WorldWideScience

Sample records for pth successfully localized

  1. Nuclear localization of the type 1 PTH/PTHrP receptor in rat tissues.

    Science.gov (United States)

    Watson, P H; Fraher, L J; Hendy, G N; Chung, U I; Kisiel, M; Natale, B V; Hodsman, A B

    2000-06-01

    The localization of PTH/PTH-related peptide (PTHrP) receptor (PTHR) has traditionally been performed by autoradiography. Specific polyclonal antibodies to peptides unique to the PTHR are now available, which allow a more precise localization of the receptor in cells and tissues. We optimized the IHC procedure for the rat PTHR using 5-microm sections of paraffin-embedded rat kidney, liver, small intestine, uterus, and ovary. Adjacent sections were analyzed for the presence of PTHR mRNA (by in situ hybridization) and PTHrP peptide. A typical pattern of staining for both receptor protein and mRNA was observed in kidney in cells lining the proximal tubules and collecting ducts. In uterus and gut, the receptor and its mRNA are present in smooth muscle layers (PTHrP target) and in glandular cuboidal cells and surface columnar epithelium. This suggests that PTH, or more likely PTHrP, plays a role in surface/secretory epithelia that is as yet undefined. In the ovary, PTHR was readily detectable in the thecal layer of large antral follicles and oocytes, and was present in the cytoplasm and/or nucleus of granulosa cells, regions that also contained receptor transcripts. PTHR protein and mRNA were found in the liver in large hepatocytes radiating outward from central veins. Immunoreactive cells were also present around the periphery of the liver but not within two or three cell layers of the surface. Clear nuclear localization of the receptor protein was present in liver cells in addition to the expected cytoplasmic/peripheral staining. PTHR immunoreactivity was present in the nucleus of some cells in every tissue examined. RT-PCR confirmed the presence of PTHR transcripts in these same tissues. Examination of the hindlimbs of PTHR gene-ablated mice showed no reaction to this antibody, whereas hindlimbs from their wild-type littermates stained positively. The results emphasize that the PTHR is highly expressed in diverse tissues and, in addition, show that the receptor

  2. PTH1-34 Alleviates Radiotherapy-induced Local Bone Loss by Improving Osteoblast and Osteocyte Survival

    Science.gov (United States)

    Chandra, Abhishek; Lin, Tiao; Tribble, Mary Beth; Zhu, Ji; Altman, Allison R.; Tseng, Weiju; Zhang, Yejia; Akintoye, Sunday O.; Cengel, Keith; Liu, X. Sherry; Qin, Ling

    2014-01-01

    Cancer radiotherapy is often complicated by a spectrum of changes in the neighboring bone from mild osteopenia to osteoradionecrosis. We previously reported that parathyroid hormone (PTH, 1–34), an anabolic agent for osteoporosis, reversed bone structural deterioration caused by multiple microcomputed tomography (microCT) scans in adolescent rats. To simulate clinical radiotherapy for cancer patients and to search for remedies, we focally irradiated the tibial metaphyseal region of adult rats with a newly available small animal radiation research platform (SARRP) and treated these rats with intermittent injections of PTH1–34. Using a unique 3D image registration method that we recently developed, we traced the local changes of the same trabecular bone before and after treatments, and observed that, while radiation caused a loss of small trabecular elements leading to significant decreases in bone mass and strength, PTH1–34 preserved all trabecular elements in irradiated bone with remarkable increases in bone mass and strength. Histomorphometry demonstrated that SARRP radiation severely reduced osteoblast number and activity, which were impressively reversed by PTH treatment. In contrast, suppressing bone resorption by alendronate failed to rescue radiation-induced bone loss and to block the rescue effect of PTH1–34. Furthermore, histological analyses revealed that PTH1–34 protected osteoblasts and osteocytes from radiation-induced apoptosis and attenuated radiation-induced bone marrow adiposity. Taken together, our data strongly support a robust radioprotective effect of PTH on trabecular bone integrity through preserving bone formation and shed light on further investigations of an anabolic therapy for radiation-induced bone damage. PMID:24998454

  3. Primary hyperparathyroidism: intraoperative PTH-measurements

    DEFF Research Database (Denmark)

    Rolighed, L; Heickendorff, L; Hessov, I

    2004-01-01

    measurement as a predictor of successful cure. MATERIAL AND METHODS: From September 1999 to April 2002 143 patients with pHPT underwent a parathyroid operation (bilateral neck exploration with identification of all parathyroid glands) with intraoperative measurements of plasma PTH (immediately prior......BACKGROUND: With the development of rapid assays and intraoperative measurement of intact parathyroid hormone (PTH), new strategies in the handling of patients with primary hyperparathyroidism (pHPT) have evolved. AIM: The aim of our study was to illustrate the performance of the intraoperative PTH...... to surgery (T0) and 5 minutes after gland excision (T5)). A positive test result was defined as plasma PTH values at T5 below 20% of T0 or a value in the normal range below 7.6 pmol/l. Hence T5 values above 20% of T0 and above 7.6 pmol/l were considered test negative. RESULTS: 122 patients (85%) were test...

  4. Improving Localization Accuracy: Successive Measurements Error Modeling

    Directory of Open Access Journals (Sweden)

    Najah Abu Ali

    2015-07-01

    Full Text Available Vehicle self-localization is an essential requirement for many of the safety applications envisioned for vehicular networks. The mathematical models used in current vehicular localization schemes focus on modeling the localization error itself, and overlook the potential correlation between successive localization measurement errors. In this paper, we first investigate the existence of correlation between successive positioning measurements, and then incorporate this correlation into the modeling positioning error. We use the Yule Walker equations to determine the degree of correlation between a vehicle’s future position and its past positions, and then propose a -order Gauss–Markov model to predict the future position of a vehicle from its past  positions. We investigate the existence of correlation for two datasets representing the mobility traces of two vehicles over a period of time. We prove the existence of correlation between successive measurements in the two datasets, and show that the time correlation between measurements can have a value up to four minutes. Through simulations, we validate the robustness of our model and show that it is possible to use the first-order Gauss–Markov model, which has the least complexity, and still maintain an accurate estimation of a vehicle’s future location over time using only its current position. Our model can assist in providing better modeling of positioning errors and can be used as a prediction tool to improve the performance of classical localization algorithms such as the Kalman filter.

  5. Primary hyperparathyroidism: intraoperative PTH-measurements

    DEFF Research Database (Denmark)

    Rolighed, L; Heickendorff, L; Hessov, I

    2004-01-01

    measurement as a predictor of successful cure. MATERIAL AND METHODS: From September 1999 to April 2002 143 patients with pHPT underwent a parathyroid operation (bilateral neck exploration with identification of all parathyroid glands) with intraoperative measurements of plasma PTH (immediately prior...

  6. Rat parathyroid hormone (rPTH) ELISAs specific for regions (2-7), (22-34) and (40-60) of the rat PTH structure: influence of sex and age.

    Science.gov (United States)

    D'Amour, Pierre; Rousseau, Louise; Hornyak, Stephen; Yang, Zan; Cantor, Tom

    2010-09-15

    Rat (r) PTH ELISAs were used to study the influence of age and sex on rPTH levels and circulating PTH molecular forms separated by HPLC. Standard curves and saturation analysis were undertaken to define epitopes. Rats were sacrificed at approximately 27, 47 and 75days. Relevant biochemical parameters and 25(OH) vitamin D were measured. Differences between sexes were analyzed by Kruskal-Wallis ANOVA, followed by Dunn's test. Epitopes were localized in regions 2-7, 22-34 and 40-60 of rPTH structure for whole (W), total (T) and carboxyl (C) rPTH ELISAs. The W-rPTH assay only detected rPTH(1-84) and N-PTH in circulation while the T-PTH assay further detected large C-rPTH fragments. The C-rPTH assay detected all circulating rPTH molecular forms including smaller C-rPTH fragments. In both sexes, weight (p<0.001), ionized calcium, creatinine, albumin and 25(OH)D values (p<0.001) increased with age, while phosphate and alkaline phosphatase decreased (p<0.001). In male rats, W-rPTH remained unchanged, while T-rPTH rose slightly (p<0.05) and C-rPTH declined by half with time (p<0.001). In female rats, W-rPTH (p<0.05), T-rPTH (p<0.001) and C-rPTH (p<0.01) all increased in older animals. In both sexes, C-rPTH/W-rPTH and C-rPTH/T-rPTH ratios decreased between 25 and 47 days, to rise again between 47 and 75 days. The initial decrease may represent an adaptation to weaning and a change of diet between 25 and 47 days while the rise corresponds to higher calcium and 25(OH)D levels between 47 and 75 days. These changes were more pronounced in female rats, indicating an influence of sex on PTH molecular form secretion or metabolism.

  7. PTH Reloaded: A New Evolutionary Perspective

    Directory of Open Access Journals (Sweden)

    Paula Suarez-Bregua

    2017-10-01

    Full Text Available The parathyroid hormone (PTH family is a group of structurally-related secreted peptides involved in bone mineral homeostasis and multitude of developmental processes in vertebrates. These peptides mediate actions through PTH receptors (PTHRs, which belong to the transmembrane G protein-coupled receptor group. To date, genes encoding for PTH and PTHR have only been identified in chordates, suggesting that this signaling pathway may be an evolutionary innovation of our phylum. In vertebrates, we found up to six PTH and three PTHR different paralogs, varying in number between mammals and teleost fishes due to the different rounds of whole-genome duplication and specific gene losses suffered between the two groups of animals. The diversification of the PTH gene family has been accompanied by both functional divergence and convergence, making sometimes difficult the comparison between PTH peptides of teleosts and mammals. Here, we review the roles of all Pth peptides in fishes, and based on the evolutionary history of PTH paralogs, we propose a new and simple nomenclature from PTH1 to PTH4. Moreover, the recent characterization of the Pth4 in zebrafish allows us to consider the prominent role of the brain-to-bone signaling pathway in the regulation of bone development and homeostasis. Finally, comparison between PTH peptides of fish and mammals allows us to discuss an evolutionary model for PTH functions related to bone mineral balance during the vertebrate transition from an aquatic to a terrestrial environment.

  8. Novel parathyroid hormone (PTH) antagonists that bind to the juxtamembrane portion of the PTH/PTH-related protein receptor.

    Science.gov (United States)

    Shimizu, Naoto; Dean, Thomas; Tsang, Janet C; Khatri, Ashok; Potts, John T; Gardella, Thomas J

    2005-01-21

    Current antagonists for the parathyroid hormone (PTH)/PTH-related protein (PTHrP) receptor (PTHR) are N-terminally truncated or N-terminally modified analogs of PTH(1-34) or PTHrP(1-34) and are thought to bind predominantly to the N-terminal extracellular (N) domain of the receptor. We hypothesized that ligands that bind only to PTHR region comprised of the extracellular loops and seven transmembrane helices (the juxtamembrane or J domain) could also antagonize the PTHR. To test this, we started with the J domain-selective agonists [Gln(10),Ala(12),Har(11),Trp(14),Arg(19) (M)]PTH(1-21), [M]PTH(1-15), and [M]PTH(1-14), and introduced substitutions at positions 1-3 that were predicted to dissociate PTHR binding and cAMP signaling activities. Strong dissociation was observed with the tri-residue sequence diethylglycine (Deg)(1)-para-benzoyl-l-phenylalanine (Bpa)(2)-Deg(3). In HKRK-B7 cells, which express the cloned human PTHR, [Deg(1,3),Bpa(2),M]PTH(1-21), [Deg(1,3),Bpa(2),M]PTH(1-15), and [Deg(1,3),Bpa(2),M]PTH(1-14) fully inhibited (IC(50)s = 100-700 nm) the binding of (125)I-[alpha-aminoisobutyric acid(1,3),M]PTH(1-15) and were severely defective for stimulating cAMP accumulation. In ROS 17/2.8 cells, which express the native rat PTHR, [Deg(1,3),Bpa(2),M]PTH(1-21) and [Deg(1,3),Bpa(2),M]PTH(1-15) antagonized the cAMP-agonist action of PTH(1-34), as did PTHrP(5-36) (IC(50)s = 0.7 microm, 2.6 microm, and 36 nm, respectively). In COS-7 cells expressing PTHR-delNt, which lacks the N domain of the receptor, [Deg(1,3),Bpa(2), M]PTH(1-21) and [Deg(1,3),Bpa(2),M]PTH(1-15) inhibited the agonist actions of [alpha-aminoisobutyric acid(1,3)]PTH(1-34) and [M]PTH(1-14) (IC(50)s approximately 1 microm), whereas PTHrP(5-36) failed to inhibit. [Deg(1,3),Bpa(2),M]PTH(1-14) inhibited the constitutive cAMP-signaling activity of PTHR-tether-PTH(1-9), in which the PTH(1-9) sequence is covalently linked to the PTHR J domain, as well as that of PTHR(cam)H223R. Thus, the J

  9. Successful commercialisation of locally fabricated bioceramics for clinical applications.

    Science.gov (United States)

    Fazan, F; Besar, I; Osman, A; Samsudin, A R; Khalid, K A

    2008-07-01

    This paper chronicled the development of a locally produced bone graft substitute based on calcium phosphate bioceramics called "GranuMaS--from concepts to clinics, and finally to its successful commercialization all within 5-year duration. It was a Prioritized Research (PR) collaborative project of 5 institutions namely SIRIM, ANM, USM, UKM and IIUM, funded by MOSTI to the amount of approximately RM2.5 millions under RM8. This paper also highlighted the requirements needed in terms of technical expertise/manpower, facilities and infrastructure, and government/institutional supports, as well as the challenge faced in developing and commercializing such product.

  10. Bone-targeting parathyroid hormone conjugates outperform unmodified PTH in the anabolic treatment of osteoporosis in rats.

    Science.gov (United States)

    Yang, Yang; Aghazadeh-Habashi, Ali; Panahifar, Arash; Wu, Yuchin; Bhandari, Krishna H; Doschak, Michael R

    2017-08-01

    Synthetic parathyroid hormone (PTH) is clinically indicated for the treatment of osteoporosis, through its anabolic effects on parathyroid hormone receptors (PTHRs), located on osteoblast cells. However, the bioavailability of PTH for bone cells is restricted by the short half-life of PTH and the widespread distribution of PTHRs in non-skeletal tissues. To impart affinity for mineralized bone surfaces, bisphosphonate (BP)-mediated PTH analogues were synthesized, characterized, and evaluated in vitro and in vivo. The successful synthesis of PTH-PEG-BP was identified on MALDI-ToF mass spectra; bone-targeting potential was evaluated by hydroxyapatite binding test; and receptor bioactivity was assessed in UMR-106 (rat osteosarcoma) cells that constitutively express PTHRs. Therapeutic efficacy was evaluated using ovariectomized rats that remained untreated for 8 weeks to allow development of osteopenia. Those rats then received daily subcutaneous injections of PTH-PEG-BP, thiol-BP vehicle, or unmodified PTH, and compared to sham-operated healthy rats at 0, 4, 8, 12, and 16 weeks. In vivo micro-CT was conducted on the proximal tibial metaphysis to measure microstructural bone parameters, and new bone formation was detected using dynamic labeling. Bone strength was assessed using three-point bending mechanical testing. Our study determined that PTH-PEG-BP conjugates significantly enhanced PTH targeting to the bone matrix while retaining full PTH bioactivity. Moreover, PTH-PEG-BP conjugates significantly increased trabecular bone quality, anabolic bone formation, and improved bone strength over systemically administered PTH alone. We highlight the promise of a novel class of bone-targeting anabolic compound for the treatment of osteoporosis and related bone disorders.

  11. Disruption of PTH receptor 1 in T cells protects against PTH-induced bone loss.

    Directory of Open Access Journals (Sweden)

    Hesham Tawfeek

    Full Text Available BACKGROUND: Hyperparathyroidism in humans and continuous parathyroid hormone (cPTH treatment in mice cause bone loss by regulating the production of RANKL and OPG by stromal cells (SCs and osteoblasts (OBs. Recently, it has been reported that T cells are required for cPTH to induce bone loss as the binding of the T cell costimulatory molecule CD40L to SC receptor CD40 augments SC sensitivity to cPTH. However it is unknown whether direct PTH stimulation of T cells is required for cPTH to induce bone loss, and whether T cells contribute to the bone catabolic activity of PTH with mechanisms other than induction of CD40 signaling in SCs. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that silencing of PTH receptor 1 (PPR in T cells blocks the bone loss and the osteoclastic expansion induced by cPTH, thus demonstrating that PPR signaling in T cells is central for PTH-induced reduction of bone mass. Mechanistic studies revealed that PTH activation of the T cell PPR stimulates T cell production of the osteoclastogenic cytokine tumor necrosis factor alpha (TNF. Attesting to the relevance of this effect, disruption of T cell TNF production prevents PTH-induced bone loss. We also show that a novel mechanism by which TNF mediates PTH induced osteoclast formation is upregulation of CD40 expression in SCs, which increases their RANKL/OPG production ratio. CONCLUSIONS/SIGNIFICANCE: These findings demonstrate that PPR signaling in T cells plays an essential role in PTH induced bone loss by promoting T cell production of TNF. A previously unknown effect of TNF is to increase SC expression of CD40, which in turn increases SC osteoclastogenic activity by upregulating their RANKL/OPG production ratio. PPR-dependent stimulation of TNF production by T cells and the resulting TNF regulation of CD40 signaling in SCs are potential new therapeutic targets for the bone loss of hyperparathyroidism.

  12. Disruption of PTH Receptor 1 in T Cells Protects against PTH-Induced Bone Loss

    Science.gov (United States)

    Tawfeek, Hesham; Bedi, Brahmchetna; Li, Jau-Yi; Adams, Jonathan; Kobayashi, Tatsuya; Weitzmann, M. Neale; Kronenberg, Henry M.; Pacifici, Roberto

    2010-01-01

    Background Hyperparathyroidism in humans and continuous parathyroid hormone (cPTH) treatment in mice cause bone loss by regulating the production of RANKL and OPG by stromal cells (SCs) and osteoblasts (OBs). Recently, it has been reported that T cells are required for cPTH to induce bone loss as the binding of the T cell costimulatory molecule CD40L to SC receptor CD40 augments SC sensitivity to cPTH. However it is unknown whether direct PTH stimulation of T cells is required for cPTH to induce bone loss, and whether T cells contribute to the bone catabolic activity of PTH with mechanisms other than induction of CD40 signaling in SCs. Methodology/Principal Findings Here we show that silencing of PTH receptor 1 (PPR) in T cells blocks the bone loss and the osteoclastic expansion induced by cPTH, thus demonstrating that PPR signaling in T cells is central for PTH-induced reduction of bone mass. Mechanistic studies revealed that PTH activation of the T cell PPR stimulates T cell production of the osteoclastogenic cytokine tumor necrosis factor α (TNF). Attesting to the relevance of this effect, disruption of T cell TNF production prevents PTH-induced bone loss. We also show that a novel mechanism by which TNF mediates PTH induced osteoclast formation is upregulation of CD40 expression in SCs, which increases their RANKL/OPG production ratio. Conclusions/Significance These findings demonstrate that PPR signaling in T cells plays an essential role in PTH induced bone loss by promoting T cell production of TNF. A previously unknown effect of TNF is to increase SC expression of CD40, which in turn increases SC osteoclastogenic activity by upregulating their RANKL/OPG production ratio. PPR-dependent stimulation of TNF production by T cells and the resulting TNF regulation of CD40 signaling in SCs are potential new therapeutic targets for the bone loss of hyperparathyroidism. PMID:20808842

  13. Modeling of Oxidized PTH (oxPTH) and Non-oxidized PTH (n-oxPTH) Receptor Binding and Relationship of Oxidized to Non-Oxidized PTH in Children with Chronic Renal Failure, Adult Patients on Hemodialysis and Kidney Transplant Recipients

    DEFF Research Database (Denmark)

    Hocher, Berthold; Oberthür, Dominik; Slowinski, Torsten;

    2013-01-01

    Background: The biological properties of oxidized and non-oxidized PTH are substantially different. Oxidized PTH (oxPTH) loses its PTH receptor-stimulating properties, whereas non-oxidized PTH (n-oxPTH) is a full agonist of the receptor. This was described in more than 20 well published studies i...

  14. Oxidation inhibits PTH receptor signaling and trafficking.

    Science.gov (United States)

    Ardura, Juan A; Alonso, Verónica; Esbrit, Pedro; Friedman, Peter A

    2017-01-22

    Reactive Oxygen Species (ROS) increase during aging, potentially affecting many tissues including brain, heart, and bone. ROS alter signaling pathways and constitute potential therapeutic targets to limit oxidative damaging effects in aging-associated diseases. Parathyroid hormone receptors (PTHR) are widely expressed and PTH is the only anabolic therapy for osteoporosis. The effects of oxidative stress on PTHR signaling and trafficking have not been elucidated. Here, we used Fluorescence Resonance Energy Transfer (FRET)-based cAMP, ERK, and calcium fluorescent biosensors to analyze the effects of ROS on PTHR signaling and trafficking by live-cell imaging. PTHR internalization and recycling were measured in HEK-293 cells stably transfected with HA-PTHR. PTH increased cAMP production, ERK phosphorylation, and elevated intracellular calcium. Pre-incubation with H2O2 reduced all PTH-dependent signaling pathways. These inhibitory effects were not a result of PTH oxidation since PTH incubated with H2O2 triggered similar responses. PTH promoted internalization and recycling of the PTHR. Both events were significantly reduced by H2O2 pre-incubation. These findings highlight the role of oxidation on PTHR signaling and trafficking, and suggest the relevance of ROS as a putative target in diseases associated with oxidative stress such as age-related osteoporosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Serum parathyroid hormone (PTH) in pregnant women determined by an immunoradiometric assay for intact PTH

    Energy Technology Data Exchange (ETDEWEB)

    Davis, O.K.; Hawkins, D.S.; Rubin, L.P.; Posillico, J.T.; Brown, E.M.; Schiff, I.

    1988-10-01

    Most studies of circulating PTH levels using traditional RIAs have supported the concept of physiological hyperparathyroidism of pregnancy, with pregnant women having serum immunoreactive PTH levels significantly higher than those in nonpregnant subjects. However, such RIAs are insensitive and often detect inactive PTH fragments, so that the correlation between PTH immunoreactivity and bioactivity is poor. Employing a new intact PTH immunoradiometric assay (Allegro-Nichols), we reassessed the effects of pregnancy on parathyroid function. The mean serum PTH level in 81 pregnant women was 14.4 +/- 6.3 (+/- SD) compared to 24.8 +/- 9.0 ng/L in 11 normally cycling nonpregnant women (P less than 0.001). The mean serum total and ionized calcium levels in the 2 groups were similar. In 5 of the pregnant women, serum bioactive PTH, determined by cytochemical bioassay, was slightly lower (7.7 +/- 3.4 ng/L) than in normal individuals (11.1 +/- 1.9 ng/L). Our findings suggest, in contrast with the results of most previous studies, that serum intact PTH may decline during pregnancy.

  16. Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.

    Science.gov (United States)

    Curtis, Ryan C; Custis, James T; Ehrhart, Nicole P; Ehrhart, E J; Condon, Keith W; Gookin, Sara E; Donahue, Seth W

    2016-01-01

    Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma.

  17. Comparison of Intact PTH and Bio-Intact PTH Assays Among Non-Dialysis Dependent Chronic Kidney Disease Patients.

    Science.gov (United States)

    Einbinder, Yael; Benchetrit, Sydney; Golan, Eliezer; Zitman-Gal, Tali

    2017-09-01

    The third-generation bio-intact parathyroid hormone (PTH) (1-84) assay was designed to overcome problems associated with the detection of C-terminal fragments by the second-generation intact PTH assay. The two assays have been compared primarily among dialysis populations. The present study evaluated the correlations and differences between these two PTH assays among patients with chronic kidney disease (CKD) stages 3 to 5 not yet on dialysis. Blood samples were collected from 98 patients with CKD stages 3 to 5. PTH concentrations were measured simultaneously by using the second-generation - PTH intact-STAT and third-generation bio-intact 1-84 PTH assays. Other serum biomarkers of bone mineral disorders were also assessed. CKD stage was calculated by using the CKD-Epidemiology Collaboration (EPI) formula. Serum bio-intact PTH concentrations were strongly correlated but significantly lower than the intact PTH concentrations (r=0.963, Pbio-intact PTH) positively correlated with urea (r=0.523, r=0.504; P=0.002, respectively), phosphorus (r=0.532, r=0.521; Pbio-intact PTH assay detected significantly lower PTH concentrations compared with intact PTH assay. Additional studies that correlate the diagnosis and management of CKD mineral and bone disorders with bone histomorphometric findings are needed to determine whether bio-intact PTH assay results are better surrogate markers in these early stages of CKD.

  18. Success and Design of Local Referenda for Land Conservation

    Science.gov (United States)

    Banzhaf, H. Spencer; Oates, Wallace E.; Sanchirico, James N.

    2010-01-01

    From 1998 to 2006, over three-quarters of the more than 1,550 U.S. referenda targeting open space passed. We analyze the success of the conservation movement at holding referenda in areas with greater ecological value and greater likelihood of supporting conservation. To do so, we first analyze the patterns in where referenda are held and in which…

  19. Intra-oral PTH administration promotes tooth extraction socket healing.

    Science.gov (United States)

    Kuroshima, S; Kovacic, B L; Kozloff, K M; McCauley, L K; Yamashita, J

    2013-06-01

    Intermittent parathyroid hormone (PTH) administration increases systemic and craniofacial bone mass. However, the effect of PTH therapy on healing of tooth extraction sites is unknown. The aims of this study were to determine the effect of PTH therapy on tooth extraction socket healing and to examine whether PTH intra-oral injection promotes healing. The mandibular first molars were extracted in rats, and subcutaneous PTH was administered intermittently for 7, 14, and 28 days. In a second study, maxillary second molars were extracted, and PTH was administered by either subcutaneous or intra-oral injection to determine the efficacy of intra-oral PTH administration. Healing was assessed by micro-computed tomography and histomorphometric analyses. PTH therapy accelerated the entire healing process and promoted both hard- and soft-tissue healing by increasing bone fill and connective tissue maturation. PTH therapy by intra-oral injection was as effective as subcutaneous injection in promoting tooth extraction socket healing. The findings suggest that PTH therapy promotes tooth extraction socket healing and that intra-oral injections can be used to administer PTH.

  20. Local Solutions for National Challenges? Exploring Local Solutions through the Case of a National Succession Planning Strategy

    Science.gov (United States)

    Collins, Mike

    2013-01-01

    The notion of localism and decentralization in national policy has come increasingly to the fore in recent years. The national succession planning strategy for headteachers in England introduced by the National College for School Leadership promoted "local solutions for a national challenge". This article deals with some aspects of the…

  1. Characteristics of Successful Local Blended Programs in the Context of the Sloan-C Pillars

    Science.gov (United States)

    Moloney, Jacqueline F.; Hickey, Charmaine P.; Bergin, Amy L.; Boccia, Judith; Polley, Kathleen; Riley, Jeannette E.

    2010-01-01

    Drawing on the University of Massachusetts experience in developing successful blended local programs, this paper suggests guiding principles that include mission-driven responsiveness to local contexts and partnerships; using low-cost marketing strategies available through local relationships and brand; attending to students' preferences for…

  2. PTH-analogs: comparable or different?

    Science.gov (United States)

    Verhaar, H J J; Lems, W F

    2009-01-01

    Because no comparative studies exist, no clear pronouncements can be made about the potential differences in effectiveness and safety between PTH 1-34 and PTH 1-84. As regards the efficacy, a convincing reduction of vertebral fractures was shown in both cases [Neer, R.M., Arnaud, C.D., Zanchetta, J.R., Prince, R., Gaich, G.A., Reginster, J.Y., Hodsman, A.B., Eriksen, E.F., Ish-Shalom, S., Genant, H.K., Wang, O., Mitlak, B.H., 2001. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N. Engl. J. Med. 344, 1434-1441; Greenspan, S.L., Bone, H.G., Ettinger, M.P., Hanley, D.A., Lindsay, R., Zanchetta, J.R., Blosch, C.M., Mathisen, A.L., Morris, S.A., Marriott, T.B., Treatment of Osteoporosis with Parathyroid Hormone Study Group, 2007. Effect of recombinant human parathyroid hormone (1-84) on vertebral fracture and bone mineral density in postmenopausal women with osteoporosis: a randomized trial. Ann. Intern. Med. 146, 326-339]. A reduction of non-vertebral fractures was shown in the case of PTH 1-34 only. Another significant resemblance is that both medicines have a strong anabolic action; this mechanism of action is essentially different from the bisphosphonates and strontium ranelate. Both medicines constitute a welcome addition to the therapeutic arsenal for patients with severe osteoporosis. More data from literature (including information on follow-up data and use in men) are available for PTH 1-34 because it has been available for longer. As regards the side effect profile, PTH 1-84 appears to have a higher incidence of hypercalcemia, hypercalciuria and nausea than teriparatide. Here, too, no comparative study exists: the differences may therefore be based on an actual difference in side effects, or it may be ascribed to differences in definitions and/or patient populations.

  3. Why Current PTH Assays Mislead Clinical Decision Making in Patients with Secondary Hyperparathyroidism.

    Science.gov (United States)

    Hocher, Berthold; Yin, Lianghong

    2017-02-10

    Preclinical studies in cell culture systems as well as in whole animal chronic kidney disease (CKD) models showed that parathyroid hormone (PTH), oxidized at the 2 methionine residues (positions 8 and 18), caused a loss of function. This was so far not considered in the development of PTH assays used in current clinical practice. Patients with advanced CKD are subject to oxidative stress, and plasma proteins (including PTH) are targets for oxidants. In patients with CKD, a considerable but variable fraction (about 70 to 90%) of measured PTH appears to be oxidized. Oxidized PTH (oxPTH) does not interact with the PTH receptor resulting in loss of biological activity. Currently used intact PTH (iPTH) assays detect both oxidized and non-oxPTH (n-oxPTH). Clinical studies demonstrated that bioactive, n-oxPTH, but not iPTH nor oxPTH, is associated with mortality in CKD patients.

  4. Altered selectivity of parathyroid hormone (PTH) and PTH-related protein (PTHrP) for distinct conformations of the PTH/PTHrP receptor.

    Science.gov (United States)

    Dean, Thomas; Vilardaga, Jean-Pierre; Potts, John T; Gardella, Thomas J

    2008-01-01

    PTH and PTHrP use the same G protein-coupled receptor, the PTH/PTHrP receptor (PTHR), to mediate their distinct biological actions. The extent to which the mechanisms by which the two ligands bind to the PTHR differ is unclear. We examined this question using several pharmacological and biophysical approaches. Kinetic dissociation and equilibrium binding assays revealed that the binding of [(125)I]PTHrP(1-36) to the PTHR was more sensitive to GTPgammaS (added to functionally uncouple PTHR-G protein complexes) than was the binding of [(125)I]PTH(1-34) ( approximately 75% maximal inhibition vs. approximately 20%). Fluorescence resonance energy transfer-based kinetic analyses revealed that PTHrP(1-36) bound to the PTHR more slowly and dissociated from it more rapidly than did PTH(1-34). The cAMP signaling response capacity of PTHrP(1-36) in cells decayed more rapidly than did that of PTH(1-34) (t(1/2) = approximately 1 vs. approximately 2 h). Divergent residue 5 in the ligand, Ile in PTH and His in PTHrP, was identified as a key determinant of the altered receptor-interaction responses exhibited by the two peptides. We conclude that whereas PTH and PTHrP bind similarly to the G protein-coupled PTHR conformation (RG), PTH has a greater capacity to bind to the G protein-uncoupled conformation (R(0)) and, hence, can produce cumulatively greater signaling responses (via R(0)-->RG isomerization) than can PTHrP. Such conformational selectivity may relate to the distinct modes by which PTH and PTHrP act biologically, endocrine vs. paracrine, and may help explain reported differences in the effects that the ligands have on calcium and bone metabolism when administered to humans.

  5. Valores de PTH en pacientes bajo tratamiento con bifosfonatos PTH Levels in Patients Treated with Bisphosphonates

    Directory of Open Access Journals (Sweden)

    MS Saavedra

    2012-06-01

    Full Text Available Se han cuestionado los rangos o valores de referencia (VR de PTH definidos en sujetos en los cuales las causas de aumento en los niveles de PTH no hayan sido exhaustivamente excluidas: un VR óptimo debe coexistir con niveles de vitamina D adecuados. En este estudio analizamos el VR en mujeres post-menopáusicas, con niveles adecuados de 25(OH D, bajo tratamiento con bifosfonatos orales. Éstos, por su mecanismo de acción, pueden producir disminución asintomática del calcio sérico y aumento secundario de PTH; por lo cual, el VR de 15 a 65 pg/ml, informado para la medición de PTH molécula intacta por electroquimioluminiscencia, podría no ser el adecuado para esta población en particular. La edad media y la desviación estándar de los sujetos fue de 71,4 ± 8,55 años, con una media para 25(OH D3, de 37,3 ng/ml, calcio iónico: 4,9 mg/dl (VR.4,3-5,3; calcio urinario: 110 mg/24 h (VR: 60-200; fósforo en suero: 3,6 mg% (VR: 2,5-4,5; fósforo en orina: 0,61 g/24hs (VR: 0,3-1,0, creatinina plasmática: 0,80 mg% (VR: 0,5-1,5 y un FGe de 74 ml/min/1,73 m² (V corte >60. Para los fíCTx la media obtenida fue 212 pg/ml, que refleja la acción antirresortiva de los bifosfonatos. El VR de PTH calculado para esta población, según las recomendaciones del CLSI C28-A3 fue de 26,2-87,7 ng/ml. De la regresión lineal múltiple (r²=0,14 de la variable dependiente PTHi con las predictoras pCTx y creatinina, ajustadas por edad, los valores de PTHi dependieron de pCTx (P= -0,024; p=0,022 y de creatinina (P = 22,294; p=0,040. Todos nuestros resultados ponen en evidencia que el aumento de los niveles de PTH en esta población se debería en parte al efecto de la terapia antirresortiva y así como del proceso de envejecimiento fisiológico natural. Conclusión: El VR empleado para la población general no sería aplicable a las mujeres posmenopaúsicas, con niveles suficientes de 25OHD3, suplementadas con calcio, bajo tratamiento con bifosfonatos orales

  6. DETERMINANTS OF THE SUCCESS OF GLOBAL AND LOCAL BRANDS IN LATIN AMERICA

    Directory of Open Access Journals (Sweden)

    Pablo Farías

    2015-08-01

    Full Text Available The purpose of this paper is to address the issue of the implementation of global and local brands in Latin America by drawing on contingency theory to develop and test hypotheses relating to how product category characteristics affect the success of global and local brands in the region. Hypotheses are tested using data obtained from top brands rankings reported in five Latin American markets (Argentina, Brazil, the Caribbean and Central America, Chile and Mexico. The study design considers estimating a logistic regression on a binomial dependent variable measuring whether 475 top brands are global or local brands, with product category characteristics as independent variables. Results reveal that product categories related to subscriptions, local tastes, high-tech, and global citizenship do have an impact on the success of global and local brands in Latin America.

  7. Succession planning for local health department top executives: reducing risk to communities.

    Science.gov (United States)

    Schmalzried, Hans; Fallon, L Fleming

    2007-06-01

    This study assessed the degree to which local health departments (LHDs) are preparing to replace retiring top executives. Questionnaires were sent to all 134 local health departments in Ohio. It is typical of many states in terms of the organization of LHDs. Ninety-two LHD top executives responded. The questionnaire addressed aspects of departmental succession planning and demographic parameters of their departments. Approximately half (51.7%) of responding LHD top executives rated having succession plans as being important. Overall, local boards of health are not very concerned about actually having a succession plan. One in four (27.6%) local health departments reported that they have succession plans. Half of those were grooming a successor. Succession planning is not a high priority among the majority of LHDs, despite the fact that 43.7% of top executives reported planning to leave their current position within six years. Experienced and continuous LHD leadership is important for strong responses to public health crises like major disease outbreaks and natural disasters. Having a succession plan in place that identifies how leadership voids are filled can help minimize risks to populations in an emergency.

  8. A Case Report of Successful Treatment of Recalcitrant Childhood Localized Scleroderma with Infliximab and Leflunomide

    OpenAIRE

    Ferguson, Ian D; Weiser, Peter; Torok, Kathryn S

    2015-01-01

    Herein we report successful treatment of an adolescent Caucasian female with severe progressive localized scleroderma (mixed subtype, including generalized morphea and linear scleroderma of the trunk/limb) using infliximab and leflunomide. The patient demonstrated improvement after the first 9 months of therapy based on her clinical examination, objective measures, and patient and parent global assessments. Infliximab is a potential treatment option for pediatric localized scleroderma patient...

  9. La proteína PthB de Xanthomonas axonopodis pv. manihotis es autoactiva en ensayos de doble hibrido

    Directory of Open Access Journals (Sweden)

    Gil Juliana

    2011-04-01

    Full Text Available La bacteriosis vascular de yuca producida por la bacteria Xanthomonas axonopodis pv. manihotis (Xam es uno de los factores limitantes para la producción de yuca. Dentro de los primeros factores de patogenicidad identificados en esta bacteria se encuentra el gen pthB. La proteína PthB pertenece a la familia de efectores PthA/AvrBs3, que se caracterizan por presentar dominios NLS (Nuclear Localization Signal y un dominio AAD (Acidic Activation Domain, lo cual sugiere que estas proteínas actúan como factores de transcripción. La identificación de las proteínas de yuca que interactúan con PthB permitiría dar luces sobre la función de esta proteína en la patogenicidad de esta bacteria. En este trabajo se clonó pthB en una fusión traduccional con el BD (Binding Domain del factor de transcripción GAL4. Después de transformar este constructo en una cepa de levadura, se observó autoactivación de los genes reporteros, incluso a concentraciones altas de 3-AT. La eliminación del primer, segundo o de los dos NLS y del AAD no eliminaron la capacidad de autoactivación de los genes reporteros mediada por PthB. Estos resultados indican la imposibilidad de su utilización en un tamizaje de una librería de ADNc de yuca para identificar las proteínas que interactúan con PthB.

  10. A Case Report of Successful Treatment of Recalcitrant Childhood Localized Scleroderma with Infliximab and Leflunomide.

    Science.gov (United States)

    Ferguson, Ian D; Weiser, Peter; Torok, Kathryn S

    2015-01-01

    Herein we report successful treatment of an adolescent Caucasian female with severe progressive localized scleroderma (mixed subtype, including generalized morphea and linear scleroderma of the trunk/limb) using infliximab and leflunomide. The patient demonstrated improvement after the first 9 months of therapy based on her clinical examination, objective measures, and patient and parent global assessments. Infliximab is a potential treatment option for pediatric localized scleroderma patients who have progression of disease or who are unable to tolerate the side effect profile of more standard systemic therapy. Larger longitudinal studies or case series are needed to confirm and further investigate infliximab's role in localized scleroderma.

  11. Cell-specific expression of the parathyroid hormone (PTH)/PTH-related peptide receptor gene in kidney from kidney-specific and ubiquitous promoters.

    Science.gov (United States)

    Amizuka, N; Lee, H S; Kwan, M Y; Arazani, A; Warshawsky, H; Hendy, G N; Ozawa, H; White, J H; Goltzman, D

    1997-01-01

    The kidney is the major site of expression of the PTH/PTH-related peptide receptor (PTHR) gene. Previously we have shown that the PTHR gene is expressed from two promoters in kidney, an upstream kidney-specific promoter (P1) and a downstream promoter (P2) that is active in a wide variety of tissues. Here, we have used immunohistochemical and transcript-specific in situ hybridization techniques to map the expression of the PTHR gene and protein and to determine the distribution of P1- and P2-driven messenger RNAs in renal tissue. Immunohistochemical and immunoelectron microscopic analysis showed that PTHR protein is expressed on both basolateral and luminal membranes of proximal tubular epithelial cells, strongly suggesting a bipolar mode of action of PTH. Receptor protein also was detected on the surface of glomerular podocytes. Strikingly, immunoelectron microscopic analysis showed that endothelial cells of the peritubular vasculature, but not the glomerular vasculature, contain high levels of PTHR protein. We found that both P1 and P2 are expressed at moderate levels in both cortical and medullary epithelial cells of nephrons, correlating well with the immunohistochemical localization of PTHR protein. However, although abundant transcripts were detected in peritubular endothelial cells with P1-specific and coding sequence probes, P2-specific expression was not observed in these cells. These results provide evidence that the physiological effects of PTH- and/or PTH-related peptide on renal tubular function may be mediated not only through direct effects on epithelial cells but also indirectly through endothelial cell-based signaling. In addition to expression in vascular endothelial cells, high levels of P1-specific, but not P2-specific, PTHR messenger RNA were detected in vascular smooth muscle. Taken together, these experiments provide evidence for strong PTHR gene expression in renal vascular tissues. Moreover, given that previous studies have shown that P2

  12. A Proposal on How to Make Educational Activities Deep-rooted in the Local Community Successful

    Science.gov (United States)

    Kaneshige, Akihiro; Momota, Masahiro; Sadano, Syuichiro; Ishitobi, Takaaki; Murashige, Kiyoshi

    The purpose of this paper is to propose what is necessary for institutions of higher education to succeed in contributive activities for the local community. First, an outline of status quo of such activities is provided. Next, a discussion of how our college plans, organizes and performs such activities with “the Planning and Coordination Office” and “the Division of Cooperation with the Local Community” as the central divisions will be offered. Following this, clarification of some of the problems to be solved in regard to the activities is discussed. Finally, it is argued that organizational and continuous approaches are essential to make the activities successful.

  13. Feasibility Study of a Standardized Novel Animal Model for Cervical Vertebral Augmentation in Sheep Using a PTH Derivate Bioactive Material

    Directory of Open Access Journals (Sweden)

    Karina Klein

    2014-08-01

    Full Text Available Prophylactic local treatment involving percutaneous vertebral augmentation using bioactive materials is a new treatment strategy in spine surgery in humans for vertebral bodies at risk. Standardized animal models for this procedure are almost non-existent. The purpose of this study was to: (i prove the efficacy of PTH derivate bioactive materials for new bone formation; and (ii create a new, highly standardized cervical vertebral augmentation model in sheep. Three different concentrations of a modified form of parathyroid hormone (PTH covalently bound to a fibrin matrix containing strontium carbonate were used. The same matrix without PTH and shams were used as controls. The bioactive materials were locally injected. Using a ventral surgical approach, a pre-set amount of material was injected under fluoroscopic guidance into the intertrabecular space of three vertebral bodies. Intravital fluorescent dyes were used to demonstrate new bone formation. After an observation period of four months, the animals were sacrificed, and vertebral bodies were processed for µCT, histomorphometry, histology and sequential fluorescence evaluation. Enhanced localized bone activity and new bone formation in the injected area could be determined for all experimental groups in comparison to the matrix alone and sham with the highest values detected for the group with a medium concentration of PTH.

  14. Altered Selectivity of Parathyroid Hormone (PTH) and PTH-Related Protein (PTHrP) for Distinct Conformations of the PTH/PTHrP Receptor

    OpenAIRE

    Dean, Thomas; Vilardaga, Jean-Pierre; Potts, John T.; Gardella, Thomas J

    2007-01-01

    PTH and PTHrP use the same G protein-coupled receptor, the PTH/PTHrP receptor (PTHR), to mediate their distinct biological actions. The extent to which the mechanisms by which the two ligands bind to the PTHR differ is unclear. We examined this question using several pharmacological and biophysical approaches. Kinetic dissociation and equilibrium binding assays revealed that the binding of [125I]PTHrP(1–36) to the PTHR was more sensitive to GTPγS (added to functionally uncouple PTHR-G protein...

  15. Local density regulates migratory songbird reproductive success through effects on double-brooding and nest predation.

    Science.gov (United States)

    Woodworth, Bradley K; Wheelwright, Nathaniel T; Newman, Amy E M; Norris, D Ryan

    2017-08-01

    Knowledge of the density-dependent processes that regulate animal populations is key to understanding, predicting, and conserving populations. In migratory birds, density-dependence is most often studied during the breeding season, yet we still lack a robust understanding of the reproductive traits through which density influences individual reproductive success. We used 27-yr of detailed, individual-level productivity data from an island-breeding population of Savannah sparrows Passerculus sandwichensis to evaluate effects of local and total annual population density on female reproductive success. Local density (number of neighbors within 50 m of a female's nest) had stronger effects on the number of young fledged than did total annual population density. Females nesting in areas of high local density were more likely to suffer nest predation and less likely to initiate and fledge a second clutch, which led to fewer young fledged in a season. Fledging fewer young subsequently decreased the likelihood of a female recruiting offspring into the breeding population in a subsequent year. Collectively, these results provide insight into the scale and reproductive mechanisms mediating density-dependent reproductive success and fitness in songbirds. © 2017 by the Ecological Society of America.

  16. Successful fetoscopic laser coagulation for twin-to-twin transfusion syndrome under local anaesthesia.

    LENUS (Irish Health Repository)

    Cooley, S

    2011-06-01

    A review of the efficacy and outcome of fifteen fetoscopic laser ablations under local anaesthesia for twin to twin transfusion syndrome (TTTS) in the National Maternity Hospital Dublin was undertaken. The mean gestation at laser was 19.7 weeks (range 16-25 weeks) with a mean gestation at delivery of 29.1 weeks (range 20-35 weeks). The overall liveborn birth rate was 79% (22 infants) and one pregnancy was still ongoing. There were four neonatal deaths secondary to complications of prematurity. The surviving eighteen infants (64%) undergo regular paediatric review. The procedure was performed successfully in all cases with local anaesthesia. In no case was there maternal discomfort that warranted the procedure to be abandoned and good visual access of the vascular anastamoses was obtained in all cases. Local anaesthesia therefore offers a safe effective anaesthetic option for fetoscopic laser coagulation in monochorionic pregnancies complicated by TTTS.

  17. Making Strategic Planning Work in Local Government: An Empirical Study of Success And Failure

    Directory of Open Access Journals (Sweden)

    Ángel IGLESIAS

    2015-10-01

    Full Text Available Since the 1990s, local governments all over Europe have launched reforms to improve local democracy, public management and efficiency in the provision of local services. Some of these reforms are inspired by what previously has worked in private management and some of them have also a macro-level approach, whose main aim is to introduce institutional reforms and reorganizations to ensure contextual problem solving by strengthening governance within the local public sector. In this context, Strategic Planning in public organizations has attracted interest among academic researchers and practitioners as an instrument for dealing with a complex environment and for the achievement of higher performance and the attainment of greater democracy. But the decision on how to introduce Strategic Planning might follow a different rationale. The hypothesis maintained in this paper is that those that are based in an endogenous rationale are more likely to succeed. To test our hypothesis this paper draws on a comparative empirical analysis concerning the design and implementation of a Strategic Planning process within two Spanish city governments: one considered to have been a failure and the other a success. Focusing on the way in which the use of Strategic Planning has to face the trade-offs between urban and economic development and democracy, the paper explores how this formal mechanism of citizen´s and business’ participation serves to establish relational processes to reinvigorate local economic development, democracy and administrative modernization only when a strong political and administrative leadership is put into motion. Overall, the study yields evidence consistent with the notion that a successful Strategic Planning at the local level has to take into account not only institutional issues, but also the communal, social and political resources that frame the deliberations propelled by the Strategic Planning process.

  18. Diabetic Foot Ulcers and Epidermal Growth Factor: Revisiting the Local Delivery Route for a Successful Outcome

    Directory of Open Access Journals (Sweden)

    Jorge Berlanga-Acosta

    2017-01-01

    Full Text Available Soon after epidermal growth factor (EGF discovery, some in vivo models appeared demonstrating its property to enhance cutaneous wound healing. EGF was the first growth factor (GF introduced in the clinical arena as a healing enhancer, exerting its mitogenic effects on epithelial, fibroblastoid, and endothelial cells via a tyrosine kinase membrane receptor. Compelling evidences from the 90s documented that, for EGF, locally prolonged bioavailability and hourly interaction with the receptor were necessary for a successful tissue response. Eventually, the enthusiasm on the clinical use of EGF to steer the healing process was wiped out as the topical route to deliver proteins started to be questioned. The simultaneous in vivo experiments, emphasizing the impact of the parenterally administered EGF on epithelial and nonepithelial organs in terms of mitogenesis and cytoprotection, rendered the theoretical fundamentals for the injectable use of EGF and shaped the hypothesis that locally infiltrating the diabetic ulcers would lead to an effective healing. Although the diabetic chronic wounds microenvironment is hostile for local GFs bioavailability, EGF local infiltration circumvented the limitations of its topical application, thus expanding its therapeutic prospect. Our clinical pharmacovigilance and basic studies attest the significance of the GF local infiltration for chronic wounds healing.

  19. Alliances for local development success factors. Comparative experiences of Spain and Peru

    Directory of Open Access Journals (Sweden)

    Elsa Del Castillo Mory

    2015-09-01

    Full Text Available Alliances are formed to overcome the constraints partners face to achieve certain goals. When the goal is to promote local development, it requires the participation of stakeholders: private sector, local government, civil associations and community groups, among others. This article seeks, through the comparative analysis of three experiences of local development led by the district of Villa El Salvador (Lima - Peru, the mining company Yanacocha (Cajamarca -Peru and the Spanish Agency for Development Iraugi Lantzen (Basque Country - Spain, to identify the success factors of cooperation agreements for local development. We believe that a better understanding of the factors associated with the success of partnerships could help those who seek the challenge of looking for possible partners, as well as those concerned with the effective management of partnerships in place. The case of Villa El Salvador shows how government support was fundamental in the establishment of the district, but the achievements of this group could not be explained without the active participation of the community. On the other hand, the experience of the company Yanacocha reminds the reader that there is still a big gap to fill in Peru in terms of the joint efforts between private enterprises and stakeholders, and that is necessary to learn from the experiences of those who have gone through part of this path. A different case is shown by the experience of the Spanish Agency Iraugi Lantzen, highlighting the challenges and opportunities that arise from a concerted action between municipal entities pursuing local development. Overall, it can be said that although there are context and situational conditions that favor the development of alliances for development, there are other factors that mediate the success of partnerships. The case studies show that the most successful cooperation experiences are those where there are key individuals that are leaders

  20. Protected Areas and Local Communities: an Inevitable Partnership toward Successful Conservation Strategies?

    Directory of Open Access Journals (Sweden)

    Gustavo S. M. Andrade

    2012-12-01

    Full Text Available Many protected areas (PAs have followed the conventional and exclusionary approach applied at Yellowstone in 1872. As such, many parks have failed to fully integrate other important factors, such as social, cultural, and political issues. In some cases, this has triggered adverse social impacts on local communities, disrupting their traditional ways of living and limiting their control of and access to natural resources. Such an outcome can undermine protection policies through conflicts between park managers and local communities. The success of conservation strategies through protected areas may lie in the ability of managers to reconcile biodiversity conservation goals with social and economic issues and to promote greater compliance of local communities with PA conservation strategies. However, there are very few quantitative studies identifying what the key factors are that lead to better compliance with PA conservation policies. To address this issue, we conducted a meta-analysis of 55 published case studies from developing countries to determine whether the level of compliance of local communities with PA regulations was related to: (1 PA age, (2 PA area, (3 the existence of a buffer zone, (4 the level of protection as defined by IUCN categories, (5 gross domestic product per capita, (6 population density in the vicinity of PAs, and (7 the level of local community participation in PA management. We found that local community participation in the PA decision-making process was the only variable that was significantly related to the level of compliance with PA polices. In general, the higher the level of participation, the higher the level of compliance. This has important implications for PA management and suggests that greater inclusion of local communities in management should be a key strategy for ensuring the integrity of PAs.

  1. Cinacalcet Reduces the Set Point of the PTH-Calcium Curve

    Science.gov (United States)

    Valle, Casimiro; Rodriguez, Mariano; Santamaría, Rafael; Almaden, Yolanda; Rodriguez, Maria E.; Cañadillas, Sagrario; Martin-Malo, Alejandro; Aljama, Pedro

    2008-01-01

    The calcimimetic cinacalcet increases the sensitivity of the parathyroid calcium-sensing receptor to calcium and therefore should produce a decrease in the set point of the parathyroid hormone (PTH)-calcium curve. For investigation of this hypothesis, nine long-term hemodialysis patients with secondary hyperparathyroidism were given cinacalcet for 2 mo, the dosage was titrated per a protocol based on intact PTH and plasma calcium concentrations. Dialysis against low- and high-calcium (0.75 and 1.75 mM) dialysate was used to generate curves describing the relationship between PTH and calcium. Compared with precinacalcet levels, cinacalcet significantly reduced mean serum calcium, intact PTH and whole PTH (wPTH; all P < 0.001). The set points for PTH-calcium curves were significantly reduced, and both maximum and minimum levels of PTH (intact and whole) were significantly decreased. The calcium-mediated inhibition of PTH secretion was more marked after cinacalcet treatment. In addition, cinacalcet shifted the inverse sigmoidal curve of wPTH/non-wPTH ratio versus calcium to the left (i.e., less calcium was required to reduce the wPTH/non-wPTH ratio). In conclusion, cinacalcet increases the sensitivity of the parathyroids to calcium, causing a marked reduction in the set point of the PTH-calcium curve, in hemodialysis patients with secondary hyperparathyroidism. PMID:18632847

  2. Space and social capital : The degree of locality in entrepreneurs' contacts and its consequences for firm success

    NARCIS (Netherlands)

    Schutjens, V.A.J.M.; Völker, B.G.M.

    2010-01-01

    Social capital is valuable for entrepreneurs starting a business. Although many small businesses are located at the entrepreneurs’ dwelling, little is known about entrepreneurs’ local ties and their relevance for firm success. Distinguishing between local and non-local social capital, this contribut

  3. Space and social capital : The degree of locality in entrepreneurs' contacts and its consequences for firm success

    NARCIS (Netherlands)

    Schutjens, V.A.J.M.; Völker, B.G.M.

    2010-01-01

    Social capital is valuable for entrepreneurs starting a business. Although many small businesses are located at the entrepreneurs’ dwelling, little is known about entrepreneurs’ local ties and their relevance for firm success. Distinguishing between local and non-local social capital, this

  4. Gene structure, transcripts and calciotropic effects of the PTH family of peptides in Xenopus and chicken

    Directory of Open Access Journals (Sweden)

    Power Deborah M

    2010-12-01

    Full Text Available Abstract Background Parathyroid hormone (PTH and PTH-related peptide (PTHrP belong to a family of endocrine factors that share a highly conserved N-terminal region (amino acids 1-34 and play key roles in calcium homeostasis, bone formation and skeletal development. Recently, PTH-like peptide (PTH-L was identified in teleost fish raising questions about the evolution of these proteins. Although PTH and PTHrP have been intensively studied in mammals their function in other vertebrates is poorly documented. Amphibians and birds occupy unique phylogenetic positions, the former at the transition of aquatic to terrestrial life and the latter at the transition to homeothermy. Moreover, both organisms have characteristics indicative of a complex system in calcium regulation. This study investigated PTH family evolution in vertebrates with special emphasis on Xenopus and chicken. Results The PTH-L gene is present throughout the vertebrates with the exception of placental mammals. Gene structure of PTH and PTH-L seems to be conserved in vertebrates while PTHrP gene structure is divergent and has acquired new exons and alternative promoters. Splice variants of PTHrP and PTH-L are common in Xenopus and chicken and transcripts of the former have a widespread tissue distribution, although PTH-L is more restricted. PTH is widely expressed in fish tissue but from Xenopus to mammals becomes largely restricted to the parathyroid gland. The N-terminal (1-34 region of PTH, PTHrP and PTH-L in Xenopus and chicken share high sequence conservation and the capacity to modify calcium fluxes across epithelia suggesting a conserved role in calcium metabolism possibly via similar receptors. Conclusions The parathyroid hormone family contains 3 principal members, PTH, PTHrP and the recently identified PTH-L. In teleosts there are 5 genes which encode PTHrP (2, PTH (2 and PTH-L and in tetrapods there are 3 genes (PTHrP, PTH and PTH-L, the exception is placental mammals which

  5. Identification of an RNA-binding protein that is phosphorylated by PTH and potentially mediates PTH-induced destabilization of Npt2a mRNA.

    Science.gov (United States)

    Murray, Rebecca D; Merchant, Michael L; Hardin, Ericka; Clark, Barbara; Khundmiri, Syed J; Lederer, Eleanor D

    2016-02-01

    Parathyroid hormone (PTH) is a key regulator of the expression and function of the type IIa sodium-phosphate cotransporter (Npt2a), the protein responsible for regulated renal phosphate reabsorption. We previously showed that PTH induces rapid decay of Npt2a mRNA through posttranscriptional mechanisms. We hypothesized that PTH-induced changes in RNA-binding protein (RBP) activity mediate the degradation of Npt2a mRNA. To address this aim, we treated opossum kidney (OK) cells, a PTH-sensitive proximal tubule cell culture model, with 100 nM PTH for 30 min and 2 h, followed by mass spectrometry characterization of the PTH-stimulated phosphoproteome. We identified 1,182 proteins differentially phosphorylated in response to PTH, including 68 RBPs. Preliminary analysis identified a phospho-RBP, hnRNPK-homology-type-splicing regulatory protein (KSRP), with predicted binding sites for the 3'-untranslated region (UTR) of Npt2a mRNA. Western blot analysis confirmed expression of KSRP in OK cells and showed PTH-dependent translocation to the nucleus. Immunoprecipitation of KSRP from control and PTH-treated cells followed by RNA isolation and RT-quantitative PCR analysis identified Npt2a mRNA from both control and PTH-treated KSRP pulldowns. Knockdown of KSRP followed by PTH treatment showed that KSRP is required for mediating PTH-stimulated reduction in sodium/hydrogen exchanger 3 mRNA, but not Npt2a mRNA. We conclude that 1) PTH is a major regulator of both transcription and translation, and 2) KSRP binds Npt2a mRNA but its role in PTH regulation of Npt2a mRNA is not clear.

  6. Distribution of genes for parathyroid hormone (PTH)-related peptide, Indian hedgehog, PTH receptor and patched in the process of experimental spondylosis in mice.

    Science.gov (United States)

    Nakase, Takanobu; Ariga, Kenta; Meng, Wenxiang; Iwasaki, Motoki; Tomita, Tetsuya; Myoui, Akira; Yonenobu, Kazuo; Yoshikawa, Hideki

    2002-07-01

    Little is known about the molecular mechanisms underlying the process of spondylosis. The authors determined the extent of genetic localization of major regulators of chondrogenesis such as Indian hedgehog (Ihh) and parathyroid hormone (PTH)-related peptide (PTHrP) and their receptors during the development of spondylosis in their previously established experimental mouse model. Experimental spondylosis was induced in 5-week-old ICR mice. The cervical spines were chronologically harvested, and histological sections were prepared. Messenger (m) RNA for PTHrP, Ihh, PTH receptor (PTHR; a receptor for PTHrP), patched (Ptc; a receptor for Ihh), bone morphogenetic protein (BMP)-6, and collagen type X (COL10; a marker for mature chondrocyte) was localized in the tissue sections by performing in situ hybridization. In the early stage, mRNA for COL10, Ihh, and BMP-6 was absent; however, mRNA for PTHrP, PTHR, and Ptc was detected in the anterior margin of the cervical discs. In the late stage, evidence of COL10 mRNA began to be detected, and transcripts for Ihh, PTHrP, and BMP-6 were localized in hypertrophic chondrocytes adjacent to the bone-forming area in osteophyte. Messenger RNA for Ptc and PTHR continued to localize at this stage. In control mice, expression of these genes was absent. The localization of PTHrP, Ihh, BMP-6, and the receptors PTHR and Ptc demonstrated in the present experimental model indicates the possible involvement of molecular signaling by PTHrP (through the PTHR), Ihh (through the Ptc), and BMP-6 in the regulation of chondrocyte maturation leading to endochondral ossification in spondylosis.

  7. Teriparatide (rhPTH) treatment in children with syndromic hypoparathyroidism.

    Science.gov (United States)

    Matarazzo, Patrizia; Tuli, Gerdi; Fiore, Ludovica; Mussa, Alessandro; Feyles, Francesca; Peiretti, Valentina; Lala, Roberto

    2014-01-01

    Subcutaneous recombinant human parathormone [rhPTH (1-34)] has been introduced for hypoparathyroidism treatment, allowing avoidance of vitamin D and calcium side effects. Our objective was to evaluate rhPTH (1-34) safety and efficacy in pediatric patients with genetically proved syndromic hypoparathyroidism. The study was a 2.5-year self-controlled trial on six pediatric patients (four males, two females, age 9.8±5.1 years) with syndromic hypoparathyroidism including three with autoimmune polyendocrinopathy candidiasis ectodermal dysplasia (APECED) syndrome, two with DiGeorge syndrome, and one with hypoparathyroidism-deafness-renal dysplasia syndrome. We compared patients' clinical and biochemical outcome of conventional treatment based on oral administration of calcium (1-1.5 g/day in three doses) plus oral calcitriol (6.5-33 ng/kg per day in two to three doses) with the outcome obtained with rhPTH (1-34) (teriparatide, 12.5 μg bid). Therapy shift was conducted introducing rhPTH (1-34) while progressively withdrawing calcium and vitamin D. Blood calcium, phosphorus, alkaline phosphatase, and urinary calcium-to-creatinine ratio (mg/mg) before and during rhPTH therapy were compared. rhPTH treatment allowed complete calcium and vitamin D withdrawal in two patients, calcium withdrawal in three and reduction of vitamin D dose in two. During rhPTH (1-34), mean blood calcium, phosphorus, and alkaline phosphatase were not significantly modified, whereas significant reduction of the calciuria-to-creatininuria ratio (0.55±0.31 vs. 0.1±0.1, p=0.02) was obtained. The number of tetanic episodes was reduced in four patients during teriparatide treatment compared to conventional treatment. In children with syndromic hypoparathyroidism, substitutive treatment with rhPTH (1-34) maintains adequate blood calcium levels and allows prompt normalization of urinary calcium excretion, through direct action on the kidney and through calcium and vitamin D therapy layoff.

  8. Dialysis membranes and PTH changes during hemodialysis in patients with secondary hyperparathyroidism.

    Science.gov (United States)

    De Francisco, A L; Amado, J A; Prieto, M; Alcalde, G; Sanz de Castro, S; Ruiz, J C; Morales, P; Arias, M

    1994-01-01

    Changes in parathyroid hormone (PTH) during hemodialysis have been explained by the influence of ionized calcium changes on PTH secretion. In this study we have investigated the influence of dialysis membranes of different permeability on PTH changes during hemodialysis. Five chronic renal failure patients underwent three consecutive hemodialysis sessions with cuprophane (CUP) polysulfone (PS) and polyacrylonitrile (PAN). Two hours of isolated ultrafiltration were followed by 3 h dialysis. A significant decrease in carboxy terminal PTH (COOH PTH) was observed with PAN (p < 0.05) but not with CUP or PS. Intact PTH decreased (p < 0.001) with all three membranes, following a significant increase in ionized calcium (p < 0.001). Sieving coefficients for COOH PTH were significantly lower with CUP than with PS (p < 0.05) or PAN (p < 0.001). Intact PTH sieving coefficients were near zero for all three membranes. COOH PTH and intact PTH clearance rates were significantly higher with PAN (p < 0.001) than with PS or CUP, either in isolated ultrafiltration or with dialysis fluid. Thus PTH changes during hemodialysis do not only depend on the increase in calcium but also on the nature of the dialysis membrane. Adsorption of PTH to the PAN membrane surface explain the high PTH clearance rates achieved with this filter.

  9. Acute and chronic regulation of circulating PTH: significance in health and in disease.

    Science.gov (United States)

    D'Amour, Pierre

    2012-08-01

    Circulating human parathyroid hormone (PTH) is immunoheterogenous. It is composed of 80% carboxyl-terminal (C) fragments and of 20% PTH(1-84). This composition contrasts with the biological activity of the hormone, which is only related to PTH(1-84), creating a paradox between circulating PTH composition and PTH bioactivity. PTH molecular forms are either secreted by the parathyroid glands or generated by the peripheral metabolism of PTH(1-84) in the liver. The kidney has a major role in the disposal of C-PTH fragments. Secretion of PTH molecular forms by the parathyroid glands is highly regulated under a variety of clinical conditions, suggesting that C-PTH fragments could exert some biological effects of their own. Recent data suggest that C-PTH fragments can exert biological actions opposite to those of PTH(1-84) by acting on a C-PTH receptor not yet cloned. They can decrease calcium concentration, phosphate excretion, bone resorption and 1,25(OH)₂ synthesis. The clinical implications of this new concept are reviewed.

  10. Phospholipase C signaling via the parathyroid hormone (PTH)/PTH-related peptide receptor is essential for normal bone responses to PTH.

    Science.gov (United States)

    Guo, Jun; Liu, Minlin; Yang, Dehong; Bouxsein, Mary L; Thomas, Clare C; Schipani, Ernestina; Bringhurst, F Richard; Kronenberg, Henry M

    2010-08-01

    We have previously shown that differentiation of hypertrophic chondrocytes is delayed in mice expressing a mutated PTH/PTHrP receptor (PTHR) (called DSEL here) that stimulates adenylyl cyclase normally but fails to activate phospholipase C (PLC). To better understand the role of PLC signaling via the PTHR in skeletal and mineral homeostasis, we examined these mice fed a normal or calcium-deficient diet. On a standard diet, DSEL mice displayed a modest decrease in bone mass. Remarkably, when fed a low-calcium diet or infused with PTH, DSEL mice exhibited strikingly curtailed peritrabecular stromal cell responses and attenuated new bone formation when compared with Wt mice. Attenuated in vitro colony formation was also observed in bone marrow cells derived from DSEL mice fed a low-calcium diet. Furthermore, PTH stimulated proliferation and increased mRNAs encoding cyclin D1 in primary osteoblasts derived from Wt but not from DSEL mice. Our data indicate that PLC signaling through the PTHR is required for skeletal homeostasis.

