australia

  11. Quartz crystal growth

    Science.gov (United States)

    Baughman, Richard J.

    1992-01-01

    A process for growing single crystals from an amorphous substance that can undergo phase transformation to the crystalline state in an appropriate solvent. The process is carried out in an autoclave having a lower dissolution zone and an upper crystallization zone between which a temperature differential (.DELTA.T) is maintained at all times. The apparatus loaded with the substance, solvent, and seed crystals is heated slowly maintaining a very low .DELTA.T between the warmer lower zone and cooler upper zone until the amorphous substance is transformed to the crystalline state in the lower zone. The heating rate is then increased to maintain a large .DELTA.T sufficient to increase material transport between the zones and rapid crystallization. .alpha.-Quartz single crystal can thus be made from fused quartz in caustic solvent by heating to 350.degree. C. stepwise with a .DELTA.T of 0.25.degree.-3.degree. C., increasing the .DELTA.T to about 50.degree. C. after the fused quartz has crystallized, and maintaining these conditions until crystal growth in the upper zone is completed.

  12. Posttraumatic growth in psychosis

    Directory of Open Access Journals (Sweden)

    Yael Mazor

    2016-12-01

    Full Text Available Objective: Recent research has shown high rates of exposure to trauma among people with serious mental illness (SMI. In addition studies suggest that psychosis and mental illness-related experiences can be extremely traumatic. While some individuals develop full blown PTSD related to these experiences, it has been noted that some may also experience posttraumatic growth (PTG. However, few studies have examined PTG as a possible outcome in people who have experienced psychosis. Method: To further understand the relationships between psychosis and PTG, 121 participants were recruited from community mental health rehabilitation centers and administered trauma and psychiatric questionnaires. Results: High levels of traumatic exposure were found in the sample. Regarding our main focus of study we observed that people who endured psychosis can experience PTG, and that PTG is mediated by meaning making and coping self-efficacy appraisal. Psychotic symptoms were found to be a major obstacle to meaning making, coping self-efficacy, and PTG, whereas negative symptoms were found to be significantly related to PTG when mediated by meaning making and coping self-efficacy. Conclusion: The current research provides preliminary evidence for potential role of meaning making and coping self-efficacy as mediators of PTG in the clinical, highly traumatized population of people with SMI who have experienced psychosis. This may have both research as well as clinical practice relevance for the field of psychiatric rehabilitation.

  13. Technical Education and Economic Growth

    Indian Academy of Sciences (India)

    Technical Education and Economic Growth. Technical Education and Economic Growth. Review of the Present Status. Expanding no.s and impairment of quality; Faculty shortage; Grim situation ... Absence of International flavour. Consequences of Low Research. Some Success Stories. New Models of Institutional Structure ...

  14. Growth curves for Laron syndrome.

    Science.gov (United States)

    Laron, Z; Lilos, P; Klinger, B

    1993-06-01

    Growth curves for children with Laron syndrome were constructed on the basis of repeated measurements made throughout infancy, childhood, and puberty in 24 (10 boys, 14 girls) of the 41 patients with this syndrome investigated in our clinic. Growth retardation was already noted at birth, the birth length ranging from 42 to 46 cm in the 12/20 available measurements. The postnatal growth curves deviated sharply from the normal from infancy on. Both sexes showed no clear pubertal spurt. Girls completed their growth between the age of 16-19 years to a final mean (SD) height of 119 (8.5) cm whereas the boys continued growing beyond the age of 20 years, achieving a final height of 124 (8.5) cm. At all ages the upper to lower body segment ratio was more than 2 SD above the normal mean. These growth curves constitute a model not only for primary, hereditary insulin-like growth factor-I (IGF-I) deficiency (Laron syndrome) but also for untreated secondary IGF-I deficiencies such as growth hormone gene deletion and idiopathic congenital isolated growth hormone deficiency. They should also be useful in the follow up of children with Laron syndrome treated with biosynthetic recombinant IGF-I.

  15. The Growth-Inequality Association:

    DEFF Research Database (Denmark)

    Bjørnskov, Christian

    2008-01-01

    This note suggests that the association between income inequality and economic growth rates might arguably depend on the political ideology of incumbent governments. Estimates indicate that under leftwing governments, inequality is negatively associated with growth while the association is positive...... under rightwing governments. This may provide a qualification to recent studies of inequality....

  16. Ecological economics and economic growth.

    Science.gov (United States)

    Victor, Peter A

    2010-01-01

    Boulding's 1966 paper on the economics of spaceship Earth established the framework for ecological economics and an understanding of economic growth. In ecological economics, economies are conceptualized as open subsystems of the closed biosphere and are subject to biophysical laws and constraints. Economic growth measured as an increase in real gross domestic product (GDP) has generally been associated with increases in the use of energy and materials and the generation of wastes. Scale, composition, and technology are the proximate determinants of environmental impacts. They are often reduced to two: scale (GDP) and intensity (impact per unit GDP). New work described in this paper defines "green" growth as intensity that declines faster than scale increases. Similarly, "brown" growth occurs when intensity declines more slowly than increases in scale, and "black" growth happens when both scale and intensity increase. These concepts are then related to the environmental Kuznets curve, which can be understood as a transition from brown to green growth. Ecological economics provides a macroperspective on economic growth. It offers broad policy principles, and it challenges the primacy of economic growth as a policy objective, but many important questions remain.

  17. U.S. Population Growth.

    Science.gov (United States)

    Dillner, Harry

    This autoinstructional lesson deals with the study of man and his environment. No previous experience or learning in this field is required. Emphasis is placed on analysis of population growth and the impact population growth and trends have on natural resource depletion. The behavioral objectives (five) are listed. The study guide for the…

  18. ICT, Innovation and Productivity Growth

    DEFF Research Database (Denmark)

    Fosse, Henrik; Jacobsen, Joannes; Sørensen, Anders

    This CEBR report presents new evidence which suggests that investments in Information and Communication Technology (ICT) further productivity growth in Danish firms by stimulating innovation activities.......This CEBR report presents new evidence which suggests that investments in Information and Communication Technology (ICT) further productivity growth in Danish firms by stimulating innovation activities....

  19. Population Growth: Crisis and Challenge.

    Science.gov (United States)

    Beaton, John R., Ed.; Doberenz, Alexander R., Ed.

    The proceedings of this first annual symposium on population growth considers the consequences of this growth, along with possible means of regulation. Topics of speeches include: Population Outlook in Asia (Irene Taeuber); Malnutrition is a Problem of Ecology (Paul Gyorgy); The Leisure Explosion (E. H. Storey); Effects of Pollution on Population…

  20. Technical Education and Economic Growth

    Indian Academy of Sciences (India)

    First page Back Continue Last page Graphics. Technical Education and Economic Growth. Technical Education and Economic Growth. Review of the Present Status. Expanding no.s and impairment of quality; Faculty shortage; Grim situation at Masters and PhD levels; Regional imbalance; Absence of International flavour ...

  1. Growth Hormone Deficiency in Adults

    Science.gov (United States)

    ... in your body Increase exercise capacity Build stronger bones: Growth hormone spurs bone formation and bone resorption (the breakdown of old ... should have a DXA bone scan to measure bone density before treatment with growth hormone. If it is abnormal, a DXA should be ...

  2. Mould growth on building materials

    DEFF Research Database (Denmark)

    Fog Nielsen, K.

    Mould growth in buildings is associated with adverse health effects among the occupants of the building. However actual growth only occurs in damp and water-damaged materials, and is an increasing problem in Denmark, due to less robust constructions, inadequate maintenance, and too little...

  3. Collisional Growth of Planetesimals

    Science.gov (United States)

    Schroeter, Thomas; Nyffenegger, Oliver; Benz, Willy

    2010-05-01

    Motivation ---------- In the current planet formation paradigm, planets form through collisions. While the size of the primordial planetesimals is not yet established, it is recognized that this collision cascade plays an crucial role not only in determining the growth rate of the bodies but also in determining their internal structure as well as bulk chemical composition. In the case of giant gaseous planets, the nucleated instability scenario begins with the formation of critical cores of order 10 Earth masses through this very process as well. Hence, the process of collisional growth underpins the early formation of all planets massive or not. The most natural and physically appropriate approach for studying these processes is to perform N-body simulations. Unfortunately, simulating the collisional dynamics of a very large number of bodies (several hundreds of millions) over very long timescales (hundred million orbits) turns out to be computationally prohibitive. Therefore, this approach remains for the moment limited to the late stages of formation when the number of bodies has become tractable. Statistical approaches while allowing treating an arbitrary number of bodies do not provide individual collision histories and therefore cannot address some of the most important issues related to the internal structure of young planets. By introducing an orbit averaging method based on a Monte Carlo technique that allows integrating the system using time steps much longer than an orbital period, we are in a position to follow the individual collision history of several tens of millions of bodies over long evolution times. Hence, this method effectively bridges the gap between the early small planetesimals and the large embryos for which the evolution can be followed using an N-body approach. Approach -------- The method is based on an orbit averaging Monte Carlo process. The essential advantage of the method is to allow for time steps that are not dictated by the

  4. Growth Hormone and Endocrinopathies

    International Nuclear Information System (INIS)

    Kim, K. W.; Choe, K. O.; Park, C. Y.; Lee, H.; Son, H. Y.; Huh, K. B.; Ryu, K. J.

    1979-01-01

    This is an analysis of 39 patients studied at the Yonsei Medical Center from January, 1976 to March 1979. Of these 35 patient were suspected of having hypothalamic insufficiency and subjected to the L-Dopa stimulation test to observe growth hormone secretary function while four acromegaly patient received the glucose loading test and L-Dopa stimulation test. The results are as follows: 1) The basal level of GH in the various disease was as follows: a) The basal level was lower than the control level but was not statistically significant b) In diabetes the mean value tended to higher than the control level but was not significant statistically c) In all four acromegaly patients the GH level was significantly higher than the control level 2) Of 13 patients with diabetes, nine had diabetic retinopathy, and of those nine, six showed increased L-Dopa response. However, of the four non retinopathic DM patients, only one showed increased response to L-Dopa. 3) Two patients out of ten with Sheehan's syndrome responded to L-Dopa stimulation. 4) One Patient of eight with pituitary chromophobe adenoma responded to L-Dopa stimulation. 5) Four acromegaly patients revealed 3 acidophilic adenoma and one chromophobe adenoma histologically. Of patients receiving the L-Dopa stimulation test. Two showed a paradoxical response. Two patients who received the glucose loading test showed suppressed response. 6) Of two craniopharyngioma patients, one showed increased GH response after L-Dopa stimulation. Increased response of GH after L-Dopa stimulation was seen in one two craniopharyngioma patients and also in one of two patients with short structure.

  5. Employment growth and regional development

    DEFF Research Database (Denmark)

    Eriksson, Rikard; Hansen, Høgni Kalsø; Winther, Lars

    2017-01-01

    This paper explores the potential drivers behind uneven regional development in the context of employment growth in Denmark and Sweden. In particular, we are interested in the roles of urbanization, industrial change and the rise of the new economy as manifested in the growth of the two economies...... in 2002–2007. The aim of this paper is, therefore, to analyse the impact of a number of key industrial sectors on regional employment growth in the two countries. The empirical analysis is based on longitudinal matched employer–employee data retrieved from official registers in each economy from 2002...... to 2007, a period of strong national growth following the crisis of early 2000. Our findings indicate that the two economies follow a similar pattern in addressing total employment growth; but looking at changes in employment levels across the national borders of these two relatively similar open...

  6. A nonpeptidyl growth hormone secretagogue.

    Science.gov (United States)

    Smith, R G; Cheng, K; Schoen, W R; Pong, S S; Hickey, G; Jacks, T; Butler, B; Chan, W W; Chaung, L Y; Judith, F

    1993-06-11

    A nonpeptidyl secretagogue for growth hormone of the structure 3-amino-3-methyl-N-(2,3,4,5-tetrahydro-2-oxo-1-([2'-(1H-tetrazol-5 -yl) (1,1'-biphenyl)-4-yl]methyl)-1H-1-benzazepin-3(R)-yl)-butanamid e (L-692,429) has been identified. L-692,429 synergizes with the natural growth hormone secretagogue growth hormone-releasing hormone and acts through an alternative signal transduction pathway. The mechanism of action of L-692,429 and studies with peptidyl and nonpeptidyl antagonists suggest that this molecule is a mimic of the growth hormone-releasing hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6). L-692,429 is an example of a nonpeptidyl specific secretagogue for growth hormone.

  7. Diauxic Growth of Propionibacterium shermanii

    Science.gov (United States)

    Lee, Inn Hee; Fredrickson, A. G.; Tsuchiya, H. M.

    1974-01-01

    Propionibacterium shermanii has been anaerobically propagated in batch and continuous culture with glucose and/or lactate as energy source. Specific growth rate on lactate was observed to be the same as that on glucose. In terms of cell density, the yield on glucose is higher than the yield on lactate. But the molar ratio of yield on glucose to that on lactate, 8.35, is in good agreement with the theoretical value of 8. In a mixture of glucose and lactate, P. shermanii showed diauxic growth. It used lactate before glucose utilization began. Neither temporary growth cessation nor two distinct growth phases were observed. A mathematical model is proposed to describe the diauxic growth. PMID:4441064

  8. A model of consumers' risk perceptions toward recombinant bovine growth hormone (rbGH): the impact of risk characteristics.

    Science.gov (United States)

    Grobe, D; Douthitt, R; Zepeda, L

    1999-08-01

    This study estimates the effect risk characteristics, described as outrage factors by Hadden, have on consumers' risk perceptions toward the food-related biotechnology, recombinant bovine growth hormone (rbGH). The outrage factors applicable to milk from rbGH treated herds are involuntary risk exposure, unfamiliarity with the product's production process, unnatural product characteristics, lack of trust in regulator's ability to protect consumers in the marketplace, and consumers' inability to distinguish milk from rbGH treated herds compared to milk from untreated herds. An empirical analysis of data from a national survey of household food shoppers reveals that outrage factors mediate risk perceptions. The results support the inclusion of outrage factors into the risk perception model for the rbGH product, as they add significantly to the explanatory power of the model and therefore reduce bias compared to a simpler model of attitudinal and demographic factors. The study indicates that outrage factors which have a significant impact on risk perceptions are the lack of trust in the FDA as a food-related information source, and perceiving no consumer benefits from farmers' use of rbGH. Communication strategies to reduce consumer risk perceptions therefore could utilize agencies perceived as more trustworthy and emphasize the benefits of rbGH use to consumers.