  11. How national context, project design, and local community characteristics influence success in community-based conservation projects.

    Science.gov (United States)

    Brooks, Jeremy S; Waylen, Kerry A; Borgerhoff Mulder, Monique

    2012-12-26

    Community-based conservation (CBC) promotes the idea that conservation success requires engaging with, and providing benefits for, local communities. However, CBC projects are neither consistently successful nor free of controversy. Innovative recent studies evaluating the factors associated with success and failure typically examine only a single resource domain, have limited geographic scope, consider only one outcome, or ignore the nested nature of socioecological systems. To remedy these issues, we use a global comparative database of CBC projects identified by systematic review to evaluate success in four outcome domains (attitudes, behaviors, ecological, economic) and explore synergies and trade-offs among these outcomes. We test hypotheses about how features of the national context, project design, and local community characteristics affect these measures of success. Using bivariate analyses and multivariate proportional odds logistic regressions within a multilevel analysis and model-fitting framework, we show that project design, particularly capacity-building in local communities, is associated with success across all outcomes. In addition, some characteristics of the local community in which projects are conducted, such as tenure regimes and supportive cultural beliefs and institutions, are important for project success. Surprisingly, there is little evidence that national context systematically influences project outcomes. We also find evidence of synergies between pairs of outcomes, particularly between ecological and economic success. We suggest that well-designed and implemented projects can overcome many of the obstacles imposed by local and national conditions to succeed in multiple domains.

  12. In vivo transcription of two promoters, PTH4 and PTH270 involved in regulation of Streptomyces differentiation

    Institute of Scientific and Technical Information of China (English)

    谭华荣; 田宇清; 杨海花; 吴畏; 董可宁; Keith F.Chater

    1997-01-01

    The promoters, PTH4 and P-TH270 involved in the regulation of Streptomyces coelicolor differentiation were subcloned into Streptomyces promoter, i.e. probe plasmid pIJ4083, and the recombinant plasmids, pIJ4470 and pIJ4471, were constructed. Two promoters could drive the expression of reporter gene encoding catechol dioxygenase when pIJ4470 and pIJ4471 were introduced into some white mutants (C85, C70, C71, C17 and C119). The total RNA was isolated from these strains containing recombinant plasmid. Probes were prepared by labelling 5 -ends of PTH4 AND PTH270 DNA fragments using radioisotope. DNA - RNA hybridization was carried out with the probes and RNAs isolated from different strains. The S1 mapping result showed that all RNAs from strains of C85/pIJ4470, C85/4471, C70/pIJ4470, C70/pIJ4471 and C17/pIJ4470 as well as C17/pIJ4471 gave rise to strong positive hy-bridization signal, whereas RNAs from C71/pIJ4470 and C71/pIJ4471 did not give any positive signal. RNAs from C119/pIJ4470 and C119/pIJ4471 gav

  13. Sequential treatment with basic fibroblast growth factor and PTH is more efficacious than treatment with PTH alone for increasing vertebral bone mass and strength in osteopenic ovariectomized rats

    DEFF Research Database (Denmark)

    Iwaniec, U.T.; Mosekilde, Li.; Mitova-Caneva, N.G.

    2002-01-01

    The study was designed 1) to determine whether treatment with basic fibroblast growth factor (bFGF) and PTH is more efficacious than treatment with PTH alone for increasing bone mass and strength and improving trabecular microarchitecture in osteopenic ovariectomized rats, and 2) to assess whether...... prior and concurrent administration of the antiresorptive agents estrogen and risedronate suppresses the bone anabolic response to treatment with bFGF alone and sequential treatment with bFGF and PTH. Three-month-old female Sprague Dawley rats were ovariectomized (OVX) or sham-operated (sham...... of OVX rats with PTH alone increased vertebral cancellous bone mass and strength to the level of vehicle-treated sham rats. Sequential treatment of OVX rats with bFGF and PTH further augmented vertebral bone mass and strength to a level above that observed in OVX rats treated with PTH alone...

  14. PTH1 receptor is involved in mediating cellular response to long-chain polyunsaturated fatty acids.

    Directory of Open Access Journals (Sweden)

    Jose Candelario

    Full Text Available The molecular pathways by which long chain polyunsaturated fatty acids (LCPUFA influence skeletal health remain elusive. Both LCPUFA and parathyroid hormone type 1 receptor (PTH1R are known to be involved in bone metabolism while any direct link between the two is yet to be established. Here we report that LCPUFA are capable of direct, PTH1R dependent activation of extracellular ligand-regulated kinases (ERK. From a wide range of fatty acids studied, varying in chain length, saturation, and position of double bonds, eicosapentaenoic (EPA and docosahexaenoic fatty acids (DHA caused the highest ERK phosphorylation. Moreover, EPA potentiated the effect of parathyroid hormone (PTH(1-34 in a superagonistic manner. EPA or DHA dependent ERK phosphorylation was inhibited by the PTH1R antagonist and by knockdown of PTH1R. Inhibition of PTH1R downstream signaling molecules, protein kinases A (PKA and C (PKC, reduced EPA and DHA dependent ERK phosphorylation indicating that fatty acids predominantly activate G-protein pathway and not the β-arrestin pathway. Using picosecond time-resolved fluorescence microscopy and a genetically engineered PTH1R sensor (PTH-CC, we detected conformational responses to EPA similar to those caused by PTH(1-34. PTH1R antagonist blocked the EPA induced conformational response of the PTH-CC. Competitive binding studies using fluorescence anisotropy technique showed that EPA and DHA competitively bind to and alter the affinity of PTH1 receptor to PTH(1-34 leading to a superagonistic response. Finally, we showed that EPA stimulates protein kinase B (Akt phosphorylation in a PTH1R-dependent manner and affects the osteoblast survival pathway, by inhibiting glucocorticoid-induced cell death. Our findings demonstrate for the first time that LCPUFAs, EPA and DHA, can activate PTH1R receptor at nanomolar concentrations and consequently provide a putative molecular mechanism for the action of fatty acids in bone.

  15. Functional characterization and evolution of PTH/PTHrP receptors: insights from the chicken

    Directory of Open Access Journals (Sweden)

    Pinheiro Pedro LC

    2012-07-01

    Full Text Available Abstract Background The parathyroid hormone (PTH-family consists of a group of structurally related factors that regulate calcium and bone homeostasis and are also involved in development of organs such as the heart, mammary gland and immune system. They interact with specific members of family 2 B1 G-protein coupled receptors (GPCRs, which have been characterised in teleosts and mammals. Two PTH/PTHrP receptors, PTH1R and PTH2R exist in mammals and in teleost fish a further receptor PTH3R has also been identified. Recently in chicken, PTH-family members involved in calcium transport were characterized and specific PTHRs are suggested to exist although they have not yet been isolated or functionally characterized. The aim of this study is to further explore the evolution and function of the vertebrate PTH/PTHrP system through the isolation, phylogenetic analysis and functional characterization of the chicken receptors. Results Two PTHRs were isolated in chicken and sequence comparison and phylogenetic analysis indicate that the chicken receptors correspond to PTH1R and PTH3R, which emerged prior to the teleost/tetrapod divergence since they are present in cartilaginous fish. The vertebrate PTH2R receptor and its ligand TIP39 have been lost from bird genomes. Chicken PTH1R and PTH3R have a divergent and widespread tissue expression and are also evident in very early embryonic stages of development. Receptor stimulation studies using HEK293 cells stably expressing the chicken PTH1R and PTH3R and monitoring cAMP production revealed they are activated by chicken 1–34 N-terminal PTH-family peptides in a dose dependent manner. PTH-L and PTHrP were the most effective peptides in activating PTH1R (EC50 = 7.7 nM and EC50 = 22.7 nM, respectively. In contrast, PTH-L (100 nM produced a small cAMP accumulation on activation of PTH3R but PTHrP and PTH (EC50 = 2.5 nM and EC50 = 22.1 nM, respectively readily activated the receptor. PTHr

  16. Successful preoperative diagnosis of the localization of adenoma of the parathyroid gland by scintiscan

    Energy Technology Data Exchange (ETDEWEB)

    Takei, Ko; Shirasu, Nobuhiko; Kobayashi, Katsumi; Komatsu, Hideki; Ueno, Akira; Uchiyama, Akira

    1985-02-01

    Successful preoperative diagnosis of the localization of adenoma of the parathyroid in 59-year-old female with hyperparathyroidism by means of double tracer scanning and computerized image subtraction was described. She had been suffering from recurrent urolithiasis and was referred to our clinic because of hypercalcemia and hypophosphatemia in November 1983. The level of serum calcium was 11.2 mg/dl and inorganic serum phosphorus 2.1 mg/dl. The activity of serum alkaline phosphatase was within normal limits. Urinary calcium excretion was elevated to the level of 262 mg/day under low calcium diet (300 mg/day). CT scan could not detect adenoma of the parathyroid. Double tracer scanning with S TI as chloride salt and /sup 99m/Tc as pertechnatate and computerized image subtraction showed abnormal thallium uptake about the lower portion of the right lobe of the thyroid gland. Neck exploration revealed a parathyroid adenoma, weighing 1.0 g behind the right lobe of the thyroid gland as was demonstrated by the preoperative subtracted scintiscan. Convalescence was uneventful and the level of serum calcium and urinary calcium excretion was normalized.

  17. Mapping single molecule sequencing reads using basic local alignment with successive refinement (BLASR: application and theory

    Directory of Open Access Journals (Sweden)

    Chaisson Mark J

    2012-09-01

    Full Text Available Abstract Background Recent methods have been developed to perform high-throughput sequencing of DNA by Single Molecule Sequencing (SMS. While Next-Generation sequencing methods may produce reads up to several hundred bases long, SMS sequencing produces reads up to tens of kilobases long. Existing alignment methods are either too inefficient for high-throughput datasets, or not sensitive enough to align SMS reads, which have a higher error rate than Next-Generation sequencing. Results We describe the method BLASR (Basic Local Alignment with Successive Refinement for mapping Single Molecule Sequencing (SMS reads that are thousands of bases long, with divergence between the read and genome dominated by insertion and deletion error. The method is benchmarked using both simulated reads and reads from a bacterial sequencing project. We also present a combinatorial model of sequencing error that motivates why our approach is effective. Conclusions The results indicate that it is possible to map SMS reads with high accuracy and speed. Furthermore, the inferences made on the mapability of SMS reads using our combinatorial model of sequencing error are in agreement with the mapping accuracy demonstrated on simulated reads.

  18. Modifications in Bone Matrix of Estrogen-Deficient Rats Treated with Intermittent PTH

    Directory of Open Access Journals (Sweden)

    Rafael Pacheco-Costa

    2015-01-01

    Full Text Available Bone matrix dictates strength, elasticity, and stiffness to the bone. Intermittent parathyroid hormone (iPTH, a bone-forming treatment, is widely used as a therapy for osteoporosis. We investigate whether low doses of intermittent PTH (1-34 change the profile of organic components in the bone matrix after 30 days of treatment. Forty 6-month-old female Wistar rats underwent ovariectomy and after 3 months received low doses of iPTH administered for 30 days: daily at 0.3 µg/kg/day (PTH03 or 5 µg/kg/day (PTH5; or 3 times per week at 0.25 µg/kg/day (PTH025. After euthanasia, distal femora were processed for bone histomorphometry, histochemistry for collagen and glycosaminoglycans, biochemical quantification of sulfated glycosaminoglycans, and hyaluronan by ELISA and TUNEL staining. Whole tibiae were used to estimate the bone mineral density (BMD. Histomorphometric analysis showed that PTH5 increased cancellous bone volume by 6% over vehicle-treated rats. In addition, PTH5 and PTH03 increased cortical thickness by 21% and 20%, respectively. Tibial BMD increased in PTH5-treated rats and this group exhibited lower levels of chondroitin sulfate; on the other hand, hyaluronan expression was increased. Hormonal administration in the PTH5 group led to decreased collagen maturity. Further, TUNEL-positive osteocytes were decreased in the cortical compartment of PTH5 whereas administration of PTH025 increased the osteocyte death. Our findings suggest that daily injections of PTH at low doses alter the pattern of organic components from the bone matrix, favoring the increase of bone mass.

  19. Deletion of PTH rescues skeletal abnormalities and high osteopontin levels in Klotho-/- mice.

    Directory of Open Access Journals (Sweden)

    Quan Yuan

    Full Text Available Maintenance of normal mineral ion homeostasis is crucial for many biological activities, including proper mineralization of the skeleton. Parathyroid hormone (PTH, Klotho, and FGF23 have been shown to act as key regulators of serum calcium and phosphate homeostasis through a complex feedback mechanism. The phenotypes of Fgf23(-/- and Klotho(-/- (Kl(-/- mice are very similar and include hypercalcemia, hyperphosphatemia, hypervitaminosis D, suppressed PTH levels, and severe osteomalacia/osteoidosis. We recently reported that complete ablation of PTH from Fgf23(-/- mice ameliorated the phenotype in Fgf23(-/-/PTH(-/- mice by suppressing serum vitamin D and calcium levels. The severe osteomalacia in Fgf23(-/- mice, however, persisted, suggesting that a different mechanism is responsible for this mineralization defect. In the current study, we demonstrate that deletion of PTH from Kl(-/- (Kl(-/-/PTH(-/- or DKO mice corrects the abnormal skeletal phenotype. Bone turnover markers are restored to wild-type levels; and, more importantly, the skeletal mineralization defect is completely rescued in Kl(-/-/PTH(-/- mice. Interestingly, the correction of the osteomalacia is accompanied by a reduction in the high levels of osteopontin (Opn in bone and serum. Such a reduction in Opn levels could not be observed in Fgf23(-/-/PTH(-/- mice, and these mice showed sustained osteomalacia. This significant in vivo finding is corroborated by in vitro studies using calvarial osteoblast cultures that show normalized Opn expression and rescued mineralization in Kl(-/-/PTH(-/- mice. Moreover, continuous PTH infusion of Kl(-/- mice significantly increased Opn levels and osteoid volume, and decreased trabecular bone volume. In summary, our results demonstrate for the first time that PTH directly impacts the mineralization disorders and skeletal deformities of Kl(-/-, but not of Fgf23(-/- mice, possibly by regulating Opn expression. These are significant new perceptions into

  20. LA PROTEÍNA PTHB DE Xanthomonas axonopodis pv. Manihotis ES AUTOACTIVA EN ENSAYOS DE DOBLE HÍBRIDO The PthB Protein from Xanthomonas axonopodis pv. Manihotis is an Autoactive in Yeast Two-Hybrid Assays

    Directory of Open Access Journals (Sweden)

    JULIANA GIL

    Full Text Available La bacteriosis vascular de yuca producida por la bacteria Xanthomonas axonopodis pv. manihotis (Xam es una enfermedad limitante para la producción de yuca. Dentro de los primeros factores de patogenicidad identificados en esta bacteria se encuentra el gen PthB. La proteína PthB pertenece a la familia de efectores PthA/AvrBs3, que se caracterizan por presentar dominios NLS (Nuclear Localization Signal y un dominio AAD (Acidic Activation Domain, lo cual sugiere que estas proteínas actúan como factores de transcripción. La identificación de las proteínas de yuca que interactúan con PthB permitiría dar luces sobre la función de esta proteína en la patogenicidad de esta bacteria. En este trabajo se clonó PthB en una fusión traduccional con el BD (Binding Domain del factor de transcripción GAL4. Después de transformar este constructo en una cepa de levadura, se observó autoactivación de los genes reporteros, incluso a concentraciones altas de 3-AT. La eliminación del primer, segundo o de los dos NLS y del AAD no eliminaron la capacidad de autoactivación de los genes reporteros mediada por PthB. Estos resultados indican la imposibilidad de su utilización en un tamizaje de una librería de ADNc de yuca para identificar las proteínas que interactúan con PthB.Cassava bacterial blight disease is caused by the gram-negative bacteria Xanthomonas axonopodis pv. manihotis (Xam, and constitutes one of the most important constraints for cassava production. One of the first determinants of pathogenicity identified in this bacterium is the PthB gene. The PthB protein belongs to the PthA/AvrBs3 family, characterized by the presence of Nuclear Localization Signal (NLS and Acidic Activation (AAD domains, suggesting that these proteins are transcription factors. The identification of cassava proteins interacting with PthB could give insights about the function of this protein in the pathogenicity of this bacterium. In this work we cloned PthB in

  1. Response to local anaesthetic injection as a predictor of successful hip surgery.

    Science.gov (United States)

    Odoom, J E; Allen, G M; Wilson, D J

    1999-07-01

    To compare the outcome of hip therapy with the response to local anaesthetic into the hip. A retrospective hip arthrographic study of 60 patients complaining of hip pain was performed. The average age of the patients was 58 +/- 20 years with ratio of men to women of 11:19. Thirty-eight of these patients underwent local anaesthetic intracapsular injection. Twenty-three (61%) obtained relief from pain whereas two (5%) experienced worsened pain. Of the 23 patients who experienced pain relief 17 (74%) had a positive post-operative course, in comparison with eight (44%) who had a positive post-operative course from the group where intra-articular local anaesthetic was not used. It was also noted that patients over 30 years of age had favourable post-operative results in the presence or absence of local anaesthetic testing. These results indicate that hip arthrography with a pain relieving intracapsular local anaesthetic injection, is a positive post-operative prognostic factor in a patient group of disparate disorders. A positive response to local anaesthetic injection into a hip may predict which patients are likely to respond well to surgery. We advise alterations to the consent procedure to add a warning concerning the small risk of increased hip pain. If further studies were to confirm our results it may be wise to recommend that local anaesthetic intracapsular injection and judgement of its efficacy should precede many surgical procedures involving the hip.

  2. Mechanisms of ligand binding to the parathyroid hormone (PTH)/PTH-related protein receptor: selectivity of a modified PTH(1-15) radioligand for GalphaS-coupled receptor conformations.

    Science.gov (United States)

    Dean, Thomas; Linglart, Agnes; Mahon, Matthew J; Bastepe, Murat; Jüppner, Harald; Potts, John T; Gardella, Thomas J

    2006-04-01

    Mechanisms of ligand binding to the PTH/PTHrP receptor (PTHR) were explored using PTH fragment analogs as radioligands in binding assays. In particular, the modified amino-terminal fragment analog, (125)I-[Aib(1,3),Nle8,Gln10,homoarginine11,Ala12,Trp14,Tyr15]rPTH(1-15)NH2, (125)I-[Aib(1,3),M]PTH(1-15), was used as a radioligand that we hypothesized to bind solely to the juxtamembrane (J) portion of the PTHR containing the extracellular loops and transmembrane helices. We also employed (125)I-PTH(1-34) as a radioligand that binds to both the amino-terminal extracellular (N) and J domains of the PTHR. Binding was examined in membranes derived from cells expressing either wild-type or mutant PTHRs. We found that the binding of (125)I-[Aib(1,3),M]PTH(1-15) to the wild-type PTHR was strongly (approximately 90%) inhibited by guanosine 5'-O-(3-thio)triphosphate (GTPgammaS), whereas the binding of (125)I-PTH(1-34) was only mildly (approximately 25%) inhibited by GTPgammaS. Of these two radioligands, only (125)I-[Aib(1,3),M]PTH(1-15) bound to PTHR-delNt, which lacks most of the receptor's N domain, and again this binding was strongly inhibited by GTPgammaS. Binding of (125)I-[Aib(1,3),M]PTH(1-15) to the constitutively active receptor, PTHR-H223R, was only mildly (approximately 20%) inhibited by GTPgammaS, as was the binding of (125)I-PTH(1-34). In membranes prepared from cells lacking Galpha(S) via knockout mutation of Gnas, no binding of (125)I-[Aib(1,3),M]PTH(1-15) was observed, but binding of (125)I-[Aib(1,3),M]PTH(1-15) was recovered by virally transducing the cells to heterologously express Galpha(S). (125)I-PTH(1-34) bound to the membranes with or without Galpha(S). The overall findings confirm the hypothesis that (125)I-[Aib(1,3),M]PTH(1-15) binds solely to the J domain of the PTHR. They further show that this binding is strongly dependent on coupling of the receptor to Galpha(S)-containing heterotrimeric G proteins, whereas the binding of (125)I-PTH(1-34) can occur

  3. Mechanisms of Ligand Binding to the Parathyroid Hormone (PTH)/PTH-Related Protein Receptor: Selectivity of a Modified PTH(1–15) Radioligand for GαS-Coupled Receptor Conformations

    Science.gov (United States)

    Dean, Thomas; Linglart, Agnes; Mahon, Matthew J.; Bastepe, Murat; Jüppner, Harald; Potts, John T.; Gardella, Thomas J.

    2011-01-01

    Mechanisms of ligand binding to the PTH/PTHrP receptor (PTHR) were explored using PTH fragment analogs as radioligands in binding assays. In particular, the modified amino-terminal fragment analog, 125I-[Aib1,3,Nle8,Gln 10,homoarginine11,Ala12 Trp14,Tyr15]rPTH(1–15)NH2, 125I-[Aib1,3,M]PTH(1–15), was used as a radioligand that we hypothesized to bind solely to the juxtamembrane (J) portion of the PTHR containing the extracellular loops and transmembrane helices. We also employed 125I-PTH(1– 34) as a radioligand that binds to both the amino-terminal extracellular (N) and J domains of the PTHR. Binding was examined in membranes derived from cells expressing either wild-type or mutant PTHRs. We found that the binding of 125I-[Aib1,3,M]PTH(1–15) to the wild-type PTHR was strongly (∼90%) inhibited by guanosine 5′-O-(3-thio)triphosphate (GTPγS), whereas the binding of 125I-PTH(1–34) was only mildly (∼25%) inhibited by GTPγS. Of these two radioligands, only 125I-[Aib1,3,M]PTH(1–15) bound to PTHR-delNt, which lacks most of the receptor's N domain, and again this binding was strongly inhibited by GTPγS. Binding of 125I-[Aib1,3,M]PTH(1–15) to the constitutively active receptor, PTHR-H223R, was only mildly (∼20%) inhibited by GTPγS, as was the binding of 125I-PTH(1–34). In membranes prepared from cells lacking GαS via knockout mutation of Gnas, no binding of 125I-[Aib1,3,M]PTH(1–15) was observed, but binding of 125I-[Aib1,3,M]PTH(1–15) was recovered by virally transducing the cells to heterologously express GαS. 125I-PTH(1–34) bound to the membranes with or without GαS. The overall findings confirm the hypothesis that 125I-[Aib1,3,M]PTH(1–15) binds solely to the J domain of the PTHR. They further show that this binding is strongly dependent on coupling of the receptor to GαS-containing heterotrimeric G proteins, whereas the binding of 125I-PTH(1–34) can occur in the absence of such coupling. Thus, 125I-[Aib1,3,M]PTH(1–15) appears to

  4. Bifunctional bisphosphonates for delivering PTH (1-34) to bone mineral with enhanced bioactivity.

    Science.gov (United States)

    Yewle, Jivan N; Puleo, David A; Bachas, Leonidas G

    2013-04-01

    The objective of this work was to demonstrate the bioactivity of parathyroid hormone (1-34) (PTH) delivered through a single molecule of bisphosphonate to improve tissue/cell interactions. Bifunctional hydrazine-bisphosphonates (HBPs) with varying length and lipophilicity were used as a drug delivery vehicle. PTH was oxidized with periodate treatment to obtain an N-terminal aldehyde that was then conjugated to HBPs. The toxicity and apoptotic properties of HBPs and HBP-PTH conjugates were studied with macrophages (RAW 264.7). It was found that one of the HBPs had significant apoptotic characteristics similar to alendronate, which is a widely prescribed drug in the treatment of osteoporosis. The improved binding affinity of PTH following conjugation to HBP was determined using a hydroxyapatite binding assay. The amount of PTH delivered to bone through HBPs was not affected by the length or lipophilicity of the HBPs. Furthermore, the improved bioactivity of PTH delivered to bone through HBPs, in comparison to adsorbed PTH, was demonstrated by quantifying the cAMP produced by pre-osteoblastic (MC3T3-E1) cells in response to PTH. The delivery of bioactive PTH to bone tissue by HBP conjugation demonstrates the potential use of HBPs in delivering therapeutic macromolecules to bone for the treatment of several skeletal diseases. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. The Anabolic Effect of PTH on Bone is Attenuated by Simultaneous Glucocorticoid Treatment

    DEFF Research Database (Denmark)

    Oxlund, Hans; Ørtoft, Gitte; Thomsen, Jesper Skovhus;

    2006-01-01

    a pronounced increase in the endocortical bone formation rate (BFR) and a smaller increase in periosteal BFR. The combination of PTH + GC resulted in a partial inhibition of the PTH-induced increase in bone formation. Serum-osteocalcin was increased by 65% in the PTH group and reduced by 39% in the GC group....... The pronounced anabolic effect of PTH injections on the endocortical and trabecular bone surfaces and less pronounced anabolic effect on periosteal surfaces were partially inhibited, but not prevented, by simultaneous GC treatment in old rats. Both cortical and cancellous bone possessed full mechanical...

  6. Novel mutations in PTH1R associated with primary failure of eruption and osteoarthritis.

    Science.gov (United States)

    Frazier-Bowers, S A; Hendricks, H M; Wright, J T; Lee, J; Long, K; Dibble, C F; Bencharit, S

    2014-02-01

    Autosomal dominant mutations in PTH1R segregate with primary failure of eruption (PFE), marked by clinical eruption failure of adult teeth without mechanical obstruction. While the diagnosis of PFE conveys a poor dental prognosis, there are no reports of PFE patients who carry PTH1R mutations and exhibit any other skeletal problems. We performed polymerase chain reaction-based mutational analysis of the PTH1R gene to determine the genetic contribution of PTH1R in 10 families with PFE. Sequence analysis of the coding regions and intron-exon boundaries of the PTH1R gene in 10 families (n = 54) and 7 isolated individuals revealed 2 novel autosomal dominant mutations in PTH1R (c.996_997insC and C.572delA) that occur in the coding region and result in a truncated protein. One family showed incomplete penetrance. Of 10 families diagnosed with PFE, 8 did not reveal functional (nonsynonymous) mutations in PTH1R; furthermore, 4 families and 1 sporadic case carried synonymous single-nucleotide polymorphisms. Five PFE patients in 2 families carried PTH1R mutations and presented with osteoarthritis. We propose that the autosomal dominant mutations of PTH1R that cause PFE may also be associated with osteoarthritis; a dose-dependent model may explain isolated PFE and osteoarthritis in the absence of other known symptoms in the skeletal system.

  7. Acetate free citrate-containing dialysate increase intact-PTH and BAP levels in the patients with low intact-PTH

    Directory of Open Access Journals (Sweden)

    Kuragano Takahiro

    2013-01-01

    Full Text Available Abstract Background Recently, acetate-free citrate containing dialysate (A(−D was developed. We have already reported about the significant effect of A(−D on metabolic acidosis, anemia, and malnutrition in maintenance hemodialysis (MHD patients. In this study, we compared the effect of A(−D and acetate containing dialysate (A(+D on serum calcium and intact-parathyroid hormone (int-PTH levels. Method Single session study: Seventeen patients were treated with A(+D in one session and also treated with A(−D in another session. Serum levels of pH, HCO3-, total (t-calcium, ionized (i-calcium, and int-PTH were evaluated at the beginning and the end of each session. Cross over study: A total of 29 patients with MHD were treated with A(+D for 4 months, switched to A(−D for next 4 months, and returned to A(+D for the final 4 months. Results In single session study, serum i-calcium and t-calcium levels significantly increased, and int-PTH levels decreased after HD with A(+D, whereas HD with A(−D did not affect iCa and int-PTH. In cross over study, if all patients were analyzed, there was no significant difference in serum int-PTH or bone alkaline phosphatase (BAP levels during each study period. In contrast, in the patients with low int-PTH ( Conclusion A(−D containing citrate could affect calcium and PTH levels, and, in 4 month period of crossover study, increased int-PTH levels pararelled with increasing BAP levels, exclusively in MHD patients with low int-PTH levels.

  8. The role of preoperative ultrasonography, computed tomography, and sestamibi scintigraphy localization in secondary hyperparathyroidism

    Science.gov (United States)

    Lee, Jae Bok; Kim, Woo Young

    2015-01-01

    Purpose The role of preoperative localization studies is controversial in surgery of secondary hyperparathyroidism (sHPT). The aim of study was to evaluate the accuracy of preoperative ultrasonography (USG), CT, and 99mTc sestamibi scintigraphy (MIBI) in localizing enlarged parathyroid glands and to find the impact of correct localization in successful parathyroidectomy. Methods We compared operative findings with the preoperative localization of ultrasonography, computerized tomography and sestamibi scintigraphy in 109 patients with sHPT and identified well-visualized locations of abnormal parathyroid glands by evaluating the sensitivity of each imaging study with regard to typical locations of glands. We investigated the effect of preoperative imaging localization on the surgical outcomes by measuring the intraoperative parathyroid hormone (ioPTH) decrement for positive or negative imaging localization. Results USG (91.5%) had the highest sensitivity and MIBI (56.1%) had the lowest among 3 modalities. The sensitivity of combined USG and CT (95.0%) was the highest among combined 2 modalities. The combination of all 3 modalities (95.4%) had the highest sensitivity among the combinations of modalities. The reduction of ioPTH in patients with positive imaging localization (86.6%) was greater than negative imaging localization (84.2%), with no significant difference (P = 0.586). The recurrence or persistence of sHPT was not correlated with preoperative imaging localization (19 patients in negative, 16 in positive; P = 0.14). Conclusion Preoperative imaging localization contributed to surgical success but not to surgical outcomes. The combination of ioPTH measurement with imaging localization might be valuable for better surgical results in sHPT. PMID:26665124

  9. Cyclooxygenase-2 suppresses the anabolic response to PTH infusion in mice.

    Directory of Open Access Journals (Sweden)

    Shilpa Choudhary

    Full Text Available We previously reported that the ability of continuously elevated PTH to stimulate osteoblastic differentiation in bone marrow stromal cell cultures was abrogated by an osteoclastic factor secreted in response to cyclooxygenase-2 (Cox2-produced prostaglandin E2. We now examine the impact of Cox2 (Ptgs2 knockout (KO on the anabolic response to continuously elevated PTH in vivo. PTH (40 μg/kg/d or vehicle was infused for 12 or 21 days in 3-mo-old male wild type (WT and KO mice in the outbred CD-1 background. Changes in bone phenotype were assessed by bone mineral density (BMD, μCT and histomorphometry. PTH infusion for both 12 and 21 days increased femoral BMD in Cox2 KO mice and decreased BMD in WT mice. Femoral and vertebral trabecular bone volume fractions were increased in KO mice, but not in WT mice, by PTH infusion. In the femoral diaphysis, PTH infusion increased cortical area in Cox2 KO, but not WT, femurs. PTH infusion markedly increased trabecular bone formation rate in the femur, serum markers of bone formation, and expression of bone formation-related genes, growth factors, and Wnt target genes in KO mice relative to WT mice, and decreased gene expression of Wnt antagonists only in KO mice. In contrast to the differential effects of PTH on anabolic factors in WT and KO mice, PTH infusion increased serum markers of resorption, expression of resorption-related genes, and the percent bone surface covered by osteoclasts similarly in both WT and KO mice. We conclude that Cox2 inhibits the anabolic, but not the catabolic, effects of continuous PTH. These data suggest that the bone loss with continuously infused PTH in mice is due largely to suppression of bone formation and that this suppression is mediated by Cox2.

  10. Local anthropogenic contamination affects the fecundity and reproductive success of an Arctic amphipod

    NARCIS (Netherlands)

    Bach, L.; Fischer, A.; Strand, J.

    2010-01-01

    This study investigates whether adaptation to life in contaminated Arctic areas carries a cost for the populations in terms of reduced fecundity and reproductive success. The benthic amphipod, Orchomenella pinguis occurs in huge densities in both clean and contaminated sites. O. pinguis was collecte

  11. Local anthropogenic contamination affects the fecundity and reproductive success of an Arctic amphipod

    DEFF Research Database (Denmark)

    Bach, Lis; Fischer, Astrid; Strand, Jakob

    2010-01-01

    to clean site individuals. These results indicated a cost of living in highly contaminated environments in terms of reduced reproductive success. This study confirms the potential of the benthic amphipod O. pinguis as a bioindicator for assessments of reproductive effects of contaminants in the Arctic...

  12. Local anthropogenic contamination affects the fecundity and reproductive success of an Arctic amphipod

    NARCIS (Netherlands)

    Bach, L.; Fischer, A.; Strand, J.

    2010-01-01

    This study investigates whether adaptation to life in contaminated Arctic areas carries a cost for the populations in terms of reduced fecundity and reproductive success. The benthic amphipod, Orchomenella pinguis occurs in huge densities in both clean and contaminated sites. O. pinguis was

  13. Sequential treatment with basic fibroblast growth factor and PTH is more efficacious than treatment with PTH alone for increasing vertebral bone mass and strength in osteopenic ovariectomized rats

    DEFF Research Database (Denmark)

    Iwaniec, U.T.; Mosekilde, Li.; Mitova-Caneva, N.G.

    2002-01-01

    The study was designed 1) to determine whether treatment with basic fibroblast growth factor (bFGF) and PTH is more efficacious than treatment with PTH alone for increasing bone mass and strength and improving trabecular microarchitecture in osteopenic ovariectomized rats, and 2) to assess whether...... prior and concurrent administration of the antiresorptive agents estrogen and risedronate suppresses the bone anabolic response to treatment with bFGF alone and sequential treatment with bFGF and PTH. Three-month-old female Sprague Dawley rats were ovariectomized (OVX) or sham-operated (sham...... into the jugular veins of all rats, and vehicle or bFGF at a dose of 250 microg/kg was injected daily for 14 d. Three groups of rats were killed at the end of bFGF treatment. The remaining rats were continued on their respective antiresorptive therapy and injected sc with vehicle or synthetic human PTH-(1...

  14. Nestling erythrocyte resistance to oxidative stress predicts fledging success but not local recruitment in a wild bird.

    Science.gov (United States)

    Losdat, Sylvain; Helfenstein, Fabrice; Blount, Jonathan D; Marri, Viviana; Maronde, Lea; Richner, Heinz

    2013-02-23

    Stressful conditions experienced by individuals during their early development have long-term consequences on various life-history traits such as survival until first reproduction. Oxidative stress has been shown to affect various fitness-related traits and to influence key evolutionary trade-offs but whether an individual's ability to resist oxidative stress in early life affects its survival has rarely been tested. In the present study, we used four years of data obtained from a free-living great tit population (Parus major; n = 1658 offspring) to test whether pre-fledging resistance to oxidative stress, measured as erythrocyte resistance to oxidative stress and oxidative damage to lipids, predicted fledging success and local recruitment. Fledging success and local recruitment, both major correlates of survival, were primarily influenced by offspring body mass prior to fledging. We found that pre-fledging erythrocyte resistance to oxidative stress predicted fledging success, suggesting that individual resistance to oxidative stress is related to short-term survival. However, local recruitment was not influenced by pre-fledging erythrocyte resistance to oxidative stress or oxidative damage. Our results suggest that an individual ability to resist oxidative stress at the offspring stage predicts short-term survival but does not influence survival later in life.

  15. PTH1R Mutants Found in Patients with Primary Failure of Tooth Eruption Disrupt G-Protein Signaling

    Science.gov (United States)

    Kollert, Sina; Rukoyatkina, Natalia; Sturm, Julia; Gambaryan, Stepan; Stellzig-Eisenhauer, Angelika; Meyer-Marcotty, Philipp; Eigenthaler, Martin; Wischmeyer, Erhard

    2016-01-01

    Aim Primary failure of tooth eruption (PFE) is causally linked to heterozygous mutations of the parathyroid hormone receptor (PTH1R) gene. The mutants described so far lead to exchange of amino acids or truncation of the protein that may result in structural changes of the expressed PTH1R. However, functional effects of these mutations have not been investigated yet. Materials and Methods In HEK293 cells, PTH1R wild type was co-transfected with selected PTH1R mutants identified in patients with PFE. The effects on activation of PTH-regulated intracellular signaling pathways were analyzed by ELISA and Western immunoblotting. Differential effects of wild type and mutated PTH1R on TRESK ion channel regulation were analyzed by electrophysiological recordings in Xenopus laevis oocytes. Results In HEK293 cells, activation of PTH1R wild type increases cAMP and in response activates cAMP-stimulated protein kinase as detected by phosphorylation of the vasodilator stimulated phosphoprotein (VASP). In contrast, the PTH1R mutants are functionally inactive and mutant PTH1R/Gly452Glu has a dominant negative effect on the signaling of PTH1R wild type. Confocal imaging revealed that wild type PTH1R is expressed on the cell surface, whereas PTH1R/Gly452Glu mutant is mostly retained inside the cell. Furthermore, in contrast to wild type PTH1R which substantially augmented K+ currents of TRESK channels, coupling of mutated PTH1R to TRESK channels was completely abolished. Conclusions PTH1R mutations affect intracellular PTH-regulated signaling in vitro. In patients with primary failure of tooth eruption defective signaling of PTH1R mutations is suggested to occur in dento-alveolar cells and thus may lead to impaired tooth movement. PMID:27898723

  16. Bleeding for the Village: Success or Failure in the Hands of Local Powerbrokers

    Science.gov (United States)

    2012-06-01

    Malaysian governments successfully managed to contain, and ultimately defeat, the Communist insurgency in Malaysia .13 The Philippines Insurrection was a...After the Soviet withdrawal in 1989, a brutal civil war between rival mujahedeen groups started, 60 and rape , pillage, and extortion became commonplace...Women being attacked, raped and killed. Therefore, after these incidents, a group of students from religious schools decided to rise against these

  17. A salt bridge between Arg-20 on parathyroid hormone (PTH) and Asp-137 on the PTH1 receptor is essential for full affinity.

    Science.gov (United States)

    Weaver, Richard E; Wigglesworth, Mark J; Donnelly, Dan

    2014-11-01

    Parathyroid hormone (PTH) acts via the receptor PTH1 and plays an important role in calcium homeostasis. PTH's interaction with the N-terminal domain of PTH1 is mediated in part by Arg-20 on the peptide which forms a number of interactions with the receptor: a charge-charge interaction with Asp-137; hydrogen bonds with the backbone of Asp-29 and Met-32; and hydrophobic interactions with Met-32 and Gln-37. The aim of this work was to establish the importance of the charge-charge interaction through the combined use of modified peptide ligands, site-directed mutations of the receptor, and pharmacological assays. The substitution of Arg-20 with norleucine resulted in a 50-fold reduction in potency at PTH1 and Asp-137-Glu while, in contrast, both Asp-137-Asn and Asp-137-Ala receptors were largely insensitive to this ligand modification. The effect of this removal of the positive charge as position 20 could be partially rescued at PTH1 and Asp-137-Glu, but not Asp-137-Asn and Asp-137-Ala, through a substitution of peptide position 20 with ornithine. The latter two receptors, which have no negative charge at position 137, displayed potency for PTH that was reduced by 40- and 117-fold, respectively. These data demonstrate that a negative charge at residue-137 is important for interacting with ligands containing a positive charge at residue-20, and that the Arg-20 interaction with Asp-137, observed in the crystal structure of the isolated N-terminal domain of PTH1, is likely to be present in the full length receptor where it provides an important affinity- and potency-generating interaction through a salt bridge. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Runx1 is critical for PTH-induced onset of mesenchymal progenitor cell chondrogenic differentiation.

    Directory of Open Access Journals (Sweden)

    Jinwu Wang

    Full Text Available Parathyroid hormone (PTH plays a critical role in the regulation of chondrogenesis. In this study, we have found for the first time that Runt-related transcription factor 1 (Runx1 contributes to PTH-induced chondrogenesis. Upon PTH treatment, limb bud mesenchymal progenitor cells in micromass culture showed an enhanced chondrogenesis, which was associated with a significant increase of chondrogenic marker gene expression, such as type II collagen and type X collagen. Runx1 was also exclusively expressed in cells treated with PTH at the onset stage of chondrogenesis. Knockdown of Runx1 completely blunted PTH-mediated chondrogenesis. Furthermore, PTH induced Runx1 expression and chondrogenesis were markedly reduced by inhibition of protein kinase A (PKA signaling. Taken together, our present study indicates that chondrogenesis induced by PTH in mesenchymal progenitor cells is mediated by Runx1, which involves the activation of PKA. These data provide a novel insight into understanding the molecular mechanisms behind PTH-enhanced cartilage regeneration.

  19. PTH (1-84) Replacement Therapy in Hypoparathyroidism: Effects on bone metabolism and structure

    DEFF Research Database (Denmark)

    Sikjær, Tanja Tvistholm; Rejnmark, Lars; Tietze, Anna

    , as an add-on therapy. We investigated the changes in bone structure and density using µCT in 44 iliac crest bone biopsies (23 on PTH treatment) obtained after 24-wks of treatment. Trabecular tunnelling was evident in 11 (48%) biopsies from the PTH-group, whereas no tunnelling was detected in the placebo...

  20. PTH (1-84) Replacement Therapy in Hypoparathyroidism: Effects on bone metabolism and structure

    DEFF Research Database (Denmark)

    Sikjær, Tanja Tvistholm; Rejnmark, Lars; Tietze, Anna

    2011-01-01

    , as an add-on therapy. We investigated the changes in bone structure and density using µCT in 44 iliac crest bone biopsies (23 on PTH treatment) obtained after 24-wks of treatment. Trabecular tunnelling was evident in 11 (48%) biopsies from the PTH-group, whereas no tunnelling was detected in the placebo...

  1. PTH [1-34] induced differentiation and mineralization of mandibular condylar cartilage.

    Science.gov (United States)

    O' Brien, Mara Heather; Dutra, Eliane Hermes; Lima, Alexandro; Nanda, Ravindra; Yadav, Sumit

    2017-06-12

    Intermittent Parathyroid Hormone (I-PTH) is the only FDA approved anabolic drug therapy available for the treatment of osteoporosis in males and postmenopausal females. The effects of I-PTH on the chondrogenic lineage of the mandibular condylar cartilage (MCC) are not well understood. To investigate the role of I-PTH on the MCC and subchondral bone, we carried out our studies using 4 to 5 week old triple transgenic mice (Col1a1XCol2a1XCol10a1). The experimental group was injected with PTH (80 μg/kg) daily for 2 weeks, while control group was injected with saline. Our histology showed that the I-PTH treatment led to an increased number of cells expressing Col1a1, Col2a1 and Col10a1. Additionally, there was an increase in cellular proliferation, increased proteoglycan distribution, increased cartilage thickness, increased TRAP activity, and mineralization. Immunohistochemical staining showed increased expression of pSMAD158 and VEGF in the MCC and subchondral bone. Furthermore our microCT data showed that I-PTH treatment led to an increased bone volume fraction, tissue density and trabecular thickness, with a decrease in trabecular spacing. Morphometric measurements showed increased mandibular length and condyle head length following I-PTH treatment. In conclusion, our study suggests that I-PTH plays a critical role in cellular proliferation, proteoglycan distribution, and mineralization of the MCC.

  2. PTH [1-34]-induced alterations predispose the mandibular condylar cartilage to mineralization.

    Science.gov (United States)

    Dutra, E H; O'Brien, M H; Gutierrez, T; Lima, A; Nanda, R; Yadav, S

    2017-06-01

    To study the effects of intermittent parathyroid hormone (PTH [1-34]) on the mandibular condylar cartilage (MCC) and subchondral bone in adult female mice. Twenty-two, 20-week-old female mice were used for in vivo experiments. The experimental mice (n=11) received daily intraperitoneal injections of PTH [1-34] for 3 weeks, while control mice (n=11) received intraperitoneal injections of 0.9% saline solution. Mice were euthanized and then micro-computed tomography (micro-CT); histology and immunostaining were carried out to assess the response. Intermittent PTH [1-34] led to early MCC breakdown and surface irregularities. Micro-CT analyses indicated that PTH [1-34] treatment led to increased bone volume fraction, tissue density and trabecular thickness, while decreasing the trabecular spacing. Histological analyses showed decreased proteoglycan secretion, increased bone turnover (TRAP staining) and increased mineralization. Furthermore, PTH [1-34] treatment showed increased apoptosis of the cells. Our immunohistochemistry showed increased expression of pSMAD158 in the MCC and subchondral bone with PTH administration, whereas sclerostin (SOST) expression was decreased. Intermittent PTH [1-34] results in early mineralization of the MCC, which may result in cartilage degeneration. Our results identified a novel mechanism by which PTH [1-34] induces alteration in the microarchitecture of the MCC and the subchondral bone. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Non-canonical signaling of the PTH receptor

    Science.gov (United States)

    Vilardaga, Jean-Pierre; Gardella, Thomas J.; Wehbi, Vanessa L.; Feinstein, Timothy N.

    2012-01-01

    The classical model of arrestin-mediated desensitization of cell-surface G protein-coupled receptors (GPCRs) is thought to be universal. However, this paradigm is incompatible with recent reports that the parathyroid hormone (PTH) receptor (PTHR), a crucial GPCR for bone and mineral ion metabolism, sustains GS activity and continues to generate cAMP for prolonged periods after ligand-wash-out; during these periods the receptor is observed mainly in endosomes, associated with the bound ligand, GS and β-arrestins. In this review, we discuss possible molecular mechanisms underlying sustained signaling by the PTHR, including modes of signal generation and attenuation within endosomes, as well as the biological relevance of such non-canonical signaling. PMID:22709554

  4. Biotic and abiotic controls of argentine ant invasion success at local and landscape scales

    Science.gov (United States)

    Menke, S.B.; Fisher, R.N.; Jetz, W.; Holway, D.A.

    2007-01-01

    Although the ecological success of introduced species hinges on biotic interactions and physical conditions, few experimental studies - especially on animals - have simultaneously investigated the relative importance of both types of factors. The lack of such research may stem from the common assumption that native and introduced species exhibit similar environmental tolerances. Here we combine experimental and spatial modeling approaches (1) to determine the relative importance of biotic and abiotic controls of Argentine ant (Linepithema humile) invasion success, (2) to examine how the importance of these factors changes with spatial scale in southern California (USA), and (3) to assess how Argentine ants differ from native ants in their environmental tolerances. A factorial field experiment that combined native ant removal with irrigation revealed that Argentine ants failed to invade any dry plots (even those lacking native ants) but readily invaded all moist plots. Native ants slowed the spread of Argentine ants into irrigated plots but did not prevent invasion. In areas without Argentine ants, native ant species showed variable responses to irrigation. At the landscape scale, Argentine ant occurrence was positively correlated with minimum winter temperature (but not precipitation), whereas native ant diversity increased with precipitation and was negatively correlated with minimum winter temperature. These results are of interest for several reasons. First, they demonstrate that fine-scale differences in the physical environment can eclipse biotic resistance from native competitors in determining community susceptibility to invasion. Second, our results illustrate surprising complexities with respect to how the abiotic factors limiting invasion can change with spatial scale, and third, how native and invasive species can differ in their responses to the physical environment. Idiosyncratic and scale-dependent processes complicate attempts to forecast where

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

    Directory of Open Access Journals (Sweden)

    Kapildev Das

    2010-01-01

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

  6. Successfully Changing the Landscape of Information Distribution: Extension Food Website Reaches People Locally and Globally

    Directory of Open Access Journals (Sweden)

    Alice Henneman

    2016-02-01

    Full Text Available The goal of the Food website was to develop Internet-based content that was relevant and reached the general public and multiplier groups, such as educators, health professionals, and media outlets. The purpose of this paper was to examine whether a multi-modal approach to information delivery through increases in and changes to content, electronic mailing list creation, and social media posting impacted user access, traffic channels, and referrals from 2010 to 2014. When comparing 2010-2011 versus 2013-2014, there was a 150% increase in total pageviews, 197% increase in unique pageviews, and a 39% increase in average time spent on a page. Since 2010, the website had over 5.2 million total pageviews, 3.1 million sessions, and 2.6 million users. In 2014, top social media referrals included Pinterest, Facebook, LinkedIn, and Twitter. Age of visitors ranged from 18 to 65+, with 45% being 18-34 years old. Approximately 70% were female. Visitors came from 229 countries/territories and 18,237 different cities. The website connects Nebraska and the world to the exciting food research and information generated at the University of Nebraska-Lincoln and is playing an increasingly important role in shaping the future of food in the local and global community.

  7. Successful transplantation of human hepatic stem cells with restricted localization to liver using hyaluronan grafts.

    Science.gov (United States)

    Turner, Rachael A; Wauthier, Eliane; Lozoya, Oswaldo; McClelland, Randall; Bowsher, James E; Barbier, Claire; Prestwich, Glenn; Hsu, Edward; Gerber, David A; Reid, Lola M

    2013-02-01

    Cell therapies are potential alternatives to organ transplantation for liver failure or dysfunction but are compromised by inefficient engraftment, cell dispersal to ectopic sites, and emboli formation. Grafting strategies have been devised for transplantation of human hepatic stem cells (hHpSCs) embedded into a mix of soluble signals and extracellular matrix biomaterials (hyaluronans, type III collagen, laminin) found in stem cell niches. The hHpSCs maintain a stable stem cell phenotype under the graft conditions. The grafts were transplanted into the livers of immunocompromised murine hosts with and without carbon tetrachloride treatment to assess the effects of quiescent versus injured liver conditions. Grafted cells remained localized to the livers, resulting in a larger bolus of engrafted cells in the host livers under quiescent conditions and with potential for more rapid expansion under injured liver conditions. By contrast, transplantation by direct injection or via a vascular route resulted in inefficient engraftment and cell dispersal to ectopic sites. Transplantation by grafting is proposed as a preferred strategy for cell therapies for solid organs such as the liver.

  8. Picard Successive Approximation Method for Solving Differential Equations Arising in Fractal Heat Transfer with Local Fractional Derivative

    Directory of Open Access Journals (Sweden)

    Ai-Min Yang

    2014-01-01

    Full Text Available The Fourier law of one-dimensional heat conduction equation in fractal media is investigated in this paper. An approximate solution to one-dimensional local fractional Volterra integral equation of the second kind, which is derived from the transformation of Fourier flux equation in discontinuous media, is considered. The Picard successive approximation method is applied to solve the temperature field based on the given Mittag-Leffler-type Fourier flux distribution in fractal media. The nondifferential approximate solutions are given to show the efficiency of the present method.

  9. PTH(1-84) Administration in Hypoparathyroidism Transiently Reduces Bone Matrix Mineralization.

    Science.gov (United States)

    Misof, Barbara M; Roschger, Paul; Dempster, David W; Zhou, Hua; Bilezikian, John P; Klaushofer, Klaus; Rubin, Mishaela R

    2016-01-01

    Patients with hypoparathyroidism have low circulating parathyroid (PTH) levels and higher cancellous bone volume and trabecular thickness. Treatment with PTH(1-84) was shown to increase abnormally low bone remodeling dynamics. In this work, we studied the effect of 1-year or 2-year PTH(1-84) treatment on cancellous and cortical bone mineralization density distribution (Cn.BMDD and Ct.BMDD) based on quantitative backscattered electron imaging (qBEI) in paired transiliac bone biopsy samples. The study cohort comprised 30 adult hypoparathyroid patients (14 treated for 1 year; 16 treated for 2 years). At baseline, Cn.BMDD was shifted to higher mineralization densities in both treatment groups (average degree of mineralization Cn.CaMean +3.9% and +2.7%, p mineralizing surface) was predictive for Cn.BMDD outcomes in the 1-year PTH(1-84) group, but not in the 2-year PTH(1-84) group. Our findings suggest higher baseline bone matrix mineralization consistent with the decreased bone turnover in hypoparathyroidism. PTH(1-84) treatment caused differential effects dependent on treatment duration that were consistent with the histomorphometric bone formation outcomes. The greater increase in bone formation during the first year of treatment was associated with a decrease in bone matrix mineralization, suggesting that PTH(1-84) exposure to the hypoparathyroid skeleton has the greatest effects on BMDD early in treatment.

  10. Optical and thermal properties of PTh-co-PANI-Ti random copolymer composite for photovoltaic application

    Directory of Open Access Journals (Sweden)

    Sanjay R. Takpire

    2015-12-01

    Full Text Available In thе present work, a polythiophene (PTh-co-polyaniline (PANI-titanium (Ti copolymer has been synthesized as a novel copolymeric composite material for photovoltaic (PV application. The focus of the study was to evaluate optical and thermal properties of the PTh-co-PANI-Ti copolymer containing different types of monomers. The optical conductivity was determined from the UV–VIS spectra that were used to calculate the extinction coefficients. The structure and morphology of composite was analyzed through field emission-electron microscopy (FESEM. The PTh-co-PANI-Ti copolymer composite exhibited significant photovoltaic (PV response to light intensity. J–V analysis showed an increase in conversion efficiency from 0.21 to 1.5 of PTh-co-PANi-Ti with illumination light intensity. PV properties demonstrated that the PTh-co-PANI-Ti exhibited the highest power conversion efficiency ɳ=1.5, with a short circuit current Isc=0.72mA, an open circuit voltage Voc=0.9V and a fill factor FF=0.51. Thermo-gravimetric (TG and differential thermal (DTA analyses were carried out for the thermal stability of the PTh-co-PANI-Ti copolymer composite. The results obtained from the characterization of PTh-co-PANI-Ti showed that many properties of PV action are present in as-synthesized material.

  11. Protein malnutrition attenuates bone anabolic response to PTH in female rats.

    Science.gov (United States)

    Ammann, P; Zacchetti, G; Gasser, J A; Lavet, C; Rizzoli, R

    2015-02-01

    PTH is indicated for the treatment of severe osteoporosis. Elderly osteoporotic patients frequently suffer from protein malnutrition, which may contribute to bone loss. It is unknown whether this malnutrition may affect the response to PTH. Therefore, the aim of the present study was to assess whether an isocaloric low-protein (LP) diet may influence the bone anabolic response to intermittent PTH in 6-month-old female rats. Six-month-old female rats were either pair fed an isocaloric LP diet (2.5% casein) or a normal-protein (NP) diet (15% casein) for 2 weeks. The rats continued on their respective diet while being treated with 5- or 40-μg/kg recombinant human PTH amino-terminal fragment 1-34 (PTH-[1-34]) daily, or with vehicle for 4 weeks. At the end of this period, areal bone mineral density, bone mineral content, microstructure, and bone strength in axial compression of proximal tibia or 3-point bending for midshaft tibia tests were measured. Blood was collected for the determination of IGF-I and osteocalcin. After 4 weeks of PTH-(1-34), the dose-dependent increase of proximal tibia bone mineral density, trabecular microstructure variables, and bone strength was attenuated in rats fed a LP diet as compared with rats on a NP intake. At the level of midshaft tibia cortical bone, PTH-(1-34) exerted an anabolic effect only in the NP but not in the LP diet group. Protein malnutrition was associated with lower IGF-I levels. Protein malnutrition attenuates the bone anabolic effects of PTH-(1-34) in rats. These results suggest that a sufficient protein intake should be recommended for osteoporotic patients undergoing PTH therapy.

  12. Using Climate Science to Inform Local Planning: Challenges and Successes from the Field

    Science.gov (United States)

    Hayhoe, K.

    2014-12-01

    Much of our society, including our agriculture, our dependence on natural resources, and our infrastructure, is built on the assumption that individual weather events and average conditions may vary from year to year, but over the long term the climate of a given region can be predicted based on past climate "normals". This assumption is no longer valid; today, human-induced climate change is altering average conditions as well as the risk of many types of weather extremes. Observed trends and projected future changes in mean climate and in the frequency and severity of temperature extremes, heat waves, heavy precipitation events, coastal flooding, and storms are clearly documented in the Third U.S. National Climate Assessment, as well as by a host of other regional impact assessments. While future projections are inherently uncertain, these assessments make one fact clear: future planning for any sector or region affected by climate change that fails to take into account long-term trends will end up with the wrong answer. This concept of non-stationarity, that future climate will differ from that experienced in the past, challenges regional planners, water managers, city managers and engineers to incorporate future climate change into present-day planning. From the perspective of scientists, translating climate projections into information that can be used by stakeholders and decision-makers presents a challenge of equal magnitude. Here, I draw on my experience working with the agriculture, ecosystem, energy, health, infrastructure, insurance, and water sectors to propose a framework for, and highlight some of the main challenges inherent to, incorporating climate information into practical, on-the-ground planning at the local to regional scale. This approach, which we have developed through working with a range of cities, states, and regions including Austin, Cambridge, California, Chicago, Delaware, the Northeast, and most recently Washington DC, is based on

  13. Decrease in the expression of the type 1 PTH/PTHrP receptor (PTH1R on chondrocytes in animals with osteoarthritis

    Directory of Open Access Journals (Sweden)

    Skwara Adrian

    2010-04-01

    Full Text Available Abstract Background To evaluate the expression of the type 1 PTH/PTHrP receptor (PTH1R on chondrocytes from hyaline cartilage over the course of osteoarthritis (OA. Methods In 12 NZW rabbits, the anterior cruciate ligament (ACL was resected to create anterior instability of the knee. In 12 control rabbits, only a sham operation, without resection of the ACL, was performed. Four animals from each group were killed at 3, 6, and 12 weeks. After opening the knee joint, OA was macroscopically graded and hyaline cartilage of the load-bearing area was evaluated histologically according to the Mankin scale and by immunostaining for PTH1R. Results There was a positive linear correlation between the time after surgery and the macroscopic and histologic OA scores. The scores in the control group were constant over the time course. Immunostaining showed significantly less expression of PTH1R in the experimental compared to the control group after 6 (P Conclusions The results show an in vivo decrease in the expression of PTH1R on chondrocytes over the time course of OA. Further studies are needed to evaluate whether new treatment approaches could evolve from this knowledge.

  14. Bovine parathyroid hormone enhances osteoclast bone resorption by modulating V-ATPase through PTH1R.

    Science.gov (United States)

    Liu, Shuangxin; Zhu, Weiping; Li, Sijia; Ma, Jianchao; Zhang, Huitao; Li, Zhonghe; Zhang, Li; Zhang, Bin; Li, Zhuo; Liang, Xinling; Shi, Wei

    2016-02-01

    The vacuolar-type H+ adenosine triphosphatase (V-ATPase) plays an important role in cellular acidification and bone resorption by osteoclasts. However, the direct effect of bovine parathyroid hormone (bPTH) on V-ATPase has not yet been elucidated. The aim of the present study was to assess the effects of bPTH on V-ATPase and osteoclasts. Osteoclasts from bone marrow (BM)-derived monocytes of C57BL/6 mice were cultured with or without bPTH. The mRNA and protein expression levels of the V-ATPase a3-subunit and d2-subunit (by RT-qPCR and western blot analysis), V-ATPase activity (using the V type ATPase Activity Assay kit) and the bone resorption function of osteoclasts (by bone resorption assay) were examined following treatment with various concentrations of bPTH (0.1, 1.0, 10 and 100 ng/ml) alone or with bPTH and its inhibitor, bafilomycin A1. Furthermore, the expression of parathyroid hormone (PTH) receptors in osteoclasts was also detected. The results revealed that the mRNA and protein expression levels of V-ATPase a3-subunit and d2-subunit increased in a dose‑dependent manner, paralleling the level of bPTH present. In addition, an increase in the concentration of bPTH was accompanied by the increased resorption capability of osteoclasts, whereas bone resorption was inhibited in the presence of bafilomycin A1. In addition, we confirmed the existence of parathyroid hormone 1 receptor (PTH1R) in osteoclasts using three different methods (RT-qPCR, western blot analysis and immunofluorescence staining). We found that bPTH enhanced the bone resorption capability of osteoclasts by modulating the expression of V-ATPase subunits, intracellular acidification and V-ATPase activity. Thus, we propose that PTH has a direct effect on osteoblasts and osteoclasts, and that this effect is mediated through PTH1R, thus contributing to bone remodeling.

  15. A decrease in intact parathyroid hormone (iPTH) levels is associated with higher mortality in prevalent hemodialysis patients.

    Science.gov (United States)

    Villa-Bellosta, Ricardo; Rodriguez-Osorio, Laura; Mas, Sebastian; Abadi, Younes; Rubert, Mercedes; de la Piedra, Concepción; Gracia-Iguacel, Carolina; Mahillo, Ignacio; Ortiz, Alberto; Egido, Jesús; González-Parra, Emilio

    2017-01-01

    The mortality of dialysis patients is 10- to 100-fold higher than in the general population. Baseline serum PTH levels, and more recently, changes in serum PTH levels (ΔPTH) over time, have been associated to mortality in dialysis patients. We explored the relationship between ΔPTH over 1 year with mortality over the next year in a prospective cohort of 115 prevalent hemodialysis patients from a single center that had median baseline iPTH levels within guideline recommendations. Median baseline iPTH levels were 205 (116.5, 400) pg/ml. ΔiPTH between baseline and 1 year was 85.2 ± 57.1 pg/ml. During the second year of follow-up, 27 patients died. ΔiPTH was significantly higher in patients who survived (+157.30 ± 25.82 pg/ml) than in those who died (+39.03 ± 60.95 pg/ml), while baseline iPTH values were not significantly different. The highest mortality (48%) was observed in patients with a decrease in ΔiPTH (ΔiPTH quartile 1, negative ΔiPTH) and the lowest (12%) mortality in quartile 3 ΔiPTH (ΔiPTH increase 101-300 pg/ml). In a logistic regression model, ΔiPTH was associated with mortality with an odds ratio (OR) of 0.998 (95% CI 0.996-0999, p = 0.038). In multivariable analysis, mortality risk was 73% and 88% lower for patients with ΔiPTH 0-100 pg/ml and 101-300 pg/ml, respectively, than for those with a decrease in ΔiPTH. In patients with a decrease in ΔiPTH, the OR for death was 4.131 (1.515-11.27)(p = 0.006). In prevalent hemodialysis patients with median baseline iPTH values within the guideline recommended range, a decrease in ΔiPTH was associated with higher mortality. Further studies are required to understand the mechanisms and therapeutic implications of this observation that challenges current clinical practice.

  16. The strategic decisions and success factors of the global integration-local responsiveness of Japanese MNCs in China

    Institute of Scientific and Technical Information of China (English)

    MAO Yunshi; WANG Jiancheng

    2007-01-01

    This article applies Foreign Direct Investment (FDI) theories to the strategic management analysis of the global integration-local responsiveness of multinational corporations (MNCs) in China, from the perspective of company characteristics (ownership advantages and internalization advantages) and environmental dynamics (locational factors) in order to analyze the success factors influencing the sales activities of Japanese MNCs in China. Based on the analysis of a survey conducted on 230 Japanese parent companies with investments in China, the empirical research findings include: Japanese MNCs in China favor global integration strategies; the more significant the ownership advantages and internalization advantages are, the greater the global integration is; the success factors of their operations in China due to global integration are present in manufacturing know-how, procurement of parts and supplies, financial power, previous investment experience in China as well as sales networks and technologies; locational advantages mainly lie in labor cost among other things; internalization factors do not have any significant correlation with the success and performance of the subsidiary company.

  17. Successful Localization of Abnormal Parathyroid Gland Using Ultrasound-Guided Methylene Blue Dye Injection in the Reoperative Neck.

    Science.gov (United States)

    Haciyanli, Mehmet; Koruyucu, Melike Bedel; Erdoğan, Nezahat Karaca; Dere, Ozcan; Sarı, Erdem; Kumkumoğlu, Yusuf; Tavusbay, Cengiz; Kamer, Erdinc

    2015-12-01

    Persistent or recurrent hyperparathyroidism is a challenging problem for endocrine surgeons. The aim of this study was to review our experience using ultrasound-guided (US-G) methylene blue dye injection for the localization and removal of abnormal parathyroid glands in patients having primary hyperparathyroidism and previous neck surgery. Between January 2012 and May 2013, six consecutive patients with primary hyperparathyroidism (PHPT) and previous neck surgery underwent focused parathyroidectomy with the use of US-G methylene blue dye injections to localize the presumed parathyroid adenoma were included in the study. We analyzed the data of six patients who underwent reoperative parathyroid surgery using US-G methylene blue dye injection retrospectively. The dye injection was performed just prior to surgery. All patients were successfully treated for their hyperparathyroidism which was confirmed by at least 50 % drop in intraoperative parathormone level 10 min after resection. There were no complications related with US-G dye injection or with surgery. US-G methylene blue dye injection is a cheap, safe, and effective method for localization of diseased parathyroid glands and guiding surgery in the reoperative neck.

  18. Terrestrial planet formation in a protoplanetary disk with a local mass depletion: A successful scenario for the formation of Mars

    Energy Technology Data Exchange (ETDEWEB)

    Izidoro, A.; Winter, O. C. [UNESP, Univ. Estadual Paulista - Grupo de Dinâmica Orbital and Planetologia, Guaratinguetá, CEP 12.516-410, São Paulo (Brazil); Haghighipour, N. [Institute for Astronomy and NASA Astrobiology Institute, University of Hawaii-Manoa, Honolulu, HI 96822 (United States); Tsuchida, M., E-mail: izidoro@feg.unesp.br, E-mail: nader@ifa.hawaii.edu [UNESP, Univ. Estadual Paulista, DCCE-IBILCE, São José do Rio Preto, CEP 15.054-000, São Paulo (Brazil)

    2014-02-10

    Models of terrestrial planet formation for our solar system have been successful in producing planets with masses and orbits similar to those of Venus and Earth. However, these models have generally failed to produce Mars-sized objects around 1.5 AU. The body that is usually formed around Mars' semimajor axis is, in general, much more massive than Mars. Only when Jupiter and Saturn are assumed to have initially very eccentric orbits (e ∼ 0.1), which seems fairly unlikely for the solar system, or alternately, if the protoplanetary disk is truncated at 1.0 AU, simulations have been able to produce Mars-like bodies in the correct location. In this paper, we examine an alternative scenario for the formation of Mars in which a local depletion in the density of the protosolar nebula results in a non-uniform formation of planetary embryos and ultimately the formation of Mars-sized planets around 1.5 AU. We have carried out extensive numerical simulations of the formation of terrestrial planets in such a disk for different scales of the local density depletion, and for different orbital configurations of the giant planets. Our simulations point to the possibility of the formation of Mars-sized bodies around 1.5 AU, specifically when the scale of the disk local mass-depletion is moderately high (50%-75%) and Jupiter and Saturn are initially in their current orbits. In these systems, Mars-analogs are formed from the protoplanetary materials that originate in the regions of disk interior or exterior to the local mass-depletion. Results also indicate that Earth-sized planets can form around 1 AU with a substantial amount of water accreted via primitive water-rich planetesimals and planetary embryos. We present the results of our study and discuss their implications for the formation of terrestrial planets in our solar system.