  9. Growth morphologies of crystal surfaces

    Science.gov (United States)

    Xiao, Rong-Fu; Alexander, J. Iwan D.; Rosenberger, Franz

    1991-03-01

    We have expanded our earlier Monte Carlo model [Phys. Rev. A 38, 2447 (1988); J. Crystal Growth 100, 313 (1990)] to three dimensions and included reevaporation after accommodation and growth on dislocation-induced steps. We found again that, for a given set of growth parameters, the critical size, beyond which a crystal cannot retain its macroscopically faceted shape, scales linearly with the mean free path in the vapor. However, the three-dimensional (3D) the systems show increased shape stability compared to corresponding 2D cases. Extrapolation of the model results to mean-free-path conditions used in morphological stability experiments leads to order-of-magnitude agreement of the predicted critical size with experimental findings. The stability region for macroscopically smooth (faceted) surfaces in the parameter space of temperature and supersaturation depends on both the surface and bulk diffusion. While surface diffusion is seen to smooth the growth morphology on the scale of the surface diffusion length, bulk diffusion is always destabilizing. The atomic surface roughness increases with increase in growth temperature and supersaturation. That is, the tendency of surface kinetics anisotropies to stabilize the growth shape is reduced through thermal and kinetic roughening. It is also found that the solid-on-solid assumption, which can be advantageously used at low temperatures and supersaturations, is insufficient to describe the growth dynamics of atomically rough interfaces where bulk diffusion governs the process. For surfaces with an emerging screw dislocation, we find that the spiral growth mechanism dominates at low temperatures and supersaturations. The polygonization of a growth spiral decreases with increasing temperature or supersaturation. When the mean free path in the nutrient is comparable to the lattice constant, the combined effect of bulk and surface diffusion reduces the terrace width of a growth spiral in its center region. At elevated

  10. Growth charts from controversy to consensus

    Directory of Open Access Journals (Sweden)

    Vaman Khadilkar

    2012-01-01

    Full Text Available Growth follows a specific set of patterns inspite of variability in children. This led to the development of growth charts . As growth provides an interplay of many factors, growth chart helps monitor growth and diagnose disease. They are also used for epidemiological purpose. There are many growth charts available. Training of health care workers to use and interpret growth chart in the children is needed for national health.

  11. Is the natural rate of growth exogenous?

    OpenAIRE

    Miguel Leon-Ledesma; Anthony P. Thirlwall

    2000-01-01

    In mainstream growth theory, including endogenous growth theory, the naturalrate of growth as defined by Harrod, is still treated as exogenous. In practice, however, both the growth of the labour force and the growth of labour productivity are endogenous to demand. This has theoretical implications for the adjustment process between the actual, warranted and natural growth rates. It also has serious implications for the way in which the growth process is viewed: whether from the supply side o...

  12. Growth of maize coleoptiles in the presence of natural and synthetic growth regulators. Growth correlations

    Directory of Open Access Journals (Sweden)

    Ewa Raczek

    2014-01-01

    Full Text Available The effect of natural (IAA, FC, ABA and synthetic (2,4-D growth substances on the increase of the fresh weight of maize coleoptile segments and change of the pH of the incubation medium, accepted here as criteria of maize coleoptile growth, was studied. The growth of maize coleoptiles depended on the concentration of the growth substances, as well as, on the composition of the incubation medium. The highest stimulation of coleoptile growth was seen with FC at a concentration of 10-4M, whereas ABA at 10-3 M gave the highest inhibition of maize coleoptile fresh weight increase and caused alkalization of the medium. The presence of K+ ions in the incubation medium enhanced the stimulatory effect of IAA and FC on the increase of the coleoptile fresh weight, whereas the presence of these ions and phosphate buffer abolished the growth-promoting effect of IAA and FC. The best correlation of the "fresh weight" and "pH" effects was found in the case of the growth of maize coleoptiles in the presence of FC (rxy = 0.67. The inhibition of maize coleoptile growth in the presence of high concentrations of IAA can be explained by the destructive effect of natural auxin at these concentrations on the integrity of mitochondrial membranes, and therefore on the normal functioning of mitochondria.

  13. Epiphyseal growth plate growth hormone receptor signaling is decreased in chronic kidney disease-related growth retardation.

    Science.gov (United States)

    Troib, Ariel; Landau, Daniel; Kachko, Leonid; Rabkin, Ralph; Segev, Yael

    2013-11-01

    Linear growth retardation in children with chronic kidney disease (CKD) has been ascribed to insensitivity to growth hormone. This resistance state has been attributed to impaired growth hormone signaling through the JAK2/STAT5 pathway in liver and skeletal muscle leading to reduced insulin-like growth factor-I (IGF-I). Here we determine whether systemic and growth plate alterations in growth hormone signaling contribute to CKD-induced linear growth retardation using partially nephrectomized and pair-fed control 20-day-old rats. Serum growth hormone did not change in rats with CKD, yet serum IGF-I levels were decreased and growth retarded. The tibial growth plate hypertrophic zone was wider and vascularization at the primary ossification center was reduced in CKD. This was associated with a decrease in growth plate vascular endothelial growth factor (VEGF) mRNA and immunostainable VEGF and IGF-I levels. Growth plate growth hormone receptor and STAT5 protein levels were unchanged, while JAK2 was reduced. Despite comparable growth hormone and growth hormone receptor levels in CKD and control rats, relative STAT5 phosphorylation was significantly depressed in CKD. Of note, the mRNA of SOCS2, an inhibitor of growth hormone signaling, was increased. Thus, linear growth impairment in CKD can in part be explained by impaired long bone growth plate growth hormone receptor signaling through the JAK2/STAT5 pathway, an abnormality that may be caused by an increase in SOCS2 expression.

  14. Determinants of human population growth.

    Science.gov (United States)

    Lutz, Wolfgang; Qiang, Ren

    2002-09-29

    The 20th century has seen unprecedented growth of the human population on this planet. While at the beginning of the century the Earth had an estimated 1.6 billion inhabitants, this number grew to 6.1 billion by the end of the century, and further significant growth is a near certainty. This paper tries to summarize what factors lie behind this extraordinary expansion of the human population and what population growth we can expect for the future. It discusses the concept of demographic transition and the preconditions for a lasting secular fertility decline. Recent fertility declines in all parts of the world now make it likely that human population growth will come to an end over the course of this century, but in parts of the developing world significant population growth is still to be expected over the coming decades. The slowing of population growth through declining birth rates, together with still increasing life expectancy, will result in a strong ageing of population age structure. Finally, this paper presents a global level systematic analysis of the relationship between population density on the one hand, and growth and fertility rates on the other. This analysis indicates that in addition to the well-studied social and economic determinants, population density also presents a significant factor for the levels and trends of human birth rates.

  15. Growth factors and new periodontology

    Directory of Open Access Journals (Sweden)

    Paknejad M

    1999-06-01

    Full Text Available Growth factors are biological mediators that have a key roll in proliferation, chemotaxy and"ndifferentiation by acting on specific receptors on the surface of cells and regulating events in wound"nhealing.They can be considered hormones that are not released in to the blood stream but have one a"nlocal action. Some of these factors can regulate premature change in GO to Gl phase in cell devesion"ncycle and even may stimulate synthesis of DNA in suitable cells, Growth substances, primarily secreted"nby fibroblasts, endothelia! cells, macrophages and platelet, include platelet derived growth factor"n(PDGF, insulin like growth factor (IGF transforming growth factor (TGFa and (3 and bone"nmorphogenetic proteins BMPs that approximately are the most important of them. (BMPs could be"nused to control events during periodontal, craniofacial and implant wound healing through favoring bone"nformation"nAccording toLynch, combination of PGDF and IGF1 would be effective in promoting growth of all the"ncomponents of the periodontium."nThe aim of this study was to characterize growth factor and review the literature to determine the"nmechanism of their function, classification and application in implant and periodontal treatment.