  19. Intermittent treatment with parathyroid hormone (PTH) as well as a non-peptide small molecule agonist of the PTH1 receptor inhibits adipocyte differentiation in human bone marrow stromal cells.

    Science.gov (United States)

    Rickard, David J; Wang, Fei-Lan; Rodriguez-Rojas, Ana-Maria; Wu, Zining; Trice, Wen J; Hoffman, Sandra J; Votta, Bartholomew; Stroup, George B; Kumar, Sanjay; Nuttall, Mark E

    2006-12-01

    Whereas continuous PTH infusion increases bone resorption and bone loss, intermittent PTH treatment stimulates bone formation, in part, via reactivation of quiescent bone surfaces and reducing osteoblast apoptosis. We investigated the possibility that intermittent and continuous PTH treatment also differentially regulates osteogenic and adipocytic lineage commitment of bone marrow stromal progenitor/mesenchymal stem cells (MSC). The MSC were cultured under mildly adipogenic conditions in medium supplemented with dexamethasone, insulin, isobutyl-methylxanthine and troglitazone (DIIT), and treated with 50 nM human PTH(1-34) for either 1 h/day or continuously (PTH replenished every 48 h). After 6 days, cells treated with PTH for 1 h/day retained their normal fibroblastic appearance whereas those treated continuously adopted a polygonal, irregular morphology. After 12-18 days numerous lipid vacuole and oil red O-positive adipocytes had developed in cultures treated with DIIT alone, or with DIIT and continuous PTH. In contrast, adipocyte number was reduced and alkaline phosphatase staining increased in the cultures treated with DIIT and 1 h/day PTH, indicating suppression of adipogenesis and possible promotion of early osteoblastic differentiation. Furthermore, intermittent but not continuous PTH treatment suppressed markers of differentiated adipocytes such as mRNA expression of lipoprotein lipase and PPARgamma as well as glycerol 3-phosphate dehydrogenase activity. All of these effects of intermittent PTH were also produced by a 1 h/day treatment with AH3960 (30 microM), a small molecule, non-peptide agonist of the PTH1 receptor. AH3960, like PTH, activates both the cAMP and calcium signaling pathways. Treatment with the adenylyl cyclase activator forskolin for 1 h/day, mimicked the anti-adipogenic effect of intermittent PTH, whereas pretreatment with the protein kinase-A inhibitor H89 prior to intermittent PTH resulted in almost complete conversion to adipocytes. In

  20. Glucocorticoid-induced osteoporosis in growing mice is not prevented by simultaneous intermittent PTH treatment

    OpenAIRE

    Postnov, Andrei; Schutter, De, Bob; Sijbers, Jan; Karperien, Marcel; Clerck, De, Luc S.

    2009-01-01

    Abstract: Glucocorticoids (GCs) are widely used in medicine for treatment of chronic diseases. Especially in children, prolonged treatment causes growth retardation and early onset of osteoporosis. Human parathyroid hormone (PTH) has an anabolic effect on bone when administrated intermittently. The aim of the present study was to examine whether a combined therapy of dexamethasone (DEX) and PTH could prevent the detrimental effects of GC on cortical and trabecular bone in the femur and verteb...

  1. P12 - PTHC1: A Continuing Cell Line Expressing PTH and Genes Involved in Calcium Homeostasis

    OpenAIRE

    Fabbri, S.; Mazzotta, C.; Ciuffi, S.; Mavilia, C; Galli, G; Zonefrati, R.; Strigoli, D.; Cavalli, L.; Cavalli, T.; Brandi, M L

    2010-01-01

    The main organs regulating serum levels of ionised calcium (Ca2+) are the parathyroids, which are composed of two different cell types: chief cells and oxyphil cells. Chief cells, through the calcium sensing receptor (CaSR), are affected by changes in calcium concentration, modifying PTH secretion in proportion to calcium levels. Current understanding of calcium regulation mechanisms connected to PTH and of the signalling pathways involved derive from in vitro studies carried out on primary c...

  2. Determining Normal Range of Vitamin D Based on PTH and Bone Mineral Density Changes

    Directory of Open Access Journals (Sweden)

    B Larijani

    2004-11-01

    Full Text Available PTH is the most important factor which control calcium homeostasis in the body in this study we tried to determine the normal range of PTH and Vitamin D with examining the relation between PTH and bone density and Vitamin D on the base of bones biological changes. Our subjects were, 20 to 69 years-old men and women of Tehran. Serum volume of PTH and vitamin D in different decades of life had significant difference. Range of serum PTH in osteporotic persons was 29.7-38 pgr/lit (95% SD. This range for non osteporotic persons was 24.33-30.2 pgr/lit. In this study ranges below 18 nmol/lit was considered as severe vitamin D deficiency and 23-36nmol/lit as mild deficiency. So the volume more than 36 nmol/lit volumes was normal range of vitamin D. it seems that biological changes of bones associate more with ranges of vitamin D which causes significant changes in PTH.

  3. Determining Normal Range of Vitamin D Based on PTH and Bone Mineral Density Changes

    Directory of Open Access Journals (Sweden)

    B Larijani

    2004-03-01

    Full Text Available PTH is the most important factor which control calcium homeostasis in the body in this study we tried to determine the normal range of PTH and Vitamin D with examining the relation between PTH and bone density and Vitamin D on the base of bones biological changes. Our subjects were, 20 to 69 years-old men and women of Tehran. Serum volume of PTH and vitamin D in different decades of life had significant difference. Range of serum PTH in osteporotic persons was 29.7-38 pgr/lit (95% SD. This range for non osteporotic persons was 24.33-30.2 pgr/lit. In this study ranges below 18 nmol/lit was considered as severe vitamin D deficiency and 23-36nmol/lit as mild deficiency. So the volume more than 36 nmol/lit volumes was normal range of vitamin D. it seems that biological changes of bones associate more with ranges of vitamin D which causes significant changes in PTH.

  4. PTH modulation of NCC activity regulates TRPV5 Ca2+ reabsorption.

    Science.gov (United States)

    Hoover, Robert S; Tomilin, Viktor; Hanson, Lauren; Pochynyuk, Oleh; Ko, Benjamin

    2016-01-15

    Since parathyroid hormone (PTH) is known to increase transient receptor potential vanilloid (TRPV)5 activity and decrease Na(+)-Cl(-) cotransporter (NCC) activity, we hypothesized that decreased NCC-mediated Na(+) reabsorption contributes to the enhanced TRPV5 Ca(2+) reabsorption seen with PTH. To test this, we used mDCT15 cells expressing functional TRPV5 and ruthenium red-sensitive (45)Ca(2+) uptake. PTH increased (45)Ca(2+) uptake to 8.8 ± 0.7 nmol·mg(-1)·min(-1) (n = 4, P NCC activity from 75.4 ± 2.7 to 20.3 ± 1.3 nmol·mg(-1)·min(-1) (n = 4, P NCC is required for RasGRP1 knockdown to impact the PTH effect on TRPV5 activity. Knockdown of with no lysine kinase (WNK)4 resulted in an attenuation of the increase in PTH-mediated TRPV5 activity. TRPV5 activity increased by 36% compared with 45% in control (n = 4, P NCC activity contributes to the response to PTH, implying a role for hormonal modulation of NCC activity in distal Ca(2+) handling.

  5. Role of amino acid side chains in region 17-31 of parathyroid hormone (PTH) in binding to the PTH receptor.

    Science.gov (United States)

    Dean, Thomas; Khatri, Ashok; Potetinova, Zhanna; Willick, Gordon E; Gardella, Thomas J

    2006-10-27

    The principal receptor-binding domain (Ser(17)-Val(31)) of parathyroid hormone (PTH) is predicted to form an amphiphilic alpha-helix and to interact primarily with the N-terminal extracellular domain (N domain) of the PTH receptor (PTHR). We explored these hypotheses by introducing a variety of substitutions in region 17-31 of PTH-(1-31) and assessing, via competition assays, their effects on binding to the wild-type PTHR and to PTHR-delNt, which lacks most of the N domain. Substitutions at Arg(20) reduced affinity for the intact PTHR by 200-fold or more, but altered affinity for PTHR-delNt by 4-fold or less. Similar effects were observed for Glu substitutions at Trp(23), Leu(24), and Leu(28), which together form the hydrophobic face of the predicted amphiphilic alpha-helix. Glu substitutions at Arg(25), Lys(26), and Lys(27) (which forms the hydrophilic face of the helix) caused 4-10-fold reductions in affinity for both receptors. Thus, the side chains of Arg(20), together with those composing the hydrophobic face of the ligand's putative amphiphilic alpha-helix, contribute strongly to PTHR-binding affinity by interacting specifically with the N domain of the receptor. The side chains projecting from the opposite helical face contribute weakly to binding affinity by different mechanisms, possibly involving interactions with the extracellular loop/transmembrane domain region of the receptor. The data help define the roles that side chains in the binding domain of PTH play in the PTH-PTHR interaction process and provide new clues for understanding the overall topology of the bimolecular complex.

  6. PTH prevents the adverse effects of focal radiation on bone architecture in young rats

    Science.gov (United States)

    Chandra, Abhishek; Lan, Shenghui; Zhu, Ji; Lin, Tiao; Zhang, Xianrong; Siclari, Valerie A.; Altman, Allison R.; Cengel, Keith A.; Liu, X. Sherry; Qin, Ling

    2013-01-01

    Radiation therapy is a common treatment regimen for cancer patients. However, its adverse effects on the neighboring bone could lead to fractures with a great impact on quality of life. The underlying mechanism is still elusive and there is no preventive or curative solution for this bone loss. Parathyroid hormone (PTH) is a current therapy for osteoporosis that has potent anabolic effects on bone. In this study, we found that focal radiation from frequent scans of the right tibiae in 1-month-old rats by micro-computed tomography severely decreased trabecular bone mass and deteriorated bone structure. Interestingly, PTH daily injections remarkably improved trabecular bone in the radiated tibiae with increases in trabecular number, thickness, connectivity, structure model index and stiffness, and a decrease in trabecular separation. Histomorphometric analysis revealed that radiation mainly decreased the number of osteoblasts and impaired their mineralization activity but had little effects on osteoclasts. PTH reversed these adverse effects and greatly increased bone formation to a similar level in both radiated and non-radiated bones. Furthermore, PTH protects bone marrow mesenchymal stem cells from radiation-induced damage, including a decrease in number and an increase in adipogenic differentiation. While radiation generated the same amount of free radicals in the bone marrow of vehicle-treated and PTH-treated animals, the percentage of apoptotic bone marrow cells was significantly attenuated in the PTH group. Taken together, our data demonstrate a radioprotective effect of PTH on bone structure and bone marrow and shed new light on a possible clinical application of anabolic treatment in radiotherapy. PMID:23466454

  7. Small Molecule Binding, Docking, and Characterization of the Interaction between Pth1 and Peptidyl-tRNA

    Directory of Open Access Journals (Sweden)

    Mary C. Hames

    2013-11-01

    Full Text Available Bacterial Pth1 is essential for viability. Pth1 cleaves the ester bond between the peptide and nucleotide of peptidyl-tRNA generated from aborted translation, expression of mini-genes, and short ORFs. We have determined the shape of the Pth1:peptidyl-tRNA complex using small angle neutron scattering. Binding of piperonylpiperazine, a small molecule constituent of a combinatorial synthetic library common to most compounds with inhibitory activity, was mapped to Pth1 via NMR spectroscopy. We also report computational docking results, modeling piperonylpiperazine binding based on chemical shift perturbation mapping. Overall these studies promote Pth1 as a novel antibiotic target, contribute to understanding how Pth1 interacts with its substrate, advance the current model for cleavage, and demonstrate feasibility of small molecule inhibition.

  8. Experience with a third-generation parathyroid hormone assay (BIO-PTH) in the diagnosis of primary hyperparathyroidism in a Brazilian population.

    Science.gov (United States)

    Bonanséa, Teresa Cristina P; Ohe, Monique Nakayama; Brandão, Cynthia; Ferrer, Cláudia de Francischi; Santos, Lívia Marcela; Lazaretti-Castro, Marise; Vieira, José Gilberto Henriques

    2016-10-01

    To evaluate the usefulness of a third-generation PTH assay in the diagnosis of primary hyperparathyroidism (PHPT). Forty-one PHPT patients (4 men and 37 women) with 61.2 ± 10.9 (mean ± SD) years, were studied and had PTH levels measured with two different methods using the same immunochemiluminescent assay plataform (Elecsys 2010 System, Roche). We compared a second-generation assay (I-PTH) with a third-generation PTH assay (Bio-PTH). Two populations of 423 and 120 healthy adults with serum 25OHD levels above 25 ng/mL were used to define normal values in the I-PTH and Bio-PTH assays respectively. Normal PTH values based in the healthy adults population were 24.2-78.0 pg/mL for the I-PTH assay and 19.9-58.5 pg/mL for Bio-PTH assay. In PHPT patients, PTH values ranged from 67 to 553 pg/mL (median: 168 pg/mL) using the I-PTH assay and from 55 to 328 pg/mL (median: 111 pg/mL) using the Bio-PTH assay. Results obtained with the Bio-PTH assay were significantly lower (p Bio-PTH showed highly significant correlation (r = 0.952, p Bio PTH = 13.44 + 0.59 x intact PTH. PHPT patients had 25OHD levels ranging from 4 to 36 ng/mL (mean 16.2 ng/mL); 35 subjects (85.3%) had values bellow 25 ng/mL. Our results demonstrate that both second and third generation PTH methods are strongly correlated in PHPT patients and control subjects. Lower results with Bio-PTH tests are expected in function of the assay specificity determined by the amino-terminal antibody used.

  9. Different spatio-temporal electroencephalography features drive the successful decoding of binaural and monaural cues for sound localization.

    Science.gov (United States)

    Bednar, Adam; Boland, Francis M; Lalor, Edmund C

    2017-03-01

    The human ability to localize sound is essential for monitoring our environment and helps us to analyse complex auditory scenes. Although the acoustic cues mediating sound localization have been established, it remains unknown how these cues are represented in human cortex. In particular, it is still a point of contention whether binaural and monaural cues are processed by the same or distinct cortical networks. In this study, participants listened to a sequence of auditory stimuli from different spatial locations while we recorded their neural activity using electroencephalography (EEG). The stimuli were presented over a loudspeaker array, which allowed us to deliver realistic, free-field stimuli in both the horizontal and vertical planes. Using a multivariate classification approach, we showed that it is possible to decode sound source location from scalp-recorded EEG. Robust and consistent decoding was shown for stimuli that provide binaural cues (i.e. Left vs. Right stimuli). Decoding location when only monaural cues were available (i.e. Front vs. Rear and elevational stimuli) was successful for a subset of subjects and showed less consistency. Notably, the spatio-temporal pattern of EEG features that facilitated decoding differed based on the availability of binaural and monaural cues. In particular, we identified neural processing of binaural cues at around 120 ms post-stimulus and found that monaural cues are processed later between 150 and 200 ms. Furthermore, different spatial activation patterns emerged for binaural and monaural cue processing. These spatio-temporal dissimilarities suggest the involvement of separate cortical mechanisms in monaural and binaural acoustic cue processing. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  10. pthG from Pantoea agglomerans pv. gypsophilae encodes an avirulence effector that determines incompatibility in multiple beet species.

    Science.gov (United States)

    Ezra, David; Barash, Isaac; Weinthal, Dan M; Gaba, Victor; Manulis, Shulamit

    2004-03-01

    SUMMARY Pantoea agglomerans pv. gypsophilae (Pag) causes root and crown gall disease on gypsophila, whereas P. agglomerans pv. betae (Pab) induces the disease on beet as well as gypsophila. Both pathovars harbour a pathogenicity plasmid (pPATH(Pag) or pPATH(Pab)) that determines disease development. We have previously isolated and partially characterized a pleiotropic gene from the pPATH(Pag), designated as pthG, that encodes a virulence factor in gypsophila and an elicitor of a hypersensitive-like response in beet roots. The present study was undertaken to characterize pthG further as an avr gene. The infiltration of beet leaves with strains expressing PthG (i.e. Pag or Pab containing pthG in trans) caused an hypersensitive reaction (HR) response within 48 h, whereas strains lacking intact pthG (i.e. Pab or Pag mutated in pthG) resulted in gall formation after 5 days. A hypersensitive reaction was elicited by PthG on multiple beet species, whereas a marker exchange mutant of Pag in pthG extended its host range on these beet species. A marker exchange mutant of Pag in hrpJ, encoding a component of the Type III secretion system, prevented HR elicitation. Mutations in each of the hrp regulatory genes (hrpY, hrpS and hrpL) substantially reduced the transcriptional activity of pthG in gypsophila cuttings. PthG could only be detected inside Pag cells during over-expression of hrpS or hrpL. Particle bombardment of GFP-PthG fusion caused cell death in beet, but not in non-host (melon) leaves. Present and previous results have established pthG as a broad-host-range avr gene that functions in multiple host plant species and the first functional avr gene in Pantoea spp.

  11. Phosphorus restriction prevents parathyroid gland growth. High phosphorus directly stimulates PTH secretion in vitro.

    Science.gov (United States)

    Slatopolsky, E; Finch, J; Denda, M; Ritter, C; Zhong, M; Dusso, A; MacDonald, P N; Brown, A J

    1996-01-01

    Dietary phosphorus (P) restriction is known to ameliorate secondary hyperparathyroidism in renal failure patients. In early renal failure, this effect may be mediated by an increase in 1,25-(OH)2D3, whereas in advanced renal failure, P restriction can act independent of changes in 1,25-(OH)2D3 and serum ionized calcium (ICa). In this study, we examined the effects of dietary P on serum PTH, PTH mRNA, and parathyroid gland (PTG) hyperplasia in uremic rats. Normal and uremic rats were maintained on a low (0.2%) or high (0.8%) P diet for 2 mo. PTG weight and serum PTH were similar in both groups of normal rats and in uremic rats fed the 0.2% P diet. In contrast, there were significant increases in serum PTH (130 +/- 25 vs. 35 +/- 3.5 pg/ml, P < 0.01), PTG weight (1.80 +/- 0.13 vs. 0.88 +/- 0.06 microg/gram of body weight, P < 0.01), and PTG DNA (1.63 +/- 0.24 vs. 0.94 +/- 0.07 microg DNA/gland, P < 0.01) in the uremic rats fed the 0.8% P diet as compared with uremic rats fed the 0.2% P diet. Serum ICa and 1,25-(OH)2D3 were not altered over this range of dietary P, suggesting a direct effect of P on PTG function. We tested this possibility in organ cultures of rat PTGs. While PTH secretion was acutely (30 min) regulated by medium calcium, the effects of medium P were not evident until 3 h. During a 6-h incubation, PTH accumulation was significantly greater in the 2.8 mM P medium than in the 0.2 mM P medium (1,706 +/- 215 vs. 1,033 +/- 209 pg/microg DNA, P < 0.02); the medium ICa was 1.25 mM in both conditions. Medium P did not alter PTH mRNA in this system, but cycloheximide (10 microg/ml) abolished the effect of P on PTH secretion. Thus, the effect of P is posttranscriptional, affecting PTH at a translational or posttranslational step. Collectively, these in vivo and in vitro results demonstrate a direct action of P on PTG function that is independent of ICa and 1,25-(OH)2D3. PMID:8647946

  12. Are PTH levels related to oxidative stress and inflammation in chronic kidney disease patients on hemodialysis?

    Directory of Open Access Journals (Sweden)

    Marcel Jaqueto

    Full Text Available Abstract Introduction: Patients at end stage renal disease have higher levels of inflammation and oxidative stress than the general population. Many factors contribute to these issues, and the parathyroid hormone (PTH is also implicated. Objective: The study was conducted in order to assess the relationship between PTH levels and inflammation and oxidative stress in hemodialysis patients. Methods: Cross-sectional study with patients of two hemodialysis facilities in Londrina, Brazil. Patients with other conditions known to generate oxidative stress and inflammation were excluded. Blood levels of PTH and biochemical parameters of inflammation (interleukins 1 and 6, tumor necrosis factor-alpha and oxidative stress (total plasma antioxidant capacity, malonic dialdehyde, lipid hydroperoxidation, advanced oxidation protein products, quantification of nitric oxide metabolites, and 8-isoprostane were measured before a dialysis session. Then, we made correlation analyses between PTH levels - either as the continuous variable or categorized into tertiles-, and inflammatory and oxidative stress biomarkers. Results: PTH did not show any correlation with the tested inflammation and oxidative stress parameters, nor as continuous variable neither as categorical variable. Conclusion: In this descriptive study, the results suggest that the inflammation and oxidative stress of hemodialysis patients probably arise from mechanisms other than secondary hyperparathyroidism.

  13. Heliconia acuminata reproductive success is independent of local floral density O sucesso reprodutivo de Heliconia acuminata é independente da densidade floral local

    Directory of Open Access Journals (Sweden)

    Emilio M. Bruna

    2004-09-01

    Full Text Available Reproductive plants in tropical forests are patchily distributed, with some in large aggregations of reproductive consepecifics while others are relatively isolated. This variation in floral density is hypothesized to have a major effect on plant reproductive success, since individuals in higher density neighborhoods can attract more or higher quality pollinators. We experimentally tested this hypothesis with populations of the understory herb Heliconia acuminata in central Amazonia. We created replicated plots in which reproductive plant density spanned the range of naturally occurring floral neighborhood size, then measured three surrogates of plant fitness in focal plants in each array. There was no significant difference between any of the three floral neighborhood treatments in total seed production, fruit set, or the number of seeds produced per fruit. Pollinator visitation rates to plants in all treatments were extremely low, with many plants not visited at all during the observation period. This could be because H. acuminata's hummingbird pollinators are unable to find the widely scattered reproductive plants, however this hypothesis appears unlikely. Instead, natural flowering plant densities may simply be below the threshold value at which neighborhood effects become important, even in "high-density" aggregations. Nutrient limitation, selective fruit abortion, and reproduction via male rather than female function may also be playing a role. We argue the absence of neighborhood effects may be a general phenomenon in central Amazonian forests, though additional experiments with other plant-pollinator systems are needed to determine the extent to which this hypothesis is supported.Plantas reprodutivas em florestas tropicas são distribuidas em manchas, com algumas em grandes agregações coespecíficas e outras relativamente isoladas. A hipótese é que esta variação na densidade de flores em um local tem um grande efeito no sucesso

  14. Tissue-specific transcription start sites and alternative splicing of the parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor gene: a new PTH/PTHrP receptor splice variant that lacks the signal peptide.

    Science.gov (United States)

    Joun, H; Lanske, B; Karperien, M; Qian, F; Defize, L; Abou-Samra, A

    1997-04-01

    The PTH/PTHrP receptor gene is expressed in bone and kidney as well as in many other tissues. Using primer extension followed by rapid cloning of amplified complementary DNA ends, we have isolated new PTH/PTHrP receptor complementary DNAs with different splicing patterns and have characterized a new upstream transcription start site. Three 5' nontranslated exons, U3, U2 and U1, located 4.8, 2.5, and 1.2 kb upstream of the exon that encodes the putative signal peptide of the classical receptor (exon S), have been characterized. Four types of splicing patterns were recognized. Type I splicing pattern is transcribed from exon U1 and is spliced to exons S and E1; this pattern was found in most tissues tested. Types II, III, and IV splicing patterns are transcribed from exon U3 and have a restricted tissue distribution. Type II splice pattern, containing exons U3, U2, and S and type III splicing pattern, containing exon U3, U2, and E1 (skipping exon S), was found only in kidney. Type IV splice pattern, containing exon U3 and S was found both in kidney and ovary. Because the type III splice variant skips exon S, translation of this splice variant initiates at a different AUG codon. The type III splice variant was weakly expressed on the cell surface of COS-7 cells, as assessed by double antibody binding assay, and no detectable ligand binding was observed on intact cells. The type III splice variant, however, increased cAMP accumulation in COS-7 cells when challenged with PTH(1-34), PTH(1-84) and hPTHrP(1-36) with EC50s that are similar to those observed in COS-7 cells expressing the type I variant but with a maximum stimulation that was lower than that observed in COS-7 cells expressing the type I variant. These data indicate low levels of cell surface expression of the type III splice variant. Treatment of COS-7 cells with tunicamycin decreased the size of the type I splice variant from a broad band of 85 kDa to a compact band of about 60 kDa. The type III splice

  15. Cell Cycle and Apoptosis Regulatory Protein (CARP)-1 is Expressed inOsteoblasts and Regulated by PTH

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Sonali; Mahalingam, Chandrika D.; Das, Varsha [Department of Internal Medicine/Endocrinology, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Jamal, Shazia [Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Levi, Edi [Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Rishi, Arun K. [Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201 (United States); VA Medical Center, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Datta, Nabanita S., E-mail: ndatta@med.wayne.edu [Department of Internal Medicine/Endocrinology, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, MI 48201 (United States)

    2013-07-12

    Highlights: •CARP-1 is identified for the first time in bone cells. •PTH downregulates CARP-1 expression in differentiated osteoblasts. •PTH displaces CARP-1 from nucleus to the cytoplasm in differentiated osteoblasts. •Downregulation of CARP-1 by PTH involves PKA, PKC and P-p38 MAPK pathways. -- Abstract: Bone mass is dependent on osteoblast proliferation, differentiation and life-span of osteoblasts. Parathyroid hormone (PTH) controls osteoblast cell cycle regulatory proteins and suppresses mature osteoblasts apoptosis. Intermittent administration of PTH increases bone mass but the mechanism of action are complex and incompletely understood. Cell Cycle and Apoptosis Regulatory Protein (CARP)-1 (aka CCAR1) is a novel transducer of signaling by diverse agents including cell growth and differentiation factors. To gain further insight into the molecular mechanism, we investigated involvement of CARP-1 in PTH signaling in osteoblasts. Immunostaining studies revealed presence of CARP-1 in osteoblasts and osteocytes, while a minimal to absent levels were noted in the chondrocytes of femora from 10 to 12-week old mice. Treatment of 7-day differentiated MC3T3-E1 clone-4 (MC-4) mouse osteoblastic cells and primary calvarial osteoblasts with PTH for 30 min to 5 h followed by Western blot analysis showed 2- to 3-fold down-regulation of CARP-1 protein expression in a dose- and time-dependent manner compared to the respective vehicle treated control cells. H-89, a Protein Kinase A (PKA) inhibitor, suppressed PTH action on CARP-1 protein expression indicating PKA-dependent mechanism. PMA, a Protein Kinase C (PKC) agonist, mimicked PTH action, and the PKC inhibitor, GF109203X, partially blocked PTH-dependent downregulation of CARP-1, implying involvement of PKC. U0126, a Mitogen-Activated Protein Kinase (MAPK) Kinase (MEK) inhibitor, failed to interfere with CARP-1 suppression by PTH. In contrast, SB203580, p38 inhibitor, attenuated PTH down-regulation of CARP-1

  16. Institutional experience of PTH evaluation on fine-needle washing after aspiration biopsy to locate hyperfunctioning parathyroid tissue

    Institute of Scientific and Technical Information of China (English)

    Massimo GIUSTI; Mara DOLCINO; Lara VERA; Carla GHIARA; Francesca MASSARO; Laura FAZZUOLI; Diego FERONE; Michele MUSSAP; Francesco MINUTO

    2009-01-01

    Assaying parathyroid hormone (PTH) in the washing liquid after fine-needle aspiration biopsy (FNAB) seems to be a valid approach to locate parathyroid tissue. PTH-FNAB was evaluated in 47 patients with a clinical picture of primary hyper-parathyroidism (PHP) and ultrasonography (US) suggestive of parathyroid lesion. The patients were subdivided into two groups on the basis of the absence or presence of US thyroid alterations. The result of PTH-FNAB was compared with those of cytology, scintigraphy and, in 24 patients, surgical outcome. PTH-FNAB samples with a value higher than that recorded in the serum and higher than our institutional cut-off were deemed to be probable samples of parathyroid tissue. Cytology proved diagnostic for benign thyroid lesions, non-diagnostic for thyroid lesions, hyperplastic parathyroid tissue, undetermined or malignant thyroid lesions and other lesions in 45%, 30%, 17%, 4%, and 4% of cases, respectively. In 47% of cases, PTH-FNAB indicated that the sample had been taken in parathyroid tissue. In patients without US alterations, the diagnostic accuracy of PTH-FNAB was greater than that of scintigraphy. After surgery, comparison between the results of PTH-FNAB and scintigraphy, in terms of positive predictive value (PPV), revealed the superiority of PTH-FNAB; PPV was 94% for FNAB and 71% for scintigraphy, while sen-sitivity was 83% and 69%, respectively. PTH-FNAB evaluation after FNAB appears to be more diagnostic than cytology and scintigraphy. Of all the procedures used, PTH-FNAB appears to be the method of choice when the target is US suggestive and reachable. PTH-FNAB appears to be a useful method of guiding surgical intervention.

  17. The effect of PTH(1-34) on fracture healing during different loading conditions

    DEFF Research Database (Denmark)

    Ellegaard, Maria; Kringelbach, Tina; Syberg, Susanne

    2013-01-01

    . Five days before fracture, half of the animals received Botulinum Toxin A injections in the muscles of the fractured leg to induce muscle paralysis (unloaded group), whereas the other half received saline injections (control group). For the following 8 weeks, half of the animals in each group received...... and control animals. PTH(1-34) treatment increased ultimate force of the fracture by 63% in both control and unloaded animals and no interaction of the two interventions could be detected. PTH(1-34) was able to stimulate bone formation in normally loaded as well as unloaded intact bone. In conclusion...

  18. Dual regulation of the parathyroid hormone (PTH)/PTH-related peptide receptor signaling by protein kinase C and beta-arrestins.

    Science.gov (United States)

    Castro, Marián; Dicker, Frank; Vilardaga, Jean-Pierre; Krasel, Cornelius; Bernhardt, Manfred; Lohse, Martin J

    2002-10-01

    We examined here the role of second messenger-dependent kinases and beta-arrestins in short-term regulation of the PTH receptor (PTHR) signaling. The inhibition of protein kinase C (PKC) in COS-7 cells transiently expressing PTHR, led to an approximately 2-fold increase in PTH-stimulated inositol phosphate (IP) and cAMP production. The inhibition of protein kinase A increased cAMP production 1.5-fold without affecting IP signaling. The effects of PKC inhibition on PTHR-mediated G(q) signaling were strongly decreased for a carboxy-terminally truncated PTHR (T480) that is phosphorylation deficient. PKC inhibition was associated with a decrease in agonist-stimulated PTHR phosphorylation and internalization without blocking PTH-dependent mobilization of beta-arrestin2 to the plasma membrane. Overexpression of beta-arrestins strongly decreased the PTHR-mediated IP signal, whereas cAMP production was impaired to a much lower extent. The regulation of PTH-stimulated signals by beta-arrestins was impaired for the truncated T480 receptor. Our data reveal mechanisms at, and distal to, the receptor regulating PTHR-mediated signaling pathways by second messenger-dependent kinases. We conclude that regulation of PTHR-mediated signaling by PKC and beta-arrestins are separable phenomena that both involve the carboxy terminus of the receptor. A major role for PKC and beta-arrestins in preferential regulation of PTHR-mediated G(q) signaling by independent mechanisms at the receptor level was established.

  19. Pseudohypoparathyroidism type Ib is not caused by mutations in the coding exons of the human parathyroid hormone (PTH)/PTH-related peptide receptor gene

    Energy Technology Data Exchange (ETDEWEB)

    Schipani, E.; Bergwitz, C.; Iida-Klein, A. [Massachusetts General Hospital, Boston, MA (United States)] [and others

    1995-05-01

    Pseudohypoparathyroidism type Ib (PHP-Ib) is thought to be from caused by a PTH/PTH-related peptide (PTHrP) receptor defect. To search for receptor mutations in genomic DNA from 17 PHP-Ib patients, three recently isolated human genomic DNA clones were further characterized by restriction enzyme mapping and nucleotide sequencing across intron/exon borders. Regions including all 14 coding exons and their splice junctions were amplified by polymerase chain reaction, and the products were analyzed by either temperature gradient gel electrophoresis or direct nucleotide sequencing. Silent polymorphisms were identified in exons G (1 of 17), M4 (1 of 17), and M7 (15 of 17). Two base changes were found in introns, 1 at the splice-donor site of the intron between exons E2 and E3 (1 of 17) and the other between exons G and M1 (2 of 17). Total ribonucleic acid from COS-7 cells expressing minigenes with or without the base change between exons E2 and E3 showed no difference by either Northern blot analysis or reverse transcriptase-polymerase chain reaction. Radioligand binding was indistinguishable for both transiently expressed constructs. A missense mutation (E546 to K546) in the receptor`s cytoplamic tail (3 of 17) was also found in 1 of 60 healthy individuals, and PTH/PTHrP receptors with this mutation were functionally indistinguishable from wild-type receptors. PHP-Ib thus appears to be rarely, if ever, caused by mutations in the coding exons of the PTH/PTHrP receptor gene. 58 refs., 4 figs., 4 tabs.

  20. A novel, mild, specific and indirect maleimido-based radioiodolabeling method; Radiolabeling of analogs derived from parathyroid hormone (PTH) and PTH-related protein (PTHrP)

    Energy Technology Data Exchange (ETDEWEB)

    Chorev, M.; Caulfield, M.P.; Roubini, E.; McKee, R.L.; Gibbons, S.W.; Chih-Tai Leu; Levy, J.J.; Rosenblatt, M.

    1992-01-01

    In an effort to design a mild, non-oxidative and site-specific means of radiolabeling bioactive molecules we have employed maleimido-sulfhydryl chemistry to produce bioactive hormone radioligands. We have prepared two novel radioiodolabeled reagents, 3'-maleimidopropanoyl-3-[sup 125]I-tyramide and its retro analog, N-maleoyl-N'-3-(4-hydroxy-3-[sup 125]I-phenyl)propanoyl ethylenediamide, by either oxidative radioiodination of the precursors or radiolabeling of the phenolic component prior to its incorporation into the radiolabeling reagents. These reagents were then used to radiolabel analogs of parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) in an efficient way, yielding reaction mixtures which were easily purified. The radioligands obtained are stable upon storage and bind in an reversible manner to a single population of binding sites displaying affinity in the low nanomolar range. The potencies of these analogs are comparable to the non-modified PTH and PTH rP analogs. This study demonstrates the utility of the novel maleimido-based indirect radioiodination approach and highlights some of its advantages over either direct oxidative procedures or acylation using the Bolton-Hunter reagent. (au).

  1. Effects of increasing age, dosage, and duration of PTH treatment on BMD increase--a meta-analysis

    DEFF Research Database (Denmark)

    Schwarz, Peter; Jorgensen, Niklas Rye; Mosekilde, Leif;

    2012-01-01

    We studied the effects of increasing age, dosage, and duration of parathyroid hormone (PTH) treatment on changes in bone mineral density (BMD). Randomized placebo controlled trials on PTH treatment in men or women were retrieved from PubMed (1951 to present), Web of Science (1945 to present...

  2. Pohnpei, FSM case study in a global health project documents its local food resources and successfully promotes local food for health.

    Science.gov (United States)

    Englberger, L; Kuhnlein, H V; Lorens, A; Pedrus, P; Albert, K; Currie, J; Pretrick, M; Jim, R; Kaufer, L

    2010-04-01

    This paper presents a summary of Pohnpei, Federated States Micronesia's involvement in a global health study focused on documenting traditional food systems in different parts of the world and providing evidence that local resources are critical for food security, nutrition and health. The Pohnpei study was based in Mand Community, Madolenihmw. The study found that there was a great diversity of foods locally available (381 food items documented), but these were underused. Overweight, obesity, diabetes, and vitamin A deficiency were identified as serious problems. Interventions included community meetings, school activities, and agriculture workshops, cooking classes, charcoal oven development, weight loss and planting competitions, poster campaigns and other relevant mass media. Significant dietary improvements were achieved following the intervention efforts, as well as positive changes in attitude towards local food including: decrease in average daily rice consumption from 846 g/person in 2005 to 544 g/person in 2007 (p = 0.0002); increase in provitamin A carotenoid intake from 227 microg/person in 2005 to 475 microg/person in 2007 (p = 0.02); increased frequency of consumption of local banana (53%), giant swamp taro (476%), local vegetables (130%); and increased dietary diversity (4.8 local food groups consumed in 2005 to 5.5 in 2007). Another positive outcome in Pohnpei was the popularization of the slogan "Let's Go Local."

  3. Differences in pollination success between local and foreign flower color phenotypes: a translocation experiment with Gentiana lutea (Gentianaceae

    Directory of Open Access Journals (Sweden)

    Javier A. Guitián

    2017-02-01

    Full Text Available Background The adaptive maintenance of flower color variation is frequently attributed to pollinators partly because they preferentially visit certain flower phenotypes. We tested whether Gentiana lutea—which shows a flower color variation (from orange to yellow in the Cantabrian Mountains range (north of Spain—is locally adapted to the pollinator community. Methods We transplanted orange-flowering individuals to a population with yellow-flowering individuals and vice versa, in order to assess whether there is a pollination advantage in the local morph by comparing its visitation rate with the foreign morph. Results Our reciprocal transplant experiment did not show clear local morph advantage in overall visitation rate: local orange flowers received more visits than foreign yellow flowers in the orange population, while both local and foreign flowers received the same visits in the yellow population; thus, there is no evidence of local adaptation in Gentiana lutea to the pollinator assemblage. However, some floral visitor groups (such as Bombus pratorum, B. soroensis ancaricus and B. lapidarius decipiens consistently preferred the local morph to the foreign morph whereas others (such as Bombus terrestris consistently preferred the foreign morph. Discussion We concluded that there is no evidence of local adaptation to the pollinator community in each of the two G. lutea populations studied. The consequences for local adaptation to pollinator on G. lutea flower color would depend on the variation along the Cantabrian Mountains range in morph frequency and pollinator community composition.

  4. In silico and functional evaluation of PTH1R mutations found in patients with primary failure of eruption (PFE).

    Science.gov (United States)

    Hendricks, H M; Bencharit, S; Seaman, W; Frazier-Bowers, S A

    2017-06-01

    The genetic basis of PFE (OMIM ID: 125350) was interrogated using molecular functional studies. PFE is a disorder that results in a poor prognosis in the eruption of teeth and by extension, in treatment with a continuous archwire. We tested the hypothesis that PTH1R mutations result in loss of function due to altered protein structure to determine (i) the fate of a functional PTH1R mutation and (ii) the resulting PTH1R protein structure of each functional mutation. We used immunofluorescence assay of COS7 cells that were transfected with either the WT or 1092delG PTH1R mutation sequence to compare the fate of the expressed protein. We also performed in silico analysis of the WT PTH1R and four different functional PTH1R mutations RESULTS: Functional studies (IFA) showed a variation in expression between the WT and mutant PTH1R. Further, in silico analysis showed structural differences between WT and mutant PTH1R proteins, particularly in the regions of the 3rd intracellular loop and the 6th transmembrane domain required for efficient PTH1R function. PTH1R mutations identified in PFE likely result from diminished function due to truncation of the protein, lack of efficient G-protein interactions and putatively attenuated signal transduction. By identifying the mode of protein dysfunction, scientist-clinicians are better prepared to recognize and thereby develop improved methods of treatment, starting at the molecular level. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Glucocorticoid-Induced Osteoporosis in Growing Mice Is Not Prevented by Simultaneous Intermittent PTH Treatment

    NARCIS (Netherlands)

    Postnov, A.; de Schutter, T.; Sijbers, J.; Karperien, Hermanus Bernardus Johannes; de Clerck, N.

    2009-01-01

    Glucocorticoids (GCs) are widely used in medicine for treatment of chronic diseases. Especially in children, prolonged treatment causes growth retardation and early onset of osteoporosis. Human parathyroid hormone (PTH) has an anabolic effect on bone when administrated intermittently. The aim of the

  6. Monitoring of intermittent PTH(1-34) treatment by serum PINP in adult ovariectomized osteopenic rats

    DEFF Research Database (Denmark)

    Halleen, Jussi; Peng, ZhiQi; Fagerlund, Katja

    , allowing measurement of serum PINP in preclinical rodent osteoporosis models. The purpose of this study was to evaluate the use of serum PINP for monitoring intermittent PTH(1-34) treatment in adult ovariectomized (OVX) osteopenic rats. Study groups included a sham-operated control group and an OVX...

  7. Changes in Vitamin D and PTH Metabolism in Incident Pediatric Crohn Disease

    Science.gov (United States)

    Prosnitz, Aaron R.; Leonard, Mary B.; Shults, Justine; Zemel, Babette S.; Hollis, Bruce W.; Denson, Lee A.; Baldassano, Robert N.; Cohen, Aaron B.; Thayu, Meena

    2015-01-01

    Background and Aims Prior studies of vitamin D metabolism in Crohn disease (CD) did not include controls or examine changes following diagnosis. This study examined associations among 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D] and parathyroid hormone (PTH) levels in incident pediatric CD, compared with controls, and following diagnosis. Methods Serum vitamin D and PTH were measured at diagnosis (n = 78), 6, 12, and a median of 43 months (n = 52) later in CD participants, and once in 221 controls. Multivariate regression was used to examine baseline associations, and quasi-least squares regression to assess subsequent changes. Results At diagnosis, 42% of CD participants were 25(OH)D deficient (<20 ng/mL). The odds ratio for deficiency was 2.1 (95% CI 1.1, 3.9; p<0.05) vs. controls, adjusted for age, race, and season. 1,25(OH)2D was lower in CD vs. controls (p<0.05), adjusted for 25(OH)D, tumor necrosis factor–α (TNF-α) and PTH. TNF-α was associated with lower 1,25(OH)2D (p<0.05), and the positive association between PTH and 1,25(OH)2D in controls was absent in CD (interaction p=0.02). Among participants with 25(OH)D <30 ng/mL, CD was associated with lower PTH (p<0.05) vs. controls. Following diagnosis, 25(OH)D and 1,25(OH)2D improved (p<0.001). At the final visit, 3% were 25(OH)D deficient, PTH was no longer low relative to 25(OH)D, and 1,25(OH)2D was significantly elevated (p<0.001), compared with controls. Conclusions Incident CD was associated with 25(OH)D and 1,25(OH)2D deficiency and a relative hypoparathyroidism that resolved following diagnosis. Inflammatory cytokine suppression of PTH and renal 1-α-hyroxylase may contribute to these alterations. PMID:22488969

  8. local

    Directory of Open Access Journals (Sweden)

    Abílio Amiguinho

    2005-01-01

    Full Text Available The process of socio-educational territorialisation in rural contexts is the topic of this text. The theme corresponds to a challenge to address it having as main axis of discussion either the problem of social exclusion or that of local development. The reasons to locate the discussion in this last field of analysis are discussed in the first part of the text. Theoretical and political reasons are there articulated because the question is about projects whose intentions and practices call for the political both in the theoretical debate and in the choices that anticipate intervention. From research conducted for several years, I use contributions that aim at discuss and enlighten how school can be a potential locus of local development. Its identification and recognition as local institution (either because of those that work and live in it or because of those that act in the surrounding context are crucial steps to progressively constitute school as a partner for development. The promotion of the local values and roots, the reconstruction of socio-personal and local identities, the production of sociabilities and the equation and solution of shared problems were the dimensions of a socio-educative intervention, markedly globalising. This scenario, as it is argued, was also, intentionally, one of transformation and of deliberate change of school and of the administration of the educative territoires.

  9. Brief report: Does PTH increase with age, independent of 25-hydroxyvitamin D, phosphate, renal function, and ionized calcium?

    Science.gov (United States)

    Carrivick, Simon J; Walsh, John P; Brown, Suzanne J; Wardrop, Robert; Hadlow, Narelle C

    2015-05-01

    Circulating PTH concentrations increase with age. It is uncertain whether an age-related PTH increase occurs independent of changes in circulating 25-hydroxyvitamin D, phosphate, renal function, and ionized calcium. The purpose of this article was to analyze the relationship between PTH and age, controlling for 25-hydroxyvitamin D, phosphate, renal function, and ionized calcium. This was a retrospective, cross-sectional study analyzing the relationship between PTH and age in 2 independent datasets (laboratory 1, n = 17 275 and laboratory 2, n = 4878). We further analyzed subgroups after excluding participants with estimated glomerular filtration rate of increase in age was associated with a 5.0% increase in PTH (95% confidence interval [CI], 4.4%-5.6%; P increase in laboratory 2 (95% CI, 3.0%-5.4%; P increase in age was associated with a 6.1% increase in PTH (95% CI, 5.5%-6.8%; P increase (95% CI 3.5%-6.2%; P increase with age, independent of 25-hydroxyvitamin D, ionized calcium, phosphate, and renal function. Further research is required to explore the underlying mechanisms and clinical relevance and to determine whether the use of age-related PTH reference ranges improves diagnostic accuracy, particularly in elderly individuals.

  10. Developmental upregulation of human parathyroid hormone (PTH)/PTH-related peptide receptor gene expression from conserved and human-specific promoters.

    Science.gov (United States)

    Bettoun, J D; Minagawa, M; Hendy, G N; Alpert, L C; Goodyer, C G; Goltzman, D; White, J H

    1998-09-01

    The parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor (PTHR) functions in skeletal development and mediates an array of other physiological responses modulated by PTH and PTHrP. PTHR gene transcription in mouse is controlled by two promoters: P1, which is highly and selectively active in kidney; and P2, which functions in a variety of tissues. P1 and P2 are conserved in human tissue; however, P1 activity in kidney is weak. We have now identified a third human promoter, P3, which is widely expressed and accounts for approximately 80% of renal PTHR transcripts in the adult. No P3 activity was detected in mouse kidney, indicating that renal PTHR gene expression is controlled by different signals in human and mouse. During development, only P2 is active at midgestation in many human tissues, including calvaria and long bone. This strongly suggests that factors regulating well conserved P2 control PTHR gene expression during skeletal development. Our results indicate that human PTHR gene transcription is upregulated late in development with the induction of both P1 and P3 promoter activities. In addition, P2-specific transcripts are differentially spliced in a number of human cell lines and adult tissues, but not in fetal tissues, giving rise to a shorter and less structured 5' UTR. Thus, our studies show that both human PTHR gene transcription and mRNA splicing are developmentally regulated. Moreover, our data indicate that renal and nonrenal PTHR gene expression are tightly coordinated in humans.

  11. Enhancement of Lumbar Fusion and Alleviation of Adjacent Segment Disc Degeneration by Intermittent PTH(1-34) in Ovariectomized Rats.

    Science.gov (United States)

    Zhou, Zhuang; Tian, Fa-Ming; Gou, Yu; Wang, Peng; Zhang, Heng; Song, Hui-Ping; Shen, Yong; Zhang, Ying-Ze; Zhang, Liu

    2016-04-01

    Osteoporosis, which is prevalent in postmenopausal or aged populations, is thought to be a contributing factor to adjacent segment disc degeneration (ASDD), and the incidence and extent of ASDD may be augmented by osteopenia. Parathyroid hormone (PTH) (1-34) has already been shown to be beneficial in osteoporosis, lumbar fusion and matrix homeostasis of intervertebral discs. However, whether PTH(1-34) has a reversing or retarding effect on ASDD in osteopenia has not been confirmed. In the present study, we evaluated the effects of intermittent PTH(1-34) on ASDD in an ovariectomized (OVX) rat model. One hundred 3-month-old female Sprague-Dawley rats underwent L4 -L5 posterolateral lumbar fusion (PLF) with spinous-process wire fixation 4 weeks after OVX surgery. Control groups were established accordingly. PTH(1-34) was intermittently administered immediately after PLF surgery and lasted for 8 weeks using the following groups (n = 20) (V = vehicle): Sham+V, OVX+V, Sham+PLF+V, OVX+PLF+V, OVX+PLF+PTH. The fused segments showed clear evidence of eliminated motion on the fusion-segment based on manual palpation. Greater new bone formation in histology was observed in PTH-treated animals compared to the control group. The extent of ASDD was significantly increased by ovariotomy. Intermittent PTH(1-34) significantly alleviated ASDD by preserving disc height, microvessel density, relative area of vascular buds, endplate thickness and the relative area of endplate calcification. Moreover, protein expression results showed that PTH(1-34) not only inhibited matrix degradation by decreasing MMP-13, ADAMTS-4 and Col-I, but also promote matrix synthesis by increasing Col-II and Aggrecan. In conclusion, PTH(1-34), which effectively improves lumbar fusion and alleviates ASDD in ovariectomized rats, may be a potential candidate to ameliorate the prognosis of lumbar fusion in osteopenia.

  12. Factors Affecting Student Success in Distance Learning Courses at a Local California Community College: Joint Governance Perspectives

    Science.gov (United States)

    Gonzalez, Luis A.

    2012-01-01

    The purpose of this study was to explore the perspectives of staff and faculty regarding factors affecting student success in distance learning at a California community college (CCC). Participants were members of the leadership group known as the distance learning committee. Data were collected through in-depth interviews using open-ended…

  13. Factors Affecting Student Success in Distance Learning Courses at a Local California Community College: Joint Governance Perspectives

    Science.gov (United States)

    Gonzalez, Luis A.

    2012-01-01

    The purpose of this study was to explore the perspectives of staff and faculty regarding factors affecting student success in distance learning at a California community college (CCC). Participants were members of the leadership group known as the distance learning committee. Data were collected through in-depth interviews using open-ended…

  14. A new embedded-atom method approach based on the pth moment approximation

    Science.gov (United States)

    Wang, Kun; Zhu, Wenjun; Xiao, Shifang; Chen, Jun; Hu, Wangyu

    2016-12-01

    Large scale atomistic simulations with suitable interatomic potentials are widely employed by scientists or engineers of different areas. The quick generation of high-quality interatomic potentials is urgently needed. This largely relies on the developments of potential construction methods and algorithms in this area. Quantities of interatomic potential models have been proposed and parameterized with various methods, such as the analytic method, the force-matching approach and multi-object optimization method, in order to make the potentials more transferable. Without apparently lowering the precision for describing the target system, potentials of fewer fitting parameters (FPs) are somewhat more physically reasonable. Thus, studying methods to reduce the FP number is helpful in understanding the underlying physics of simulated systems and improving the precision of potential models. In this work, we propose an embedded-atom method (EAM) potential model consisting of a new manybody term based on the pth moment approximation to the tight binding theory and the general transformation invariance of EAM potentials, and an energy modification term represented by pairwise interactions. The pairwise interactions are evaluated by an analytic-numerical scheme without the need to know their functional forms a priori. By constructing three potentials of aluminum and comparing them with a commonly used EAM potential model, several wonderful results are obtained. First, without losing the precision of potentials, our potential of aluminum has fewer potential parameters and a smaller cutoff distance when compared with some constantly-used potentials of aluminum. This is because several physical quantities, usually serving as target quantities to match in other potentials, seem to be uniquely dependent on quantities contained in our basic reference database within the new potential model. Second, a key empirical parameter in the embedding term of the commonly used EAM model is

  15. Acute hypotension induced by aortic clamp vs. PTH provokes distinct proximal tubule Na+ transporter redistribution patterns

    DEFF Research Database (Denmark)

    Leong, Patrick K K; Yang, Li E; Lin, Harrison W

    2004-01-01

    clearance. There was, however, no significant change in glomerular filtration rate (GFR) or subcellular distribution of NHE3 and NaPi2. In contrast, high-dose PTH rapidly (blood pressure to 51 +/- 3 mmHg, decreased urine output, and shifted NHE3 and NaPi2 out of the low......-density membranes enriched in apical markers. PTH at much lower doses (blood pressure and was diuretic. In conclusion, acute hypotension per se increases proximal tubule Na(+) reabsorption without changing NHE3 or NaPi2 subcellular distribution, indicating that trafficking...... in renal cortical membranes fractionated on sorbitol density gradients. Aortic clamp-induced acute hypotension (from 100 +/- 3 to 78 +/- 2 mmHg) provoked a 62% decrease in urine output and a significant decrease in volume flow from the proximal tubule detected as a 66% decrease in endogenous lithium...

  16. Establishment and characterization of a human ovarian small cell carcinoma, hypercalcemic type, cell line (OS-1) secreting PTH, PthrP and ACTH--special reference to the susceptibility of anti-cancer drugs.

    Science.gov (United States)

    Ohi, Satoshi; Niimi, Shigeki; Okada, Naoya; Yamada, Kyosuke; Tachibana, Toshiaki; Hashimoto, Hisashi; Nakajima, Masako; Yasuda, Mitsuru; Tanaka, Tadao; Sato, Kahei; Ishikawa, Hiroshi

    2004-12-01

    We successfully established a novel cell line (OS-1) derived from human ovarian small cell carcinoma, hypercalcemic type secreted PTH, PTH-rP and ACTH. The OS-1 cell line was established from metastatic focus of uterus. A patient was 25-year-old Japanese woman. The first she received left ovariectomy on April 2002. The histopathological diagnosis was ovarian small cell carcinoma, pT2c, Nx, Mx. Then on June 2003, metastatic focus of uterus was ectomied. A part of the recurrent tumor of uterus was cut into small pieces with razor blades, and dissociated with 0.1% trypsin-0.02% EDTA/ PBS(-) solution at room temperature. The single cells and small cell clusters were seeded into 60mm dishes and cultured in growth medium (GM: DMEM/F12 supplemented with 20% fetal bovine serum and 0.1% non-essential amino acids solution) at 37 degrees C, 4.7% CO2 in humidified air. Medium was exchanged twice a week. The OS-1 cells grew as floating cultures in the dishes. Radioimmunoassay of the conditioned media was revealed that the cultures secreted large amount of PTH, PTHrP and ACTH simultaneously. Susceptibilities of anti-cancer drugs to the OS-1 cells were examined using oxygen electrode meter (Daikin), and the results suggested VLB and TXL were effective, and CDDP, CPT-11, VP-16, VCR, CPA, MMC and CBDCA were not effective. In our knowledge, it is the first report that the cell line secreting PTH, PTHrP and ACTH was successfully established from ovarian small cell carcinoma, hypercalcemic type. We expect that OS-1 cell line contribute to study on the mechanism of ectopic hormone secretion and susceptibility of anti cancer drugs to the small cell carcinoma.

  17. Successful combination treatment of a patient with progressive juvenile localized scleroderma (morphea) using imatinib, corticosteroids, and methotrexate.

    Science.gov (United States)

    Inamo, Yasuji; Ochiai, Toyoko

    2013-01-01

    We report a case of progressive juvenile localized scleroderma (JLS or morphea) treated with a combination of imatinib, corticosteroids, and methotrexate. This therapy halted the progressive skin thickening and the hand and finger joint deformity in the early stages of the disease. We conclude that imatinib used in addition to standard treatment with systemic corticosteroids and methotrexate may be of therapeutic benefit for individuals with JLS.

  18. P-th moment and almost sure stability of stochastic switched nonlinear systems.

    Science.gov (United States)

    Gu, Haibo; Gao, Caixia

    2016-01-01

    This paper mainly tends to utilize [Formula: see text]-type function to investigate p-th moment and almost sure stability for a class of stochastic switched nonlinear systems. Based on the multiple Lyapunov functions approach, some sufficient conditions are derived to check the stability criteria of stochastic switched nonlinear systems. One numerical example is provided to demonstrate the effectiveness of the proposed results.

  19. SWOT ANALYSIS MICRO SMALL MEDIUM ENTREPRISE (MSME GEULIS CRAFT UMBRELLA TO SUCCESS IN LOCAL ECONOMIC DEVELOPMENT RESOURCES DISTRICT TASIKMALAYA

    Directory of Open Access Journals (Sweden)

    K. Dianta A. Sebayang

    2012-03-01

    Full Text Available Development of local economic resources, a new trend in the effort to increase the income of the community and the region. Local factors that determine both in terms of natural resources (raw materials and human resources (labor. This paper attempts to present how small and medium enterprises "Kerajinan Payung Geulis" try to improve economic development based on the development of local economic resources in Tasikmalaya. This study aims to illustrate the potential of entrepreneurs that include the competence and commitment of entrepreneurs in small business business, and to illustrate the strength of business / competitive position, business profile and entrepreneur influenced by environmental condition of external and internal environment, seen from the positive and negative side. The research was conducted on umbrella industry of handicraft business in Tasikmalaya. The method used in this research is descriptive analysis by using SWOT analysis. The results show many problems encountered and very complex, such as: low quality of human resources, limited business capital, low access to markets, access to financial institutions / banks are absent, administrative procedures ignorance, sustainability and limited capacity production; Coupled with the business climate is not conducive to the development of SMEs and entrepreneurship.

  20. Solution Structure of Archaeoglobus fulgidis Peptidyl-tRNA Hydrolase(Pth2) Provides Evidence for an Extensive Conserved Family of Pth2 Enzymes in Archaea, Bacteria and Eukaryotes.

    Energy Technology Data Exchange (ETDEWEB)

    Powers, Robert; Mirkovic, Nebojsa; Goldsmith-Fischman, Sharon; Acton, Thomas; Chiang, Yiwen; Huang, Yuanpeng; Ma, LiChung; Rajan, Paranji K.; Cort, John R.; Kennedy, Michael A.; Liu, Jinfeng; Rost, Burkhard; Honig, Barry; Murray, Diana; Montelione, Gaetano

    2005-11-01

    The solution structure of protein AF2095 from the thermophilic archaea Archaeglobus fulgidis, a 123-residue (13.6 kDa) protein, has been determined by NMR methods. The structure of AF2095 is comprised of four a-helices and a mixed b-sheet consisting of four parallel and anti-parallel b-strands, where the a-helices sandwich the b-sheet. Sequence and structural comparison of AF2095 with proteins from Homo sapiens, Methanocaldococcus jannaschii and Sulfolobus solfataricus, reveals that AF2095 is a peptidyl-tRNA hydrolase (Pth2). This structural comparison also identifies putative catalytic residues and a tRNA interaction region for AF2095. The structure of AF2095 is also similar to the structure of protein TA0108 from archaea Thermoplasma acidophilum, which is deposited in the Protein Database but not functionally annotated. The NMR structure of AF2095 has been further leveraged to obtain good quality structural models for 55 other proteins. Although earlier studies have proposed that the Pth2 protein family is restricted to archeal and eukaryotic organisms, the similarity of the AF2095 structure to human Pth2, the conservation of key active-site residues, and the good quality of the resulting homology models demonstrate a large family of homologous Pth2 proteins that are conserved in eukaryotic, archaeal and bacterial organisms, providing novel insights in the evolution of the Pth and Pth2 enzyme families.

  1. PTH/PTHrP Receptor Mediates Cachexia in Models of Kidney Failure and Cancer.

    Science.gov (United States)

    Kir, Serkan; Komaba, Hirotaka; Garcia, Ana P; Economopoulos, Konstantinos P; Liu, Wei; Lanske, Beate; Hodin, Richard A; Spiegelman, Bruce M

    2016-02-09

    Cachexia is a wasting syndrome associated with elevated basal energy expenditure and loss of adipose and muscle tissues. It accompanies many chronic diseases including renal failure and cancer and is an important risk factor for mortality. Our recent work demonstrated that tumor-derived PTHrP drives adipose tissue browning and cachexia. Here, we show that PTH is involved in stimulating a thermogenic gene program in 5/6 nephrectomized mice that suffer from cachexia. Fat-specific knockout of PTHR blocked adipose browning and wasting. Surprisingly, loss of PTHR in fat tissue also preserved muscle mass and improved muscle strength. Similarly, PTHR knockout mice were resistant to cachexia driven by tumors. Our results demonstrate that PTHrP and PTH mediate wasting through a common mechanism involving PTHR, and there exists an unexpected crosstalk mechanism between wasting of fat tissue and skeletal muscle. Targeting the PTH/PTHrP pathway may have therapeutic uses in humans with cachexia. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. PTH has the potential to rescue disturbed bone growth in achondroplasia.

    Science.gov (United States)

    Ueda, Koso; Yamanaka, Yoshitaka; Harada, Daisuke; Yamagami, Emi; Tanaka, Hiroyuki; Seino, Yoshiki

    2007-07-01

    Achondroplasia (Ach), the most common form of short-limb short stature, and related disorders are caused by constitutively active point mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Recent studies have provided a large body of evidence for the role of the proliferation and differentiation of chondrocytes in these disorders. Furthermore, a G380R mutation in FGFR3 (FGFR3(Ach)), which results in achondroplasia, induces apoptosis in the chondrogenic cell line ATDC5. This is associated with a decrease in the expression of PTHrP, which shares the same receptor with PTH, and it is significant that PTHrP rescues these cells from apoptosis. Fetuses derived from transgenic mice expressing FGFR3(Ach) under the control of the type II collagen promoter (AchTG) or from wild-type mice were obtained on the 15th day of pregnancy. The femurs were collected from these specimens and cultured for 4 days with PTH. The effects of PTH treatment were then determined by morphometric and histological analyses, in situ hybridization of type X collagen mRNA, and the TUNEL assay. AchTG femurs showed suppressed growth compared with wild type (0.29+/-0.10 mm vs. 0.46+/-0.06 mm, respectively; ptreatments improved the growth velocity in the femurs of the AchTG (0.50+/-0.06 mm; pachondroplasia.

  3. PTH-dependence of the effectiveness of cinacalcet in hemodialysis patients with secondary hyperparathyroidism.

    Science.gov (United States)

    Akizawa, Tadao; Kurita, Noriaki; Mizobuchi, Masahide; Fukagawa, Masafumi; Onishi, Yoshihiro; Yamaguchi, Takuhiro; Ellis, Alan R; Fukuma, Shingo; Alan Brookhart, M; Hasegawa, Takeshi; Kurokawa, Kiyoshi; Fukuhara, Shunichi

    2016-04-13

    Cinacalcet lowers parathyroid hormone levels. Whether it can prolong survival of people with chronic kidney disease (CKD) complicated by secondary hyperparathyroidism (SHPT) remains controversial, in part because a recent randomized trial excluded patients with iPTH <300 pg/ml. We examined cinacalcet's effects at different iPTH levels. This was a prospective case-cohort and cohort study involving 8229 patients with CKD stage 5D requiring maintenance hemodialysis who had SHPT. We studied relationships between cinacalcet initiation and important clinical outcomes. To avoid confounding by treatment selection, we used marginal structural models, adjusting for time-dependent confounders. Over a mean of 33 months, cinacalcet was more effective in patients with more severe SHPT. In patients with iPTH ≥ 500 pg/ml, the reduction in the risk of death from any cause was about 50% (Incidence Rate Ratio [IRR] = 0.49; 95% Confidence Interval [95% CI]: 0.29-0.82). For a composite of cardiovascular hospitalization and mortality, the association was not statistically significant, but the IRR was 0.67 (95% CI: 0.43-1.06). These findings indicate that decisions about using cinacalcet should take into account the severity of SHPT.

  4. Structure, morphology and corrosion resistance of Ni–Mo+PTh composite coatings

    Indian Academy of Sciences (India)

    J Niedbała

    2015-06-01

    Ni–Mo+PTh composite coatings were prepared from nickel–molybdenum galvanic bath with the addition of thiophene (Th) and HClO4 as result of two processes: induced Ni–Mo alloy deposition and PTh polymerization. A scanning electron microscope was used for surface morphology characterization of the coatings. The Scanning ElectrochemicalWorkstationM370 was used to the surface map of the tested composite coatings. The chemical composition of the coatings was determined by the energy-dispersive spectroscopy (EDS) method. It was stated that the surface of the coatings are characterized by the presence of Ni–Mo particles and polythiophene agglomerates. Electrochemical corrosion investigations of coatings were carried out in the 5 M KOH solution, using voltammetry and electrochemical impedance spectroscopy (EIS) methods. On the basis of these research works it was found that the composite Ni–Mo+PTh coatings are more corrosion resistant in alkaline solution than Ni–Mo. The reasons for this are the presence of the polymer on the surface of the coatings and a decrease of corrosion active surface area of the coatings.

  5. Bone Is a Major Target of PTH/PTHrP Receptor Signaling in Regulation of Fetal Blood Calcium Homeostasis.

    Science.gov (United States)

    Hirai, Takao; Kobayashi, Tatsuya; Nishimori, Shigeki; Karaplis, Andrew C; Goltzman, David; Kronenberg, Henry M

    2015-08-01

    The blood calcium concentration during fetal life is tightly regulated within a narrow range by highly interactive homeostatic mechanisms that include transport of calcium across the placenta and fluxes in and out of bone; the mechanisms of this regulation are poorly understood. Our findings that endochondral bone-specific PTH/PTHrP receptor (PPR) knockout (KO) mice showed significant reduction of fetal blood calcium concentration compared with that of control littermates at embryonic day 18.5 led us to focus on bone as a possibly major determinant of fetal calcium homeostasis. We found that the fetal calcium concentration of Runx2 KO mice was significantly higher than that of control littermates, suggesting that calcium flux into bone had a considerable influence on the circulating calcium concentration. Moreover, Runx2:PTH double mutant fetuses showed calcium levels similar to those of Runx2 KO mice, suggesting that part of the fetal hypocalcemia in PTH KO mice was caused by the increment of the mineralized bone mass allowed by the formation of osteoblasts. Finally, Rank:PTH double mutant mice had a blood calcium concentration even lower than that of the either Rank KO or PTH KO mice alone at embryonic day 18.5. These observations in our genetic models suggest that PTH/PTHrP receptor signaling in bones has a significant role of the regulation of fetal blood calcium concentration and that both placental transport and osteoclast activation contribute to PTH's hypercalcemic action. They also show that PTH-independent deposition of calcium in bone is the major controller of fetal blood calcium level.

  6. PTH1–34 Blocks Radiation-induced Osteoblast Apoptosis by Enhancing DNA Repair through Canonical Wnt Pathway*

    Science.gov (United States)

    Chandra, Abhishek; Lin, Tiao; Zhu, Ji; Tong, Wei; Huo, Yanying; Jia, Haoruo; Zhang, Yejia; Liu, X. Sherry; Cengel, Keith; Xia, Bing; Qin, Ling

    2015-01-01

    Focal radiotherapy for cancer patients has detrimental effects on bones within the radiation field and the primary clinical signs of bone damage include the loss of functional osteoblasts. We reported previously that daily injection of parathyroid hormone (PTH, 1–34) alleviates radiation-induced osteopenia in a preclinical radiotherapy model by improving osteoblast survival. To elucidate the molecular mechanisms, we irradiated osteoblastic UMR 106-01 cells and calvarial organ culture and demonstrated an anti-apoptosis effect of PTH1–34 on these cultures. Inhibitor assay indicated that PTH exerts its radioprotective action mainly through protein kinase A/β-catenin pathway. γ-H2AX foci staining and comet assay revealed that PTH efficiently promotes the repair of DNA double strand breaks (DSBs) in irradiated osteoblasts via activating the β-catenin pathway. Interestingly, Wnt3a alone also blocked cell death and accelerated DNA repair in primary osteoprogenitors, osteoblastic and osteocytic cells after radiation through the canonical signaling. Further investigations revealed that both Wnt3a and PTH increase the amount of Ku70, a core protein for initiating the assembly of DSB repair machinery, in osteoblasts after radiation. Moreover, down-regulation of Ku70 by siRNA abrogated the prosurvival effect of PTH and Wnt3a on irradiated osteoblasts. In summary, our results identify a novel role of PTH and canonical Wnt signaling in regulating DSB repair machinery and apoptosis in osteoblasts and shed light on using PTH1–34 or Wnt agonist as possible therapy for radiation-induced osteoporosis. PMID:25336648

  7. Successful Re-resection for Locally Recurrent Retroperitoneal Liposarcoma at Four Years After Ex Vivo Tumor Resection and Autotransplantation of the Liver: A Case Report.

    Science.gov (United States)

    Kobayashi, T; Miura, K; Ishikawa, H; Soma, D; Zhang, Z; Yuza, K; Hirose, Y; Takizawa, K; Nagahashi, M; Sakata, J; Kameyama, H; Kosugi, S; Wakai, T

    2016-05-01

    Surgical resection should be considered for isolated locally recurrent retroperitoneal liposarcomas. We experienced a case of successful re-resection for locally recurrent retroperitoneal liposarcomas 4 years after ex vivo tumor resection and autotransplantation of the liver. A 75-year-old man was admitted to our hospital. His diagnosis was local recurrence of liposarcomas. He had previously undergone ex vivo tumor resection and autologous orthotopic liver transplantation for a retroperitoneal tumor 4 years earlier. The resected tumor size was 23.5 × 15.5 × 12.5 cm. The tumor was revealed by means of histopathologic study to be a myxoid liposarcoma. Follow-up computerized tomography showed 2 recurrent tumors in the retropancreatic and para-aortic lesions. Although adhesion was severe within the operative field, we successfully performed complete en bloc re-resection of each recurrent tumor. The operative time was 250 minutes, and blood loss was 300 mL. The resected tumor sizes were 3.9 × 3.2 × 1.5 cm and 4.5 × 3.3 × 3.0 cm. The tumors were revealed by means of histopathologic study to be dedifferentiated liposarcomas. Postoperative complications included intestinal obstruction and colocutaneous fistula formation, both of which were treated surgically. The patient was discharged in an ambulatory state at 80 days after re-resection of the recurrent tumors. At the time of writing, he was alive with no evidence of recurrence, 14 months after re-resection and 62 months after primary ex vivo tumor resection. This is the first case of successful surgical re-resection for locally recurrent liposarcoma after ex vivo tumor resection and autotransplantation of the liver.

  8. Suppression of Wnt signaling by Dkk1 attenuates PTH-mediated stromal cell response and new bone formation.

    Science.gov (United States)

    Guo, Jun; Liu, Minlin; Yang, Dehong; Bouxsein, Mary L; Saito, Hiroaki; Galvin, R J Sells; Kuhstoss, Stuart A; Thomas, Clare C; Schipani, Ernestina; Baron, Roland; Bringhurst, F Richard; Kronenberg, Henry M

    2010-02-03

    Parathyroid hormone (PTH) suppresses Dickkopf 1 (Dkk1) expression in osteoblasts. To determine whether this suppression is essential for PTH-mediated Wnt signaling and bone formation, we examined mice that overexpress Dkk1 in osteoblasts (Dkk1 mice). Dkk1 mice were osteopenic due to abnormal osteoblast and osteoclast activity. When fed a low-calcium diet, and in two other models of hyperparathyroidism, these mice failed to develop the peritrabecular stromal cell response ("osteitis fibrosis") and new bone formation seen in wild-type mice. Despite these effects of Dkk1 overexpression, PTH still activated Wnt signaling in Dkk1 mice and in osteoblastic cells cultured from these mice. In cultured MC3T3E1 preosteoblastic cells, PTH dramatically suppressed Dkk1 expression, induced PKA-mediated phosphorylation of beta-catenin, and significantly enhanced Lef1 expression. Our findings indicate that the full actions of PTH require intact Wnt signaling but that PTH can activate the Wnt pathway despite overexpression of Dkk1.

  9. A Case of Sublingual Ranula That Responded Successfully to Localized Injection Treatment with OK-432 after Healing from Drug Induced Hypersensitivity Syndrome

    Directory of Open Access Journals (Sweden)

    Kunio Yoshizawa

    2016-01-01

    Full Text Available A ranula is a mucus retention cyst or pseudocyst caused by leakage of mucus from the sublingual gland and generally occurs in the oral floor. In addition, drug induced hypersensitivity syndrome (DIHS is a rare but well-recognized serious adverse effect characterized by fever, skin rashes, generalized lymphadenopathy, hepatitis, and hepatosplenomegaly and oral stomatitis. This paper presents the first case of successfully treated sublingual ranula with localized injection of OK-432 after healing from drug induced hypersensitivity syndrome, which has previously been unreported in the literature. We present the case of a 38-year-old Japanese woman with sublingual ranula that responded successfully to localized injection treatment with OK-432 after healing from drug induced hypersensitivity syndrome. She was affected with cutaneous myositis and interstitial lung disease when she was 26 years old. At the age 34 years, she received additional oral treatment of diaminodiphenyl-sulfone due to deterioration of the cutaneous myositis, which resulted in drug induced hypersensitivity syndrome (DIHS with severe oral stomatitis. Local injection of OK-432 to the ranula may be a very safe and useful treatment method even if the patient has a history of drug allergy and has connective tissue disease such as cutaneous myositis.

  10. A Case of Sublingual Ranula That Responded Successfully to Localized Injection Treatment with OK-432 after Healing from Drug Induced Hypersensitivity Syndrome

    Science.gov (United States)

    Yoshizawa, Kunio; Moroi, Akinori; Kawashiri, Shuichi; Ueki, Koichiro

    2016-01-01

    A ranula is a mucus retention cyst or pseudocyst caused by leakage of mucus from the sublingual gland and generally occurs in the oral floor. In addition, drug induced hypersensitivity syndrome (DIHS) is a rare but well-recognized serious adverse effect characterized by fever, skin rashes, generalized lymphadenopathy, hepatitis, and hepatosplenomegaly and oral stomatitis. This paper presents the first case of successfully treated sublingual ranula with localized injection of OK-432 after healing from drug induced hypersensitivity syndrome, which has previously been unreported in the literature. We present the case of a 38-year-old Japanese woman with sublingual ranula that responded successfully to localized injection treatment with OK-432 after healing from drug induced hypersensitivity syndrome. She was affected with cutaneous myositis and interstitial lung disease when she was 26 years old. At the age 34 years, she received additional oral treatment of diaminodiphenyl-sulfone due to deterioration of the cutaneous myositis, which resulted in drug induced hypersensitivity syndrome (DIHS) with severe oral stomatitis. Local injection of OK-432 to the ranula may be a very safe and useful treatment method even if the patient has a history of drug allergy and has connective tissue disease such as cutaneous myositis. PMID:27144039

  11. Locally advanced breast implant associated anaplastic large cell lymphoma: A case report of successful treatment with radiation and chemotherapy

    Directory of Open Access Journals (Sweden)

    Christopher Fleighton Estes

    2015-02-01

    Full Text Available The development of breast implant associated anaplastic large cell lymphoma (ALCL is a rare phenomenon. A typical presentation is an effusion associated with a breast implant. Less commonly, disease can become more advanced locoregionally or distantly. The optimal treatment schema is a topic of debate: localized ALCL can potentially be cured with implant removal alone, while other cases in the literature, including those that are more advanced, have been treated with varying combinations of surgery, chemotherapy, and external beam radiotherapy. This is a case report of breast implant ALCL with pathologically proven lymph node involvement, the fifth such patient reported. Our patient experienced a favorable outcome with radiation therapy and chemotherapy.

  12. Daily nasal spray of hPTH(1-34) for 3 months increases bone mass in osteoporotic subjects: a pilot study.

    Science.gov (United States)

    Matsumoto, T; Shiraki, M; Hagino, H; Iinuma, H; Nakamura, T

    2006-10-01

    Although intermittent parathyroid hormone (PTH) injection can lead to strong anabolic effects on bone, daily subcutaneous injection is a disadvantage for patient acceptance. We have developed a nasal spray formula of parathyroid peptide [hPTH(1-34)] with peak serum hPTH(1-34) concentrations by nasal spray of 1,000 microg similar to those by subcutaneous injections of 20 microg hPTH(1-34). To determine the clinical efficacy and safety of nasal hPTH(1-34) spray, a randomized, open-labeled clinical trial was conducted in subjects with osteoporosis. Ninety osteoporotic subjects age 52-84 years (mean 66.5 years) were randomly assigned to receive either 250 microg (PTH250, n=31), 500 microg (PTH500, n=30), or 1,000 microg (PTH1000, n=29) of daily nasal hPTH(1-34) spray for 3 months. All received daily supplements of 300 mg calcium and 200 IU vitamin D(3). Daily nasal hPTH(1-34) spray for 3 months increased lumbar bone mineral density (L-BMD) in a dose-dependent manner, and the PTH1000 group showed a 2.4% increase in L-BMD from baseline. Only the 1,000-microg dose produced consistent and statistically significant changes in markers of bone turnover; after 3 months, median serum type I procollagen N-propeptide (PINP) and osteocalcin increased 14.8% and 19.4% from baseline, while urinary type I collagen N-telopeptide (NTX) decreased 16.4%. Seven subjects developed transient hypercalcemia at 3 h after nasal hPTH(1-34) spray, but none of the subjects developed sustained hypercalcemia. These observations demonstrate that nasal hPTH(1-34) spray is safe and well tolerated and can rapidly increase L-BMD. The results warrant further studies to examine its long-term efficacy on bone mass and fractures.

  13. Locally advanced adenocarcinoma of the rectum presenting with necrotising fasciitis of the perineum: successful management with early aggressive surgery and multimodal therapy.

    Science.gov (United States)

    Ferreira, Luís; Alexandrino, Henrique; Soares Leite, Júlio; Castro Sousa, Francisco

    2015-12-16

    Colorectal cancer is a common malignant neoplasm and its treatment usually involves surgery associated, in some cases, depending on the staging, with chemoradiotherapy. Necrotising fasciitis of the perineum is a highly lethal infection of the perineum, perirectal tissues and genitals, requiring emergency surgical debridement, broad-spectrum antibiotics and control of sepsis. We present the case of a 59-year-old man with necrotising fasciitis of the perineum as the first clinical manifestation of locally advanced adenocarcinoma of the rectum, in which successful management consisted of early and aggressive surgical debridement, followed by multimodal therapy with curative intent. 2 years and 6 months after surgery the patient is well, with no evidence of local or systemic relapse.

  14. Targeted ablation of the PTH/PTHrP receptor in osteocytes impairs bone structure and homeostatic calcemic responses.

    Science.gov (United States)

    Powell, William F; Barry, Kevin J; Tulum, Irena; Kobayashi, Tatsuya; Harris, Stephen E; Bringhurst, F Richard; Pajevic, Paola Divieti

    2011-04-01

    Parathyroid hormone (PTH) is a major physiologic regulator of calcium, phosphorous, and skeletal homeostasis. Cells of the osteoblastic lineage are key targets of PTH action in bone, and recent evidence suggests that osteocytes might be important in the anabolic effects of PTH. To understand the role of PTH signaling through the PTH/PTHrP receptors (PPR) in osteocytes and to determine the role(s) of these cells in mediating the effects of the hormone, we have generated mice in which PPR expression is specifically ablated in osteocytes. Transgenic mice in which the 10 kb-Dmp1 promoter drives a tamoxifen-inducible Cre-recombinase were mated with animals in which exon 1 of PPR is flanked by lox-P sites. In these animals, osteocyte-selective PPR knockout (Ocy-PPR(cKO) mice) could be induced by administration of tamoxifen. Histological analysis revealed a reduction in trabecular bone and mild osteopenia in Ocy-PPR(cKO) mice. Reduction of trabeculae number and thickness was also detected by micro-computed tomography analysis whereas bone volume fraction (BV/TV%) was unchanged. These findings were associated with an increase in Sost and sclerostin expression. When Ocy-PPR(cKO) mice were subjected to a low-calcium diet to induce secondary hyperparathyroidism, their blood calcium levels were significantly lower than littermate controls. Moreover, PTH was unable to suppress Sost and sclerostin expression in the Ocy-PPR(cKO) animals, suggesting an important role of PTH signaling in osteocytes for proper bone remodeling and calcium homeostasis.

  15. Blood-pressure-independent wall thickening of intramyocardial arterioles in experimental uraemia: evidence for a permissive action of PTH.

    Science.gov (United States)

    Amann, K; Törnig, J; Flechtenmacher, C; Nabokov, A; Mall, G; Ritz, E

    1995-11-01

    Abnormalities in cardiovascular structures, e.g. LV hypertrophy and thickening of vessels (arteries, arterioles, veins) are hallmarks of renal failure. They are in part independent of elevated blood pressure. Parathyroid hormone (PTH) has been shown to affect cardiac function and has also been identified as a permissive factor in the genesis of cardiac fibrosis. The present study in rats with experimental renal failure was designed to examine whether PTH was permissive for wall thickening of intramyocardial arterioles as well. Male SD rats were sham operated or subtotally nephrectomized and maintained for 2 weeks. Subgroups of subtotally nephrectomized (SNX) rats were parathyroidectomized (PTX). Saline or rat 1, 34 PTH was administered by osmotic minipump. Eucalcaemia was maintained in PTX animals by a high-calcium diet (3%). Serum calcium was not statistically different between the groups. After perfusion fixation, intramyocardial arterioles were assessed using stereological techniques (wall thickness; wall/lumen ratio; minimal lumen diameter; length density). In random samples of the left ventricle, wall thickness of arterioles was 2.2 +/- 0.25 microns in sham-op controls and 2.76 +/- 0.41 in SNX (n = at least 8 animals per group). SNX-PTX animals+solvent did not differ significantly from sham-op controls (2.08 +/- 0.42 microns), while SNX-PTX animals+PTH had values not significantly different from SNX (2.59 +/- 0.54 microns). Differences in wall thickness were not paralleled by differences in systolic blood pressure (sham-op 110 +/- 13.3 mmHg; SNX 138 +/- 8.4 mmHg, SNX-PTX+solvent 142 +/- 5.2 mmHg; SNX-PTX+PTH 148 +/- 5.7 mmHg). PTH treated animals showed signs of marked vascular smooth-muscle cell and endothelial-cell activation. The data suggest that wall thickening of intramyocardial arterioles in short-term experimental uraemia is dependent upon the presence of PTH (permissive effect).

  16. Activation of a Non-cAMP/PKA Signaling Pathway Downstream of the PTH/PTHrP Receptor Is Essential for a Sustained Hypophosphatemic Response to PTH Infusion in Male Mice

    Science.gov (United States)

    Song, Lige; Liu, Minlin; Segawa, Hiroko; Miyamoto, Ken-Ichi; Bringhurst, F. Richard; Kronenberg, Henry M.; Jüppner, Harald

    2013-01-01

    PTH increases urinary Pi excretion by reducing expression of two renal cotransporters [NaPi-IIa (Npt2a) and NaPi-IIc (Npt2c)]. In contrast to acute transporter regulation that is cAMP/protein kinase A dependent, long-term effects require phospholipase C (PLC) signaling by the PTH/PTHrP receptor (PPR). To determine whether the latter pathway regulates Pi through Npt2a and/or Npt2c, wild-type mice (Wt) and animals expressing a mutant PPR incapable of PLC activation (DD) were tested in the absence of one (Npt2a−/− or Npt2c−/−) or both phosphate transporters (2a/2c-dko). PTH infusion for 8 days caused a rapid and persistent decrease in serum Pi in Wt mice, whereas serum Pi in DD mice fell only transiently for the first 2 days. Consistent with these findings, fractional Pi excretion index was increased initially in both animals, but this increase persisted only when the PPR Wt was present. The hypophosphatemic response to PTH infusion was impaired only slightly in PPR Wt/Npt2c−/− or DD/Npt2c−/− mice. Despite lower baselines, PTH infusion in PPR Wt/Npt2a−/− mice decreased serum Pi further, an effect that was attenuated in DD/Npt2a−/− mice. Continuous PTH had no effect on serum Pi in 2a/2c-dko mice. PTH administration increased serum 1,25 dihydroxyvitamin D3 levels in Wt and DD mice and increased levels above the elevated baseline with ablation of either but not of both transporters. Continuous PTH elevated serum fibroblast growth factor 23 and blood Ca2+ equivalently in all groups of mice. Our data indicate that PLC signaling at the PPR contributes to the long-term effect of PTH on Pi homeostasis but not to the regulation of 1,25 dihydroxyvitamin D3, fibroblast growth factor 23, or blood Ca2+. PMID:23515284

  17. Evidence for a role of intracellular stored parathyroid hormone in producing hysteresis of the PTH-calcium relationship in normal humans

    DEFF Research Database (Denmark)

    Schwarz, Peter; Madsen, J C; Rasmussen, A Q

    1998-01-01

    OBJECTIVE: Despite the clear recognition that extracellular ionized calcium controls PTH secretion, there have been suggestions of hysteresis in the relationship between extracellular ionized calcium and PTH during recovery from induced hypo- and hypercalcaemia in vivo in humans. In this study, we...... examined the possibility that release of intracellular stored PTH during induced hypocalcaemia may explain hysteresis. VOLUNTEERS: Eleven volunteers, five women and six men, were recruited to participate in the study. DESIGN: A series of three protocols of repeated induction of hypocalcaemia or sequential...... of PTH or a markedly blunted peak. Thus, the PTH response during the initial induction of and the first recovery from hypocalcaemia in our protocol 3 showed significant hysteresis in the relationship between blood ionized calcium and PTH (P

  18. PTH Test

    Science.gov (United States)

    Advertisement Proceeds from website advertising help sustain Lab Tests Online. AACC is a not-for-profit organization and does not endorse non-AACC products and services. Advertising & Sponsorship: Policy | Opportunities ...

  19. Ablation of the PTHrP gene or the PTH/PTHrP receptor gene leads to distinct abnormalities in bone development

    OpenAIRE

    Lanske, Beate; Amling, Michael; Neff, Lynn; Guiducci, Jennifer; Baron, Roland; Kronenberg, Henry M.

    1999-01-01

    Parathyroid hormone (PTH) and parathyroid hormone–related peptide (PTHrP) bind to and activate the same PTH/PTHrP receptor. Deletion of either the PTHrP gene or the PTH/PTHrP receptor gene leads to acceleration of differentiation of growth plate chondrocytes. To explore further the functional relationships of PTHrP and the PTH/PTHrP receptor, bones of knockout mice were analyzed early in development, and the phenotypes of double-knockout mice were characterized.

  20. A semimechanistic model of the time-course of release of PTH into plasma following administration of the calcilytic JTT-305/MK-5442 in humans.

    Science.gov (United States)

    Cabal, Antonio; Mehta, Khamir; Ross, David S; Shrestha, Rajiv P; Comisar, Wendy; Denker, Andrew; Pai, Sudhakar M; Ishikawa, Tomohiro

    2013-08-01

    JTT-305/MK-5442 is a calcium-sensing receptor (CaSR) allosteric antagonist being investigated for the treatment of osteoporosis. JTT-305/MK-5442 binds to CaSRs, thus preventing receptor activation by Ca(2+) . In the parathyroid gland, this results in the release of parathyroid hormone (PTH). Sharp spikes in PTH secretion followed by rapid returns to baseline are associated with bone formation, whereas sustained elevation in PTH is associated with bone resorption. We have developed a semimechanistic, nonpopulation model of the time-course relationship between JTT-305/MK-5442 and whole plasma PTH concentrations to describe both the secretion of PTH and the kinetics of its return to baseline levels. We obtained mean concentration data for JTT-305/MK-5442 and whole PTH from a multiple dose study in U.S. postmenopausal women at doses of 5, 10, 15, and 20 mg. We hypothesized that PTH is released from two separate sources: a reservoir that is released rapidly (within minutes) in response to reduction in Ca(2+) binding, and a second source released more slowly following hours of reduced Ca(2+) binding. We modeled the release rates of these reservoirs as maximum pharmacologic effect (Emax ) functions of JTT-305/MK-5442 concentration. Our model describes both the dose-dependence of PTH time of occurrence for maximum drug concentration (Tmax ) and maximum concentration of drug (Cmax ), and the extent and duration of the observed nonmonotonic return of PTH to baseline levels following JTT-305/MK-5442 administration.

  1. All-atom simulation study of protein PTH(1-34) by using the Wang-Landau sampling method

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seung-Yeon [Korea National University of Transportation, Chungju (Korea, Republic of); Kwak, Woo-Seop [Chosun University, Gwangju (Korea, Republic of)

    2014-12-15

    We perform simulations of the N-terminal 34-residue protein fragment PTH(1-34), consisting of 581 atoms, of the 84-residue human parathyroid hormone by using the all-atom ECEPP/3 force field and the Wang-Landau sampling method. Through a massive high-performance computation, the density of states and the partition function Z(T), as a continuous function of T, are obtained for PTH(1-34). From the continuous partition function Z(T), the partition function zeros of PTH(1-34) are evaluated for the first time. From both the specific heat and the partition function zeros, two characteristic transition temperatures are obtained for the all-atom protein PTH(1-34). The higher transition temperature T{sub 1} and the lower transition temperature T{sub 2} of PTH(1-34) can be interpreted as the collapse temperature T{sub θ} and the folding temperature T{sub f} , respectively.

  2. Expedited isolation of natural product peptidyl-tRNA hydrolase inhibitors from a Pth1 affinity column

    Directory of Open Access Journals (Sweden)

    Harkirat S. Sethi

    2017-05-01

    Full Text Available New antibiotics and new antibiotic targets are needed to counter the development of bacterial drug resistance that threatens to return the human population to the pre-antibiotic era. Bacterial peptidyl-tRNA hydrolase (Pth1 is a promising new antibiotic target in the early stages of development. While inhibitory activity has been observed in a variety of natural products, bioactive fractionation has been a bottleneck for inhibitor isolation. To expedite the isolation of inhibitory compounds from complex mixtures, we constructed a Pth1 affinity column and used it to isolate inhibitory compounds from crude natural products. Recombinantly produced S. typhimurium Pth1 was covalently attached to a column matrix and the inhibitory activity isolated from ethanol extracts of Salvinia minima. The procedure reported here demonstrates that isolation of Pth1 inhibitory compounds from complex natural product extracts can be greatly expedited over traditional bioactive fractionation, decreasing time and expense. The approach is generally applicable to Pth1s from other bacterial species and opens an avenue to advance and accelerate inhibitor development against this promising antimicrobial target.

  3. Controlling successive ionic layer absorption and reaction cycles to optimize silver nanoparticle-induced localized surface plasmon resonance effects on the paper strip

    Science.gov (United States)

    Lee, Jae-Chul; Kim, Wansun; Park, Hun-Kuk; Choi, Samjin

    2017-03-01

    This study investigates why a silver nanoparticle (SNP)-induced surface-enhanced Raman scattering (SERS) paper chip fabricated at low successive ionic layer absorption and reaction (SILAR) cycles leads to a high SERS enhancement factor (7 × 108) with an inferior nanostructure and without generating a hot spot effect. The multi-layered structure of SNPs on cellulose fibers, verified by magnified scanning electron microscopy (SEM) and analyzed by a computational simulation method, was hypothesized as the reason. The pattern of simulated local electric field distribution with respect to the number of SILAR cycles showed good agreement with the experimental Raman intensity, regardless of the wavelength of the excitation laser sources. The simulated enhancement factor at the 785-nm excitation laser source (2.8 × 109) was 2.5 times greater than the experimental enhancement factor (1.1 × 109). A 532-nm excitation laser source exhibited the highest maximum local electric field intensity (1.9 × 1011), particularly at the interparticle gap called a hot spot. The short wavelength led to a strong electric field intensity caused by strong electromagnetic coupling arising from the SNP-induced local surface plasmon resonance (LSPR) effects through high excitation energy. These findings suggest that our paper-based SILAR-fabricated SNP-induced LSPR model is valid for understanding SNP-induced LSPR effects.

  4. Noncanonical GPCR signaling arising from a PTH receptor–arrestin–Gβγ complex

    Science.gov (United States)

    Wehbi, Vanessa L.; Stevenson, Hilary P.; Feinstein, Timothy N.; Calero, Guillermo; Romero, Guillermo; Vilardaga, Jean-Pierre

    2013-01-01

    G protein-coupled receptors (GPCRs) participate in ubiquitous transmembrane signal transduction processes by activating heterotrimeric G proteins. In the current “canonical” model of GPCR signaling, arrestins terminate receptor signaling by impairing receptor–G-protein coupling and promoting receptor internalization. However, parathyroid hormone receptor type 1 (PTHR), an essential GPCR involved in bone and mineral metabolism, does not follow this conventional desensitization paradigm. β-Arrestins prolong G protein (GS)-mediated cAMP generation triggered by PTH, a process that correlates with the persistence of arrestin–PTHR complexes on endosomes and which is thought to be associated with prolonged physiological calcemic and phosphate responses. This presents an inescapable paradox for the current model of arrestin-mediated receptor–G-protein decoupling. Here we show that PTHR forms a ternary complex that includes arrestin and the Gβγ dimer in response to PTH stimulation, which in turn causes an accelerated rate of GS activation and increases the steady-state levels of activated GS, leading to prolonged generation of cAMP. This work provides the mechanistic basis for an alternative model of GPCR signaling in which arrestins contribute to sustaining the effect of an agonist hormone on the receptor. PMID:23297229

  5. Noncanonical GPCR signaling arising from a PTH receptor-arrestin-Gβγ complex.

    Science.gov (United States)

    Wehbi, Vanessa L; Stevenson, Hilary P; Feinstein, Timothy N; Calero, Guillermo; Romero, Guillermo; Vilardaga, Jean-Pierre

    2013-01-22

    G protein-coupled receptors (GPCRs) participate in ubiquitous transmembrane signal transduction processes by activating heterotrimeric G proteins. In the current "canonical" model of GPCR signaling, arrestins terminate receptor signaling by impairing receptor-G-protein coupling and promoting receptor internalization. However, parathyroid hormone receptor type 1 (PTHR), an essential GPCR involved in bone and mineral metabolism, does not follow this conventional desensitization paradigm. β-Arrestins prolong G protein (G(S))-mediated cAMP generation triggered by PTH, a process that correlates with the persistence of arrestin-PTHR complexes on endosomes and which is thought to be associated with prolonged physiological calcemic and phosphate responses. This presents an inescapable paradox for the current model of arrestin-mediated receptor-G-protein decoupling. Here we show that PTHR forms a ternary complex that includes arrestin and the Gβγ dimer in response to PTH stimulation, which in turn causes an accelerated rate of G(S) activation and increases the steady-state levels of activated G(S), leading to prolonged generation of cAMP. This work provides the mechanistic basis for an alternative model of GPCR signaling in which arrestins contribute to sustaining the effect of an agonist hormone on the receptor.

  6. Low bone turnover and low BMD in Down syndrome: effect of intermittent PTH treatment.

    Directory of Open Access Journals (Sweden)

    Tristan W Fowler

    Full Text Available Trisomy 21 affects virtually every organ system and results in the complex clinical presentation of Down syndrome (DS. Patterns of differences are now being recognized as patients' age and these patterns bring about new opportunities for disease prevention and treatment. Low bone mineral density (BMD has been reported in many studies of males and females with DS yet the specific effects of trisomy 21 on the skeleton remain poorly defined. Therefore we determined the bone phenotype and measured bone turnover markers in the murine DS model Ts65Dn. Male Ts65Dn DS mice are infertile and display a profound low bone mass phenotype that deteriorates with age. The low bone mass was correlated with significantly decreased osteoblast and osteoclast development, decreased bone biochemical markers, a diminished bone formation rate and reduced mechanical strength. The low bone mass observed in 3 month old Ts65Dn mice was significantly increased after 4 weeks of intermittent PTH treatment. These studies provide novel insight into the cause of the profound bone fragility in DS and identify PTH as a potential anabolic agent in the adult low bone mass DS population.

  7. PTH(1-34) and zoledronic acid have differing longitudinal effects on juvenile mouse femur strength and morphology.

    Science.gov (United States)

    Bartlow, Christopher M; Oest, Megan E; Mann, Kenneth A; Zimmerman, Nicholas D; Butt, Bilal B; Damron, Timothy A

    2016-09-21

    Treatment of secondary pediatric osteoporosis-particularly that due to chronic diseases, immobilization, and necessary medical treatments-is currently limited by a poor understanding of the long-term efficacy and safety of skeletal metabolism modifying drugs. This study aimed to characterize longitudinal effects of representative anabolic (parathyroid hormone, PTH) and anti-catabolic (zoledronic acid, ZA) drugs on skeletal morphology, mechanical strength, and growth in juvenile mice. BALB/cJ mice aged 4 weeks were given PTH(1-34) or vehicle (control) daily for 8 weeks, or 4 weekly doses of ZA, and evaluated at time points 0-26 weeks after treatment initiation. There were no enduring differences in body length or mass between treatment groups. ZA increased femur size as early as week 0, including increased distal femur bone volume and diaphyseal cross-sectional area, persisting through week 26. PTH treatment only transiently increased bone size, including distal femur volume at weeks 4-12. ZA decreased diaphyseal cortical tissue mineral density (TMD) at 12-26 weeks versus controls; PTH decreased TMD only at 2 weeks (vs. controls). ZA increased bending strength at 0-12 weeks and flexural strength at week 4 (vs. controls), but decreased flexural strength and modulus at week 26. PTH treatment increased bending strength only at 4 weeks, and did not affect flexural strength. Overall, ZA rapidly and persistently increased femur strength and size, but compromised bone material quality long-term. In healthy juvenile mice, limited-duration PTH treatment did not exert a strong anabolic effect, and had no adverse effects on femur strength, morphology, or growth. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

  8. Simultaneous control of PTH and CaxP Is sustained over three years of treatment with cinacalcet HCl.

    Science.gov (United States)

    Sprague, Stuart M; Evenepoel, Pieter; Curzi, Mario P; González, Maria Teresa; Husserl, Fred E; Kopyt, Nelson; Sterling, Lulu Ren; Mix, Chris; Wong, Gordon

    2009-09-01

    Chronic kidney disease (CKD) is commonly complicated by secondary hyperparathyroidism (SHPT), leading to increased risk of morbidity and mortality. SHPT is a progressive disease often requiring long-term therapy to control parathyroid hormone (PTH) and mineral imbalances. Vitamin D sterols and phosphate binders, used as traditional therapies to lower PTH and phosphorus, may provide inadequate long-term control for many dialysis patients. Cinacalcet, by simultaneously lowering PTH, calcium, phosphorus, and calcium-phosphorus levels, may maintain PTH and mineral balance in these individuals. However, as with traditional therapies, long-term data are limited. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENT: Dialysis subjects from at least one of five lead-in studies (double-blind placebo-controlled, including one extension trial) completing up to 52 wk of either cinacalcet or placebo were eligible for this open-label extension study, including an 8-wk dose titration (initiated at 30 mg/d), followed by 24-wk maintenance and up to 132 wk of follow-up. Final efficacy analysis was at week 180. Three hundred thirty-four of 589 enrolled subjects received cinacalcet from the beginning of the lead-in study. Weekly median PTH values were < or =300 pg/ml (weeks 16 through 180) and median CaxP values were < or =55 mg(2)/dl(2) (weeks 4 through 180). Similar results were exhibited in the 255 subjects who initially received placebo. Among the patients exposed to cinacalcet from the beginning of the lead-in study, 3% of subjects exhibited treatment-related serious adverse events. Cinacalcet effectively maintained PTH, Ca and P reductions in dialysis subjects for up to 180 wk.

  9. Simultaneous Control of PTH and Ca×P Is Sustained over Three Years of Treatment with Cinacalcet HCl

    Science.gov (United States)

    Evenepoel, Pieter; Curzi, Mario P.; González, Maria Teresa; Husserl, Fred E.; Kopyt, Nelson; Sterling, Lulu Ren; Mix, Chris; Wong, Gordon

    2009-01-01

    Background & objectives: Chronic kidney disease (CKD) is commonly complicated by secondary hyperparathyroidism (SHPT), leading to increased risk of morbidity and mortality. SHPT is a progressive disease often requiring long-term therapy to control parathyroid hormone (PTH) and mineral imbalances. Vitamin D sterols and phosphate binders, used as traditional therapies to lower PTH and phosphorus, may provide inadequate long-term control for many dialysis patients. Cinacalcet, by simultaneously lowering PTH, calcium, phosphorus, and calcium-phosphorus levels, may maintain PTH and mineral balance in these individuals. However, as with traditional therapies, long-term data are limited. Design, setting, participants, & measurement: Dialysis subjects from at least one of five lead-in studies (double-blind placebo-controlled, including one extension trial) completing up to 52 wk of either cinacalcet or placebo were eligible for this open-label extension study, including an 8-wk dose titration (initiated at 30 mg/d), followed by 24-wk maintenance and up to 132 wk of follow-up. Final efficacy analysis was at week 180. Results: Three hundred thirty-four of 589 enrolled subjects received cinacalcet from the beginning of the lead-in study. Weekly median PTH values were ≤300 pg/ml (weeks 16 through 180) and median Ca×P values were ≤55 mg2/dl2 (weeks 4 through 180). Similar results were exhibited in the 255 subjects who initially received placebo. Among the patients exposed to cinacalcet from the beginning of the lead-in study, 3% of subjects exhibited treatment-related serious adverse events. Conclusions: Cinacalcet effectively maintained PTH, Ca and P reductions in dialysis subjects for up to 180 wk. PMID:19696213

  10. ZP2307, a novel cyclic PTH(1-17) analog, reversed established osteopenia in adult ovariectomized rats

    DEFF Research Database (Denmark)

    Vääräniemi, Jukka; Morko, Jukka; Peng, ZhiQi

    -17) analog, ZP2307, with a high efficacy and potency on the human PTH receptor in vitro. This study characterized the effects of intermittent treatment with ZP2307 on established osteopenia in adult ovariectomized (OVX) rats. Female Sprague-Dawley rats were ovariectomized at 6 months of age. After 6 weeks......-34). This study demonstrated that the intermittent treatment with ZP2307, the novel cyclic PTH(1-17) analog, is effective in reversing the established osteopenia in adult OVX rats to normal conditions. Due to its broad dose response relationship, ZP2307 may have a wider therapeutic window and a better safety...

  11. A Successfully Treated Case of Gastrointestinal Stromal Tumor Causing Severe Anemia and Localized Peritonitis Showing Angina Pectoris Resulting in Watershed Cerebral Infarction

    Directory of Open Access Journals (Sweden)

    Yoshihide Sehara

    2017-01-01

    Full Text Available Ischemic stroke following acute myocardial infarction is a rare but a serious complication. Because the pathophysiology of stroke is dynamic, it is often hard to identify the cause of stroke. Here, we present the case of a 75-year-old man with ischemic stroke following angina pectoris caused by severe anemia and localized peritonitis due to gastrointestinal stromal tumor of small intestine. On admission, he showed consciousness disturbance, fever, and left hemiplegia. The electrocardiogram on admission showed ST-segment depression in V2 to V6 which was normalized 4 hours later. The ultrasound cardiogram showed the mild hypokinesis in the apical portion of left ventricle which was also normalized later. The magnetic resonance imaging and angiography showed ischemic stroke in watershed area between right anterior and middle cerebral arteries area and stenosis of distal portion of right middle cerebral artery. The computed tomography of abdomen showed a mass of small intestine. We decided to perform curative surgery after transfusion and successfully resected the mass of the small intestine, which was revealed to be a gastrointestinal stromal tumor (GIST. This is a successfully treated case of GIST in which the complicated pathophysiology of watershed cerebral infarction following angina pectoris might be clearly revealed.

  12. Relationship between fasting glucose, vitamin D and PTH in early postmenopausal women

    DEFF Research Database (Denmark)

    við Streym, Susanna; Rejnmark, Lars; Vestergaard, Peter;

    2010-01-01

      Abstract Relationship between fasting glucose, vitamin D and PTH in early postmenopausal women Súsanna við Streym Thomsen (1), Lars Rejnmark (1), Peter Vestergaard (1), Christine Brot (2), Pia Eiken (3), Pernille Hermann (4) Leif Mosekilde (1). (1) Department of Medicine and Endocrinology C...... postmenopausal Caucasian women (n=2016) aged 45 to 58 years old. Measurements: Fasting blood glucose was measured after an overnight fast by standard laboratory methods. Serum levels of 25OHD were measured by a competitive assay using rachitic rat binding protein. The fat and lean mass was measured by DXA...... between fasting blood glucose and 25OHD and all studied indices. In a multivariate linear regression analyzing fasting blood glucose was significantly associated with BMI (b=0.038 ±0.007 (SE), 2p

  13. The Crystal Structure of TAL Effector PthXo1 Bound to Its DNA Target

    Energy Technology Data Exchange (ETDEWEB)

    Mak, Amanda Nga-Sze; Bradley, Philip; Cernadas, Raul A.; Bogdanove, Adam J.; Stoddard, Barry L. (FHCRC); (Iowa State)

    2012-02-10

    DNA recognition by TAL effectors is mediated by tandem repeats, each 33 to 35 residues in length, that specify nucleotides via unique repeat-variable diresidues (RVDs). The crystal structure of PthXo1 bound to its DNA target was determined by high-throughput computational structure prediction and validated by heavy-atom derivatization. Each repeat forms a left-handed, two-helix bundle that presents an RVD-containing loop to the DNA. The repeats self-associate to form a right-handed superhelix wrapped around the DNA major groove. The first RVD residue forms a stabilizing contact with the protein backbone, while the second makes a base-specific contact to the DNA sense strand. Two degenerate amino-terminal repeats also interact with the DNA. Containing several RVDs and noncanonical associations, the structure illustrates the basis of TAL effector-DNA recognition.

  14. Gene controlled by promoter--PTH4 depending on whiG of Streptomyces coelicolor

    Institute of Scientific and Technical Information of China (English)

    谭华荣; 杨海花; 田宇清; 吴畏; 董可宁; K.F.Chater

    1996-01-01

    The downstream gene controlled by promoter--PTH4 which is related to Streptomycesdifferentiation was cloned, and its sequence was determined by the dideoxy chain termination method. The results indicated that the 1597 bp of DNA fragment conferred a complete open reading frame (ORF). In searches of databases, the deduced product of the ORF was not homologous with any known proteins; it may be a new protein. The function of the gene was studied using the strategy of gene disruption; the actinorhodin could not be produced when this gene was disrupted. Therefore, this gene may be related to actinorhodin biosynthesis in Streptomyces coelicolor, and the result also shows that this gene may play a role in multiple level regulation of differentiation genes in Streptomyces.

  15. ZP2307, a novel, cyclic PTH(1-17) analog that augments bone mass in ovariectomized rats

    DEFF Research Database (Denmark)

    Neerup, Trine Skovlund Ryge; Stahlhut, Martin; Petersen, Jørgen S

    2011-01-01

    Daily injections of human parathyroid hormone (1-34), hPTH(1-34), provide a highly effective treatment option for severe osteoporosis. However, PTH analogs shorter than 28 amino acids do not retain any bone augmenting potential. Here, we present ZP2307 ([Ac₅c¹, Aib³, Leu⁸, Gln¹⁰, Har¹¹, Ala¹², Trp......¹⁴, Asp¹⁷]PTH(1-17)-NH₂), a novel, chemically modified and cyclized hPTH(1-17) analog, that augments bone mass in ovariectomized, osteopenic rats. Subcutaneous administration of this structurally constrained, K¹³-D¹⁷ side-chain-to-side-chain cyclized peptide reversed bone loss and increased bone...... mineral density (BMD) up to or above baseline levels in rat long bones and vertebrae. Highly significant effects of ZP2307 were achieved at doses of 40-320 nmol/kg. Micro-CT and histomorphometric analyses showed that ZP2307 improved quantitative and qualitative parameters of bone structure. Biomechanical...

  16. Stretching dependence of the vibration modes of a single-molecule Pt-H-2-Pt bridge

    DEFF Research Database (Denmark)

    Djukic, D.; Thygesen, Kristian Sommer; Untiedt, C.

    2005-01-01

    isotope substitution is obtained. The stretching dependence for each of the modes allows uniquely classifying them as longitudinal or transversal modes. The interpretation of the experiment in terms of a Pt-H-2-Pt bridge is verified by density-functional theory calculations for the stability, vibrational...

  17. Identification of Six Novel PTH1R Mutations in Families with a History of Primary Failure of Tooth Eruption

    DEFF Research Database (Denmark)

    Risom, Lotte; Christoffersen, Line Borck; Daugaard-Jensen, Jette

    2013-01-01

    Primary Failure of tooth Eruption (PFE) is a non-syndromic disorder which can be caused by mutations in the parathyroid hormone receptor 1 gene (PTH1R). Traditionally, the disorder has been identified clinically based on post-emergent failure of eruption of permanent molars. However, patients wit...

  18. In vivo PTH provokes apical NHE3 and NaPi2 redistribution and Na-K-ATPase inhibition

    DEFF Research Database (Denmark)

    Zhang, Y; Norian, J M; Magyar, C E

    1999-01-01

    The aim of this study was to test the hypothesis that in vivo administration of parathyroid hormone (PTH) provokes diuresis/natriuresis through redistribution of proximal tubule apical sodium cotransporters (NHE3 and NaPi2) to internal stores and inhibition of basolateral Na-K-ATPase activity...

  19. ALX 111: ALX1-11, parathyroid hormone (1-84) - NPS Allelix, PREOS, PTH, recombinant human parathyroid hormone, rhPTH (1-84).

    Science.gov (United States)

    2003-01-01

    ALX 111 [parathyroid hormone (1-84) - NPS Allelix, recombinant human parathyroid hormone, rhPTH (1-84), PREOS] is a full-length, recombinant human parathyroid hormone. It has potential as an anti-osteoporotic agent, due to its properties as a bone formation stimulant. This profile has been selected from R&D Insight, a pharmaceutical intelligence database produced by Adis International Ltd. It has been recommended that ALX 111 should be given for 1 to 2 years and may be given in combination with an antiresorptive agent, such as estrogen or a bisphosphonate. In December 1999, Allelix Biopharmaceuticals merged with NPS Pharmaceuticals. This combined company is operating as NPS Pharmaceuticals in the US and as NPS Allelix in Canada. The merger has enabled a phase III study of ALX 111 to begin in the US, Europe and South America. NPS harmaceuticals has signed an agreement with Bio-Imaging Technologies, which will provide all image handling and analysis for this trial. Until 1994, Allelix Biopharmaceuticals and Glaxo in Canada were involved in a joint venture to investigate the efficacy of ALX 111 in osteoporosis. Allelix was subsequently, until September 1998, collaborating with Astra of Sweden in developing ALX 111. Astra had acquired exclusive worldwide rights to ALX 111 and was responsible for development of the agent. However, Astra returned all rights to ALX 111 to Allelix as a result of its merger with Zeneca to form AstraZeneca. In December 1999, Allelix Biopharmaceuticals merged with NPS Pharmaceuticals. This combined company is operating as NPS Pharmaceuticals in the US and as NPS Allelix in Canada. The merger has enabled a phase III study of ALX 111 to begin in the US, Europe and South America. The phase III trial of ALX 111 for the treatment of osteoporosis has completed patient enrolment, and phase II trials have been completed in Canada and the Netherlands. The 18-month, phase III, multicentre, placebo-controlled trial (Treatment of Osteoporosis with

  20. Mice lacking bone sialoprotein (BSP) lose bone after ovariectomy and display skeletal site-specific response to intermittent PTH treatment.

    Science.gov (United States)

    Wade-Gueye, Ndéye Marième; Boudiffa, Maya; Laroche, Norbert; Vanden-Bossche, Arnaud; Fournier, Carole; Aubin, Jane E; Vico, Laurence; Lafage-Proust, Marie-Hélène; Malaval, Luc

    2010-11-01

    Bone sialoprotein (BSP) belongs to the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, whose members play multiple and distinct roles in the development, turnover, and mineralization of bone and dentin. The functions of BSP in bone remodeling are not yet well established. We previously showed that BSP knockout (BSP(-/-)) mice exhibit a higher trabecular bone volume, concomitant with lower bone remodeling, than wild-type (BSP(+/+)) mice. To determine whether bone turnover can be stimulated in the absence of BSP, we subjected BSP(+/+) and BSP(-/-) mice to catabolic [ovariectomy (OVX)] or anabolic (intermittent PTH administration) hormonal challenges. BSP(-/-) mice progressively develop hypocalcemia and high serum PTH between 2 and 4 months of age. Fifteen and 30 d after OVX, microtomography analysis showed a significant decrease of trabecular bone volume in tibiae of both genotypes. Histomorphometric parameters of bone formation and resorption were significantly increased by OVX. PTH treatment resulted in an increase of trabecular thickness and both bone formation and resorption parameters at all skeletal sites in both genotypes and a decrease of trabecular bone volume in tibiae of BSP(+/+) but not BSP(-/-) mice. PTH increased cortical thickness and bone area in BSP(+/+) but not BSP(-/-) mice and stimulated the bone formation rate specifically in the endosteum of BSP(+/+) mice and the periosteum of BSP(-/-) mice. PTH enhanced the expression of RANKL, MEPE, and DMP1 in both genotypes but increased OPG and OPN expression only in BSP(-/-) mice. In conclusion, despite the low basal turnover, both catabolic and anabolic challenges increase bone formation and resorption in BSP(-/-) mice, suggesting that compensatory pathways are operative in the skeleton of BSP-deficient mice. Although up-regulation of one or several other SIBLINGs is a possible mechanism, further studies are needed to analyze the interplay and cross-regulation involved in

  1. ZP2307, a novel, cyclic PTH(1-17) analog that augments bone mass in ovariectomized rats.

    Science.gov (United States)

    Neerup, Trine S R; Stahlhut, Martin; Petersen, Jørgen S; Daugaard, Jens R; Jensen, Jens-Erik B; Peng, Zhiqi; Morko, Jukka; Thorkildsen, Christian

    2011-06-01

    Daily injections of human parathyroid hormone (1-34), hPTH(1-34), provide a highly effective treatment option for severe osteoporosis. However, PTH analogs shorter than 28 amino acids do not retain any bone augmenting potential. Here, we present ZP2307 ([Ac₅c¹, Aib³, Leu⁸, Gln¹⁰, Har¹¹, Ala¹², Trp¹⁴, Asp¹⁷]PTH(1-17)-NH₂), a novel, chemically modified and cyclized hPTH(1-17) analog, that augments bone mass in ovariectomized, osteopenic rats. Subcutaneous administration of this structurally constrained, K¹³-D¹⁷ side-chain-to-side-chain cyclized peptide reversed bone loss and increased bone mineral density (BMD) up to or above baseline levels in rat long bones and vertebrae. Highly significant effects of ZP2307 were achieved at doses of 40-320 nmol/kg. Micro-CT and histomorphometric analyses showed that ZP2307 improved quantitative and qualitative parameters of bone structure. Biomechanical testing of rat femora confirmed that ZP2307 dramatically increased bone strength. Over a broad maximally effective dose range (40-160 nmol/kg) ZP2307 did not increase serum concentrations of ionized free calcium above normal levels. Only at the highest dose (320 nmol/kg) ZP2307 induced hypercalcemic calcium levels in the ovariectomized rats. To our knowledge ZP2307 is the smallest PTH peptide analog known to exert augmentation of bone. Our findings suggest that ZP2307 has the potential to effectively augment bone mass over a broad dose range without a concomitant increase in the serum concentration of ionized free calcium above the normal range.

  2. 1,25 (OH)2D3 enhances PTH-induced Ca2+ transients in preosteoblasts by activating L-type Ca2+ channels

    Science.gov (United States)

    Li, W.; Duncan, R. L.; Karin, N. J.; Farach-Carson, M. C.

    1997-01-01

    We previously demonstrated electrophysiologically that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] shifts the activation threshold of L-type Ca2+ channels in osteoblasts toward the resting potential and prolongs mean open time. Presently, we used single-cell Ca2+ imaging to study the combined effects of 1,25(OH)2D3 and parathyroid hormone (PTH) during generation of Ca2+ transients in fura 2-loaded MC3T3-E1 cells. Pretreatment with 1,25(OH)2D3 concentrations, which alone did not produce Ca2+ transients, consistently enhanced Ca2+ responses to PTH. Enhancement was dose dependent over the range of 1 to 10 nM and was blocked by pretreatment with 5 microM nitrendipine during pretreatment. A 1,25(OH)2D3 analog that activates L-type channels and shifts their activation threshold also enhanced PTH responses. In contrast, an analog devoid of membrane Ca2+ effects did not enhance PTH-induced Ca2+ transients. The PTH-induced Ca2+ transient involved activation of a dihydropyridine-insensitive cation channel that was inhibited by Gd3+. Together, these data suggest that 1,25(OH)2D3 increases osteoblast responsiveness to PTH through rapid modification of L-type Ca2+ channel gating properties, whose activation enhances Ca2+ entry through other channels such as the PTH-responsive, Gd(3+)-sensitive cation channel.

  3. All five host-range variants of Xanthomonas citri carry one pthA homolog with 17.5 repeats that determines pathogenicity on citrus, but none determine host-range variation.

    Science.gov (United States)

    Al-Saadi, Abdulwahid; Reddy, Joseph D; Duan, Yong P; Brunings, Asha M; Yuan, Qiaoping; Gabriel, Dean W

    2007-08-01

    Citrus canker disease is caused by five groups of Xanthomonas citri strains that are distinguished primarily by host range: three from Asia (A, A*, and A(w)) and two that form a phylogenetically distinct clade and originated in South America (B and C). Every X. citri strain carries multiple DNA fragments that hybridize with pthA, which is essential for the pathogenicity of wide-host-range X. citri group A strain 3213. DNA fragments that hybridized with pthA were cloned from a representative strain from all five groups. Each strain carried one and only one pthA homolog that functionally complemented a knockout mutation of pthA in 3213. Every complementing homolog was of identical size to pthA and carried 17.5 nearly identical, direct tandem repeats, including three new genes from narrow-host-range groups C (pthC), A(w) (pthAW), and A* (pthA*). Every noncomplementing paralog was of a different size; one of these was sequenced from group A* (pthA*-2) and was found to have an intact promoter and full-length reading frame but with 15.5 repeats. None of the complementing homologs nor any of the noncomplementing paralogs conferred avirulence to 3213 on grapefruit or suppressed avirulence of a group A* strain on grapefruit. A knockout mutation of pthC in a group C strain resulted in loss of pathogenicity on lime, but the strain was unaffected in ability to elicit an HR on grapefruit. This pthC- mutant was fully complemented by pthA, pthB, or pthC. Analysis of the predicted amino-acid sequences of all functional pthA homologs and nonfunctional paralogs indicated that the specific sequence of the 17th repeat may be essential for pathogenicity of X. citri on citrus.

  4. MKP1-dependent PTH modulation of bone matrix mineralization in female mice is osteoblast maturation stage specific and involves P-ERK and P-p38 MAPKs.

    Science.gov (United States)

    Mahalingam, Chandrika D; Sampathi, Bharat Reddy; Sharma, Sonali; Datta, Tanuka; Das, Varsha; Abou-Samra, Abdul B; Datta, Nabanita S

    2013-03-01

    Limited information is available on the role of MAPK phosphatase 1 (MKP1) signaling in osteoblasts. We have recently reported distinct roles for MKP1 during osteoblast proliferation, differentiation, and skeletal responsiveness to parathyroid hormone (PTH). As MKP1 regulates the phosphorylation status of MAPKs, we investigated the involvement of P-ERK and P-p38 MAPKs in MKP1 knockout (KO) early and mature osteoblasts with respect to mineralization and PTH response. Calvarial osteoblasts from 9-14-week-old WT and MKP1 KO male and female mice were examined. Western blot analysis revealed downregulation and sustained expressions of P-ERK and P-p38 with PTH treatment in differentiated osteoblasts derived from KO males and females respectively. Exposure of early osteoblasts to p38 inhibitor, SB203580 (S), markedly inhibited mineralization in WT and KO osteoblasts from both genders as determined by von Kossa assay. In osteoblasts from males, ERK inhibitor U0126 (U), not p38 inhibitor (S), prevented the inhibitory effects of PTH on mineralization in early or mature osteoblasts. In osteoblasts from KO females, PTH sustained mineralization in early osteoblasts and decreased mineralization in mature cells. This effect of PTH was attenuated by S in early osteoblasts and by U in mature KO cells. Changes in matrix Gla protein expression with PTH in KO osteoblasts did not correlate with mineralization, indicative of MKP1-dependent additional mechanisms essential for PTH action on osteoblast mineralization. We conclude that PTH regulation of osteoblast mineralization in female mice is maturation stage specific and involves MKP1 modulation of P-ERK and P-p38 MAPKs.

  5. PTH (1–34), but not strontium ranelate counteract loss of trabecular thickness and bone strength in disuse osteopenic rats

    DEFF Research Database (Denmark)

    Brüel, Annemarie; Vegger, Jens Bay; Raffalt, Anders Christer;

    2013-01-01

    +PTH+SrR (n=12 in each group). PTH was given as injections (SC) at a dosage of 60 μg/kg/d, and SrR as 900 mg/kg/d in the diet. The experiment lasted for 4weeks.BTX resulted in lower trabecular bone formation rate (−68%) and periosteal bone formation rate (−91%), and a higher fraction of osteoclast......) and periosteal (5-fold increase vs. BTX) bone formation rate, trabecular thickness (+25% vs. BTX) and femoral neck strength (+24% vs. BTX). In contrast, SrR did not influence BTX-induced loss of bone formation rate, trabecular bone volume fraction, trabecular thickness, or bone strength. Finally, no additive...

  6. Anode activation polarization on Pt(h k l) electrodes in dilute sulphuric acid electrolyte

    Science.gov (United States)

    Mann, R. F.; Amphlett, J. C.; Peppley, B. A.; Thurgood, C. P.

    Proton exchange membrane (PEM) fuel cells have been under development for many years and appear to be the potential solution for many electricity supply applications. Modelling and computer simulation of PEM fuel cells have been equally active areas of work as a means of developing better understanding of cell and stack operation, facilitating design improvements and supporting system simulation studies. The prediction of activation polarization in our previous PEM modelling work, as in most PEM models, concentrated on the cathode losses. Anode losses are commonly much smaller and tend to be ignored compared to cathode losses. Further development of the anode activation polarization term is being undertaken in order to broaden the application and usefulness of PEM models in general. Previously published work on the kinetics of the hydrogen oxidation reaction using Pt(h k l) electrodes in dilute H 2SO 4 has been examined and further developed for eventual application to the modelling of PEM fuel cells. New correlations for the exchange current density are developed for Pt(1 0 0), Pt(1 1 0) and Pt(1 1 1) electrodes. Predictive equations for the anode activation polarization are also proposed. In addition, terminology has been modified to make the correlation approach and, eventually, the modelling method more easily understood and used by those without an extensive background in electrochemistry.

  7. Multiple regression technique for Pth degree polynominals with and without linear cross products

    Science.gov (United States)

    Davis, J. W.

    1973-01-01

    A multiple regression technique was developed by which the nonlinear behavior of specified independent variables can be related to a given dependent variable. The polynomial expression can be of Pth degree and can incorporate N independent variables. Two cases are treated such that mathematical models can be studied both with and without linear cross products. The resulting surface fits can be used to summarize trends for a given phenomenon and provide a mathematical relationship for subsequent analysis. To implement this technique, separate computer programs were developed for the case without linear cross products and for the case incorporating such cross products which evaluate the various constants in the model regression equation. In addition, the significance of the estimated regression equation is considered and the standard deviation, the F statistic, the maximum absolute percent error, and the average of the absolute values of the percent of error evaluated. The computer programs and their manner of utilization are described. Sample problems are included to illustrate the use and capability of the technique which show the output formats and typical plots comparing computer results to each set of input data.

  8. Hyperphosphatemia is a combined function of high serum PTH and high dietary protein intake in dialysis patients

    OpenAIRE

    Streja, Elani; Lau, Wei Ling; Goldstein, Leanne; Sim, John J.; Molnar, Miklos Z.; Nissenson, Allen R; Csaba P Kovesdy; Kalantar-Zadeh, Kamyar

    2013-01-01

    Elevated serum phosphorus is associated with higher death risk in hemodialysis patients. Previous studies have suggested that both higher serum parathyroid hormone (PTH) level and higher dietary protein intake may contribute to higher serum phosphorus levels. However, it is not well known how these two factors simultaneously contribute to the combined risk of hyperphosphatemia in real patient-care scenarios. We hypothesized that the likelihood of hyperphosphatemia increases across higher seru...

  9. A new human NHERF1 mutation decreases renal phosphate transporter NPT2a expression by a PTH-independent mechanism.

    Directory of Open Access Journals (Sweden)

    Marie Courbebaisse

    Full Text Available BACKGROUND: The sodium-hydrogen exchanger regulatory factor 1 (NHERF1 binds to the main renal phosphate transporter NPT2a and to the parathyroid hormone (PTH receptor. We have recently identified mutations in NHERF1 that decrease renal phosphate reabsorption by increasing PTH-induced cAMP production in the renal proximal tubule. METHODS: We compared relevant parameters of phosphate homeostasis in a patient with a previously undescribed mutation in NHERF1 and in control subjects. We expressed the mutant NHERF1 protein in Xenopus Oocytes and in cultured cells to study its effects on phosphate transport and PTH-induced cAMP production. RESULTS: We identified in a patient with inappropriate renal phosphate reabsorption a previously unidentified mutation (E68A located in the PDZ1 domain of NHERF1.We report the consequences of this mutation on NHERF1 function. E68A mutation did not modify cAMP production in the patient. PTH-induced cAMP synthesis and PKC activity were not altered by E68A mutation in renal cells in culture. In contrast to wild-type NHERF1, expression of the E68A mutant in Xenopus oocytes and in human cells failed to increase phosphate transport. Pull down experiments showed that E68A mutant did not interact with NPT2a, which robustly interacted with wild type NHERF1 and previously identified mutants. Biotinylation studies revealed that E68A mutant was unable to increase cell surface expression of NPT2a. CONCLUSIONS: Our results indicate that the PDZ1 domain is critical for NHERF1-NPT2a interaction in humans and for the control of NPT2a expression at the plasma membrane. Thus we have identified a new mechanism of renal phosphate loss and shown that different mutations in NHERF1 can alter renal phosphate reabsorption via distinct mechanisms.

  10. Effect of chronic elevation of plasma calcium concentration by PTH or vitamin D3on blood pressure and hypotensive activity of nifedipine in rats

    NARCIS (Netherlands)

    Jonkman, F.A.M.; Thoolen, M.J.M.C.; Wilffert, B.

    1984-01-01

    The influence of a chronically elevated total plasma calcium concentration on blood pressure and heart rate was investigated in conscious normotensive rats. The plasma calcium concentration was elevated by continuous subcutaneous infusion with parathormone (PTH) after parathyreoidectomy, and by oral

  11. Pharmacokinetics of teriparatide (rhPTH[1-34]) and calcium pharmacodynamics in postmenopausal women with osteoporosis.

    Science.gov (United States)

    Satterwhite, Julie; Heathman, Michael; Miller, Paul D; Marín, Fernando; Glass, Emmett V; Dobnig, Harald

    2010-12-01

    Teriparatide (rhPTH[1-34]) affects calcium metabolism in a pattern consistent with the known actions of endogenous parathyroid hormone (PTH). This report describes the pharmacokinetics and resulting serum calcium response to teriparatide in postmenopausal women with osteoporosis. Pharmacokinetic samples for this analysis were obtained from 360 women who participated in the Fracture Prevention Trial. Postmenopausal women with osteoporosis received daily subcutaneous injections of either teriparatide 20 μg (4.86 μmol) or placebo, median 21 months' treatment. Serum teriparatide and calcium concentrations were measured throughout the study. An indirect-response model was developed to describe the pharmacokinetic-pharmacodynamic relationship between teriparatide concentrations and serum calcium response. The pharmacokinetics of teriparatide were characterized by rapid absorption (maximum concentration achieved within 30 min) and rapid elimination (half-life of 1 h), resulting in a total duration of exposure to the peptide of approximately 4 h. Teriparatide transiently increased serum calcium, with the maximum effect observed at approximately 4.25 h (median increase 0.4 mg/dl [0.1 mmol/l]). Calcium concentrations returned to predose levels by 16-24 h after each dose. Persistent hypercalcemia was not observed; one teriparatide 20 μg-treated patient had a predose serum calcium value above the normal range but transient increase in serum calcium, consistent with the known effects of endogenous PTH on mineral metabolism. The excursion in serum calcium is brief, due to the short length of time that teriparatide concentrations are elevated.

  12. Serum BAP as the clinically useful marker for predicting BMD reduction in diabetic hemodialysis patients with low PTH.

    Science.gov (United States)

    Ueda, Misako; Inaba, Masaaki; Okuno, Senji; Maeno, Yoshifumi; Ishimura, Eiji; Yamakawa, Tomoyuki; Nishizawa, Yoshiki

    2005-07-22

    With decrease of serum PTH in hemodialysis (HD) patients, other factors besides parathyroid hormone (PTH) become important in regulating bone metabolism. We investigated which serum bone metabolic marker is the best to predict the bone mineral density (BMD) reduction in HD patients with serum PTHBAP), intact osteocalcin (OC), and N-terminal propeptide of type I collagen (PINP), and the bone resorption markers, deoxypyridinoline (DPD), pyridinoline (PYD), and beta-crossLaps (beta-CTx) were measured in serum from 137 HD patients. BMD of all patients was measured twice, approximately 1.5 years before and 1.5 years after measurement of their markers of bone metabolism. In all 137 HD patients, serum BAP was the only marker significantly higher in those with BMD reduction than in those without. In 42 diabetes mellitus (DM) HD patients with serum PTHBAP was again the only marker to discriminate those with BMD reduction from those without. At serum PTHBAP retained tendency toward higher value. These findings suggest that serum BAP might be the most sensitive to identify small changes of bone metabolism in low bone turnover state. Retrospective study confirmed the usefulness of serum BAP in clinical practice by significantly higher values in those with bone loss at PTHBAP is a clinically useful bone formation marker to predict the BMD reduction in DM HD patients with low level of PTH.

  13. Arsenic may be involved in fluoride-induced bone toxicity through PTH/PKA/AP1 signaling pathway.

    Science.gov (United States)

    Zeng, Qi-bing; Xu, Yu-yan; Yu, Xian; Yang, Jun; Hong, Feng; Zhang, Ai-hua

    2014-01-01

    Chronic exposure to combined fluoride and arsenic continues to be a major public health problem worldwide, affecting thousands of people. In recent years, more and more researchers began to focus on the interaction between the fluorine and the arsenic. In this study, the selected investigation site was located in China. The study group was selected from people living in fluoride-arsenic polluted areas due to burning coal. The total number of participants was 196; including the fluoride-arsenic anomaly group (130) and the fluoride-arsenic normal group (63). By observing the changes in gene and protein expression of PTH/PKA/AP1 signaling pathway, the results show that fluoride can increase the expression levels of PTH, PKA, and AP1, but arsenic can only affect the expression of AP1; fluoride and arsenic have an interaction on the expression of AP1. Further study found that fluoride and arsenic can affect the mRNA expression level of c-fos gene (AP1 family members), and have an interaction on the expression of c-fos, but not c-jun. The results indicate that PTH/PKA/AP1 signaling pathway may play an important role in bone toxicity of fluoride. Arsenic can affect the expression of c-fos, thereby affecting the expression of transcription factor AP1, indirectly involved in fluoride-induced bone toxicity. Copyright © 2013. Published by Elsevier B.V.