  16. The relative value of growth.

    Science.gov (United States)

    Mass, Nathaniel J

    2005-04-01

    Most executives would say that adding a point of growth and gaining a point of operating-profit margin contribute about equally to shareholder value. Margin improvements hit the bottom line immediately, while growth compounds value over time. But the reality is that the two are rarely equivalent. Growth often is far more valuable than managers think. For some companies, convincing the market that they can grow by just one additional percentage point can be worth six, seven, or even ten points of margin improvement. This article presents a new strategic metric, called the relative value of growth (RVG), which gives managers a clear picture of how growth projects and margin improvement initiatives affect shareholder value. Using basic balance sheet and income sheet data, managers can determine their companies' RVGs, as well as those of their competitors. Calculating RVGs gives managers insights into which corporate strategies are working to deliver value and whether their companies are pulling the most powerful value-creation levers. The author examines a number of well-known companies and explains what their RVG numbers say about their strategies. He reviews the unspoken assumption that growth and profits are incompatible over the long term and shows that a fair number of companies are effective at delivering both. Finally, he explains how managers can use the RVG framework to help them define strategies that balance growth and profitability at both the corporate and business unit levels.

  17. GROWTH RATE OF ARABIAN FOALS

    Directory of Open Access Journals (Sweden)

    M. PIESZKA

    2007-10-01

    Full Text Available Arabian horses are treated as one of the most noble horse breed in the world. It isalso one of the oldest breed known as a root of many other breeds. Opposite toThoroughbred horses Arabian ones are very healthy, easy to keep with low fodderdemand. They are still incredibly resistant to environmental conditions. Growth anddevelopment of foals is also very interesting because it is more similar to growth ofprimitive than to noble foals. The object of this study was to analyse the growth rateof Arabian foals bred in Poland. 382 foals born in Bialka Stud in 1983-2003 weretaken under consideration. The height at withers, girth and cannon circumferencemeasured at 1 day and 6 and 18 months of life were analysed. On this base thegrowth rate was calculated. Horses were divided into different groups accordingtheir year of birth, sex, coat colour and sire and dam lines. The statistical differencesbetween particular groups were evaluated. It was stated that year of birth affectedsignificantly the growth rate of Arabian foals. Colts were characterized bysignificantly higher growth rate of cannon circumference. Horses of different coatcolour did not differ in growth rate of any parameter. Affiliation to particular sireand dam lines had some effects on growth rate of Arabian foals.

  18. Pro Poor Growth in Cameroon

    Directory of Open Access Journals (Sweden)

    Samuel Fambon

    2017-06-01

    Full Text Available The purpose of this paper is to analyze the relationship between economic growth, poverty and income distribution in Cameroon, using both the data derived from three Cameroonian household surveys and the Poverty Equivalent Growth Rate (PEGR methodology developed by Kakwani et al. (2004, The study found that economic growth in Cameroon was pro poor over the period 1996–2007, which suggests that instead of increasing the economic growth rate alone, the poverty equivalent growth rate should also be maximized to achieve the poverty reduction objective, meaning that on the one hand, the growth rate should be boosted, and on the other, the distribution of income should also be concurrently improved. A decomposition of changes in poverty using the Kakwani (1997 approach reveal that the growth component dominates the redistribution component in the reduction of poverty. This suggests that the fall in absolute poverty over the survey period may be attributed to an increase in average household income, and not to the redistributive policies of the government.

  19. Sociological explanations of economic growth.

    Science.gov (United States)

    Marsh, R M

    1988-01-01

    Even if questions of how resources are distributed within and between societies are the main concern, it is necessary to continue to grapple with the issue of the causes of economic growth since economic growth and level of development continue to be among the most important causes of inequality, poverty, unemployment, and the quality of life. This paper's dependent variable is the economic growth rate of 55 less developed countries (LDCs) over 2 time periods. 1970-78 and 1965-84. The causal model consists of control variables--level of development and domestic investment in 1965--and a variety of independent variables drawn from major sociological theories of economic growth published during the last 3 decades. Multiple regression analysis shows that, net of the effects of the 2 control variables, the variables which have the strongest effect on economic growth are: 1) direct foreign investment, which has a negative effect, 2) the proportion of the population in military service, and 3) the primary school enrollment ratio, both of which have positive effects on economic growth. On the other hand, variables drawn from some theories receive no empirical support. The mass media of communications, ethnolinguistic heterogeneity, democracy and human rights, income inequality, and state-centric theory's key variable, state strength, all fail to show any significant impact on economic growth rates when the control variables and the significant independent variables are held constant. The theoretical implications of these findings are discussed.

  20. Growth in chronic kidney disease.

    Science.gov (United States)

    Janjua, Halima S; Mahan, John D

    2011-09-01

    Poor growth is a common sequela of CKD in childhood. It not only affects the psychosocial development of a child but also has significant effects even in the adult life. The multifactorial etiology and severe consequences of growth failure in CKD warrant evaluation of all the modifiable and nonmodifiable causes. Treatment strategies must be directed toward the specific factors for each child with CKD. Among the various metabolic, nutritional, and hormonal disturbances complicating CKD, disordered growth hormone (GH) and insulin-like growth factor-1 axis are important contributors toward poor growth in children with CKD. CKD is recognized as a state of GH resistance rather than GH deficiency, with multiple mechanisms contributing to this GH resistance. Recombinant GH (rGH) therapy can be used in this population to accelerate growth velocity. Although its use has been shown to be effective and safe in children with CKD, there continues to be some uncertainty and reluctance among practitioners and families regarding its usage, thereby resulting in a surprisingly low use in children with CKD. This review focuses on the pathogenesis of growth failure, its effect, and management strategies in children with CKD. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  1. Scaling Behavior of Firm Growth

    Science.gov (United States)

    Stanley, Michael H. R.; Nunes Amaral, Luis A.; Buldyrev, Sergey V.; Havlin, Shlomo; Leschhorn, Heiko; Maass, Philipp; Salinger, Michael A.; Stanley, H. Eugene

    1996-03-01

    The theory of the firm is of considerable interest in economics. The standard microeconomic theory of the firm is largely a static model and has thus proved unsatisfactory for addressing inherently dynamic issues such as the growth of economies. In recent years, many have attempted to develop richer models that provide a more accurate representation of firm dynamics due to learning, innovative effort, and the development of organizational infrastructure. The validity of these new, inherently dynamic theories depends on their consistency with the statistical properties of firm growth, e.g. the relationship between growth rates and firm size. Using the Compustat database over the time period 1975-1991, we find: (i) the distribution of annual growth rates for firms with approximately the same sales displays an exponential form with the logarithm of growth rate, and (ii) the fluctuations in the growth rates --- measured by the width of this distribution --- scale as a power law with the firm sales. We place these findings of scaling behavior in the context of conventional economics by considering firm growth dynamics with temporal correlations and also, by considering a hierarchical organization of the departments of a firm.

  2. Growth Data - Characterization of Sexual Growth Dimorphism in Sablefish

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Sexual growth dimorphism (SGD) is a common phenomenon in nature. Numerous marine fishes exhibit SGD, with females often growing faster and attaining larger sizes...