  14. The relationship of PTH Bst BI polymorphism, calciotropic hormone levels, and dental fluorosis of children in China.

    Science.gov (United States)

    Wen, Shibao; Li, Anqi; Cui, Liuxin; Huang, Qi; Chen, Hongyang; Guo, Xiaoyi; Luo, Yixin; Hao, Qianyun; Hou, Jiaxiang; Ba, Yue

    2012-06-01

    The aim of this study was to explore the association of parathyroid hormone (PTH) gene Bst BI polymorphism, calciotropic hormone levels, and dental fluorosis of children. A case-control study was conducted in two counties (Kaifeng and Tongxu) in Henan Province, China in 2005-2006. Two hundred and twenty-five children were recruited and divided into three groups including dental fluorosis group (DFG), non-dental fluorosis group (NDFG) from high fluoride areas, and control group (CG). Urine fluoride content was determined using fluoride ion selective electrode; PTH Bst BI were genotyped using PCR-RFLP; osteocalcin (OC) and calcitonin (CT) levels in serum were detected using radioimmunoassay. Genotype distributions were BB 85.3% (58/68), Bb 14.7% (10/68) for DFG; BB 77.6% (52/67), Bb 22.4% (15/67) for NDFG; and BB 73.3% (66/90), Bb 27.7% (24/90) for CG. No significant difference of Bst BI genotypes was observed among three groups (P > 0.05). Serum OC and urine fluoride of children were both significantly higher in DFG and NDFG than in CG (P 0.05). Serum OC level of children with BB genotype was significantly higher compared to those with Bb genotype in high fluoride areas (P dental fluorosis and PTH Bst BI polymorphism. Serum OC might be a more sensitive biomarker for detecting early stages of dental fluorosis, and further studies are needed.

  15. Correlation between plasma calcium, parathyroid hormone (PTH) and the metabolic syndrome (MetS) in a community-based cohort of men and women.

    Science.gov (United States)

    Ahlström, Tommy; Hagström, Emil; Larsson, Anders; Rudberg, Claes; Lind, Lars; Hellman, Per

    2009-11-01

    In recent years, an association has been noted between several abnormalities that characterize the metabolic syndrome (MetS) and primary hyperparathyroidism (pHPT). These abnormalities include dyslipidaemia, obesity, insulin resistance and hypertension. The correlations between plasma calcium, parathyroid hormone (PTH) and the variables in the MetS in a normal population are still unclear. To describe correlations between plasma calcium and PTH and the various abnormalities present in the MetS in a healthy population. We studied 1016 healthy individuals from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) population of 70 years old, by means of plasma analyses of calcium, PTH, creatinine, lipids, insulin and glucose, as well as by standardized blood pressure measurements. Further, body mass index (BMI) and waist circumference were determined. The more National Cholesterol Education Program (NCEP) criteria for the MetS that were met, the higher the s-PTH and albumin-corrected s-calcium. Further, positive correlations between plasma calcium and BMI (P = 0.0003), waist circumference (P = 0.0009) and insulin resistance (P = 0.079) were found. PTH and BMI (P < 0.0001), waist circumference (P < 0.0001), systolic blood pressure (P = 0.0034), diastolic blood pressure (P = 0.0008), serum triglycerides (P = 0.0003) and insulin resistance (P = 0.0003) were positively correlated, whereas serum high density lipoproteins (HDL) (P = 0.036) and PTH were negatively correlated. We conclude that PTH correlates with several of the metabolic factors included in the MetS within a normocalcaemic population. In addition, individuals with mild pHPT present significantly more NCEP criteria for MetS. We postulate that increased levels of PTH in pHPT may be associated with the increased cardiovascular morbidity and mortality seen in pHPT.

  16. Variations of snow petrel breeding success in relation to sea-ice extent: detecting local response to large-scale processes?

    NARCIS (Netherlands)

    Olivier, F.; Franeker, van J.A.; Creuwels, J.C.S.; Woehler, E.J.

    2005-01-01

    Demographic parameters were estimated for snow petrels Pagodroma nivea nesting at the study colony of Reeve Hill near Casey station, Antarctica between 1984 and 2003. Average breeding success for the colony varied from 18.2% to 76.5%. Breeding effort, hatching and fledging success were subject to a

  17. Intermittent PTH (1-34) injection rescues the retarded skeletal development and postnatal lethality of mice mimicking human achondroplasia and thanatophoric dysplasia.

    Science.gov (United States)

    Xie, Yangli; Su, Nan; Jin, Min; Qi, Huabing; Yang, Junbao; Li, Can; Du, Xiaolan; Luo, Fengtao; Chen, Bo; Shen, Yue; Huang, Haiyang; Xian, Cory J; Deng, Chuxia; Chen, Lin

    2012-09-15

    Achondroplasia (ACH) and thanatophoric dysplasia (TD) are caused by gain-of-function mutations of fibroblast growth factor receptor 3 (FGFR3) and they are the most common forms of dwarfism and lethal dwarfism, respectively. Currently, there are few effective treatments for ACH. For the neonatal lethality of TD patients, no practical effective therapies are available. We here showed that systemic intermittent PTH (1-34) injection can rescue the lethal phenotype of TD type II (TDII) mice and significantly alleviate the retarded skeleton development of ACH mice. PTH-treated ACH mice had longer naso-anal length than ACH control mice, and the bone lengths of humeri and tibiae were rescued to be comparable with those of wild-type control mice. Our study also found that the premature fusion of cranial synchondroses in ACH mice was partially corrected after the PTH (1-34) treatment, suggesting that the PTH treatment may rescue the progressive narrowing of neurocentral synchondroses that cannot be readily corrected by surgery. In addition, we found that the PTH treatment can improve the osteopenia and bone structure of ACH mice. The increased expression of PTHrP and down-regulated FGFR3 level may be responsible for the positive effects of PTH on bone phenotype of ACH and TDII mice.

  18. Frequency of papillary tubal hyperplasia (PTH), salpingoliths and transition from adenoma to borderline ovarian tumors (BOT): A systematic analysis of 74 BOT with different histologic types.

    Science.gov (United States)

    Horn, Lars-Christian; Angermann, Karolin; Hentschel, Bettina; Einenkel, Jens; Höhn, Anne Kathrin

    2017-02-06

    Borderline ovarian tumors (BOT) arise from cystadenomas and represent a transition step within the development of low-grade ovarian carcinomas (Type I tumors). That pathway mirrors the adenoma-to-carcinoma sequence known for colorectal cancer. It has been suggested that papillary tubal hyperplasia (PTH) and salpingoliths may be associated with the development of BOT. To evaluate the frequency of the presence of benign cystadenoma and its transition to BOT in a given patient as well as the presence of PTH and salpingoliths we re-valuated in 74 consecutive cases of BOT with different histologic types. The majority of cases represented serous-BOT (60.8%), followed by mucinous BOT (25.7%), other histologic types were rare. 86.5% showed an adenoma-BOT sequence, which was seen in all mucinous BOT but was missed in 15.6% of serous BOT. Two cases had salpingoliths without associated PTH. PTH was seen in four out of the 74 (5.4%) BOT and occurred only in cases with serous histology. The vast majority of BOT represent a transition from benign cystadenoma to BOT in cases with mucinous and serous histology. Salpingoliths are rarely seen in association with BOT and occurred exclusively in BOT with serous histology. PTH may represent a distinct lesion but is rarely seen in association with BOT, especially in those with non-serous histology. Further studies are needed to evaluate the frequency and pathogenetic association of PTH with BOT.

  19. PTH stimulated growth and decreased Col-X deposition are phosphotidylinositol-3,4,5 triphosphate kinase and mitogen activating protein kinase dependent in avian sterna.

    Science.gov (United States)

    Harrington, Erik Kern; Coon, David J; Kern, Matthew F; Svoboda, Kathy K H

    2010-02-01

    Type X collagen (Col-X) deposition is a marker of terminal differentiation during chondrogenesis, in addition to appositional growth and apoptosis. The parathyroid hormone/parathyroid hormone related peptide (PTH/PTHrP) receptor, or PPR, is a G-Protein coupled receptor (GPCR), which activates several downstream pathways, moderating chondrocyte differentiation, including suppression of Col-X deposition. An Avian sterna model was used to analyze the PPR GPCR downstream kinase role in growth rate and extracellular matrix (ECM) including Col-II, IX, and X. Phosphatidylinositol kinase (PI3K), mitogen activating protein kinase (MAPK) and protein kinase A (PKA) were inhibited with specific established inhibitors LY294002, PD98059, and H89, respectively to test the hypothesis that they could reverse/inhibit the PTH/PTHrP pathway. Excised E14 chick sterna were PTH treated with or without an inhibitor and compared to controls. Sternal length was measured every 24 hr. Cultured sterna were immuno-stained using specific antibodies for Col-II, IX, or X and examined via confocal microscopy. Increased growth in PTH-treated sterna was MAPK, PI3K, and PKA dose dependent, suggesting growth was regulated through multiple pathways. Col-X deposition was rescued in PTH-treated sterna in the presence of PI3K or MAPK inhibitors, but not with the PKA inhibitor. All three inhibitors moderately disrupted Col-II and Col-IX deposition. These results suggest that PTH can activate multiple pathways during chondrocyte differentiation.

  20. Feasibility of unilateral parathyroidectomy in patients with primary hyperparathyroidism and negative or discordant localization studies.

    Science.gov (United States)

    Calò, Pietro Giorgio; Medas, Fabio; Loi, Giulia; Erdas, Enrico; Pisano, Giuseppe; Nicolosi, Angelo

    2016-06-01

    The purpose of this study was to examine the feasibility of unilateral parathyroidectomy in patients with primary hyperparathyroidism and negative or discordant localization studies. We included in our study 72 patients with preoperative diagnosis of primary hyperparathyroidism who had negative or discordant preoperative studies. In 66 patients, studies were discordant while in six were both negative. In 40 (55.6 %) patients initial approach was a bilateral exploration. In 32 cases (44.4 %) initial surgery was a unilateral exploration: in 26 conservative approach was successful, in six mini-invasive surgery failed and a bilateral exploration was necessary due to IOPTH negative test (five cases) or to the impossibility to find a pathological gland during exploration (one case). Intra-operative PTH test showed a sensitivity of 93.2 %, a specificity of 92.3 %, and an accuracy of 93.1 %. Multiple gland disease was found in 8 (11.1 %) patients (two double adenoma and six multiple gland hyperplasia). Mean operative time was lower in unilateral exploration group (87.9 ± 43.8 min). Comparing unilateral surgery in negative or discordant studies with 77 consecutive patients who underwent focused surgery with positive and concordant studies, conversion to bilateral exploration rate was statistically significantly higher in the first group (15.6 %). We believe that unilateral parathyroidectomy can be safely performed also in patients with discordant localization studies with a high cure rate; in these cases, however, the use of intra-operative PTH is absolutely necessary. We suggest the need for referral of these patients to high-volume medical centers for thyroid and parathyroid surgery.

  1. Successful treatment of osseous lesion associated with palatoradicular groove using local drug delivery and guided tissue regeneration: A report of two cases

    Directory of Open Access Journals (Sweden)

    Jayaprakash S Gadagi

    2012-01-01

    Full Text Available Developmental grooves are not rare and often appear on maxillary lateral and central incisors and are an important predisposing factor to localized periodontal disease. Various techniques have been adopted to eliminate the groove and regenerate lost periodontium. This report of two cases describes the technique of using the local drug delivery system with chlorehexidine and the guided tissue regeneration (GTR to control the disease progression and regeneration.

  2. Successful treatment of osseous lesion associated with palatoradicular groove using local drug delivery and guided tissue regeneration: A report of two cases

    OpenAIRE

    Jayaprakash S Gadagi; Sugumari Elavarasu; Divya Ananda; Thamaraiselvan Murugan

    2012-01-01

    Developmental grooves are not rare and often appear on maxillary lateral and central incisors and are an important predisposing factor to localized periodontal disease. Various techniques have been adopted to eliminate the groove and regenerate lost periodontium. This report of two cases describes the technique of using the local drug delivery system with chlorehexidine and the guided tissue regeneration (GTR) to control the disease progression and regeneration.

  3. Therapeutic effect of human parathyroid hormone1 - 34 ( rhPTH1 - 34) on osteoporosis of ovariectomized rats%rhPTH(1-34)对骨质疏松大鼠的作用及对sclerostin的影响

    Institute of Scientific and Technical Information of China (English)

    富勇; 唐永亮; 赵承斌; 张军

    2011-01-01

    [目的]探讨人重组甲状旁腺素1 - 34(rhPTH1 - 34)对骨质疏松的治疗作用以及与血钙、磷代谢和生长因子的关系.[方法]用摘除大鼠双侧卵巢的方式制备骨质疏松模型,实验动物分为3个组:模型对照组(OVX组,摘除大鼠双侧卵巢不作任何处理);rhPTH1 - 34治疗组(PTH组,摘除大鼠双侧卵巢12周后用rhPTH1 - 34治疗8周);假手术组(sham组,仅切除卵巢周围的脂肪组织约3 g,术后12周纳入实验).应用第4代双能X线骨密度仪测量大鼠股骨上段骨密度值(BMD);用ELISA法测定血清硬化蛋白(sclerostin)水平及骨钙素(BGP)浓度;用自动生化仪测定血清碱性磷酸酶(ALP).[结果]rhPTH1 - 34治疗组、sham组均较OVX组股骨上段骨密度增高,组间比较差异有显著性(P<0.01).rhPTH1 - 34治疗组血清BGP浓度值升高及sclerostin值降低,与OVX组比较差异有显著性(P<0.01).各组血清钙、磷含量无明显变化,与OVX组比较差异无显著性,ALP值治疗组与OVX组无明显差异.[结论] rhPTHl - 34能够预防股骨上段骨密度丢失,并且血清BGP浓度值升高及sclerostin值降低,但对Ca、P、ALP含量无明显作用.%[Objective] To observe the therapeutic effect of human parathyroid hormonel -34 (rhPTHl -34) on osteoporosis of ovariectomized rats and its relation to blood calcium, phosphorus and growth factors. [Methods] Seventy - four ovariectomized (OVX) rats were divided into model control group (OVX group without any treatment) , rhPTHl -34 treatment group ( PTH group with treatment for 8 weeks) , and sham operation group. BMD of femur were measured with Hologic dual energy X - ray 4500 W bone desitometer in rats. Serum sclerostin levels and BGP concentrations were determined by ELISA. [Results] BMD of the femur in rhPTHl - 34 group and sham group were higher than those in OVX control group ( P < 0. 01) . The serum sclerostin and BGP in rhPTHl -34 group were significantly different with OVX control group (P

  4. Functional Pairing of Class B1 Ligand-GPCR in Cephalochordate Provides Evidence of the Origin of PTH and PACAP/Glucagon Receptor Family.

    Science.gov (United States)

    On, Jason S W; Duan, Cumming; Chow, Billy K C; Lee, Leo T O

    2015-08-01

    Several hypotheses have been proposed regarding the origin and evolution of the secretin family of peptides and receptors. However, identification of homologous ligand-receptor pairs in invertebrates and vertebrates is difficult because of the low levels of sequence identity between orthologs of distant species. In this study, five receptors structurally related to the vertebrate class B1 G protein-coupled receptor (GPCR) family were characterized from amphioxus (Branchiostoma floridae). Phylogenetic analysis showed that they clustered with vertebrate parathyroid hormone receptors (PTHR) and pituitary adenylate cyclase-activating polypeptide (PACAP)/glucagon receptors. These PTHR-like receptors shared synteny with several PTH and PACAP/glucagon receptors identified in spotted gar, Xenopus, and human, indicating that amphioxus preserves the ancestral chordate genomic organization of these receptor subfamilies. According to recent data by Mirabeau and Joly, amphioxus also expresses putative peptide ligands including homologs of PTH (bfPTH1 and 2) and PACAP/GLUC-like peptides (bfPACAP/GLUCs) that may interact with these receptors. Functional analyses showed that bfPTH1 and bfPTH2 activated one of the amphioxus receptors (bf98C) whereas bfPACAP/GLUCs strongly interacted with bf95. In summary, our data confirm the presence of PTH and PACAP/GLUC ligand-receptor pairs in amphioxus, demonstrating that functional homologs of vertebrate PTH and PACAP/glucagon GPCR subfamilies arose before the cephalochordate divergence from the ancestor of tunicates and vertebrates. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Tribes Communities Success Stories

    Data.gov (United States)

    U.S. Environmental Protection Agency — This data describes successful EPA projects and partnerships which are restoring local communities and watersheds within the San Francisco Bay Delta Watershed.

  6. Association between very low PTH levels and poor survival rates in haemodialysis patients: results from the French ARNOS cohort.

    Science.gov (United States)

    Jean, G; Lataillade, D; Genet, L; Legrand, E; Kuentz, F; Moreau-Gaudry, X; Fouque, D

    2011-01-01

    A very low parathyroid hormone (PTH) level (VLPL) is associated with an increased risk of adynamic bone disease, vascular calcification, and mortality in haemodialysis (HD) patients. The aim of the study was to assess the frequency, the associated factors, and the prognosis of non-surgical VLPL in a cohort of prevalent HD patients. In July 2005, a cross-sectional study was performed on the French ARNOS cohort in 1,348 prevalent HD patients from 24 dialysis centres in the Rhône-Alpes area. Patients with a baseline intact PTH level <50 pg/ml (VLPL, Group 1) and ≥ 50 pg/ml (Group 2) were compared and a 42-month survival analysis was performed. Patients with prevalent or incident parathyroidectomy were excluded. We studied 1,138 prevalent HD patients. As compared to patients of Group 2 (n = 1,019), patients with VLPL (Group 1, n = 119) had lower serum albumin levels (34.5 ± 5 vs. 36.4 ± 5 g/l, p < 0.0001), less protein intake (nPCR 0.99 ± 0.28 vs. 1.1 ± 0.28 g/kg/day, p = 0.01), higher calcaemia (2.30 ± 0.2 vs. 2.26 ± 0.2 mmol/l, p = 0.01) and were more frequently treated with calcium carbonate (67 vs. 54%, p < 0.001). Patients with VLPL had a higher mortality rate (HR: 1.4 (1.07-1.8), p = 0.006) after adjustment for age, gender, diabetes, and dialysis vintage. The odds ratios of mortality for patients with VLPL remained higher in all calcaemia and serum albumin quartiles. Only 3/119 patients in Group 1 did not receive any PTH-lowering therapies (i.e. calcium carbonate (67%), alfacalcidol (38%), cinacalcet (10.1%), and dialysate calcium ≥ 1.5 mmol/l (94%)). In this observational French cohort, VLPL was observed in 10% of prevalent HD patients and was associated with poor survival rates. An inadequate therapeutic strategy could be responsible for this observation. The real consequences of this iatrogenic adynamic bone disease remain hypothetical, but it may be related to the risk of developing vascular calcification. It is hypothesized that a more adequate

  7. Influence of Secondary Hyperparathyroidism Induced by Low Dietary Calcium, Vitamin D Deficiency, and Renal Failure on Circulating Rat PTH Molecular Forms.

    Science.gov (United States)

    D'Amour, Pierre; Rousseau, Louise; Hornyak, Stephen; Yang, Zan; Cantor, Tom

    2011-01-01

    Rats(r) with secondary hyperparathyroidism were studied to define the relationship between vitamin D metabolites and rPTH levels measured by 3 different rat ELISAs. Controls and renal failure (RF) rats were on a normal diet, while 2 groups on a low-calcium (-Ca) or a vitamin D-deficient (-D) diet. RF was induced surgically. Mild RF rats had normal calcium and 25(OH)D but reduced 1,25(OH)(2)D levels (P < .001) with a 2.5-fold increased in rPTH (P < .001). Severe RF rats and those on a -Ca or -D diet had reduced calcium (P < .01) and 25(OH)D levels (P < .05), with rPTH increased by 2 (-Ca diet; P < .05), 4 (-D diet; P < .001), and 20-folds (RF; P < .001) while 1,25(OH)(2)D was high (-Ca diet: P < .001) or low (-D diet, RF: P < .001). 25(OH)D and 1,25(OH)(2)D were positively and negatively related on the -Ca and -D diets, respectively. rPTH molecular forms behaved as expected in RF and on -Ca diet, but not on -D diet with more C-rPTH fragments when less were expected. This may be related to the short-time course of this study compared to prior studies.

  8. Evaluating the Role of PTH in Promotion of Chondrosarcoma Cell Proliferation and Invasion by Inhibiting Primary Cilia Expression

    Directory of Open Access Journals (Sweden)

    Wei Xiang

    2014-10-01

    Full Text Available Chondrosarcoma is characterized by secretion of a cartilage-like matrix, with high proliferation ability and metastatic potential. Previous studies have shown that parathyroid hormone-related protein (PTHrP has a close relationship with various tumor types. The objectives of this study were to research the function played by PTHrP in human chondrosarcoma, especially targeting cell proliferation and invasion, and to search for the potential interaction between PTHrP and primary cilia in tumorigenesis. Surgical resection tissues and the human chondrosarcoma cell line SW1353 were used in the scientific research. Cells were stimulated with an optimum concentration of recombinant PTH (1-84, and siRNA was used to interfere with internal PTHrP. Cell proliferation and invasion assays were applied, including MTS-8 cell proliferation assay, Western blot, RT-PCR, Transwell invasion assay, and immunohistochemistry and immunofluorescence assays. A high level of PTHrP expression was found in human chondrosarcoma tissues, and recombinant PTH exhibited positive promotion in tumor cell proliferation and invasion. In the meantime, PTHrP could inhibit the assembly of primary cilia and regulate downstream gene expression. These findings indicate that PTHrP can regulate tumor cell proliferation and invasion ability, possibly through suppression of primary cilia assembly. Thus, restricting PTHrP over-expression is a feasible potential therapeutic method for chondrosarcoma.

  9. A van der Waals DFT study of PtH2 systems absorbed on pristine and defective graphene

    Science.gov (United States)

    López-Corral, Ignacio; Piriz, Sebastián; Faccio, Ricardo; Juan, Alfredo; Avena, Marcelo

    2016-09-01

    We used a density functional that incorporates van der Waals interactions to study hydrogen adsorption onto Pt atoms attached to carbon-vacancies on graphene layers, considering molecular and dissociated hydrogen-platinum coordination structures. PtH2 complexes adsorbed on several sites of pristine graphene were also studied for comparison. Our results indicate that both a Kubas-type dihydrogen complex and a classic hydride without Hsbnd H bond are the preferential PtH2 systems on the vacancy site of graphene. In contrast, the Kubas complex is unstable onto pristine graphene and the hydride is obtained at all adsorption sites. Our simulations suggest that the C-vacancy decreases the reactivity of the metal decoration, allowing a non-dissociative hydrogen adsorption. The H2 molecule is oriented almost perpendicular to the outermost Csbnd Pt bond, interacting also with the graphene surface through σ-H and π-C states. This stabilization of the Kubas-type complex could play a very important role for hydrogen storage in Pt-decorated carbon adsorbents with vacancies.

  10. Theoretical Modeling of Water Exchange on [Pd(H(2)O)(4)](2+), [Pt(H(2)O)(4)](2+), and trans-[PtCl(2)(H(2)O)(2)].

    Science.gov (United States)

    Deeth, Robert J.; Elding, Lars I.

    1996-08-14

    Density functional theory is applied to modeling the exchange in aqueous solution of H(2)O on [Pd(H(2)O)(4)](2+), [Pt(H(2)O)(4)](2+), and trans-[PtCl(2)(H(2)O)(2)]. Optimized structures for the starting molecules are reported together with trigonal bipyramidal (tbp) systems relevant to an associative mechanism. While a rigorous tbp geometry cannot by symmetry be the actual transition state, it appears that the energy differences between model tbp structures and the actual transition states are small. Ground state geometries calculated via the local density approximation (LDA) for [Pd(H(2)O)(4)](2+) and relativistically corrected LDA for the Pt complexes are in good agreement with available experimental data. Nonlocal gradient corrections to the LDA lead to relatively inferior structures. The computed structures for analogous Pd and Pt species are very similar. The equatorial M-OH(2) bonds of all the LDA-optimized tbp structures are predicted to expand by 0.25-0.30 Å, while the axial bonds change little relative to the planar precursors. This bond stretching in the transition state counteracts the decrease in partial molar volume caused by coordination of the entering water molecule and can explain qualitatively the small and closely similar volumes of activation observed. The relatively higher activation enthalpies of the Pt species can be traced to the relativistic correction of the total energies while the absolute DeltaH() values for exchange on [Pd(H(2)O)(4)](2+) and [Pt(H(2)O)(4)](2+) are reproduced using relativistically corrected LDA energies and a simple Born model for hydration. The validity of the latter is confirmed via some simple atomistic molecular mechanics estimates of the relative hydration enthalpies of [Pd(H(2)O)(4)](2+) and [Pd(H(2)O)(5)](2+). The computed DeltaH() values are 57, 92, and 103 kJ/mol compared to experimental values of 50(2), 90(2), and 100(2) kJ/mol for [Pd(H(2)O)(4)](2+), [Pt(H(2)O)(4)](2+), and trans-[PtCl(2)(H(2)O)(2

  11. Deletion of the Distal Tnfsf11 RL-D2 Enhancer That Contributes to PTH-Mediated RANKL Expression in Osteoblast Lineage Cells Results in a High Bone Mass Phenotype in Mice.

    Science.gov (United States)

    Onal, Melda; St John, Hillary C; Danielson, Allison L; Pike, J Wesley

    2016-02-01

    Receptor activator of nuclear factor-κB ligand (RANKL) is a tumor necrosis factor (TNF)-like cytokine that is necessary for osteoclast formation and survival. Elevated RANKL synthesis is associated with both increased osteoclast number and bone resorption. Earlier studies identified an enhancer 76 kb upstream of the Tnfsf11 transcriptional start site (TSS) termed RL-D5 or the distal control region (DCR) that modulates RANKL expression in response to PTH, 1,25(OH)2D3,, and an array of cytokines. Mice lacking RL-D5 exhibit high bone mass associated with decreased RANKL expression in bone, spleen, and thymus. In addition to RL-D5, genome-wide studies have identified 9 additional Tnfsf11 enhancers residing upstream of the gene's TSS, which provide RANKL cell type-specificity and responsiveness to local and systemic factors. ChIP-chip analyses has revealed inducible vitamin D receptor (VDR) and cAMP response element-binding protein (CREB) binding at an enhancer termed RL-D2 23 kb upstream of the Tnfsf11 TSS in osteoblastic ST2 cells. Herein, we use ChIP-seq analyses to confirm this finding and then delete this enhancer from the mouse genome to determine its physiological role in vivo. RL-D2(-/-) primary stromal cells showed decreased RANKL-induction by both forskolin and 1,25(OH)2D3 ex vivo. Consistent with this, the parathyroid hormone (PTH) induction of RANKL expression was significantly blunted in RL-D2(-/-) mice in vivo. In contrast, lack of RL-D2 had no effect on 1,25(OH)2D3 induction of RANKL in vivo. Similar to the results found in RL-D5(-/-) mice, lack of RL-D2 led to decreased skeletal RANKL expression, resulting in decreased osteoclast numbers and a progressive increase in bone mineral density. Lack of RL-D2 increased cancellous bone mass in femur and spine but did not alter femoral cortical bone thickness. These results highlight the role of distal enhancers in the regulation of RANKL expression by PTH and perhaps 1,25(OH)2D3 and suggest that the RL-D2 and

  12. PTH对骨代谢双重作用的研究进展%Research progress of the dual effects of PTH on bone metabolism

    Institute of Scientific and Technical Information of China (English)

    万启龙; 王强; 李祖兵

    2011-01-01

    The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts plays a key role in bone remodeling. PTH is one of the important hormones which regulate calcium and phosphate homeostasis. PTH has dual effects on bone metabolism: continuous administration of PTH causes bone resorption, intermittent administration induces bone formation, but the mechanism is unclear. It will be the research focus to identify the mechanism, and this will be helpful to use the anabolic actions of PTH for osteoporosis treatment. In future, using the dual effects of PTH on bone metabolism may be a novel therapy for bone malformation. Supported by National Natural Science Foundation of China (30672341).%成骨细胞参与的骨形成与破骨细胞参与的骨吸收之间的动态平衡,是骨改建过程中的关键.甲状旁腺激素(PTH)是维持机体钙、磷代谢平衡的重要激素.PTH对骨代谢具有双重效应:间歇应用PTH促进骨形成;而持续应用PTH会诱发骨吸收,但其机制仍不明确.明确PTH对骨代谢双重效应的机制,是今后研究的重点,将有助于更好地应用PTH骨合成效应治疗骨质疏松症,并有可能利用其双重效应治疗骨发育畸形.

  13. High dose ESAs are associated with high iPTH levels in hemodialysis patients with end-stage kidney disease: a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Lan eChen

    2015-11-01

    Full Text Available Objective: Anemia and secondary hyperparathyroidism are the two most common complications associated with chronic kidney disease (CKD. Erythropoiesis-stimulating agents (ESAs are widely used in the management of anemia in hemodialysis patients. A reverse correlation has been established between hyperparathyroidism and hemoglobin levels. The aim of this retrospective study is to evaluate the relationship of high dose ESAs and hyperparathyroidism in hemodialysis patients with anemia. Methods: A total of 240 uremic patients maintained on regular hemodialysis were enrolled into this study. Among them, 142 patients were treated with Epiao® (epoetin-alfa and 98 patients were treated with Recormon® (epoetin-beta. The target hemoglobin concentration was 110-130 g/L. Laboratory measurements including hemoglobin, calcium, phosphorus, albumin, intact-parathyroid hormone (iPTH, serum ferritin and transferrin saturation were collected. Results: Hemoglobin concentration increased as iPTH level decreased by stratification. However, no significant association between anemia and calcium or phosphorus level was found. Patients with iPTH levels within 150-300 pg/mL had the highest levels of hemoglobin, serum ferritin and transferrin saturation. Patients treated with Recormon and Epiao had similar hemoglobin concentrations. However, the dose of Recormon for anemia treatment was significantly less than that the dose of Epiao (P<0.05. The level of iPTH in the Recormon group was significantly lower than in the Epiao group. In patients with hemoglobin levels between 110-130 g/L (P<0.05, iPTH level was found to be significantly lower in patients treated with lower doses of ESAs than in patients treated with higher doses of ESAs, no matter which ESA was used (Recormon or Epiao, P<0.05. Conclusions: The dose of ESAs might be positively associated with iPTH level, suggesting that a reasonable hemoglobin target can be achieved by using the lowest possible ESA dose.

  14. Intersectoral Action to Enhance the Social Inclusion of Socially Vulnerable Youth through Sport: An Exploration of the Elements of Successful Partnerships between Youth Work Organisations and Local Sports Clubs

    Directory of Open Access Journals (Sweden)

    Niels Hermens

    2015-06-01

    Full Text Available Research shows that participation in sport is positively related to self-esteem, self-regulation skills, and social inclusion. As socially vulnerable youngsters participate less frequently in sports activities than their average peers, youth work organisations try to guide their clients (i.e., socially vulnerable youngsters to local sports clubs and inclusive sports activities. Inclusive sports activities, however, cannot be provided by youth work organisations alone. Therefore, in the Netherlands, intersectoral action involving both youth work organisations and local sports clubs has emerged. Because youth workers and stakeholders in local sports clubs are not used to collaborating with each other, we explored the factors that contribute to the quality and performance of such intersectoral actions. On the basis of five open interviews with youth workers and three focus groups with stakeholders in local sports clubs, we described factors relating to the organisation of intersectoral action among youth workers and local sports clubs that are preconditions for the success of this specific type of intersectoral action.

  15. The abnormal phenotypes of cartilage and bone in calcium-sensing receptor deficient mice are dependent on the actions of calcium, phosphorus, and PTH.

    Directory of Open Access Journals (Sweden)

    Jingning Liu

    2011-09-01

    Full Text Available Patients with neonatal severe hyperparathyroidism (NSHPT are homozygous for the calcium-sensing receptor (CaR mutation and have very high circulating PTH, abundant parathyroid hyperplasia, and severe life-threatening hypercalcemia. Mice with homozygous deletion of CaR mimic the syndrome of NSHPT. To determine effects of CaR deficiency on skeletal development and interactions between CaR and 1,25(OH(2D(3 or PTH on calcium and skeletal homeostasis, we compared the skeletal phenotypes of homozygous CaR-deficient (CaR(-/- mice to those of double homozygous CaR- and 1α(OHase-deficient [CaR(-/-1α(OHase(-/-] mice or those of double homozygous CaR- and PTH-deficient [CaR(-/-PTH(-/-] mice at 2 weeks of age. Compared to wild-type littermates, CaR(-/- mice had hypercalcemia, hypophosphatemia, hyperparathyroidism, and severe skeletal growth retardation. Chondrocyte proliferation and PTHrP expression in growth plates were reduced significantly, whereas trabecular volume, osteoblast number, osteocalcin-positive areas, expression of the ALP, type I collagen, osteocalcin genes, and serum ALP levels were increased significantly. Deletion of 1α(OHase in CaR(-/- mice resulted in a longer lifespan, normocalcemia, lower serum phosphorus, greater elevation in PTH, slight improvement in skeletal growth with increased chondrocyte proliferation and PTHrP expression, and further increases in indices of osteoblastic bone formation. Deletion of PTH in CaR(-/- mice resulted in rescue of early lethality, normocalcemia, increased serum phosphorus, undetectable serum PTH, normalization in skeletal growth with normal chondrocyte proliferation and enhanced PTHrP expression, and dramatic decreases in indices of osteoblastic bone formation. Our results indicate that reductions in hypercalcemia play a critical role in preventing the early lethality of CaR(-/- mice and that defects in endochondral bone formation in CaR(-/- mice result from effects of the marked elevation in serum

  16. Differential conformational requirements for activation of G proteins and the regulatory proteins arrestin and G protein-coupled receptor kinase in the G protein-coupled receptor for parathyroid hormone (PTH)/PTH-related protein.

    Science.gov (United States)

    Vilardaga, J P; Frank, M; Krasel, C; Dees, C; Nissenson, R A; Lohse, M J

    2001-09-07

    After stimulation with agonist, G protein-coupled receptors (GPCRs) activate G proteins and become phosphorylated by G protein-coupled receptor kinases (GRKs), and most of them translocate cytosolic arrestin proteins to the cytoplasmic membrane. Agonist-activated GPCRs are specifically phosphorylated by GRKs and are targeted for endocytosis by arrestin proteins, suggesting a connection between GPCR conformational changes and interaction with GRKs and arrestins. Previously, we showed that by substitution of histidine for residues at the cytoplasmic side of helix 3 (H3) and helix 6 (H6) of the parathyroid hormone (PTH) receptor (PTHR), a zinc metal ion-binding site is engineered that prevents PTH-stimulated G(s) activation (Sheikh, S. P., Vilardaga, J.-P., Baranski, T. J., Lichtarge, O., Iiri, T., Meng, E. C., Nissenson, R. A., and Bourne, H. R. (1999) J. Biol. Chem. 274, 17033-17041). These data suggest that relative movements between H3 and H6 are critical for G(s) activation. Does this molecular event play a similar role in activation of GRK and arrestin and in PTHR-mediated G(q) activation? To answer this question, we utilized the two previously described mutant forms of PTHR, H401 and H402, which contain a naturally present histidine residue at position 301 in H3 and a second substituted histidine residue at positions 401 and 402 in H6, respectively. Both mutant receptors showed inhibition of PTH-stimulated inositol phosphate and cAMP generation in the presence of increasing concentrations of Zn(II). However, the mutants showed no Zn(II)-dependent impairment of phosphorylation by GRK-2. Likewise, the mutants were indistinguishable from wild-type PTHR in the ability to translocate beta-arrestins/green fluorescent protein to the cell membrane and were also not affected by sensitivity to Zn(II). These results suggest that agonist-mediated phosphorylation and internalization of PTHR require conformational switches of the receptor distinct from the cAMP and inositol

  17. [A case of locally advanced breast cancer successfully treated with wide resection and reconstruction of chest wall with A-O metallic plates].

    Science.gov (United States)

    Imamura, H; Tatsuta, M; Masuda, N; Miya, A; Ezumi, K; Shimizu, J; Ikeda, M; Ishida, H; Masutani, S; Kawasaki, T; Furukawa, H; Satomi, T

    2001-10-01

    A 63-year-old female with locally advanced breast cancer was treated with preoperative chemotherapy using docetaxel. The therapeutic regimen was comprised of four cycles at 3-week intervals. One cycle consisted of 80 mg of docetaxel which was administered on day 1. A remarkable response was confirmed. The side effects such as leukopenia, general fatigue and alopecia were moderate and had no influence on the patient's QOL. After preoperative chemotherapy, a full thickness chest wall resection was performed. Chest wall defect was reconstructed with orthopedic A-O metallic plates, Marlex mesh and rectus abdominis myocutaneous flap. These metal plates were very useful because it was easy to bend and twist them manually to fit the defect at the time of operation. Moreover, the curved metal plates preserved the cone form of the chest cage. The postoperative course was favourable without frail chest or wound infection.

  18. Detection and Characterization of Parathyroid Adenoma/Hyperplasia for Preoperative Localization: Comparison Between {sup 11}C-Methionine PET/CT and {sup 99m}Tc-Sestamibi Scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Chun, In Kook; Cheon, Gi Jeong; Paeng, Jin Chul; Kang, Keon Wook; Chung, Junekey; Lee, Dong Soo [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2013-09-15

    {sup 11}C-Methionine PET/CT (Met-PET/CT) is a useful imaging method for detection of parathyroid adenoma; however, the reported detection rate has been variable. The current study was intended to investigate detection sensitivity and preoperative localization of parathyroid adenoma (PA) or parathyroid hyperplasia (PH) on Met-PET/CT compared with {sup 99m}Tc-sestamibi (MIBI) scintigraphy in patients with primary hyperparathyroidism (HPT) or suspected PA. Met-PET/CT and MIBI scintigraphy images were reviewed by two nuclear medicine physicians unaware of pathologic results. Detection sensitivities and preoperative localization of detected parathyroid tissues into five predefined segments were evaluated by visual assessment and semiquantitative analysis with ratio of standardized uptake values (SUVR) between parathyroid tissue and normal lung as reference. Linear regression analysis with SUVR and serum parathyroid hormone (sPTH) was performed for characterization of PA or PH. Predicted PTH (pPTH) was calculated and compared with sPTH in PH and PA. Each pPTH was obtained for a calculated SUVR by using linear regression model from the result of previous linear regression analysis between SUVR and sPTH. In 16 patients, detection sensitivities of Met-PET/CT and MIBI scintigraphy were 91.7 % (11/12) and 41.7 % (5/12) for PA and PH including both biopsy-confirmed and clinically-suspected cases, and 100 % (8/8) and 50 % (4/8) for pathologically confirmed PA and PH cases only, respectively. Met-PET/CT showed higher performance than MIBI scintigraphy in localization of parathyroid tissues; correct localization rate was 87.5 % (7/8) on Met-PET/CT and 50 % (4/8) on MIBI scintigraphy. In semi-quantitative analysis, SUVR was linearly associated with sPTH by linear regression analysis (sPTH=39.53ΧSUVR-89.84, p=0.0383). There was a borderline significant difference in pPTH between PH and PA (35.1 vs 204.7±164.0, p=0.052),while there was no significant difference in sPTH between PH

  19. 地方性知识:工程成功“嵌入”社会何以可能∗%Local Knowledge:Why Engineering can Embed in Society Successfully

    Institute of Scientific and Technical Information of China (English)

    陈绍军; 朱运亮; 李如春

    2015-01-01

    Local knowledge in the process of engineering embedding society is a social regulation which affects the interdynamic relation between the project and society,including text and discourse,com-mon sense and society structure.As a typical traditional category,whether to comply with local knowl-edge determines the success of local knowledge embedding social engineering.In social engineering a-nalysis,participant observation helps to identify local knowledge,and local knowledge of social engi-neering is mainly for mutual eligibility,diversity and vulnerability.On this basis,combined with spe-cific engineering cases,this paper introduces the applications of social analysis of engineering from the view of local knowledge.The author holds the opinion that respecting,protecting and utilizing local knowledge properly can ensure engineering embeds in society successfully.%工程社会中的地方性知识是影响工程与社会之间互构关系的社会规范,包括文本与话语、常识、社会结构三种类型。作为典型的小传统范畴,是否遵从地方性知识决定了工程能否成功“嵌入”社会。在工程社会性分析中,参与观察有助于识别地方性知识,地方性知识的工程社会性主要表现为互适性、差异性、脆弱性。在上述分析的基础上,结合具体的工程案例,对地方性知识视角在工程社会性分析中的应用进行了介绍,认为只有尊重、保护及合理利用地方性知识才能确保工程成功“嵌入”社会。

  20. El español en Internet: aciertos y errores en sitios web localizados del inglés (The Spanish language in the Internet: successes and errors in localized websites

    Directory of Open Access Journals (Sweden)

    María Isabel Diéguez Morales

    2011-12-01

    Full Text Available En este artículo se presentan aciertos, errores y técnicas de traducción en la localización web del inglés al español de Chile. Esta investigación se enmarca en los Estudios Descriptivos de la Traducción (Toury, 2004 y en la teoría funcional (Nord, 1997/2005. El estudio abarcó una submuestra de 14 sitios web originales y localizados de organizaciones asociadas a AMCHAM Chile (Directorio 2006. Para el análisis contrastivo, se procedió a identificar y clasificar los aciertos, errores, y las diferentes técnicas de traducción utilizadas (préstamo, amplificación, adaptación, entre otras. En el caso de los errores, se propone una traducción funcionalmente adecuada. Con esta investigación se pretende contribuir al análisis descriptivo crítico de la localización de sitios web con el fin de optimizar la formación de localizadores. (This article presents successes, errors, and translation techniques in localized websites from English to Chilean Spanish. The investigation is framed in the field of Descriptive Translation Studies (Toury, 2004, and the Skopostheory (Nord, 1997/2005. The study is based on a subsample of 14 original and localized websites of organizations belonging to AMCHAM Chile (2006 Directory. For the contrastive analysis, successes, errors, and the different translation techniques used (loanword, amplification, adaptation, among others were identified and classified. In the case of the errors, a functional translation was proposed. The aim is to contribute to the critical descriptive analysis of web localization in order to improve the training of localizers.

  1. Alteração do teor de cálcio no banho de DP para 2,5 mEq/L é eficaz no reestabelecimento dos valores preconizados por diretrizes atuais em pacientes com PTH < 150 pg/dL Low-calcium peritoneal dialysis solution is effective in bringing PTH levels to the range recommended by current guidelines in patients with PTH levels < 150 pg/dL

    Directory of Open Access Journals (Sweden)

    Thyago Proença de Moraes

    2010-09-01

    Full Text Available INTRODUÇÃO/OBJETIVO: A doença óssea adinâmica (DOA é um achado comum em diálise peritoneal (PD e é considerada fator de risco para desenvolvimento de fraturas e doença cardiovascular. Dados do BRAZPD apontam as soluções de cálcio a 3,5 mEq/L presentes na maioria das prescrições no país, que possui quase 9.000 pacientes em PD. É comum o balanço positivo de cálcio com concentrações a 3,5 mEq/L contribuindo para o desenvolvimento de DOA. Diretrizes atuais recomendam um PTHi na DRC V em diálise entre 2 e 9 vezes (150-500 pg/mL o valor máximo da normalidade. O objetivo deste estudo foi avaliar a resposta em 6 meses do PTH-i após a conversão para solução de cálcio a 2,5 mEq/L de pacientes que usavam soluções com cálcio a 3,5 mEq/L e com PTH-i basal INTRODUCTION/OBJECTIVE: Adinamic bone disease (ABD is a common finding in peritoneal dialysis (PD and is associated with higher risk of developing cardiovascular and bone disease. Data from BRAZPD indicates that 3.5 mEq/L calcium PD solutions represents the majority of PD prescriptions in the country. A positive calcium balance can contribute to ABD development. Currently guidelines suggest that PTH-i levels in end stage renal disease should be kept from 150-300 pg/mL. The purpose of this study is to evaluate 6 month PTH-i response after conversion to 2.5 mEq/L calcium PD solution in patients with baseline PTH-i levels < 150 pg/mL. METHODS: Prospective, observational study of all prevalent patients (at least 90 days on therapy on PD of a single Brazilian center from January 2008 to May 2009. Inclusion criteria (1 be in use of a PD solution with 3.5mEq/L of calcium; (2 baseline PTH leves < 150 pg/ mL. According to clinical practice patients could be switched to PD solutions with 2.5 mEq/L of calcium. RESULTS: 35 patients (age 62 ± 17 years were included. Of these 22 were converted to 2.5 mEq/L calcium solutions. Diabetic nephropathy (36% was the main cause of renal disease

  2. Smarandache p次方阶数的计算%The Computation of Smarandache Orders of p-th Powers

    Institute of Scientific and Technical Information of China (English)

    张瑾

    2015-01-01

    对于奇素数 p 和正整数n ,设 zn = min {m m ∈ N,npm ≡1(mod (n +1)p )},称为 n 的 Smarandache p 次方阶数。运用初等方法给出了 zn 的计算公式,并且纠正了现有结果中的错误。%For any odd prime p and any positive integer n,let zn = min {m m ∈ N,npm ≡1(mod (n + 1)p )},which is called the Smarandache Orders of p-th Power of n.In this paper,using some elementary methods,a formula of zn is given and certain wrong conclusions in previous results are corrected.

  3. Update on the efficacy, safety, and adherence to treatment of full length parathyroid hormone, PTH (1-84, in the treatment of postmenopausal osteoporosis

    Directory of Open Access Journals (Sweden)

    Luca Pietrogrande

    2009-11-01

    Full Text Available Luca PietrograndeDipartimento di Medicina Chirurgia e Odontoiatria Polo San Paolo, Università degli Studi di Milano, Milan, ItalyAbstract: Full length (1-84 parathyroid hormone (PTH was introduced in Europe as a treatment for postmenopausal osteoporosis in 2006. The efficacy of PTH (1-84 in the prevention of vertebral fractures is very high, and is similar to that of teriparatide. Its action in the prevention of femoral fractures has yet to be fully demonstrated, but the incidence of such fractures in trials was very low, and a decrease in nonvertebral fractures was seen in high-risk patients. The effect on bone mineral density (BMD was clearly demonstrated in the spine and also in the hip. The effects on BMD were evident and increased progressively with treatment until 36 months. After its discontinuation there was a clear decrease in BMD if no antiresorptive treatment was initiated. Increases in bone volumetric density and bone volume in trabecular sites were also reported. Moreover, a bone volume increase was detected in cortical sites. Hypercalcemia and hypercalciuria are frequent consequences of PTH treatment, but rarely have clinical effects and are usually well controlled by reducing calcium and vitamin D supplementation.Keywords: PTH (1-84, full-length parathyroid hormone, osteoporosis treatment

  4. Metabolic alkalosis transition in renal proximal tubule cells facilitates an increase in CYP27B1, while blunting responsiveness to PTH

    Science.gov (United States)

    Parathyroid hormone (PTH) is the central activator of renal proximal 1-alpha-hydroxylase (CYP27B1), the enzyme responsible for synthesis of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Past studies have documented a disruption of CYP27B1 activity in chronic metabolic acidosis in vivo, while simulated ac...

  5. Ihh and PTH1R signaling in limb mesenchyme is required for proper segmentation and subsequent formation and growth of digit bones.

    Science.gov (United States)

    Amano, Katsuhiko; Densmore, Michael; Fan, Yi; Lanske, Beate

    2016-02-01

    Digit formation is a process, which requires the proper segmentation, formation and growth of phalangeal bones and is precisely regulated by several important factors. One such factor is Ihh, a gene linked to BDA1 and distal symphalangism in humans. In existing mouse models, mutations in Ihh have been shown to cause multiple synostosis in the digits but lead to perinatal lethality. To better study the exact biological and pathological events which occur in these fused digits, we used a more viable Prx1-Cre;Ihh(fl/fl) model in which Cre recombinase is expressed during mesenchymal condensation in the earliest limb buds at E9.5 dpc and found that mutant digits continuously fuse postnatally until phalanges are finally replaced by an unsegmented "one-stick bone". Mutant mice displayed osteocalcin-positive mature osteoblasts, but had reduced proliferation and abnormal osteogenesis. Because of the close interaction between Ihh and PTHrP during endochondral ossification, we also examined the digits of Prx1-Cre;PTH1R(fl/fl) mice, where the receptor for PTHrP was conditionally deleted. Surprisingly, we found PTH1R deletion caused symphalangism, demonstrating another novel function of PTH1R signaling in digit formation. We characterized the symphalangism process whereby initial cartilaginous fusion prevented epiphyseal growth plate formation, resulting in resorption and replacement of the remaining cartilage by bony tissue. Chondrocyte differentiation displayed abnormal directionality in both mutants. Lastly, Prx1-Cre;Ihh(fl/fl);Jansen Tg mice, in which a constitutively active PTH1R allele was introduced into Ihh mutants, were established to address the possible involvement of PTH1R signaling in Ihh mutant digits. These rescue mice failed to show significantly improved phenotype, suggesting that PTH1R signaling in chondrocytes is not sufficient to restore digit formation. Our results demonstrate that Ihh and PTH1R signaling in limb mesenchyme are both essential to regulate

  6. The Bone-Protective Effect of Genistein in the Animal Model of Bilateral Ovariectomy: Roles of Phytoestrogens and PTH/PTHR1 Against Post-Menopausal Osteoporosis

    Directory of Open Access Journals (Sweden)

    Jian-Bo Wang

    2011-12-01

    Full Text Available Genistein, a major phytoestrogen of soy, is considered a potential drug for the prevention and treatment of post-menopausal osteoporosis. Mounting evidence suggested a positive correlation between genistein consumption and bone health both in vivo and in vitro. Earlier studies have revealed that genistein acted as a natural estrogen analogue which activated estrogen receptor and exerted anti-osteoporotic effect. However, it remains unclear whether PTH, the most crucial hormone that regulates mineral homeostasis, participates in the process of genistein-mediated bone protection. In the present study, we compared the therapeutic effects between genistein and nilestriol and investigated whether PTH and its specific receptor PTHR1 altered in response to genistein-containing diet in the animal model of ovariectomy. Our results showed that genistein administration significantly improved femoral mechanical properties and alleviates femoral turnover. Genistein at all doses (4.5 mg/kg, 9.0 mg/kg and 18.0 mg/kg per day, respectively exerted improved bending strength and b-ALP limiting effects than nilestriol in the present study. However, genistein administration did not exert superior effects on bone protection than nilestriol. We also observed circulating PTH restoration in ovariectomized rats receiving genistein at the dose of 18 mg/kg per day. Meanwhile, PTHR1 abnormalities were attenuated in the presence of genistein as confirmed by RT-PCR, Western blot and immunohistochemistry. These findings strongly support the idea that besides serving as an estrogen, genistein could interact with PTH/PTHR1, causing a superior mineral restoring effect than nilestriol on certain circumstance. In conclusion, our study reported for the first time that the anti-osteoporotic effect of genistein is partly PTH/PTHR1-dependent. Genistein might be a potential option in the prevention and treatment of post-menopausal osteoporosis with good tolerance, more clinical benefits

  7. Bone healing induced by local delivery of an engineered parathyroid hormone prodrug.

    Science.gov (United States)

    Arrighi, Isabelle; Mark, Silke; Alvisi, Monica; von Rechenberg, Brigitte; Hubbell, Jeffrey A; Schense, Jason C

    2009-03-01

    Regenerative medicine requires innovative therapeutic designs to accommodate high morphogen concentrations in local depots, provide their sustained presence, and enhance cellular invasion and directed differentiation. Here we present an example for inducing local bone regeneration with a matrix-bound engineered active fragment of human parathyroid hormone (PTH(1-34)), linked to a transglutaminase substrate for binding to fibrin as a delivery and cell-invasion matrix with an intervening plasmin-sensitive link (TGplPTH(1-34)). The precursor form displays very little activity and signaling to osteoblasts, whereas the plasmin cleavage product, as it would be induced under the enzymatic influence of cells remodeling the matrix, was highly active. In vivo animal bone-defect experiments showed dose-dependent bone formation using the PTH-fibrin matrix, with evidence of both osteoconductive and osteoinductive bone-healing mechanisms. Results showed that this PTH-derivatized matrix may have potential utility in humans as a replacement for bone grafts or to repair bone defects.

  8. Evaluation of Conventional Imaging Techniques on Preoperative Localization in Primary Hyperparathyroidism

    Directory of Open Access Journals (Sweden)

    Mesut Ozkaya

    2015-02-01

    Full Text Available We aimed to evaluate the diagnostic and preoperative localization capacity of 99mTc methoxyisobutylnitrile (MIBI parathyroid scintigraphy and ultrasonography (USG in enlarged parathyroid glands in the primary hyperparathyroidism (pHPT as well as the relationship between the success rate of these techniques and biochemical values. In this study, we retrospectively evaluated 39 patients with clinical and biological evidence of pHPT who referred to the university hospital for MIBI parathyroid scintigraphy. Patients were examined with USG and double-phase MIBI parathyroid scintigraphy for the detection of enlarged parathyroid glands. Preoperative serum intact parathyroid hormone (iPTH levels, calcium (Ca, phosphate and alkaline phosphatase measurements were obtained. A total of 45 parathyroid lesions in 39 patients were reviewed. Thirty-four patients had a single adenoma and 5 patients with multi-gland disease had 11 abnormal parathyroid glands including three adenomas, whereas the remaining 8 glands showed hyperplasia. The overall sensitivities of MIBI parathyroid scintigraphy, USG and combined techniques were 85.3%, 72.5% and 90.4%, respectively; the positive predictive values (PPV were 89.7%, 85.2% and 92.6%, respectively. The most successful approach for detection of enlarged parathyroid glands in hyperparathyroidism is the concurrent application of USG and MIBI parathyroid scintigraphy modalities. The concomitancy of thyroid diseases decreases the sensitivity of both MIBI parathyroid scintigraphy and USG in enlarged parathyroid glands.

  9. Successful ageing

    DEFF Research Database (Denmark)

    Bülow, Morten Hillgaard; Söderqvist, Thomas

    2014-01-01

    Since the late 1980s, the concept of ‘ successful ageing’ has set the frame for discourse about contemporary ageing research. Through an analysis of the reception to John W. Rowe and Robert L. Kahn's launch of the concept of ‘ successful ageing’ in 1987, this article maps out the important themes...... and discussions that have emerged from the interdisciplinary field of ageing research. These include an emphasis on interdisciplinarity; the interaction between biology, psycho-social contexts and lifestyle choices; the experiences of elderly people; life-course perspectives; optimisation and prevention...... strategies; and the importance of individual, societal and scientific conceptualisations and understandings of ageing. By presenting an account of the recent historical uses, interpretations and critiques of the concept, the article unfolds the practical and normative complexities of ‘ successful ageing’....

  10. Successful ageing

    DEFF Research Database (Denmark)

    Bülow, Morten Hillgaard; Söderqvist, Thomas

    2014-01-01

    Since the late 1980s, the concept of ‘ successful ageing’ has set the frame for discourse about contemporary ageing research. Through an analysis of the reception to John W. Rowe and Robert L. Kahn's launch of the concept of ‘ successful ageing’ in 1987, this article maps out the important themes...... and discussions that have emerged from the interdisciplinary field of ageing research. These include an emphasis on interdisciplinarity; the interaction between biology, psycho-social contexts and lifestyle choices; the experiences of elderly people; life-course perspectives; optimisation and prevention...... strategies; and the importance of individual, societal and scientific conceptualisations and understandings of ageing. By presenting an account of the recent historical uses, interpretations and critiques of the concept, the article unfolds the practical and normative complexities of ‘ successful ageing’....

  11. Citation Success

    DEFF Research Database (Denmark)

    Vaio, Gianfranco Di; Waldenström, Daniel; Weisdorf, Jacob Louis

    2012-01-01

    This study examines the determinants of citation success among authors who have recently published their work in economic history journals. Besides offering clues about how to improve one's scientific impact, our citation analysis also sheds light on the state of the field of economic history....... Consistent with our expectations, we find that full professors, authors appointed at economics and history departments, and authors working in Anglo-Saxon and German countries are more likely to receive citations than other scholars. Long and co-authored articles are also a factor for citation success. We...... find similar patterns when assessing the same authors' citation success in economics journals. As a novel feature, we demonstrate that the diffusion of research — publication of working papers, as well as conference and workshop presentations — has a first-order positive impact on the citation rate....

  12. Dark Skies: Local Success, Global Challenge

    Science.gov (United States)

    Lockwood, G. W.

    2009-01-01

    The Flagstaff, Arizona 1987 lighting code reduced the growth rate of man-made sky glow by a third. Components of the code include requirements for full cutoff lighting, lumens per acre limits in radial zones around observatories, and use of low-pressure sodium monochromatic lighting for roadways and parking lots. Broad public acceptance of Flagstaff's lighting code demonstrates that dark sky preservation has significant appeal and few visibility or public safety negatives. An inventory by C. Luginbuhl et al. of the light output and shielding of a sampling of various zoning categories (municipal, commercial, apartments, single-family residences, roadways, sports facilities, industrial, etc.), extrapolated over the entire city, yields a total output of 139 million lumens. Commercial and industrial sources account for 62% of the total. Outdoor sports lighting increases the total by 24% on summer evenings. Flagstaff's per capita lumen output is 2.5 times greater than the nominal 1,000 lumens per capita assumed by R. Garstang in his early sky glow modeling work. We resolved the discrepancy with respect to Flagstaff's measured sky glow using an improved model that includes substantial near ground attenuation by foliage and structures. A 2008 university study shows that astronomy contributes $250M annually to Arizona's economy. Another study showed that the application of lighting codes throughout Arizona could reduce energy consumption significantly. An ongoing effort led by observatory directors statewide will encourage lighting controls in currently unregulated metropolitan areas whose growing sky glow threatens observatory facilities more than 100 miles away. The national press (New York Times, the New Yorker, the Economist, USA Today, etc.) have publicized dark sky issues but frequent repetition of the essential message and vigorous action will be required to steer society toward darker skies and less egregious waste.

  13. Citation Success

    DEFF Research Database (Denmark)

    Di Vaio, Gianfranco; Waldenström, Daniel; Weisdorf, Jacob Louis

    affects citations. In regard to author-specific characteristics, male authors, full professors and authors working economics or history departments, and authors employed in Anglo-Saxon countries, are more likely to get cited than others. As a ‘shortcut' to citation success, we find that research diffusion......This study analyses determinants of citation success among authors publishing in economic history journals. Bibliometric features, like article length and number of authors, are positively correlated with the citation rate up to a certain point. Remarkably, publishing in top-ranked journals hardly...

  14. Vitamin D Metabolites and Their Association with Calcium, Phosphorus, and PTH Concentrations, Severity of Illness, and Mortality in Hospitalized Equine Neonates.

    Directory of Open Access Journals (Sweden)

    Ahmed M Kamr

    Full Text Available Hypocalcemia is a frequent abnormality that has been associated with disease severity and outcome in hospitalized foals. However, the pathogenesis of equine neonatal hypocalcemia is poorly understood. Hypovitaminosis D in critically ill people has been linked to hypocalcemia and mortality; however, information on vitamin D metabolites and their association with clinical findings and outcome in critically ill foals is lacking. The goal of this study was to determine the prevalence of vitamin D deficiency (hypovitaminosis D and its association with serum calcium, phosphorus, and parathyroid hormone (PTH concentrations, disease severity, and mortality in hospitalized newborn foals.One hundred newborn foals ≤72 hours old divided into hospitalized (n = 83; 59 septic, 24 sick non-septic [SNS] and healthy (n = 17 groups were included. Blood samples were collected on admission to measure serum 25-hydroxyvitamin D3 [25(OHD3], 1,25-dihydroxyvitamin D3 [1,25(OH 2D3], and PTH concentrations. Data were analyzed by nonparametric methods and univariate logistic regression. The prevalence of hypovitaminosis D [defined as 25(OHD3 <9.51 ng/mL] was 63% for hospitalized, 64% for septic, and 63% for SNS foals. Serum 25(OHD3 and 1,25(OH 2D3 concentrations were significantly lower in septic and SNS compared to healthy foals (P<0.0001; P = 0.037. Septic foals had significantly lower calcium and higher phosphorus and PTH concentrations than healthy and SNS foals (P<0.05. In hospitalized and septic foals, low 1,25(OH2D3 concentrations were associated with increased PTH but not with calcium or phosphorus concentrations. Septic foals with 25(OHD3 <9.51 ng/mL and 1,25(OH 2D3 <7.09 pmol/L were more likely to die (OR=3.62; 95% CI = 1.1-12.40; OR = 5.41; 95% CI = 1.19-24.52, respectively.Low 25(OHD3 and 1,25(OH2D3 concentrations are associated with disease severity and mortality in hospitalized foals. Vitamin D deficiency may contribute to a pro-inflammatory state in equine

  15. Citation Success

    DEFF Research Database (Denmark)

    Di Vaio, Gianfranco; Waldenström, Daniel; Weisdorf, Jacob Louis

    This study analyses determinants of citation success among authors publishing in economic history journals. Bibliometric features, like article length and number of authors, are positively correlated with the citation rate up to a certain point. Remarkably, publishing in top-ranked journals hardl...

  16. Citation Success

    DEFF Research Database (Denmark)

    Vaio, Gianfranco Di; Waldenström, Daniel; Weisdorf, Jacob Louis

    2012-01-01

    This study examines the determinants of citation success among authors who have recently published their work in economic history journals. Besides offering clues about how to improve one's scientific impact, our citation analysis also sheds light on the state of the field of economic history. Co...

  17. Successful ageing

    DEFF Research Database (Denmark)

    Kusumastuti, Sasmita; Derks, Marloes G. M.; Tellier, Siri;

    2016-01-01

    . METHODS: We performed a novel, hypothesis-free and quantitative analysis of citation networks exploring the literature on successful ageing that exists in the Web of Science Core Collection Database using the CitNetExplorer software. Outcomes were visualized using timeline-based citation patterns...

  18. Effects of add on PTH(1-84) substitution therapy in hypoparathyroidism: results from a double-blind randomised controlled study

    DEFF Research Database (Denmark)

    Sikjær, Tanja Tvistholm; Rejnmark, Lars; Mosekilde, Leif

    -phosphate levels within the physiological range. Compared with placebo, participants randomised to PTH (1-84) reduced their daily dose of calcium supplements by 68 % (pvitamin D dose by 53% (p...Conventional treatment of hypoparathyroidism (hypoPT) with calcium supplements and active vitamin D analoges causes a high renal calcium excretion and over-mineralized bone. We studied 62 patients with known hypoPT randomised to 6 months of treatment with either PTH(1-84) 100 µg/d s.c. or similar...... and 7 were not in need of active vitamin D. With the actual add on therapy there were no change in renal calcium excretion in response to treatment. Compared with placebo, bone mineral density (BMD) decreased significantly at the hip (-1.59 ± 0.57%), lumbar spine (-1.76 ± 1.03%) and whole body (-1...

  19. "Success"ful Reading Instruction.

    Science.gov (United States)

    George, Carol J.

    1986-01-01

    The Success in Reading and Writing Program at a K-2 school in Fort Jackson, South Carolina, teaches children of varied races and abilities to read and write using newspapers, dictionaries, library books, magazines, and telephone directories. These materials help students develop language skills in a failure-free atmosphere. Includes two…

  20. A Novel Cyclic PTH(1-17) analog with bone anabolic activity and efficacy sufficient to treat established osteopenia in adult ovariectomized rats

    DEFF Research Database (Denmark)

    Morko, Jukka; Peng, ZhiQi; Vääräniemi, Jukka;

    osteopenia was confirmed by peripheral quantitative computed tomography (pQCT). Treatment was started at 7 weeks after the operations and continued for 6 weeks. The osteopenic rats were treated subcutaneously, once a day with ZP2307 at doses of 2.0, 6.0, 20.0, 60.0 and 200.0 µg/kg/d, and with PTH(1-34) used...

  1. The repeat domain of the type III effector protein PthA shows a TPR-like structure and undergoes conformational changes upon DNA interaction.

    Science.gov (United States)

    Murakami, Mário Tyago; Sforça, Mauricio Luis; Neves, Jorge Luiz; Paiva, Joice Helena; Domingues, Mariane Noronha; Pereira, André Luiz Araujo; Zeri, Ana Carolina de Mattos; Benedetti, Celso Eduardo

    2010-12-01

    Many plant pathogenic bacteria rely on effector proteins to suppress defense and manipulate host cell mechanisms to cause disease. The effector protein PthA modulates the host transcriptome to promote citrus canker. PthA possesses unusual protein architecture with an internal region encompassing variable numbers of near-identical tandem repeats of 34 amino acids termed the repeat domain. This domain mediates protein-protein and protein-DNA interactions, and two polymorphic residues in each repeat unit determine DNA specificity. To gain insights into how the repeat domain promotes protein-protein and protein-DNA contacts, we have solved the structure of a peptide corresponding to 1.5 units of the PthA repeat domain by nuclear magnetic resonance (NMR) and carried out small-angle X-ray scattering (SAXS) and spectroscopic studies on the entire 15.5-repeat domain of PthA2 (RD2). Consistent with secondary structure predictions and circular dichroism data, the NMR structure of the 1.5-repeat peptide reveals three α-helices connected by two turns that fold into a tetratricopeptide repeat (TPR)-like domain. The NMR structure corroborates the theoretical TPR superhelix predicted for RD2, which is also in agreement with the elongated shape of RD2 determined by SAXS. Furthermore, RD2 undergoes conformational changes in a pH-dependent manner and upon DNA interaction, and shows sequence similarities to pentatricopeptide repeat (PPR), a nucleic acid-binding motif structurally related to TPR. The results point to a model in which the RD2 structure changes its compactness as it embraces the DNA with the polymorphic diresidues facing the interior of the superhelix oriented toward the nucleotide bases.

  2. Vitamin D status and PTH in young men: a cross-sectional study on associations with bone mineral density, body composition and glucose metabolism

    DEFF Research Database (Denmark)

    Frost, M; Abrahamsen, B; Nielsen, T L

    2010-01-01

    Although vitamin D and bone metabolism are closely related, few studies have addressed the effects of vitamin D status on bone in men at time of peak bone mass. The objectives of this study were to evaluate the prevalence of vitamin D inadequacy in a cross-sectional study in young men...... and the effects of vitamin D and parathyroid hormone (PTH) on bone mass, bone markers and metabolic function....

  3. Vitamin D binding protein genotype is associated with serum 25-hydroxyvitamin D and PTH concentrations, as well as bone health in children and adolescents in Finland.

    Science.gov (United States)

    Pekkinen, Minna; Saarnio, Elisa; Viljakainen, Heli T; Kokkonen, Elina; Jakobsen, Jette; Cashman, Kevin; Mäkitie, Outi; Lamberg-Allardt, Christel

    2014-01-01

    Vitamin D binding protein (DBP)/group-specific component (Gc), correlates positively with serum vitamin D metabolites, and phenotype influences serum 25-hydroxyvitamin D (S-25(OH)D) concentration. The protein isoform has been associated with decreased bone mineral density (BMD) and increased fracture risk. We examined the role of GC genotypes in S-25(OH)D status and BMD in 231 Finnish children and adolescents aged 7-19 yr. BMD was measured with DXA from lumbar spine (LS), total hip, and whole body, and for 175 subjects, radial volumetric BMD was measured with pQCT. Background characteristic and total dietary intakes of vitamin D and calcium were collected. The concentrations of 25(OH)D, parathyroid hormone (PTH), calcium and other markers of calcium homeostasis were determined from blood and urine. Genotyping was based on single-nucleotide polymorphism (rs4588) in the GC gene. The genotype distribution was: GC 1/1 68%, GC 1/2 26% and GC 2/2 6%. A significant difference emerged in 25(OH)D and PTH concentrations between the genotypes, (p = 0.001 and 0.028 respectively, ANCOVA). There was also a linear trend in: Gc 2/2 had the lowest 25(OH)D and PTH concentrations (p = 0.025 and 0.012, respectively). Total hip bone mineral content was associated with GC genotype (BMC) (p = 0.05, ANCOVA) in boys. In regression analysis, after adjusting for relevant covariates, GC genotype was associated with LS BMC and strength and strain index (SSI) Z-score in both genders, and LS BMD in boys. In conclusion, the present study demonstrates the association between GC genotypes and S-25(OH)D and PTH concentrations. The results show the influence of DBP genetic variation on bone mass accrual in adolescence.

  4. Vitamin D binding protein genotype is associated with serum 25-hydroxyvitamin D and PTH concentrations, as well as bone health in children and adolescents in Finland.

    Directory of Open Access Journals (Sweden)

    Minna Pekkinen

    Full Text Available Vitamin D binding protein (DBP/group-specific component (Gc, correlates positively with serum vitamin D metabolites, and phenotype influences serum 25-hydroxyvitamin D (S-25(OHD concentration. The protein isoform has been associated with decreased bone mineral density (BMD and increased fracture risk. We examined the role of GC genotypes in S-25(OHD status and BMD in 231 Finnish children and adolescents aged 7-19 yr. BMD was measured with DXA from lumbar spine (LS, total hip, and whole body, and for 175 subjects, radial volumetric BMD was measured with pQCT. Background characteristic and total dietary intakes of vitamin D and calcium were collected. The concentrations of 25(OHD, parathyroid hormone (PTH, calcium and other markers of calcium homeostasis were determined from blood and urine. Genotyping was based on single-nucleotide polymorphism (rs4588 in the GC gene. The genotype distribution was: GC 1/1 68%, GC 1/2 26% and GC 2/2 6%. A significant difference emerged in 25(OHD and PTH concentrations between the genotypes, (p = 0.001 and 0.028 respectively, ANCOVA. There was also a linear trend in: Gc 2/2 had the lowest 25(OHD and PTH concentrations (p = 0.025 and 0.012, respectively. Total hip bone mineral content was associated with GC genotype (BMC (p = 0.05, ANCOVA in boys. In regression analysis, after adjusting for relevant covariates, GC genotype was associated with LS BMC and strength and strain index (SSI Z-score in both genders, and LS BMD in boys. In conclusion, the present study demonstrates the association between GC genotypes and S-25(OHD and PTH concentrations. The results show the influence of DBP genetic variation on bone mass accrual in adolescence.

  5. Fast algorithm for computing a primitive /2 to power p + 1/p-th root of unity in GF/q squared/

    Science.gov (United States)

    Reed, I. S.; Truong, T. K.; Miller, R. L.

    1978-01-01

    A quick method is described for finding the primitive (2 to power p + 1)p-th root of unity in the Galois field GF(q squared), where q = (2 to power p) - 1 and is known as a Mersenne prime. Determination of this root is necessary to implement complex integer transforms of length (2 to power k) times p over the Galois field, with k varying between 3 and p + 1.

  6. Effect on thyroid function and serum PTH, BGP, CT of small dose of iodine 131 combined with Methimazole in patients with hyperthyroidism

    Institute of Scientific and Technical Information of China (English)

    Jia-Yin Qiu; Yan Zhu; Qing-Hong Xi

    2016-01-01

    Objective:To observe the effect Effect on thyroid function and serum PTH, BGP, CT of small dose of iodine 131 combined with Methimazole in patients with hyperthyroidism. Methods:A total of 104 patients with hyperthyroidism willing be incorporated into the study were randomly divided into the observation group (54 cases) and the control group (50 cases). The control group was treated with Methimazole, and the observation group was given a small dose of iodine 131 the basised on the control group. For 2 months, to observe the changes of thyroid function (TT3, TT4, FT3, FT4 and TSH) and bone metabolism related indexes (PTH, BGP and CT) of the two groups. Results:(1) After treatment, TT3, FT3, TT4 and FT4 of the two groups decreased with before, and the observation group improved more significantly than the control group, with statistical difference;TSH of the two groups had no significant change. (2) After treatment, BGP and CT of the two groups decreased and PTH increased, the observation group improved more significantly than the control group, with statistical difference. Conclusion:small dose of iodine 131 combined with Methimazole can correct thyroid function and bone metabolism quickly in patients with hyperthyroidism.

  7. Substernal oxyphil parathyroid adenoma producing PTHrP with hypercalcemia and normal PTH level

    Directory of Open Access Journals (Sweden)

    Rubini Domenico

    2008-02-01

    Full Text Available Abstract Background Parathyroid adenoma is the most common cause of primary hyperparathyroidism. Preoperative serum calcium and intact-parathyroid hormone levels are the most useful diagnostic parameters that allow differentiating primary hyperparathyroidism from non-parathyroid-dependent hypercalcemia. Parathyroidectomy is the definitive treatment for primary hyperparathyroidism. Approximately 5% of patients who underwent parathyroidectomy present with persistent or recurrent hyperparathyroidism due to ectopic localization of the adenoma. Functioning oxyphil parathyroid adenoma is an uncommon histological form, seldom causing primary hyperparathyroidism. Parathyroid adenoma with hypercalcemia exhibiting normal parathyroid hormone level is rare. An incidence of 5% to 33% has been documented in the literature; no etiologic explanation has been given. In 1987, parathyroid-hormone-related peptide was isolated as a causative factor of humeral hypercalcemia of malignancy. The presence of parathyroid-hormone-related peptide in parathyroid tissue under normal and pathological conditions has been described in the literature; however, its role in causing hyperparathyroidism has not yet been defined. Case presentation We present a case of persistent hypercalcemia with a normal level of intact-parathyroid hormone due to a substernal parathyroid adenoma, treated with radioguided parathyroidectomy. The final histological diagnosis was oxyphil adenoma, positive for parathyroid-hormone-related peptide antigens. Conclusion In clinical practice, this atypical biochemical presentation of primary hyperparathyroidism should be considered in the differential diagnosis of hypercalcemia. The parathyroid-hormone-related peptide should be considered not only in the presence of malignancy.

  8. Serum PTH reference values established by an automated third-generation assay in vitamin D-replete subjects with normal renal function: consequences of diagnosing primary hyperparathyroidism and the classification of dialysis patients.

    Science.gov (United States)

    Souberbielle, Jean-Claude; Massart, Catherine; Brailly-Tabard, Sylvie; Cormier, Catherine; Cavalier, Etienne; Delanaye, Pierre; Chanson, Philippe

    2016-03-01

    To determine parathyroid hormone (PTH) reference values in French healthy adults, taking into account serum 25-hydroxyvitamin D (25OHD), renal function, age, gender, and BMI. We studied 898 healthy subjects (432 women) aged 18-89 years with a normal BMI and estimated glomerular filtration rate (eGFR), 81 patients with surgically proven primary hyperparathyroidism (PHPT), and 264 dialysis patients. 25OHD and third-generation PTH assays were implemented on the LIAISON XL platform. Median PTH and 25OHD values in the 898 healthy subjects were 18.8  ng/l and 23.6  ng/ml respectively. PTH was lower in subjects with 25OHD ≥30  ng/ml than in those with lower values. Among the 183 subjects with 25OHD ≥30  ng/ml, those aged ≥60 years (n=31) had higher PTH values than younger subjects, independent of 25OHD, BMI, and eGFR (P<0.001). Given the small number of subjects aged ≥60 years, we adopted the 95% CI of PTH values for the entire group of 183 vitamin D-replete subjects (9.4-28.9  ng/l) as our reference values. With 28.9  ng/l as the upper limit of normal (ULN) rather than the manufacturer's ULN of 38.4  ng/l, the percentage of PHPT patients with 'high' PTH values rose to 90.1% from 66.6% (P<0.001), and 18.6% of the dialysis patients were classified differently in view of the KDIGO target range (two to nine times the ULN). When only subjects with 25OHD ≥30  ng/ml were included in the reference population, the PTH ULN fell by 22.4%, diagnostic sensitivity for PHPT improved, and the classification of dialysis patients was modified. © 2016 European Society of Endocrinology.

  9. Time course of 25(OHD3 vitamin D3 as well as PTH (parathyroid hormone during fracture healing of patients with normal and low bone mineral density (BMD

    Directory of Open Access Journals (Sweden)

    Wöfl Christoph

    2013-01-01

    Full Text Available Abstract Background Until now the exact biochemical processes during healing of metaphyseal fractures of healthy and osteoporotic bone remain unclear. Especially the physiological time courses of 25(OHD3 (Vitamin D as well as PTH (Parathyroid Hormone the most important modulators of calcium and bone homeostasis are not yet examined sufficiently. The purpose of this study was to focus on the time course of these parameters during fracture healing. Methods In the presented study, we analyse the time course of 25(OHD3 and PTH during fracture healing of low BMD level fractures versus normal BMD level fractures in a matched pair analysis. Between March 2007 and February 2009 30 patients older than 50 years of age who had suffered a metaphyseal fracture of the proximal humerus, the distal radius or the proximal femur were included in our study. Osteoporosis was verified by DEXA measuring. The time courses of 25(OHD3 and PTH were examined over an eight week period. Friedmann test, the Wilcoxon signed rank test and the Mann-Withney U test were used as post-hoc tests. A p-value ≤ 0.05 was considered significant. Results Serum levels of 25(OHD3 showed no differences in both groups. In the first phase of fracture healing PTH levels in the low BMD level group remained below those of the normal BMD group in absolute figures. Over all no significant differences between low BMD level bone and normal BMD level bone could be detected in our study. Conclusions The time course of 25(OHD3 and PTH during fracture healing of patients with normal and low bone mineral density were examined for the first time in humans in this setting and allowing molecular biological insights into fracture healing in metaphyseal bones on a molecural level. There were no significant differences between patients with normal and low BMD levels. Hence further studies will be necessary to obtain more detailed insight into fracture healing in order to provide reliable decision criteria for

  10. Local food and tourism

    DEFF Research Database (Denmark)

    Boesen, Morten; Sundbo, Donna; Sundbo, Jon

    2017-01-01

    This article investigates the question: Why local food networks succeed or fail in collaborating with local tourism actors to create more tourism based on local food? The article focuses on entrepreneurial local food networks and their collaboration with local tourism actors. Emphasis...... is on the actions and attitude logics of local food networks and tourism actors, and whether their respective logics fit as a factor to explain why or why not development of local food concepts lead to increased local tourism. Six local food networks and their collaboration with local tourism actors are studied...... by using observation supplemented with other qualitative methods. Analysis of these networks reveals that successful collaboration is characterised by the food networks and tourism actors having at least one logic in common. The fitting logics that lead to success are primarily celebrity and civic logics...

  11. Focused parathyroidectomy without intraoperative parathormone testing is safe after pre-operative localization with (18)F-Fluorocholine PET/CT.

    Science.gov (United States)

    Hocevar, M; Lezaic, L; Rep, S; Zaletel, K; Kocjan, T; Sever, M J; Zgajnar, J; Peric, B

    2017-01-01

    A focused surgical approach based on pre-operative localization replaced the classical four-gland exploration in patients with primary hyperparathyroidism (PHP). Sestamibi scanning and ultrasound are most often used localization modalities with reported sensitivity of 54-100% for identification of single gland disease. The aim of this study was to analyze the results of pre-operative localization with (18)F-Fluorocholine PET/CT (FCh-PET) in patients with PHP. A retrospective review of 151 patients with PHP who underwent surgery after pre-operative localization with FCh-PET was performed. Only a focused parathyroidectomy without ioPTH testing had been done in patients with single adenoma on FCh-PET. Primary outcome was operative failure, defined as persistent PHP. According to pre-operative FCh-PET 126 (83,4%) patients had single adenoma, 22 (14,5%) multiglandular disease and the test was negative in only two patients. Intraoperative failure experienced 4/126 patients (3,3%) with single adenoma. Removed parathyroid glands were normal in three and hyperplastic in one patient with intraoperative failure. A limited bilateral neck exploration with ioPTH testing was used in 14/22 patients with double adenoma and a classical four-gland exploration without ioPTH testing was used in 8/22 patients with more than two pathological glands according to pre-operative FCh-PET. Intraoperative failure experienced 2/22 patients (9,1%). In two patients with negative FCh-PET a classical four-gland exploration without ioPTH testing was used and one experienced intraoperative failure. A preoperative localization with FCh-PET is a reliable test in patients with PHP. Patients with a single adenoma on FCh-PET can safely undergo a focused parathyroidectomy without ioPTH testing.

  12. Successful Aging

    Directory of Open Access Journals (Sweden)

    Taufiqurrahman Nasihun

    2015-06-01

    Full Text Available The emerging concept of successful aging is based on evidence that in healthy individual when they get aged, there are  considerable variations in physiological functions alteration. Some people exhibiting greater, but others very few or no age related alteration. The first is called poor aging and the later is called successful pattern of aging (Lambert SW, 2008. Thus, in the simple words the successful aging concept is define as an opportunity of old people to stay  active and productive condition despite they get aged chronologically. Aging itself might be defined as the progressive accumulation of changes with time associated with or responsible for the ever-increasing susceptibility to disease and death which accompanies advancing age (Harman D, 1981. The time needed to accumulate changes is attributable to aging process. The marked emerging questions are how does aging happen and where does aging start? To answer these questions and because of the complexity of aging process, there are more than 300 aging theories have been proposed to explain how and where aging occured and started respectively. There are too many to enumerate theories and classification of aging process. In summary, all of these aging theories can be grouped into three clusters: 1. Genetics program theory, this theory suggests that aging is resulted from program directed by the genes; 2. Epigenetic theory, in these theory aging is resulted from environmental random events not determined by the genes; 3. Evolutionary theory, which propose that aging is a medium for disposal mortal soma in order to avoid competition between organism and their progeny for food and space, did not try to explain how aging occur, but possibly answer why aging occur (De la Fuente. 2009. Among the three groups of aging theories, the epigenetic theory is useful to explain and try to solve the enigma of aging which is prominently caused by internal and external environmental influences

  13. PTH levels and not serum phosphorus levels are a predictor of the progression of kidney disease in elderly patients with advanced chronic kidney disease.

    Science.gov (United States)

    Toapanta Gaibor, Néstor Gabriel; Nava Pérez, Nathasha Carolina; Martínez Echevers, Yeleine; Montes Delgado, Rafael; Guerrero Riscos, María Ángeles

    At present, there is a high incidence of elderly patients with advanced chronic kidney disease (CKD) and it is important to know the long term progression and the factors that influence it. To analyse the progression of advanced CKD in elderly patients and the influence of bone-mineral metabolism. Retrospective study of 125 patients ≥70years of age with CKD stages 4-5 who started follow-up from January 1, 2007 to December 31, 2008, showing the progression of CKD (measured by the slope of the regression line of the estimated glomerular filtration rate [eGFR] by MDRD-4) over 5years. Progression in the entire group (median and 25th and 75th percentiles): -1.15 (-2.8/0.17) ml/min/1.73m(2)/year, CKD-4: -1.3 (-2.8/0.03) ml/min/1.73m(2)/year, CKD-5: -1.03 (-3.0/0.8) ml/min/1.73m(2)/year; the slope of the regression line was positive in 35 patients (28%: CKD does not progress) and negative in 90 patients (72%: CKD progresses). Negative correlation (Spearman) (slower progression): PTH, albumin/Cr ratio and daily Na excretion (all baseline measurements). No correlation with eGFR, serum P, urinary P excretion, protein intake and intake of P (all baseline measurements). In the linear regression analysis (dependent variable: slope of progression): albuminuria and PTH (both at baseline measurements) influenced this variable independently. Logistic regression (progresses vs. does not progress): PTH, albuminuria and eGFR (all at baseline measurements) influenced significantly. In our group of elderly patients, impairment of renal function is slow, particularly in CKD-5 patients. Albuminuria and PTH at baseline levels are prognostic factors in the evolution of renal function. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  14. Influence of hemoperfusion combined with hemodialysis on inflammatory factors, serum hcy, PTH and β2-MG of patients with chronic renal failure

    Institute of Scientific and Technical Information of China (English)

    Yu Yin; Rui Li; Jian-Rong Hao

    2015-01-01

    Objective:To analyze the influence of hemoperfusion combined with hemodialysis on serum inflammatory factors, homocysteine (Hcy), parathyroid hormone (PTH) andβ2microglobulin (β2-MG) and other indexes in patients with chronic renal failure.Methods:94 cases with chronic renal failure from December 2013 to January 2015 in our hospital were randomly divided into two groups, according to the order of treatment. The control group of 47 patients with regular hemodialysis treatment, the observation group of 47 cases with blood perfusion combined with hemodialysis treatment. The serum interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factorβ (TNF-β), high sensitive C reactive protein (hs-CRP), phosphorus (P), Hcy, PTH, BUN,β2-MG and Scr indexes of two groups of patients before and after treatment were detected.Results:After treatment, serum IL-1, IL-6, TNF-β and hs-CRP levels of observation group were (1.72±0.16) ng/L, (12.38±1.67) ng/L, (1.26±0.31) mg/L, (6.78±1.42) ng/mL, were significantly decreased compared with the group before treatmentand control group after treatment (P<0.05). After treatment, serum PTH, Hcy and P levels of observation group were (24.53±4.82) μmol/L, (21.65±2.38) pmol/L, (1.50±0.29) mmol/L, were significantly decreased compared with the group before treatment and control group after treatment (P<0.05). After treatment,β2-MG, BUN, Scr levels of observation group were (1.92±0.26) mg/L,(6.76±1.23) mmol/L, (410.62±13.20) μmol/L, were significantly decreased compared with the group before treatment and control group after treatment. The skin itching relieving rate of observation group was 91.49% (43/47) was significantly higher than the control groups’ 59.57% (19/47), the differences were statistically significant.Conclusion:The curative effect of blood perfusion combined with hemodialysis in the treatment of chronic renal failure is significant, can effectively reduce the serum level of inflammatory factors, can clean out

  15. Functional roles of the nuclear localization signal of parathyroid hormone-related protein (PTHrP) in osteoblastic cells.

    Science.gov (United States)

    García-Martín, A; Ardura, J A; Maycas, M; Lozano, D; López-Herradón, A; Portal-Núñez, S; García-Ocaña, A; Esbrit, P

    2014-06-01

    PTHrP is an important regulator of bone remodelling, apparently by acting through several sequence domains. We here aimed to further delineate the functional roles of the nuclear localization signal (NLS) comprising the 88-107 amino acid sequence of PTHrP in osteoblasts. PTHrP mutants from a human PTHrP (-36/+139) cDNA (wild type) cloned into pcDNA3.1 plasmid with deletion (Δ) of the signal peptide (SP), NLS, T(107), or T107A replacing T(107) by A(107) were generated and stably transfected into osteoblastic MC3T3-E1 cells. In these cells, intracellular trafficking, cell proliferation and viability, as well as cell differentiation were evaluated. In these transfected cells, PTHrP was detected in the cytoplasm and also in the nucleus, except in the NLS mutant. Meanwhile, the PTH type 1 receptor (PTH1R) accumulates in the cytoplasm except for the ΔSP mutant in which the receptor remains at the cell membrane. PTHrP-wild type cells showed enhanced growth and viability, as well as an increased matrix mineralization, alkaline phosphatase activity, and osteocalcin gene expression; and these features were inhibited or abolished in ΔNLS or ΔT(107) mutants. Of note, these effects of PTHrP overexpression on cell growth and function were similarly decreased in the ΔSP mutant after PTH1R small interfering RNA transfection or by a PTH1R antagonist. The present in vitro findings suggest a mixed model for PTHrP actions on osteoblastic growth and function whereby this protein needs to be secreted and internalized via the PTH1R (autocrine/paracrine pathway) before NLS-dependent shuttling to the nucleus (intracrine pathway).

  16. Ensuring a successful family business management succession

    OpenAIRE

    Desbois, Joris

    2016-01-01

    Succession is the biggest long-term challenge that most family businesses face. Indeed, leaders ‘disposition to plan for their succession is frequently the key factor defining whether their family business subsists or stops. The research seeks to find out how to manage successfully the business management succession over main principles. This work project aims at researching the key points relevant to almost all family firms, to have a viable succession transition and positioni...

  17. Increase in cell-surface localization of parathyroid hormone receptor by cytoskeletal protein 4.1G.

    Science.gov (United States)

    Saito, Masaki; Sugai, Maki; Katsushima, Yuriko; Yanagisawa, Teruyuki; Sukegawa, Jun; Nakahata, Norimichi

    2005-11-15

    The cell-surface localization of GPCRs (G-protein-coupled receptors) has emerged as one of critical factors of the GPCR-mediated signal transduction. It has been reported that the C-termini of GPCRs contain the sequences for sorting the receptors to cell surface. In the present study, we have searched for proteins that interact with the C-terminus of PTH (parathyroid hormone)/PTH-related protein receptor (PTHR) by using the yeast two-hybrid system, and identified a cytoskeletal protein 4.1G (generaltype 4.1 protein) as an interactant with the C-terminus. Immunohistochemical study revealed that both PTHR and 4.1G were co-localized on plasma membranes, when they were transiently expressed in COS-7 cells. When 4.1G or the C-terminal domain of 4.1G (4.1G-CTD), a dominant-negative form of 4.1G, was co-expressed with PTHR in COS-7 cells, 4.1G, but not 4.1G-CTD, facilitated the cell-surface localization of PTHR, determined by cell-surface biotinylation assay. PTH-(1-34) caused phosphorylation of ERK (extracellular-signal-regulated kinase) 1/2 in PTHR-expressed cells mainly mediated through EGF (epidermal growth factor) receptor. The phosphorylation was enhanced by the expression of 4.1G, but not 4.1G-CTD. PTH-(1-34) elevated [Ca2+]i (intracellular Ca2+ concentration) independent of EGF receptor activation, and the elevation was enhanced by the expression of 4.1G, but not 4.1G-CTD. These data indicate that 4.1G facilitates the cell-surface localization of PTHR through its interaction with the C-terminus of the receptor, resulting in the potentiation of PTHR-mediated signal transduction.

  18. Role of p38MAPK in signal transduction of low density ESW and Iow dose intermittent rhPTH1 -34's action on bone formation of cultured rat osteoblasts%p38MAPK在低能ESW和间歇rhPTH1-34促进ROB成骨的信号转导中的作用

    Institute of Scientific and Technical Information of China (English)

    王李; 刘长剑; 罗宗键

    2011-01-01

    [ Objective] To investigate the role of p38MAPK in the signal path way of low density ESW and low dose intermittent rhPTH1 -34 stimulation's action on rat osteoblasts. [ Methods] After stimulations of 0. 18 rmJ/mm2 ESW and 10-11 mol/L intermittent rhPTHI - 34,the specific inhibitor of p38MAPK was added for finding the role of p38MAPK in the intracellular signal path way. The rat osteoblasts were collected, and cultured was detected, proliferation of these cells was observed by MTI and bone formation by measuring ALP activity. The expression of p - p38MAPK was detected by Western blot. [ Results] Enhaning effect on bone formation by ESW can be significantly inhibited by SB203580, a inhibitor of p38MAPK( P <0.05 ). But the enhancement of ROBs' bone formation by intermittent rhPTHI -34 can not be inhibited by SB203580. Suitable ESW stimulation can improve the expression of p38MAPK, but intermittent rhPTH1 - 34 stimulation can not. [ Conclusions] Suitable ESW stimulation can enhance bone formation of ROB by activation of p38MAPK. The enhancement of ROBs' bone formation by intermittent rhlPFH1 -34 stimulation dosen' t depend on activation of p38MAPK.%[目的]探讨低能体外冲击波(ESW)和间歇人重组甲状旁腺素(rhPTH1-34)刺激引起的体外培养大鼠成骨细胞(ROB)成骨的细胞内信号转导中p38MAPK的作用.[方法]分别用有效的低能ESW刺激和间歇rhPTH1-34作用于ROB,并设立加入p38MAPK抑制剂SB203580组,来观察ROB增殖、成骨指标及Western Blot检测的p38MAPK磷酸化激活变化.[结果]p38MAPK抑制剂SB203580能明显抑制120次0.18 mJ/mm2ESW刺激引起的ROB细胞增殖和成骨作用(P0.05).ESW应力刺激可促进P-p38MAPK表达,但间歇rhPTH1-34不能促进P-p38MAPK表达.[结论]适当的ESW应力刺激可通过激活p38MAPK促进体外培养ROB增殖和成骨;但p38MAPK并不参与10-11 mol/L间歇rhPTH1-34刺激引起的ROB细胞增殖和成骨的细胞信号转导.

  19. Simulation Study on PTH Mode of Diesel-Electric Hybrid Propulsion System%柴-电混合动力系统应急推进模式仿真研究

    Institute of Scientific and Technical Information of China (English)

    周庆波; 艾钢; 赵同宾; 金锋

    2011-01-01

    Power take me home (PTH) mode is motor single propulsion and it makes ship much safer. Simulation study on PTH mode of diesel-electric hybrid propulsion ship based on AMESim, control the clutch engage pressure achieve soft engagement and study on pitch of CPP load methods to make the ship start. The simulation results can be used as reference and direction of diesel-electric hybrid propulsion ship's PTH propulsion system design.%柴-电混合动力的应急推进( PTH)模式是将轴带电机作为电动机单独推进,增加了船舶的安全性.应用AMESim软件,对柴-电混合动力船舶的应急推进模式进行建模和仿真,研究通过,控制离合器接排压力实现柔性接排,以及调距桨螺距加载方法实现顺利起航,仿真结果可为柴-电混合动力船舶应急推进系统设计提供参考和指导.

  20. The association between body composition, 25(OH)D, and PTH and bone mineral density in black African and Asian Indian population groups.

    Science.gov (United States)

    George, Jaya A; Micklesfield, L K; Norris, S A; Crowther, N J

    2014-06-01

    There are few data on the contribution of body composition to bone mineral density (BMD) in non-Caucasian populations. We therefore studied the contribution of body composition, and possible confounding of 25-hydroxyvitamin D and PTH, to BMD at various skeletal sites in black African (BA) and Asian Indian (AI) subjects. This was a cross-sectional study in Johannesburg, South Africa. BMD, body fat, and lean mass were measured using dual x-ray absorptiometry and abdominal fat distribution by ultrasound in 714 healthy subjects, aged 18-65 years. Whole-body (subtotal), hip, femoral neck, and lumbar spine (lumbar) BMD were significantly higher in BA than AI subjects (P < .001 for all). Whole-body lean mass positively associated with BMD at all sites in both ethnic groups (P < .001 for all) and partially explained the higher BMD in BA females compared with AI females. Whole-body fat mass correlated positively with lumbar BMD in BA (P = .001) and inversely with subtotal BMD in AI subjects (P < .0001). Visceral adiposity correlated inversely with subtotal BMD in the BA (P = .037) and with lumbar BMD in the AI group (P = .005). No association was found between serum 25-hydroxyvitamin D and BMD. PTH was inversely associated with hip BMD in the BA group (P = .01) and with subtotal (P = .002), hip (P = .001), and femoral BMD (P < .0001) in the AI group. Significant differences in whole-body and site-specific BMD between the BA and AI groups were observed, with lean mass the major contributor to BMD at all sites in both groups. The contribution of other components of body composition differed by site and ethnic group.

  1. One Year of Abaloparatide, a Selective Activator of the PTH1 Receptor, Increased Bone Formation and Bone Mass in Osteopenic Ovariectomized Rats Without Increasing Bone Resorption.

    Science.gov (United States)

    Varela, Aurore; Chouinard, Luc; Lesage, Elisabeth; Smith, Susan Y; Hattersley, Gary

    2017-01-01

    Abaloparatide is a novel 34-amino acid peptide selected to be a potent and selective activator of the parathyroid hormone receptor (PTH1R) signaling pathway with 41% homology to PTH(1-34) and 76% homology to PTHrP(1-34). A 12-month treatment study was conducted in osteopenic ovariectomized (OVX) rats to characterize the mechanisms by which abaloparatide increases bone mass. Sprague-Dawley (SD) rats were subjected to OVX or sham surgery at age 6 months and left untreated for 3 months to allow OVX-induced bone loss. Ten OVX rats were euthanized after this bone depletion period, and the remaining OVX rats received daily subcutaneous injections of vehicle (n = 18) or abaloparatide at 1, 5, or 25 μg/kg/d (n = 18/dose level) for 12 months. Sham controls (n = 18) received vehicle daily. Bone densitometry and biochemical markers of bone formation and resorption were assessed longitudinally, and L3 vertebra and tibia were collected at necropsy for histomorphometry. Abaloparatide increased biochemical bone formation markers without increasing bone resorption markers or causing hypercalcemia. Abaloparatide increased histomorphometric indices of bone formation on trabecular, endocortical, and periosteal surfaces without increasing osteoclasts or eroded surfaces. Abaloparatide induced substantial increases in trabecular bone volume and density and improvements in trabecular microarchitecture. Abaloparatide stimulated periosteal expansion and endocortical bone apposition at the tibial diaphysis, leading to marked increases in cortical bone volume and density. Whole-body bone mineral density (BMD) remained stable in OVX-Vehicle controls while increasing 25% after 12 months of abaloparatide (25 μg/kg). Histomorphometry and biomarker data suggest that gains in cortical and trabecular bone mass were attributable to selective anabolic effects of abaloparatide, without evidence for stimulated bone resorption. © 2016 American Society for Bone and Mineral Research.

  2. Planning farm succession: how to be successful

    OpenAIRE

    Stephens, Mike

    2011-01-01

    Planning farm succession is really good farm planning in its broadest aspect. Unfortunately very few farmers and their families have devoted sufficient time to working out how the farm business will be transferred. After demonstrating the importance of the farm succession issue, this article goes on to explaining a method of successfully tackling the process.

  3. Mice lacking AMP-activated protein kinase α1 catalytic subunit have increased bone remodelling and modified skeletal responses to hormonal challenges induced by ovariectomy and intermittent PTH treatment

    Science.gov (United States)

    Jeyabalan, J; Shah, M; Viollet, B; Roux, J P; Chavassieux, P; Korbonits, M; Chenu, C

    2012-01-01

    AMP-activated protein kinase (AMPK) is a key regulator of cellular and body energy homeostasis. We previously demonstrated that AMPK activation in osteoblasts increases in vitro bone formation while deletion of the Ampkα1 (Prkaa1) subunit, the dominant catalytic subunit expressed in bone, leads to decreased bone mass in vivo. To investigate the cause of low bone mass in the Ampkα1−/− mice, we analysed bone formation and resorption in the tibia of these mice by dynamic histomorphometry and determined whether bone turnover can be stimulated in the absence of the Ampkα1 subunit. We subjected 12-week-old Ampkα1+/+ and Ampkα1−/− mice to ovariectomy (OVX), intermittent PTH (iPTH) administration (80 μg/kg per day, 5 days/week) or both OVX and iPTH hormonal challenges. Tibiae were harvested from these mice and bone micro-architecture was determined by micro-computed tomography. We show for the first time that Ampkα1−/− mice have a high bone turnover at the basal level in favour of bone resorption. While both Ampkα1+/+ and Ampkα1−/− mice lost bone mass after OVX, the bone loss in Ampkα1−/− mice was lower compared with controls. iPTH increased trabecular and cortical bone indexes in both ovariectomised Ampkα1+/+ and Ampkα1−/− mice. However, ovariectomised Ampkα1−/− mice showed a smaller increase in bone parameters in response to iPTH compared with Ampkα1+/+ mice. By contrast, non-ovariectomised Ampkα1−/− mice responded better to iPTH treatment than non-ovariectomised Ampkα1+/+ mice. Overall, these data demonstrate that Ampkα1−/− mice are less affected by changes in bone turnover induced by OVX but respond better to the anabolic challenge induced by iPTH. These results suggest that AMPKα1 activation may play a role in the hormonal regulation of bone remodelling. PMID:22700192

  4. Severe hypocalcemia secondary to hypomagnesaemia, successfully treated by self-administered subcutaneous magnesium Hipocalcemia severa, secundaria a hipomagnesemia, tratada con éxito mediante auto-administración subcutánea de magnesio

    OpenAIRE

    J. J. Alfaro Martínez; F. Botella Romero; C. Lamas Oliveira; A. Hernández López

    2009-01-01

    We report the case of a patient with recurrent severe hypocalcemia, secondary to hypomagnesaemia, and prerenal renal failure, due to ileostomy losses after a colectomy, who needed several admissions to the hospital through more than one year. Finally, he was successfully treated by self-administered subcutaneous magnesium: he reached and maintained normal levels of serum calcium, magnesium and PTH, no more hospital admission were needed and he resumed a normal life.Se trata de un paciente con...

  5. Severe hypocalcemia secondary to hypomagnesaemia, successfully treated by self-administered subcutaneous magnesium Hipocalcemia severa, secundaria a hipomagnesemia, tratada con éxito mediante auto-administración subcutánea de magnesio

    OpenAIRE

    2009-01-01

    We report the case of a patient with recurrent severe hypocalcemia, secondary to hypomagnesaemia, and prerenal renal failure, due to ileostomy losses after a colectomy, who needed several admissions to the hospital through more than one year. Finally, he was successfully treated by self-administered subcutaneous magnesium: he reached and maintained normal levels of serum calcium, magnesium and PTH, no more hospital admission were needed and he resumed a normal life.Se trata de un paciente con...

  6. Italian Succession Procedure

    OpenAIRE

    De Tullio, Giandomenico

    2012-01-01

    Italian inheritance law based on the Roman law of succession including legitimate succession and testamentary succession. The importance of drafting an Italian will and the legal requirements according to Italian Law.

  7. Cochlear implant patients underwent successful MRI examination after local bandaging:a case report%电子耳蜗植入术患者局部包扎后行MRI检查成功1例

    Institute of Scientific and Technical Information of China (English)

    保国华; 曹克利

    2012-01-01

    Summary A female patient, now 6 years old. received cochlear implant in the right ear at the age of 2(February .2006). In August 16. 2010. a cervical spine MR1 examination was required due to the cervical spine injury in order to confirm the diagnosis. Considering the cochlea coil may interfere with the MKI examination results, a local bandaging around the ear was given to isolate cochlear magnetic field. The results of cervical spine MR1 ex aminations showed no obvious disturbance, which suggests that we could further explore this method clinically.

  8. Successful xenotransplantation of microencapsulated newborn pig parathyroid cells in the treatment of hypoparathyroidism in rats

    Institute of Scientific and Technical Information of China (English)

    林乐岷; 宋一民; 宋纯; 许评; 宋春芳

    2003-01-01

    Objective To study the effect of xenotransplantation with pig parathyroid cells, which was prepared using cell microencapsulation technique, on the treatment of hypoparathyroidism in rats without immunosuppressor. Methods Parathyroid cells were isolated from 10 healthy newborn pigs and encapsulated in alginate-polylysine-alginate (APA) membranes. Thirty-two aparathyroid Wistar rats were randomly allocated to microcapsule, non-microcapsule, empty microcapsule, and control groups. Each rat was injected intraperitoneally with encapsulated porcine parathyroid cells, free porcine parathyroid cells, empty capsules or 0.9% NaCl, respectively. Total serum calcium and parathyroid hormone levels were monitored continuously for 40 weeks. And then, the transplant beds were retrieved and subjected to morphologic and electron microscopic examination. Results In those animals xenotransplanted with microencapsulated porcine parathyroid cells, the calcium and PTH levels were consistently within the normal range during the 40 weeks. In contrast, no therapeutic effects were observed in rats in the non-microcapsule group. Furthermore, neither empty capsules nor 0.9% NaCl were shown to have any effect on the recipient's serum calcium or PTH levels. After 40 weeks, electron microscopic examination demonstrated that the parathyroid cells within the microcapsules had survived well in vivo. Conclusions Xenotransplantation of microencapsulated newborn pig parathyroid cells can successfully treat hypoparathyroidism in rats without using immunosuppressive drugs. The results of this study show the possible clinical use of microencapsulated porcine parathyroid cells.

  9. The role of serum total and free 25-hydroxyvitamin D and PTH values in defining vitamin D status at the end of winter: a representative survey.

    Science.gov (United States)

    Szabó, Boglárka; Tabák, Ádám G; Toldy, Erzsébet; Szekeres, László; Szili, Balázs; Bakos, Bence; Balla, Bernadett; Kósa, János Pál; Lakatos, Péter; Takács, István

    2017-01-01

    We sought the lowest serum total 25-hydroxyvitamin D (t-25OHD) values in geographic areas with four seasons and investigated whether the calculation of serum free 25-hydroxyvitamin D (f-25OHD) could provide additional information on vitamin D status. This is a representative, cross-sectional study restricted to a sampling period at the end of winter, using a non-probability, stratified sample of the adult community-dwelling Hungarian population (n = 882). We measured t-25OHD, vitamin D binding protein (DBP), parathyroid hormone (PTH), and albumin levels. f-25OHD concentrations were calculated. We assessed environmental factors that could affect vitamin D levels and diseases possibly related to vitamin D deficiency. Mean t-25OHD values of the total population were 41.3 ± 20.6 nmol/L. t-25OHD levels were below 75, 50, and 30 nmol/L in 97, 77, and 34 % of participants not receiving vitamin D supplementation, respectively. t-25OHD values weakly positively correlated with DBP (r = 0.174; p = 0.000), strongly with f-25OHD (r = 0.70; p = 0.000). The association between t-25OHD and f-25OHD and between t-25OHD and PTH were non-linear (p squared term = 0.0004 and 0.004, respectively). t-25OHD levels were not affected by gender, age, place of residence; however, they were related to body mass index, sunbed sessions, and tropical travel. In contrast, f-25OHD levels were different in males and females but were not related to obesity. t- and f-25OHD were lower among people with cardiovascular diseases (p = 0.012). Nearly the entire Hungarian population is vitamin D insufficient at the end of winter. The use of t-25OHD could show a spurious association with obesity; however, it does not reflect the obvious sex difference.

  10. Moderate ingestion of alcohol is associated with acute ethanol-induced suppression of circulating CTX in a PTH-independent fashion.

    Science.gov (United States)

    Sripanyakorn, Supannee; Jugdaohsingh, Ravin; Mander, Adrian; Davidson, Sarah L; Thompson, Richard Ph; Powell, Jonathan J

    2009-08-01

    The "J shape" curve linking the risk of poor bone health to alcohol intake is now well recognized from epidemiological studies. Ethanol and nonethanol components of alcoholic beverages could influence bone remodeling. However, in the absence of a solid underlying mechanism, the positive association between moderate alcoholic intake and BMD remains questionable because of confounding associated social factors. The objective of this work was to characterize the short-term effects of moderate alcohol consumption on circulating bone markers, especially those involved in bone resorption. Two sequential blood-sampling studies were undertaken in fasted healthy volunteers (age, 20-47 yr) over a 6-h period using beer of different alcohol levels (2% ethanol; p 6 h). The early effect on bone resorption is well described after the intake of energy, mediated by glucagon-like peptide-2, but the late effect of moderate alcohol ingestion is novel, seems to be ethanol specific, and is mediated in a non-calcitonin- and a non-PTH-dependent fashion, thus providing a mechanism for the positive association between moderate alcohol ingestion and BMD.

  11. Twenty-year follow-up of a familial case of PTH1R-associated primary failure of tooth eruption.

    Science.gov (United States)

    Kanno, Cláudia Misue; de Oliveira, José Américo; Garcia, José Fernando; Roth, Helmut; Weber, Bernhard H F

    2017-03-01

    Nonsyndromic primary failure of eruption (PFE) is a rare autosomal dominant disorder of dental eruption with no obvious dental or soft tissue interference. The purposes of this study were to genetically and clinically characterize a family with many members affected by PFE and to describe the natural evolution of the disorder. Three generations of a family with 18 members, 10 of them clinically affected by PFE, were evaluated periodically during 20 years of clinical follow-up. PFE was observed in varying degrees of severity in both sexes. Clinical presentation became more severe in adulthood. One patient had spontaneous reeruption of 2 posterior teeth. Cervical root resorptions were observed in 3 members. Genetic analysis showed a deleterious heterozygous mutation in intron 9 of the PTH1R gene (c.639-2A>G) and diagnosed an additional affected member. The long-term follow-up of PFE cases in this family permitted the following observations: (1) the onset occurred from the preemergence to the postemergence phases, (2) PFE appeared to be closely related to ankylosis, (3) affected teeth maintained the eruptive potential even in adulthood, (4) the earlier the onset the more severe the open bite, and (5) cervical root resorptions occurred in 3 affected members. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  12. Comparison of calcium carbonate and aluminium hydroxide as phosphate binders on biochemical bone markers, PTH(1-84), and bone mineral content in dialysis patients

    DEFF Research Database (Denmark)

    Jespersen, B; Jensen, J D; Nielsen, H K;

    1991-01-01

    Bone mineral content, estimated by single-photon absorptiometry of the forearm, serum values of intact parathyroid hormone (PTH(1-84], osteocalcin, alkaline phosphatase, 1,25-dihydroxycholecalciferol (1,25(OH)2D3), and aluminium were determined during treatment with calcium carbonate (CaCO3...... 0.05), osteocalcin decreased (89% versus 117%, P less than 0.01), alkaline phosphatase decreased (92% versus 116%, P less than 0.05), and aluminium decreased (56% versus 189%, P less than 0.05). 1,25(OH)2D3 remained unchanged in both periods. No increase in soft-tissue calcification was demonstrated......) or aluminium hydroxide (Al(OH)3) in 11 dialysis patients participating in a randomised cross-over study. Each treatment period lasted 6 months. Serum phosphorus was maintained in the range 1.5-2.0 mmol/l. During Al(OH)3 treatment bone mineral content (BMC) decreased by 11% per half-year (mean), but only by 3...

  13. Systemic but no local effects of combined zoledronate and parathyroid hormone treatment in experimental autoimmune arthritis.

    Directory of Open Access Journals (Sweden)

    Kresten Krarup Keller

    Full Text Available INTRODUCTION: Local bone erosions and osteoporosis in rheumatoid arthritis (RA are the result of a more pronounced bone resorption than bone formation. Present treatment strategies for RA inhibit inflammation, but do not directly target bone erosions. The aim of the study was in experimental arthritis to investigate the juxtaarticular and systemic effects of simultaneous osteoclast inhibition with zoledronate (ZLN and osteoblast stimulation with parathyroid hormone (PTH. METHODS: Arthritis was induced in 36 SKG mice. The mice were randomized to three treatment groups and an untreated group: ZLN, PTH, PTH+ZLN, and untreated. Arthritis score and ankle width measurements were performed. Histological sections were cut from the right hind paw, and design-based stereological estimators were used to quantify histological variables of bone volume and bone formation and resorption. The femora were DXA- and μCT-scanned, and the bone strength was determined at the femoral neck and mid-diaphysis. RESULTS: Locally, we found no differences in arthritis score or ankle width throughout the study. Similarly, none of the treatments inhibited bone erosions or stimulated bone formation in the paw. Systemically, all treatments improved bone mineral density, strength of the femoral neck and mid-diaphysis, and μCT parameters of both cortical and trabecular bone. In addition, there was an additive effect of combination treatment compared with single treatments for most trabecular parameters including bone mineral density and bone volume fraction. CONCLUSIONS: No local effect on bone was found by the combined action of inhibiting bone resorption and stimulating bone formation. However, a clear systemic effect of the combination treatment was demonstrated.

  14. Inmunoterapia local Local immunotherapy

    Directory of Open Access Journals (Sweden)

    E. Lasa

    2003-01-01

    Full Text Available La inmunoterapia específica, junto con la evitación del alergeno y el tratamiento sintomático, forma parte del tratamiento de la patología alérgica. La modalidad más antigua, más conocida y mejor estudiada es la inmunoterapia subcutánea (ITSC, cuya eficacia tanto a corto como a largo plazo, ha sido ampliamente demostrada en numerosos estudios. Sin embargo, a pesar de haberse demostrado segura, no está exenta de efectos adversos y precisa ser administrada bajo supervisión de personal médico. Esto ha animado a buscar nuevas vías de administración de eficacia similar, con un buen perfil de seguridad, y de buena cumplimentación por parte del paciente. De las distintas alternativas estudiadas la más relevante es la inmunoterapia sublingual (ITSL. En ésta, se administra el antígeno en forma de gotas debajo de la lengua. Existen diferentes pautas de administración en función del alergeno implicado. La dosis óptima de tratamiento está aún sin determinar, hallándose en este momento en un rango amplio de dosis respecto a la inmunoterapia subcutánea. Su mecanismo de acción es poco conocido aunque en diversos estudios se han observado cambios inmunológicos. La ITSL ha mostrado un buen perfil de seguridad con escasos efectos secundarios, habitualmente de carácter local. Asimismo se han realizado distintos ensayos clínicos en los que se ha demostrado su eficacia en el tratamiento de la alergia respiratoria tanto en niños como en adultos. Por ello, aunque aún existen datos sin resolver respecto a esta vía de administración de inmunoterapia, ha sido propuesta por la OMS como una alternativa válida a la ITSC.Specific immunotherapy, together with avoidance of the allergen and symptomatic treatment, forms part of the treatment of allergic pathology. The oldest, best known and most studied form is subcutaneous immunotherapy (SCIT, whose efficacy, both in the short and the long term, has been widely demonstrated in numerous studies

  15. Documenting localities

    CERN Document Server

    Cox, Richard J

    1996-01-01

    Now in paperback! Documenting Localities is the first effort to summarize the past decade of renewed discussion about archival appraisal theory and methodology and to provide a practical guide for the documentation of localities.This book discusses the continuing importance of the locality in American historical research and archival practice, traditional methods archivists have used to document localities, and case studies in documenting localities. These chapters draw on a wide range of writings from archivists, historians, material culture specialists, historic preservationists

  16. Influence of recombinant plasmid pCKM-mPTH to the serum calcium concentration of the animal models of hypoparathyroidism%重组质粒pCKM-mPTH对甲状旁腺功能低下症动物模型血钙的影响

    Institute of Scientific and Technical Information of China (English)

    梁月强; 刘大钺; 曹劲; 朱易凡; 李江波; 林景能

    2011-01-01

    Objectivs To study the influence of recombinant plasmid pCKM-mPTH to the serum calcium concentration of the SD rats of hypoparathyroidism model. Methods 60 SD rats of hypoparathyroidism models were randomly divided into three groups, which were injected intramuscular pcDNA3.1 ( + ) empty vector, mPTH plasmids and pCKM-mPTH plasmid via muscle. At different times, rats were measured serum parathyroid hormone ( PTH ) concentration using radioimmunoassay, and serum calcium concentration using MTB colorimetric assay.Results After being injected with mPTH and pCKM-mPTH plasmid, serum PTH and calcium appeared significantly increased and fell later, but that of pCKM-mPTH plasmid groups fell more slowly, which continued nearly 30 days. Conclusion Recombinant plasmid pCKM-mPTH can effectively regulate the concentration of serum calcium after transfecting SD rats of hypoparathyroidism model. Furthermore, its transfection efficiency and the maintenance of time are superior to non-pCKM promoter mPTH plasmid.%目的 研究重组pCKM-mPTH质粒在SD大鼠甲状旁腺功能低下症模型治疗中对血钙浓度的影响.方法 将60只SD大鼠制作甲状旁腺功能低下症模型后,随机分为3组,分别肌注pcDNA3.1(+)空质粒、mPTH质粒和pCKM-mPTH质粒,不同时间用放免法测定血清甲状旁腺素(PTH)浓度,采用MTB比色法检测血清钙浓度.结果 动物模型在注射mPTH和pCKM-mPTH质粒后,其血清PTH和钙浓度均出现显著升高,之后出现回落,但pCKM-mPTH质粒组回落较缓慢,其作用维持近30天.结论 质粒pCKM-mPTH在SD大鼠体内合成的甲状旁腺素能有效的调节血清钙的浓度,且转染效率和维持时间优于不含pCKM启动子的mPTH质粒.

  17. Fertility Clinic Success Rates

    Science.gov (United States)

    ... and Autism 2013 Assisted Reproductive Technology Fertility Clinic Success Rates Report Recommend on Facebook Tweet Share Compartir 2013 ART Fertility Clinic Success Rates Report [PDF - 1MB] Bookmarks and thumbnails are ...

  18. USAR recruiting success factors

    OpenAIRE

    Thomas, George W.; Kocher, Kathryn M.; Gandolfo, Robin Ragsdale

    1987-01-01

    This study attempts to identify attributes associated with successful recruiters, to evaluate existing data on recruiter performance and characteristics, and to develop a model to aid in the selection of personnel who are likely to become successful recruiters. Conventional multivariate statistical techniques have not proved adequate in identifying successful recruiters, largely because of the absence of reliable and valid measures of recruiter success. This study applies a relatively new met...

  19. Success in Science, Success in Collaboration

    Energy Technology Data Exchange (ETDEWEB)

    Johnston, Mariann R. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-08-25

    This is a series of four different scientific problems which were resolved through collaborations. They are: "Better flow cytometry through novel focusing technology", "Take Off®: Helping the Agriculture Industry Improve the Viability of Sustainable, Large-Production Crops", "The National Institutes of Health's Models of Infectious Disease Agent Study (MIDAS)", and "Expanding the capabilities of SOLVE/RESOLVE through the PHENIX Consortium." For each one, the problem is listed, the solution, advantages, bottom line, then information about the collaboration including: developing the technology, initial success, and continued success.

  20. Local architecture

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Local architecture refers to structures built in the countryside,such as temples,memorial halls,residences, stores,pavilions, bridges,decorated archways, and wells. Because these structures were all built by focal craftsmen and villagers in the traditional local style, they are generally called local architecture.

  1. Predicting Classroom Success.

    Science.gov (United States)

    Kessler, Ronald P.

    A study was conducted at Rancho Santiago College (RSC) to identify personal and academic factors that are predictive of students' success in their courses. The study examined the following possible predictors of success: language and math test scores; background characteristics; length of time out of high school; high school background; college…

  2. Ingredients for successful partnerships

    NARCIS (Netherlands)

    S.M. Pfisterer (Stella)

    2011-01-01

    textabstractFor the development of new cross-sector partnerships it is required to know what the essence of successful partnership projects is. Which factors influence success or failure of partnerships is highly related to the specific context where partnerships operate. The literature on critical

  3. Successful grant writing

    NARCIS (Netherlands)

    Koppelman, Gerard H.; Holloway, John W.

    2012-01-01

    Obtaining research funding is central to the research process. However many (clinician-) scientists receive little, or no, training in the process of writing a successful grant application. In an era of reductions in research budgets and application success rates, the ability to construct a well pre

  4. Three Tiers to Success

    Science.gov (United States)

    Barton, Rhonda; Stepanek, Jennifer

    2009-01-01

    This article discusses a three-tiered, differentiated curriculum in a response to intervention (RTI) framework that has successfully raised achievement at all levels, but is particularly successful with ninth-grade students. Walla Walla (Washington) School District implemented the three-tiered intervention program as a series of differentiated…

  5. What is Success

    Institute of Scientific and Technical Information of China (English)

    Zhao; Lifang

    2015-01-01

    <正>Success is actually a feeling.Like confidence and satisfaction,it is a positive feeling which appears after individuals reach their own ideal dreams,fulfill their tasks.But everyone havetheir own opinions so that there are various thoughts on the theme what is success.

  6. Student Success Center Toolkit

    Science.gov (United States)

    Jobs For the Future, 2014

    2014-01-01

    "Student Success Center Toolkit" is a compilation of materials organized to assist Student Success Center directors as they staff, launch, operate, and sustain Centers. The toolkit features materials created and used by existing Centers, such as staffing and budgeting templates, launch materials, sample meeting agendas, and fundraising…

  7. Exploring MBA Career Success

    Science.gov (United States)

    Hay, Amanda; Hodgkinson, Myra

    2006-01-01

    Purpose: The purpose of this paper is to examine the meaning of career success in relation to the attainment of an MBA degree, for a group of experienced managers. In so doing, the paper aims to consider the adequacy of MBA career success, defined solely in terms of external criteria. Design/methodology/approach: A total of 36 in-depth interviews…

  8. Writing successful UX proposals

    CERN Document Server

    Hass, Chris

    2016-01-01

    Bringing new project funding and business opportunities to your organization is a vital part of UX professionals' growth and success. Writing Successful UX Proposals teaches the proven techniques for assessing proposal requests, writing successful commercial and government funding proposals, and enhancing your business development skills. This book will teach UX practitioners how to succeed in UX business development by mastering the following goals: * Understand how to assess a request for proposals* Understand the "anatomy" of a proposal response * Speak the business language of those who will be evaluating the proposed approach* Recognize the successes of others and build upon their advice Complete with case studies, tricks and tips, and real-world examples throughout, this is a must-have resource for UX professionals interested in honing their proposal writing skills and setting themselves up for success. * Provides unique sales and proposal writing insights tailored to the UX arena (including both resear...

  9. Successful systems sustaining change.

    Science.gov (United States)

    Bullas, Sheila; Bryant, John

    2007-01-01

    Much has been published on the success and particularly the failure of IT projects; still failures are commonplace. This prospective study focused from the outset on assessing risk of failure and addressing critical success factors. The aim was to apply existing methods in a challenging acute care hospital where success demanded rapid achievement of sustainable improvements in clinical and administrative processes. The implementations were part of the English National Programme for IT. The desired outcomes required the integration of accepted tools and techniques to provide a pragmatic approach to systems implementation: Lean, Six Sigma, PRINCE2 and Benefits Management. The outcome and further insights into success and failure of IT projects in healthcare are described. In particular lessons are identified related to the business need for the project and the successful achievement of the required benefits and business change.

  10. Local Helioseismology

    Directory of Open Access Journals (Sweden)

    Gizon Laurent

    2005-11-01

    Full Text Available We review the current status of local helioseismology, covering both theoretical and observational results. After a brief introduction to solar oscillations and wave propagation through inhomogeneous media, we describe the main techniques of local helioseismology: Fourier-Hankel decomposition, ring-diagram analysis, time-distance helioseismology, helioseismic holography, and direct modeling. We discuss local helioseismology of large-scale flows, the solar-cycle dependence of these flows, perturbations associated with regions of magnetic activity, and solar supergranulation.

  11. Towards successful SPP treatment of local materials for road building

    CSIR Research Space (South Africa)

    Paige-Green

    2009-06-17

    Full Text Available This report discusses the use of certain proprietary soil stabilisers in low volume roads in South Africa. Although ionic soil stabilisers have been in use for many years, they have not been marketed to their fullest potential and in many cases have...

  12. Bone mineralization is regulated by signaling cross talk between molecular factors of local and systemic origin: the role of fibroblast growth factor 23.

    Science.gov (United States)

    Sapir-Koren, Rony; Livshits, Gregory

    2014-01-01

    Body phosphate homeostasis is regulated by a hormonal counter-balanced intestine-bone-kidney axis. The major systemic hormones involved in this axis are parathyroid hormone (PTH), 1,25-dihydroxyvitamin-D, and fibroblast growth factor-23 (FGF23). FGF23, produced almost exclusively by the osteocytes, is a phosphaturic hormone that plays a major role in regulation of the bone remodeling process. Remodeling composite components, bone mineralization and resorption cycles create a continuous influx-efflux loop of the inorganic phosphate (Pi) through the skeleton. This "bone Pi loop," which is formed, is controlled by local and systemic factors according to phosphate homeostasis demands. Although FGF23 systemic actions in the kidney, and for the production of PTH and 1,25-dihydroxyvitamin-D are well established, its direct involvement in bone metabolism is currently poorly understood. This review presents the latest available evidence suggesting two aspects of FGF23 bone local activity: (a) Regulation of FGF23 production by both local and systemic factors. The suggested local factors include extracellular levels of Pi and pyrophosphate (PPi), (the Pi/PPi ratio), and another osteocyte-derived protein, sclerostin. In addition, 1,25-dihydroxyvitamin-D, synthesized locally by bone cells, may contribute to regulation of FGF23 production. The systemic control is achieved via PTH and 1,25-dihydroxyvitamin-D endocrine functions. (b) FGF23 acts as a local agent, directly affecting bone mineralization. We support the assumption that under balanced physiological conditions, sclerostin, by para- autocrine signaling, upregulates FGF23 production by the osteocyte. FGF23, in turn, acts as a mineralization inhibitor, by stimulating the generation of the major mineralization antagonist-PPi.

  13. PLANT SUCCESSION ON SICILIAN TERRACES

    Directory of Open Access Journals (Sweden)

    J. RUHL

    2007-01-01

    Full Text Available 189 phytosociological relevés have been made in five areas of Sicily, three on volcanic substrates and two on limestones, to study plant community succession trends within abandoned terraced vineyards and cereal fields. Disturbance status and abandonment age was recorded for each sample plot. DCA of these relevés suggests that four are the most important factors driving succession, i.e. geological substrate, bioclimate, age of abandonment and disturbance. In most cases - if there are some dispersal centres near the old fields - undisturbed and less disturbed terraces evolve quite rapidly towards the local potential “climax” community. Different trends have been recorded on the areas which underwent and still undergo frequent and severe disturbance: succession is biased or even blocked in a steady state, so that grassland, garrigue, mantle or herb-dominated communities prevail. The species composition of the plant communities subject to disturbance seems to be strongly connected with the time gap between abandonment and first disturbance occurrence. The “mixed” ecological-structural-phytosociological approach here adopted to describe plant communities was quite effective to interpret abandoned terraces communities and their dynamism.

  14. PLANT SUCCESSION ON SICILIAN TERRACES

    Directory of Open Access Journals (Sweden)

    J. RUHL

    2007-04-01

    Full Text Available 189 phytosociological relevés have been made in five areas of Sicily, three on volcanic substrates and two on limestones, to study plant community succession trends within abandoned terraced vineyards and cereal fields. Disturbance status and abandonment age was recorded for each sample plot. DCA of these relevés suggests that four are the most important factors driving succession, i.e. geological substrate, bioclimate, age of abandonment and disturbance. In most cases - if there are some dispersal centres near the old fields - undisturbed and less disturbed terraces evolve quite rapidly towards the local potential “climax” community. Different trends have been recorded on the areas which underwent and still undergo frequent and severe disturbance: succession is biased or even blocked in a steady state, so that grassland, garrigue, mantle or herb-dominated communities prevail. The species composition of the plant communities subject to disturbance seems to be strongly connected with the time gap between abandonment and first disturbance occurrence. The “mixed” ecological-structural-phytosociological approach here adopted to describe plant communities was quite effective to interpret abandoned terraces communities and their dynamism.

  15. Maximizing PTH Anabolic Osteoporosis Therapy

    Science.gov (United States)

    2014-09-01

    Mm00435452_m1 Osterix (Sp7 transcription factor) Mm00504574_m1 Pthr1 (parathyroid hormone receptor 1) Mm00441046_m1 Pthrp (parathyroid hormone...peptide ( Pthrp ) in either genotype (Table 7). Our preliminary evaluation of gene expression in the tibia showed that the RNA profiles at 3 weeks of...0.0036 0.4394 Pthr1 0.86 ± 0.23 1.59 ± 0.40 0.68 ± 0.28 1.38 ± 0.68 0.2223 \\0.0001 0.9071 Pthrp 0.75 ± 0.18 1.10 ± 0.44 0.89 ± 0.44 1.00 ± 0.44

  16. Parathyroid hormone (PTH) blood test

    Science.gov (United States)

    ... excess calcium supplements or certain antacids, that contain calcium carbonate or sodium bicarbonate (baking soda) Parathyroid glands do ... More 25-hydroxy vitamin D test Bone tumor Calcium ... level Malabsorption Milk-alkali syndrome Multiple endocrine neoplasia (MEN) I Multiple ...

  17. Maximizing PTH Anabolic Osteoporosis Therapy

    Science.gov (United States)

    2015-09-01

    Medical and Molecular Genetics, IUSM11 5. Center for Computational Biology and Bioinformatics, IUSM12 6. Department of Pediatrics, IUSM13 7. Herman B...67 Hesse , 2012; Yu et al., 2011]. This limits its effectiveness to treat a chronic degenerative disease. Recent 68 advances in bone-forming agents...Seq significance tool. Bioinformatics. 29(15):1922-4. 665 666 Baron R, Hesse E. 2012 Update on bone anabolics in osteoporosis treatment: rationale

  18. Successful grant writing.

    Science.gov (United States)

    Koppelman, Gerard H; Holloway, John W

    2012-03-01

    Obtaining research funding is central to the research process. However many (clinician-) scientists receive little, or no, training in the process of writing a successful grant application. In an era of reductions in research budgets and application success rates, the ability to construct a well presented, clear, articulate proposal is becoming more important than ever. Obtaining grants is a method to achieve your long term research goals. If you are able to formulate these long term goals, it is relevant to explore the market and investigate all potential grant opportunities. Finally, we will provide an outline of key elements of successful research grants.

  19. Software Maintenance Success Recipes

    CERN Document Server

    Reifer, Donald J

    2011-01-01

    Dispelling much of the folklore surrounding software maintenance, Software Maintenance Success Recipes identifies actionable formulas for success based on in-depth analysis of more than 200 real-world maintenance projects. It details the set of factors that are usually present when effective software maintenance teams do their work and instructs on the methods required to achieve success. Donald J. Reifer--an award winner for his contributions to the field of software engineering and whose experience includes managing the DoD Software Initiatives Office--provides step-by-step guidance on how t

  20. Local food:

    DEFF Research Database (Denmark)

    Sundbo, Donna Isabella Caroline

    2013-01-01

    Recently there has been more focus on food in general and local food in particular. But what is local food? And what are the perceptions of this concept according to theory and to providers and consumers of local food? This article first summarises and compares three different theoretical...... as expressed by a group of Danish providers and consumers is empirically investigated through interviews, observation and surveys. From this, qualitative and quantitative data are generated, the analysis of which shows how varied perceptions of local food are. The elements of which the perceptions consist...... are identified and then categorised according to whether they pertain to the food product itself or the production methods and facilities and whether they describe physical or social properties of local food. From this a model with four categories is developed. It is found that properties of the product are more...

  1. Geothermal district heating: basics to success

    Energy Technology Data Exchange (ETDEWEB)

    Lunis, B.C.

    1985-01-01

    A district heating system using geothermal energy is a viable and economic option in many locations. A successful system, however, is dependent upon a variety of factors, and it is the purpose of this presentation to accent those items that are proving to have significant impact upon the successful operation of geothermal district heating systems. (These lessons can also apply to other sources of energy.) The six major basics to success that are discussed in this paper are economic viability, an adequate geothermal resource, simplicity of design, a closed loop system, a local champion, and good public relations.

  2. 浙江省维持性透析患者钙磷甲状旁腺激素水平调查%Serum calcium, phosphate, and iPTH levels of dialysis patients in Zhejiang Province

    Institute of Scientific and Technical Information of China (English)

    徐春萍; 余碧影; 杨毅; 张萍; 陈江华

    2012-01-01

    Objective To analyze serum calcium, phosphate, and intact parathyroid hormone (iPTH) levels of dialysis patients in Zhejiang Province in 2011. Methods We collected these data from hemodialysis and peritoneal dialysis patients in Zhejiang Province in 2011. We then analyzed the compliance rate of serum calcium, phosphorus, iPTH according to the Kidney Disease: Improving Global Outcomes (KDIGO) guideline standards. Results The compliance rate of serum calcium, phosphorus and iPTH was 58.1%, 27.2% and 56.3%, respectively, in hemodialysis patients, and was 71.1%, 44.2% and 65.6%, respectively, in peritoneal dialysis patients. Conclusion Serum calcium, phosphorus and iPTH should be carefully monitored and controlled in dialysis patients, especially in hemodialysis patients.%目的 调查2011年浙江省维持性透析患者的血清钙、磷、甲状旁腺激素水平.方法 统计2011年浙江省血液透析和腹膜透析患者血清钙、磷、全段甲状旁腺激素的资料,根据肾脏病改善全球预后(Kidney Disease:Improving Global Outcomes,KDIGO)指南标准,分析患者的钙、磷、iPTH的达标率.结果 2011年浙江省维持性透析患者中,血液透析患者血清钙、磷、iPTH的达标率分别为58.1%、27.2%、56.3%,腹膜透析患者的达标率分别是71.1%、44.2%、65.6%.结论 有相当比例的透析患者未能较好的控制血清钙、磷和iPTH水平,尤其是血磷的达标率更低,在血液透析患者中更加明显.