  3. Normative human brain volume growth.

    Science.gov (United States)

    Peterson, Mallory; Warf, Benjamin C; Schiff, Steven J

    2018-03-02

    OBJECTIVE While there is a long history of interest in measuring brain growth, as of yet there is no definitive model for normative human brain volume growth. The goal of this study was to analyze a variety of candidate models for such growth and select the model that provides the most statistically applicable fit. The authors sought to optimize clinically applicable growth charts that would facilitate improved treatment and predictive management for conditions such as hydrocephalus. METHODS The Weibull, two-term power law, West ontogenic, and Gompertz models were chosen as potential models. Normative brain volume data were compiled from the NIH MRI repository, and the data were fit using a nonlinear least squares regression algorithm. Appropriate statistical measures were analyzed for each model, and the best model was characterized with prediction bound curves to provide percentile estimates for clinical use. RESULTS Each model curve fit and the corresponding statistics were presented and analyzed. The Weibull fit had the best statistical results for both males and females, while the two-term power law generated the worst scores. The statistical measures and goodness of fit parameters for each model were provided to assure reproducibility. CONCLUSIONS The authors identified the Weibull model as the most effective growth curve fit for both males and females. Clinically usable growth charts were developed and provided to facilitate further clinical study of brain volume growth in conditions such as hydrocephalus. The authors note that the homogenous population from which the normative MRI data were compiled limits the study. Gaining a better understanding of the dynamics that underlie childhood brain growth would yield more predictive growth curves and improved neurosurgical management of hydrocephalus.

  4. The biophysics of neuronal growth

    International Nuclear Information System (INIS)

    Franze, Kristian; Guck, Jochen

    2010-01-01

    For a long time, neuroscience has focused on biochemical, molecular biological and electrophysiological aspects of neuronal physiology and pathology. However, there is a growing body of evidence indicating the importance of physical stimuli for neuronal growth and development. In this review we briefly summarize the historical background of neurobiophysics and give an overview over the current understanding of neuronal growth from a physics perspective. We show how biophysics has so far contributed to a better understanding of neuronal growth and discuss current inconsistencies. Finally, we speculate how biophysics may contribute to the successful treatment of lesions to the central nervous system, which have been considered incurable until very recently.

  5. Juvenile eye growth, when completed?

    DEFF Research Database (Denmark)

    Fledelius, Hans C; Christensen, Anders S; Fledelius, Christian

    2014-01-01

    PURPOSE: To test Sorsby's classical statement of axial eye growth as completed at the age of 13 years, with a view also to differentiating between basic eye growth and juvenile elongation associated with eventual refractive change towards myopia. METHODS: (i) A total of 160 healthy eyes close...... about age 13 as general limit found support from the cross-sectional data, which suggested stable emmetropic eye size from about 11-12 years, with an average apparently outgrown male emmetropic value of 23.5 mm versus females' 22.9 mm. The longitudinal data, however, showed emmetropic growth also beyond...

  6. Growth and yield of Giant Sequoia

    Science.gov (United States)

    David J. Dulitz

    1986-01-01

    Very little information exists concerning growth and yield of giant sequoia (Sequoiadendron giganteum [Lindl.] Buchholz). For old-growth trees, diameter growth is the single factor adding increment since maximum height has been obtained. Diameter growth averages 0.04 inches per year in normal old-growth trees but will fluctuate with changes in the...

  7. Growth Enhancement of Desulfovibrio indonesiensis NCIMB 13468 ...

    African Journals Online (AJOL)

    The results obtained revealed a ten times growth induction in 50-100% extracts after 1 day of growth when compared with untreated D. vulgaris and D. indonensiensis. After 2 days of growth, there was 100 times growth induction in 70 - 100 % extracts, 100 times growth induction in 5-100 % extract after 3 days and 10, 000 ...

  8. National Survey of Family Growth

    Data.gov (United States)

    U.S. Department of Health & Human Services — The National Survey of Family Growth (NSFG) gathers information on family life, marriage and divorce, pregnancy, infertility, use of contraception, and men's and...

  9. Traffic fatalities and economic growth

    Science.gov (United States)

    2003-04-01

    As countries develop death rates usually fall, especially for diseases that affect the young and result in substantial life-years lost. Deaths due to traffic accidents are a notable exception: the growth in motor vehicles that accompanies economic gr...

  10. The Market for Smart Growth

    Science.gov (United States)

    Based on several studies of market demand, the authors determined that consumer demand for smart growth would translate into more than 600,000 houses out of the approximately 2 million new housing units built in 2007.

  11. Growth Hormone Deficiency in Children

    Science.gov (United States)

    ... with GHD receive treatment with daily injections of synthetic (manufactured) human GH, a prescription medicine. The GH, given at home, is injected under the skin. Growth is usually monitored every 3 to 6 ...

  12. VT Designated Growth Center Boundary

    Data.gov (United States)

    Vermont Center for Geographic Information — Growth centers aim to align public infrastructure and private building investments with a local framework of policies and regulations to ensure that 20 years of...

  13. Unbalanced Growth, Senescence and Aging.

    Science.gov (United States)

    Polymenis, Michael; Kennedy, Brian K

    2017-01-01

    Usually, cells balance their growth with their division. Coordinating growth inputs with cell division ensures the proper timing of division when sufficient cell material is available and affects the overall rate of cell proliferation. At a very fundamental level, cellular replicative lifespan-defined as the number of times a cell can divide, is a manifestation of cell cycle control. Hence, control of mitotic cell divisions, especially when the commitment is made to a new round of cell division, is intimately linked to replicative aging of cells. In this chapter, we review our current understanding, and its shortcomings, of how unbalanced growth and division, can dramatically influence the proliferative potential of cells, often leading to cellular and organismal aging phenotypes. The interplay between growth and division also underpins cellular senescence (i.e., inability to divide) and quiescence, when cells exit the cell cycle but still retain their ability to divide.

  14. Corruption, Growth, and Public Finances

    OpenAIRE

    Vito Tanzi; Hamid R Davoodi

    2000-01-01

    The paper discusses some channels through which corruption affects growth such as the impact of corruption on enterprises, on the allocation of talent, and on investment. It also discusses the impact of corruption on some aspects of public finance.

  15. Epitaxial growth of hybrid nanostructures

    Science.gov (United States)

    Tan, Chaoliang; Chen, Junze; Wu, Xue-Jun; Zhang, Hua

    2018-02-01

    Hybrid nanostructures are a class of materials that are typically composed of two or more different components, in which each component has at least one dimension on the nanoscale. The rational design and controlled synthesis of hybrid nanostructures are of great importance in enabling the fine tuning of their properties and functions. Epitaxial growth is a promising approach to the controlled synthesis of hybrid nanostructures with desired structures, crystal phases, exposed facets and/or interfaces. This Review provides a critical summary of the state of the art in the field of epitaxial growth of hybrid nanostructures. We discuss the historical development, architectures and compositions, epitaxy methods, characterization techniques and advantages of epitaxial hybrid nanostructures. Finally, we provide insight into future research directions in this area, which include the epitaxial growth of hybrid nanostructures from a wider range of materials, the study of the underlying mechanism and determining the role of epitaxial growth in influencing the properties and application performance of hybrid nanostructures.

  16. Filamentous Growth in Eremothecium Fungi

    DEFF Research Database (Denmark)

    Oskarsson, Therese

    , this thesis deals with some of the aspects of hyphal growth, which is an important virulence factor for pathogenic fungi infecting both humans and plants. Hyphal establishment through continuous polar growth is a complex process, requiring the careful coordination of a large subset of proteins involved...... in polarity establishment and maintenance, cytoskeleton dynamics and intracellular transport. The first part of this thesis addresses the A. gossypii Arf3 small GTPase and its GEF- and GAP regulators; Yel1 and Gts1, which has been implicated in polar growth in a wide range of organisms. We could demonstrate......-regulatory activity of AgGts1, the protein could have additional actin organizing properties. In the second and third part, this thesis addresses the use of A. gossypii and its relative E. cymbalariae as model organisms for filamentous growth. A series of assays analyzed the capability of Eremothecium genus fungi...