  3. Definição de valores de corte para medida de PTH intraoperatório no tratamento cirúrgico do hiperparatiroidismo secundário e terciário

    Directory of Open Access Journals (Sweden)

    Monique Nakayama Ohe

    2013-08-01

    Full Text Available Avaliamos medida de PTH intraoperatório (IO-PTH no intuito de melhorar índices de sucesso no tratamento cirúrgico do hiperparatiroidismo associado à doença renal. MÉTODO: Oitenta e seis pacientes realizaram paratiroidectomia total com autoimplante em musculatura pré-esternal entre abril de 2000 e outubro de 2009 com 26,5 meses de seguimento em média, prospectivo. Foram divididos em dois grupos: hiperparatiroidismo secundário (HPS - pacientes em diálise e hiperparatiroidismo terciário (HPT - transplantados renais. Medido IO-PTH (Elecsys-PTH-Immunoassay/Roche na indução anestésica (IOPTH-0' e 20 minutos (IOPTH-20' após a retirada das paratireoides. RESULTADOS: 80,2% (69/86 do total de pacientes apresentaram queda de 80% ou mais do IOPTH-20' e todos se curaram. Em 11/86 (12,7% pacientes, foi observada queda entre 70-79%, sendo que dois (18,1% deles evoluíram com falha cirúrgica. 6/86 (6,9% pacientes apresentaram redução de IOPTH-20' menor do que 70%: dois foram curados; três apresentaram paratireoide supranumerária/ectópica que foi localizada e removida; um paciente evoluiu com persistência da doença após término da cirurgia com a retirada de quatro paratireoides. CONCLUSÃO: Queda do IOPTH-20' de 80% ou mais foi preditor de cura em todos os pacientes renais durante o período avaliado. Redução menor que 70% sugere paratireoide hiperfuncionante não reconhecida/supranumerária, sendo preditor de falha cirúrgica em 66.6%. A queda marginal de 70%-79% delega ao cirurgião experiente a decisão de continuar ou não o procedimento cirúrgico.

  4. Temporal changes in tissue 1α,25-dihydroxyvitamin D3, vitamin D receptor target genes, and calcium and PTH levels after 1,25(OH)2D3 treatment in mice.

    Science.gov (United States)

    Chow, Edwin C Y; Quach, Holly P; Vieth, Reinhold; Pang, K Sandy

    2013-05-01

    The vitamin D receptor (VDR) maintains a balance of plasma calcium and 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], its natural active ligand, by directly regulating the calcium ion channel (TRPV6) and degradation enzyme (CYP24A1), and indirectly regulating the parathyroid hormone (PTH) for feedback regulation of the synthetic enzyme CYP27B1. Studies that examined the intricate relationships between plasma and tissue 1,25(OH)2D3 levels and changes in VDR target genes and plasma calcium and PTH are virtually nonexistent. In this study, we investigated temporal correlations between tissue 1,25(OH)2D3 concentrations and VDR target genes in ileum and kidney and plasma calcium and PTH concentrations in response to 1,25(OH)2D3 treatment in mice (2.5 μg/kg ip, singly or q2d × 4). After a single ip dose, plasma 1,25(OH)2D3 peaked at ∼0.5 h and then decayed biexponentially, falling below basal levels after 24 h and then returning to baseline after 8 days. Upon repetitive ip dosing, plasma, ileal, renal, and bone 1,25(OH)2D3 concentrations rose and decayed in unison. Temporal profiles showed increased expressions of ileal Cyp24a1 and renal Cyp24a1, Mdr1/P-gp, and VDR but decreased renal Cyp27b1 mRNA after a time delay in VDR activation. Increased plasma calcium and attenuated PTH levels and increased ileal and renal Trpv6 expression paralleled the changes in tissue 1,25(OH)2D3 concentrations. Gene changes in the kidney were more sustained than those in intestine, but the magnitudes of change for Cyp24a1 and Trpv6 were lower than those in intestine. The data revealed that 1,25(OH)2D3 equilibrates with tissues rapidly, and VDR target genes respond quickly to exogenously administered 1,25(OH)2D3.

  5. Successful project management

    CERN Document Server

    Young, Trevor L

    2016-01-01

    Successful Project Management, 5th edition, is an essential guide for anyone who wants to improve the success rate of their projects. It will help managers to maintain a balance between the demands of the customer, the project, the team and the organization. Covering the more technical aspects of a project from start to completion it contains practised and tested techniques, covering project conception and start-up, how to manage stake holders, effective risk management, project planning and launch and execution. Also including a brand new glossary of key terms, it provides help with evaluating your project as well as practical checklists and templates to ensure success for any ambitious project manager. With over one million copies sold, the hugely popular Creating Success series covers a wide variety of topic, with the latest editions including new chapters such as Tough Conversations and Treating People Right. This indispensable business skills collection is suited to a variety of roles, from someone look...

  6. Goodbye Career, Hello Success.

    Science.gov (United States)

    Komisar, Randy

    2000-01-01

    Success in today's economy means throwing out the old career rules. The "noncareer" career is driven by passion for the work and has the fluidity and flexibility needed in the contemporary workplace. (JOW)

  7. Human Resource Outsourcing Success

    Directory of Open Access Journals (Sweden)

    Hasliza Abdul-Halim

    2014-07-01

    Full Text Available The existing literature on partnership seems to take the relationship between partnership quality and outsourcing success for granted. Therefore, this article aims at examining the role of service quality in strengthening the relationship between partnership quality and human resource (HR outsourcing success. The samples were obtained from 96 manufacturing organizations in Penang, Malaysia. The results showed that partnership quality variables such as trust, business understanding, and communication have significant positive impact on HR outsourcing success, whereas in general, service quality was found to partially moderate these relationships. Therefore, comprehending the HR outsourcing relationship in the context of service quality may assist the organizations to accomplish HR outsourcing success by identifying areas of expected benefits and improvements.

  8. Goodbye Career, Hello Success.

    Science.gov (United States)

    Komisar, Randy

    2000-01-01

    Success in today's economy means throwing out the old career rules. The "noncareer" career is driven by passion for the work and has the fluidity and flexibility needed in the contemporary workplace. (JOW)

  9. Research into Success

    Directory of Open Access Journals (Sweden)

    Bogomir Novak

    1997-12-01

    Full Text Available As competition is becoming ever more fierce, research into the prerequisites for success is gaining ground. By most people, success is perceived as an external phenomenon, but it is in fact the consequence of a person's readiness to perform in the world (of business. In the paper, Novak distinguishes between internal, external and group success. The essence of interna!success, which is the condition for the other two types of success, is assuming responsibility for, and exercising self-control over one's psychic phenomena. This in fact means that one needs to "reprogramme" the old patterns of behaviour and substitute them for the new, which leads to personality changes based on the understanding and acceptance of the self and others as they are. In realizing personal abilities, motives and goals, mental guiding laws must also be taken into account. Nowadays, the overall success of an organization is an important indicator of the quality of gro up work. The working patterns of individuals comply with the patterns used by his or her colleagues. When we do something for ourselves, we do it for others. In certain organizations, through accepted ways of communication all people become successful, and no body needs to be paid off. Employees wholly identify themselves with their organization, and vice versa. This three-part paradigm (I-Others-Community is the basis for various models of practical training for success, which are often idealized, but are primarily aimed at abolishing passivity and flaws in the system and its wider environment.

  10. Staffing for Success

    Science.gov (United States)

    Perozzi, Brett; Seifert, Tricia; Al-Sharif, Mary Ann Bodine

    2016-01-01

    This chapter explores institutional capacity building in cross-border student affairs and services. The focus is on human capital and its importance to international higher education within local contexts.

  11. The Economic Vitality Formula of Success

    Science.gov (United States)

    Konopnicki, Patrick M.

    2012-01-01

    An economic vitality formula of success can be accomplished by creating partnerships between local career and technical education (CTE), and workforce development and economic development entities. Student industry certifications; dynamic partnerships; programs and projects focused on science, technology, engineering, and mathematics (STEM); and…

  12. Global Optimality of the Successive Maxbet Algorithm.

    Science.gov (United States)

    Hanafi, Mohamed; ten Berge, Jos M. F.

    2003-01-01

    It is known that the Maxbet algorithm, which is an alternative to the method of generalized canonical correlation analysis and Procrustes analysis, may converge to local maxima. Discusses an eigenvalue criterion that is sufficient, but not necessary, for global optimality of the successive Maxbet algorithm. (SLD)

  13. The Economic Vitality Formula of Success

    Science.gov (United States)

    Konopnicki, Patrick M.

    2012-01-01

    An economic vitality formula of success can be accomplished by creating partnerships between local career and technical education (CTE), and workforce development and economic development entities. Student industry certifications; dynamic partnerships; programs and projects focused on science, technology, engineering, and mathematics (STEM); and…

  14. Net Locality

    DEFF Research Database (Denmark)

    de Souza e Silva, Adriana Araujo; Gordon, Eric

    Provides an introduction to the new theory of Net Locality and the profound effect on individuals and societies when everything is located or locatable. Describes net locality as an emerging form of location awareness central to all aspects of digital media, from mobile phones, to Google Maps, to...... of emerging technologies, from GeoCities to GPS, Wi-Fi, Wiki Me, and Google Android....

  15. Net Locality

    DEFF Research Database (Denmark)

    de Souza e Silva, Adriana Araujo; Gordon, Eric

    Provides an introduction to the new theory of Net Locality and the profound effect on individuals and societies when everything is located or locatable. Describes net locality as an emerging form of location awareness central to all aspects of digital media, from mobile phones, to Google Maps, to...... of emerging technologies, from GeoCities to GPS, Wi-Fi, Wiki Me, and Google Android....

  16. Successful ageing for psychiatrists.

    Science.gov (United States)

    Peisah, Carmelle

    2016-04-01

    This paper aims to explore the concept and determinants of successful ageing as they apply to psychiatrists as a group, and as they can be applied specifically to individuals. Successful ageing is a heterogeneous, inclusive concept that is subjectively defined. No longer constrained by the notion of "super-ageing", successful ageing can still be achieved in the face of physical and/or mental illness. Accordingly, it remains within the reach of most of us. It can, and should be, person-specific and individually defined, specific to one's bio-psycho-social and occupational circumstances, and importantly, reserves. Successful professional ageing is predicated upon insight into signature strengths, with selection of realistic goal setting and substitution of new goals, given the dynamic nature of these constructs as we age. Other essential elements are generativity and self-care. Given that insight is key, taking a regular stock or inventory of our reserves across bio-psycho-social domains might be helpful. Importantly, for successful ageing, this needs to be suitably matched to the professional task and load. This lends itself to a renewable personal ageing plan, which should be systemically adopted with routine expectations of self-care and professional responsibility. © The Royal Australian and New Zealand College of Psychiatrists 2015.

  17. Local Contexts

    Directory of Open Access Journals (Sweden)

    Philippe Schlenker

    2009-07-01

    Full Text Available The dynamic approach posits that a presupposition must be satisfied in its local context. But how is a local context derived from the global one? Extant dynamic analyses must specify in the lexical entry of any operator what its 'Context Change Potential' is, and for this very reason they fail to be sufficiently explanatory. To circumvent the problem, we revise two assumptions of the dynamic approach: we take the update process to be derivative from a classical, non-dynamic semantics -- which obviates the need for dynamic lexical entries; and we deny that a local context encodes what the speech act participants 'take for granted.' Instead, we take the local context of an expression E in a sentence S to be the smallest domain that one may restrict attention to when assessing E without jeopardizing the truth conditions of S. To match the results of dynamic semantics, local contexts must be computed incrementally, using only information about the expressions that precede E. This version of the theory can be shown to be nearly equivalent to the dynamic theory of Heim 1983 -- but unlike the latter, it is entirely predictive. We also suggest that local contexts can, at some cost, be computed symmetrically, taking into account information about all of S (except E; this leads to gradient predictions, whose assessment is left for future research. doi:10.3765/sp.2.3 BibTeX info

  18. Local measurement for structural health monitoring

    Institute of Scientific and Technical Information of China (English)

    G.Z.Qi; Guo Xun; Qi Xiaozhai; W. Dong; P.Chang

    2005-01-01

    Localized nature of damage in structures requires local measurements for structural health monitoring. The local measurement means to measure the local, usually higher modes of the vibration in a structure. Three fundamental issues about the local measurement for structural health monitoring including (1) the necessity of making local measurement, (2) the difficulty of making local measurement and (3) how to make local measurement are addressed in this paper. The results from both the analysis and the tests show that the local measurement can successfully monitor the structural health status as long as the local modes are excited. Unfortunately, the results also illustrate that it is difficult to excite local modes in a structure.Therefore, in order to carry structural health monitoring into effect, we must (1) ensure that the local modes are excited, and (2) deploy enough sensors in a structure so that the local modes can be monitored.

  19. Untangling Performance from Success

    CERN Document Server

    Yucesoy, Burcu

    2015-01-01

    Fame, popularity and celebrity status, frequently used tokens of success, are often loosely related to, or even divorced from professional performance. This dichotomy is partly rooted in the difficulty to distinguish performance, an individual measure that captures the actions of a performer, from success, a collective measure that captures a community's reactions to these actions. Yet, finding the relationship between the two measures is essential for all areas that aim to objectively reward excellence, from science to business. Here we quantify the relationship between performance and success by focusing on tennis, an individual sport where the two quantities can be independently measured. We show that a predictive model, relying only on a tennis player's performance in tournaments, can accurately predict an athlete's popularity, both during a player's active years and after retirement. Hence the model establishes a direct link between performance and momentary popularity. The agreement between the performa...

  20. Succeeding with succession planning.

    Science.gov (United States)

    McConnell, C R

    1996-12-01

    Succession planning is the process of identifying people who could presently move into key positions or could do so after specifically targeted development occurs. The process identifies the better people in the organization and takes a consistent approach to assembling, analyzing, and retaining information about potential leaders and planning for their further development. At its simplest level, it is the development of a backup and potential successor to each manager; at is most formal, it is a documented plan for management succession at all levels in the organization. Strongly supportive of a policy of development and promotion from within the organization, succession planning also represents a proactive posture in respect to inevitable management turnover. In these days of rapid change in health care, no modern organization that expects to keep up with increasing competition can afford to drift--or even to let a single department drift--while replacements are recruited for managers who resign, retire, or otherwise leave.

  1. Successful aging at work

    NARCIS (Netherlands)

    Zacher, Hannes

    2015-01-01

    The expression successful aging at work and related terms such as active, healthy, and productive aging at work are frequently used by organizational researchers and practitioners. However, there are no concrete definitions or theoretical frameworks that explain their meaning, assumptions, and

  2. Successful School Composting.

    Science.gov (United States)

    Mahar, Rhea Dawn

    2001-01-01

    School composting programs that have met the challenges inherent in long-term composting have several traits in common: a supportive educational program, schoolwide participation, and a consistent maintenance program. Examines the elements of success, offers examples of incorporating composting into the curriculum, and describes three methods of…

  3. Ensuring Students' Success

    Science.gov (United States)

    Oblinger, James L.

    2006-01-01

    James L. Oblinger, Chancellor of North Carolina State University, argues that higher education must continually evolve new methods of teaching and learning to support students' lifelong skills and impending careers. Part of ensuring students' success lies in finding alternative learning models, such as the Student-Centered Activities for Large…

  4. Success in Entrepreneurship

    DEFF Research Database (Denmark)

    Iversen, Jens; Malchow-Møller, Nikolaj; Sørensen, Anders

    2016-01-01

    What makes a successful entrepreneur? Using Danish register data, we find strong support for the hypothesis that theoretical skills from schooling and practical skills acquired through wage-work are complementary inputs in the human capital earnings function of entrepreneurs. In fact, we find tha...

  5. Pathways to School Success

    Science.gov (United States)

    University of Pittsburgh Office of Child Development, 2012

    2012-01-01

    In 2006, the University of Pittsburgh Office of Child Development began implementing a multi-year school readiness project in several area schools. Evidence from both research and the field point to several key elements that foster school readiness and create pathways to school success for all children. This paper presents components of a…

  6. Models of Success

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Wu Renbao made national celebrity for his commitment to achieving common prosperity among his co-villagers in Huaxi Village, Jiangsu Province.Wu's recipe for success was to take advantage of collective strength by encouraging mutual assistance between villages and households.

  7. International Student Success

    Science.gov (United States)

    Smith, Clayton

    2016-01-01

    This article, with a focus on North American postsecondary education, identifies international students as a strategic enrollment management institutional priority; presents themes in the international student retention, satisfaction, and success research literature; and describes related best practices. It also presents the findings from an…

  8. Mindfulness and Student Success

    Science.gov (United States)

    Leland, Matt

    2015-01-01

    Mindfulness has long been practiced in Eastern spiritual traditions for personal improvement, and educators and educational institutions have recently begun to explore its usefulness in schools. Mindfulness training can be valuable for helping students be more successful learners and more connected members of an educational community. To determine…

  9. FOCUS: Sustainable Mathematics Successes

    Science.gov (United States)

    Mireles, Selina V.; Acee, Taylor W.; Gerber, Lindsey N.

    2014-01-01

    The FOCUS (Fundamentals of Conceptual Understanding and Success) Co-Requisite Model Intervention (FOCUS Intervention) for College Algebra was developed as part of the Developmental Education Demonstration Projects (DEDP) in Texas. The program was designed to use multiple services, courses, and best practices to support student completion of a…

  10. Success in Entrepreneurship

    DEFF Research Database (Denmark)

    Iversen, Jens; Malchow-Møller, Nikolaj; Sørensen, Anders

    2016-01-01

    What makes a successful entrepreneur? Using Danish register data, we find strong support for the hypothesis that theoretical skills from schooling and practical skills acquired through wage-work are complementary inputs in the human capital earnings function of entrepreneurs. In fact, we find...

  11. Ramada, A Successful Example

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    <正>After entry into the WTO, China’s hotels are being challenged by the global economy and overseas counterparts. They should seek creation and development to fight against the fierce competition. Ramada Pudong Hotel, managed by the Shanghai Airport Group Civil Aviation Property Company Ltd, has become a successful example in creative management.

  12. Characteristics of Successful Entrepreneurs.

    Science.gov (United States)

    McClelland, David C.

    1987-01-01

    Comparison of characteristics of 12 average and 12 superior small business people in three developing nations (India, Malawi, and Ecuador) found proactive qualities such as initiative and assertiveness, achievement orientation, and commitment to others characteristic of successful entrepreneurs. Other expected qualities (self-confidence,…

  13. Ensuring Students' Success

    Science.gov (United States)

    Oblinger, James L.

    2006-01-01

    James L. Oblinger, Chancellor of North Carolina State University, argues that higher education must continually evolve new methods of teaching and learning to support students' lifelong skills and impending careers. Part of ensuring students' success lies in finding alternative learning models, such as the Student-Centered Activities for Large…

  14. Characteristics of Successful Entrepreneurs.

    Science.gov (United States)

    McClelland, David C.

    1987-01-01

    Comparison of characteristics of 12 average and 12 superior small business people in three developing nations (India, Malawi, and Ecuador) found proactive qualities such as initiative and assertiveness, achievement orientation, and commitment to others characteristic of successful entrepreneurs. Other expected qualities (self-confidence,…

  15. Successful Bilingual Education Programs

    Science.gov (United States)

    Montecel, Maria Robledo; Cortez, Josie

    2004-01-01

    This article describes a research project carried out by the Intercultural Development Research Association (IDRA). IDRA's primary research question for this study was, "What contributed to the success of a bilingual education classroom as evidenced by LEP student academic achievement?" In addition to the student data, qualitative and contextual…

  16. Locals Collection

    Directory of Open Access Journals (Sweden)

    Stephen Hastings-King

    2010-03-01

    Full Text Available A locals collection is a set of parameters that are used to delimit data-mining operations. This piece uses a collection of locals from around Essex Massachusetts to shape and delimit an interrogation of post-reality in contemporary America. It explores the notion of crisis, the possibility of a crisis of empire that may or may not emerge in a media-space that does not allow crisis of empire to be mentioned and relations this maybe-crisis to the various levels of economic dysfunction that have become evident since late 2008. But mostly this piece explores ways in which particular stories about particular people do and do not link/link to these larger-scale narratives. This is the first of a potential series of locals collections that will mine the American post-real.

  17. Are P.T.H. plasma levels useful for the selection of patients with secondary hyperparathyroidism for preoperative MIBI ({sup 99m}Tc)/{sup 123}I dual-isotope scintigraphy?;La concentration plasmatique de PTH permet-elle de selectionner les patients atteints d'hyperparathyroidie secondaire pour beneficier de la scintigraphie double isotope MIBI ({sup 99m}Tc)/{sup 123}I preoperatoire?

    Energy Technology Data Exchange (ETDEWEB)

    Balogova, S.; Sauer, A.M.; Dudczak, J.; Pascal, O.; Kerrou, K.; Huchet, V.; Montravers, F.; Talbot, J.N. [Universite Pierre-et-Marie-Curie, Service de medecine nucleaire, hopital Tenon, 75 - Paris (France); Perie, S.; Lacau St-Guily, J. [Universite Pierre-et-Marie-Curie, ORL, hopital Tenon, 75 - Paris (France); Nataf, V. [Universite Pierre-et-Marie-Curie, hopital Tenon, Service de radiopharmacie, 75 - Paris (France); Balogova, S. [Faculte de medecine, universite Comenius, Bratislava (Slovakia)

    2010-07-15

    The utility of preoperative scintigraphy in case of secondary hyperparathyroidism is questioned by some authors. Obviously, an imaging modality that will detect all hyperplastic glands, including the ectopic ones, would be of interest in those patients at high risk for surgery. However, scintigraphy has a limited detection rate in some patients. We investigated whether one of the following parameters would identify a subgroup of patients in whom the detection rate would be optimal: age, gender, hemodialysis and duration since its onset, and plasma levels of parathyrin (P.T.H.). Methods: Retrospective series of 38 patients referred for preoperative parathyroid scintigraphy due to secondary hyperparathyroidism who then underwent para thyroidectomy. Scintigraphy was performed 20 min and then 3 h after injection of 8 MBq/kg of sestamibi ({sup 99m}Tc) with a previous ingestion of 0.1 MBq/kg iodine-123, 3 h before. Result: No significant correlation was observed between the number of glands detected on scintigraphy (and confirmed by postoperative histology) and plasma P.T.H. levels (r = -0.17). A weak positive correlation (r = +0.34) was noted in the group of six non-hemo dialysed patients. No significant relationship between this number of detected glands and a clinical parameter was observed. Conclusion: In our experience, these parameters do not permit to select, among patients with secondary hyperparathyroidism and scheduled for para thyroidectomy, those who will better benefit from parathyroid scintigraphy. (authors)

  18. Going Local

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Becoming more Chinese is the key to success in China, according to top foreign brands Ma Mingyu and her husband have spent the last few weekends shuttling between auto dealer-ships in Beijing to choose their first family car. And they've noticed a common selling point in the brochures for almost every foreign auto: a

  19. Localized shocks

    CERN Document Server

    Roberts, Daniel A; Susskind, Leonard

    2014-01-01

    We study products of precursors of spatially local operators, $W_{x_{n}}(t_{n}) ... W_{x_1}(t_1)$, where $W_x(t) = e^{-iHt} W_x e^{iHt}$. Using chaotic spin-chain numerics and gauge/gravity duality, we show that a single precursor fills a spatial region that grows linearly in $t$. In a lattice system, products of such operators can be represented using tensor networks. In gauge/gravity duality, they are related to Einstein-Rosen bridges supported by localized shock waves. We find a geometrical correspondence between these two descriptions, generalizing earlier work in the spatially homogeneous case.

  20. What Does Successful Aging Mean? Lay Perception of Successful Aging Among Elderly Singaporeans.

    Science.gov (United States)

    Feng, Qiushi; Straughan, Paulin Tay

    2017-03-01

    We explore the culturally specific meaning of successful aging in Singapore, an ethnically diverse city-state in Asia. We aim to investigate lay perceptions of successful aging among the elderly individuals in Singapore and further examine variations of these perceptions. We applied a mixed-method research design. Firstly, we conducted qualitative interviews with 49 elderly respondents, generating 12 main subjective components of successful aging. Next, we did a national survey with a sample of 1,540 local residents aged 50 to 69 years, in which respondents were asked to evaluate the importance of each subjective component of successful aging. We used the regression models and latent class analysis to analyze the correlatives of successful aging and to classify the elderly individuals by perception types. Among 12 components of successful aging, those related to self-sufficiency received the highest acknowledgment among the elderly individuals in Singapore. At least half of them simultaneously highlighted independence from family and dependence on family. Malays and Indians in Singapore valued more of the roles of spouse and children in successful aging, as compared with Chinese. The latent class analysis classified four groups of the elderly individuals according to their lay views on successful aging. As compared with the western model of successful aging, the elderly individuals in Singapore perceived successful aging with a strong focus on familism. These lay perceptions also significantly varied among these elderly individuals.

  1. Local language

    NARCIS (Netherlands)

    Monique Turkenburg

    2002-01-01

    Original title: Taal lokaal. Children of immigrants living in the Netherlands have for years had the opportunity to receive lessons in their mother tongue at primary school. Since 1998 this has been referred to as minority language teaching (OALT in Dutch), and has been the responsibility of local

  2. Small(pox) success?

    Science.gov (United States)

    Birn, Anne-Emanuelle

    2011-02-01

    The 30th anniversary of the World Health Organization's (WHO) official certification of smallpox eradication was marked by a slew of events hailing the campaign's dramatic tale of technological and organizational triumph against an ancient scourge. Yet commemorations also serve as moments of critical reflection. This article questions the acclaim showered upon smallpox eradication as the single greatest public health success in history. It examines how and why smallpox eradication and WHO's concurrent social justice-oriented primary health care approach (following from the Declaration of Alma-Ata) became competing paradigms. It synthesizes critiques of eradication's shortcomings and debunks some of the myths surrounding the global eradication campaign as a public health priority and necessity, and as a Cold War victory of cooperation. The article concludes with thoughts on integrating technical and social-political aspects of health within the context of welfare states as the means to achieving widespread and enduring global public health success.

  3. Small(pox success?

    Directory of Open Access Journals (Sweden)

    Anne-Emanuelle Birn

    Full Text Available The 30th anniversary of the World Health Organization's (WHO official certification of smallpox eradication was marked by a slew of events hailing the campaign's dramatic tale of technological and organizational triumph against an ancient scourge. Yet commemorations also serve as moments of critical reflection. This article questions the acclaim showered upon smallpox eradication as the single greatest public health success in history. It examines how and why smallpox eradication and WHO's concurrent social justice-oriented primary health care approach (following from the Declaration of Alma-Ata became competing paradigms. It synthesizes critiques of eradication's shortcomings and debunks some of the myths surrounding the global eradication campaign as a public health priority and necessity, and as a Cold War victory of cooperation. The article concludes with thoughts on integrating technical and social-political aspects of health within the context of welfare states as the means to achieving widespread and enduring global public health success.

  4. Styles of success

    DEFF Research Database (Denmark)

    Dahlgaard, Jens Jørn; Nørgaard, Anders; Jakobsen, Søren

    1997-01-01

    of business excellence points to a clear agenda for success. Setting clear strategic goals and the ability to take a long-term view of an organization's direction, combined with other leadership attributes such as creativity, teambuilding and learning, are principal keys to creating an excellent organization......Corporate success stories tend to emphasize the "great men" theory of history. But now a European research project established the managerial attributes that can turn an ordinary leader into one ideal for the pursuit of business excellence. The emergence of five leadership styles as crucial drivers...... lower value on the teambuilding and strategic competencies than is required for business excellence. By contrast, their "ideal" leader is heavily characterized by being a creative, inspiring, and active problem-solver....

  5. Styles of success

    DEFF Research Database (Denmark)

    Dahlgaard, Jens Jørn; Nørgaard, Anders; Jakobsen, Søren

    1997-01-01

    Corporate success stories tend to emphasize the "great men" theory of history. But now a European research project established the managerial attributes that can turn an ordinary leader into one ideal for the pursuit of business excellence. The emergence of five leadership styles as crucial drivers...... of business excellence points to a clear agenda for success. Setting clear strategic goals and the ability to take a long-term view of an organization's direction, combined with other leadership attributes such as creativity, teambuilding and learning, are principal keys to creating an excellent organization....... Leaders seeking to achive business excellence must view the high-level attainment of these sets of leadership competencies as their paramount objective. In striving for business excellence, European leaders may encounter resistance among their employees. Crucially, European employees place a markedly...

  6. Profile of success

    DEFF Research Database (Denmark)

    Dahlgaard, Jens Jørn; Nørgaard, Anders; Jakobsen, Søren

    1998-01-01

    What management skills must Europe's business leaders improve to achieve business excellence? Which country's leaders are best placed for success? Does the next generation have what it takes to compete? In the second half of their study of the leadership styles that drive business excellence, Jens...... Dahlgaard, Anders Nørgaard and Søren Jakobsen describe an excellent leadership profile that provides the answers....

  7. Successful time management

    CERN Document Server

    Forsyth, Patrick

    2016-01-01

    Packed with tips and techniques, Successful Time Management serves as a guide to reviewing and assessing new work practices to improve time management. It includes great time-saving ideas, practical solutions, checklists, and advice on controlling paperwork, delegating and working with others, prioritizing to focus on key issues, and getting and staying organized. This new third edition contains new practical tips on using email in a time effective manner and dealing with other internet-based tools and apps to help productivity.

  8. Principles of successful partnerships.

    Science.gov (United States)

    Mangold, Kara; Denke, Nancy J; Gorombei, Deb; Ostroski, Tammy L; Root, Lynda

    2014-01-01

    Health care providers must understand and value the unique contributions of all interdisciplinary professionals, with the goal of optimizing the wellness or illness needs of each patient. Work cannot be done in silos, and the ability to develop and sustain effective professional partnerships is essential. Health care teams must work within a complex environment that depends on the shared efforts of multiple professionals to successfully provide care in a fragmented, highly stressed system. Implementing partnerships that foster relationships through shared interests, vision, and values can aid in the coordination of resources to provide a more positive patient experience and outcome. The development of partnerships requires time and acceptance of shared risks and responsibilities. In return, involved parties will be able to build trust, share rewards, and expand the possibilities of what can be accomplished. The purpose of this review is to describe results-oriented partnerships, which include the attributes of collaboration, coordination, and communication. Essential concepts and practical tools for success are reviewed to offer new and existing partnerships a lens through which to view interdisciplinary interactions that can contribute to organizational success and longevity. Potential pitfalls that may impact patient services and organizational health are also discussed.

  9. Independent Local Political Parties in the Netherlands

    NARCIS (Netherlands)

    Voerman, G.; Boogers, M.

    2010-01-01

    In the last 15 years, the Netherlands has witnessed the enormous growth of independent local parties and of their electoral support. In order to assess the success of independent locals in the Netherlands, this paper explores how independent local parties distinguish themselves ideologically, organi

  10. Successful Succession in Family Businesses : Individual Level Factors and Succession Planning Models.

    OpenAIRE

    Aleem, Majid; Islam, Md. Shariful

    2009-01-01

    Individual level factors related to the successor have a central role to play in the succession process of the business. When these factors are viewed in relation to succession planning models, these factors have a direct relation to the succession models in terms of success or failure of the succession process. The major contributing factor to the success or failure of the succession process is that of the leadership provided to the organization by the predecessor. These leadership qualities...

  11. Successfully Developing Joint Leaders

    Science.gov (United States)

    2010-07-26

    officer’s pyramid representing his career, there is merely the word “joint”. Therefore, unless the officer adamantly pursues a joint assignment it...had the chance to participate in Bosnia stability operations. It is how we were taught to work with locals and the experiences I took with me that...Drug Ops, OAF, OEF, OIF, Bosnia , Unconventional) - When you participated in an operation was there any “joint” involvement? If “yes”, did you feel

  12. Local Linearizability

    OpenAIRE

    Haas, Andreas; Henzinger, Thomas A.; Holzer, Andreas; Kirsch, Christoph M.; Lippautz, Michael; Payer, Hannes; Sezgin, Ali; Sokolova, Ana; Veith, Helmut

    2015-01-01

    The semantics of concurrent data structures is usually given by a sequential specification and a consistency condition. Linearizability is the most popular consistency condition due to its simplicity and general applicability. Nevertheless, for applications that do not require all guarantees offered by linearizability, recent research has focused on improving performance and scalability of concurrent data structures by relaxing their semantics. In this paper, we present local linearizability,...

  13. Successful learning in the global economy

    DEFF Research Database (Denmark)

    Jørgensen, Sanne Lehmann

    2012-01-01

    This article aims to subject some of the hypotheses concerning the potential of knowledge upgrading for firms engaged in various vertical and horizontal networks to a critical examination. The theories are applied to a Thai context and use the case of the auto parts industry to evaluate the process...... of knowledge upgrading in local firms. The article concludes that neither embeddedness in local networks nor linkages with transnational corporations are sufficient for Thai firms to upgrade their knowledge base to become successful actors in the global economy. Instead it points to the importance of focusing...

  14. Effects Of Predator Exclosures On Nesting Success Of Killdeer

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Nests of shorebirds are often destroyed by predators and in some instances predation may cause severe local declines in breeding success and in size of a breeding...

  15. Negotiating Successfully in Asia

    Directory of Open Access Journals (Sweden)

    Michael Benoliel

    2013-08-01

    Full Text Available Cross-cultural negotiations are complex, challenging, and difficult to navigate because much of the Asian culture is unstated, implicit, and internalized in subtle behavioral patterns. It is like an iceberg; more is invisible and less is visible. To understand how the Asian negotiation values and practices are different from those in the West, I describe briefly the Asian cultural roots, highlight the major dimensions that differentiate cultures, explore the factors that influence the Asian negotiation processes and outcomes, and provide a list of practical suggestions for negotiating successful deals with Asian negotiators.

  16. Successful product realization strategies

    Science.gov (United States)

    Peeples, John; Boulton, William R.

    1995-02-01

    Product realization is the process of defining, designing, developing, and delivering products to the market. While the main thrust of this JTEC panel was to conduct a complete investigation of the state of Japanese low-cost electronic packaging technologies, it is very difficult to totally separate the development of technology and products from the product realization process. Japan's electronics firms adhere to a product realization strategy based on a strong customer focus, a consistent commitment to excellence in design, and a cost-effective approach to technology commercialization. The Japanese product-pull strategy has been a successful driver and influencing factor in every aspect of the product development cycle.

  17. Successful innovation by motivation

    Directory of Open Access Journals (Sweden)

    Petra Koudelková

    2015-10-01

    Full Text Available Innovation is one of the most important factors for business growth. Human capital plays a significant role in the successful process of innovation. This article deals with employee motivation in the innovation process and the main scientific aim of this study is to present results of research that was undertaken in the Czech Republic at the beginning of 2013. Questionnaires were used for the survey and statistical analyses such as Chi square test or Hierarchical cluster analysis were used for data processing. This study also provides a theoretical and practical overview of business innovation in the Czech Republic.

  18. Implant success!!!.....simplified

    Directory of Open Access Journals (Sweden)

    Luthra Kaushal

    2009-01-01

    Full Text Available The endeavor towards life-like restoration has helped nurture new vistas in the art and science of implant dentistry. The protocol of "restoration-driven implant placement" ensures that the implant is an apical extension of the ideal future restoration and not the opposite. Meticulous pre-implant evaluation of soft and hard tissues, diagnostic cast and use of aesthetic wax-up and radiographic template combined with surgical template can simplify the intricate roadmap for appropriate implant treatment. By applying the harmony of artistic skill, scientific knowledge and clinical expertise, we can simply master the outstanding implant success in requisites of aesthetics, phonetics and function.

  19. SUCCESS OUTSIDE THE CITY

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    @@ Coming as a much-needed boon for the countryside,this year's No.1 Document,jointly released by the Central Committee of the Communist Party of China and the State Council,pledges a series of concrete measures to propel improvements in the rural economy and the livelihood of farmers.Nevertheless,rural prosperity in line with the success of urban areas will prove to be a challenge.The foundation of the agriculture sector remains fluid,and farmers lack a stable source of income and a reliable social safety net.

  20. Localization of abnormal parathyroid gland(s) using thallium-201/iodine-123 subtraction scintigraphy in patients with primary hyperparathyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Picard, D.; D' Amour, P.; Carrier, L.; Chartrand, R.; Poisson, R.

    1987-01-01

    Tl-201/I-123 subtraction scintigraphy was performed in 17 patients with clinical symptoms and biochemical measurements suggestive of primary hyperparathyroidism. Nineteen abnormal sites were identified. These results were correlated with PTH measurements and surgical findings. Three sites were considered unrelated to the parathyroid glands, two corresponding to palpable thyroid nodules and one to muscle uptake of unknown origin. One scintigram did not reveal either of two abnormal glands while two others were considered falsely positive in view of surgical failure. Fourteen sites corresponded to abnormal parathyroid gland at surgery; five glands, weighing more than 2000 mg, could be correctly located on the Tl-201 scintigraphy prior to the subtraction procedure; six glands, weighing between 500 and 2000 mg, were easily localized after the subtraction procedure; three glands, weighing between 180 and 200 mg, were correctly localized after further manipulation of the subtraction procedure. In a patient with parathyroid hyperplasia, one gland, weighing 150 mg, was not located and another was not found upon surgery. Overall sensitivity was 87.5%. A positive correlation between PTH levels, tumor weight, and ease of detection on scintigraphy was found. This correlation was particularly useful in excluding large abnormal uptake related to thyroid disorder or artifact. The results suggest that Tl-201/I-123 parathyroid scintigraphy could become an alternative to Tl-201/Tc-99m parathyroid scintigraphy, with possibly improved detection of low weight abnormal parathyroid glands.

  1. LEIR commissioning successfully completed

    CERN Multimedia

    2006-01-01

    An important milestone has been passed in the preparation of the injector complex to supply ions to the LHC experiments. The LEIR lead-ion beam, seen on one of the control screens just before the PS injection region. The Low-Energy Ion Ring - LEIR for short - has passed its first tests with flying colours. On 12 May, the ring that will accumulate lead ions for the LHC was shut down after seven months of tests (see Bulletin 44/2005). 'The commissioning phase was a resounding success,' enthuses a satisfied Michel Chanel, head of the LEIR construction project. After several months of fine-tuning, the LEIR team has achieved its aim of producing the kind of beam required for first lead-ion collisions in the LHC in 2008. This involved creating bunches containing 230 million ions, in line with the specifications for those first beams. This success can be put down to the machine's outstanding design and components. 'It's a great achivement by all the teams involved in the machine's construction,' underlines Christian...

  2. Thermodynamics "beyond" local equilibrium

    Science.gov (United States)

    Vilar, Jose; Rubi, Miguel

    2002-03-01

    Nonequilibrium thermodynamics has shown its applicability in a wide variety of different situations pertaining to fields such as physics, chemistry, biology, and engineering. As successful as it is, however, its current formulation considers only systems close to equilibrium, those satisfying the so-called local equilibrium hypothesis. Here we show that diffusion processes that occur far away from equilibrium can be viewed as at local equilibrium in a space that includes all the relevant variables in addition to the spatial coordinate. In this way, nonequilibrium thermodynamics can be used and the difficulties and ambiguities associated with the lack of a thermodynamic description disappear. We analyze explicitly the inertial effects in diffusion and outline how the main ideas can be applied to other situations. [J.M.G. Vilar and J.M. Rubi, Proc. Natl. Acad. Sci. USA 98, 11081-11084 (2001)].

  3. El nivel de la hormona paratiroidea (PTH y no el de fósforo sérico es predictor de la progresión de la enfermedad renal en pacientes mayores con enfermedad renal crónica avanzada

    Directory of Open Access Journals (Sweden)

    Néstor Gabriel Toapanta Gaibor

    2017-03-01

    Conclusiones: En nuestro grupo de pacientes de edad avanzada el deterioro de la función renal es muy lento, especialmente en los pacientes en estadio 5. La albuminuria y la PTH al inicio del seguimiento son factores pronósticos en la evolución de su función renal.

  4. In vitro refolding with simultaneous purification of recombinant human parathyroid hormone (rhPTH 1-34) from Escherichia coli directed by protein folding size exclusion chromatography (PF-SEC): implication of solution additives and their role on aggregates and renaturation.

    Science.gov (United States)

    Vemula, Sandeep; Vemula, Sushma; Dedaniya, Akshay; Ronda, Srinivasa Reddy

    2016-01-01

    Recombinant proteins are frequently hampered by aggregation during the refolding and purification process. A simple and rapid method for in vitro refolding and purification of recombinant human parathyroid hormone (rhPTH 1-34) expressed in Escherichia coli with protein folding size exclusion chromatography (PF-SEC) was developed in the present work. Discrete effects of potential solution additives such as urea, polypolyethylene glycol, proline, and maltose on the refolding with simultaneous purification of rhPTH were investigated. The results of individual additives indicated that both maltose and proline had remarkable influences on the efficiency of refolding with a recovery yield of 65 and 66% respectively. Further, the synergistic effect of these additives on refolding was also explored. These results demonstrate that the additive combinations are more effective for inhibiting protein aggregation during purification of rhPTH in terms of recovery yield, purity, and specific activity. The maltose and proline combination system achieved the highest renatured rhPTH having a recovery yield of 78%, a purity of ≥99%, and a specific activity of 3.31 × 10(3) cAMP pM/cell respectively, when compared to the classical dilution method yield (41%) and purity (97%). In addition, the role of maltose and proline in a combined system on protein aggregation and refolding has been explained. The molecular docking (in silico) scores of maltose (-10.91) and proline (-9.0) support the in vitro results.

  5. Localization capacity of human listeners

    DEFF Research Database (Denmark)

    Hammershøi, Dorte

    2009-01-01

    For some scenarios and situations, successful localization of the sound is vital for the hearing experience. One aspect of this is the natural limits of the human localization capacity, incl. dependence on e.g. direction and distance. When addressed in laboratory experiments, the significance...... of other modalities are controlled in different ways, yet figures will inherently reflect properties of the test situation as well as the capacity of the individual. The present paper will review some contemporary localization experiments, with a specific view to the "absolute" acuity, the measures used...

  6. Human localization and performance measures

    DEFF Research Database (Denmark)

    Hammershøi, Dorte

    2009-01-01

    Localization is for some scenarios and situations vital for the success of hearing, e. g. when listening out single sources in multi-source environments, or when navigating primarily by audible information. It is therefore of interest to know the limits of the human localization capacity, and its...... dependence on e.g. direction and distance. When addressed in laboratory experiments, the significance of other modalities are controlled in different ways, yet figures will inherently reflect properties of the test situation as well. The present paper will discuss the methodologies of localization...... experiments, generally and by examples....

  7. LHC synchronization test successful

    CERN Multimedia

    The synchronization of the LHC's clockwise beam transfer system and the rest of CERN's accelerator chain was successfully achieved last weekend. Tests began on Friday 8 August when a single bunch of a few particles was taken down the transfer line from the SPS accelerator to the LHC. After a period of optimization, one bunch was kicked up from the transfer line into the LHC beam pipe and steered about 3 kilometres around the LHC itself on the first attempt. On Saturday, the test was repeated several times to optimize the transfer before the operations group handed the machine back for hardware commissioning to resume on Sunday. The anti-clockwise synchronization systems will be tested over the weekend of 22 August.Picture:http://lhc-injection-test.web.cern.ch/lhc-injection-test/

  8. Iridium: failures & successes

    Science.gov (United States)

    Christensen, CarissaBryce; Beard, Suzette

    2001-03-01

    This paper will provide an overview of the Iridium business venture in terms of the challenges faced, the successes achieved, and the causes of the ultimate failure of the venture — bankruptcy and system de-orbit. The paper will address technical, business, and policy issues. The intent of the paper is to provide a balanced and accurate overview of the Iridium experience, to aid future decision-making by policy makers, the business community, and technical experts. Key topics will include the history of the program, the objectives and decision-making of Motorola, the market research and analysis conducted, partnering strategies and their impact, consumer equipment availability, and technical issues — target performance, performance achieved, technical accomplishments, and expected and unexpected technical challenges. The paper will use as sources trade media and business articles on the Iridium program, technical papers and conference presentations, Wall Street analyst's reports, and, where possible, interviews with participants and close observers.

  9. SUCCESS OUTSIDE THE CITY

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Coming as a much-needed boon for the countryside, this year’s No.1 Document, jointly released by the Central Committee of the Communist Party of China and the State Council, pledges a series of concrete measures to propel improvements in the rural economy and the livelihood of farmers. Nevertheless, rural prosperity in line with the success of urban areas will prove to be a challenge. The foundation of the agriculture sector remains fluid, and farmers lack a stable source of income and a reliable social safety net. So how can China promote the sustained development of its agriculture sector and social improvements to the countryside? Experts and economists provide suggestions to achieving these goals.

  10. Fluoridation: strategies for success.

    Science.gov (United States)

    Isman, R

    1981-07-01

    Of 19 referenda on community water fluoridation held in the first six months of 1980, 17 were defeated. Among the postulated reasons are a growing distrust of government and the health establishment. The public remains largely ignorant of the purpose and benefits of fluoridation. The emotionalism surrounding the issue has made it difficult to generate public support outside of the health professions. Opponents have also learned to fight fluoridation with increasingly sophisticated techniques. Some of the strategies used in recent successful campaigns in Oakland, California, and Portland, Oregon are described; recommendations that can be applied to communities considering fluoridation include careful wording of ballot measures so they are unequivocally clear and simple; timing ballot measures with elections likely to draw the largest voter turnout; broadening the base of political and financial support; using a figurehead if possible; and making maximum use of the media.

  11. A metric for success

    Science.gov (United States)

    Carver, Gary P.

    1994-05-01

    The federal agencies are working with industry to ease adoption of the metric system. The goal is to help U.S. industry compete more successfully in the global marketplace, increase exports, and create new jobs. The strategy is to use federal procurement, financial assistance, and other business-related activities to encourage voluntary conversion. Based upon the positive experiences of firms and industries that have converted, federal agencies have concluded that metric use will yield long-term benefits that are beyond any one-time costs or inconveniences. It may be time for additional steps to move the Nation out of its dual-system comfort zone and continue to progress toward metrication. This report includes 'Metric Highlights in U.S. History'.

  12. Overcome barriers to career success

    Energy Technology Data Exchange (ETDEWEB)

    Raudsepp, E.

    1983-04-01

    A test is given to determine if an engineer suffers from one of the three barriers to technical success: fear of success, fear of failure, or perfectionism. As in most such tests, the middle way is best. Successful engineers know that perfection cannot be attained, that they don't have time to worry about failure or success, and that by aiming and perservering in doing things well, success can be achieved.

  13. Developing a successful robotics program.

    Science.gov (United States)

    Luthringer, Tyler; Aleksic, Ilija; Caire, Arthur; Albala, David M

    2012-01-01

    Advancements in the robotic surgical technology have revolutionized the standard of care for many surgical procedures. The purpose of this review is to evaluate the important considerations in developing a new robotics program at a given healthcare institution. Patients' interest in robotic-assisted surgery has and continues to grow because of improved outcomes and decreased periods of hospitalization. Resulting market forces have created a solid foundation for the implementation of robotic surgery into surgical practice. Given proper surgeon experience and an efficient system, robotic-assisted procedures have been cost comparable to open surgical alternatives. Surgeon training and experience is closely linked to the efficiency of a new robotics program. Formally trained robotic surgeons have better patient outcomes and shorter operative times. Training in robotics has shown no negative impact on patient outcomes or mentor learning curves. Individual economic factors of local healthcare settings must be evaluated when planning for a new robotics program. The high cost of the robotic surgical platform is best offset with a large surgical volume. A mature, experienced surgeon is integral to the success of a new robotics program.

  14. Local Professionals for Local Market

    Institute of Scientific and Technical Information of China (English)

    Wen Xiaojie

    2010-01-01

    @@ In the past three decades,the Chinese hotel industry has developed at a rapid pace,with the number of hotels-especially high star hotelsgrowing fast.In Beijing alone,there arc nearly 60 five-star hotels.With the development of the hotel industry.China has also begun to see the number of local hotel professionals,including senior managers,increase.Wen Xiaojie,Deputy General Manager and Owner's Representative of Sofitel Wanda Beijing,is among the most outstanding senior hotel managers.

  15. Reconstruction of Anacostia wetlands: success?

    Science.gov (United States)

    Hammerschlag, R.S.; Perry, M.C.

    2002-01-01

    Historically, the tidal Anacostia River in Washington, D.C. had been an extensive system of freshwater tidal marshes replete with a full array of wetland vegetation dominated by wild rice. The local Nacochtank Indians had found the abundant fish and wildlife sufficient to sustain their daily lives. White man's intrusion upon the landscape gradually brought about deterioration of the natural (and associated cultural) system. Total demise followed mid-20th century dredge and fill channelization, which was conducted from the confluence of the Anacostia with the Potomac near the heart of Washington, D.C. to the terminus of the tidal regime at Bladensburg, Maryland. The National Park Service (NPS) became the manager for much of the land along the Anacostia, particularly the eastern bank. As part of its planning effort, the NPS envisioned returning portions of the Anacostia under its control to a natural system as a vignette. The concept was based on bringing back as comprehensive a collection of vegetation and wildlife as possible through the reestablishment of tidal marshes at Kenilworth and Kingman. The resultant wetlands were to be made accessible to the public both logistically and through a well designed interpretative program. In fact, this vision has been realized due to an impressive cooperative effort among a number of Federal and local agencies and organizations. In 1993, 32 acres of freshwater tidal marsh were reconstructed at Kenilworth. Based upon the 5-year monitoring program that has been in place since reconstruction, several generalizations may be made concerning the degree of success of the marsh reconstruction. Water quality in the marsh system and nearby tidal waters has not been noticeably improved. The poor quality may be clue to the overwhelmingly high loads (e.g., sediment, nutrients, etc.) brought in on the twice daily tidal cycle from the Anacostia and to the relatively small volume of water which actually interacts with the emergent marsh

  16. What Constitutes Success in Pacific Island Community Conserved Areas?

    Directory of Open Access Journals (Sweden)

    Joanna C. Axford

    2008-12-01

    Full Text Available In recent years, few if any community conserved areas (CCAs in the Pacific island region have been regarded as being successful. However, as success is rarely defined, what constitutes "success" is not clear. This paper reports an investigation into the way "outsiders" perceive success in Pacific island CCAs. An exploratory survey revealed six umbrella themes of success: the locus of control; local benefits; resource aspects; management; external stakeholder involvement; and sustainability. Multivariate analysis distinguished two groups, a Big picture group and a Locally focused group. These differ in how they define success, as well as their organizational alignment. The Big picture group, largely from funder agencies and international NGOs, were focused on the broad issues of success, especially the sustainability of CCAs. The Locally focused group was concerned with the practical workings and needs of successful CCAs in the Pacific; many in this group were based with Pacific island governments and NGOs or CCAs. The study concludes that success in CCAs should not be defined solely on project objectives, especially when these have been developed by an external entity or under their guidance. If they are, high rates of failure are to be expected.

  17. Success Factor of Woody Biomass Supply Chains in Japan

    OpenAIRE

    Ahl, Amanda; Eklund, Johanna

    2016-01-01

    There is an abundance of forest in Japan, yet a lack of utilization of woody biomass in energy systems. Small-scale woody biomass can enable a supply chain based on domestic forest integrated with local industry and demands, in turn facilitating local vitalization. Successful creation of collective energy systems is strongly connected to supply chain design based on local conditions and stakeholder integration. A supply chain perspective is key in enabling woody biomass energy systems. In the...

  18. Success and adaptation

    CERN Multimedia

    2013-01-01

    Yesterday morning, the last colliding proton beams of 2013 were extracted from the LHC, heralding the start of the machine’s first long shutdown (LS1) and crowning its first three glorious years of running. I hardly need to tell the CERN community what a fabulous performance all the people running the machine, the experiments, the computing and all supporting infrastructures put in. Those people are you, and you all know very well what a great job everyone did.   Nevertheless, I would like to express my thanks to all the people who made this first LHC run such a success. Re-measuring the whole Standard Model in such a short period, and then completing it with the discovery of what looks increasingly like the Higgs boson, is no mean feat. What I’d like to focus on today is another aspect of our field: its remarkable ability to adapt. When I started out in research, experiments involved a handful of people and lasted a few years at most. The timescale for the development of ...

  19. Assessing call centers’ success:

    Directory of Open Access Journals (Sweden)

    Hesham A. Baraka

    2013-07-01

    This paper introduces a model to evaluate the performance of call centers based on the Delone and McLean Information Systems success model. A number of indicators are identified to track the call center’s performance. Mapping of the proposed indicators to the six dimensions of the D&M model is presented. A Weighted Call Center Performance Index is proposed to assess the call center performance; the index is used to analyze the effect of the identified indicators. Policy-Weighted approach was used to assume the weights with an analysis of different weights for each dimension. The analysis of the different weights cases gave priority to the User satisfaction and net Benefits dimension as the two outcomes from the system. For the input dimensions, higher priority was given to the system quality and the service quality dimension. Call centers decision makers can use the tool to tune the different weights in order to reach the objectives set by the organization. Multiple linear regression analysis was used in order to provide a linear formula for the User Satisfaction dimension and the Net Benefits dimension in order to be able to forecast the values for these two dimensions as function of the other dimensions

  20. Local Warming

    CERN Document Server

    Vanderbei, Robert J

    2012-01-01

    Using 55 years of daily average temperatures from a local weather station, I made a least-absolute-deviations (LAD) regression model that accounts for three effects: seasonal variations, the 11-year solar cycle, and a linear trend. The model was formulated as a linear programming problem and solved using widely available optimization software. The solution indicates that temperatures have gone up by about 2 degrees Fahrenheit over the 55 years covered by the data. It also correctly identifies the known phase of the solar cycle; i.e., the date of the last solar minimum. It turns out that the maximum slope of the solar cycle sinusoid in the regression model is about the same size as the slope produced by the linear trend. The fact that the solar cycle was correctly extracted by the model is a strong indicator that effects of this size, in particular the slope of the linear trend, can be accurately determined from the 55 years of data analyzed. The main purpose for doing this analysis is to demonstrate that it i...

  1. Rehydrate locally.

    Science.gov (United States)

    Djokoto, E

    1997-11-01

    In 1991, in the northern region of Ghana, during the cholera epidemic, 10 rural health centers replied to a questionnaire regarding cholera case referrals. The results were as follows: 6 centers referred serious cases to hospitals, 2 did not receive patients because of fear of infection, and 2 received all patients. Although no patients admitted to the rural health centers died, many of the referred patients did. Of 14 cases referred to a hospital, 3 died in transit, 4 died at the hospital, and 7 survived. Deaths might be prevented if patients were treated promptly and locally with oral rehydration solutions based on cereals and rice; these are easy to prepare, superior to, and more available than standard oral rehydration salts (ORS). One mother walked 5 miles to a rural health post with her sick baby on her back, only to find that the dehydrated child had died on the way. During the 1991 cholera epidemic in Ghana, the author treated several patients in their homes; all recovered. Prompt and frequent rehydration in the home is the best treatment for diarrhea and cholera.

  2. Verbal Behavior and Courtroom Success.

    Science.gov (United States)

    Parkinson, Michael G.

    1981-01-01

    Identifies characteristics of successful courtroom speech for prosecuting attorneys, defense attorneys, and accuseds using computer-based content analysis and rater judgments of verbal behaviors. Demonstrates that verbal aggression is an important factor for successful prosecutors, equivocation is important to success for defense attorneys, and…

  3. Organisation of a local revision course for postgraduate examinations.

    Science.gov (United States)

    Sharif, K; Weaver, J; Afnan, M; Newton, J

    Revision courses for postgraduate examinations are usually held at central teaching hospitals. The ingredients for these courses, however, are available at most local hospitals. This article describes the practicalities of organising a successful local revision course for postgraduate examinations.

  4. The Role of Local Leaders in Community Development Programmes ...

    African Journals Online (AJOL)

    The Role of Local Leaders in Community Development Programmes in Ideato Local Government ... (= 3.80); monitoring and evaluation of projects (= 3.78); and fund raising for projects (= 3.76). ... It was concluded that for sustained success to

  5. Quantum Locality?

    Energy Technology Data Exchange (ETDEWEB)

    Stapp, Henry

    2011-11-10

    vagaries that he cites do not upset the proof in question. It is show here in detail why the precise statement of this theorem justifies the specified application of CQT. It is also shown, in response to his challenge, why a putative proof of locality that he has proposed is not valid.

  6. Decentralization Policy and Effectiveness of Local Government Organization in Indonesia

    OpenAIRE

    Abdullah, Muh. Tang

    2014-01-01

    In the era of decentralization policy implementation, the local bureaucracy (Indonesian: Organisasi Perangkat Daerah) has strategic position in the local government system. It is so as the instruments and the fundamental base of the local government in implementing its affairs and as the media to realize the vision, mission, and the objectives of local government. The successful of local government is determined by the effectiveness of the local bureaucracy. This study aims to examine the eff...

  7. Predicting gram-positive bacterial protein subcellular localization based on localization motifs.

    Science.gov (United States)

    Hu, Yinxia; Li, Tonghua; Sun, Jiangming; Tang, Shengnan; Xiong, Wenwei; Li, Dapeng; Chen, Guanyan; Cong, Peisheng

    2012-09-07

    The subcellular localization of proteins is closely related to their functions. In this work, we propose a novel approach based on localization motifs to improve the accuracy of predicting subcellular localization of Gram-positive bacterial proteins. Our approach performed well on a five-fold cross validation with an overall success rate of 89.5%. Besides, the overall success rate of an independent testing dataset was 97.7%. Moreover, our approach was tested using a new experimentally-determined set of Gram-positive bacteria proteins and achieved an overall success rate of 96.3%.

  8. Measurement of the profiles of disorder-induced localized resonances by local tuning

    CERN Document Server

    Lian, J; Yüce, E; Combrié, S; De Rossi, A; Mosk, A P; .,

    2016-01-01

    Near the band edge of photonic crystal waveguides, localized modes appear due to disorder. We demonstrate a new method to elucidate spatial profile of the localized modes in such systems using precise local tuning. Using deconvolution with the known thermal profile, the spatial profile of a localized mode with quality factor ($Q$) $>10^5$ is successfully reconstructed with a resolution of $2.5 \\ \\mu $m.

  9. Measurement of global and local resonance terms

    CERN Document Server

    Tomás, R; Calaga, R; Fischer, W; Franchi, A; Rumolo, Giovanni

    2005-01-01

    Recently, resonance driving terms were successfully measured in the CERN SPS and the BNL RHIC from the Fourier spectrum of beam position monitor (BPM) data. Based on these measurements a new analysis has been derived to extract truly local observables from BPM data. These local observables are called local resonance terms since they share some similarities with the global resonance terms. In this paper we derive these local terms analytically and present experimental measurements of sextupolar global and local resonance terms in RHIC. Nondestructive measurements of these terms using ac dipoles are also presented.

  10. Cinacalcet lowering of serum fibroblast growth factor-23 concentration may be independent from serum Ca, P, PTH and dose of active vitamin D in peritoneal dialysis patients: a randomized controlled study

    Science.gov (United States)

    2013-01-01

    Background Elevated serum level of fibroblast growth factor-23 (FGF23) is associated with adverse outcomes in dialyzed patients. Objectives The CUPID study compared the efficacy of a cinacalcet-based regimen with conventional care (vitamin D and P binders) for achieving the stringent NKF-K/DOQI targets for peritoneal dialysis (PD) patients. Additionally, we analyzed change in FGF23 levels between two treatments to explore the cinacalcet effect in lowering FGF23. Design Multicenter, open-labeled, randomized controlled study. Setting Seven university-affiliated hospitals in Korea. Participants Overall, 66 peritoneal dialysis patients were enrolled. Intervention Sixty six patients were randomly assigned to treatment with either cinacalcet + oral vitamin D (cinacalcet group, n = 33) or oral vitamin D alone (control group, n = 33) to achieve K/DOQI targets. CUPID included a 4-week screening for vitamin D washout, a 12-week dose-titration, and a 4-week assessment phases. We calculated mean values of iPTH, Ca, P, Ca x P, during assessment phase and final FGF23 to assess the outcome. Main outcome measures Achievement of >30% reduction of iPTH from baseline (primary) and FGF23 reduction (secondary). Results 72.7% (n = 24) of the cinacalcet group and 93.9% (n = 31) of the control group completed the study. Cinacalcet group received 30.2 ± 18.0 mg/day of cinacalcet and 0.13 ± 0.32 μg/d oral vitamin D (P < 0.001 vs. control with 0.27 ± 0.18 μg/d vitamin D). The proportion of patients who reached the primary endpoint was not statistically different (48.5% vs. 51.5%, cinacalcet vs. control, P = 1.000). After treatment, cinacalcet group experienced a significant reduction in FGF23 levels (median value from 3,960 to 2,325 RU/ml, P = 0.002), while an insignificant change was shown for control group (from 2,085 to 2,415 RU/ml). The percent change of FGF23 after treatment was also significantly different between the two groups (− 42.54% vs. 15.83%, P = 0.008). After adjustment

  11. Building Successful Information Systems – a Key for Successful Organization

    Directory of Open Access Journals (Sweden)

    Doina ROSCA

    2010-12-01

    Full Text Available Building Successful Information Systems – a Key for Successful OrganizationAbstract: An Information System (IS can have a major impact on corporate strategy and organizational success. The involvement of managers and decision makers in all aspects of information systems is a major factor for organizational success, including higher profits and lower costs. Some of the benefits business organization seek to achieve through information systems include: better safety, competitive advantage, fewer errors, greater accuracy, higher quality products, improved communications, increased efficiency and productivity, more efficient administration, superior financial and managerial decision making.

  12. Successful overwintering of Aedes albopictus in Germany.

    Science.gov (United States)

    Pluskota, Björn; Jöst, Artur; Augsten, Xenia; Stelzner, Lilith; Ferstl, Ina; Becker, Norbert

    2016-08-01

    The Asian tiger mosquito (Aedes albopictus) is of great concern to public health authorities due to its vector competence and rapid spread across the globe. In 2015, two large local breeding populations of Ae. albopictus were discovered in southwest Germany. In spring 2016, we were able to demonstrate the first evidence of a successful overwintering in Germany of this originally tropical mosquito species in different research projects. Particularly noteworthy is the successful hatching of diapause eggs of an Italian strain (Calabria), which overwintered successfully in the field in St. Georgen im Schwarzwald (Baden-Wuerttemberg) at 820 m above sea level. Furthermore, within the scope of a larvae monitoring, the first larvae that hatched in the field were detected on the April 09, 2016 in a rain barrel within the Heidelberg population. Our first results show that self-extinction due to an unsuccessful overwintering cannot be assumed for populations of the Asian tiger mosquito which settled in Germany in previous years. The evidence of a successful overwintering of a large number of diapause eggs and the hatching of the first larvae in field conditions opens the control year against Ae. albopictus in southwest Germany.

  13. A Bell inequality with local violation

    CERN Document Server

    Cabello, Adan

    2009-01-01

    We introduce a Bell-like inequality for testing the Kochen-Specker with locality theorem and the free will theorem. Remarkably, quantum mechanics violates this inequality even though the quantum correlations between the distant systems admit a local description. The violation is due to the correlations between successive compatible measurements on one of the local systems. The violation is robust against imperfections, and can be observed in actual experiments.

  14. Successful learning in the global economy?

    DEFF Research Database (Denmark)

    Lehmann, Sanne

    2012-01-01

    of knowledge upgrading in local firms. The article concludes that neither embeddedness in local networks nor linkages with transnational corporations are sufficient for Thai firms to upgrade their knowledge base to become successful actors in the global economy. Instead it points to the importance of focusing...... more on the capacity to learn and apply new knowledge to the existing knowledge base and on the barriers to diffusion and further development of knowledge embedded in the pre–existing organisational practices of firms.......This article aims to subject some of the hypotheses concerning the potential of knowledge upgrading for firms engaged in various vertical and horizontal networks to a critical examination. The theories are applied to a Thai context and use the case of the auto parts industry to evaluate the process...

  15. Successful cinacalcet treatment of refractory secondary hyperparathyroidism due to multiple lung parathyroid adenomas

    Science.gov (United States)

    Sugi, Orie; Kimata, Naoki; Miwa, Naoko; Otsubo, Shigeru; Nitta, Kosaku; Akiba, Takashi

    2010-01-01

    We describe a 56-year-old woman who presented with end-stage renal disease due to pregnancy-induced hypertension and secondary hyperparathyroidism (sHPT). She had started hemodialysis and underwent a subtotal parathyroidectomy (PTx). However, intact parathyroid hormone (iPTH) levels increased gradually. Eventually, she underwent a second PTx. However, therapy failed to significantly decrease iPTH levels. A third PTx was performed, but no pathological parathyroid tissue was found. Computed tomography scan indicated the presence of multiple ectopic lung nodules and 26 nodules were surgically removed from the left lung. Despite surgical treatment, iPTH levels remained high. Additional maxacalcitol failed to decrease iPTH levels, cinacalcet was then started. iPTH levels decreased and the cinacalcet dose could be reduced to maintenance doses of 60 mg/day. Throughout the 1.6 years of treatment, serum iPTH, alkaline phosphatase (ALP) and bone alkaline phosphatase (BAP) were normalized. As a consequence, bone pain gradually disappeared. Bone mineral density (BMD) was improved by administration of cinacalcet. In conclusion, cinacalcet was effective in this patient with refractory and inoperable sHPT. In addition, it improves their BMD and relieves bone pain. PMID:25984040

  16. Defining and Measuring Academic Success

    Directory of Open Access Journals (Sweden)

    Travis T. York

    2015-03-01

    Full Text Available Despite, and perhaps because of its amorphous nature, the term - academic success' is one of the most widely used constructs in educational research and assessment within higher education. This paper conducts an analytic literature review to examine the use and operationalization of the term in multiple academic fields. Dominant definitions of the term are conceptually evaluated using Astin's I-E-O model resulting in the proposition of a revised definition and new conceptual model of academic success. Measurements of academic success found throughout the literature are presented in accordance with the presented model of academic success. These measurements are provided with details in a user-friendly table (Appendix B. Results also indicate that grades and GPA are the most commonly used measure of academic success. Finally, recommendations are given for future research and practice to increase effective assessment of academic success.