  17. Growth hormone stimulation test (image)

    Science.gov (United States)

    ... stimulation test is usually performed to identify if hGH (human growth hormone) is deficient. The test is ... amino acid arginine in a vein to raise hGH levels. The test measures the ability of the ...

  18. Neurofibromatosis type 1 growth charts.

    Science.gov (United States)

    Clementi, M; Milani, S; Mammi, I; Boni, S; Monciotti, C; Tenconi, R

    1999-12-03

    Growth abnormalities such as macrocephaly and short stature have been described and are considered a consistent finding in neurofibromatosis type 1 (NF1), one of the most common autosomal dominant disorders in man. We present here a clinical study on the growth profile of a sample of NF1 patients collected through a population-based registry that covers three contiguous regions of North-East Italy (NEI-NF Registry). Auxometric traits of 528 NF1 patients have been measured with the aim of drawing growth charts for height, weight, and head circumference (OFC). Height velocity charts were based on a subset of 143 children who underwent multiple measurements. No differences in height were apparent between NF1 and normal subjects up to age 7 (girls) and 12 (boys) years; subsequently, the 50th centile of NF1 subjects tends to overlap with the 25th centile of normal subjects, and the 3rd centile is much lower in NF1 subjects than in normal subjects, mainly during adolescence. The negatively skewed distribution of height seems to indicate that height growth impairment affects only a proportion of NF1 subjects; height growth impairment does not seem related to disease severity. As for weight, our data suggest that slight overweight is a characteristic of adult NF1 subjects (mainly among males), independent of disease severity. Height growth velocity is normal during childhood for both sexes, whereas the pubertal spurt is slightly anticipated and reduced in NF1 boys but not in girls. Our data confirm previous observations that macrocrania affects most NF1 subjects; the shape of the head growth curve is similar in NF1 and normal girls, whereas NF1 boys present an OFC pubertal growth spurt much more pronounced and delayed than normal boys. The disproportion between OFC and height seems to be related to disease severity in boys but not in girls. Growth charts presented here can be useful in neurofibromatosis clinics for the identification of the effects of secondary growth

  19. Limits to the growth debate

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, L.

    The first two major studies sponsored by the club of Rome were the report of the Meadows team at MIT, The Limits to Growth, published in 1972, and the Mesarovic and Pestel report, Mankind at the Turning Point, published in 1974. When the Club of Rome met in Philadelphia in April of 1976, its pronouncements reflected a frame of mind quite different from that of 1972. Recently, Herman Kahn and his colleagues at the Hudson Institute have published The Next 200 Years, a book evidently inspired as much by antagonism to the limits-to-growth school of thought as by affirmative faith in its own vision of technological optimism. The author discusses the content of the studies and summarizes his own position in four areas. (1) While no trend of growth of anything can continue indefinitely in the real world, there are not global physical limits to economic growth within a time frame susceptible to plausible foresight or relevant to policy making. (2) In some world regions, notably South Asia and tropical Africa, population growth rates do indeed threaten to create a kind of Malthusian trap, and the rapid reduction of fertility is critically important to their development prospects and urgent in time. (3) For other parts of the world, both rates and directions of growth will be more influenced by changes in preferences for consumption and in attitudes toward production than by physical constraints, although higher energy costs and environmental pressures will also be important influences in generating such changes in growth patterns. (4) Probable changes in directions of growth will generate new and important issues in international economic and political relations, with both dangers and opportunities for the evolving world order. (MCW)

  20. Labor Quality Growth in Germany

    OpenAIRE

    Guido Schwerdt; Jarkko Turunen

    2009-01-01

    Extending the common baseline model in various dimensions does not fundamentally change the low contribution of labor quality to productivity growth in Germany. Labor quality growth is low owing to a small increase in the share of workers with higher education, a negative contribution from a higher share of females and declines in relative returns. The contribution of actual labor market experience is lower than suggested by an age proxy.

  1. Governance Quality and Economic Growth

    OpenAIRE

    Tao Kong

    2011-01-01

    Among both academics and the wider development community there seems to be a general acceptance of the value of good governance and its role in promoting economic growth. However, beyond this general statement, there is a lack of deeper theoretical understanding as to why good governance is expected to foster economic growth and how such effects may take place. We de.ne governance quality as the capacity of a government to internalize externality. A theoretical model is developed to formally ...

  2. Path selection during wormhole growth

    OpenAIRE

    Yang, Y.; Hakim, S. S.; Bruns, S.; Uesugi, K.; Dalby, K. N.; Stipp, S. L. S.; Sørensen, H. O.

    2017-01-01

    Growth of wormholes in porous media can lead to self-organization of flow networks with an overwhelming geometric complexity. Despite decades of study, the mechanism by which a dominant wormhole develops its path during growth remains elusive. Here we show that the trajectory of a growing wormhole can be predicted by identifying the flowpath with a so-called minimum cumulative surface. Our theoretical analysis indicates that the cumulative surface determines the position of the dissolution fr...

  3. Diamond growth in mantle fluids

    OpenAIRE

    Bureau, Hélène; Frost, Daniel J.; Bolfan-casanova, Nathalie; Leroy, Clémence; Esteve, Imène; Cordier, Patrick

    2016-01-01

    International audience; In the upper mantle, diamonds can potentially grow from various forms of media (solid, gas, fluid) with a range of compositions (e.g. graphite, C–O–H fluids, silicate or carbonate melts). Inclusions trapped in diamonds are one of the few diagnostic tools that can constrain diamond growth conditions in the Earth's mantle. In this study, inclusion-bearing diamonds have been synthesized to understand the growth conditions of natural diamonds in the upper mantle. Diamonds ...

  4. Placental Adaptations in Growth Restriction

    Directory of Open Access Journals (Sweden)

    Song Zhang

    2015-01-01

    Full Text Available The placenta is the primary interface between the fetus and mother and plays an important role in maintaining fetal development and growth by facilitating the transfer of substrates and participating in modulating the maternal immune response to prevent immunological rejection of the conceptus. The major substrates required for fetal growth include oxygen, glucose, amino acids and fatty acids, and their transport processes depend on morphological characteristics of the placenta, such as placental size, morphology, blood flow and vascularity. Other factors including insulin-like growth factors, apoptosis, autophagy and glucocorticoid exposure also affect placental growth and substrate transport capacity. Intrauterine growth restriction (IUGR is often a consequence of insufficiency, and is associated with a high incidence of perinatal morbidity and mortality, as well as increased risk of cardiovascular and metabolic diseases in later life. Several different experimental methods have been used to induce placental insufficiency and IUGR in animal models and a range of factors that regulate placental growth and substrate transport capacity have been demonstrated. While no model system completely recapitulates human IUGR, these animal models allow us to carefully dissect cellular and molecular mechanisms to improve our understanding and facilitate development of therapeutic interventions.

  5. Phenomenology of stochastic exponential growth

    Science.gov (United States)

    Pirjol, Dan; Jafarpour, Farshid; Iyer-Biswas, Srividya

    2017-06-01

    Stochastic exponential growth is observed in a variety of contexts, including molecular autocatalysis, nuclear fission, population growth, inflation of the universe, viral social media posts, and financial markets. Yet literature on modeling the phenomenology of these stochastic dynamics has predominantly focused on one model, geometric Brownian motion (GBM), which can be described as the solution of a Langevin equation with linear drift and linear multiplicative noise. Using recent experimental results on stochastic exponential growth of individual bacterial cell sizes, we motivate the need for a more general class of phenomenological models of stochastic exponential growth, which are consistent with the observation that the mean-rescaled distributions are approximately stationary at long times. We show that this behavior is not consistent with GBM, instead it is consistent with power-law multiplicative noise with positive fractional powers. Therefore, we consider this general class of phenomenological models for stochastic exponential growth, provide analytical solutions, and identify the important dimensionless combination of model parameters, which determines the shape of the mean-rescaled distribution. We also provide a prescription for robustly inferring model parameters from experimentally observed stochastic growth trajectories.

  6. Human Population: Fundamentals of Growth and Change.

    Science.gov (United States)

    Stauffer, Cheryl Lynn, Ed.

    This booklet focuses on eight elements of population dynamics: "Population Growth and Distribution"; "Natural Increase and Future Growth"; "Effect of Migration on Population Growth"; "Three Patterns of Population Change"; "Patterns of World Urbanization"; "The Status of Women";…

  7. Protecting water resources with smart growth.

    Science.gov (United States)

    2004-05-01

    Protecting Water Resources with : Smart Growth is intended for audiences already familiar with smart : growth, who now seek specific ideas : on how techniques for smarter growth : can be used to protect their water : resources. This document is one...

  8. Re-imagining the Growth Process

    DEFF Research Database (Denmark)

    Clarke, Jean; Holt, Robin; Blundel, Richard

    2014-01-01

    We investigate the role and influence of the biological metaphor 'growth' in studies of organizations, specifically in entrepreneurial settings. We argue that we need to reconsider metaphorical expressions of growth processes in entrepreneurship studies in order to better understand growth...

  9. The Political Economy of Growth: A Review

    OpenAIRE

    Hazama, Yasushi

    2008-01-01

    This cursory literature review discusses the direct and indirect effects of institutions, governance, and democracy on economic growth, and the following conclusions are drawn. First, institutions and governance have a positive effect on growth. Even reforms that are less than comprehensive can stimulate, though not sustain, growth. Second, democracy neither promotes nor hampers growth directly. It secures stability and resilience in growth. It also exerts impacts on sources of growth but its...

  10. Growth and Predictors of Growth Restraint in Moderately Preterm Children Aged 0 to 4 Years

    NARCIS (Netherlands)

    Bocca-Tjeertes, I.F.; Kerstjens, J.M.; Reijneveld, S.A.; de Winter, A.F.; Bos, A.F.

    2011-01-01

    OBJECTIVE: To describe growth in moderately preterm-born children, determine the prevalence of growth restraint at the age of 4, and identify predictors of growth restraint. We hypothesized that growth in moderately preterm-born children differs from growth in term-born children and that growth

  11. A role of placental growth factor in hair growth.

    Science.gov (United States)

    Yoon, Sun-Young; Yoon, Ji-Seon; Jo, Seong Jin; Shin, Chang Yup; Shin, Jong-Yeon; Kim, Jong-Il; Kwon, Ohsang; Kim, Kyu Han

    2014-05-01

    The dermal papilla (DP) comprises specialized mesenchymal cells at the bottom of the hair follicle and plays a pivotal role in hair formation, anagen induction and the hair cycle. In this study, DPs were isolated from human hair follicles and serially subcultured. From each subculture at passages 1, 3, and 5 (n=4), we compared gene expression profiles using mRNA sequencing. Among the growth factors that were down-regulated in later passages of human DP cells (hDPCs), placental growth factor (PlGF) was selected. To elucidate the effect of PlGF on hair growth. We evaluated the effect of PlGF on hDPCs and on ex vivo hair organ culture. We investigated the effect of PlGF on an in vivo model of depilation-induced hair regeneration. We confirmed that the mRNA and protein expression levels of PlGF significantly decreased following subculture of the cells. It was shown that PlGF enhanced hair shaft elongation in ex vivo hair organ culture. Furthermore, PlGF significantly accelerated hair follicle growth and markedly prolonged anagen hair growth in an in vivo model of depilation-induced hair regeneration. PlGF prevented cell death by increasing the levels of phosphorylated extracellular signal-regulated kinase (ERK) and cyclin D1 and promoted survival by up-regulation of phosphorylated Akt and Bcl2, as determined by Western blotting. Our results suggest that PlGF plays a role in the promotion of hair growth and therefore may serve as an additional therapeutic target for the treatment of alopecia. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  12. Green growth in the Netherlands

    International Nuclear Information System (INIS)

    Balde, K.; Boelens, A.; Brinksma, E.; Edens, B.; Hiethaar, S.; Klein, P.; Schenau, S.

    2011-04-01

    In 2009 the Ministerial Council Meeting of the Organisation for Economic Co-operation and Development (OECD) committed itself to a green growth strategy. Such a strategy fosters economic growth and development while ensuring that natural resources can continue to provide the ecosystem services on which our well-being relies. It also endorses investment, competition and innovation which will underpin sustained growth and give rise to new economic opportunities. Green growth provides both a policy strategy for implementing this economic transformation and a monitoring framework with a proposed set of indicators. This report presents an overview of the state of green growth in the Netherlands. It should be regarded as a benchmark for a more thorough and comprehensive assessment of green growth in the future. It is based on the set of indicators proposed by the OECD in their intermediate report of February 2011. Data relevant to the Dutch situation are presented for twenty of these indicators, illustrating the observed trends. The indicators are grouped in four themes. For the first theme, environmental efficiency of production, on the whole the indicators show increased efficiency. However, indicators such as greenhouse gas intensity, energy efficiency and material intensity show only relative decoupling, which on its own is not enough to ensure green growth. In addition, the increase in environmental efficiency is partly explained by substitution of imports for domestic production, which is not conducive to green growth on a global scale: the efficiency gains in domestic production, for example, are offset by increases in foreign greenhouse gas emissions. Water use and agricultural nutrient surpluses are the only indicators where absolute decoupling has occurred. The second theme contains indicators regarding the natural assets base. This group of indicators provides a mixed picture. Natural gas reserves are decreasing and the overall level of threat to animal

  13. Chitin promotes Mycobacterium ulcerans growth.

    Science.gov (United States)

    Sanhueza, Daniel; Chevillon, Christine; Colwell, Rita; Babonneau, Jérémie; Marion, Estelle; Marsollier, Laurent; Guégan, Jean-François

    2016-06-01

    Mycobacterium ulcerans(MU) is the causative agent of Buruli ulcer, an emerging human infectious disease. However, both the ecology and life cycle of MU are poorly understood. The occurrence of MU has been linked to the aquatic environment, notably water bodies affected by human activities. It has been hypothesized that one or a combination of environmental factor(s) connected to human activities could favour growth of MU in aquatic systems. Here, we testedin vitrothe growth effect of two ubiquitous polysaccharides and five chemical components on MU at concentration ranges shown to occur in endemic regions. Real-time PCR showed that chitin increased MU growth significantly providing a nutrient source or environmental support for thebacillus, thereby, providing a focus on the association between MU and aquatic arthropods. Aquatic environments with elevated population of arthropods provide increased chitin availability and, thereby, enhanced multiplication of MU. If calcium very slightly enhanced MU growth, iron, zinc, sulphate and phosphate did not stimulate MU growth, and at the concentration ranges of this study would limit MU population in natural ecosystems. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Phytochrome, plant growth and flowering

    Science.gov (United States)

    King, R. W.; Bagnall, D. J.