  17. Recurrent pancreatitis in a patient with familial hypocalciuric hypercalcaemia treated successfully with cinacalcet

    Science.gov (United States)

    Grossman, Ashley; Druce, Maralyn

    2014-01-01

    Summary A 22-year-old female student presented with a history of recurrent pancreatitis. The commonest causes of pancreatitis, including drugs, gallstones, corticosteroids, excess alcohol and hypertriglyceridaemia, were excluded. She was found to have an elevated serum calcium level that was considered to be the cause of her pancreatitis, with a detectable serum parathyroid hormone (PTH). An initial diagnosis of primary hyperparathyroidism was made. However, two neck explorations failed to reveal a parathyroid adenoma. She was referred to our unit three years later as her episodes of pancreatitis were becoming more frequent and her calcium level remained persistently elevated. Her investigations were as follows: elevated adjusted calcium level of 2.79 mmol/l (2.2–2.58), PTH level of 4.2 pmol/l (0.6–6.0), low 24 h urine calcium of 0.3 mmol/l and a urine calcium:creatinine ratio of A mutation in the calcium-sensing receptor gene. Although the hypercalcaemia of FHH is usually without sequelae due to the generalised changes in calcium sensing, in the presence of this complication she was started on cinacalcet 30 mg daily. She had one further episode of pancreatitis with calcium levels ranging between 2.53 and 2.66 mmol/l. Her cinacalcet was gradually increased to 30 mg three times daily, maintaining her calcium levels in the range of 2.15–2.20 mmol/l. She has not had a further episode of pancreatitis for more than 2 years. FHH is usually a benign condition with minimal complications from hypercalcaemia. Pancreatitis has been reported rarely, and no clear management strategy has been defined in these cases. Cinacalcet was successfully used in treating recurrent pancreatitis in a patient with FHH by maintaining calcium levels in the lower part of the reference range. Whether or not this is an effective long-term treatment remains yet to be seen. Learning points FHH is an important differential diagnosis for hypercalcaemia.FHH can rarely cause

  18. Successful cognitive and emotional aging

    OpenAIRE

    Jeste, Dilip V.; Depp, Colin A.; Vahia, Ipsit V.

    2010-01-01

    We review the definitions, determinants, and ways of enhancing successful cognitive and emotional aging. Objective definitions of successful aging based on physical health emphasize outcomes including freedom from disability and disease, whereas subjective definitions center on well-being, social connectedness, and adaptation. Most older people do not meet objective criteria for successful aging, while a majority meet the subjective criteria. Older people with severe mental ...

  19. Succession planning and individual development.

    Science.gov (United States)

    Goudreau, Kelly A; Hardy, Jacalyn

    2006-06-01

    The authors present a framework for a succession planning and individual development initiative implemented in a Veterans Health Administration facility. Foundational strategic goals and a conceptual framework in the Veterans Affairs system provide the structure for the 3 facility-level succession planning and individual development programs. Outcomes of the programs are promising with 2 of 3 programs demonstrating clear succession planning outcomes and the other one showing positive preliminary results.

  20. SUCCESS@Seneca: Facilitating Student and Staff Success

    Science.gov (United States)

    Fishman, Steve; Decandia, Lisa

    2006-01-01

    SUCCESS@Seneca has teamed up with the General Arts and Science programs at Seneca's Newnham campus. The design of an integrated service delivery model addresses numerous student success and retention related activities by providing the essential connection between academics and college resources. The program focuses on the promotion and support of…

  1. Evolution, Appearance, and Occupational Success

    National Research Council Canada - National Science Library

    Little, Anthony C; Roberts, S. Craig

    2012-01-01

    .... In this article, we review evidence linking physical appearance to occupational success and evaluate the hypothesis that appearance based biases are consistent with predictions based on evolutionary...

  2. Preparation of polythiophene conductive composite membrane by gas-phase polymerization%原位气相聚合法合成制备PTh/PVDF导电复合膜的研究

    Institute of Scientific and Technical Information of China (English)

    李泽全; 杜军; 范兴; 陶长元

    2004-01-01

    在低温低压条件下,以FeCl3为氧化剂,通过原位气相聚合法合成制备PTh(聚噻吩)/PVDF(聚偏氟乙烯)导电复合膜,探讨了制备条件对复合膜性能的影响.ATR-IR光谱测试结果证实,该复合膜的光谱图中出现了聚噻吩的特征吸收峰.扫描电镜观察表明,该复合膜的表观形貌随聚合进行而逐步变化.四探针法测试结果显示,该复合膜的电导率为0.1~1.0S·cm-1.滤速法测定结果说明,该复合膜的平均孔径随聚合反应时间增加而逐渐减小.

  3. PATH TO PERSONAL AND ORGANIZATIONAL BUSINESS SUCCESS

    Directory of Open Access Journals (Sweden)

    Ljiljana Stošić Mihajlović

    2014-07-01

    Full Text Available Success is not a precise term and people have different definitions of success. The first step towards achieving personal success is to decide what it represents to each of us. No matter which version of success is accepted as notoriously, people who want to get to the top you should find out as much detail as possible about the behavior of large and important individuals who have achieved their dream . Neither success nor a business, does not come overnight. The main recommendation is to at least try to be good with more people. One of the processes by which people influence the emotions of others is an emotional "contagion". It is the process by which feeling, facial expressions and behavior of a person transferred to another person or even a group of people . When a person expresses a particular emotion, nonverbal reactions of those around her begin to automatically mimic, mirror image, her facial expressions, body language and tone of voice. For example, when we close colleague cheerfully recounts how he got a raise, it is very likely that we will unconsciously begin smile , take a more open body posture and talk louder. The muscles of the brain to signal our facial expression and posture so that we will soon have to begin to experience the same emotion. But this “transfer" occurs in the case of negative emotions The success of the company is determined by its organizational structure and opportunities in the region. Management measures management company regulated by its organizational structure, but it can not influence the situation in the region. Therefore, the company must adapt to the conditions prevailing in their environment. Organizational Behavior companies is a way to adapt to changes in its environment, and the establishment of interpersonal relationships in its structure. The essence of modern relationships in organizations is based on teamwork, and that means almost perfect functioning of the entire system of business

  4. Succession Planning for Library Instruction

    Science.gov (United States)

    Sobel, Karen; Drewry, Josiah

    2015-01-01

    Detailed succession planning helps libraries pass information from one employee to the next. This is crucial in preparing for hiring, turnover, retirements, training of graduate teaching assistants in academic libraries, and other common situations. The authors of this article discuss succession planning for instruction programs in academic…

  5. RE 05: engineering successful products

    NARCIS (Netherlands)

    Atlee, Joanne M.; Wieringa, Roel J.

    2006-01-01

    At the Requirements Engineering conference series, researchers and practitioners exchange experiences, discuss problems, and propose solutions. The theme of RE 05--Engineering Successful Products--reflects the understanding that high-quality requirements are at the heart of successful products. To b

  6. Succession Planning for Library Instruction

    Science.gov (United States)

    Sobel, Karen; Drewry, Josiah

    2015-01-01

    Detailed succession planning helps libraries pass information from one employee to the next. This is crucial in preparing for hiring, turnover, retirements, training of graduate teaching assistants in academic libraries, and other common situations. The authors of this article discuss succession planning for instruction programs in academic…

  7. Succession planning: securing the future.

    Science.gov (United States)

    Bolton, Julia; Roy, Wendy

    2004-12-01

    Succession planning is an essential business strategy for healthcare organizations, given the impending retirement of the huge Baby Boomer cohort of experienced nurses. It ensures that there will be qualified candidates when key vacancies occur. The authors describe the critical elements of a succession plan and suggest ways to implement them. The model can be applied to leadership and clinical positions.

  8. Success Analysis for School Administrators.

    Science.gov (United States)

    Carranza, Elihu

    The success analysis approach consists of individual and group exercises through which participants, in sharing meaning-centered experiences, identify their strengths and needs and clarify values operative in both past and expected successes. This approach constitutes a rational and practical perspective whereby students, teachers, staff, and…

  9. Success and Women's Career Adjustment.

    Science.gov (United States)

    Russell, Joyce E. A.; Burgess, Jennifer R. D.

    1998-01-01

    Women still face barriers to career success and satisfaction: stereotypes, assumptions, organizational culture, human resource practices, and lack of opportunities. Despite individual and organizational strategies, many women leave to become entrepreneurs. There is a need to investigate how women define career success. (SK)

  10. Success Analysis for School Administrators.

    Science.gov (United States)

    Carranza, Elihu

    The success analysis approach consists of individual and group exercises through which participants, in sharing meaning-centered experiences, identify their strengths and needs and clarify values operative in both past and expected successes. This approach constitutes a rational and practical perspective whereby students, teachers, staff, and…

  11. Decentralisation in developing countries: preconditions for successful implementation

    Directory of Open Access Journals (Sweden)

    Yasin Olum

    2014-07-01

    Full Text Available Decentralisation has been implemented and is being implemented in many developing countries without much success. Although several unique factors inhibit the implementation of decentralisation in individual countries, the paper argues that there are six pre-conditions that these countries should fulfill before decentralisation can be successfully implemented. These preconditions are: institutional mechanisms; creation of spaces for participation; political will and civil will; capacity development at the local level; careful implementation; and democratic governance.

  12. Severe hypocalcemia secondary to hypomagnesaemia, successfully treated by self-administered subcutaneous magnesium Hipocalcemia severa, secundaria a hipomagnesemia, tratada con éxito mediante auto-administración subcutánea de magnesio

    Directory of Open Access Journals (Sweden)

    J. J. Alfaro Martínez

    2009-06-01

    Full Text Available We report the case of a patient with recurrent severe hypocalcemia, secondary to hypomagnesaemia, and prerenal renal failure, due to ileostomy losses after a colectomy, who needed several admissions to the hospital through more than one year. Finally, he was successfully treated by self-administered subcutaneous magnesium: he reached and maintained normal levels of serum calcium, magnesium and PTH, no more hospital admission were needed and he resumed a normal life.Se trata de un paciente con hipocalcemia severa recurrente, secundaria a hipomagensemia, y fracaso renal agudo prerrenal secundario a perdidas digestivas a través de una ileostomía, tras una colectomía. Por este motivo necesitó varios ingresos hospitalarios a lo largo de más de un año. Finalmente fue tratado con éxito mediante autoadministración subcutánea de magnesio. Con este tratamiento mantuvo niveles nornmales de calcio, magnesio y PTH, no requirió más ingresos hospitalarios y recuperó una vida normal.

  13. SUCCESSION MANAGEMENT: UPAYA HUMAN RESOURCE PLANNING MENUJU SUCCESS CORPORATE

    Directory of Open Access Journals (Sweden)

    Rini Kuswati

    2010-06-01

    create a more flexible and dynamic approach for preparing future executive and have the leadership necessary ready to meet the business challenges of the remainder of the decade and beyond. Succession management allows the corporate leadership to instill a more dynamic process became easier to integrate with the firm’s strategic initiatives. It better aligns organizational thinking with the external environment where the discontinuities make it possible to anticipate the full spectrum of change that a corporation will confront. It is the leadership and succession philosophy that focuses on developing the creativity and flexibility that allows for a more rapid response to change. So succession management as one way to became the success corporate.

  14. Successful adaptation strategies according expatriates

    NARCIS (Netherlands)

    van Oudenhoven, JP; van der Zee, KI; van Kooten, M

    2001-01-01

    The present study examined which personal characteristics underlie four types of allegiances that expatriates may have to the parent firm and the local firm. The four types are free agents: low allegiance to either firm; going native expatriates: high allegiance to the local firm and a low

  15. Successful adaptation strategies according expatriates

    NARCIS (Netherlands)

    van Oudenhoven, JP; van der Zee, KI; van Kooten, M

    2001-01-01

    The present study examined which personal characteristics underlie four types of allegiances that expatriates may have to the parent firm and the local firm. The four types are free agents: low allegiance to either firm; going native expatriates: high allegiance to the local firm and a low allegianc

  16. Local Duality for 2-Dimensional Local Ring

    Indian Academy of Sciences (India)

    Belgacem Draouil

    2008-11-01

    We prove a local duality for some schemes associated to a 2-dimensional complete local ring whose residue field is an -dimensional local field in the sense of Kato–Parshin. Our results generalize the Saito works in the case =0 and are applied to study the Bloch–Ogus complex for such rings in various cases.

  17. Succession Planning in Australian Farming

    Directory of Open Access Journals (Sweden)

    John Hicks

    2012-11-01

    Full Text Available The theme of this paper is that succession planning in Australian farming is under-developed.It may be linked to economic and social change which suggests that farmers need to adapt togenerational change but this is being resisted or ignored. The implications of this are the slowdecline of family farming, a poor transfer of skills and knowledge to subsequent generationsof farmers in some parts of the agricultural sector and the potential for an extension of thefinancial services industry to develop a more effective raft of succession planning measuresto mitigate the effects of a traditional approach to succession in agriculture.

  18. Predicting Success in Elementary Algebra

    Science.gov (United States)

    Mogull, R. G.; Rosengarten, W., Jr.

    1974-01-01

    The purpose of this study was to develop a device for predicting student success in a high school Elementary Algebra course. It was intended to assist guidance counselors in advising students in selecting the most appropriate mathematics course. (Editor)

  19. Leadership for Successful School Desegregation.

    Science.gov (United States)

    Sommerville, Joseph C.

    1980-01-01

    A review of the literature and questionnaire responses shows that superintendents who successfully meet the challenge of school desegregation assess the situation of each school, provide for communication, focus on potential student benefits, and demonstrate personal commitment. (Author/MLF)

  20. Human capital and career success

    DEFF Research Database (Denmark)

    Frederiksen, Anders; Kato, Takao

    Denmark’s registry data provide accurate and complete career history data along with detailed personal characteristics (e.g., education, gender, work experience, tenure and others) for the population of Danish workers longitudinally. By using such data from 1992 to 2002, we provide rigorous...... evidence for the first time for the population of workers in an entire economy (as opposed to case study evidence) on the effects of the nature and scope of human capital on career success (measured by appointments to top management). First, we confirm the beneficial effect of acquiring general human...... capital formally through schooling for career success, as well as the gender gap in career success rates. Second, broadening the scope of human capital by experiencing various occupations (becoming a generalist) is found to be advantageous for career success. Third, initial human capital earned through...

  1. Success Factors of PLM Projects

    Institute of Scientific and Technical Information of China (English)

    谭月梅; 李莉敏; 胡庆夕; 方明伦

    2004-01-01

    Product Lifecycle Management (PLM) is a business strategy beginning to gain wide acceptance. Concerning the implementation of PLM projects, six success factors are presented and analyzed in details in this paper.

  2. The neurobiology of successful abstinence.

    Science.gov (United States)

    Garavan, H; Brennan, K L; Hester, R; Whelan, R

    2013-08-01

    This review focuses on the neurobiological processes involved in achieving successful abstinence from drugs of abuse. While there is clinical and public health value in knowing if the deficits associated with drug use correct with abstinence, studying the neurobiology that underlies successful abstinence can also illuminate the processes that enable drug-dependent individuals to successfully quit. Here, we review studies on human addicts that assess the neurobiological changes that arise with abstinence and the neurobiological predictors of successfully avoiding relapse. The literature, while modest in size, suggests that abstinence is associated with improvement in prefrontal structure and function, which may underscore the importance of prefrontally mediated cognitive control processes in avoiding relapse. Given the implication that the prefrontal cortex may be an important target for therapeutic interventions, we also review evidence indicating the efficacy of cognitive control training for abstinence.

  3. Success Teaching Spelling with Music.

    Science.gov (United States)

    Martin, Mariellen

    1983-01-01

    A spelling approach which incorporates music on a cassette with spelling, pronunciation, and definition of specific words was successful in improving junior high learning disabled students' spelling performance, self-esteem, and sequential memories. (CL)

  4. The characteristics of successful entrepreneurs

    National Research Council Canada - National Science Library

    Pokrajcic, Dragana

    2004-01-01

    .... The psychological characteristic theory of entrepreneur argues that successful entrepreneurs possess certain personality traits that mark them out as special, and tries to determine and to evaluate these special traits...

  5. Success Teaching Spelling with Music.

    Science.gov (United States)

    Martin, Mariellen

    1983-01-01

    A spelling approach which incorporates music on a cassette with spelling, pronunciation, and definition of specific words was successful in improving junior high learning disabled students' spelling performance, self-esteem, and sequential memories. (CL)

  6. Organizational Climate for Successful Aging.

    Science.gov (United States)

    Zacher, Hannes; Yang, Jie

    2016-01-01

    Research on successful aging at work has neglected contextual resources such as organizational climate, which refers to employees' shared perceptions of their work environment. We introduce the construct of organizational climate for successful aging (OCSA) and examine it as a buffer of the negative relationship between employee age and focus on opportunities (i.e., beliefs about future goals and possibilities at work). Moreover, we expected that focus on opportunities, in turn, positively predicts job satisfaction, organizational commitment, and motivation to continue working after official retirement age. Data came from 649 employees working in 120 companies (M age = 44 years, SD = 13). We controlled for organizational tenure, psychological climate for successful aging (i.e., individuals' perceptions), and psychological and organizational age discrimination climate. Results of multilevel analyses supported our hypotheses. Overall, our findings suggest that OCSA is an important contextual resource for successful aging at work.

  7. Building a Successful Technology Cluster

    Science.gov (United States)

    Silicon Valley is the iconic cluster—a dense regional network of companies, universities, research institutions, and other stakeholders involved in a single industry. Many regions have sought to replicate the success of Silicon Valley, which has produced technological innov...

  8. Biosphere reserves: Attributes for success.

    Science.gov (United States)

    Van Cuong, Chu; Dart, Peter; Hockings, Marc

    2017-03-01

    Biosphere reserves established under the UNESCO Man and the Biosphere Program aim to harmonise biodiversity conservation and sustainable development. Concerns over the extent to which the reserve network was living up to this ideal led to the development of a new strategy in 1995 (the Seville Strategy) to enhance the operation of the network of reserves. An evaluation of effectiveness of management of the biosphere reserve network was called for as part of this strategy. Expert opinion was assembled through a Delphi Process to identify successful and less successful reserves and investigate common factors influencing success or failure. Ninety biosphere reserves including sixty successful and thirty less successful reserves in 42 countries across all five Man and the Biosphere Program regions were identified. Most successful sites are the post-Seville generation while the majority of unsuccessful sites are pre-Seville that are managed as national parks and have not been amended to conform to the characteristics that are meant to define a biosphere reserve. Stakeholder participation and collaboration, governance, finance and resources, management, and awareness and communication are the most influential factors in the success or failure of the biosphere reserves. For success, the biosphere reserve concept needs to be clearly understood and applied through landscape zoning. Designated reserves then need a management system with inclusive good governance, strong participation and collaboration, adequate finance and human resource allocation and stable and responsible management and implementation. All rather obvious but it is difficult to achieve without commitment to the biosphere reserve concept by the governance authorities. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Enterprise architecture for business success

    CERN Document Server

    Wijegunaratne, Inji; Evans-Greenwood, Peter

    2014-01-01

    Enterprise Architecture (EA) has evolved to become a prominent presence in today's information systems and technology landscape. The EA discipline is rich in frameworks, methodologies, and the like. However, the question of 'value' for business ;professionals remains largely unanswered - that is, how best can Enterprise Architecture and Enterprise Architects deliver value to the enterprise? Enterprise Architecture for Business Success answers this question. Enterprise Architecture for Business Success is primarily intended for IT professionals working in the area of Enterprise Architectu

  10. Geometry success in 20 mins

    CERN Document Server

    Editors, LearningExpress

    2010-01-01

    Whether you're new to geometry or just looking for a refresher, this completely revised and updated third edition of Geometry Success in 20 Minutes a Day offers a 20-step lesson plan that provides quick and thorough instruction in practical, critical skills. Stripped of unnecessary math jargon but bursting with geometry essentials, Geometry Success in 20 Minutes a Day is an invaluable resource for both students and adults.

  11. Pollination success of Lotus corniculatus (L.) in an urban context

    Science.gov (United States)

    Pellissier, Vincent; Muratet, Audrey; Verfaillie, Fabien; Machon, Nathalie

    2012-02-01

    Most anthropogenic activities are known to have deleterious effects on pollinator communities. However, little is known about the influence of urbanization on pollination ecosystem services. Here, we assessed the pollination service on Lotus corniculatus (L.), a self-sterile, strictly entogamous Fabaceae commonly observed in urban and suburban areas. We assessed the pollination success of artificial Lotus corniculatus populations at three levels: at large scale, along an urbanization gradient; at intermediate scale, based on landscape fragmentation within a 250 m radius and at local scale based on floral resource abundance and local habitat type. The main findings were that the pollination success, when assessed with the number of fruit produced per inflorescence, was lower in urban areas than in suburban ones, and was negatively affected by the number of impervious spaces in the neighborhood. The relationship between the number of fruits and the distance to the nearest impervious space was either positive or negative, depending on the gray/green ratio (low vs. high). Finally, on a local scale, floral resource abundance had a negative effect on pollination success when L. corniculatus populations were located in paved courtyards, and a positive one when they were located in parks. Pollination success seems to be explained by two intertwined gradients: landscape fragmentation estimated by the number of impervious spaces in a 250 m radius around L. corniculatus populations, and the behavior of bumblebees toward birdsfoot trefoil and floral displays, which appears to differ depending on whether a neighborhood is densely or sparsely urbanized. An abundance of attracting floral resources seems to enhance pollination success for L. corniculatus if it is not too isolated from other green spaces. These results have important implications for the sustainability of pollination success in towns by identifying local and landscape factors that influence reproductive success of

  12. The characteristics of successful entrepreneurs

    Directory of Open Access Journals (Sweden)

    Pokrajčić Dragana M.

    2004-01-01

    Full Text Available This paper examines the economic, psychological and social-behavioral theories of the entrepreneur in order to determine the characteristics of a successful entrepreneur. The major contribution of economic theories of the entrepreneur is better understanding of the entrepreneur and his/her role in economic development. The psychological characteristic theory of entrepreneur argues that successful entrepreneurs possess certain personality traits that mark them out as special, and tries to determine and to evaluate these special traits. The social-behavioral theories stress the influence of experience, knowledge, social environment and ability to learn on the entrepreneur’s success as well as his/her personality traits. Neither of the examined theories of entrepreneur gives a satisfactory explanation of the entrepreneur’s success, but taken as a whole, they can explain key factors of entrepreneur’s success. The entrepreneur’s success comes about as a result of his/her personality traits, ability to learn from experience and ability to adjust to his/her environment.

  13. Expression of PTHrP and PTHR (PTH/PTHrP-r) mRNAs and polypeptides in bovine ovary and stimulation of bovine blastocyst development in vitro following PTHrP treatment during oocyte maturation.

    Science.gov (United States)

    Watson, P H; Westhusin, M E; Watson, A J

    2001-03-01

    Parathyroid hormone related protein (PTHrP) and its receptor have well-established roles in the development and regulation of many tissues, including bone and mammary gland. The objectives of this study were: (1) to characterize the distribution of mRNAs encoding parathyroid hormone (PTH)-related protein (PTHrP) and receptor (PTHR) in bovine ovary; (2) to characterize the distribution of PTHrP and PTHR polypeptides in bovine ovary; (3) to examine the influences of PTHrP (1-141) treatment during bovine oocyte maturation in vitro on blastocyst development. mRNAs encoding PTHrP and PTHR were detected by in situ hybridization methods in oocytes, and granulosa cells in all follicles from primordial to large antral. PTHrP and PTHR polypeptides displayed distinct distribution patterns with PTHrP polypeptides primarily confined to oocytes from primordial to large antral follicles. PTHrP polypeptides were detectable but at a reduced level in ovarian stroma and in granulosa and thecal layers. PTHR polypeptides were detected in oocytes of all follicular stages but were predominantly found in ovarian stroma, granulosa and theca follicular layers. Supplementation of serum-free cSOFMaa oocyte maturation medium with PTHrP (1-141) resulted in a concentration-dependent increase in development to the blastocyst stage in vitro. The results suggest that granulosa cells may be a primary site of PTHrP production and release. Oocytes from all follicular stages stained strongly for PTHrP polypeptides and PTHrP enhanced development to the blastocyst stage in vitro.

  14. Effect Modifying Role of Serum Calcium on Mortality-Predictability of PTH and Alkaline Phosphatase in Hemodialysis Patients: An Investigation Using Data from the Taiwan Renal Registry Data System from 2005 to 2012.

    Directory of Open Access Journals (Sweden)

    Yen-Chung Lin

    Full Text Available Predicting mortality in dialysis patients based on low intact parathyroid hormone levels is difficult, because aluminum intoxication, malnutrition, older age, race, diabetes, or peritoneal dialysis may influence these levels. We investigated the clinical implications of low parathyroid hormone levels in relation to the mortality of dialysis patients using sensitive, stratified, and adjusted models and a nationwide dialysis database. We analyzed data from 2005 to 2012 that were held on the Taiwan Renal Registry Data System, and 94,983 hemodialysis patients with valid data regarding their intact parathyroid levels were included in this study. The patient cohort was subdivided based on the intact parathyroid hormone and alkaline phosphatase levels. The mean hemodialysis duration within this cohort was 3.5 years. The mean (standard deviation age was 62 (14 years. After adjusting for age, sex, diabetes, the hemodialysis duration, serum albumin levels, hematocrit levels, calcium levels, phosphate levels, and the hemodialysis treatment adequacy score, the single-pool Kt/V, the crude and adjusted all-cause mortality rates increased when alkaline phosphatase levels were higher or intact parathyroid hormone levels were lower. In general, at any given level of serum calcium or phosphate, patients with low intact parathyroid hormone levels had higher mortality rates than those with normal or high iPTH levels. At a given alkaline phosphatase level, the hazard ratio for all-cause mortality was 1.33 (p 9.5 mg/dL, but in the group with intact parathyroid hormone levels > 300 pg/mL and serum calcium levels > 9.5 mg/dL, the hazard ratio was 0.92 (95% confidence interval 0.85-1.01. Hence, maintaining albumin-corrected high serum calcium levels at > 9.5 mg/dL may correlate with poor prognoses for patients with low intact parathyroid hormone levels.

  15. Lithostratigraphy of the upper Oligocene–Miocene succession in Denmark

    DEFF Research Database (Denmark)

    Rasmussen, Erik Skovbjerg; Dybkjær, Karen; Piasecki, Stefan

    2010-01-01

    The Upper Oligocene – Miocene succession of onshore Denmark is about 250 m thick and is composed of interdigitating, coarse-grained fluvio-deltaic and mud-rich marine sediments; it is best exposed in coastal cliffs in eastern and northern Jylland but is also seen locally inland. These sediments...

  16. VT Certified Local Governments

    Data.gov (United States)

    Vermont Center for Geographic Information — Vermont established its Certified Local Government (CLG) program in 1985 to better help local governments integrate historic preservation concerns with planning and...

  17. Research on Iris Region Localization Algorithms

    Directory of Open Access Journals (Sweden)

    Pravin S.Patil

    2014-10-01

    Full Text Available Iris recognition is a biometric technique that offers premium performance. Iris localization is critical to the success of an iris recognition system, since data that is falsely represented as iris pattern data will corrupt the biometric templates generated, resulting in poor recognition rates. So far different algorithms for iris localization having been proposed. This paper explored four efficient methods for iris localization, out of these three methods of iris localization in circular form and one methods of unwrapping the iris in to a flat bed. Experimental results are reported to demonstrate performance evaluation of every implemented algorithms. Conclusion based on comparisons can provide most significant information for further research. A CASIA and UPOL iris databases of iris images has been used for implementation of iris localization General Term Biometrics,Iris Recognition,Iris Localization

  18. Leadership Succession and Successful Leadership: The Case of Laura Martinez

    Science.gov (United States)

    Garza, Encarnacion, Jr.; Murakami-Ramalho, Elizabeth; Merchant, Betty

    2011-01-01

    This case study follows the work of principal Laura Martinez as moving from leading Stevens Elementary for 9 years, and now opening a new P-8th grade academy in the same south Texas urban, inner-city district. The purpose of this case study was to observe successful leadership and the principal's strategies both in her previous and present school,…

  19. The International Successful School Principalship Project: Success Sustained?

    Science.gov (United States)

    Moos, Lejf; Johansson, Olof

    2009-01-01

    Purpose: The purpose of this paper is to synthesize the findings of the follow-up studies of successful school principals in six countries: Australia, Denmark, England, Norway, Sweden, and the USA. Design/methodology/approach: Data were categorized according to stakeholder expectations, the concept and practice of leadership, and the…

  20. Leadership Succession and Successful Leadership: The Case of Laura Martinez

    Science.gov (United States)

    Garza, Encarnacion, Jr.; Murakami-Ramalho, Elizabeth; Merchant, Betty

    2011-01-01

    This case study follows the work of principal Laura Martinez as moving from leading Stevens Elementary for 9 years, and now opening a new P-8th grade academy in the same south Texas urban, inner-city district. The purpose of this case study was to observe successful leadership and the principal's strategies both in her previous and present school,…

  1. Local reduction in physics

    Science.gov (United States)

    Rosaler, Joshua

    2015-05-01

    A conventional wisdom about the progress of physics holds that successive theories wholly encompass the domains of their predecessors through a process that is often called "reduction." While certain influential accounts of inter-theory reduction in physics take reduction to require a single "global" derivation of one theory's laws from those of another, I show that global reductions are not available in all cases where the conventional wisdom requires reduction to hold. However, I argue that a weaker "local" form of reduction, which defines reduction between theories in terms of a more fundamental notion of reduction between models of a single fixed system, is available in such cases and moreover suffices to uphold the conventional wisdom. To illustrate the sort of fixed-system, inter-model reduction that grounds inter-theoretic reduction on this picture, I specialize to a particular class of cases in which both models are dynamical systems. I show that reduction in these cases is underwritten by a mathematical relationship that follows a certain liberalized construal of Nagel/Schaffner reduction, and support this claim with several examples. Moreover, I show that this broadly Nagelian analysis of inter-model reduction encompasses several cases that are sometimes cited as instances of the "physicist's" limit-based notion of reduction.

  2. Succession planning. A strategy for taking charge.

    Science.gov (United States)

    Bower, F L

    2000-01-01

    This article on succession planning includes a definition of succession planning, the reasons for and components of succession planning, and why succession planning is important to the leadership of an organization, unit, division or department. Each component of succession planning, that is, vision, networking, and mentorship, is described, with examples that are intended to guide the reader to initiate and evaluate succession planning.

  3. Drilling successful from ROV Ventana

    Science.gov (United States)

    Stakes, Debra S.; McFarlane, James A. R.; Holloway, G. Leon; Greene, H. Gary

    Cores of granite and deformed sediment from the walls of Monterey Canyon were successfully recovered from December 30 to 31, 1992, by Monterey Bay Aquarium Research Institute's (MBARI) Remotely Operated Vehicle (ROV) Ventana using a small-diameter, double-barrel drill with a diamond bit. This HSTR (Holloway-Stakes-Tengdin-Rajcula) drill was developed to drill cores horizontally from sulfide/sulfate walls of active black smokers. The drill was first successfully used by the submersible Alvin in October 1991 to drill into massive sulfide chimneys, on the Juan de Fuca Ridge (Eos, June 30, 1992, p. 273), and it was subsequently used with equal success on the chalcopyrite-rich chimneys from 21°N and 9°N on the East Pacific Rise. The recent December dives, however, marked the first time that drilling has ever been attempted from the smaller ROV and the first time coring into the harder igneous rock substrate has been attempted.

  4. Success factors in technology development

    Science.gov (United States)

    Preston, John T.

    1995-01-01

    Universities in the U.S. have a significant impact on business through the transfer of technology. This paper describes goals and philosophy of the Technology Licensing Office at the Massachusetts Institute of Technology. This paper also relates the critical factors for susscessful technology transfer, particularly relating to new business formation. These critical factors include the quality of the technology, the quality of the management, the quality of the investor, the passion for success, and the image of the company. Descriptions of three different levels of investment are also given and the most successful level of investment for starting a new company is reviewed. Licensing to large companies is also briefly reviewed, as this type of licensing requires some different strategies than that of licensing to start-up companies. High quality critical factors and intelligent investment create rewards for the parties and successful ventures.

  5. Mission Success for Combustion Science

    Science.gov (United States)

    Weiland, Karen J.

    2004-01-01

    This presentation describes how mission success for combustion experiments has been obtained in previous spaceflight experiments and how it will be obtained for future International Space Station (ISS) experiments. The fluids and combustion facility is a payload planned for the ISS. It is composed of two racks: the fluids Integrated rack and the Combustion INtegrated Rack (CIR). Requirements for the CIR were obtained from a set of combustion basis experiments that served as surrogates for later experiments. The process for experiments that fly on the ISS includes proposal selection, requirements and success criteria definition, science and engineering reviews, mission operations, and postflight operations. By following this process, the microgravity combustion science program has attained success in 41 out of 42 experiments.

  6. Fast Success and Slow Failure

    DEFF Research Database (Denmark)

    Mors, Louise; Waguespack, David

    Full Abstract: Do the benefits of cross boundary collaborations outweigh the costs? We seek to answer this question by examining 5079 collaborations in the Internet Engineering Task Force (IETF). Our findings suggest that crossing formal boundaries is positively related to success and efficiency...... of the collaboration. Yet there are high costs associated with cross boundary collaborations for unsuccessful projects, as these take longer to fail, and therefore hold up resources that could be reallocated to other projects. We find that even with a boost in success, the costs are higher than the likelihood...... of success, suggesting that firms are better off investing in nondiverse projects. This finding has important implications for how we think about the benefits of seeking novelty....

  7. Developing a Successful HIV Vaccine.

    Science.gov (United States)

    Gallo, Robert C

    2015-07-15

    Human immunodeficiency virus (HIV) genome integration indicates that persistent sterilizing immunity will be needed for a successful vaccine candidate. This suggests a need for broad antibodies targeting the Env protein. Immunogens targeting gp120 have been developed that block infection in monkeys and mimic the modest success of the RV144 clinical trial in that protection is short-lived following a decline in antibody-depending cell-mediated cytotoxicity-like antibodies. Attempts to induce antibody persistence have been complicated by a loss of efficacy, presumably by increasing the number of HIV-target cells. The key seems to be achieving an immune balance.

  8. Successive quadratic programming multiuser detector

    Institute of Scientific and Technical Information of China (English)

    Mu Xuewen; Zhang Yaling; Liu Sanyang

    2007-01-01

    Based on the semidefinite programming relaxation of the CDMA maximum likelihood multiuser detection problem,a detection strategy by the successive quadratic programming algorithm is presented. Coupled with the randomized cut generation scheme, the suboptimal solution of the multiuser detection problem in obtained. Compared to the interior point methods previously reported based on semidefinite programming, simulations demonstrate that the successive quadratic programming algorithm often yields the similar BER performances of the multiuser detection problem. But the average CPU time of this approach is significantly reduced.

  9. Integrins as Therapeutic Targets: Successes and Cancers

    Directory of Open Access Journals (Sweden)

    Sabine Raab-Westphal

    2017-08-01

    Full Text Available Integrins are transmembrane receptors that are central to the biology of many human pathologies. Classically mediating cell-extracellular matrix and cell-cell interaction, and with an emerging role as local activators of TGFβ, they influence cancer, fibrosis, thrombosis and inflammation. Their ligand binding and some regulatory sites are extracellular and sensitive to pharmacological intervention, as proven by the clinical success of seven drugs targeting them. The six drugs on the market in 2016 generated revenues of some US$3.5 billion, mainly from inhibitors of α4-series integrins. In this review we examine the current developments in integrin therapeutics, especially in cancer, and comment on the health economic implications of these developments.

  10. Role of MR imaging in surgical planning and prediction of successful surgical repair of pelvic organ prolapse

    Directory of Open Access Journals (Sweden)

    Ebtesam Moustafa Kamal

    2013-09-01

    Conclusion: Magnetic resonance imaging can accurately localize pelvic floor defects, evaluate success or failure of surgical procedures, predict the need for more extensive reconstruction, and identify complications.

  11. Limits to local government

    NARCIS (Netherlands)

    Rob Gilsing

    2005-01-01

    Original title: Bestuur aan banden. A great deal is expected of local authority youth policy: the idea is that the local authority is in a better position than central government to develop policy that is tailored to the local situation. Moreover, it is felt that it is easier for local authorities

  12. The localization of 10% of the pathologic glands in secondary hyperparathyroidism depends on the surgeon experience

    Directory of Open Access Journals (Sweden)

    José Luis D’Addino

    2015-07-01

    Full Text Available Methods for preoperative localization of parathyroidin secondary hyperparathyroidism are controversial in the literature and have different and dissimilar sensitivity. With the objective to determine the correlation between preoperative ultrasound, scintigraphy MIBI and intraoperative findings in secondary hyperparathyroidism we review our 10 years statistic.Between2004-2014, 100 patients underwent parathyroidectomy due to secondary hyperparathyroidism. Data obtained from medical records included: preoperative serum parathormona, ultrasound, scintigraphy. Positive predictive value and negative predictive value were analyzed in correlation with intraoperative findings.The method of calculation of ROC curves and area under the curve and other screening values (confidence index, index of validity and likelihood ratio were used. 68% were women; mean age was 52,7 years. Mean PTH value was 1486 pg/ml. The specificity and sensitivity of preoperative ultrasound were 94,44% and 30,14%, respectively. PPV was 93,62% and NPV was 33,33%. For scintigraphy, the sensitivity was 25,34%, specificity 98,15%, PPV was 97,37% and NPV was 32,72%. The ultrasound diagnosed 94 glands among a possibility of 400, the scintigraphy showed 76 and the surgery founded 292. Recurrence, 22%. Ultrasound and scintigraphy allow the localization of pathological parathyroid; however, in 10% of cases,glands could not be detected preoperatively, making surgeons experience fundamental in gland localization

  13. Local real analysis in locally homogeneous spaces

    CERN Document Server

    Bramanti, Marco

    2011-01-01

    We introduce the concept of locally homogeneous space, and prove in this context L^p and Holder estimates for singular and fractional integrals, as well as L^p estimates on the commutator of a singular or fractional integral with a BMO or VMO function. These results are motivated by local a-priori estimates for subelliptic equations.

  14. Local Experiences in Community Health

    Directory of Open Access Journals (Sweden)

    Sébastien Fleuret

    2015-08-01

    Full Text Available This paper presents the findings of international research with an original approach anchored in health geography, which illustrates the importance of place as a dimension in community health. The aim of the research is to identify the success factors in the processes used to build community health initiatives at the local level. The study is based on interviews encoded and analysed using the framework of the grounded theory. Three main themes—the place, the community and healthcare supply—and two cross-cutting issues referring to 18 explanatory dimensions are identified. These findings are then put to the test in France through an action research approach. Overall, the work suggest avenues to enable the transferability of successful elements of community health initiatives.

  15. Maternal Cohabitation and Educational Success

    Science.gov (United States)

    Raley, R. Kelly; Frisco, Michelle L.; Wildsmith, Elizabeth

    2005-01-01

    Despite the dramatic increase in children's experiences in cohabiting families, little is known about how living in such families affects children's academic success. Extrapolating from two theoretical frameworks that have been commonly used to explain the association between parental divorce and educational outcomes, the authors constructed…

  16. Academic Success at Selective Institutions.

    Science.gov (United States)

    Felix, Oscar

    2003-01-01

    Examined success factors of eight under-prepared students at Colorado State University. Four major themes emerged from the data: pre-college experiences, struggles, positive campus experiences and support, and student growth. Findings were conceptualized within a student resiliency framework. (EV)

  17. Lobomycosis Successfully Treated with Posaconazole

    Science.gov (United States)

    Bustamante, Beatriz; Seas, Carlos; Salomon, Martín; Bravo, Francisco

    2013-01-01

    Lobomycosis is a chronic subcutaneous mycosis for which no standard treatment is available to date. We describe a patient in Peru with lobomycosis on the left earlobe that was successfully treated with posaconazole for 27 months. No evidence of recurrence was observed after five years of follow-up. PMID:23546805

  18. Parents, School Success, and Health

    Centers for Disease Control (CDC) Podcasts

    2009-08-03

    In this podcast, Dr. William Jeynes, CDC Parenting Speaker Series guest, discusses the importance of parental involvement in children's academic success and lifelong health.  Created: 8/3/2009 by National Center on Birth Defects and Developmental Disabilities (NCBDDD).   Date Released: 8/3/2009.

  19. Trusted advisers build business success

    NARCIS (Netherlands)

    V.M. Strike (Vanessa)

    2010-01-01

    textabstractThe role of the trusted and most loyal adviser has been a crucial one to family concerns throughout the ages. During the Korean Joseon Dynasty, Kim Cheo-Seon, a eunuch, advised successive kings wisely. Sir Francis Walsingham, Principal Secretary to Queen Elizabeth I of England, is rememb

  20. Successful I.D. Encounters.

    Science.gov (United States)

    Poorman, Margaret J.

    Instructional Development (I.D.) encounters are dependent for success on such variables as power, politics, promotion, and organizational placement. I.D. consultants must be aware of power bases or orientation of other personnel and clients, e.g., these four "power personalities" which affect their efforts in managing I.D. encounters: the gate…

  1. Emotional Intelligence and Successful Leadership.

    Science.gov (United States)

    Maulding, Wanda S.

    Cognitive intelligence is often equated with eventual success in many areas. However, there are many instances where people of high IQ flounder whereas those of modest IQ do surprisingly well. Author and renowned psychologist Daniel Goleman believes that the explanation for this fact lies in abilities called "emotional intelligence,"…

  2. Measuring Success: Evaluating Educational Programs

    Science.gov (United States)

    Fisher, Yael

    2010-01-01

    This paper reveals a new evaluation model, which enables educational program and project managers to evaluate their programs with a simple and easy to understand approach. The "index of success model" is comprised of five parameters that enable to focus on and evaluate both the implementation and results of an educational program. The integration…

  3. of the Intestate Succession Act

    African Journals Online (AJOL)

    10332324

    substitution in terms of the Intestate Succession Act 81 of 1987. See the ... the Court explained the reasons for the difference between its .... (b) Each surviving spouse should inherit a child's share of the intestate estate or so ... the Black Administration Act 38 of 1927 and the Births and Deaths Registration Act 51 of 1992. 36.

  4. Practices of Successful School Leaders

    Science.gov (United States)

    Dolph, Dave; Grant, Stephen

    2010-01-01

    Leadership is a discipline that has been studied to improve organizational effectiveness and efficiency. Owing to the attention and emphasis that education has been subject to in recent decades, the study of successful school leadership presents an area worth examining (Smith & Piele, 1997). Therefore, the research underpinning this article…

  5. The Passion of Successful Leadership

    Science.gov (United States)

    Day, Christopher

    2004-01-01

    This paper reports multiperspective research on 10 successful, experienced headteachers working in a range of urban and suburban schools of different sizes (with different school populations and free school meals indices of between 20% and 62%). All had raised the levels of measurable pupil attainments in their schools and all were highly regarded…

  6. Archery: Success through Classroom Instruction.

    Science.gov (United States)

    Hensley, Ralph W.

    1982-01-01

    For maximum early success in mastering the sport of archery, the first few days of instruction should be taken in the classroom. Two positions, the grip and the anchor, which can be taught and rehearsed in the classroom, are described. (JN)

  7. Components of Successful Magnet Schools.

    Science.gov (United States)

    Bryant, Faye B.

    This paper identifies and discusses components of successful magnet programs. It is based on a review of existing research literature and information gathered directly from school districts. First, the paper discusses separately the following elements, which are considered "core components": (1) leadership; (2) organizational structure; (3)…

  8. Emotion regulation and successful aging.

    Science.gov (United States)

    Suri, Gaurav; Gross, James J

    2012-08-01

    Despite normative declines in old age, healthy elderly typically report surprisingly high levels of well-being. It is not clear why this is so. A study by Brassen and colleagues suggests that one factor may be reduced responsiveness to regret. These findings highlight the role of emotion regulation in successful aging.

  9. Trusted advisers build business success

    NARCIS (Netherlands)

    V.M. Strike (Vanessa)

    2010-01-01

    textabstractThe role of the trusted and most loyal adviser has been a crucial one to family concerns throughout the ages. During the Korean Joseon Dynasty, Kim Cheo-Seon, a eunuch, advised successive kings wisely. Sir Francis Walsingham, Principal Secretary to Queen Elizabeth I of England, is rememb

  10. Defining and Measuring Academic Success

    Science.gov (United States)

    York, Travis T.; Gibson, Charles; Rankin, Susan

    2015-01-01

    Despite, and perhaps because of its amorphous nature, the term "academic success" is one of the most widely used constructs in educational research and assessment within higher education. This paper conducts an analytic literature review to examine the use and operationalization of the term in multiple academic fields. Dominant…

  11. Successful Teachers Practice Perpetual Learning

    Science.gov (United States)

    Main, Marisa

    2007-01-01

    Successful teaching involves continuous learning, stimulation, motivation, and networking with other art educators. To help art teachers improve themselves, SchoolArts magazine recently organized the Folk Art Traditions and Beyond Seminar at Ghost Ranch in Santa Fe. In this article, the author describes the highlights of the Folk Art Traditions…

  12. What Is Needed for Success

    Institute of Scientific and Technical Information of China (English)

    肖婧

    2007-01-01

    <正>Every one of us expects success in our daily life and work. However, we can’t avoid various kinds of failures. Some people will persist in their effort and finally get suc- cess, while others will lose their hearts easily for not having achieved what they have aimed at.

  13. Trusted advisers build business success

    NARCIS (Netherlands)

    V.M. Strike (Vanessa)

    2010-01-01

    textabstractThe role of the trusted and most loyal adviser has been a crucial one to family concerns throughout the ages. During the Korean Joseon Dynasty, Kim Cheo-Seon, a eunuch, advised successive kings wisely. Sir Francis Walsingham, Principal Secretary to Queen Elizabeth I of England, is

  14. Successful Components of Interdisciplinary Education.

    Science.gov (United States)

    Shepard, Katherine; And Others

    1985-01-01

    This article presents 10 ideas for developing successful interdisciplinary curricula as suggested in the allied health literature. Implementation of the ideas is illustrated by examples from a clinical geriatric course involving physical therapy, physician assistant, nurse practitioner, and medical students. (Author/CT)

  15. Defining local food

    DEFF Research Database (Denmark)

    Eriksen, Safania Normann

    2013-01-01

    Despite evolving local food research, there is no consistent definition of “local food.” Various understandings are utilized, which have resulted in a diverse landscape of meaning. The main purpose of this paper is to examine how researchers within the local food systems literature define local...... food, and how these definitions can be used as a starting point to identify a new taxonomy of local food based on three domains of proximity....

  16. Localized coherence of freak waves

    Science.gov (United States)

    Latifah, Arnida L.; van Groesen, E.

    2016-09-01

    This paper investigates in detail a possible mechanism of energy convergence leading to freak waves. We give examples of a freak wave as a (weak) pseudo-maximal wave to illustrate the importance of phase coherence. Given a time signal at a certain position, we identify parts of the time signal with successive high amplitudes, so-called group events, that may lead to a freak wave using wavelet transform analysis. The local coherence of the critical group event is measured by its time spreading of the most energetic waves. Four types of signals have been investigated: dispersive focusing, normal sea condition, thunderstorm condition and an experimental irregular wave. In all cases presented in this paper, it is shown that a high correlation exists between the local coherence and the appearance of a freak wave. This makes it plausible that freak waves can be developed by local interactions of waves in a wave group and that the effect of waves that are not in the immediate vicinity is minimal. This indicates that a local coherence mechanism within a wave group can be one mechanism that leads to the appearance of a freak wave.

  17. Planning a Successful Tech Show

    Science.gov (United States)

    Nikirk, Martin

    2011-01-01

    Tech shows are a great way to introduce prospective students, parents, and local business and industry to a technology and engineering or career and technical education program. In addition to showcasing instructional programs, a tech show allows students to demonstrate their professionalism and skills, practice public presentations, and interact…

  18. Local perturbations perturb—exponentially–locally

    Energy Technology Data Exchange (ETDEWEB)

    De Roeck, W., E-mail: wojciech.deroeck@fys.kuleuven.be; Schütz, M., E-mail: marius.schutz@fys.kuleuven.be [Instituut voor Theoretische Fysica, K. U. Leuven, Celestijnenlaan 200D, B-3001 Heverlee (Belgium)

    2015-06-15

    We elaborate on the principle that for gapped quantum spin systems with local interaction, “local perturbations [in the Hamiltonian] perturb locally [the groundstate].” This principle was established by Bachmann et al. [Commun. Math. Phys. 309, 835–871 (2012)], relying on the “spectral flow technique” or “quasi-adiabatic continuation” [M. B. Hastings, Phys. Rev. B 69, 104431 (2004)] to obtain locality estimates with sub-exponential decay in the distance to the spatial support of the perturbation. We use ideas of Hamza et al. [J. Math. Phys. 50, 095213 (2009)] to obtain similarly a transformation between gapped eigenvectors and their perturbations that is local with exponential decay. This allows to improve locality bounds on the effect of perturbations on the low lying states in certain gapped models with a unique “bulk ground state” or “topological quantum order.” We also give some estimate on the exponential decay of correlations in models with impurities where some relevant correlations decay faster than one would naively infer from the global gap of the system, as one also expects in disordered systems with a localized groundstate.

  19. Maximizing PTH Anabolic Osteoporosis Therapy. Revision

    Science.gov (United States)

    2016-09-01

    of Pediatrics (Y.H., F.-C.Y.), Indiana University School of Medicine; Herman B Wells Center for Pediatric Research (Y.H., F.-C.Y.); Cellular and...2011;7:647–656. 2. Baron R, Hesse E. Update on bone anabolics in osteoporosis treat- ment: rationale, current status, and perspectives. J Clin

  20. Telehealth success: evaluation framework development.

    Science.gov (United States)

    Hebert, M

    2001-01-01

    Implementing telehealth applications represents a substantial investment of resources, which is one reason why success is of great interest. Many research and evaluation studies have investigated measures of successful telehealth systems. However, the term "telehealth" represents a wide range of variables including clinical application, characteristics of the information being transmitted, temporal relationships of data transfer and the organizational context. These sources of variability pose many challenges for evaluation as well as for building a cumulative history of research. A conceptual framework is required that assists in categorizing results and drawing conclusions based on an accumulation of findings. One measure of "success" in health care is quality patient care and this reflects a primary reason for ICT investments. For this reason, Donabedian's work in evaluating quality provides the basis for the proposed framework. DeLone and McLean's definitions of IS success assist in conceptualizing Donabedian's structure-outcome-process variables in a telehealth context. Multiple evaluation approaches have been used to address different types of questions. Prior to the technologies being introduced to clinical care, there are usually many studies to demonstrate their effectiveness. Health Technology Assessment examines a broader context than the technology alone, including costs and comparing alternatives that would exist in the absence of telehealth. It considers performance measures; outcomes; summary measures, operational considerations, and other issues. Program Evaluation examines use of the technology to provide a service or deliver a program. Evaluation questions often address whether the program goals have been met and if it is operating as expected. Perhaps of greater concern than the evaluation approach taken is generalizability of findings. Recent studies have given inadequate attention to defining what is done (i.e. comparison of telehealth to most

  1. Coevolutionary success-driven multigames

    CERN Document Server

    Szolnoki, Attila

    2014-01-01

    Wealthy individuals may be less tempted to defect than those with comparatively low payoffs. To take this into consideration, we introduce coevolutionary success-driven multigames in structured populations. While the core game is always the weak prisoner's dilemma, players whose payoffs from the previous round exceed a threshold adopt only a minimally low temptation to defect in the next round. Along with the strategies, the perceived strength of the social dilemma thus coevolves with the success of each individual player. We show that the lower the threshold for using the small temptation to defect, the more the evolution of cooperation is promoted. Importantly, the promotion of cooperation is not simply due to a lower average temptation to defect, but rather due to a dynamically reversed direction of invasion along the interfaces that separate cooperators and defectors on regular networks. Conversely, on irregular networks, in the absence of clear invasion fronts, the promotion of cooperation is due to inte...

  2. Key to Language Learning Success

    Directory of Open Access Journals (Sweden)

    Oktavian Mantiri

    2015-01-01

    Full Text Available This paper looks at the important elements of language learning and teaching i.e. the role of teachers as well as the attitude and motivation of learners. Teachers undoubtedly play crucial roles in students’ language learning outcome which could ignite or diminish students’ motivation. Positive attitudes and motivation – instrumental or integrative and intrinsic or extrinsic – are key to successful learning. Therefore it is paramount for language teachers as well as learners to know these roles and nurture the best possible ways where language teaching and learning will thrive. This paper also suggested that both stake-holders should be open to holistic approach of language learning and that other factors such as the environment could play an important part in language teaching and learning success.

  3. Successful renal transplantation during pregnancy.

    Science.gov (United States)

    Hold, Phoebe M; Wong, Christopher F; Dhanda, Raman K; Walkinshaw, Steve A; Bakran, Ali

    2005-09-01

    Little is known about the implications of performing a renal transplant on a patient who is already pregnant. This case study reports a successful outcome of pregnancy, diagnosed coincidentally following renal transplantation at 13 weeks gestation. The recipient was a 23-year-old woman with chronic kidney disease who received a live-related renal transplant from her father. Pregnancy was discovered at routine ultrasound scanning of the renal allograft at 5 days posttransplant and estimated at 13 weeks gestation. She received ciclosporin monotherapy as immunosuppression throughout the pregnancy, and was given valacyclovir as prophylaxis against cytomegalovirus (CMV) infection. Renal function remained stable throughout the pregnancy, which progressed normally, resulting in the vaginal delivery of a healthy, liveborn male infant at 37 weeks gestation. This case study demonstrates that transplantation during pregnancy can have a successful outcome.

  4. Institutional Influences on Succession Intentions

    DEFF Research Database (Denmark)

    Boyd, Britta; Fietze, Simon

    International research shows that entrepreneurial intentions (EI) largely depend on the institutional context. Family business research indicates that succession intentions (SI) similarly vary among countries but explanations up to now are mainly based on cultural differences. Especially in Nordic...... welfare countries entrepreneurial but also succession intention are lower than in countries with other welfare models. Therefore we investigate how SI differs in 17 countries with regards to the institutional context by combining the Global University Entrepreneurial Spirit Students’ Survey (GUESSS......) and the Comparative Welfare Entitlements Dataset (CWED). With this study we fill a research gap by analyzing the influence of social policy measured by the total generosity index on SI of students. The regression results show that SI among other variables depends on the welfare model in certain institutional contexts...

  5. Erp Systems Critical Success Factors

    Directory of Open Access Journals (Sweden)

    Islam K. Sowan

    2015-06-01

    Full Text Available The Enterprise Resources Planning (ERP systems are one of the highly complex systems in the information systems field; the implementations of this type of systems need a long time, high cost, and a lot of resources. Many factors affect the successful implementation of ERP system. The critical success factors (CSFs can be categorized as general, ICT related and software engineering or system life cycle (SLC related. This paper is a survey paper that identifies ERP systems CSFs in general and software engineering CSFs in specific. Also an agile methodology for ERP systems' implementations will be presented. Many existing ERP systems were surveyed and presented from ICT / software engineering point of view.

  6. Principles of successful cancer screening.

    Science.gov (United States)

    Smith, R A

    1999-10-01

    Screening for cancer is the application of various tests to apparently healthy individuals in order to identify who among them has occult disease, which may be either invasive disease or a precursor lesion. For any given cancer site, the potential of screening to reduce morbidity and mortality is based on well-defined criteria for the evaluation of screening effectiveness and on acceptable performance to be realized in the average community setting. Screening programs are most successful when they are organized into a system that leads to high rates of participation, high quality, and constant surveillance and evaluation. If the elements that contribute to a successful screening program are not well organized and integrated, then the fullest potential of screening will not be realized.

  7. The composition of international success

    DEFF Research Database (Denmark)

    Helles, Rasmus; Lai, Signe Sophus

    ) in well-travelled series, whereas the less-travelled series have a higher proportion of scenes set in private homes or suburban exterior locations. We conclude the analysis by linking the traits of the well-travelled series to notions of cultural proximity and cross-cultural recognisability, and note......Danish television series have in recent years enjoyed an unprecedented level of international success, with series such as Borgen (2010-13) and The Killing (2007-12) travelling to multiple countries in Europe and beyond. Several explanations for the success have been put forward – ranging from...... or more European markets) compared to the series that do not. Typically, content analysis of television series is focused on identifying bias, for example in the portrayal of women or minority groups (Gerding and Signorielli, 2014). In this analysis, we extent the coding frame to include aesthetic...

  8. Writing a successful business plan.

    Science.gov (United States)

    Haag, A B

    1997-01-01

    1. In creating and building a business, the entrepreneur assumes all the responsibilities for its development and management, as well as the risks and risks and rewards. Many businesses do not survive because business owners fail to develop an effective plan. 2. The business plan focuses on major areas of concern and their contribution to the success of a new business. The finished product communicates the product/service to others and provides the basis for the financial proposal. 3. Planning helps identify customers, market area, pricing strategy, and competitive conditions. It aids in decision making and is an essential guide for operating a business successfully and measuring progress. 4. The business plan not only serves as a mechanism for obtaining any needed financial resources, but also indicates the future direction of the company.

  9. Challenges for Success in Startups

    Science.gov (United States)

    Spitzer, Richard

    2000-03-01

    The basic challenges to a startup company such as IME have stemmed from the need to balance the business world's goal of fast entry into the market place with the necessity for a solid foundation in technology. Our technology base is broad - indeed it has the makings of a new industry - and the lure of quick commercial success in a specific application could easily make IME vulnerable to the R&D might of giant international companies. The essential challenges for success play out in business/technology decision tradeoffs: (i) preserving equity and viability while keeping R&D momentum and establishing intellectual property, (ii) attracting investors while maintaining focus on long-range goals, and (iii) developing a complete team while protecting capital resources. This balancing act keeps the company agile and resilient, qualities that large corporations could emulate with profit.

  10. 糖尿病肾病与慢性肾小球肾炎血液透析患者血钙、磷及甲状旁腺激素水平比较%Comparison of calcium, phosphorus, and PTH levels in patients with diabetic nephropathy and chronic glomerulo-nephritis underwent hemodialysis

    Institute of Scientific and Technical Information of China (English)

    潘锐

    2015-01-01

    目的:评估并分析糖尿病肾病及慢性肾小球肾炎血液透析患者血钙、血磷及甲状旁腺激素水平。方法选择2012年2月至2014年6月于洛阳市第一中医院进行血液透析治疗的患者90例,其中糖尿病肾病患者39例,慢性肾小球肾炎患者51例,分别观察分析其血钙、血磷、甲状旁腺素水平及甲状旁腺素达标率。结果糖尿病肾病患者与慢性肾小球肾炎患者血钙水平比较差异未见统计学意义(P >0.05);糖尿病患者血磷水平低于慢性肾小球肾炎患者,甲状旁腺激素水平低于慢性肾小球肾炎,甲状旁腺素水平达标率高于慢性肾小球肾炎,差异均有统计学意义(P 0. 05); The serum phosphorus and PTH levels in patients with diabetes were lower than those of patients with chronic glomerulonephritis (P < 0. 05), and the PTH standard-reaching rate was higher in patients with diabetic nephropathy, all of the differences were significant (P < 0. 05). Conclusions The serum phosphor-us and PTH levels are lower and PTH standard-reaching rate is higher in patients with diabetic nephropathy than that of pa-tients with chronic glomerulonephritis, and therefore individualized treatment should be adopted according to different cau-ses to patients underwent hemodialysis, and closely monitoring their electrolytes and related hormone levels.

  11. Study on the effect of different dialysis method in eliminating PTH and IL-6 levels of diabetic nephropathy patients with renal failure%不同透析方法对糖尿病肾病患者 PTH及IL-6的影响

    Institute of Scientific and Technical Information of China (English)

    刘大军; 张晨; 李德天

    2015-01-01

    目的:观察分析不同透析方法对清除糖尿病性肾衰患者甲状旁腺激素(PTH)及白细胞介素6(IL-6)的影响。方法将我院2011年6月至2014年12月116例糖尿病肾病肾衰患者随机分为两组,高通量组患者进行高通量透析治疗,低通量组患者进行常规低通量治疗。两组患者均连续透析3个月,透析治疗前后分别测定两组患者尿素氮、血肌酐、白蛋白水平、CRP、IL-6、PTH、Ca、P和Hb水平变化情况。结果治疗前,两组患者的血肌酐、CRP、IL-6、PTH、血清Ca、P、Hb、FINS和HOMA-IR水平相比较无明显差异(P>0.05);治疗后,两组患者白蛋白水平、FPG水平相比较差异无统计学意义(P>0.05);两组患者尿素氮、血肌酐、CRP、IL-6、PTH和FINS、HOMA-IR水平比治疗前均明显降低(P0. 05). Albumin levels, FPG levels of two groups patients had no significant differ-ence before and after treatment (P>0. 05). Urea nitrogen, serum creatinine, albumin, CRP, IL-6, PTH levels and FINS, HO-MA-IR of two groups′ patients were obviously reduced after treatment (P<0. 05). Urea nitrogen, serum creatinine, CRP, IL-6, PTH levels, FINS and HOMA-IR of the high-flux group patients were significantly lower than those of the low-flux group patients (P<0. 05). Hb level of two groups′patients were significant elevated and that of the high-flux group patients were higher than the low-flux group patients (P<0. 05). Conclusion The effect of different dialysis method in eliminating PTH and IL-6 levels of dia-betic patients with renal failure are different. High flux can better improve the clinical symptoms and it is advantageous to the treat-ment of diabetic patients with renal failure.

  12. The Successive Mean Quantization Transform

    OpenAIRE

    Nilsson, Mikael; Dahl, Mattias; Claesson, Ingvar

    2005-01-01

    This paper presents the Successive Mean Quantization Transform (SMQT). The transform reveals the organization or structure of the data and removes properties such as gain and bias. The transform is described and applied in speech processing and image processing. The SMQT is considered as an extra processing step for the mel frequency cepstral coefficients commonly used in speech recognition. In image processing the transform is applied in automatic image enhancement and dynamic range compress...

  13. Fumigation success for California facility.

    Science.gov (United States)

    Hacker, Robert

    2010-02-01

    As Robert Hacker, at the time director of facilities management at the St John's Regional Medical Center in Oxnard, California, explains, the hospital, one of the area's largest, recently successfully utilised a new technology to eliminate mould, selecting a cost and time-saving fumigation process in place of the traditional "rip and tear" method. Although hospital managers knew the technology had been used extremely effectively in other US buildings, this was reportedly among the first ever healthcare applications.

  14. Key to Language Learning Success

    OpenAIRE

    2015-01-01

    This paper looks at the important elements of language learning and teaching i.e. the role of teachers as well as the attitude and motivation of learners. Teachers undoubtedly play crucial roles in students’ language learning outcome which could ignite or diminish students’ motivation. Positive attitudes and motivation – instrumental or integrative and intrinsic or extrinsic – are key to successful learning. Therefore it is paramount for language teachers as well as learners to know these rol...

  15. The Successive Mean Quantization Transform

    OpenAIRE

    Nilsson, Mikael; Dahl, Mattias; Claesson, Ingvar

    2005-01-01

    This paper presents the Successive Mean Quantization Transform (SMQT). The transform reveals the organization or structure of the data and removes properties such as gain and bias. The transform is described and applied in speech processing and image processing. The SMQT is considered as an extra processing step for the mel frequency cepstral coefficients commonly used in speech recognition. In image processing the transform is applied in automatic image enhancement and dynamic range compress...

  16. What influences crowdfunding campaign success.

    OpenAIRE

    Drabløs, Christian

    2015-01-01

    Crowdfunding is a recently emerged market for entrepreneurs; it represents a new and growing source of potential capital. The potential crowdfunding is starting to reach it potential, and has beginning to go mainstream. There is a gap in the research on crowdfunding and within the field of what separates a successful campaign from a failed one. To explore the variables influencing crowdfunding campaign this paper looks into academic articles, the crowdfunding platforms, general...

  17. Emerging Prospects for Repository Success

    Energy Technology Data Exchange (ETDEWEB)

    Isaacs, T

    2006-01-12

    Recent events are again raising some old issues and creating new opportunities regarding the future disposition of the used, or spent, fuel from nuclear power plants. Handling these challenges well will not only help set the stage for a robust nuclear energy future, but will reflect the growing linkages among nuclear power, nuclear waste management, international security, and public and political acceptance. The emerging global nuclear regime may make spent fuel management not only more important, but improve chances of success.

  18. Delivering success in Milton Keynes.

    Science.gov (United States)

    2004-01-01

    The national roll out of the new procurement route, for publicly funded health schemes over 1 million Pound, has recently been implemented and NHS Trusts are quite naturally looking to the pilot regions for a demonstration of what can be achieved. One such example is the successful delivery of the new Treatment Centre for Milton Keynes General Hospital NHS Trust by Norwest Hoist Construction and its supply chain.

  19. Weight Maintenance: Determinants of Success

    Science.gov (United States)

    2005-12-15

    submitted in partial fulfillment of the requirements for the degree of MASTER OF DIETETIC ADMINISTRATION In Nutrition and Food Sciences Approved: Tamara...Determinants Of Success by Cynthia Mitchell, Master of Dietetic Administration Utah State University, 2005 Major Professor: Tamara Vitale Department...a concern. Current data suggest that these foods are often higher in energy, fat and sodium, but deficient in fiber , vitamins A and C and folate

  20. Innovation, Key to Lasting Success

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    @@ Oerlikon Textile will be exhibiting at ITMA ASIA 2010 in Shanghai on its 750- -plus stand C 51/C 52 in hall W2 from 22 to 26 June 2010. Highlights of the five brands under the umbrella of the textile machinery manufacturer include the new Autoconer X5 winding machine, a new FDY technology and the Era embroidery machine. Their technological innovations illustrate the slogan under which Oerlikon Textile is appearing at the show: Innovation remains the key to success.