    1994-01-01

    Attempts to use artificially lit cabinets to grow plants identical to those growing in sunlight have provided compelling evidence of the importance of light quality for plant growth. Changing the balance of red (R) to far-red (FR) radiation, but with a fixed photosynthetic input can shift the phytochrome photoequilibrium in a plant and generate large differences in plant growth. With FR enrichment the plants elongate, and may produce more leaf area and dry matter. Similar morphogenic responses are also obtained when light quality is altered only briefly (15-30 min) at the end-of-the-day. Conversely, for plants grown in natural conditions the response of plant form to selective spectral filtering has again shown that red and far-red wavebands are important as found by Kasperbauer and coworkers. Also, where photosynthetic photon flux densities (PPFD) of sunlight have been held constant, the removal of far-red alone alters plant growth. With FR depletion plants grown in sunlight are small, more branched and darker green. Here we examine the implications for plant growth and flowering when the far-red composition of incident radiation in plant growth chambers is manipulated.

  15. American growth and Napoleonic Wars

    Directory of Open Access Journals (Sweden)

    Vergil Hasan

    2013-01-01

    Full Text Available Four years after the French Revolution, in 1793 a series of wars among France and other major powers of Europe began and they lasted until 1815. There is disagreement among economic historians about the effects of these wars on the trend of US economic growth. This paper aims to answer the following question. Did America as a neutral nation take advantage of economic possibilities caused by Europe at war through trade? To put it differently, this paper questions whether there was an export-led growth due to the war. To answer this question, we re-examined the export-led growth hypothesis for the period 1790-1860 using the ARDL methodology. Based on this methodology, a cointegrated relationship is found among the variables of real GDP, labor, exports and exchange rates. The results suggest that the economic growth of the US was not export-driven. In addition, parallel to the results of unit root tests with structural breaks, the coefficient of the dummy variable was statistically significant in the long run, implying that the war did have a significant effect on the economic growth trend of the US.

  16. Growth factors in cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Negar Khalighi

    2016-01-01

    Full Text Available Introduction: Cystic fibrosis is one of the most common autosomal recessive diseases that affects sweat glands and mucosa. CF is a hereditary disease with annual incidence of about 2500 new cases in United Kingdom. Insulin-like growth factor-1 (IGF-1 and insulin-like growth factor binding protein-3 levels decrease in CF. The aim of this study was to assess the role of growth peptides in patients with CF. Method: We searched PubMed, Google scholar, IranMedex, and Scientific Information Database (SID in September 2012 to April 2014. We included clinical studies with available abstracts and full texts that were in English or Persian languages. Manual searching was conducted within the reference lists of articles. Two reviewers independently applied eligibility criteria, assessed quality, and extracted data.Result: The earliest study was published in 1997 and the most recent one was in 2014. Study participants were adults in 3 studies (20% and 12 studies (80% were conducted in children. Patients with CF have lower levels of IGF-1 and there is a significant correlation between IGF-1 levels and growth index in patients with CF.Conclusions: IGF-1 decreases in children with CF and might be the cause of poor growth and low body mass index in these children.

  17. Universality in stochastic exponential growth.

    Science.gov (United States)

    Iyer-Biswas, Srividya; Crooks, Gavin E; Scherer, Norbert F; Dinner, Aaron R

    2014-07-11

    Recent imaging data for single bacterial cells reveal that their mean sizes grow exponentially in time and that their size distributions collapse to a single curve when rescaled by their means. An analogous result holds for the division-time distributions. A model is needed to delineate the minimal requirements for these scaling behaviors. We formulate a microscopic theory of stochastic exponential growth as a Master Equation that accounts for these observations, in contrast to existing quantitative models of stochastic exponential growth (e.g., the Black-Scholes equation or geometric Brownian motion). Our model, the stochastic Hinshelwood cycle (SHC), is an autocatalytic reaction cycle in which each molecular species catalyzes the production of the next. By finding exact analytical solutions to the SHC and the corresponding first passage time problem, we uncover universal signatures of fluctuations in exponential growth and division. The model makes minimal assumptions, and we describe how more complex reaction networks can reduce to such a cycle. We thus expect similar scalings to be discovered in stochastic processes resulting in exponential growth that appear in diverse contexts such as cosmology, finance, technology, and population growth.

  18. Phytochrome, plant growth and flowering

    Energy Technology Data Exchange (ETDEWEB)

    King, R.W.; Bagnall, D.J. [CSIRO, Canberra (Australia)

    1994-12-31

    Attempts to use artificially lit cabinets to grow plants identical to those growing in sunlight have provided compelling evidence of the importance of light quality for plant growth. Changing the balance of red (R) to far-red (FR) radiation, but with a fixed photosynthetic input can shift the phytochrome photoequilibrium in a plant and generate large differences in plant growth. With FR enrichment the plants elongate, and may produce more leaf area and dry matter. Similar morphogenic responses are also obtained when light quality is altered only briefly (15-30 min) at the end-of-the-day. Conversely, for plants grown in natural conditions the response of plant form to selective spectral filtering has again shown that red and far-red wavebands are important as found by Kasperbauer and coworkers. Also, where photosynthetic photon flux densities (PPFD) of sunlight have been held constant, the removal of far-red alone alters plant growth. As shown for chrysanthemum, with FR depletion plants grown in sunlight are small, more branched and darker green. We examine the implications for plant growth and flowering when the far-red composition of incident radiation in plant growth chambers is manipulated.

  19. Modeling microbial growth and dynamics.

    Science.gov (United States)

    Esser, Daniel S; Leveau, Johan H J; Meyer, Katrin M

    2015-11-01

    Modeling has become an important tool for widening our understanding of microbial growth in the context of applied microbiology and related to such processes as safe food production, wastewater treatment, bioremediation, or microbe-mediated mining. Various modeling techniques, such as primary, secondary and tertiary mathematical models, phenomenological models, mechanistic or kinetic models, reactive transport models, Bayesian network models, artificial neural networks, as well as agent-, individual-, and particle-based models have been applied to model microbial growth and activity in many applied fields. In this mini-review, we summarize the basic concepts of these models using examples and applications from food safety and wastewater treatment systems. We further review recent developments in other applied fields focusing on models that explicitly include spatial relationships. Using these examples, we point out the conceptual similarities across fields of application and encourage the combined use of different modeling techniques in hybrid models as well as their cross-disciplinary exchange. For instance, pattern-oriented modeling has its origin in ecology but may be employed to parameterize microbial growth models when experimental data are scarce. Models could also be used as virtual laboratories to optimize experimental design analogous to the virtual ecologist approach. Future microbial growth models will likely become more complex to benefit from the rich toolbox that is now available to microbial growth modelers.

  20. SME Cooperation on Innovation & Growth

    DEFF Research Database (Denmark)

    Brink, Tove; Neville, Mette

    2016-01-01

    The research in this paper reveals how cooperation of SMEs can enable innovation and growth. The research is conducted in a four-year period with 24 SMEs participating from different industry branches. The research is now in the late part of the 3rd. year starting in 2013 and finished January 2017....... Preliminary findings are revealed here and discussed with the SMEs. Shorter-term cooperation and especially longer-term collaboration is important for SMEs to enable innovation and growth. The content of collaboration is based on the cross-disciplinary trinity of organisational- and managerial development......, business model development and financial development. The trinity requires time to get the specific insight on application for each SME. An enhanced contribution is made to the field of SMEs, to academia and to public bodies to understand the needed initiatives to support SMEs for innovation and growth...